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Rheumatoid Arthritis Journey

By Maureen SalamonHealthDay Reporter THURSDAY, June 20 (HealthDay News) The common belief that rheumatoid arthritis patients dont benefit from knee replacement surgery as much as those with the more common osteoarthritis has been challenged by the findings from a pair of studies by New York City scientists. Researchers from the Hospital for Special Surgery also found, [...]

Eating lots of foods loaded with salt may do more than raise your blood pressure: Researchers report that it could also contribute to the development of autoimmune diseases, where the bodys immune system mistakenly mounts an attack upon some part of the body. Three new studies suggest salt may be a prime suspect in a wide range of autoimmune diseases, including multiple sclerosis (MS), psoriasis, rheumatoid arthritis and ankylosing spondylitis (arthritis of the spine).

TUESDAY, Feb. 5 (HealthDay News) Older women whove had regular exposure to sunlight may be less likely to develop rheumatoid arthritis, new findings indicate. This beneficial effect which is believed to be due to ultraviolet B (UV-B) in sunlight was only evident in older women. This may be because younger women are [...]

Genes specific to the X chromosome are among newly identified genes linked to rheumatoid arthritis and could help explain why women are more likely than men to develop the disease, researchers say. Women have two X chromosomes while men have an X and a Y chromosome.

WEDNESDAY, Nov. 28 (HealthDay News) Patients with rheumatoid arthritis are more likely to suffer hip dislocation after hip replacement surgery than those with osteoarthritis, a new study says. In addition, rheumatoid arthritis patients have a higher infection risk after total knee replacement than osteoarthritis patients, the study authors found. Rheumatoid arthritis, which is felt throughout the [...]

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Rheumatoid Arthritis Condition Center - Health.com

Recommendation and review posted by simmons

Arthritis and other rheumatic diseases are characterized by pain, swelling and limited movement in joints and connective tissues in the body. According to the Centers for Disease Control and Prevention, nearly 70 million people in the U.S. have some form of arthritis or chronic joint symptoms.

Unfamiliar with some arthritis terms? See our Arthritis Glossary

The Rehabilitation Institute of Chicago (RIC)is here to help you, whether you are noticing mild symptoms of arthritis or you have had joint pain for many years. Here at the Arthritis Center we are committed to treating you as a whole person, not just your condition, through a team effort carefully coordinated by a physician expert in arthritis care.

RIC offers comprehensive arthritis rehabilitation for people whose functional abilities have been affected by arthritis (osteoarthritis, psoriatic, rheumatoid), hip fractures, joint replacement, orthopedic conditions, osteoporosis, spine disfiguration as well as balance, rheumatologic or musculoskeletal disorders. Medical services are provided through all levels of care including inpatient and day rehabilitation and outpatient therapy.Some of the therapies offered at RIC include the newest arthritis drugs, injectable therapies, individual and group therapy and much more.

See the services offered dealing with arthritis

Our physiatrists and rheumatologists lead teams that include rehabilitation nurses, physical and occupational therapists, as well as alternative health providers who specialize in arthritis and joint pain.

RIC's Arthritis Experts

Our ongoing research into arthritis prevention and treatment puts the Rehabilitation Institute of Chicago at the forefront of the knowledge curve, allowing us to offer the benefits of that knowledge to you. In addition, if you are interested in arthritis and pain research, there may be opportunities to participate in research studies at RIC.

Current Arthritis Research

It is important for those living with arthritis to have all the tools necessary to build self-empowerment and determination to set goals and live life to the fullest.

Explore our resources for Living With Arthritis

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Arthritis & Joint Conditions - Rehabilitation Institute of ...

Recommendation and review posted by simmons

Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminata, is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a wide range of signs and symptoms,[1][2] including physical, mental,[2] and sometimes psychiatric problems.[3] MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms).[4] Between attacks, symptoms may disappear completely; however, permanent neurological problems often occur, especially as the disease advances.[4]

While the cause is not clear, the underlying mechanism is thought to be either destruction by the immune system or failure of the myelin-producing cells.[5] Proposed causes for this include genetics and environmental factors such as infections.[2][6] MS is usually diagnosed based on the presenting signs and symptoms and the results of supporting medical tests.

There is no known cure for multiple sclerosis. Treatments attempt to improve function after an attack and prevent new attacks.[2] Medications used to treat MS while modestly effective can have adverse effects and be poorly tolerated. Many people pursue alternative treatments, despite a lack of evidence. The long-term outcome is difficult to predict, with good outcomes more often seen in women, those who develop the disease early in life, those with a relapsing course, and those who initially experienced few attacks.[7]Life expectancy is on average 5 to 10 years lower than that of an unaffected population.[1]

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system.[8] As of 2008, between 2 and 2.5 million people are affected globally with rates varying widely in different regions of the world and among different populations.[9] In 2013, 20,000 people died from MS, up from 12,000 in 1990.[10] The disease usually begins between the ages of 20 and 50 and is twice as common in women as in men.[11] The name multiple sclerosis refers to scars (scleraebetter known as plaques or lesions) in particular in the white matter of the brain and spinal cord.[12] MS was first described in 1868 by Jean-Martin Charcot.[12] A number of new treatments and diagnostic methods are under development.

A person with MS can have almost any neurological symptom or sign; with autonomic, visual, motor, and sensory problems being the most common.[1] The specific symptoms are determined by the locations of the lesions within the nervous system, and may include loss of sensitivity or changes in sensation such as tingling, pins and needles or numbness, muscle weakness, very pronounced reflexes, muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems with speech or swallowing, visual problems (nystagmus, optic neuritis or double vision), feeling tired, acute or chronic pain, and bladder and bowel difficulties, among others.[1] Difficulties thinking and emotional problems such as depression or unstable mood are also common.[1]Uhthoff's phenomenon, a worsening of symptoms due to exposure to higher than usual temperatures, and Lhermitte's sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS.[1] The main measure of disability and severity is the expanded disability status scale (EDSS), with other measures such as the multiple sclerosis functional composite being increasingly used in research.[13][14][15]

The condition begins in 85% of cases as a clinically isolated syndrome over a number of days with 45% having motor or sensory problems, 20% having optic neuritis, and 10% having symptoms related to brainstem dysfunction, while the remaining 25% have more than one of the previous difficulties.[16] The course of symptoms occurs in two main patterns initially: either as episodes of sudden worsening that last a few days to months (called relapses, exacerbations, bouts, attacks, or flare-ups) followed by improvement (85% of cases) or as a gradual worsening over time without periods of recovery (10-15% of cases).[11] A combination of these two patterns may also occur[4] or people may start in a relapsing and remitting course that then becomes progressive later on.[11] Relapses are usually not predictable, occurring without warning.[1] Exacerbations rarely occur more frequently than twice per year.[1] Some relapses, however, are preceded by common triggers and they occur more frequently during spring and summer.[17] Similarly, viral infections such as the common cold, influenza, or gastroenteritis increase their risk.[1]Stress may also trigger an attack.[18] Women with MS who become pregnant experience fewer relapses; however, during the first months after delivery the risk increases.[1] Overall, pregnancy does not seem to influence long-term disability.[1] Many events have not been found to affect relapse rates including vaccination, breast feeding,[1] physical trauma,[19] and Uhthoff's phenomenon.[17]

The cause of MS is unknown; however, it is believed to occur as a result of some combination of genetic and environmental factors such as infectious agents.[1] Theories try to combine the data into likely explanations, but none has proved definitive. While there are a number of environmental risk factors and although some are partly modifiable, further research is needed to determine whether their elimination can prevent MS.[20]

MS is more common in people who live farther from the equator, although exceptions exist.[1][21] These exceptions include ethnic groups that are at low risk far from the equator such as the Samis, Amerindians, Canadian Hutterites, New Zealand Mori,[22] and Canada's Inuit,[11] as well as groups that have a relatively high risk close to the equator such as Sardinians,[11] inland Sicilians,[23]Palestinians and Parsis.[22] The cause of this geographical pattern is not clear.[11] While the north-south gradient of incidence is decreasing,[21] as of 2010 it is still present.[11]

MS is more common in regions with northern European populations[1] and the geographic variation may simply reflect the global distribution of these high-risk populations.[11] Decreased sunlight exposure resulting in decreased vitamin D production has also been put forward as an explanation.[24][25][26] A relationship between season of birth and MS lends support to this idea, with fewer people born in the northern hemisphere in November as compared to May being affected later in life.[27] Environmental factors may play a role during childhood, with several studies finding that people who move to a different region of the world before the age of 15 acquire the new region's risk to MS. If migration takes place after age 15, however, the person retains the risk of his home country.[1][20] There is some evidence that the effect of moving may still apply to people older than 15.[1]

MS is not considered a hereditary disease; however, a number of genetic variations have been shown to increase the risk.[28] The probability is higher in relatives of an affected person, with a greater risk among those more closely related.[2] In identical twins both are affected about 30% of the time, while around 5% for non-identical twins and 2.5% of siblings are affected with a lower percentage of half-siblings.[1][2][29] If both parents are affected the risk in their children is 10 times that of the general population.[11] MS is also more common in some ethnic groups than others.[30]

Specific genes that have been linked with MS include differences in the human leukocyte antigen (HLA) systema group of genes on chromosome 6 that serves as the major histocompatibility complex (MHC).[1] That changes in the HLA region are related to susceptibility has been known since the 1980s,[31] and additionally this same region has been implicated in the development of other autoimmune diseases such as diabetes type I and systemic lupus erythematosus.[31] The most consistent finding is the association between multiple sclerosis and alleles of the MHC defined as DR15 and DQ6.[1] Other loci have shown a protective effect, such as HLA-C554 and HLA-DRB1*11.[1] Overall, it has been estimated that HLA changes account for between 20 and 60% of the genetic predisposition.[31] Modern genetic methods (genome-wide association studies) have discovered at least twelve other genes outside the HLA locus that modestly increase the probability of MS.[31]

Many microbes have been proposed as triggers of MS, but none have been confirmed.[2] Moving at an early age from one location in the world to another alters a person's subsequent risk of MS.[6] An explanation for this could be that some kind of infection, produced by a widespread microbe rather than a rare one, is related to the disease.[6] Proposed mechanisms include the hygiene hypothesis and the prevalence hypothesis. The hygiene hypothesis proposes that exposure to certain infectious agents early in life is protective, the disease being a response to a late encounter with such agents.[1] The prevalence hypothesis proposes that the disease is due to an infectious agent more common in regions where MS is common and where in most individuals it causes an ongoing infection without symptoms. Only in a few cases and after many years does it cause demyelination.[6][32] The hygiene hypothesis has received more support than the prevalence hypothesis.[6]

Evidence for a virus as a cause include: the presence of oligoclonal bands in the brain and cerebrospinal fluid of most people with MS, the association of several viruses with human demyelination encephalomyelitis, and the occurrence of demyelination in animals caused by some viral infection.[33]Human herpes viruses are a candidate group of viruses. Individuals having never been infected by the Epstein-Barr virus are at a reduced risk of getting MS, whereas those infected as young adults are at a greater risk than those having had it at a younger age.[1][6] Although some consider that this goes against the hygiene hypothesis, since the non-infected have probably experienced a more hygienic upbringing,[6] others believe that there is no contradiction, since it is a first encounter with the causative virus relatively late in life that is the trigger for the disease.[1] Other diseases that may be related include measles, mumps and rubella.[1]

Smoking has been shown to be an independent risk factor for MS.[24]Stress may be a risk factor although the evidence to support this is weak.[20] Association with occupational exposures and toxinsmainly solventshas been evaluated, but no clear conclusions have been reached.[20]Vaccinations were studied as causal factors; however, most studies show no association.[20] Several other possible risk factors, such as diet and hormone intake, have been looked at; however, evidence on their relation with the disease is "sparse and unpersuasive".[24]Gout occurs less than would be expected and lower levels of uric acid have been found in people with MS. This has led to the theory that uric acid is protective, although its exact importance remains unknown.[34]

The three main characteristics of MS are the formation of lesions in the central nervous system (also called plaques), inflammation, and the destruction of myelin sheaths of neurons. These features interact in a complex and not yet fully understood manner to produce the breakdown of nerve tissue and in turn the signs and symptoms of the disease.[1] Additionally, MS is believed to be an immune-mediated disorder that develops from an interaction of the individual's genetics and as yet unidentified environmental causes.[2] Damage is believed to be caused, at least in part, by attack on the nervous system by a person's own immune system.[1]

The name multiple sclerosis refers to the scars (sclerae better known as plaques or lesions) that form in the nervous system. These lesions most commonly affect the white matter in the optic nerve, brain stem, basal ganglia, and spinal cord, or white matter tracts close to the lateral ventricles.[1] The function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of the body. The peripheral nervous system is rarely involved.[2]

To be specific, MS involves the loss of oligodendrocytes, the cells responsible for creating and maintaining a fatty layerknown as the myelin sheathwhich helps the neurons carry electrical signals (action potentials).[1] This results in a thinning or complete loss of myelin and, as the disease advances, the breakdown of the axons of neurons. When the myelin is lost, a neuron can no longer effectively conduct electrical signals.[2] A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell's myelin sheath.[35] Repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons.[35] These scars are the origin of the symptoms and during an attack magnetic resonance imaging (MRI) often shows more than ten new plaques.[1] This could indicate that there are a number of lesions below which the brain is capable of repairing itself without producing noticeable consequences.[1] Another process involved in the creation of lesions is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons.[1] A number of lesion patterns have been described.[36]

Apart from demyelination, the other sign of the disease is inflammation. Fitting with an immunological explanation, the inflammatory process is caused by T cells, a kind of lymphocyte that plays an important role in the body's defenses.[2] T cells gain entry into the brain via disruptions in the bloodbrain barrier. The T cells recognize myelin as foreign and attack it, explaining why these cells are also called "autoreactive lymphocytes".[1]

The attack of myelin starts inflammatory processes, which triggers other immune cells and the release of soluble factors like cytokines and antibodies. Further breakdown of the bloodbrain barrier, in turn cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins.[2] Inflammation can potentially reduce transmission of information between neurons in at least three ways.[1] The soluble factors released might stop neurotransmission by intact neurons. These factors could lead to or enhance the loss of myelin, or they may cause the axon to break down completely.[1]

The bloodbrain barrier is a part of the capillary system that prevents the entry of T cells into the central nervous system. It may become permeable to these types of cells secondary to an infection by a virus or bacteria. After it repairs itself, typically once the infection has cleared, T cells may remain trapped inside the brain.[2]Gadolinium cannot cross a normal BBB and, therefore, Gadolinium-enhanced MRI is used to show BBB breakdowns.[37]

Multiple sclerosis is typically diagnosed based on the presenting signs and symptoms, in combination with supporting medical imaging and laboratory testing.[16] It can be difficult to confirm, especially early on, since the signs and symptoms may be similar to those of other medical problems.[1][38] The McDonald criteria, which focus on clinical, laboratory, and radiologic evidence of lesions at different times and in different areas, is the most commonly used method of diagnosis[9] with the Schumacher and Poser criteria being of mostly historical significance.[39] While the above criteria allow for a non-invasive diagnosis, some state that the only definitive proof is an autopsy or biopsy where lesions typical of MS are detected.[1][40][41]

Clinical data alone may be sufficient for a diagnosis of MS if an individual has had separate episodes of neurologic symptoms characteristic of the disease.[40] In those who seek medical attention after only one attack, other testing is needed for the diagnosis. The most commonly used diagnostic tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentials. Magnetic resonance imaging of the brain and spine may show areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously as a contrast agent to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.[40][42] Testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation in the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis, which are inflammation markers found in 7585% of people with MS.[40][43] The nervous system in MS may respond less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual- and sensory-evoked potentials.[44]

Several phenotypes (commonly named types), or patterns of progression, have been described. Phenotypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis but also for treatment decisions. In 1996, the United States National Multiple Sclerosis Society described four clinical courses.[4] This set of courses was later reviewed by an international panel in 2013, adding clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) as phenotypes, but leaving the main structure untouched.[45]

The relapsing-remitting subtype is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits that occur during attacks may either resolve or leave problems, the latter in about 40% of attacks and being more common the longer a person has had the disease.[1][16] This describes the initial course of 80% of individuals with MS.[1] When deficits always resolve between attacks, this is sometimes referred to as benign MS,[46] although people will still build up some degree of disability in the long term.[1] On the other hand, the term malignant multiple sclerosis is used to describe people with MS having reached significant level of disability in a short period.[47] The relapsing-remitting subtype usually begins with a clinically isolated syndrome (CIS). In CIS, a person has an attack suggestive of demyelination, but does not fulfill the criteria for multiple sclerosis.[1][48] 30 to 70% of persons experiencing CIS later develop MS.[48]

Secondary progressive MS occurs in around 65% of those with initial relapsing-remitting MS, who eventually have progressive neurologic decline between acute attacks without any definite periods of remission.[1][4] Occasional relapses and minor remissions may appear.[4] The most common length of time between disease onset and conversion from relapsing-remitting to secondary progressive MS is 19years.[49]

The primary progressive subtype occurs in approximately 1020% of individuals, with no remission after the initial symptoms.[16][50] It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements.[4] The usual age of onset for the primary progressive subtype is later than of the relapsing-remitting subtype. It is similar to the age that secondary progressive usually begins in relapsing-remitting MS, around 40 years of age.[1]

Progressive relapsing MS describes those individuals who, from onset, have a steady neurologic decline but also have clear superimposed attacks. This is the least common of all subtypes.[4]

Unusual types of MS have been described; these include Devic's disease, Balo concentric sclerosis, Schilder's diffuse sclerosis, and Marburg multiple sclerosis. There is debate on whether they are MS variants or different diseases.[51] Multiple sclerosis behaves differently in children, taking more time to reach the progressive stage.[1] Nevertheless, they still reach it at a lower average age than adults usually do.[1]

Although there is no known cure for multiple sclerosis, several therapies have proven helpful. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of MS have several adverse effects. Alternative treatments are pursued by some people, despite the shortage of supporting evidence.

During symptomatic attacks, administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the usual therapy,[1] with oral corticosteroids seeming to have a similar efficacy and safety profile.[52] Although, in general, effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery.[53] The consequences of severe attacks that do not respond to corticosteroids might be treatable by plasmapheresis.[1]

As of 2014, nine disease-modifying treatments have been approved by regulatory agencies for relapsing-remitting multiple sclerosis (RRMS) including: interferon beta-1a, interferon beta-1b, glatiramer acetate, mitoxantrone, natalizumab, fingolimod,[54]teriflunomide,[55]dimethyl fumarate[56] and alemtuzumab.[57] Their cost effectiveness as of 2012 is unclear.[58]

In RRMS they are modestly effective at decreasing the number of attacks.[54] The interferons and glatiramer acetate are first-line treatments[16] and are roughly equivalent, reducing relapses by approximately 30%.[59] Early-initiated long-term therapy is safe and improves outcomes.[60][61] Natalizumab reduces the relapse rate more than first-line agents; however, due to issues of adverse effects is a second-line agent reserved for those who do not respond to other treatments[16] or with severe disease.[59] Mitoxantrone, whose use is limited by severe adverse effects, is a third-line option for those who do not respond to other medications.[16] Treatment of clinically isolated syndrome (CIS) with interferons decreases the chance of progressing to clinical MS.[1][62] Efficacy of interferons and glatiramer acetate in children has been estimated to be roughly equivalent to that of adults.[63] The role of some newer agents such as fingolimod, teriflunomide, and dimethyl fumarate, as of 2011, is not yet entirely clear.[64]

No treatment has been shown to change the course of primary progressive MS[16] and as of 2011 only one medication, mitoxantrone, has been approved for secondary progressive MS.[65] In this population tentative evidence supports mitoxantrone moderately slowing the progression of the disease and decreasing rates of relapses over two years.[66][67]

The disease-modifying treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferons (up to 90% with subcutaneous injections and 33% with intramuscular injections).[68] Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known as lipoatrophy, may develop.[68] Interferons may produce flu-like symptoms;[69] some people taking glatiramer experience a post-injection reaction with flushing, chest tightness, heart palpitations, and anxiety, which usually lasts less than thirty minutes.[70] More dangerous but much less common are liver damage from interferons,[71]systolic dysfunction (12%), infertility, and acute myeloid leukemia (0.8%) from mitoxantrone,[66][72] and progressive multifocal leukoencephalopathy occurring with natalizumab (occurring in 1 in 600 people treated).[16][73]

Fingolimod may give rise to hypertension and slowed heart rate, macular edema, elevated liver enzymes or a reduction in lymphocyte levels.[64] Tentative evidence supports the short-term safety of teriflunomide, with common side effects including: headaches, fatigue, nausea, hair loss, and limb pain.[54] There have also been reports of liver failure and PML with its use and it is dangerous for fetal development.[64] Most common side effects of dimethyl fumarate are flushing and gastrointestinal problems.[56][64] While dimethyl fumarate may lead to a reduction in the white blood cell count there were no reported cases of opportunistic infections during trials.[74][75]

Both medications and neurorehabilitation have been shown to improve some symptoms, though neither changes the course of the disease.[76] Some symptoms have a good response to medication, such as an unstable bladder and spasticity, while others are little changed.[1] For neurologic problems, a multidisciplinary approach is important for improving quality of life; however, it is difficult to specify a 'core team' as many health services may be needed at different points in time.[1] Multidisciplinary rehabilitation programs increase activity and participation of people with MS but do not influence impairment level.[77] There is limited evidence for the overall efficacy of individual therapeutic disciplines,[78][79] though there is good evidence that specific approaches, such as exercise,[80][81] and psychology therapies, in particular cognitive behavioral approaches are effective.[82]

Over 50% of people with MS may use complementary and alternative medicine, although percentages vary depending on how alternative medicine is defined.[83] The evidence for the effectiveness for such treatments in most cases is weak or absent.[83][84] Treatments of unproven benefit used by people with MS include: dietary supplementation and regimens,[83][85][86] vitamin D,[87]relaxation techniques such as yoga,[83]herbal medicine (including medical cannabis),[83][88]hyperbaric oxygen therapy,[89]self-infection with hookworms, reflexology and acupuncture.[83][90] Regarding the characteristics of users, they are more frequently women, have had MS for a longer time, tend to be more disabled and have lower levels of satisfaction with conventional healthcare.[83]

no data

<13

1316

1619

1922

2225

2528

2831

3134

3437

3740

4043

>43

The expected future course of the disease depends on the subtype of the disease; the individual's sex, age, and initial symptoms; and the degree of disability the person has.[7] Female sex, relapsing-remitting subtype, optic neuritis or sensory symptoms at onset, few attacks in the initial years and especially early age at onset, are associated with a better course.[7][91]

The average life expectancy is 30 years from the start of the disease, which is 5 to 10 years less than that of unaffected people.[1] Almost 40% of people with MS reach the seventh decade of life.[91] Nevertheless, two-thirds of the deaths are directly related to the consequences of the disease.[1]Suicide is more common, while infections and other complications are especially dangerous for the more disabled.[1] Although most people lose the ability to walk before death, 90% are capable of independent walking at 10 years from onset, and 75% at 15 years.[91][92]

MS is the most common autoimmune disorder of the central nervous system.[8] As of 2010, the number of people with MS was 22.5million (approximately 30 per 100,000) globally, with rates varying widely in different regions.[9][11] It is estimated to have resulted in 18,000 deaths that year.[93] In Africa rates are less than 0.5 per 100,000, while they are 2.8 per 100,000 in South East Asia, 8.3 per 100,000 in the Americas, and 80 per 100,000 in Europe.[9] Rates surpass 200 per 100,000 in certain populations of Northern European descent.[11] The number of new cases that develop per year is about 2.5 per 100,000.[9]

Rates of MS appear to be increasing; this, however, may be explained simply by better diagnosis.[11] Studies on populational and geographical patterns have been common[32] and have led to a number of theories about the cause.[6][20][24]

MS usually appears in adults in their late twenties or early thirties but it can rarely start in childhood and after 50 years of age.[9][11] The primary progressive subtype is more common in people in their fifties.[50] Similar to many autoimmune disorders, the disease is more common in women, and the trend may be increasing.[1][21] As of 2008, globally it is about two times more common in women than in men.[9] In children, it is even more common in females than males,[1] while in people over fifty, it affects males and females almost equally.[50]

The French neurologist Jean-Martin Charcot (18251893) was the first person to recognize multiple sclerosis as a distinct disease in 1868.[94] Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of MS now known as Charcot's triad 1 are nystagmus, intention tremor, and telegraphic speech (scanning speech), though these are not unique to MS. Charcot also observed cognition changes, describing his patients as having a "marked enfeeblement of the memory" and "conceptions that formed slowly".[12]

Before Charcot, Robert Carswell (17931857), a British professor of pathology, and Jean Cruveilhier (17911873), a French professor of pathologic anatomy, had described and illustrated many of the disease's clinical details, but did not identify it as a separate disease.[94] Specifically, Carswell described the injuries he found as "a remarkable lesion of the spinal cord accompanied with atrophy".[1] Under the microscope, Swiss pathologist Georg Eduard Rindfleisch (18361908) noted in 1863 that the inflammation-associated lesions were distributed around blood vessels.[95][96] During the 20th century theories about the cause and pathogenesis were developed and effective treatments began to appear in the 1990s.[1]

There are several historical accounts of people who probably had MS and lived before or shortly after the disease was described by Charcot.

A young woman called Halldora who lived in Iceland around 1200 suddenly lost her vision and mobility but, after praying to the saints, recovered them seven days after. Saint Lidwina of Schiedam (13801433), a Dutch nun, may be one of the first clearly identifiable people with MS. From the age of 16 until her death at 53, she had intermittent pain, weakness of the legs, and vision losssymptoms typical of MS.[97] Both cases have led to the proposal of a "Viking gene" hypothesis for the dissemination of the disease.[98]

Augustus Frederick d'Este (17941848), son of Prince Augustus Frederick, Duke of Sussex and Lady Augusta Murray and the grandson of GeorgeIII of the United Kingdom, almost certainly had MS. D'Este left a detailed diary describing his 22 years living with the disease. His diary began in 1822 and ended in 1846, although it remained unknown until 1948. His symptoms began at age 28 with a sudden transient visual loss (amaurosis fugax) after the funeral of a friend. During his disease, he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life.[99][100] Another early account of MS was kept by the British diarist W. N. P. Barbellion, nom-de-plume of Bruce Frederick Cummings (18891919), who maintained a detailed log of his diagnosis and struggle.[100] His diary was published in 1919 as The Journal of a Disappointed Man.[101]

There is ongoing research looking for more effective, convenient, and tolerable treatments for relapsing-remitting MS; creation of therapies for the progressive subtypes; neuroprotection strategies; and effective symptomatic treatments.[102]

During the 2000s and 2010s, there has been approval of several oral drugs that are expected to gain in popularity and frequency of use.[103] Several more oral drugs are under investigation, one being laquinimod, which was announced in August 2012 and is in a third phase III trial after mixed results in the previous ones.[104] Similarly, studies aimed to improve the efficacy and ease of use of already existing therapies are occurring. This includes the use of new preparations such as the PEGylated version of interferon--1a, which it is hoped may be given at less frequent doses with similar effects.[105][106] Request for approval of peginterferon beta-1a is expected during 2013.[106]

Monoclonal antibodies have also raised high levels of interest. Alemtuzumab, daclizumab, and CD20 monoclonal antibodies such as rituximab, ocrelizumab and ofatumumab have all shown some benefit and are under study as potential treatments.[75] Their use has also been accompanied by the appearance of potentially dangerous adverse effects, the most important of which being opportunistic infections.[103] Related to these investigations is the development of a test for JC virus antibodies, which might help to determine who is at greater risk of developing progressive multifocal leukoencephalopathy when taking natalizumab.[103] While monoclonal antibodies will probably have some role in the treatment of the disease in the future, it is believed that it will be small due to the risks associated with them.[103]

Another research strategy is to evaluate the combined effectiveness of two or more drugs.[107] The main rationale for using a number of medications in MS is that the involved treatments target different mechanisms and, therefore, their use is not necessarily exclusive.[107]Synergies, in which one drug improves the effect of another are also possible, but there can also be drawbacks such as the blocking of the action of the other or worsened side-effects.[107] There have been several trials of combined therapy, yet none have shown positive enough results to be considered as a useful treatment for MS.[107]

Research on neuroprotection and regenerative treatments, such as stem cell therapy, while of high importance, are in the early stages.[108] Likewise, there are not any effective treatments for the progressive variants of the disease. Many of the newest drugs as well as those under development are probably going to be evaluated as therapies for PPMS or SPMS.[103]

While diagnostic criteria are not expected to change in the near future, work to develop biomarkers that help with diagnosis and prediction of disease progression is ongoing.[103] New diagnostic methods that are being investigated include work with anti-myelin antibodies, and studies with serum and cerebrospinal fluid, but none of them has yielded reliably positive results.[110]

At the current time, there are no laboratory investigations that can predict prognosis. Several promising approaches have been proposed including: interleukin-6, nitric oxide and nitric oxide synthase, osteopontin, and fetuin-A.[110] Since disease progression is the result of degeneration of neurons, the roles of proteins showing loss of nerve tissue such as neurofilaments, tau, and N-acetylaspartate are under investigation.[110] Other effects include looking for biomarkers that distinguish between those who will and will not respond to medications.[110]

Improvement in neuroimaging techniques such as positron emission tomography (PET) or magnetic resonance imaging (MRI) carry a promise for better diagnosis and prognosis predictions, although the effect of such improvements in daily medical practice may take several decades.[103] Regarding MRI, there are several techniques that have already shown some usefulness in research settings and could be introduced into clinical practice, such as double-inversion recovery sequences, magnetization transfer, diffusion tensor, and functional magnetic resonance imaging.[111] These techniques are more specific for the disease than existing ones, but still lack some standardization of acquisition protocols and the creation of normative values.[111] There are other techniques under development that include contrast agents capable of measuring levels of peripheral macrophages, inflammation, or neuronal dysfunction,[111] and techniques that measure iron deposition that could serve to determine the role of this feature in MS, or that of cerebral perfusion.[111] Similarly, new PET radiotracers might serve as markers of altered processes such as brain inflammation, cortical pathology, apoptosis, or remylienation.[112] Antibiodies against the Kir4.1 potassium channel may be related to MS.[113]

In 2008, vascular surgeon Paolo Zamboni suggested that MS involves narrowing of the veins draining the brain, which he referred to as chronic cerebrospinal venous insufficiency (CCSVI). He found CCSVI in all patients with MS in his study, performed a surgical procedure, later called in the media the "liberation procedure" to correct it, and claimed that 73% of participants improved.[114] This theory received significant attention in the media and among those with MS, especially in Canada.[115] Concerns have been raised with Zamboni's research as it was neither blinded nor controlled, and its assumptions about the underlying cause of the disease is not backed by known data.[116] Also, further studies have either not found a similar relationship or found one that is much less strong one,[117] raising serious objections to the hypothesis.[118] The "liberation procedure" has been criticized for resulting in serious complications and deaths with unproven benefits.[116] It is, thus, as of 2013 not recommended for the treatment of MS.[119] Additional research investigating the CCSVI hypothesis are under way.[120]

More here:
Multiple sclerosis - Wikipedia, the free encyclopedia

Recommendation and review posted by simmons

CTL019 is a clinical trial of T cell therapyfor patients with B cell cancers such as acute lymphoblastic leukemia (ALL), B cell non-Hodgkin lymphoma (NHL), and the adult disease chronic lymphocytic leukemia (CLL). At this time, The Children's Hospital of Philadelphia is the only hospital enrolling pediatric patientson this trial.

In July 2014, CTL019 was awarded Breakthrough Therapy designation by the U.S. Food and Drug Administration for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia (ALL). The investigational therapy is the first personalized cellular therapy for the treatment of cancer to receive this important classification.

In this clinical trial, immune cells called T cells are taken from a patient's own blood. These cells are genetically modified to express a protein which will recognize and bind to a target called CD19, which is found on cancerous B cells. This is how T cell therapy works:

30 patients with acute lymphoblastic leukemia (25 children and 5 adults) have been treatedusing T cell therapy.Of those patients:

The most recent results were published in The New England Journal of Medicine in October 2014. Scientists at The Childrens Hospital of Philadelphia and the University of Pennsylvania are very hopeful that CTL019 could in the future be an effective therapy for patients with B cell cancers. However, because so few patients have been treated, and because those patients have been followed for a relatively shorttime,it is critical that more adult and pediatric patients are enrolled in the study to determine whether a larger group of patients with B cell cancers will have the same response, and maintain that response.

At this point CHOP's capability to enroll patients is limited because of the need to manufacture the T cell product used in this therapy. Our goal is to boost enrollment soon, by increasing our manufacturing capabilities and by broadening this study to other pediatric hospitals.

T cell therapy is a treatment for children and adolescents with fairly advanced B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas, but not other leukemias or pediatric cancers. It is an option for those patients who have very resistant ALL.

Roughly 85 percent of ALL cases are treated very successfully with standard chemotherapy. For the remaining 15 percent of cases, representing a substantial number of children in the United States, chemotherapy only works temporarily or not at all. This is not a treatment for newly diagnosed leukemia, only for patients whose leukemia is not responding to chemotherapy,and whose disease has come back after a bone marrow transplant.

It is important to note that while results of this study are encouraging, it is still very early in testing and that not all children who qualify for the trial will have the same result.

Referring physicians and families are encouraged to consider the potential benefits of clinical trials early in the cancer treatment process. In the case of CTL019 and other cell therapies, it is critical that cells are collected from the patient before they are too sick. Also, intensive chemotherapy will decrease the number of normal T cells we need to collect from the patient.

While most childhood cancers are cured by standard treatment protocols, learning about the many new experimental therapies available at CHOP soon after diagnosis may keep more options open for patients who relapse.

Stephan Grupp, MD, PhD, leads CTL019 efforts at The Childrens Hospital of Philadelphia. His research builds on an ongoing collaboration with the team that originally designed the CTL019 cells as a treatment for B cell leukemias, and first used the cell therapy against chronic lymphocytic leukemia (CLL) in adults.

Richard Aplenc, MD, PhD, MSCE, and Susan Rheingold, MD,are the first points of contact for any pediatric patient considering T cell therapy,andwill help families navigate the process of coming to CHOP for a second opinion. These CHOP oncologists are among the nation's leading experts in pediatric leukemia.

Carl H. June, MD, of the Perelman School of Medicine at the University of Pennsylvania, led the research group that announced unprecedented results in August 2011 in treating three adult patients with advanced cases of CLL.

Dr. Grupp and his colleagues adapted the CTL019 treatment to combat ALL, the most common childhood cancer. Initial results of this clinical trial were published by The New England Journal of Medicine on March 25, 2013.

The CTL019 therapy represents a new approach to cancer treatment called immunotherapy or cell therapy. The idea behind immunotherapy is to use our bodies own immune cells, which fight infection, to kill off cancer cells.

Cancer researchers have spent more than a decade studying immunotherapy as a possible treatment for cancer. Over the years they solved many of the problems associated with this type of treatment, including learning how to induce the cells to recognize cancer and how to grow cells in a lab in way that it would be safe to re-infuse them into patients.

The final hurdle in this research was the most difficult to jump: learning how to engineer a cell that would continue to grow in the body for more than a few days, and then remain in the body for an extended period of time to continue controlling a patients disease for the long-term. CTL019 reflects a solution to this last problem, making the trial unique compared to earlier forms of cell therapy.

In using CTL019 cells to treat his first pediatric patient, Dr. Grupp found that the very activity that destroyed leukemia cells also stimulated a highly activated immune response called cytokine release syndrome. The child became very ill and had to be admitted to the intensive care unit.

Dr. Grupp and his team decided to counteract these toxic side effects by using two immunomodulating drugs that blunted the overactive immune response and rapidly relieved the childs treatment-related symptoms. These results were effective enough that this approach is now being successfully incorporated into CTL019 treatments for adults as well.

Dr. Grupp presented an abstract describing this treatment of CTL019-associated cytokine release syndrome at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2012.

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T Cell Therapy (CTL019) | The Children's Hospital of ...

Recommendation and review posted by simmons

Hypogonadism can occur for a number of reasons. Certain men have hypogonadism since birth while others may develop this condition later in life. Two types of hypogonadism are:

Primary hypogonadism (testicular failure) - Low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.

Hypogonadotropic hypogonadism - Idiopathic gonadotropin or LHRH deficiency or pituitary - hypothalamic injury from tumors, trauma, or radiation.

Characterized by low serum testosterone levels, but with gonadotropins in the normal or low range. Men develop testicular suppression with decreased libido, impotence, decreased ejaculate volume, loss of body and facial hair, weakness, fatigue and often anemia. On testing, blood levels of testosterone are low and should be replaced. In the United States, testosterone may begiven as a bi-weekly intramuscular injection, a patch form, or a gel preparation. In other countries, oral preparations of testosterone are available.

Women develop ovarian suppression with irregular periods or absence of periods (amenorrhea), infertility, decreased libido, decreased vaginal secretions, breast atrophy, and osteoporosis. Blood levels of estradiol are low. Estrogen should be replaced and can be given orally as Premarin or Estrace, or can be given as a patch applied twice weekly. Women taking estrogen also need to take progesterone replacement (unless they have undergone a hysterectomy). Annual pap smears and mammograms are mandatory.

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If you are a nurse or medical professional, register for PNA CEU Membership and earn CEU credits to learn about the symptoms, diagnosis and treatment options for patients with pituitary disorders. Help PNA reduce the time it takes for patients to get an accurate diagnosis.

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Hypogonadism | Disorders | Knowledge Base

Recommendation and review posted by Bethany Smith

George Reed's heart wasn't doing so well: He's 71, and after suffering a heart attack years earlier, Reed had undergone open heart surgery and was put on multiple medications. But nothing seemed to help the dizziness and chest pain he experienced daily.

"I'd get dizzy and just fall over -- sometimes twice a day. I would run my head into the concrete. I was a bloody mess," the Perry, Ohio, native says. Despite his doctor's best efforts, Reed continued to experience angina, a type of chest pain that occurs when the heart doesn't get enough oxygen-rich blood; it can be accompanied by dizziness. So when he was recommended for an experimental study that would inject his own stem cells into his damaged heart, Perry signed on. "I needed something to change," he says.

Researchers gave Reed a drug commonly used in bone marrow transplants that stimulates the marrow to make more stem cells. Then they removed some of Reed's blood, isolated the stem cells and injected them into and around the damaged areas of his heart.

"The goal was to grow new blood vessels with stem cells from the patient's own body," says Dr. Tim Henry, a co-author of the study and director of research at the Minneapolis Heart Institute Foundation.

Within a few months, Reed, along with many of the other 100 or so patients at 26 hospital centers who'd received this stem cell treatment, reported feeling better than he had in years.

"When it started kicking in, I felt like a kid. I felt good," Reed says. He wasn't passing out and falling down anymore.

For Jay Homstad, 49, who was part of the Minnesota branch of the study, he felt the changes most in his ability to walk and be active.

"My activity level increased tenfold. Before, I struggled with chest pain every day. My activity level was about as close to zero as you could get. Now I can participate ... just in life. It may sound silly, but the best part is that in the wintertime I could go out and walk with my dog along the Red River. When you're walking through snow that is waist deep, you can tell there's a difference," Homstad says.

Homstad had had about a dozen surgeries and nine stents put in before he enrolled in the study, but he still struggled with angina daily. Within a few months of the stem cell shots, he could walk farther, and his chest pain subsided and was kept at bay for nearly four years.

"These are people for whom other treatment hasn't worked. They're debilitated by their chest pain, but their other options are really limited, that's why we picked them," says Henry. If the positive results seen in this study hold up in the next phase of the study, which is set to begin enrollment in the fall, this type of cardiac stem cell injection could be added to the arsenal of weapons against angina. The upcoming phase three trial has already been approved by the Food and Drug Administration.

Shot to the Heart, Before It's too Late

While several smaller studies have suggested that injecting stem cells into damaged heart tissue might be effective, this study, in its scope and rigor, was the first of its kind. A total of 167 patients were recruited and randomly assigned to receive a lower dose of stem cells, a higher dose or a placebo. The patients didn't know who got what treatment, and neither did the doctors treating them.

When tracked for a year after the injection, patients who received the lower dose of stem cells could last longer during a treadmill exercise than those who had received the placebo, and they averaged seven fewer episodes of chest pain in a week. To put this in perspective, a popular drug to treat angina, Ranolazine, reduced chest pain by fewer than two episodes a week in clinical trials.

Although the goal of the stem cell shots was to grow new blood vessels, it's impossible to tell if these stem cells were actually growing into blood vessels or if they were just triggering some other kind of healing process in the body, Henry says. Tests in animal models, however, do suggest that new blood vessels are forming, says Dr. Marco Costa, a co-author of the study and George Reed's doctor at UH Case Medical Center in Cleveland.

For now, the only gauge of the injections is improvement in symptoms.

Despite the positive results of the study, cardiologists remain "cautiously optimistic" about stem cells as a treatment for angina.

"The number of patients is relatively small, so this trial would probably not carry much scientific weight," says Dr. Jeff Brinker, a professor of cardiology at Johns Hopkins University. The results did justify the next, larger trial, he says, which would offer more answers as to whether this treatment is actually working the way researchers suspect.

The fact that lower doses of stem cells were puzzlingly more effective than larger ones is cause for caution, says Dr. Steve Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

"The jury is still out for stem cell therapies to treat heart disease," says Dr. Cam Paterson, a cardiologist at the University of North Carolina at Chapel Hill.

But the results so far provide cautious hope for heart patients like George Reed and Jay Homstad.

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Injecting the Heart With Stem Cells Helps Chest Pain - ABC ...

Recommendation and review posted by Bethany Smith

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Stem Cell Research is an amazing field right now, and promises to be a powerful and potent tool to help us live longer and healthier lives. Just last month, for example, Stem Cell Therapy was used to restore sight in patients with severe retinal deterioration, allowing them to see clearer than they had in years, or even decades.

Now, there is another form of Stem Cell Treatment on the horizonthis one of a very different form. Stem Cells have now been used as a mechanism to deliver medical treatment designed to eliminate cancer cells, even in hard to reach places. One issue with current cancer treatments is that, treatments that are effective at treating tumors on the surface of the brain cannot be performed safely when the tumor is deeper within the brains tissues.

Stem Cells have the fantastic ability to transform into any other kind of cell within the human body, given the appropriate stimulation. As of today, most of these cells come from Embryonic Lines, but researchers are learning how to backwards engineer cells in the human body, reverting them back to their embryonic state. These cells are known as Induced Pluripotent Stem Cells.

How Does This Stem Cell Cancer Treatment Work?

Using genetic engineering, it is possible to create stem cells that are designed to release a chemical known as Pseudomonas Exotoxin, which has the ability to destroy certain tumor cells in the human brain.

What is Pseudomonas Exotoxin?

Pseudomonas Exotoxin is a compound that is naturally released by a form of bacteria known as Pseudomonas Aeruginosa. This chemical is toxic to brain tumor cells because it prevents polypeptides from growing longer, essentially preventing the polypeptides from growing and reproducing. When used in a specific manner, this toxin has the ability to destroy cancerous and malignant tissue without negatively impacting healthy tissue. In addition to its potential as a cancer treatment, there is also evidence that the therapy could be used for the treatment of Hepatitis B.

PE and Similar Toxins Have been Used Therapeutically in the Past

As of now, this chemical, which we will refer to for the rest of the article as PE, has been used as a cancer treatment before, but there are major limitations regarding the use of PE for particular cancers, not because of the risks of the treatment, but because of the lack of an effective method to deliver the medication to where it is needed.

For example, similar chemicals have been highly effective in the treatment of a large number of blood cancers, but havent been nearly as effective in larger, more inaccessible tumors. The chemicals break down or become metabolized before they can fully do their job.

How do Stem Cells Increase the Effectiveness of PE Cancer Treatment

Right now, PE has to be created in a laboratory before it is administered, which is not very effective for these embedded cancers. By using Stem Cells as an intermediary, it is possible to deliver the medication to deeper areas of the brain more effectively, theoretically highly increasing the efficacy of the treatment.

The leader of this Stem Cell Research is Harvard researcher Dr. Khalis Shah. His goal was to find an effective means to treat these deep brain tumors which are not easily treated by methods available today. In utilizing Stem Cells, Dr. Shah has potentially found a means by which the stem cells can constantly deliver this Cancer Toxin to the tumor area. The cells remain active and are fed by the body, which allows them to provide a steady stream of treatment that is impossible to provide via any other known method.

This research is still in its early stages, and has not yet reached human trials, but in mice, the PE Toxin worked exactly as hypothesized and was able to starve out tumors by preventing them from replicating effectively.

Perhaps this might seem a bit less complicated than it actually is. One of the major hurdles that had to be overcome was that this Toxin would normally be strong enough to kill the cell that hosted it. In order for the Stem Cells to release the cancer, they had to be able to withstand the effects of PE, themselves. Using genetic engineering, Dr. Shah and his associates were able to create a cell that is capable of both producing and withstanding the effects of the toxin.

Stem Cell delivered medical therapy is a 21st century form of medical treatment that researchers are just beginning to learn how to effectively utilize. Essentially, this treatment takes a stem cell and converts it into a unique symbiotic tool capable of feeding off of the host for energy in order to perform a potentially life-saving function. Its really quite fascinating.

How Does PE Not Damage or Kill Brain Cells Indiscriminately?

You might be concerned about the idea of a patient having a toxin injected into the brain to cure a disease. It sounds almost like a dangerous, tribal, homeopathic remedy. In reality, the researchers have been able to harness the destructive power of the toxin and re-engineer it so that it directly targets cancer cells while having limited negative effects on healthy, non-cancerous tissue.

The toxin does its damage after it has been absorbed by a cell. By retooling the toxin so that it does not readily absorb into healthy cells, the dangers associated with having such a potentially dangerous toxin in the brain are seriously and significantly mitigated.

Beyond that, Dr. Shah and his associates have been able to take steps to effectively turn off PE while it is inside the host stem cell, and only activates when it has entered the cancerous tissue. Dr. Shah explains that, although this research has only been conducted in animal subjects, there is no known reason why the effectiveness and safety of the treatment would not be applicable to human patients.

In this treatment, surgeons remove as much of the tumor as possible from the brain, and insert the engineered Stem Cells submerged in a sterile gel in the area where the tumor was removed or partially still exists. Researchers found that, when they used this treatment on laboratory rats, they could tell through imaging and analysis that the modified PE toxin effectively killed the cancer cells, and that this cancer treatment effectively lengthened the life of the rat, as compared to control subjects.

Whats the Next Step?

Of course, cancer treatment is far more complex than a single treatment, no matter how effective that treatment may be. Because human cancer treatment is a comprehensive therapy approach, the end goal of this research is to create a form of therapy in which the method used in animal subjects is combined with other existing approaches, increasing and maximizing the effectiveness of the comprehensive treatment.

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A recent change in how well we understand stem cells may make it easier for scientists and researchers to gather stem cells for use in scientific research as well as medical application. A new study was released in the research publication, Cell, which was performed by representatives from the University of California San Francisco.

One of the issues which hinder the use of stem cells as a more widespread treatment or field of research is that researchers and patients have a bottleneck of available healthy stem cell lines which can be used for research. Researchers hope that this new discovery will allow future scientific discoveries and applications in the areas of creating new and healthy tissue for patients with kidney failure or any other form of organ tissue failure. The future of medical therapy lies with Stem Cell Research, but many other forms of treatment, including Hormone Replacement Therapy, are already in practice today.

Researchers have discovered that it is possible to essentially flip a switch in an adult cell, reverting it back to the preliminary state at which cells existed in one of the earliest stages of developmentthe embryonic stem cell. Medical researchers hypothesize that Stem Cell treatments could be used for a variety of medical health issues which plague the world today, including kidney failure, liver disease, and Type-1 and Type-2 Diabetes.

Use of Embryonic Stem Cells Contentious

There is an ethical issue in Stem Cell Research today. Many Pro-Life Advocates are vociferously against the use of Embryonic Stem Cells harvested from procedures such as fertility treatments designed for conception. They believe that the use of embryonic stem cells harvested from donors and couples looking to conceive is unethical.

Using current research, it may be possible to bypass this ethical quandary completely by using adult cells and converting them into embryonic stem cells. Furthermore, because these stem cells are genetic derivatives of the patient from which the adult cells were harvested, this potentially paves the way for patient-specific medical treatments using stem cells.

After adult cells have been converted back into Embryonic Stem Cells, it will be possible to convert them into any possible cell that the patient needs or would benefit from.

Hijacking the Blueprint of the Cell Allows Scientists to Revert Adult Cells to their Earliest State

Researchers have increased the capacity to produce Embryonic Stem Cells by identifying previously unrecognized biochemical processes which tell human cells how to develop. In essence, researchers have discovered how the body blueprints cells, and can change the blueprints so that a new cell is made.

By utilizing these newly recognized pathways, it is possible to create new stem cells more quickly than ever before. One of the researchers explains the implications of this research. Dr. Miguel Ramalho-Santos is an associate professor of obstetrics, medicine, and cancer research at the University of California San Francisco. Dr. Ramalho-Santos is also a member of the Broad Center of Regenerative Medicine and Stem Cell Research.

He explains that these stem cell discoveries have the ability to alter the way that the medical sciences can take advantage of stem cells with regard to both cancer research and regenerative medicine. Dr. Ramalho-Santos was the lead researcher for this study, and the research was largely funded by the Director of the National Institutes of Health New Innovator Award, granted to promising young researchers which are leading highly innovative and promising medical research studies.

Dr. Ramalho-Santos research builds off of earlier research which discovered that it was possible to take adult cells and turn them back into embryonic stem cells. These stem cells dont have any inherent aging processes, and they can be turned into any other kind of tissue. In the process of this conversion, the adult cells lose all of their unique characteristics, leaving them in an ultimately immature and malleable state.

This earlier research was conducted by researchers from UC San Francisco in partnership with Dr. Shinya Yamanaka from Kyoto University and Gladstone Institutes. These entities all gained a piece of the Nobel Prize in Physiology or Medicine from their part in the study.

Pluripotent Stem Cells vs. Embryonic Stem Cells

Thus far, weve described these cells as Embryonic Stem Cells, but in fact, the more accurate term for these cells are Induced Pluripotent Stem Cells (IPS). These cells are biologically and functionally similar to Embryonic Stem Cells, but have a different name because they are sourced from adult cells. The difference between Induced Pluripotent Stem Cells and Embryonic Stem Cells is that Induced Pluripotent Stem Cells do seem to retain some of the characteristics of their previous state, which appears to limit their ability to convert into any other type of cell. This new research identifies new pathways by which it may be possible to increase the number of cells that an individual IPS Cell can turn into, perhaps allowing them to convert into any other kind of human cell.

Induced Pluripotent Stem Cells are not explicitly considered an alternative to Embryonic Stem Cells, but are considered a different approach to produce similar cells. If researchers fully uncover the mechanisms of how to reprogram these cells, it will lower many barriers to stem cell research and the availability of stem cell treatments.

As of today, researchers have figured out how to make these Induced Pluripotent Stem Cells, but the percentage of adult cells which are reverted successfully is quite low, and frequently, these cells still show some aspects of specialization, which limits their use.

How Do Scientists Make Stem Cells From Adult Cells?

There are genes within every cell which have the ability to induce pluripotency, reverting the cell to an earlier stage of specialization. The initial stage of this process is the result of activating Yamanaka Factors, specific genes that initiate this reversion process.

As of today, this process of de-maturation is not completely understood, and researchers realized from the start that the cells they created were not truly identical to Embryonic Stem Cells, because they still showed signs of their former lives, which often prevented them from being successfully reprogrammed.

The new research conducted by Dr. Ramalho-Santos appears to increase our knowledge regarding how these cells work, and how to program them more effectively. Dr. Ramalho-Santos and his team discovered more genes associated with these programming/reprogramming processes, and by manipulating them, they have increased the viability and range of particular stem cells.

It appears that these genetic impulses are constantly at play to maintain the structure and function of a cell, and that by systematically removing these safeguards, it is possible to increase the ability to alter these cells.

This research increases researchers ability to produce these stem cells, by increasing the ability of medical scientists to produce adequate numbers of stem cells, while also increasing the range of potential treatment options by more effectively inducing the total pluripotency which is available in Embryonic Stem Cells. This research may also help scientists treat certain forms of cancer which are the result of malfunctions of these genes.

Introduction

[Note: Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.]

[Note: Many of the genes described in this summary are found in the Online Mendelian Inheritance in Man (OMIM) database. When OMIM appears after a gene name or the name of a condition, click on OMIM for a link to more information.]

The genetics of skin cancer is an extremely broad topic. There are more than 100 types of tumors that are clinically apparent on the skin; many of these are known to have familial components, either in isolation or as part of a syndrome with other features. This is, in part, because the skin itself is a complex organ made up of multiple cell types. Furthermore, many of these cell types can undergo malignant transformation at various points in their differentiation, leading to tumors with distinct histology and dramatically different biological behaviors, such as squamous cell carcinoma (SCC) and basal cell cancer (BCC). These have been called nonmelanoma skin cancers or keratinocytic cancers.

Figure 1 is a simple diagram of normal skin structure. It also indicates the major cell types that are normally found in each compartment. Broadly speaking, there are two large compartmentsthe avascular cellular epidermis and the vascular dermiswith many cell types distributed in a largely acellular matrix.[1]

Figure 1. Schematic representation of normal skin. The relatively avascular epidermis houses basal cell keratinocytes and squamous epithelial keratinocytes, the source cells for BCC and SCC, respectively. Melanocytes are also present in normal skin and serve as the source cell for melanoma. The separation between epidermis and dermis occurs at the basement membrane zone, located just inferior to the basal cell keratinocytes.

The outer layer or epidermis is made primarily of keratinocytes but has several other minor cell populations. The bottom layer is formed of basal keratinocytes abutting the basement membrane. The basement membrane is formed from products of keratinocytes and dermal fibroblasts, such as collagen and laminin, and is an important anatomical and functional structure. As the basal keratinocytes divide and differentiate, they lose contact with the basement membrane and form the spinous cell layer, the granular cell layer, and the keratinized outer layer or stratum corneum.

The true cytologic origin of BCC remains in question. BCC and basal cell keratinocytes share many histologic similarities, as is reflected in the name. Alternatively, the outer root sheath cells of the hair follicle have also been proposed as the cell of origin for BCC.[2] This is suggested by the fact that BCCs occur predominantly on hair-bearing skin. BCCs rarely metastasize but can invade tissue locally or regionally, sometimes following along nerves. A tendency for superficial necrosis has resulted in the name rodent ulcer.[3]

Some debate remains about the origin of SCC; however, these cancers are likely derived from epidermal stem cells associated with the hair follicle.[4] A variety of tissues, such as lung and uterine cervix, can give rise to SCC, and this cancer has somewhat differing behavior depending on its source. Even in cancer derived from the skin, SCC from different anatomic locations can have moderately differing aggressiveness; for example, SCC from glabrous (smooth, hairless) skin has a lower metastatic rate than SCC arising from the vermillion border of the lip or from scars.[3]

Additionally, in the epidermal compartment, melanocytes distribute singly along the basement membrane and can transform into melanoma. Melanocytes are derived from neural crest cells and migrate to the epidermal compartment near the eighth week of gestational age. Langerhans cells, or dendritic cells, are a third cell type in the epidermis and have a primary function of antigen presentation. These cells reside in the skin for an extended time and respond to different stimuli, such as ultraviolet radiation or topical steroids, which cause them to migrate out of the skin.[5]

The dermis is largely composed of an extracellular matrix. Prominent cell types in this compartment are fibroblasts, endothelial cells, and transient immune system cells. When transformed, fibroblasts form fibrosarcomas and endothelial cells form angiosarcomas, Kaposi sarcoma, and other vascular tumors. There are a number of immune cell types that move in and out of the skin to blood vessels and lymphatics; these include mast cells, lymphocytes, mononuclear cells, histiocytes, and granulocytes. These cells can increase in number in inflammatory diseases and can form tumors within the skin. For example, urticaria pigmentosa is a condition that arises from mast cells and is occasionally associated with mast cell leukemia; cutaneous T-cell lymphoma is often confined to the skin throughout its course. Overall, 10% of leukemias and lymphomas have prominent expression in the skin.[6]

Epidermal appendages are also found in the dermal compartment. These are derivatives of the epidermal keratinocytes, such as hair follicles, sweat glands, and the sebaceous glands associated with the hair follicles. These structures are generally formed in the first and second trimesters of fetal development. These can form a large variety of benign or malignant tumors with diverse biological behaviors. Several of these tumors are associated with familial syndromes. Overall, there are dozens of different histological subtypes of these tumors associated with individual components of the adnexal structures.[7]

Finally, the subcutis is a layer that extends below the dermis with varying depth, depending on the anatomic location. This deeper boundary can include muscle, fascia, bone, or cartilage. The subcutis can be affected by inflammatory conditions such as panniculitis and malignancies such as liposarcoma.[8]

These compartments give rise to their own malignancies but are also the region of immediate adjacent spread of localized skin cancers from other compartments. The boundaries of each skin compartment are used to define the staging of skin cancers. For example, an in situ melanoma is confined to the epidermis. Once the cancer crosses the basement membrane into the dermis, it is invasive. Internal malignancies also commonly metastasize to the skin. The dermis and subcutis are the most common locations, but the epidermis can also be involved in conditions such as Pagetoid breast cancer.

The skin has a wide variety of functions. First, the skin is an important barrier preventing extensive water and temperature loss and providing protection against minor abrasions. These functions can be aberrantly regulated in cancer. For example, in the erythroderma associated with advanced cutaneous T-cell lymphoma, alterations in the regulations of body temperature can result in profound heat loss. Second, the skin has important adaptive and innate immunity functions. In adaptive immunity, antigen-presenting cells engender a TH1, TH2, and TH17 response.[9] In innate immunity, the immune system produces numerous peptides with antibacterial and antifungal capacity. Consequently, even small breaks in the skin can lead to infection. The skin-associated lymphoid tissue is one of the largest arms of the immune system. It may also be important in immune surveillance against cancer. Immunosuppression, which occurs during organ transplant, is a significant risk factor for skin cancer. The skin is significant for communication through facial expression and hand movements. Unfortunately, areas of specialized function, such as the area around the eyes and ears, are common places for cancer to occur. Even small cancers in these areas can lead to reconstructive challenges and have significant cosmetic and social ramifications.[1]

While the appearance of any one skin cancer can vary, there are general physical presentations that can be used in screening. BCCs most commonly have a pearly rim (see Figure 3) or can appear somewhat eczematous. They often ulcerate (see Figure 3). SCCs frequently have a thick keratin top layer (see Figure 4). Both BCCs and SCCs are associated with a history of sun-damaged skin. Melanomas are characterized by asymmetry, border irregularity, color variation, a diameter of more than 6 mm, and evolution (ABCDE criteria). (Refer to What Does Melanoma Look Like? on NCIs website for more information about the ABCDE criteria.) Photographs representing typical clinical presentations of these cancers are shown below.

Enlarge

Figure 2. Superficial basal cell carcinoma (left panel) and nodular basal cell carcinoma (right panel).

Enlarge

Figure 3. Ulcerated basal cell carcinoma (left panel) and ulcerated basal cell carcinoma with characteristic pearly rim (right panel).

Enlarge

Figure 4. Squamous cell carcinoma on the face with thick keratin top layer (left panel) and squamous cell carcinoma on the leg (right panel).

Enlarge

Figure 5. Melanomas with characteristic asymmetry, border irregularity, color variation, and large diameter.

Basal cell carcinoma (BCC) is the most common malignancy in people of European descent, with an associated lifetime risk of 30%.[1] While exposure to ultraviolet (UV) radiation is the risk factor most closely linked to the development of BCC, other environmental factors (such as ionizing radiation, chronic arsenic ingestion, and immunosuppression) and genetic factors (such as family history, skin type, and genetic syndromes) also potentially contribute to carcinogenesis. In contrast to melanoma, metastatic spread of BCC is very rare and typically arises from large tumors that have evaded medical treatment for extended periods of time. BCCs can invade tissue locally or regionally, sometimes following along nerves. A tendency for superficial necrosis has resulted in the name rodent ulcer. With early detection, the prognosis for BCC is excellent.

Sun exposure is the major known environmental factor associated with the development of skin cancer of all types. There are different patterns of sun exposure associated with each major type of skin cancer (BCC, squamous cell carcinoma [SCC], and melanoma).

While there is no standard measure, sun exposure can be generally classified as intermittent or chronic, and the effects may be considered acute or cumulative. Intermittent sun exposure is obtained sporadically, usually during recreational activities, and particularly by indoor workers who have only weekends or vacations to be outdoors and whose skin has not adapted to the sun. Chronic sun exposure is incurred by consistent, repetitive sun exposure, during outdoor work or recreation. Acute sun exposure is obtained over a short time period on skin that has not adapted to the sun. Depending on the time of day and a persons skin type, acute sun exposure may result in sunburn. In epidemiology studies, sunburn is usually defined as burn with pain and/or blistering that lasts for 2 or more days. Cumulative sun exposure is the additive amount of sun exposure that one receives over a lifetime. Cumulative sun exposure may reflect the additive effects of intermittent sun exposure, chronic sun exposure, or both.

Specific patterns of sun exposure appear to lead to different types of skin cancer among susceptible individuals. Intense intermittent recreational sun exposure has been associated with melanoma and BCC,[2,3] while chronic occupational sun exposure has been associated with SCC. Given these data, dermatologists routinely counsel patients to protect their skin from the sun by avoiding mid-day sun exposure, seeking shade, and wearing sun-protective clothing, although evidence-based data for these practices are lacking. The data regarding skin cancer risk reduction by regular sunscreen use are variable. One randomized trial of sunscreen efficacy demonstrated statistically significant protection for the development of SCC but no protection for BCC,[4] while another randomized study demonstrated a trend for reduction in multiple occurrences of BCC among sunscreen users [5] but no significant reduction in BCC or SCC incidence.[6]

Level of evidence (sun-protective clothing, avoidance of sun exposure): 4aii

Level of evidence (sunscreen): 1aii

Tanning bed use has also been associated with an increased risk of BCC. A study of 376 individuals with BCC and 390 control subjects found a 69% increased risk of BCC in individuals who had ever used indoor tanning.[7] The risk of BCC was more pronounced in females and individuals with higher use of indoor tanning.[8]

Environmental factors other than sun exposure may also contribute to the formation of BCC and SCC. Petroleum byproducts (e.g., asphalt, tar, soot, paraffin, and pitch), organophosphate compounds, and arsenic are all occupational exposures associated with cutaneous nonmelanoma cancers.[9-11]

Arsenic exposure may occur through contact with contaminated food, water, or air. While arsenic is ubiquitous in the environment, its ambient concentration in both food and water may be increased near smelting, mining, or coal-burning establishments. Arsenic levels in the U.S. municipal water supply are tightly regulated; however, control is lacking for potable water obtained through private wells. As it percolates through rock formations with naturally occurring arsenic, well water may acquire hazardous concentrations of this material. In many parts of the world, wells providing drinking water are contaminated by high levels of arsenic in the ground water. The populations in Bangladesh, Taiwan, and many other locations have high levels of skin cancer associated with elevated levels of arsenic in the drinking water.[12-16] Medicinal arsenical solutions (e.g., Fowlers solution and Bells asthma medication) were once used to treat common chronic conditions such as psoriasis, syphilis, and asthma, resulting in associated late-onset cutaneous malignancies.[17,18] Current potential iatrogenic sources of arsenic exposure include poorly regulated Chinese traditional/herbal medications and intravenous arsenic trioxide utilized to induce remission in acute promyelocytic leukemia.[19,20]

Aerosolized particulate matter produced by combustion of arsenic-containing materials is another source of environmental exposure. Arsenic-rich coal, animal dung from arsenic-rich regions, and chromated copper arsenatetreated wood produce airborne arsenical particles when burned.[21-23] Burning of these products in enclosed unventilated settings (such as for heat generation) is particularly hazardous.[24]

Clinically, arsenic-induced skin cancers are characterized by multiple recurring SCCs and BCCs occurring in areas of the skin that are usually protected from the sun. A range of cutaneous findings are associated with chronic or severe arsenic exposure, including pigmentary variation (poikiloderma of the skin) and Bowen disease (SCC in situ).[25]

However, the effect of arsenic on skin cancer risk may be more complex than previously thought. Evidence from in vivo models indicate that arsenic, alone or in combination with itraconazole, can inhibit the hedgehog pathway in cells with wild-type or mutated Smoothened by binding to GLI2 proteins; in this way, these drugs demonstrated inhibition of BCC growth in these animal models.[26,27] Additionally, the effect of arsenic on skin cancer risk may be modified by certain variants in nucleotide excision repair genes (xeroderma pigmentosum [XP] types A and D).[28]

The high-risk phenotype consists of individuals with the following physical characteristics:

Specifically, people with more highly pigmented skin demonstrate lower incidence of BCC than do people with lighter pigmented skin. Individuals with Fitzpatrick skin types I or II were shown to have a twofold increased risk of BCC in a small case-control study.[29] (Refer to the Pigmentary characteristics section in the Melanoma section of this summary for a more detailed discussion of skin phenotypes based upon pigmentation.) Blond or red hair color was associated with increased risk of BCC in two large cohorts: the Nurses Health Study and the Health Professionals Follow-Up Study.[30]

Immunosuppression also contributes to the formation of nonmelanoma (keratinocyte) skin cancers. Among solid-organ transplant recipients, the risk of SCC is 65 to 250 times higher, and the risk of BCC is 10 times higher than in the general population.[31-33] Nonmelanoma skin cancers in high-risk patients (i.e., solid-organ transplant recipients and chronic lymphocytic leukemia patients) occur at a younger age and are more common, more aggressive, and have a higher risk of recurrence and metastatic spread than nonmelanoma skin cancers in the general population.[34,35] Among patients with an intact immune system, BCCs outnumber SCCs by a 4:1 ratio; in transplant patients, SCCs outnumber BCCs by a 2:1 ratio.

This increased risk has been linked to the level of immunosuppression and UV exposure. As the duration and dosage of immunosuppressive agents increases, so does the risk of cutaneous malignancy; this effect is reversed with decreasing the dosage of, or taking a break from, immunosuppressive agents. Heart transplant recipients, requiring the highest rates of immunosuppression, are at much higher risk of cutaneous malignancy than liver transplant recipients, in whom much lower levels of immunosuppression are needed to avoid rejection.[31,36] The risk appears to be highest in geographic areas of high UV radiation exposure: when comparing Australian and Dutch organ transplant populations, the Australian patients carried a fourfold increased risk of developing SCC and a fivefold increased risk of developing BCC.[37] This speaks to the importance of rigorous sun avoidance among high-risk immunosuppressed individuals.

Individuals with BCCs and/or SCCs report a higher frequency of these cancers in their family members than do controls. The importance of this finding is unclear. Apart from defined genetic disorders with an increased risk of BCC, a positive family history of any skin cancer is a strong predictor of the development of BCC.

A personal history of BCC or SCC is strongly associated with subsequent BCC or SCC. There is an approximate 20% increased risk of a subsequent lesion within the first year after a skin cancer has been diagnosed. The mean age of occurrence for these nonmelanoma skin cancers is the mid-60s.[38-43] In addition, several studies have found that individuals with a history of skin cancer have an increased risk of a subsequent diagnosis of a noncutaneous cancer;[44-47] however, other studies have contradicted this finding.[48-51] In the absence of other risk factors or evidence of a defined cancer susceptibility syndrome, as discussed below, skin cancer patients are encouraged to follow screening recommendations for the general population for sites other than the skin.

Mutations in the gene coding for the transmembrane receptor protein PTCH1, or PTCH, are associated with basal cell nevus syndrome (BCNS) and sporadic cutaneous BCCs. PTCH1, the human homolog of the Drosophila segment polarity gene patched (ptc), is an integral component of the hedgehog signaling pathway, which serves many developmental (appendage development, embryonic segmentation, neural tube differentiation) and regulatory (maintenance of stem cells) roles.

In the resting state, the transmembrane receptor protein PTCH1 acts catalytically to suppress the seven-transmembrane protein Smoothened (Smo), preventing further downstream signal transduction.[52] Stoichiometric binding of the hedgehog ligand to PTCH1 releases inhibition of Smo, with resultant activation of transcription factors (GLI1, GLI2), cell proliferation genes (cyclin D, cyclin E, myc), and regulators of angiogenesis.[53,54] Thus, the balance of PTCH1 (inhibition) and Smo (activation) manages the essential regulatory downstream hedgehog signal transduction pathway. Loss-of-function mutations of PTCH1 or gain-of-function mutations of Smo tip this balance toward constitutive activation, a key event in potential neoplastic transformation.

Demonstration of allelic loss on chromosome 9q22 in both sporadic and familial BCCs suggested the potential presence of an associated tumor suppressor gene.[55,56] Further investigation identified a mutation in PTCH1 that localized to the area of allelic loss.[57] Up to 30% of sporadic BCCs demonstrate PTCH1 mutations.[58] In addition to BCC, medulloblastoma and rhabdomyosarcoma, along with other tumors, have been associated with PTCH1 mutations. All three malignancies are associated with BCNS, and most people with clinical features of BCNS demonstrate PTCH1 mutations, predominantly truncation in type.[59]

Truncating mutations in PTCH2, a homolog of PTCH1 mapping to chromosome 1p32.1-32.3, have been demonstrated in both BCC and medulloblastoma.[60,61] PTCH2 displays 57% homology to PTCH1, differing in the conformation of the hydrophilic region between transmembrane portions 6 and 7, and the absence of C-terminal extension.[62] While the exact role of PTCH2 remains unclear, there is evidence to support its involvement in the hedgehog signaling pathway.[60,63]

BCNS, also known as Gorlin Syndrome, Gorlin-Goltz syndrome, and nevoid basal cell carcinoma syndrome, is an autosomal dominant disorder with an estimated prevalence of 1 in 57,000 individuals.[64] The syndrome is notable for complete penetrance and extremely variable expressivity, as evidenced by evaluation of individuals with identical genotypes but widely varying phenotypes.[59,65] The clinical features of BCNS differ more among families than within families.[66] BCNS is primarily associated with germline mutations in PTCH1, but families with this phenotype have also been associated with alterations in PTCH2 and SUFU.[67-69]

As detailed above, PTCH1 provides both developmental and regulatory guidance; spontaneous or inherited germline mutations of PTCH1 in BCNS may result in a wide spectrum of potentially diagnostic physical findings. The BCNS mutation has been localized to chromosome 9q22.3-q31, with a maximum logarithm of the odd (LOD) score of 3.597 and 6.457 at markers D9S12 and D9S53.[64] The resulting haploinsufficiency of PTCH1 in BCNS has been associated with structural anomalies such as odontogenic keratocysts, with evaluation of the cyst lining revealing heterozygosity for PTCH1.[70] The development of BCC and other BCNS-associated malignancies is thought to arise from the classic two-hit suppressor gene model: baseline heterozygosity secondary to germline PTCH1 mutation as the first hit, with the second hit due to mutagen exposure such as UV or ionizing radiation.[71-75] However, haploinsufficiency or dominant negative isoforms have also been implicated for the inactivation of PTCH1.[76]

The diagnosis of BCNS is typically based upon characteristic clinical and radiologic examination findings. Several sets of clinical diagnostic criteria for BCNS are in use (refer to Table 1 for a comparison of these criteria).[77-80] Although each set of criteria has advantages and disadvantages, none of the sets have a clearly superior balance of sensitivity and specificity for identifying mutation carriers. The BCNS Colloquium Group proposed criteria in 2011 that required 1 major criterion with molecular diagnosis, two major criteria without molecular diagnosis, or one major and two minor criteria without molecular diagnosis.[80] PTCH1 mutations are found in 60% to 85% of patients who meet clinical criteria.[81,82] Most notably, BCNS is associated with the formation of both benign and malignant neoplasms. The strongest benign neoplasm association is with ovarian fibromas, diagnosed in 14% to 24% of females affected by BCNS.[74,78,83] BCNS-associated ovarian fibromas are more likely to be bilateral and calcified than sporadic ovarian fibromas.[84] Ameloblastomas, aggressive tumors of the odontogenic epithelium, have also been proposed as a diagnostic criterion for BCNS, but most groups do not include it at this time.[85]

Originally posted here:
IPS Cell Therapy IPS Cell Therapy

Recommendation and review posted by Bethany Smith

Top 10 list of important, easy to understand facts for patients about stem cell treatments

For better or worse, I am in the unique position of being a stem cell scientist and also a patient. Looking on the bright side this gives me a unique perspective on things.

I know there are thousands of people out there looking for more practical information about stem cell therapies and treatments. These folks understandably are using the Internet to look for some clear, good info on stem cell treatments either for themselves or their loved ones. Too often the info that is out there is either wrong, misleading, or overly complex.

So in this post I want to address this need speaking as a scientist, patient advocate and cancer survivor in the form of 10 key facts to help you guide your way through the jungle of stuff out there about stem cells.

1) Stem cells are essentially a type of drug or biological and possibly permanent in nature. Yeah, they are extremely unusual drugs, but they are drugs. The FDA considers them drugs. Unlike other drugs, once a patient receives a stem cell drug, it will not necessarily simply go away like other drugs because a stem cell drug consists of living cells that often behave in unpredictable ways. What this means is if the stem cells are doing bad things your doctor has no way to stop it.

2) Like any medical product, even aspirin, stem cells treatments will have side effects. Not maybe. Definitely. Our hope is the side effects will be relatively mild.

3) The only stem cell treatment explicitly approved by the FDA for use in the U.S. is bone marrow transplantation. What this means is that any other stem cell treatment you see advertised on Facebook or Google or elsewhere that indicates it will be given to you inside the U.S. may in fact be illegal and unsafe. The exception to this is if it is part of an FDA-approved clinical trial.

4) If you venture outside the U.S. for a stem cell treatment, use extra caution and have a knowledgeable physician inside the U.S. guiding you. We have to avoid the trap of thinking that only the U.S. can offer advanced medical treatments, but on the other hand within the U.S. you have the added safety of the FDA, which is trying to protect you. In the vast majority of other countries regulatory agencies are practically non-existent or are far less strict than the FDA.

5) Stem cells are not a cure all. I am as excited as anybody about the potential of stem cells to treat a whole bunch of diseases and injuries, but they are not some kind of miracle cure for everything. When a doctor offers to inject some kind of stem cells or a stem cell-derived product into a patient either into the bloodstream or into a specific place that is injured such as a shoulder, we just do not know at this point if it will do any good with the exception of bone marrow transplant.

6) Dont let celebrities be your guide to medical care. The number of famous people getting stem cell treatments is increasing including sports stars and politicians. Dont let what these folks do influence what you decide to do about your health. Just because they are famous do not believe for one minute that they are any more informed than you or your personal doctor about medical treatments or stem cells. If anything I think sometimes famous people are more reckless with their health than average people like you and me.

7) Reach out to scientists as a source of info. As a scientist I am always happy to hear from people outside the scientific community with questions about stem cells and other research. I cant speak for all stem cell scientists but you might be surprised at how likely it is that if you send them a very short, clear email with one or two questions that they will respond and be helpful. We cant or shouldnt offer medical advice, but we can give our perspectives on stem cell research and its clinical potential, etc. Just do not cold call scientists as you are unlikely to find them that way and even if you do, they may be cranky. Email.

8 )The people selling you non-FDA approved stem cell treatments want your money. Unlike stem cell researchers, the people out there advertising stem cell treatments that are not FDA approved are only really after one thing: your money. As such they will do their best to convince you that their treatment is safe and effective. They may offer patient testimonials either from patients who truly believe they were helped or from people who are paid to say the treatment helped them. The bottom line is that the sellers of dubious stem cell treatments simply want your money.

9) There is no such thing as completely proven safe and if something sounds too good to be true, it probably is. I am contacted fairly regularly by patients or their families and they often mention that the doctors offering stem cell treatments told them that the treatments are proven safeor that umbilical cord blood cannot harm you.or that your own stem cells cannot harm you..or that adult stem cells are harmless. Ill believe it when the FDA says it is so and you should be skeptical too.

10) The most important thing is data and you have a right to see it before treatment.Before you or a loved one get a stem cell treatment, ask two key questions. First, is the treatment FDA approved and if not, why not? Second, can you please show me the data that proves your treatment is safe and effective. See what kind of answer you get. If they criticize the FDA then that is a warning flag. If they refuse to show you data, then that is a big red warning flag. They may say it is confidential or that it is not published yet, but as a patient you have a right to see the data, assuming they have any data at all.

These facts will hopefully change over the coming years, but right now I think they represent reality. I know as patients we need hope, but these unapproved stem cell treatments will at best take your money for nothing, and at worst will endanger you or your loved ones.

The post above is for information only and is not medical advice. All medical decisions should be made by patients in consultation with their personal physicians.

See original here:
Patients guide to treatments | Knoepfler Lab Stem Cell Blog

Recommendation and review posted by Bethany Smith

Introduction

[Note: Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.]

[Note: Many of the genes described in this summary are found in the Online Mendelian Inheritance in Man (OMIM) database. When OMIM appears after a gene name or the name of a condition, click on OMIM for a link to more information.]

The genetics of skin cancer is an extremely broad topic. There are more than 100 types of tumors that are clinically apparent on the skin; many of these are known to have familial components, either in isolation or as part of a syndrome with other features. This is, in part, because the skin itself is a complex organ made up of multiple cell types. Furthermore, many of these cell types can undergo malignant transformation at various points in their differentiation, leading to tumors with distinct histology and dramatically different biological behaviors, such as squamous cell carcinoma (SCC) and basal cell cancer (BCC). These have been called nonmelanoma skin cancers or keratinocytic cancers.

Figure 1 is a simple diagram of normal skin structure. It also indicates the major cell types that are normally found in each compartment. Broadly speaking, there are two large compartmentsthe avascular cellular epidermis and the vascular dermiswith many cell types distributed in a largely acellular matrix.[1]

Figure 1. Schematic representation of normal skin. The relatively avascular epidermis houses basal cell keratinocytes and squamous epithelial keratinocytes, the source cells for BCC and SCC, respectively. Melanocytes are also present in normal skin and serve as the source cell for melanoma. The separation between epidermis and dermis occurs at the basement membrane zone, located just inferior to the basal cell keratinocytes.

The outer layer or epidermis is made primarily of keratinocytes but has several other minor cell populations. The bottom layer is formed of basal keratinocytes abutting the basement membrane. The basement membrane is formed from products of keratinocytes and dermal fibroblasts, such as collagen and laminin, and is an important anatomical and functional structure. As the basal keratinocytes divide and differentiate, they lose contact with the basement membrane and form the spinous cell layer, the granular cell layer, and the keratinized outer layer or stratum corneum.

The true cytologic origin of BCC remains in question. BCC and basal cell keratinocytes share many histologic similarities, as is reflected in the name. Alternatively, the outer root sheath cells of the hair follicle have also been proposed as the cell of origin for BCC.[2] This is suggested by the fact that BCCs occur predominantly on hair-bearing skin. BCCs rarely metastasize but can invade tissue locally or regionally, sometimes following along nerves. A tendency for superficial necrosis has resulted in the name "rodent ulcer."[3]

Some debate remains about the origin of SCC; however, these cancers are likely derived from epidermal stem cells associated with the hair follicle.[4] A variety of tissues, such as lung and uterine cervix, can give rise to SCC, and this cancer has somewhat differing behavior depending on its source. Even in cancer derived from the skin, SCC from different anatomic locations can have moderately differing aggressiveness; for example, SCC from glabrous (smooth, hairless) skin has a lower metastatic rate than SCC arising from the vermillion border of the lip or from scars.[3]

Additionally, in the epidermal compartment, melanocytes distribute singly along the basement membrane and can transform into melanoma. Melanocytes are derived from neural crest cells and migrate to the epidermal compartment near the eighth week of gestational age. Langerhans cells, or dendritic cells, are a third cell type in the epidermis and have a primary function of antigen presentation. These cells reside in the skin for an extended time and respond to different stimuli, such as ultraviolet radiation or topical steroids, which cause them to migrate out of the skin.[5]

The dermis is largely composed of an extracellular matrix. Prominent cell types in this compartment are fibroblasts, endothelial cells, and transient immune system cells. When transformed, fibroblasts form fibrosarcomas and endothelial cells form angiosarcomas, Kaposi sarcoma, and other vascular tumors. There are a number of immune cell types that move in and out of the skin to blood vessels and lymphatics; these include mast cells, lymphocytes, mononuclear cells, histiocytes, and granulocytes. These cells can increase in number in inflammatory diseases and can form tumors within the skin. For example, urticaria pigmentosa is a condition that arises from mast cells and is occasionally associated with mast cell leukemia; cutaneous T-cell lymphoma is often confined to the skin throughout its course. Overall, 10% of leukemias and lymphomas have prominent expression in the skin.[6]

Epidermal appendages are also found in the dermal compartment. These are derivatives of the epidermal keratinocytes, such as hair follicles, sweat glands, and the sebaceous glands associated with the hair follicles. These structures are generally formed in the first and second trimesters of fetal development. These can form a large variety of benign or malignant tumors with diverse biological behaviors. Several of these tumors are associated with familial syndromes. Overall, there are dozens of different histological subtypes of these tumors associated with individual components of the adnexal structures.[7]

Finally, the subcutis is a layer that extends below the dermis with varying depth, depending on the anatomic location. This deeper boundary can include muscle, fascia, bone, or cartilage. The subcutis can be affected by inflammatory conditions such as panniculitis and malignancies such as liposarcoma.[8]

These compartments give rise to their own malignancies but are also the region of immediate adjacent spread of localized skin cancers from other compartments. The boundaries of each skin compartment are used to define the staging of skin cancers. For example, an in situ melanoma is confined to the epidermis. Once the cancer crosses the basement membrane into the dermis, it is invasive. Internal malignancies also commonly metastasize to the skin. The dermis and subcutis are the most common locations, but the epidermis can also be involved in conditions such as Pagetoid breast cancer.

The skin has a wide variety of functions. First, the skin is an important barrier preventing extensive water and temperature loss and providing protection against minor abrasions. These functions can be aberrantly regulated in cancer. For example, in the erythroderma associated with advanced cutaneous T-cell lymphoma, alterations in the regulations of body temperature can result in profound heat loss. Second, the skin has important adaptive and innate immunity functions. In adaptive immunity, antigen-presenting cells engender a TH1, TH2, and TH17 response.[9] In innate immunity, the immune system produces numerous peptides with antibacterial and antifungal capacity. Consequently, even small breaks in the skin can lead to infection. The skin-associated lymphoid tissue is one of the largest arms of the immune system. It may also be important in immune surveillance against cancer. Immunosuppression, which occurs during organ transplant, is a significant risk factor for skin cancer. The skin is significant for communication through facial expression and hand movements. Unfortunately, areas of specialized function, such as the area around the eyes and ears, are common places for cancer to occur. Even small cancers in these areas can lead to reconstructive challenges and have significant cosmetic and social ramifications.[1]

While the appearance of any one skin cancer can vary, there are general physical presentations that can be used in screening. BCCs most commonly have a pearly rim (see Figure 3) or can appear somewhat eczematous. They often ulcerate (see Figure 3). SCCs frequently have a thick keratin top layer (see Figure 4). Both BCCs and SCCs are associated with a history of sun-damaged skin. Melanomas are characterized by asymmetry, border irregularity, color variation, a diameter of more than 6 mm, and evolution (ABCDE criteria). (Refer to What Does Melanoma Look Like? on NCI's website for more information about the ABCDE criteria.) Photographs representing typical clinical presentations of these cancers are shown below.

Enlarge

Figure 2. Superficial basal cell carcinoma (left panel) and nodular basal cell carcinoma (right panel).

Enlarge

Figure 3. Ulcerated basal cell carcinoma (left panel) and ulcerated basal cell carcinoma with characteristic pearly rim (right panel).

Enlarge

Figure 4. Squamous cell carcinoma on the face with thick keratin top layer (left panel) and squamous cell carcinoma on the leg (right panel).

Enlarge

Figure 5. Melanomas with characteristic asymmetry, border irregularity, color variation, and large diameter.

Basal cell carcinoma (BCC) is the most common malignancy in people of European descent, with an associated lifetime risk of 30%.[1] While exposure to ultraviolet (UV) radiation is the risk factor most closely linked to the development of BCC, other environmental factors (such as ionizing radiation, chronic arsenic ingestion, and immunosuppression) and genetic factors (such as family history, skin type, and genetic syndromes) also potentially contribute to carcinogenesis. In contrast to melanoma, metastatic spread of BCC is very rare and typically arises from large tumors that have evaded medical treatment for extended periods of time. BCCs can invade tissue locally or regionally, sometimes following along nerves. A tendency for superficial necrosis has resulted in the name "rodent ulcer." With early detection, the prognosis for BCC is excellent.

Sun exposure is the major known environmental factor associated with the development of skin cancer of all types. There are different patterns of sun exposure associated with each major type of skin cancer (BCC, squamous cell carcinoma [SCC], and melanoma).

While there is no standard measure, sun exposure can be generally classified as intermittent or chronic, and the effects may be considered acute or cumulative. Intermittent sun exposure is obtained sporadically, usually during recreational activities, and particularly by indoor workers who have only weekends or vacations to be outdoors and whose skin has not adapted to the sun. Chronic sun exposure is incurred by consistent, repetitive sun exposure, during outdoor work or recreation. Acute sun exposure is obtained over a short time period on skin that has not adapted to the sun. Depending on the time of day and a person's skin type, acute sun exposure may result in sunburn. In epidemiology studies, sunburn is usually defined as burn with pain and/or blistering that lasts for 2 or more days. Cumulative sun exposure is the additive amount of sun exposure that one receives over a lifetime. Cumulative sun exposure may reflect the additive effects of intermittent sun exposure, chronic sun exposure, or both.

Specific patterns of sun exposure appear to lead to different types of skin cancer among susceptible individuals. Intense intermittent recreational sun exposure has been associated with melanoma and BCC,[2,3] while chronic occupational sun exposure has been associated with SCC. Given these data, dermatologists routinely counsel patients to protect their skin from the sun by avoiding mid-day sun exposure, seeking shade, and wearing sun-protective clothing, although evidence-based data for these practices are lacking. The data regarding skin cancer risk reduction by regular sunscreen use are variable. One randomized trial of sunscreen efficacy demonstrated statistically significant protection for the development of SCC but no protection for BCC,[4] while another randomized study demonstrated a trend for reduction in multiple occurrences of BCC among sunscreen users [5] but no significant reduction in BCC or SCC incidence.[6]

Level of evidence (sun-protective clothing, avoidance of sun exposure): 4aii

Level of evidence (sunscreen): 1aii

Tanning bed use has also been associated with an increased risk of BCC. A study of 376 individuals with BCC and 390 control subjects found a 69% increased risk of BCC in individuals who had ever used indoor tanning.[7] The risk of BCC was more pronounced in females and individuals with higher use of indoor tanning.[8]

Environmental factors other than sun exposure may also contribute to the formation of BCC and SCC. Petroleum byproducts (e.g., asphalt, tar, soot, paraffin, and pitch), organophosphate compounds, and arsenic are all occupational exposures associated with cutaneous nonmelanoma cancers.[9-11]

Arsenic exposure may occur through contact with contaminated food, water, or air. While arsenic is ubiquitous in the environment, its ambient concentration in both food and water may be increased near smelting, mining, or coal-burning establishments. Arsenic levels in the U.S. municipal water supply are tightly regulated; however, control is lacking for potable water obtained through private wells. As it percolates through rock formations with naturally occurring arsenic, well water may acquire hazardous concentrations of this material. In many parts of the world, wells providing drinking water are contaminated by high levels of arsenic in the ground water. The populations in Bangladesh, Taiwan, and many other locations have high levels of skin cancer associated with elevated levels of arsenic in the drinking water.[12-16] Medicinal arsenical solutions (e.g., Fowlers solution and Bells asthma medication) were once used to treat common chronic conditions such as psoriasis, syphilis, and asthma, resulting in associated late-onset cutaneous malignancies.[17,18] Current potential iatrogenic sources of arsenic exposure include poorly regulated Chinese traditional/herbal medications and intravenous arsenic trioxide utilized to induce remission in acute promyelocytic leukemia.[19,20]

Aerosolized particulate matter produced by combustion of arsenic-containing materials is another source of environmental exposure. Arsenic-rich coal, animal dung from arsenic-rich regions, and chromated copper arsenatetreated wood produce airborne arsenical particles when burned.[21-23] Burning of these products in enclosed unventilated settings (such as for heat generation) is particularly hazardous.[24]

Clinically, arsenic-induced skin cancers are characterized by multiple recurring SCCs and BCCs occurring in areas of the skin that are usually protected from the sun. A range of cutaneous findings are associated with chronic or severe arsenic exposure, including pigmentary variation (poikiloderma of the skin) and Bowen disease (SCC in situ).[25]

However, the effect of arsenic on skin cancer risk may be more complex than previously thought. Evidence from in vivo models indicate that arsenic, alone or in combination with itraconazole, can inhibit the hedgehog pathway in cells with wild-type or mutated Smoothened by binding to GLI2 proteins; in this way, these drugs demonstrated inhibition of BCC growth in these animal models.[26,27] Additionally, the effect of arsenic on skin cancer risk may be modified by certain variants in nucleotide excision repair genes (xeroderma pigmentosum [XP] types A and D).[28]

The high-risk phenotype consists of individuals with the following physical characteristics:

Specifically, people with more highly pigmented skin demonstrate lower incidence of BCC than do people with lighter pigmented skin. Individuals with Fitzpatrick skin types I or II were shown to have a twofold increased risk of BCC in a small case-control study.[29] (Refer to the Pigmentary characteristics section in the Melanoma section of this summary for a more detailed discussion of skin phenotypes based upon pigmentation.) Blond or red hair color was associated with increased risk of BCC in two large cohorts: the Nurses Health Study and the Health Professionals Follow-Up Study.[30]

Immunosuppression also contributes to the formation of nonmelanoma (keratinocyte) skin cancers. Among solid-organ transplant recipients, the risk of SCC is 65 to 250 times higher, and the risk of BCC is 10 times higher than in the general population.[31-33] Nonmelanoma skin cancers in high-risk patients (i.e., solid-organ transplant recipients and chronic lymphocytic leukemia patients) occur at a younger age and are more common, more aggressive, and have a higher risk of recurrence and metastatic spread than nonmelanoma skin cancers in the general population.[34,35] Among patients with an intact immune system, BCCs outnumber SCCs by a 4:1 ratio; in transplant patients, SCCs outnumber BCCs by a 2:1 ratio.

This increased risk has been linked to the level of immunosuppression and UV exposure. As the duration and dosage of immunosuppressive agents increases, so does the risk of cutaneous malignancy; this effect is reversed with decreasing the dosage of, or taking a break from, immunosuppressive agents. Heart transplant recipients, requiring the highest rates of immunosuppression, are at much higher risk of cutaneous malignancy than liver transplant recipients, in whom much lower levels of immunosuppression are needed to avoid rejection.[31,36] The risk appears to be highest in geographic areas of high UV radiation exposure: when comparing Australian and Dutch organ transplant populations, the Australian patients carried a fourfold increased risk of developing SCC and a fivefold increased risk of developing BCC.[37] This speaks to the importance of rigorous sun avoidance among high-risk immunosuppressed individuals.

Individuals with BCCs and/or SCCs report a higher frequency of these cancers in their family members than do controls. The importance of this finding is unclear. Apart from defined genetic disorders with an increased risk of BCC, a positive family history of any skin cancer is a strong predictor of the development of BCC.

A personal history of BCC or SCC is strongly associated with subsequent BCC or SCC. There is an approximate 20% increased risk of a subsequent lesion within the first year after a skin cancer has been diagnosed. The mean age of occurrence for these nonmelanoma skin cancers is the mid-60s.[38-43] In addition, several studies have found that individuals with a history of skin cancer have an increased risk of a subsequent diagnosis of a noncutaneous cancer;[44-47] however, other studies have contradicted this finding.[48-51] In the absence of other risk factors or evidence of a defined cancer susceptibility syndrome, as discussed below, skin cancer patients are encouraged to follow screening recommendations for the general population for sites other than the skin.

Mutations in the gene coding for the transmembrane receptor protein PTCH1, or PTCH, are associated with basal cell nevus syndrome (BCNS) and sporadic cutaneous BCCs. PTCH1, the human homolog of the Drosophila segment polarity gene patched (ptc), is an integral component of the hedgehog signaling pathway, which serves many developmental (appendage development, embryonic segmentation, neural tube differentiation) and regulatory (maintenance of stem cells) roles.

In the resting state, the transmembrane receptor protein PTCH1 acts catalytically to suppress the seven-transmembrane protein Smoothened (Smo), preventing further downstream signal transduction.[52] Stoichiometric binding of the hedgehog ligand to PTCH1 releases inhibition of Smo, with resultant activation of transcription factors (GLI1, GLI2), cell proliferation genes (cyclin D, cyclin E, myc), and regulators of angiogenesis.[53,54] Thus, the balance of PTCH1 (inhibition) and Smo (activation) manages the essential regulatory downstream hedgehog signal transduction pathway. Loss-of-function mutations of PTCH1 or gain-of-function mutations of Smo tip this balance toward constitutive activation, a key event in potential neoplastic transformation.

Demonstration of allelic loss on chromosome 9q22 in both sporadic and familial BCCs suggested the potential presence of an associated tumor suppressor gene.[55,56] Further investigation identified a mutation in PTCH1 that localized to the area of allelic loss.[57] Up to 30% of sporadic BCCs demonstrate PTCH1 mutations.[58] In addition to BCC, medulloblastoma and rhabdomyosarcoma, along with other tumors, have been associated with PTCH1 mutations. All three malignancies are associated with BCNS, and most people with clinical features of BCNS demonstrate PTCH1 mutations, predominantly truncation in type.[59]

Truncating mutations in PTCH2, a homolog of PTCH1 mapping to chromosome 1p32.1-32.3, have been demonstrated in both BCC and medulloblastoma.[60,61] PTCH2 displays 57% homology to PTCH1, differing in the conformation of the hydrophilic region between transmembrane portions 6 and 7, and the absence of C-terminal extension.[62] While the exact role of PTCH2 remains unclear, there is evidence to support its involvement in the hedgehog signaling pathway.[60,63]

BCNS, also known as Gorlin Syndrome, Gorlin-Goltz syndrome, and nevoid basal cell carcinoma syndrome, is an autosomal dominant disorder with an estimated prevalence of 1 in 57,000 individuals.[64] The syndrome is notable for complete penetrance and extremely variable expressivity, as evidenced by evaluation of individuals with identical genotypes but widely varying phenotypes.[59,65] The clinical features of BCNS differ more among families than within families.[66] BCNS is primarily associated with germline mutations in PTCH1, but families with this phenotype have also been associated with alterations in PTCH2 and SUFU.[67-69]

As detailed above, PTCH1 provides both developmental and regulatory guidance; spontaneous or inherited germline mutations of PTCH1 in BCNS may result in a wide spectrum of potentially diagnostic physical findings. The BCNS mutation has been localized to chromosome 9q22.3-q31, with a maximum logarithm of the odd (LOD) score of 3.597 and 6.457 at markers D9S12 and D9S53.[64] The resulting haploinsufficiency of PTCH1 in BCNS has been associated with structural anomalies such as odontogenic keratocysts, with evaluation of the cyst lining revealing heterozygosity for PTCH1.[70] The development of BCC and other BCNS-associated malignancies is thought to arise from the classic two-hit suppressor gene model: baseline heterozygosity secondary to germline PTCH1 mutation as the first hit, with the second hit due to mutagen exposure such as UV or ionizing radiation.[71-75] However, haploinsufficiency or dominant negative isoforms have also been implicated for the inactivation of PTCH1.[76]

The diagnosis of BCNS is typically based upon characteristic clinical and radiologic examination findings. Several sets of clinical diagnostic criteria for BCNS are in use (refer to Table 1 for a comparison of these criteria).[77-80] Although each set of criteria has advantages and disadvantages, none of the sets have a clearly superior balance of sensitivity and specificity for identifying mutation carriers. The BCNS Colloquium Group proposed criteria in 2011 that required 1 major criterion with molecular diagnosis, two major criteria without molecular diagnosis, or one major and two minor criteria without molecular diagnosis.[80] PTCH1 mutations are found in 60% to 85% of patients who meet clinical criteria.[81,82] Most notably, BCNS is associated with the formation of both benign and malignant neoplasms. The strongest benign neoplasm association is with ovarian fibromas, diagnosed in 14% to 24% of females affected by BCNS.[74,78,83] BCNS-associated ovarian fibromas are more likely to be bilateral and calcified than sporadic ovarian fibromas.[84] Ameloblastomas, aggressive tumors of the odontogenic epithelium, have also been proposed as a diagnostic criterion for BCNS, but most groups do not include it at this time.[85]

Other associated benign neoplasms include gastric hamartomatous polyps,[86] congenital pulmonary cysts,[87] cardiac fibromas,[88] meningiomas,[89-91] craniopharyngiomas,[92] fetal rhabdomyomas,[93] leiomyomas,[94] mesenchymomas,[95] and nasal dermoid tumors. Development of meningiomas and ependymomas occurring postradiation therapy has been documented in the general pediatric population; radiation therapy for syndrome-associated intracranial processes may be partially responsible for a subset of these benign tumors in individuals with BCNS.[96-98] Radiation therapy of medulloblastomas may result in many cutaneous BCCs in the radiation ports. Similarly, treatment of BCC of the skin with radiation therapy may result in induction of large numbers of additional BCCs.[73,74,94]

The diagnostic criteria for BCNS are described in Table 1 below.

Of greatest concern with BCNS are associated malignant neoplasms, the most common of which is BCC. BCC in individuals with BCNS may appear during childhood as small acrochordon-like lesions, while larger lesions demonstrate more classic cutaneous features.[99] Nonpigmented BCCs are more common than pigmented lesions.[100] The age at first BCC diagnosis associated with BCNS ranges from 3 to 53 years, with a mean age of 21.4 years; the vast majority of individuals are diagnosed with their first BCC before age 20 years.[78,83] Most BCCs are located on sun-exposed sites, but individuals with greater than 100 BCCs have a more uniform distribution of BCCs over the body.[100] Case series have suggested that up to 1 in 200 individuals with BCC demonstrate findings supportive of a diagnosis of BCNS.[64] BCNS has rarely been reported in individuals with darker skin pigmentation; however, significantly fewer BCCs are found in individuals of African or Mediterranean ancestry.[78,101,102] Despite the rarity of BCC in this population, reported cases document full expression of the noncutaneous manifestations of BCNS.[102] However, in individuals of African ancestry who have received radiation therapy, significant basal cell tumor burden has been reported within the radiation port distribution.[78,94] Thus, cutaneous pigmentation may protect against the mutagenic effects of UV but not ionizing radiation.

Variants associated with an increased risk of BCC in the general population appear to modify the age of BCC onset in individuals with BCNS. A study of 125 individuals with BCNS found that a variant in MC1R (Arg151Cys) was associated with an early median age of onset of 27 years (95% confidence interval [CI], 2034), compared with individuals who did not carry the risk allele and had a median age of BCC of 34 years (95% CI, 3040) (hazard ratio [HR], 1.64; 95% CI, 1.042.58, P = .034). A variant in the TERT-CLPTM1L gene showed a similar effect, with individuals with the risk allele having a median age of BCC of 31 years (95% CI, 2837) relative to a median onset of 41 years (95% CI, 3248) in individuals who did not carry a risk allele (HR, 1.44; 95% CI, 1.081.93, P = .014).[103]

Many other malignancies have been associated with BCNS. Medulloblastoma carries the strongest association with BCNS and is diagnosed in 1% to 5% of BCNS cases. While BCNS-associated medulloblastoma is typically diagnosed between ages 2 and 3 years, sporadic medulloblastoma is usually diagnosed later in childhood, between the ages of 6 and 10 years.[74,78,83,104] A desmoplastic phenotype occurring around age 2 years is very strongly associated with BCNS and carries a more favorable prognosis than sporadic classic medulloblastoma.[105,106] Up to three times more males than females with BCNS are diagnosed with medulloblastoma.[107] As with other malignancies, treatment of medulloblastoma with ionizing radiation has resulted in numerous BCCs within the radiation field.[74,89] Other reported malignancies include ovarian carcinoma,[108] ovarian fibrosarcoma,[109,110] astrocytoma,[111] melanoma,[112] Hodgkin disease,[113,114] rhabdomyosarcoma,[115] and undifferentiated sinonasal carcinoma.[116]

Odontogenic keratocystsor keratocystic odontogenic tumors (KCOTs), as renamed by the World Health Organization working groupare one of the major features of BCNS.[117] Demonstration of clonal loss of heterozygosity (LOH) of common tumor suppressor genes, including PTCH1, supports the transition of terminology to reflect a neoplastic process.[70] Less than one-half of KCOTs from individuals with BCNS show LOH of PTCH1.[76,118] The tumors are lined with a thin squamous epithelium and a thin corrugated layer of parakeratin. Increased mitotic activity in the tumor epithelium and potential budding of the basal layer with formation of daughter cysts within the tumor wall may be responsible for the high rates of recurrence post simple enucleation.[117,119] In a recent case series of 183 consecutively excised KCOTs, 6% of individuals demonstrated an association with BCNS.[117] A study that analyzed the rate of PTCH1 mutations in BCNS-associated KCOTs found that 11 of 17 individuals carried a germline PTCH1 mutation and an additional 3 individuals had somatic mutations in this gene.[120] Individuals with germline PTCH1 mutations had an early age of KCOT presentation. KCOTs occur in 65% to 100% of individuals with BCNS,[78,121] with higher rates of occurrence in young females.[122]

Palmoplantar pits are another major finding in BCC and occur in 70% to 80% of individuals with BCNS.[83] When these pits occur together with early-onset BCC and/or KCOTs, they are considered diagnostic for BCNS.[123]

Several characteristic radiologic findings have been associated with BCNS, including lamellar calcification of falx cerebri;[124,125] fused, splayed or bifid ribs;[126] and flame-shaped lucencies or pseudocystic bone lesions of the phalanges, carpal, tarsal, long bones, pelvis, and calvaria.[82] Imaging for rib abnormalities may be useful in establishing the diagnosis in younger children, who may have not yet fully manifested a diagnostic array on physical examination.

Table 2 summarizes the frequency and median age of onset of nonmalignant findings associated with BCNS.

Individuals with PTCH2 mutations may have a milder phenotype of BCNS than those with PTCH1 mutations. Characteristic features such as palmar/plantar pits, macrocephaly, falx calcification, hypertelorism, and coarse face may be absent in these individuals.[127]

A 9p22.3 microdeletion syndrome that includes the PTCH1 locus has been described in ten children.[128] All patients had facial features typical of BCNS, including a broad forehead, but they had other features variably including craniosynostosis, hydrocephalus, macrosomia, and developmental delay. At the time of the report, none had basal cell skin cancer. On the basis of their hemizygosity of the PTCH1 gene, these patients are presumably at an increased risk of basal cell skin cancer.

Germline mutations in SUFU, a major negative regulator of the hedgehog pathway, have been identified in a small number of individuals with a clinical phenotype resembling that of BCNS.[68,69] These mutations were first identified in individuals with childhood medulloblastoma,[129] and the incidence of medulloblastoma appears to be much higher in individuals with BCNS associated with SUFU mutations than in those with PTCH1 mutations.[68] SUFU mutations may also be associated with an increased predisposition to meningioma.[91,130] Conversely, odontogenic jaw keratocysts appear less frequently in this population. Some clinical laboratories offer genetic testing for SUFU mutations for individuals with BCNS who do not have an identifiable PTCH1 mutation.

Rombo syndrome, a very rare genetic disorder associated with BCC, has been outlined in three case series in the literature.[131-133] The cutaneous examination is within normal limits until age 7 to 10 years, with the development of distinctive cyanotic erythema of the lips, hands, and feet and early atrophoderma vermiculatum of the cheeks, with variable involvement of the elbows and dorsal hands and feet.[131] Development of BCC occurs in the fourth decade.[131] A distinctive grainy texture to the skin, secondary to interspersed small, yellowish, follicular-based papules and follicular atrophy, has been described.[131,133] Missing, irregularly distributed and/or misdirected eyelashes and eyebrows are another associated finding.[131,132]

Bazex-Dupr-Christol syndrome, another rare genodermatosis associated with development of BCC, has more thorough documentation in the literature than Rombo syndrome. Inheritance is accomplished in an X-linked dominant fashion, with no reported male-to-male transmission.[134-136] Regional assignment of the locus of interest to chromosome Xq24-q27 is associated with a maximum LOD score of 5.26 with the DXS1192 locus.[137] Further work has narrowed the potential location to an 11.4-Mb interval on chromosome Xq25-27; however, the causative gene remains unknown.[138]

Characteristic physical findings include hypotrichosis, hypohidrosis, milia, follicular atrophoderma of the cheeks, and multiple BCC, which manifest in the late second decade to early third decade.[134] Documented hair changes with Bazex-Dupr-Christol syndrome include reduced density of scalp and body hair, decreased melanization,[139] a twisted/flattened appearance of the hair shaft on electron microscopy,[140] and increased hair shaft diameter on polarizing light microscopy.[136] The milia, which may be quite distinctive in childhood, have been reported to regress or diminish substantially at puberty.[136] Other reported findings in association with this syndrome include trichoepitheliomas; hidradenitis suppurativa; hypoplastic alae; and a prominent columella, the fleshy terminal portion of the nasal septum.[141,142]

A rare subtype of epidermolysis bullosa simplex (EBS), Dowling-Meara (EBS-DM), is primarily inherited in an autosomal dominant fashion and is associated with mutations in either keratin-5 (KRT5) or keratin-14 (KRT14).[143] EBS-DM is one of the most severe types of EBS and occasionally results in mortality in early childhood.[144] One report cites an incidence of BCC of 44% by age 55 years in this population.[145] Individuals who inherit two EBS mutations may present with a more severe phenotype.[146] Other less phenotypically severe subtypes of EBS can also be caused by mutations in either KRT5 or KRT14.[143] Approximately 75% of individuals with a clinical diagnosis of EBS (regardless of subtype) have KRT5 or KRT14 mutations.[147]

Characteristics of hereditary syndromes associated with a predisposition to BCC are described in Table 3 below.

(Refer to the Brooke-Spiegler Syndrome, Multiple Familial Trichoepithelioma, and Familial Cylindromatosis section in the Rare Skin Cancer Syndromes section of this summary for more information about Brooke-Spiegler syndrome.)

As detailed further below, the U.S. Preventive Services Task Force does not recommend regular screening for the early detection of any cutaneous malignancies, including BCC. However, once BCC is detected, the National Comprehensive Cancer Network guidelines of care for nonmelanoma skin cancers recommends complete skin examinations every 6 to 12 months for life.[158]

The BCNS Colloquium Group has proposed guidelines for the surveillance of individuals with BCNS (see Table 4).

Level of evidence: 5

Avoidance of excessive cumulative and sporadic sun exposure is important in reducing the risk of BCC, along with other cutaneous malignancies. Scheduling activities outside of the peak hours of UV radiation, utilizing sun-protective clothing and hats, using sunscreen liberally, and strictly avoiding tanning beds are all reasonable steps towards minimizing future risk of skin cancer. For patients with particular genetic susceptibility (such as BCNS), avoidance or minimization of ionizing radiation is essential to reducing future tumor burden.

Level of evidence: 2aii

The role of various systemic retinoids, including isotretinoin and acitretin, has been explored in the chemoprevention and treatment of multiple BCCs, particularly in BCNS patients. In one study of isotretinoin use in 12 patients with multiple BCCs, including 5 patients with BCNS, tumor regression was noted, with decreasing efficacy as the tumor diameter increased.[159] However, the results were insufficient to recommend use of systemic retinoids for treatment of BCC. Three additional patients, including one with BCNS, were followed long-term for evaluation of chemoprevention with isotretinoin, demonstrating significant decrease in the number of tumors per year during treatment.[159] Although the rate of tumor development tends to increase sharply upon discontinuation of systemic retinoid therapy, in some patients the rate remains lower than their pretreatment rate, allowing better management and control of their cutaneous malignancies.[159-161] In summary, the use of systemic retinoids for chemoprevention of BCC is reasonable in high-risk patients, including patients with XP, as discussed in the Squamous Cell Carcinoma section of this summary.

A patients cumulative and evolving tumor load should be evaluated carefully in light of the potential long-term use of a medication class with cumulative and idiosyncratic side effects. Given the possible side-effect profile, systemic retinoid use is best managed by a practitioner with particular expertise and comfort with the medication class. However, for all potentially childbearing women, strict avoidance of pregnancy during the systemic retinoid courseand for 1 month after completion of isotretinoin and 3 years after completion of acitretinis essential to avoid potentially fatal and devastating fetal malformations.

Level of evidence (retinoids): 2aii

In a phase II study of 41 patients with BCNS, vismodegib (an inhibitor of the hedgehog pathway) has been shown to reduce the per-patient annual rate of new BCCs requiring surgery.[162] Existing BCCs also regressed for these patients during daily treatment with 150 mg of oral vismodegib. While patients treated had visible regression of their tumors, biopsy demonstrated residual microscopic malignancies at the site, and tumors progressed after the discontinuation of the therapy. Adverse effects included taste disturbance, muscle cramps, hair loss, and weight loss and led to discontinuation of the medication in 54% of subjects. Based on the side-effect profile and rate of disease recurrence after discontinuation of the medication, additional study regarding optimal dosing of vismodegib is ongoing.

Level of evidence (vismodegib): 1aii

Treatment of individual basal cell cancers in BCNS is generally the same as for sporadic basal cell cancers. Due to the large number of lesions on some patients, this can present a surgical challenge. Field therapy with imiquimod or photodynamic therapy are attractive options, as they can treat multiple tumors simultaneously.[163,164] However, given the radiosensitivity of patients with BCNS, radiation as a therapeutic option for large tumors should be avoided.[78] There are no randomized trials, but the isolated case reports suggest that field therapy has similar results as in sporadic basal cell cancer, with higher success rates for superficial cancers than for nodular cancers.[163,164]

Consensus guidelines for the use of methylaminolevulinate photodynamic therapy in BCNS recommend that this modality may best be used for superficial BCC of all sizes and for nodular BCC less than 2 mm thick.[165] Monthly therapy with photodynamic therapy may be considered for these patients as clinically indicated.

Level of evidence (imiquimod and photodynamic therapy) : 4

In addition to its effects on the prevention of BCCs in patients with BCNS, vismodegib may also have a palliative effect on KCOTs found in this population. An initial report indicated that the use of GDC-0449, the hedgehog pathway inhibitor now known as vismodegib, resulted in resolution of KCOTs in one patient with BCNS.[166] Another small study found that four of six patients who took 150 mg of vismodegib daily had a reduction in the size of KCOTs.[167] None of the six patients in this study had new KCOTs or an increase in the size of existing KCOTs while being treated, and one patient had a sustained response that lasted 9 months after treatment was discontinued.

Level of evidence (vismodegib): 3diii

Squamous cell carcinoma (SCC) is the second most common type of skin cancer and accounts for approximately 20% of cutaneous malignancies. Although most cancer registries do not include information on the incidence of nonmelanoma skin cancer, annual incidence estimates range from 1 million to 3.5 million cases in the United States.[1,2]

Mortality is rare from this cancer; however, the morbidity and costs associated with its treatment are considerable.

Sun exposure is the major known environmental factor associated with the development of skin cancer of all types; however, different patterns of sun exposure are associated with each major type of skin cancer. (Refer to the Sun exposure section in the Basal Cell Carcinoma section of this summary for more information.) This section focuses on sun exposure and increased risk of cutaneous SCC.

Unlike basal cell carcinoma (BCC), SCC is associated with chronic exposure, rather than intermittent intense exposure to ultraviolet (UV) radiation. Occupational exposure is the characteristic pattern of sun exposure linked with SCC.[3] A case-control study in southern Europe showed increased risk of SCC when lifetime sun exposure exceeded 70,000 hours. People whose lifetime sun exposure equaled or exceeded 200,000 hours had an odds ratio (OR) 8 to 9 times that of the reference group.[4] A Canadian case-control study did not find an association between cumulative lifetime sun exposure and SCC; however, sun exposure in the 10 years before diagnosis and occupational exposure were found to be risk factors.[5]

In addition to environmental radiation, exposure to therapeutic radiation is another risk factor for SCC. Individuals with skin disorders treated with psoralen and ultraviolet-A radiation (PUVA) had a threefold to sixfold increase in SCC.[6] This effect appears to be dose-dependent, as only 7% of individuals who underwent fewer than 200 treatments had SCC, compared with more than 50% of those who underwent more than 400 treatments.[7] Therapeutic use of ultraviolet-B (UVB) radiation has also been shown to cause a mild increase in SCC (adjusted incidence rate ratio, 1.37).[8] Devices such as tanning beds also emit UV radiation and have been associated with increased SCC risk, with a reported OR of 2.5 (95% confidence interval [CI], 1.73.8).[9]

Investigation into the effect of ionizing radiation on SCC carcinogenesis has yielded conflicting results. One population-based case-control study found that patients who had undergone therapeutic radiation had an increased risk of SCC at the site of previous radiation (OR, 2.94) as compared with individuals who had not undergone radiation treatments.[10] Cohort studies of radiology technicians, atomic-bomb survivors, and survivors of childhood cancers have not shown an increased risk of SCC, although the incidence of BCC was increased in all of these populations.[11-13] For those who develop SCC at previously radiated sites that are not sun-exposed, the latent period appears to be quite long; these cancers may be diagnosed years or even decades after the radiation exposure.[14]

The effect of other types of radiation, such as cosmic radiation, is also controversial. Pilots and flight attendants have a reported incidence of SCC that ranges between 2.1 and 9.9 times what would be expected; however, the overall cancer incidence is not consistently elevated. Some attribute the high rate of nonmelanoma skin cancers in airline flight personnel to cosmic radiation, while others suspect lifestyle factors.[15-20]

The influence of arsenic on the risk of nonmelanoma skin cancer is discussed in detail in the Other environmental factors section in the Basal Cell Carcinoma section of this summary. Like BCCs, SCCs appear to be associated with exposure to arsenic in drinking water and combustion products.[21,22] However, this association may hold true only for the highest levels of arsenic exposure. Individuals who had toenail concentrations of arsenic above the 97th percentile were found to have an approximately twofold increase in SCC risk.[23] For arsenic, the latency period can be lengthy; invasive SCC has been found to develop at an average of 20 years after exposure.[24]

Current or previous cigarette smoking has been associated with a 1.5-fold to 2-fold increase in SCC risk,[25-27] although one large study showed no change in risk.[28] Available evidence suggests that the effect of smoking on cancer risk seems to be greater for SCC than for BCC.

Additional reports have suggested weak associations between SCC and exposure to insecticides, herbicides, or fungicides.[29]

Like melanoma and BCC, SCC occurs more frequently in individuals with lighter skin than in those with darker skin.[3,30] However, SCC can also occur in individuals with darker skin. An Asian registry based in Singapore reported an increase in skin cancer in that geographic area, with an incidence rate of 8.9 per 100,000 person-years. Incidence of SCC, however, was shown to be on the decline.[30] SCC is the most common form of skin cancer in black individuals in the United States and in certain parts of Africa; the mortality rate for this disease is relatively high in these populations.[31,32] Epidemiologic characteristics of, and prevention strategies for, SCC in those individuals with darker skin remain areas of investigation.

Freckling of the skin and reaction of the skin to sun exposure have been identified as other risk factors for SCC.[33] Individuals with heavy freckling on the forearm were found to have a 14-fold increase in SCC risk if freckling was present in adulthood, and an almost threefold risk if freckling was present in childhood.[33,34] The degree of SCC risk corresponded to the amount of freckling. In this study, the inability of the skin to tan and its propensity to burn were also significantly associated with risk of SCC (OR of 2.9 for severe burn and 3.5 for no tan).

The presence of scars on the skin can also increase the risk of SCC, although the process of carcinogenesis in this setting may take years or even decades. SCCs arising in chronic wounds are referred to as Marjolins ulcers. The mean time for development of carcinoma in these wounds is estimated at 26 years.[35] One case report documents the occurrence of cancer in a wound that was incurred 59 years earlier.[36]

Immunosuppression also contributes to the formation of nonmelanoma skin cancers. Among solid-organ transplant recipients, the risk of SCC is 65 to 250 times higher, and the risk of BCC is 10 times higher than that observed in the general population, although the risks vary with transplant type.[37-40] Nonmelanoma skin cancers in high-risk patients (solid-organ transplant recipients and chronic lymphocytic leukemia patients) occur at a younger age, are more common and more aggressive, and have a higher risk of recurrence and metastatic spread than these cancers do in the general population.[41,42] Additionally, there is a high risk of second SCCs.[43,44] In one study, over 65% of kidney transplant recipients developed subsequent SCCs after their first diagnosis.[43] Among patients with an intact immune system, BCCs outnumber SCCs by a 4:1 ratio; in transplant patients, SCCs outnumber BCCs by a 2:1 ratio.

This increased risk has been linked to an interaction between the level of immunosuppression and UV radiation exposure. As the duration and dosage of immunosuppressive agents increase, so does the risk of cutaneous malignancy; this effect is reversed with decreasing the dosage of, or taking a break from, immunosuppressive agents. Heart transplant recipients, requiring the highest rates of immunosuppression, are at much higher risk of cutaneous malignancy than liver transplant recipients, in whom much lower levels of immunosuppression are needed to avoid rejection.[37,45,46] The risk appears to be highest in geographic areas with high UV exposure.[46] When comparing Australian and Dutch organ transplant populations, the Australian patients carried a fourfold increased risk of developing SCC and a fivefold increased risk of developing BCC.[47] This finding underlines the importance of rigorous sun avoidance, particularly among high-risk immunosuppressed individuals.

Certain immunosuppressive agents have been associated with increased risk of SCC. Kidney transplant patients who received cyclosporine in addition to azathioprine and prednisolone had a 2.8-fold increase in risk of SCC over those kidney transplant patients on azathioprine and prednisolone alone.[37] In cardiac transplant patients, increased incidence of SCC was seen in individuals who had received OKT3 (muromonab-CD3), a murine monoclonal antibody against the CD3 receptor.[48]

A personal history of BCC or SCC is strongly associated with subsequent SCC. A study from Ireland showed that individuals with a history of BCC had a 14% higher incidence of subsequent SCC; for men with a history of BCC, the subsequent SCC risk was 27% higher.[49] In the same report, individuals with melanoma were also 2.5 times more likely to report a subsequent SCC. There is an approximate 20% increased risk of a subsequent lesion within the first year after a skin cancer has been diagnosed. The mean age of occurrence for these nonmelanoma skin cancers is the middle of the sixth decade of life.[26,50-54]

Although the literature is scant on this subject, a family history of SCC may increase the risk of SCC in first-degree relatives (FDRs). Review of the Swedish Family Center Database showed that individuals with at least one sibling or parent affected with SCC, in situ SCC (Bowen disease), or actinic keratosis had a twofold to threefold increased risk of invasive and in situ SCC relative to the general population.[55,56] Increased number of tumors in parents was associated with increased risk to the offspring. Of note, diagnosis of the proband at an earlier age was not consistently associated with a trend of increased incidence of SCC in the FDR, as would be expected in most hereditary syndromes because of germline mutations. Further analysis of the Swedish population-based data estimates genetic risk effects of 8% and familial shared-environmental effects of 18%.[57] Thus, shared environmental and behavioral factors likely account for some of the observed familial clustering of SCC.

See the original post:
Genetics of Skin Cancer - National Cancer Institute

Recommendation and review posted by Bethany Smith

Psoriasis is a long-lasting autoimmune disease characterized by patches of abnormal skin.[1] These skin patches are typically red, itchy, and scaly. They may vary in severity from small and localized to complete body coverage.[2] Injury to the skin can trigger psoriatic skin changes at that spot, which is known as Koebner phenomenon.[3]

There are five main types of psoriasis: plaque, guttate, inverse, pustular, and erythrodermic.[1] Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases. It typically presents with red patches with white scales on top. Areas of the body most commonly affected are the back of the forearms, shins, around the belly button, and the scalp.[4] Guttate psoriasis has drop shapped lesions.[1] Pustular psoriasis presents with small non-infectious pus filled blisters.[5] Inverse psoriasis forms red patches in skin folds.[1] Erythrodermic psoriasis occurs when the rash becomes very widespread, and can develop from any of the other types. Fingernails and toenails are affected in most people at some point in time. This may include pits in the nails or changes in nail color.[4]

Psoriasis is generally thought to be a genetic disease which is triggered by environmental factors.[2] In twin studies, identical twins are three times more likely to both be affected compared to non-identical twins; this suggests that shared genetic risk factors predispose to psoriasis. Symptoms often worsen during winter and with certain medications such as beta blockers or NSAIDs.[4] Infections and psychological stress may also play a role.[1][2] Psoriasis is not contagious. The underlying mechanism involves the immune system reacting to skin cells. Diagnosis is typically based on the signs and symptoms.[4]

There is no cure for psoriasis. However, various treatments can help control the symptoms.[4] These treatments may include steroid creams, vitamin D3 cream, ultraviolet light, and immune system suppressing medications such as methotrexate.[1] About 75% of people can be managed with creams alone.[4] The disease affects 24% of the population.[6] Both males and females are affected with equal frequency.[1] Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, Crohn's disease, and depression.[4] Psoriatic arthritis affects up to 30% of individuals with psoriasis.[5]

Psoriasis vulgaris (also known as chronic stationary psoriasis or plaque-like psoriasis) is the most common form and affects 85%90% of people with psoriasis.[7] Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery-white scaly skin. These areas are called plaques and are most commonly found on the elbows, knees, scalp, and back.[7][8]Psoriatic erythroderma (erythrodermic psoriasis) involves widespread inflammation and exfoliation of the skin over most of the body surface. It may be accompanied by severe itching, swelling, and pain. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic glucocorticoids.[9] This form of psoriasis can be fatal as the extreme inflammation and exfoliation disrupt the body's ability to regulate temperature and perform barrier functions.[10]

A person's arm covered with plaque psoriasis

Pustular psoriasis appears as raised bumps filled with noninfectious pus (pustules).[11] The skin under and surrounding the pustules is red and tender.[12] Pustular psoriasis can be localized, commonly to the hands and feet (palmoplantar pustulosis), or generalized with widespread patches occurring randomly on any part of the body. Acrodermatitis continua is a form of localized psoriasis limited to the fingers and toes that may spread to the hands and feet.[12]Pustulosis palmaris et plantaris is another form of localized pustular psoriasis similar to acrodermatitis continua with pustules erupting from red, tender, scaly skin found on the palms of the hands and the soles of the feet.[12]

Generalized pustular psoriasis (pustular psoriasis of von Zumbusch), also known as impetigo herpetiformis during pregnancy,[13] is a rare and severe form of psoriasis that may require hospitalization. The development of generalized pustular psoriasis is often caused by an infection, abrupt withdrawal of topical corticosteroid treatment, pregnancy, hypocalcemia, medications, or following an irritating topical treatment for plaque psoriasis.[12] This form of psoriasis is characterized by an acute onset of numerous pustules on top of tender red skin. This skin eruption is often accompanied by a fever, muscle aches, nausea, and an elevated white blood cell count.[12]Annular pustular psoriasis (APP), a rare form of generalized pustular psoriasis, is the most common type seen during childhood.[13] APP tends to occur in women more frequently than in men, and is usually less severe than other forms of generalized pustular psoriasis such as impetigo herpetiformis.[13] This form of psoriasis is characterized by ring-shaped plaques with pustules around the edges and yellow crusting.[13] APP most often affects the torso, neck, arms, and legs.[13]

Additional types of psoriasis affecting the skin include inverse psoriasis, guttate psoriasis, oral psoriasis, and seborrheic-like psoriasis.[14]

Inverse psoriasis (also known as flexural psoriasis) appears as smooth, inflamed patches of skin. The patches frequently affect skin folds, particularly around the genitals (between the thigh and groin), the armpits, in the skin folds of an overweight abdomen (known as panniculus), between the buttocks in the intergluteal cleft, and under the breasts in the inframammary fold. Heat, trauma, and infection are thought to play a role in the development of this atypical form of psoriasis.[15]Napkin psoriasis is a subtype of psoriasis common in infants characterized by red papules with silver scale in the diaper area that may extend to the torso or limbs.[16] Napkin psoriasis is often misdiagnosed as napkin dermatitis.[17]

Guttate psoriasis is characterized by numerous small, scaly, red or pink, droplet-like lesions (papules). These numerous spots of psoriasis appear over large areas of the body, primarily the trunk, but also the limbs and scalp. Guttate psoriasis is often triggered by a streptococcal infection, typically streptococcal pharyngitis.[15] The reverse is not true.

Oral psoriasis is very rare,[18] in contrast to lichen planus, another common papulosquamous disorder that commonly involves both the skin and mouth. When psoriasis involves the oral mucosa (the lining of the mouth), it may be asymptomatic,[18] but it may appear as white or grey-yellow plaques.[18]Fissured tongue is the most common finding in those with oral psoriasis and has been reported to occur in 6.5-20% of people with psoriasis affecting the skin. The microscopic appearance of oral mucosa affected by geographic tongue (migratory stomatitis) is very similar to the appearance of psoriasis.[19] However, modern studies have failed to demonstrate any link between the two conditions.[20]

Seborrheic-like psoriasis is a common form of psoriasis with clinical aspects of psoriasis and seborrheic dermatitis, and may be difficult to distinguish from the latter. This form of psoriasis typically manifests as red plaques with greasy scales in areas of higher sebum production such as the scalp, forehead, skin folds next to the nose, skin surrounding the mouth, skin on the chest above the sternum, and in skin folds.[16]

Psoriatic arthritis is a form of chronic inflammatory arthritis that has a highly variable clinical presentation and frequently occurs in association with skin and nail psoriasis.[21][22] It typically involves painful inflammation of the joints and surrounding connective tissue and can occur in any joint, but most commonly affects the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis.[21] Psoriatic arthritis can also affect the hips, knees, spine (spondylitis), and sacroiliac joint (sacroiliitis).[23] About 30% of individuals with psoriasis will develop psoriatic arthritis.[7] Skin manifestations of psoriasis tend to occur before arthritic manifestations in about 75% of cases.[22]

Psoriasis can affect the nails and produces a variety of changes in the appearance of finger and toe nails. Nail psoriasis occurs in 40-45% of people with psoriasis affecting the skin and has a lifetime incidence of 80-90% in those with psoriatic arthritis.[24] These changes include pitting of the nails (pinhead-sized depressions in the nail is seen in 70% with nail psoriasis), whitening of the nail, small areas of bleeding from capillaries under the nail, yellow-reddish discoloration of the nails known as the oil drop or salmon spot, thickening of the skin under the nail (subungual hyperkeratosis), loosening and separation of the nail (onycholysis), and crumbling of the nail.[24]

In addition to the appearance and distribution of the rash, specific medical signs may be used by medical practitioners to assist with diagnosis. These may include Auspitz's sign (pinpoint bleeding when scale is removed), Koebner phenomenon (psoriatic skin lesions induced by trauma to the skin),[16] and itching and pain localized to papules and plaques.[15][16]

The cause of psoriasis is not fully understood, but a number of theories exist.

Around one-third of people with psoriasis report a family history of the disease, and researchers have identified genetic loci associated with the condition. Identical twin studies suggest a 70% chance of a twin developing psoriasis if the other twin has the disorder. The risk is around 20% for nonidentical twins. These findings suggest both a genetic susceptibility and an environmental response in developing psoriasis.[25]

Psoriasis has a strong hereditary component, and many genes are associated with it, but it is unclear how those genes work together. Most of the identified genes relate to the immune system, particularly the major histocompatibility complex (MHC) and T cells. Genetic studies are valuable due to their ability to identify molecular mechanisms and pathways for further study and potential drug targets.[26]

Classic genome-wide linkage analysis has identified nine loci on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9). Within those loci are genes on pathways that lead to inflammation. Certain variations (mutations) of those genes are commonly found in psoriasis.[26]Genome-wide association scans have identified other genes that are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signal proteins, which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.[26]

The major determinant is PSORS1, which probably accounts for 35%50% of psoriasis heritability. It controls genes that affect the immune system or encode skin proteins that are overabundant with psoriasis. PSORS1 is located on chromosome 6 in the major histocompatibility complex (MHC), which controls important immune functions. Three genes in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C variant HLA-Cw6,[27] which encodes a MHC class I protein; CCHCR1, variant WWC, which encodes a coiled protein that is overexpressed in psoriatic epidermis; and CDSN, variant allele 5, which encodes corneodesmosin, a protein which is expressed in the granular and cornified layers of the epidermis and upregulated in psoriasis.[26]

Two major immune system genes under investigation are interleukin-12 subunit beta (IL12B) on chromosome 5q, which expresses interleukin-12B; and IL23R on chromosome 1p, which expresses the interleukin-23 receptor, and is involved in T cell differentiation. Interleukin-23 receptor and IL12B have both been strongly linked with psoriasis.[27] T cells are involved in the inflammatory process that leads to psoriasis.[26] These genes are on the pathway that up-regulate tumor necrosis factor- and nuclear factor B, two genes involved in inflammation.[26] Recently, the first gene directly linked to psoriasis has been identified. A rare mutation in the gene encoding for the CARD14 protein plus an environmental trigger was enough to cause plaque psoriasis (the most common form of psoriasis).[28][29]

Conditions reported as accompanying a worsening of the disease include chronic infections, stress, and changes in season and climate.[27] Others include hot water, scratching psoriasis skin lesions, skin dryness, excessive alcohol consumption, cigarette smoking, and obesity.[27][30][31]

People with advanced HIV/AIDS often exhibit psoriasis.[32] The rate of psoriasis in HIV-positive individuals is comparable to that of HIV-negative individuals, however, psoriasis tends to be more severe in people infected with HIV.[33] A much higher rate of psoriatic arthritis occurs in HIV-positive individuals with psoriasis than in those without the infection.[33] The immune response in those infected with HIV is typically characterized by cellular signals from Th2 subset of CD4+ helper T cells,[32] whereas the immune response in psoriasis vulgaris is characterized by a pattern of cellular signals typical of Th1 subset of CD4+ helper T cells and Th17 helper T cells.[34][35] It is hypothesized that the diminished CD4+-T cell presence causes an overactivation of CD8+-T cells, which are responsible for the exacerbation of psoriasis in HIV-positive people. Psoriasis in those with HIV/AIDS is often severe and may be untreatable with conventional therapy.[36]

Drug-induced psoriasis may occur with beta blockers,[5]lithium,[5]antimalarial medications,[5]non-steroidal anti-inflammatory drugs,[5]terbinafine, calcium channel blockers, captopril, glyburide, granulocyte colony-stimulating factor,[5]interleukins, interferons,[5]lipid-lowering drugs,[14]:197 and paradoxically TNF inhibitors such as infliximab or adalimumab.[37] Withdrawal of corticosteroids (topical steroid cream) can aggravate psoriasis due to the rebound effect of corticosteroids.[38]

Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin.[39] Abnormal production of skin cells (especially during wound repair) and an overabundance of skin cells result from the sequence of pathological events in psoriasis.[12] Skin cells are replaced every 35 days in psoriasis rather than the usual 2830 days.[40] These changes are believed to stem from the premature maturation of keratinocytes induced by an inflammatory cascade in the dermis involving dendritic cells, macrophages, and T cells (three subtypes of white blood cells).[7][33] These immune cells move from the dermis to the epidermis and secrete inflammatory chemical signals (cytokines) such as tumor necrosis factor-, interleukin-1, interleukin-6, and interleukin-22.[26] These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate.[26] One hypothesis is that psoriasis involves a defect in regulatory T cells, and in the regulatory cytokine interleukin-10.[26]

Gene mutations of proteins involved in the skin's ability to function as a barrier have been identified as markers of susceptibility for the development of psoriasis.[41][42]

DNA released from dying cells acts as an inflammatory stimulus in psoriasis[43] and stimulates the receptors on certain dendritic cells, which in turn produce the cytokine interferon-.[43] In response to these chemical messages from dendritic cells and T cells, keratinocytes also secrete cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-, which signal downstream inflammatory cells to arrive and stimulate additional inflammation.[26]

Dendritic cells bridge the innate immune system and adaptive immune system. They are increased in psoriatic lesions[39] and induce the proliferation of T cells and type 1 helper T cells (Th1). Targeted immunotherapy as well as psoralen and ultraviolet A (PUVA) therapy can reduce the number of dendritic cells and favors a Th2 cell cytokine secretion pattern over a Th1/Th17 cell cytokine profile.[26][34] Psoriatic T cells move from the dermis into the epidermis and secrete interferon- and interleukin-17.[44] Interleukin-23 is known to induce the production of interleukin-17 and interleukin-22.[39][44] Interleukin-22 works in combination with interleukin-17 to induce keratinocytes to secrete neutrophil-attracting cytokines.[44]

A diagnosis of psoriasis is usually based on the appearance of the skin. Skin characteristics typical for psoriasis are scaly, erythematous plaques, papules, or patches of skin that may be painful and itch.[15] No special blood tests or diagnostic procedures are needed to make the diagnosis.[12][45]

The differential diagnosis of psoriasis includes dermatological conditions similar in appearance such as discoid eczema, seborrhoeic eczema, pityriasis rosea (may be confused with guttate psoriasis), nail fungus (may be confused with nail psoriasis) or cutaneous T cell lymphoma (50% of individuals with this cancer are initially misdiagnosed with psoriasis).[38] Dermatologic manifestations of systemic illnesses such as the rash of secondary syphilis may also be confused with psoriasis.[38]

If the clinical diagnosis is uncertain, a skin biopsy or scraping may be performed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy will show clubbed epidermal projections that interdigitate with dermis on microscopy. Epidermal thickening is another characteristic histologic finding of psoriasis lesions.[12][46] The stratum granulosum layer of the epidermis is often missing or significantly decreased in psoriatic lesions; the skin cells from the most superficial layer of skin are also abnormally as they never fully mature. Unlike their mature counterparts, these superficial cells keep their nucleus.[12] Inflammatory infiltrates can typically be visualized on microscopy when examining skin tissue or joint tissue affected by psoriasis. Epidermal skin tissue affected by psoriatic inflammation often has many CD8+ T cells while a predominance of CD4+ T cells make up the inflammatory infiltrates of the dermal layer of skin and the joints.[12]

Psoriasis is classified as a papulosquamous disorder and is most commonly subdivided into different categories based on histological characteristics.[2][5] Variants include plaque, pustular, guttate, and flexural psoriasis. Each form has a dedicated ICD-10 code.[47] Psoriasis can also be classified into nonpustular and pustular types.[48]

Another classification scheme considers genetic and demographic factors. Type 1 has a positive family history, starts before the age of 40, and is associated with the human leukocyte antigen, HLA-Cw6. Conversely, type 2 does not show a family history, presents before age 40, and is not associated with HLA-Cw6.[49] Type 1 accounts for about 75% of persons with psoriasis.[50]

The classification of psoriasis as an autoimmune disease has sparked considerable debate. Researchers have proposed differing descriptions of psoriasis and psoriatic arthritis; some authors have classified them as autoimmune diseases[12][27][51] while others have classified them as distinct from autoimmune diseases and referred to them as immune-mediated inflammatory diseases.[26][52][53]

There is no consensus about how to classify the severity of psoriasis. Mild psoriasis has been defined as a percentage of body surface area (BSA)10, a Psoriasis Area Severity Index (PASI) score 10, and a dermatology life quality index (DLQI) score 10.[54] Moderate to severe psoriasis was defined by the same group as BSA >10 or PASI score >10 and a DLQI score >10.[54] The DLQI is a 10 question tool used to measure the impact of several dermatologic diseases on daily functioning. The DLQI score ranges from 0 (minimal impairment) to 30 (maximal impairment) and is calculated with each answer being assigned 0-3 points with higher scores indicating greater social or occupational impairment.[55]

The psoriasis area severity index (PASI) is the most widely used measurement tool for psoriasis. PASI assesses the severity of lesions and the area affected and combines these two factors into a single score from 0 (no disease) to 72 (maximal disease).[56] Nevertheless, the PASI can be too unwieldy to use outside of research settings, which has led to attempts to simplify the index for clinical use.[57]

While no cure is available for psoriasis,[38] many treatment options exist. Topical agents are typically used for mild disease, phototherapy for moderate disease, and systemic agents for severe disease.[58]

Topical corticosteroid preparations are the most effective agents when used continuously for 8 weeks; retinoids and coal tar were found to be of limited benefit and may be no better than placebo.[59] Greater benefit has been observed with very potent corticosteroids when compared to potent corticosteroids. Vitamin D analogues such as paricalcitol were found to be significantly superior to placebo. Combination therapy with vitamin D and a corticosteroid was superior to either treatment alone and vitamin D was found to be superior to coal tar for chronic plaque psoriasis.[60]

Moisturizers and emollients such as mineral oil, petroleum jelly, calcipotriol, and decubal (an oil-in-water emollient) were found to increase the clearance of psoriatic plaques. Emollients have been shown to be even more effective at clearing psoriatic plaques when combined with phototherapy.[61] However, certain emollients have no impact on psoriasis plaque clearance or may even decrease the clearance achieved with phototherapy. The emollient salicylic acid is structurally similar to para-aminobenzoic acid (PABA), commonly found in sunscreen, and is known to interfere with phototherapy in psoriasis. Coconut oil, when used as an emollient in psoriasis, has been found to decrease plaque clearance with phototherapy.[61] Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turnover, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol, corticosteroids (i.e. desoximetasone), fluocinonide, vitamin D3 analogs (for example, calcipotriol), and retinoids are routinely used. The use of the finger tip unit may be helpful in guiding how much topical treatment to use.[30][62]

Vitamin D analogues may be useful with steroids; however, alone have a higher rate of side effects.[63] They may allow less steroids to be used.[64]

Another topical therapy used to treat psoriasis is a form of balneotherapy, which involves daily baths in the Dead Sea. This is usually done for four weeks with the benefit attributed to sun exposure. This is cost-effective and it has been propagated as an effective way to treat psoriasis without medication.[65] Decreases of PASI scores greater than 75% and remission for several months have commonly been observed.[65] Side-effects may be mild such as itchiness, folliculitis, sunburn, poikiloderma, and a theoretical risk of nonmelanoma skin cancer or melanoma has been suggested.[65] However, more recent studies have determined that there does not appear to be increased risk of melanoma in the long-term.[66] Data are inconclusive with respect to nonmelanoma skin cancer risk, but support the idea that the therapy is associated with an increased risk of benign forms of sun-induced skin damage such as, but not limited to, actinic elastosis or liver spots.[66] Dead Sea balneotherapy is also effective for psoriatic arthritis.[66]

Phototherapy in the form of sunlight has long been used for psoriasis.[58]Wavelengths of 311313nanometers are most effective, and special lamps have been developed for this application.[58] The exposure time should be controlled to avoid over exposure and burning of the skin. The UVB lamps should have a timer that will turn off the lamp when the time ends. The amount of light used is determined by a person's skin type.[58] Increased rates of cancer from treatment appear to be small.[58] Narrow band UVB light (NBUVB) phototherapy has been demonstrated to have similar efficacy to PUVA.[67]

A major mechanism of NBUVB is the induction of DNA damage in the form of pyrimidine dimers. This type of phototherapy is useful in the treatment of psoriasis because the formation of these dimers interferes with the cell cycle and stops it. The interruption of the cell cycle induced by NBUVB opposes the characteristic rapid division of skin cells seen in psoriasis.[67] The activity of many types of immune cells found in the skin is also effectively suppressed by NBUVB phototherapy treatments. The most common short-term side effect of this form of phototherapy is redness of the skin; less common side effects of NBUVB phototherapy are itching and blistering of the treated skin, irritation of the eyes in the form of conjunctival inflammation or inflammation of the cornea, or cold sores due to reactivation of the herpes simplex virus in the skin surrounding the lips. Eye protection is usually given during phototherapy treatments.[67]

Psoralen and ultraviolet A phototherapy (PUVA) combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. The mechanism of action of PUVA is unknown, but probably involves activation of psoralen by UVA light, which inhibits the abnormally rapid production of the cells in psoriatic skin. There are multiple mechanisms of action associated with PUVA, including effects on the skin's immune system. PUVA is associated with nausea, headache, fatigue, burning, and itching. Long-term treatment is associated with squamous cell carcinoma (but not with melanoma).[31][68] A combination therapy for moderate to severe psoriasis using PUVA plus acitretin resulted in benefit, but acitretin use has been associated with birth defects and liver damage.[69]

Psoriasis resistant to topical treatment and phototherapy may be treated with systemic therapies including oral medications or injectable treatments.[70] Patients undergoing systemic treatment must have regular blood and liver function tests to check for medication toxicities.[70]Pregnancy must be avoided for most of these treatments. The majority of people experience a recurrence of psoriasis after systemic treatment is discontinued.

Non-biologic systemic treatments frequently used for psoriasis include methotrexate, ciclosporin, hydroxycarbamide, fumarates such as dimethyl fumarate, and retinoids.[71] Methotrexate and ciclosporin are drugs that suppress the immune system; retinoids are synthetic forms of vitamin A. These agents are also regarded as first-line treatments for psoriatic erythroderma.[9]

Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalised immunosuppressive drug therapies such as methotrexate, biologics target specific aspects of the immune system contributing to psoriasis.[71] These medications are generally well-tolerated and limited long-term outcome data have demonstrated biologics to be safe for long-term use in moderate to severe plaque psoriasis.[71][72] However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection.[71] Professional guidelines regard biologics as third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments.[72] The safety of biologics during pregnancy has not been assessed. European guidelines recommend avoiding biologics if a pregnancy is planned; anti-TNF therapies such as infliximab are not recommended for use in chronic carriers of the hepatitis B virus or individuals infected with HIV.[71]

Several monoclonal antibodies target cytokines, the molecules that cells use to send inflammatory signals to each other. TNF- is one of the main executor inflammatory cytokines. Four monoclonal antibodies (MAbs) (infliximab, adalimumab, golimumab, and certolizumab pegol) and one recombinant TNF- decoy receptor, etanercept, have been developed to inhibit TNF- signaling. Additional monoclonal antibodies have been developed against pro-inflammatory cytokines interleukin-12, interleukin-23 and interleukin-17[73] and inhibit the inflammatory pathway at a different point than the anti-TNF- antibodies.[26] IL-12 and IL-23 share a common domain, p40, which is the target of the recently FDA-approved ustekinumab.[27]

Two drugs that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal antibody that specifically targets the CD11a subunit of LFA-1.[71] It also blocks the adhesion molecules on the endothelial cells that line blood vessels, which attract T cells. Efalizumab was voluntarily withdrawn from the European market in February 2009 and from the US market in June 2009 by the manufacturer due to the medication's association with cases of progressive multifocal leukoencephalopathy.[71] Alefacept also blocks the molecules that dendritic cells use to communicate with T cells and even causes natural killer cells to kill T cells as a way of controlling inflammation.[26]

Individuals with psoriasis may develop neutralizing antibodies against monoclonal antibodies. Neutralization occurs when an antidrug antibody prevents a monoclonal antibody such as infliximab from binding antigen in a laboratory test. Specifically, neutralization occurs when the antidrug antibody binds to infliximab's antigen binding site instead of TNF-. When infliximab no longer binds tumor necrosis factor alpha, it no longer decreases inflammation, and the psoriasis may worsen. Neutralizing antibodies have not been reported against etanercept, a biologic-drug that is a fusion protein composed of two TNF- receptors. The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF- receptor, and the development of immune tolerance.[74]

Limited evidence suggests removal of the tonsils may benefit people with chronic plaque psoriasis, guttate psoriasis, and palmoplantar pustulosis.[75][76]

Uncontrolled studies have suggested that individuals with psoriasis or psoriatic arthritis may benefit from a diet supplemented with fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).[77] Conflicting evidence exists indicating that there may be an increased incidence of psoriasis in people with celiac disease. Psoriatic disease severity decreased after 3 months of a gluten free diet in patients with anti-gliadin antibodies.[77]

Most people with psoriasis experience nothing more than mild skin lesions that can be treated effectively with topical therapies.[59]

Psoriasis is known to have a negative impact on the quality of life of both the affected person and the individual's family members.[27] Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Itching and pain can interfere with basic functions, such as self-care and sleep.[40] Participation in sporting activities, certain occupations, and caring for family members can become difficult activities for those with plaques located on their hands and feet.[40] Plaques on the scalp can be particularly embarrassing, as flaky plaque in the hair can be mistaken for dandruff.[78]

Individuals with psoriasis may feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psoriasis has been associated with low self-esteem and depression is more common among those with the condition.[2] People with psoriasis often feel prejudiced against due to the commonly held incorrect belief that psoriasis is contagious.[40] Psychological distress can lead to significant depression and social isolation; a high rate of thoughts about suicide has been associated with psoriasis.[17] Many tools exist to measure the quality of life of patients with psoriasis and other dermatological disorders. Clinical research has indicated individuals often experience a diminished quality of life.[79] Children with psoriasis may encounter bullying.[80]

Several conditions are associated with psoriasis. These occur more frequently in older people. Nearly half of individuals with psoriasis over the age of 65 have at least three comorbidities, and two-thirds have at least two comorbidities.[81]

Psoriasis has been associated with obesity[2] and several other cardiovascular and metabolic disturbances. The incidence of diabetes is 27% higher in people affected by psoriasis than in those without the condition.[82] Severe psoriasis may be even more strongly associated with the development of diabetes than mild psoriasis.[82] Younger people with psoriasis may also be at increased risk for developing diabetes.[81][83] Individuals with psoriasis or psoriatic arthritis have a slightly higher risk of heart disease and heart attacks when compared to the general population. Cardiovascular disease risk appeared to be correlated with the severity of psoriasis and its duration. There is no strong evidence to suggest that psoriasis is associated with an increased risk of death from cardiovascular events. Methotrexate may provide a degree of protection for the heart.[31][81]

The odds of having hypertension are 1.58 times higher in people with psoriasis than those without the condition; these odds are even higher with severe cases of psoriasis. A similar association was noted in people who have psoriatic arthritisthe odds of having hypertension were found to be 2.07 times greater when compared to odds of the general population. The link between psoriasis and hypertension is not currently understood. Mechanisms hypothesized to be involved in this relationship include the following: dysregulation of the renin-angiotensin system, elevated levels of endothelin 1 in the blood, and increased oxidative stress.[83][84] The incidence of the heart rhythm abnormality atrial fibrillation is 1.31 times higher in people with mild psoriasis and 1.63 times higher in people with severe psoriasis.[85] There may be a slightly increased risk of stroke associated with psoriasis, especially in severe cases.[31][86] Treating high levels of cholesterol with statins has been associated with decreased psoriasis severity, as measured by PASI score, and has also been associated with improvements in other cardiovascular disease risk factors such as markers of inflammation.[87] These cardioprotective effects are attributed to ability of statins to improve blood lipid profile and because of their anti-inflammatory effects. Statin use in those with psoriasis and hyperlipidemia was associated with decreased levels of high-sensitivity C-reactive protein and TNF as well as decreased activity of the immune protein LFA-1.[87] Compared to individuals without psoriasis, those affected by psoriasis are more likely to satisfy the criteria for metabolic syndrome.[12][85]

The rates of Crohn's disease and ulcerative colitis are increased when compared with the general population, by a factor of 3.8 and 7.5 respectively.[2] Few studies have evaluated the association of multiple sclerosis with psoriasis, and the relationship has been questioned.[2][88] Psoriasis has been associated with a 16% increase in overall relative risk for non-skin cancer.[31] People with psoriasis have a 52% increased risk cancers of the lung and bronchus, a 205% increase in the risk of developing cancers of the upper gastrointestinal tract, a 31% increase in the risk of developing cancers of the urinary tract, a 90% increase in the risk of developing liver cancer, and a 46% increase in the risk of developing pancreatic cancer.[31] The risk for development of non-melanoma skin cancers is also increased. Psoriasis increases the risk of developing squamous cell carcinoma of the skin by 431% and increases the risk of basal cell carcinoma by 100%.[31] There is no increased risk of melanoma associated with psoriasis.[31]

Psoriasis is estimated to affect 2-4% of the population of the western world.[6] The rate of psoriasis varies according to age, gender, region and ethnicity; a combination of environmental and genetic factors is thought to be responsible for these differences.[6] It can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years. Approximately one third of psoriasis patients report being diagnosed before age 20.[89] Psoriasis affects both sexes equally.[49]

People with inflammatory bowel disease such as Crohn's disease or ulcerative colitis are at an increased risk of developing psoriasis.[37] Psoriasis is more common in countries farther from the equator.[37] Persons of white European ancestry are more likely to have psoriasis and the condition is relatively uncommon in African Americans and extremely uncommon in Native Americans.[38]

Scholars believe psoriasis to have been included among the various skin conditions called tzaraath (translated as leprosy) in the Hebrew Bible, a condition imposed as a punishment for slander. The patient was deemed "impure" (see tumah and taharah) during their afflicted phase and is ultimately treated by the kohen.[90] However, it is more likely that this confusion arose from the use of the same Greek term for both conditions. The Greeks used the term lepra () for scaly skin conditions. They used the term psora to describe itchy skin conditions.[90] It became known as Willan's lepra in the late 18th century when English dermatologists Robert Willan and Thomas Bateman differentiated it from other skin diseases. Leprosy, they said, is distinguished by the regular, circular form of patches, while psoriasis is always irregular. Willan identified two categories: leprosa graecorum and psora leprosa.[91]

Psoriasis is thought to have first been described in Ancient Rome by Cornelius Celsus. The disease was first classified by English physician Thomas Willan. The British dermatologist Thomas Bateman described a possible link between psoriasis and arthritic symptoms in 1813.[92]

The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. In the 18th and 19th centuries, Fowler's solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis.[90]Mercury was also used for psoriasis treatment during this time period.[90]Sulfur, iodine, phenol were also commonly used treatments for psoriasis during this era when it was incorrectly believed that psoriasis was an infectious disease.[90] Coal tars were widely used with ultraviolet light irradiation as a topical treatment approach in the early 1900s.[90][93] During the same time period, psoriatic arthritis cases were treated with intravenously administered gold preparations in the same manner as rheumatoid arthritis.[93] All of these treatments have been replaced with modern topical and systemic therapies.

The word psoriasis is from Greek , meaning "itching condition" or "being itchy"[94] from psora, "itch" and -iasis, "action, condition".

The International Federation of Psoriasis Associations (IFPA) is the global umbrella organization for national and regional psoriasis patient associations and also gathers the leading experts in psoriasis and psoriatic arthritis research for scientific conferences every three years.[95] The Psoriasis International Network, a program of the Fondation Ren Touraine, gathers dermatologists, rheumatologists and other caregivers involved in the management of psoriasis. Non-profit organizations the National Psoriasis Foundation in the United States, the Psoriasis Association in the United Kingdom, and Psoriasis Australia offer advocacy and education about psoriasis in their respective countries.

Diseases of the skin and appendages by morphology

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Psoriasis - Wikipedia, the free encyclopedia

Recommendation and review posted by simmons

Regenexx Knee Stem Cell Therapy for Injuries and ArthritisChris Centeno2015-08-07T15:30:40+00:00

The Regenexx family ofnon-surgical stem cell and blood platelet procedures offer next-generation injection treatments for those who are suffering from knee pain or may be facing knee surgery or knee replacement due to common tendon, ligament and bone injuries, arthritis and other degenerative conditions.

As an alternative to knee surgery or knee replacement, Regenexx procedures may help alleviate knee pain and the conditions that cause it with a same-day office injection procedure. Unlike traditional surgery, Regenexx patients are typically encouraged to walk the same day, and most patients experience very little down time from the procedure.

Knee Patient Results | Regenexx SD Procedure Overview | ACL Injuries | Meniscus Tears

This is not a complete list of conditions treated, but the most common knee conditions we have treated throughout the years. If you are experiencing knee pain, injury, or arthritis, please contact us or complete the candidacy form below to learn more about whether the Regenexx Procedures are right for you.

This Regenexx-SD (same-day) bone marrow derived stem cell treatment outcome data analysis is part of the Regenexx data download of patients who were tracked in the Regenexx advanced patient registry.

This Regenexx-SD (same-day) bone marrow derived stem cell treatment outcome data analysis is part of the Regenexx data download of patients who were tracked in the Regenexx advanced patient registry following treatment for Meniscus Tears.

This data utilizes LEFS (Lower Extremity Functional Scale) data from our knee arthritis patients treated with stem cell injections. Functional questionnaires ask the patients questions such as how well they can walk, run, climb stairs, etc. The improvements following the Regenexx-SD procedure are highly statistically significant.

If you are considering a knee replacement, watch the video in the sidebar of this page and read about how stem cells stack up against knee replacements.

BioMed Research International;Volume 2014, Article ID 370621,.Centeno CJ.

Introduction. We investigated the use of autologous bone marrow concentrate (BMC) with and without an adipose graft, fortreatment of knee osteoarthritis (OA). Methods. Treatment registry data for patients who underwent BMC procedures with andwithout an adipose graft were analyzed. Pre- and posttreatment outcomes of interest included the lower extremity functional scale(LEFS), the numerical pain scale (NPS), and a subjective percentage improvement rating. Multivariate analyses were performedto examine the effects of treatment type adjusting for potential confounding factors. The frequency and type of adverse events(AE) were also examined. Results. 840 procedures were performed, 616 without and 224 with adipose graft. The mean LEFS scoreincreased by 7.9 and 9.8 in the two groups (out of 80), respectively, and the mean NPS score decreased from 4 to 2.6 and from 4.3to 3 in the two groups, respectively. AE rates were 6% and 8.9% in the two groups, respectively. Although pre- and posttreatmentimprovements were statistically significant, the differences between the groups were not. Conclusion. BMC injections for knee OAshowed encouraging outcomes and a low rate of AEs. Addition of an adipose graft to the BMC did not provide a detectible benefitover BMC alone.

Two time Super Bowl Champ Jarvis Greens story. From a young boy struggling to get through a football practice, to a 2X Super Bowl Champion, Jarvis tells his story of pain and struggle following knee surgeries, and his return to form following a Regenexx Stem Cell Procedure.

If you are interested in learning whether you are a good candidate for the Regenexx Procedure, please complete the Regenexx Procedure Candidate Form below or call us at 888-525-3005.

Link:
Knee Stem Cell Therapy - Surgery & Replacement Alternative

Recommendation and review posted by Bethany Smith

Genetic engineering is the deliberate, controlled manipulation of the genes in an organism with the intent of making that organism better in some way. This is usually done independently of the natural reproductive process. The result is a so-called genetically modified organism (GMO). To date, most of the effort in genetic engineering has been focused on agriculture.

Proponents of genetic engineering claim that it has numerous benefits, including the production of food-bearing plants that are resistant to extreme weather and adverse climates, insect infestations, disease, molds, and fungi. In addition, it may be possible to reduce the amount of plowing necessary in the farming process, thereby saving energy and minimizing soil erosion. A major motivation is the hope of producing abundant food at low cost to reduce world hunger, both directly (by feeding GMOs to human beings) and indirectly (by feeding GMOs to livestock and fish, which can in turn be fed to humans).

Genetic engineering carries potential dangers, such as the creation of new allergens and toxins, the evolution of new weeds and other noxious vegetation, harm to wildlife, and the creation of environments favorable to the proliferation of molds and fungi (ironically, in light of the purported advantage in that respect). Some scientists have expressed concern that new disease organisms and increased antibiotic resistance could result from the use of GMOs in the food chain.

The darkest aspect of genetic engineering is the possibility that a government or institution might undertake to enhance human beings by means of genetic engineering. Some see the possibility of using this technology to create biological weapons.

Genetic engineering is also known as genetic modification.

This was last updated in May 2007

Link:
What is genetic engineering? - Definition from WhatIs.com

Recommendation and review posted by Bethany Smith

Genetic Engineering (GE) is a highly complicated and advanced branch of science which involves a wide range of techniques used in changing the genetic material in the DNA code in a living organism. 'Genetic Engineering' means the deliberate modification of the characters of an organism by the manipulation of its genetic material.Genetic engineering comes under the broad heading of Biotechnology. There is a great scope in this field as the demand for genetic engineers are growing in India as well as abroad.

A cell is the smallest living unit, the basic structural and functional unit of all living matter, whether a plant, an animal, humans or a fungus. While some organisms are single celled, others like plants, animals, humans etc are made up of a lot more cells. For eg humans have approximately 3 million cells. A cell is composed of a 'cell membrane' enclosing the whole cell, many 'organelles' equivalent to the organs in the body and a 'nucleus' which is the command centre of the cell. Inside the nucleus are the chromosomes which is the storage place for all genetic (hereditary) information which determines the nature and characteristics of an organism. This information is written along the thin thread, called DNA, a nucleic acid which constitutes the genes (units of heredity). The DNA governs cell growth and is responsible for the transmission of genetic information from one generation to the next.

Genetic engineering aims to re-arrange the sequence of DNA in gene using artificial methods. The work of a genetic engineer involves extracting the DNA out of one organism, changing it using chemicals or radiation and subsequently putting it back into the same or a different organism. For eg: genes and segments of DNA from one species is taken and put into another species. They also study how traits and characteristics are transmitted through the generations, and how genetic disorders are caused. Their research involves researching the causes and discovering potential cures if any.

Genetic engineering have specialisations related to plants, animals and human beings. Genetic engineering in plants and animals may be to improve certain natural characteristics of value, to increase resistance to disease or damage and to develop new characteristics etc. It is used to change the colour, size, texture etc of plants otherwise known as GM (Genetically Modified) foods.GE in humans can be to correct severe hereditary defects by introducing normal genes into cells in place of missing or defective ones.

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Genetic Engineering Careers in India : How to become a ...

Recommendation and review posted by Bethany Smith

A portrait of Khan Noonien Singh, a man who was a product of genetic engineering

Genetic engineering, or genetic manipulation was a process in which the DNA of an organism was selectively altered through artificial means. Genetic engineering was often used to produce "custom" organisms, such as for agricultural or medical purposes, as well as to produce biogenic weapons. The most common application of genetic engineering on intelligent beings in the Federation was corrective DNA resequencing for genetic disorders. A far more dubious application of genetic engineering was the genetic enhancement of individuals to produce improved senses, strength, intelligence, etc.

During Earth's 20th century, efforts to produce "superhumans" resulted in the Eugenics Wars. Genetically engineered individuals such as Khan Noonien Singh attempted to seize power. (TOS: "Space Seed")

This would lead to the banning of genetic engineering on Earth by the mid-22nd century, even research which could be used to cure critical illnesses. This ban was implemented because of the general fear of creating more tyrants such as Khan. It was also felt that parents would feel compelled to have their children genetically engineered, especially if "enhanced" individuals were allowed to compete in normal society.

Some, including geneticist Arik Soong, argued that it was simply convenient for humanity to denounce the attempts at genetic "improvement" of humanity, that it was inherently evil because of the Eugenics Wars. He argued that the source of the problem, in fact, wasn't the technology, but humanity's own inability to use it wisely. Imprisoned for, among other crimes, stealing the embryos of a number of Augment children, Soong wrote long treatises on the subject of genetic augmentations and improvements. His works were routinely taken and placed into storage (although his jailers often told him that his work was vaporized). Captain Jonathan Archer expressed his hope to Soong that research into genetic engineering that could cure life-threatening diseases would someday be resumed. (ENT: "Borderland", "The Augments")

Others, however, chose to establish isolated colonies, as became the case with the Genome colony on Moab IV, which was established in 2168. It became a notable and successful example of Human genetic engineering in which every individual was genetically tailored from birth to perform a specific role in society. However, after a five-day visit by the USS Enterprise-D when the ship came to the colony in an effort to save it from an approaching neutron star which, eventually, the craft was able to effectively redirect twenty-three colonists left the colony aboard the craft, possibly causing significant damage to the structure of their society. The reason for the societal split was that those who left the colony had realized their organized, pre-planned world had certain limitations, lacking opportunities to grow that were offered by the Enterprise. (TNG: "The Masterpiece Society")

By the 24th century, the United Federation of Planets allowed limited use of genetic engineering to correct existing genetically related medical conditions. Persons known to be genetically enhanced, however, were not allowed to serve in Starfleet, and were especially banned from practicing medicine. (TNG: "Genesis", DS9: "Doctor Bashir, I Presume")

Nevertheless, some parents attempted to secretly have their children genetically modified. (DS9: "Doctor Bashir, I Presume") Unfortunately, most of these operations were performed by unqualified physicians, resulting in severe psychological problems in the children due to their enhancements being only partially successful, such as a patient's senses being enhanced while their ability to process the resulting data remained at a Human norm. (DS9: "Statistical Probabilities")

In some cases, genetic engineering can be permitted to be performed in utero when dealing with a developing fetus to correct any potential genetic defects that could handicap the child as they grew up. Chakotay's family history included a defective gene that made those who possessed it prone to hallucinations, the gene afflicting his grandfather in Chakotay's youth, although the gene was suppressed in Chakotay himself. (VOY: "The Fight") In 2377, The Doctor performed prenatal genetic modification on Miral Paris to correct a spinal deviation, a congenital defect that tends to run in Klingon families; Miral's mother had undergone surgery to correct the defect in herself at a young age. (VOY: "Lineage")

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Genetic engineering - Memory Alpha, the Star Trek Wiki

Recommendation and review posted by Bethany Smith

Vocabulary: selective breeding, recombinant DNA, artificial selection, inbreeding, hybridization, genetic engineering, restriction enzyme, cloning, genetic mapping, Human Genome Project

Genetic Engineering Throughout recorded history, humans have used selective breeding and other methods to produce organisms with desirable traits. Our current understanding of genetics and heredity allows for the manipulation of genes and the development of new combinations of traits and new varieties of organisms. This includes various aspects of DNA technology, including recombinant DNA technology. Scientists have also developed many ways of determining the genetic makeup of different organisms, including humans.

Selective Breeding For thousands of years new varieties of cultivated plants and domestic animals have resulted from selective breeding for particular traits. Some selective breeding techniques include artificial selection, where individuals with desirable traits are mated to produce offspring with those traits. A variation of this process traditionally used in agriculture is inbreeding, where the offspring produced by artificial selection are mated with one another to reinforce those desirable traits. Hybridization is a special case of selective breeding. This involves crossing two individuals with different desirable traits to produce offspring with a combination of both desirable traits. An example of this are Santa Gertrudis cattle, which were developed by breeding English shorthorn cattle, which provided for good beef, but lacked heat resistance, with Brahman cattle from India which were highly resistant to heat and humidity. The Santa Gertrudis breed of cattle has excellent beef, and thrives in hot, humid environments.

An Example of Selective Breeding

Brahman cattle: Good resistance to heat but poor beef.

English shorthorn cattle: Good beef but poor heat resistance.

Santa Gertrudis cattle: Formed by crossing Brahman and English shorthorns; has good heat resistance and beef.

Genetic Engineering In recent years new varieties of farm plants and animals have been engineered bymanipulating their genetic instructions to produce new characteristics. This technology is known as genetic engineering or recombinant DNA technology. Different enzymes can be used to cut, copy (clone), and move segments of DNA. An important category of enzyme used to cut a section of a gene and its DNA from an organism is known as a restriction enzyme. When this piece of DNA, which has been cut out of one organism, is placed in another organism, that section of gene will express the characteristics that were expressed by this gene in the organism it was taken from.

An Example of Genetic Engineering

Knowledge of genetics, including genetic engineering, is making possible new fields of health care. Genetic engineering is being used to engineer many new types of more efficient plants and animals, as well as provide chemicals needed for human health care. It may be possible to use aspect of genetic engineering to correct some human health defects. Some examples of chemicals being mass produced by human genes in bacteria include insulin, human growth hormone, and interferon. Substances from genetically engineered organisms have reduced the cost and side effects of replacing missing human body chemicals. While genetic engineering technology has many practical benefits, its use has also raised many legitimate ethical concerns.

Other Genetic Technologies Cloning involves producing a group of genetically identical offspring from the cells of an organism. This technique may greatly increase agricultural productivity. Plants and animals with desirable qualities can be rapidly produced from the cells of a single organism.

Genetic mapping, which is the location of specific genes inside the chromosomes of cells makes it possible to detect, and perhaps in the future correct defective genes that may lead to poor health. The human genome project has involved the mapping of the major genes influencing human traits, thus allowing humans to know the basic framework of their genetic code

Knowledge of genetics is making possible new fields of health care. Genetic mapping in combination with genetic engineering and other genetic technologies may make it possible to correct defective genes that may lead to poor health.

There are many ethical concerns to these advanced genetic technologies, including possible problems associated with the cloning of humans. Another down side to genetic mapping technologies it is possible that some organizations may use this genetic information against individuals.

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Genetic Engineering - Oswego City School District Regents ...

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Long gone are the days when health care providers told people with arthritis to rest their joints. In fact, physical activity can reduce pain and improve function, mobility, mood, and quality of life for most adults with many types of arthritis including osteoarthritis, rheumatoid arthritis, fibromyalgia, and lupus. Physical activity can also help people with arthritis manage other chronic conditions such as diabetes, heart disease, and obesity. Most people with arthritis can safely participate in a self-directed physical activity program or join one of many programs available in communities across the country. Some people may benefit from physical or occupational therapy. A 2-page fact sheet summarizing physical activity for people with arthritis is available.

Regular physical activity is just as important for people with arthritis or other rheumatic conditions as it is for all children and adults. Scientific studies have shown that participation in moderate-intensity, low-impact physical activity improves pain, function, mood, and quality of life without worsening symptoms or disease severity. Being physically active can also delay the onset of disability if you have arthritis. But people with arthritis may have a difficult time being physically active because of symptoms (e.g., pain, stiffness), their lack of confidence in knowing how much and what to do, and unclear expectations of when they will see benefits. Both aerobic and muscle strengthening activities are proven to work well, and both are recommended for people with arthritis.

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Adults with arthritis should follow either the Active Adult or Active Older Adult Guidelines, whichever meets your personal health goals and matches your abilities. People with arthritis should also include daily flexibility exercises to maintain proper joint range of motion and do balance exercises if they are at risk of falling.

Follow the Active Adult recommendations if you are younger than age 65, have normal function and no limitations in your usual activities, and do not have any other severe chronic conditions such as diabetes, heart disease, or cancer.

Aerobic activity per week =

AND

Muscle strengthening activities at least 2 days per week.

Aerobic activity per week =

AND

Muscle strengthening activities at least 2 days per week.

Follow the Active Older Adult recommendations if you are older than age 65, have poor function and are limited in some of your usual activities, or you have other chronic conditions besides arthritis.

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Aerobic activity per week =

AND

Muscle strengthening activities at least 2 days per week.

Include activities that promote balance at least 3 days per week.

Aerobic activity per week =

AND

Muscle strengthening activities at least 2 days per week.

Include activities that promote balance at least 3 days per week.

What types of activities count?

Aerobic activities. Aerobic activity is also called "cardio," endurance, or conditioning exercise. It is any activity that makes your heart beat faster and makes you breathe a little harder than when you are sitting, standing or lying. You want to do activity that is moderate or vigorous intensity and that does not twist or "pound" your joints too much. Some people with arthritis can do vigorous activities such as running and can even tolerate some activities that are harder on the joints like basketball or tennis. You should choose the activities that are right for you and that are enjoyable. Remember, each person is different, but there are a wide variety of activities that you can do to meet the Guidelines.

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Examples of Moderate and Vigorous Intensity Aerobic Activities

Muscle strengthening activities. You should do activities that strengthen your muscles at least 2 days per week in addition to your aerobic activities. Muscle strengthening activities are especially important for people with arthritis because having strong muscles takes some of the pressure off the joints.

You can do muscle strengthening exercises in your home, at a gym, or at a community center. You should do exercises that work all the major muscle groups of the body (e.g., legs, hips, back, abdomen, chest, shoulders, and arms). You should do at least 1 set of 812 repetitions for each muscle group. There are many ways you can do muscle strengthening activities:

Balance activities. Many older adults and some adults with arthritis and other chronic diseases may be prone to falling. If you are worried about falling or are at risk of falling, you should include activities that improve balance at least 3 days per week as part of your activity plan. Balance activities can be part of your aerobic or your muscle strengthening activities. Examples of activities that improve balance include the following

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Stay flexible. In addition to the activities recommended above, flexibility exercises are also important. Many people with arthritis have joint stiffness that makes daily tasks such as bathing and fixing meals difficult. Doing daily flexibility exercises for all upper (e.g., neck, shoulder, elbow, wrist, and finger) and lower (e.g., low back, hip, knee, ankle, and toes) joints of the body helps maintain essential range of motion.

If you have arthritis, you should follow either the Active Adult or Active Older Adult recommendations, whichever meets your personal health goals and matches your abilities. You should do this activity in addition to your usual daily activity. You may notice that the recommended amount and type of activity are the same for the Active Adult and Active Older Adult except for the additional recommendation to include activities that promote balance. Read some additional details for the Active Older Adult below:

Prevent falls. Have you fallen in the past? Do you have trouble walking? If so, you may be at high risk of falling. Activities that improve or maintain balance should be included in your physical activity plan. Examples of activities that have been proven to help balance include walking backwards, standing on one leg, and Tai Chi. Some exercise classes offered in many local communities include exercises that are good for balance.

Stay active. Any physical activity is better than none. If you cannot do 150 minutes of moderate intensity activity every week, it is important to be as active as your health allows. People with arthritis often have symptoms that come and go. This may mean that one week you can do 150 minutes of moderate intensity activity and the next week you cant. You may have to change your activity level depending on your arthritis symptoms, but try to stay as active as your symptoms allow. Learn how to modify your activity with these tips for S.M.A.R.T. activity.

Adjust the level of effort. Some activities take more effort for older adults and those with low fitness or poor function. For example, walking at a brisk pace for a 23-year-old healthy male is moderate intensity, but the same activity may be vigorous activity for a 77-year-old male with diabetes. You should adjust the level of effort during activity so that it is comfortable for you. Find out how to measure your level of effort.

Talk to your doctor. If you have arthritis or another chronic health condition, you should already be under the care of a doctor or other health care provider. Health care providers and certified exercise professionals can answer your questions about how much and what types of activity are right for you.

How hard are you working? Moderate intensity activity makes your heart beat a little faster and you breathe a little harder. You can talk easily while doing moderate intensity activity, but you may not be able to sing comfortably.

Vigorous intensity activity makes your heart beat much faster and you may not be able to talk comfortably without stopping to catch your breath.

Relative intensity can be estimated using a scale of 0 to 10 where sitting is 0 and 10 is the highest level of effort possible. Moderate intensity activity is a 5 or 6 and vigorous intensity activity is a 7 or 8. The talk test is a simple way to measure relative intensity. In general, if you're doing moderate-intensity activity you can talk, but not sing, during the activity. If you are doing vigorous-intensity activity, you will not be able to say more than a few words without pausing for a breath.

Read more about measuring physical activity intensity.

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Safe, enjoyable physical activity is possible for most every adult with arthritis. The most important thing to remember is to find out what works best for you. At first glance, 150 minutes of activity per week sounds like a lot, but if you pay attention to the following tips you will be well on your way to getting the recommended amount of activity in no time!

Studies show that some increase in pain, stiffness, and swelling is normal when starting an activity program. If you have increased swelling or pain that does not get better with rest then talk to your health care provider. It may take 68 weeks for your joints to accommodate to your increased activity level, but sticking with your activity program will result in long-term pain relief.

Here is an easy way to remember these tips: Make S.M.A.R.T choices!

Start low, and go slow.

Many adults with arthritis are inactive, even though their doctor may have told them being active will help their arthritis. You may want to be more active but just dont know where to start or how much to do. You may be worried that using your joints and muscles may make your arthritis worse. The good news is that the opposite is true, physical activity will help your arthritis! The first key to starting activity safely is to start low. This may mean you can only walk 5 minutes at a time every other day. The second key is to go slow. People with arthritis may take more time for their body to adjust to a new level of activity. For example, healthy children can usually increase the amount of activity a little each week, while older adults and those with chronic conditions may take 34 weeks to adjust to a new activity level. You should add activity in small amounts, at least 10 minutes at a time, and allow enough time for your body to adjust to the new level before adding more activity. Click here for real life examples of how to progress activity levels safely.

Modify activity as needed.

Remember, any activity is better than none. Your arthritis symptoms, such as pain, stiffness and fatigue, may come and go and you may have good days and bad days. You may want to stop activity completely when your arthritis symptoms increase. It is important that you first try to modify your activity to stay as active as possible without making your symptoms worse. Here are some ways you can do this:

When your symptoms have returned to normal, slowly increase your activity back to your starting level.

Activities should be "joint friendly."

People with arthritis can do many types of moderate or vigorous intensity activities, some people with arthritis can even run marathons! If you are unsure of what types of activity are best for you, a general rule is to do activities that are easy on the joints like walking, bicycling, water aerobics, or dancing. These activities have a low risk of injury and do not twist or "pound" the joints too much. It is also important to pick a variety of activities that you enjoy, this will help keep you from getting bored and make it easier to stick with your activity plan.

Recognize safe places and ways to be active.

Safety is important for starting and maintaining your activity plan. If you are currently inactive or do not have confidence in planning your own physical activity, a class designed just for people with arthritis may be a good option for you. Some people with arthritis feel safer by starting an activity program in a class with a trained instructor and get support from and gain confidence by participating with the other people with arthritis. Local chapters of the Arthritis Foundation offer 2 classes, the Arthritis Foundation Exercise Program and the Arthritis Foundation Aquatics Program, in many communities. For a list of more exercise programs, click here.

If you currently do some activity or feel confident that you can safely plan your own activity program, you should look for safe places to be physically active. For example, if you walk in your neighborhood or a local park make sure the sidewalks or pathways are level and free of obstructions, are well-lighted, and are separated from heavy traffic.

Talk to a health professional.

You should already be under the care of a health care professional for your arthritis, who is a good source of information about physical activity. Health care professionals and certified exercise professionals can answer your questions about how much and what types of activity match your abilities and health goals.

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I dont do any activity now, how do I start?

Meet Jean, a 48-year-old grandmother.

Jean is 48 years old and has rheumatoid arthritis. Her doctor has told her to increase her physical activity because it will help her arthritis. Jean wants to be able to walk to and from the park and play with her grandchildren. Right now, she does not have the stamina to walk to the park which is only a 15 minute walk from her house. Jean is also not very confident she knows how to safely start and increase her activity level. She is worried she will make her arthritis symptoms worse.

Start low.

The nurse in Jeans doctors office told her about group exercise programs that are just for people with arthritis. There are classes every week at the community center close to Jeans neighborhood. Jean works full-time but doesnt have to start work until 10:00AM. She found out one of the classes, the Arthritis Foundation Aquatics Program (AFAP), meets at 8:00AM on Mondays, Wednesdays and Fridays. The class lasts for 60 minutes, which allows her enough time to shower, dress, and get to work on time. Jean went to the community center to sign up but was concerned she may not be able to do 60 minutes of activity at one time. The instructor assured her that the exercises can be modified and the instructors are trained to help each person work at their own level.

Go slow.

For the next 4 months, Jean attends the AFAP class 3 days per week. The first 4 weeks she cannot do all the exercises and has to take a lot of breaks, so she was working at a moderate effort for about 1015 minutes each class (3045 minutes of aerobic activity per week). By the 7th week, she can do 20 minutes per class and by the 3rd month she is up to 30 minutes (90 minutes of aerobic activity per week). Jean feels great and can tell she has more stamina. Over the next 4 weeks Jean slowly increases the time she is working at a moderate effort each class until she can do the entire 60 minute class without stopping (180 minutes of moderate aerobic activity per week).

Get advice.

Although Jean feels the AFAP has helped strengthen her muscles and given her more stamina, she now feels she should do more muscle strengthening exercises. For Christmas, her children gave her a gift certificate for 4 free sessions with a certified exercise specialist at a local fitness center. At her first session, she asked for instructions on how she can do muscle strengthening exercises at home. The fitness professional gave her some elastic resistance bands and showed her how to use them to strengthen all the major muscle groups of the body. Jean is now using the resistance and 2 days per week in addition to her aquatics classes.

I do some activity now, how can I safely increase my activity to gain more health benefits?

Meet Steve, an active 69-year-old retiree.

Steve is a 69-year old-retired accountant who has been physically active all his life but has been diagnosed with osteoarthritis in his knee. Now that he is retired, Steve has the time to increase his activity level even more. Steves goal is to increase his total activity per week and to do some vigorous intensity activity because he knows it is good for his heart and may reduce his risk of getting some cancers. Steve currently does 180 minutes of moderate intensity activity each week including

Adding more activity.

Steve wants to increase his total activity to at least 300 minutes per week of moderate intensity activity. He decides that without too much trouble he can easily add 1 more day of golf, adding 60 minutes of moderate intensity activity each week. Steves wife recently joined a local seniors tennis league and has been bugging him to play tennis with her. Steve hasnt played tennis in a long time so he signed up for 4 weeks of tennis lessons at the parks and recreation department in his town. After the lessons, he and his wife started playing doubles tennis 2 days per week for an hour each time (60 minutes of moderate intensity activity, 120 minutes per week). He continues to lift weights 2 days per week. Steve has successfully added 180 minutes of moderate intensity activity and now gets a total of 360 minutes per week.

Trading up to vigorous activity.

After doing this level of activity for 4 months, Steve wants to trade some of the moderate intensity activity he does for vigorous intensity activity. He decides that on 2 of the 3 days he uses the stationary bicycle at home, he will instead use the stair climber or elliptical machines at his fitness center. Because one minute of vigorous intensity activity equals about 2 minutes of moderate intensity, Steve plans to do 20 minutes on 2 days each week when he is at the gym. Steves activity program now includes

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Some soreness or aching in joints and surrounding muscles during and after exercise is normal for people with arthritis. This is especially true in the first 4 to 6 weeks of starting an exercise program. However, most people with arthritis find if they stick with exercise they will have significant long-term pain relief. Here are some tips to help you manage pain during and after exercise:

Signs you should see your health care provider:

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More:
CDC - Arthritis - Physical Activity for Arthritis - Overview

Recommendation and review posted by simmons

Melatonin and Multiple Sclerosis: Why MS Symptoms May Improve as the Days Get Shorter Sep. 10, 2015 Researchers have found an explanation that could lead to a deeper understanding of multiple sclerosis and more targeted treatment options for patients. By first looking broadly at possible ... read more People With Multiple Sclerosis May Have Double the Risk of Dying Early May 27, 2015 New research suggests people with multiple sclerosis (MS) may have double the risk of dying early compared to people without MS, with those younger than 59 at a three times higher ... read more Discovery of a Treatment to Block the Progression of Multiple Sclerosis May 20, 2015 A drug that could halt the progression of multiple sclerosis may soon be developed thanks to a new ... read more Multiple Sclerosis: Scientists Identify Cause of Movement, Balance Problems May 19, 2015 New research into the causes of the excessive inflammation that drives multiple sclerosis has identified a faulty 'brake' within immune cells, a brake that should be controlling the ... read more Antiviral Compound May Protect Brain from Pathogens, West Nile Virus, Study Shows May 15, 2015 An antiviral compound may protect the brain from invading pathogens, researchers have found. Studying West Nile virus infection in mice, scientists showed that interferon-lambda tightens the ... read more Cytokine May Play Major Role in Multiple Sclerosis Apr. 29, 2015 Multiple sclerosis (MS) is caused by immune cells that activate a cascade of chemicals in the brain, attacking and degrading the insulation that keeps neuronal signals moving. These chemicals, called ... read more Potential New Treatment for Multiple Sclerosis Apr. 27, 2015 Scientists have discovered a way to prevent the development of multiple sclerosis in mice. Using a drug that blocks the production of a certain type of immune cell linked to inflammation and ... read more Alarming Rise in Cost of MS Drugs Over Past Two Decades Apr. 24, 2015 A new study shows an 'alarming rise' over the last 20 years in the costs of drugs used to slow the progression of multiple sclerosis or reduce the frequency of attacks. A substantial ... read more What Happens When Multiple Sclerosis Patients Stop Taking Their Medication? Apr. 21, 2015 We know a lot about what happens when therapy is started with MS patients, but we know very little about what happens when therapy is stopped. A new international, multi-site study found that almost ... read more Extending Natalizumab Up to 8 Weeks Shown Safe and Effective in Patients With Multiple Sclerosis, Report Says Apr. 20, 2015 Extending the dose of natalizumab from four weeks up to eight weeks was shown to be well-tolerated and effective in patients, and resulted in no cases of the potentially fatal side effect progressive ... read more Epilepsy Drug May Preserve Eyesight for People With Multiple Sclerosis Apr. 16, 2015 A drug commonly taken to prevent seizures in epilepsy may surprisingly protect the eyesight of people with multiple sclerosis (MS), according to a new ... read more Experimental Drug May Repair Nerve Damage in Multiple Sclerosis Apr. 14, 2015 A new study suggests that an investigational drug for multiple sclerosis (MS) may repair myelin, the fatty material that protects nerves and is damaged in MS, according to a new ... read more Study of Processing Speed Impact on Cognitive Training Apr. 10, 2015 Treatment with the modified Story Memory Technique (mSMT) may be affected by processing speed, researchers report. mSMT is a 10-session cognitive intervention protocol shown to improve new learning ... read more Multiple Sclerosis Patients Could Benefit from Brain Boost Study Apr. 6, 2015 Multiple sclerosis patients could one day benefit from treatments that boost their brain function, a study suggests. Increasing the activity of neurons could be beneficial in people with the disease, ... read more Mar. 31, 2015 A unique pattern of immune molecules in the cerebrospinal fluid of people with myalgic encephalomyelitis/chronic fatigue syndrome have been discovered, providing insights into the basis for cognitive ... read more Neurological Diseases Share Common Blood-Brain Barrier Defects Mar. 30, 2015 Although stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis (ALS) and traumatic brain injury each affect the central nervous system differently, a new study finds that they share ... read more Mar. 23, 2015 Where ALS comes from and how it progresses are mysteries that continue to vex medical science. But recent research has found three proteins that could shed some light on the mechanisms behind this ... read more Mar. 17, 2015 A new drug-like molecule that can halt inflammation has shown promise in preventing the progression of multiple sclerosis. Researchers developed the molecule inhibit a key signal that triggers ... read more Blood Pressure Drug Protects Against Symptoms of Multiple Sclerosis in Animal Models Mar. 13, 2015 An FDA-approved drug for high blood pressure, guanabenz, prevents myelin loss and alleviates clinical symptoms of multiple sclerosis (MS) in animal models, according to a new study. The drug appears ... read more From Chick to Bedside: Removing the Wnt Barrier Mar. 5, 2015 Kick starting a process that might repair the damage done in cerebral palsy and multiple sclerosis could begin with disabling a driver that helps block regeneration, say ... read more

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Read this article:
Multiple Sclerosis News -- ScienceDaily

Recommendation and review posted by simmons

Multiple sclerosis can cause a variety of symptoms: changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty moving; difficulties with coordination and balance; problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, phosphenes or diplopia), fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology (mainly major depression). The main clinical measure in progression of the disability and severity of the symptoms is the Expanded Disability Status Scale or EDSS.[1]

The initial attacks are often transient, mild (or asymptomatic), and self-limited. They often do not prompt a health care visit and sometimes are only identified in retrospect once the diagnosis has been made after further attacks. The most common initial symptoms reported are: changes in sensation in the arms, legs or face (33%), complete or partial vision loss (optic neuritis) (20%), weakness (13%), double vision (7%), unsteadiness when walking (5%), and balance problems (3%); but many rare initial symptoms have been reported such as aphasia or psychosis.[2][3] Fifteen percent of individuals have multiple symptoms when they first seek medical attention.[4]

Bladder problems (See also urinary system and urination) appear in 7080% of people with multiple sclerosis (MS) and they have an important effect both on hygiene habits and social activity.[5][6] Bladder problems are usually related with high levels of disability and pyramidal signs in lower limbs.[7]

The most common problems are an increase in frequency and urgency (incontinence) but difficulties to begin urination, hesitation, leaking, sensation of incomplete urination, and retention also appear. When retention occurs secondary urinary infections are common.

There are many cortical and subcortical structures implicated in urination[8] and MS lesions in various central nervous system structures can cause these kinds of symptoms.

Treatment objectives are the alleviation of symptoms of urinary dysfunction, treatment of urinary infections, reduction of complicating factors and the preservation of renal function. Treatments can be classified in two main subtypes: pharmacological and non-pharmacological. Pharmacological treatments vary greatly depending on the origin or type of dysfunction and some examples of the medications used are:[9]alfuzosin for retention,[10]trospium and flavoxate for urgency and incontinency,[11][12] and desmopressin for nocturia.[13][14] Non pharmacological treatments involve the use of pelvic floor muscle training, stimulation, biofeedback, pessaries, bladder retraining, and sometimes intermittent catheterization.[15][16]

Bowel problems affect around 70% of the patients, with around 50% of the patients suffering from constipation and up to 30% from fecal incontinence.[16] Cause of bowel impairments in MS patients is usually either a reduced gut motility or an impairment in neurological control of defecation. The former is commonly related to immobility or secondary effects from drugs used in the treatment of the disease.[16] Pain or problems with defecation can be helped with a diet change which includes among other changes an increased fluid intake, oral laxatives or suppositories and enemas when habit changes and oral measures are not enough to control the problems.[16][17]

Some of the most common deficits affect recent memory, attention, processing speed, visual-spatial abilities and executive function.[18] Symptoms related to cognition include emotional instability and fatigue including neurological fatigue. Commonly a form of cognitive disarray is experienced, where specific cognitive processes may remain unaffected, but cognitive processes as a whole are impaired. Cognitive deficits are independent of physical disability and can occur in the absence of neurological dysfunction.[19] Severe impairment is a major predictor of a low quality of life, unemployment, caregiver distress,[20] and difficulty in driving;[21] limitations in a patient's social and work activities are also correlated with the extent of impairment.[19]

Cognitive impairments occur in about 40 to 60 percent of patients with multiple sclerosis,[22] with the lowest percentages usually from community-based studies and the highest ones from hospital-based. Impairments may present at the beginning of the disease.[23] Probable multiple sclerosis sufferers, meaning after a first attack but before a secondary confirmatory one, have up to 50 percent of patients with impairment at onset.[24]Dementia is rare and occurs in only five percent of patients.[19]

Measures of tissue atrophy are well correlated with, and predict, cognitive dysfunction. Neuropsychological outcomes are highly correlated with linear measures of sub-cortical atrophy. Cognitive impairment is the result of not only tissue damage, but tissue repair and adaptive functional reorganization.[20]Neuropsychological testing is important for determining the extent of cognitive deficits. Neuropsychological rehabilitation may help to reverse or decrease the cognitive deficits although studies on the issue have been of low quality.[25]Acetylcholinesterase inhibitors are commonly used to treat Alzheimer's disease related dementia and so are thought to have potential in treating the cognitive deficits in multiple sclerosis. They have been found to be effective in preliminary clinical trials.[25]

Emotional symptoms are also common and are thought to be both a normal response to having a debilitating disease and the result of damage to specific areas of the central nervous system that generate and control emotions.

Clinical depression is the most common neuropsychiatric condition: lifetime depression prevalence rates of 4050% and 12-month prevalence rates around 20% have been typically reported for samples of people with MS; these figures are considerably higher than those for the general population or for people with other chronic illnesses.[26][27] Brain imaging studies have tried to relate depression to lesions in certain regions of the brain have met with variable success. On balance the evidence seems to favour an association with neuropathology in the left anterior temporal/parietal regions.[28]

Other feelings such as anger, anxiety, frustration, and hopelessness also appear frequently and suicide is a very real threat since it results in 15% of deaths in MS sufferers.[29]

Rarely psychosis may also be featured.[30]

Fatigue is very common and disabling in MS with a close relationship to depressive symptomatology.[31] When depression is reduced fatigue also tends to reduce and it is recommended that patients should be evaluated for depression before other therapeutic approaches are used.[32] In a similar way other factors such as disturbed sleep, chronic pain, poor nutrition, or even some medications can all contribute to fatigue and medical professionals are encouraged to identify and modify them.[33] There are also different medications used to treat fatigue; such as amantadine,[34][35] or pemoline;[36][37] as well as psychological interventions of energy conservation;[38][39] but their effects are small[citation needed] and for these reasons fatigue is a difficult symptom to manage. Fatigue has also been related to specific brain areas in MS using magnetic resonance imaging.[40]

Internuclear ophthalmoplegia is a disorder of conjugate lateral gaze. The affected eye shows impairment of adduction. The partner eye diverges from the affected eye during abduction, producing diplopia; during extreme abduction, compensatory nystagmus can be seen in the partner eye. Diplopia means double vision while nystagmus is involuntary eye movement characterized by alternating smooth pursuit in one direction and a saccadic movement in the other direction.

Internuclear ophthalmoplegia occurs when MS affects a part of the brain stem called the medial longitudinal fasciculus, which is responsible for communication between the two eyes by connecting the abducens nucleus of one side to the oculomotor nucleus of the opposite side. This results in the failure of the medial rectus muscle to contract appropriately, so that the eyes do not move equally (called disconjugate gaze).

Different drugs as well as optic compensatory systems and prisms can be used to improve these symptoms.[41][42][43][44] Surgery can also be used in some cases for this problem.[45]

Restrictions in mobility (walking, transfers, bed mobility etc.) are common in individuals suffering from multiple sclerosis. Within 10 years after the onset of MS one-third of patients reach a score of 6 on the Expanded Disability Status Scale (EDSS), requiring the use of a unilateral walking aid, and by 30 years the proportion increases to 83%. Within five years of onset the EDSS is six in 50% of those with the progressive form of MS.[46]

A wide range of impairments may exist in MS sufferers which can act either alone or in combination to impact directly on a person's balance, function and mobility. Such impairments include fatigue, weakness, hypertonicity, low exercise tolerance, impaired balance, ataxia and tremor.[47]

Interventions may be aimed at the individual impairments that reduce mobility or at the level of disability. This second level intervention includes provision, education, and instruction in the use of equipment such as walking aids, wheelchairs, motorized scooters and car adaptations as well as instruction on compensatory strategies to accomplish an activity for example undertaking safe transfers by pivoting in a flexed posture rather than standing up and stepping around.

Up to 50% of patients with MS will develop an episode of optic neuritis and 20% of the time optic neuritis is the presenting sign of MS. The presence of demyelinating white matter lesions on brain MRIs at the time of presentation for optic neuritis is the strongest predictor in developing clinical diagnosis of MS. Almost half of the patients with optic neuritis have white matter lesions consistent with multiple sclerosis.

At five year follow-ups the overall risk of developing MS is 30%, with or without MRI lesions. Patients with a normal MRI still develop MS (16%), but at a lower rate compared to those patients with three or more MRI lesions (51%). From the other perspective, however, 44% of patients with any demyelinating lesions on MRI at presentation will not have developed MS ten years later.[48][49]

Individuals experience rapid onset of pain in one eye followed by blurry vision in part or all its visual field. Flashes of light (phosphenes) may also be present.[50]Inflammation of the optic nerve causes loss of vision most usually by the swelling and destruction of the myelin sheath covering the optic nerve.

The blurred vision usually resolves within 10 weeks but individuals are often left with less vivid color vision, especially red, in the affected eye.[citation needed]

A systemic intravenous treatment with corticosteroids may quicken the healing of the optic nerve, prevent complete loss of vision and delay the onset of other symptoms.[citation needed]

Pain is a common symptom in MS. A recent study systematically pooling results from 28 studies (7101 patients) estimates that pain affects 63% of people with MS.[51] These 28 studies described pain in a large range of different people with MS. The authors found no evidence that pain was more common in people with progressive types of MS, in females compared to males, in people with different levels of disability, or in people who had had MS for different periods of time.

Pain can be severe and debilitating, and can have a profound effect on the quality of life and mental health of the sufferer.[52] Certain types of pain are thought to sometimes appear after a lesion to the ascending or descending tracts that control the transmission of painful stimulus, such as the anterolateral system, but many other causes are also possible.[43] The most prevalent types of pain are thought to be headaches (43%), dysesthetic limb pain (26%), back pain (20%), painful spasms (15%), painful Lhermitte's phenomenon (16%) and Trigeminal Neuralgia (3%).[51] These authors did not however find enough data to quantify the prevalence of painful optic neuritis.

Acute pain is mainly due to optic neuritis, trigeminal neuralgia, Lhermitte's sign or dysesthesias.[53]Subacute pain is usually secondary to the disease and can be a consequence of spending too much time in the same position, urinary retention, or infected skin ulcers. Chronic pain is common and harder to treat.[citation needed]

Trigeminal neuralgia (or "tic douloureux") is a disorder of the trigeminal nerve that causes episodes of intense pain in the eyes, lips, nose, scalp, forehead, and jaw, affecting 2-4% of MS patients.[51] The episodes of pain occur paroxysmally (suddenly) and the patients describe it as trigger area on the face, so sensitive that touching or even air currents can bring an episode of pain. Usually it is successfully treated with anticonvulsants such as carbamazepine,[54] or phenytoin[55] although others such as gabapentin[56] can be used.[57] When drugs are not effective, surgery may be recommended. Glycerol rhizotomy (surgical injection of glycerol into a nerve) has been studied[58] although the beneficial effects and risks in MS patients of the procedures that relieve pressure on the nerve are still under discussion.[59][60]

Lhermitte's sign is an electrical sensation that runs down the back and into the limbs and is produced by bending the neck forwards. The sign suggests a lesion of the dorsal columns of the cervical cord or of the caudal medulla, correlating significantly with cervical MRI abnormalities.[61] Between 25 and 40% of MS patients report having Lhermitte's sign during the course of their illness.[62][63][64] It is not always experienced as painful, but about 16% of people with MS will experience painful Lhermitte's sign.[51]

Dysesthesias are disagreeable sensations produced by ordinary stimuli. The abnormal sensations are caused by lesions of the peripheral or central sensory pathways, and are described as painful feelings such as burning, wetness, itching, electric shock or pins and needles. Both Lhermitte's sign and painful dysesthesias usually respond well to treatment with carbamazepine, clonazepam or amitriptyline.[65][66][67] A related symptom is a pleasant, yet unsettling sensation which has no normal explanation (such as sensation of gentle warmth arising from touch by clothing)

Sexual dysfunction (SD) is one of many symptoms affecting persons with a diagnosis of MS. SD in men encompasses both erectile and ejaculatory disorder. The prevalence of SD in men with MS ranges from 75 to 91%.[68] Erectile dysfunction appears to be the most common form of SD documented in MS. SD may be due to alteration of the ejaculatory reflex which can be affected by neurological conditions such as MS.[69] Sexual dysfunction is also prevalent in female MS patients, typically lack of orgasm, probably related to disordered genital sensation.

Spasticity is characterised by increased stiffness and slowness in limb movement, the development of certain postures, an association with weakness of voluntary muscle power, and with involuntary and sometimes painful spasms of limbs.[33] Painful spasms affect about 15% of people with MS overall.[51] A physiotherapist can help to reduce spasticity and avoid the development of contractures with techniques such as passive stretching.[70] There is evidence, albeit limited, of the clinical effectiveness of THC and CBD extracts,[71]baclofen,[72]dantrolene,[73]diazepam,[74] and tizanidine.[75][76][77] In the most complicated cases intrathecal injections of baclofen can be used.[78] There are also palliative measures like castings, splints or customised seatings.[33]

Speech problems include slurred speech, low tone of voice (dysphonia), decreased talking speed, and problems with articulation of sounds (dysarthria). A related problem, since it involves similar anatomical structures, is swallowing difficulties (dysphagia).[79]

Some MS patients develop rapid onset of numbness, weakness, bowel or bladder dysfunction, and/or loss of muscle function, typically in the lower half of the body.[citation needed] This is the result of MS attacking the spinal cord. The symptoms and signs depend upon the nerve cords involved and the extent of the involvement.

Prognosis for complete recovery is generally poor. Recovery from transverse myelitis usually begins between weeks 2 and 12 following onset and may continue for up to 2 years in some patients and as many as 80% of individuals with transverse myelitis are left with lasting disabilities.[citation needed]

Tremor is an unintentional, somewhat rhythmic, muscle movement involving to-and-fro movements (oscillations) of one or more parts of the body. It is the most common of all involuntary movements and can affect the hands, arms, head, face, vocal cords, trunk, and legs. Ataxia is an unsteady and clumsy motion of the limbs or torso due to a failure of the gross coordination of muscle movements. People with ataxia experience a failure of muscle control in their arms and legs, resulting in a lack of balance and coordination or a disturbance of gait.

Tremor and ataxia are frequent in MS and present in 25 to 60% of patients. They can be very disabling and embarrassing, and are difficult to manage.[80] The origin of tremor in MS is difficult to identify but it can be due to a mixture of different factors such as damage to the cerebellar connections, weakness, spasticity, etc.

Many medications have been proposed to treat tremor; however their efficacy is very limited. Medications that have been reported to provide some relief are isoniazid,[81][82][83][84]carbamazepine,[54]propranolol[85][86][87] and gluthetimide[88] but published evidence of effectiveness is limited.[89]Physical therapy is not indicated as a treatment for tremor or ataxia although the use of orthese devices can help. An example is the use of wrist bandages with weights, which can be useful to increase the inertia of movement and therefore reduce tremor.[90] Daily use objects are also adapted so they are easier to grab and use.

If all these measures fail patients are candidates for thalamus surgery. This kind of surgery can be both a thalamotomy or the implantation of a thalamic stimulator. Complications are frequent (30% in thalamotomy and 10% in deep brain stimulation) and include a worsening of ataxia, dysarthria and hemiparesis. Thalamotomy is a more efficacious surgical treatment for intractable MS tremor though the higher incidence of persistent neurological deficits in patients receiving lesional surgery supports the use of deep brain stimulation as the preferred surgical strategy.[91]

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Stemcentrx scientists working with targeted molecules that can kill some types of lung cancer. MIT Tech Review Image.

A stem cell biotech in the news this week was one thathad mostly flown under the radar previously.

Stemcentrx hasa focus on killing cancer stem cells as a novel approach to treating cancer. Antonio Regalado had a nice articleyesterday on the company. He reports that Stemcentrx has around a half a billion in funding. It is valued in the billions. These are very unusual figures for a stem cell biotech.

Stemcentrx isdeveloping novel cancer therapeutics such as antibodies that target cancer stem cells. Their development pipeline at least in part uses a model of serial xenograft tumor transplantation in mice.Cancer stem cells are also sometimes called tumor initiating cells (TIC). As a cancer stem cell researcher myself, I find Stemcentrx intriguing.

The company published an encouraging bit of preclinical data recently in Science Translational Medicinewith a team of authors including leading company scientist, Scott Dylla. In this paper the team presented evidence that they have a product in the form of a loaded antibody (conjugated to a toxin) against a molecule called DLL3 important to TIC biological function and survival. DLL3 is part of the Notch signaling pathway. Stay tuned tomorrow for my interview with Dr. Dylla.

They showed that this anti-DLL3 antibody,SC16LD6.5, exhibited anti-tumor activities in xenograft models of pulmonary neuroendocrine tumors such as small cell lung cancer. The company also has a clinical trial ongoing but not currently recruiting using this drug, and they have another trial for ovarian cancer based on antibody targeting as well.

SC16LD6.5 also exhibited some degree of toxicity in rats and a non-human primate model so thats a possible issue moving forward, but the toxic effects were at least partially reversible and when youre dealing with a deadly disease some toxicity for treatment is kind of to be expected.

Can Stemcentrx survive and hopefully even thrive as a company selling products that kill cancer stem cells? Well have a clearer picture on this in a few years, but in general biotechs of this type in this arena have a high failure rate. We need to keep in mind the long, sobering path ahead between these kinds of preclinical result and getting an approved drug to patients.

At the same time, this team has the money and talent to potentially succeed, and again, theres that half a billion in funding, which all by itself makes this stem cell biotech noordinary company. Theres another unique thing going on here: famed tech investor Peter Thiel is one of the major funders of the company.

Those of us in the cancer stem cell field have long been engaged in the debate overwhether these special cells exist in specific solid tumors and their functions in tumorigenesis. I believe they are present and important in some, but not all of such tumors. The controversial nature of TICs in lung cancer specifically makes SC16LD6.5 a high-risk, high reward kind ofproduct.

More weapons against lung cancer will be of coursea good thing and targeting cancer stem cells is an innovative approach. The company isrecruiting for many positions including scientists so if you are interested take a look.

I hope Stemcentrx succeeds and I look forward to reading more of their work as the years go by.

The winner of the inaugural Ogawa-Yamanaka Prize is Dr. Masayo Takahashi, MD, PhD.

According to the Gladstone Institutepress release, Dr. Takahashi was awarded the prize for her trailblazing work leading the first clinical trial to use induced pluripotent stem (iPS) cells in humans.

The prize, including a $150,000 cash award, will be given at a ceremony next week at the Gladstone on September 16. If you are interested in listening in, you can register for the webcast here.

Dr. Takahashi started the first ever human clinical study using iPS cells, which is focused on treating of macular degeneration using retinal pigmented epithelial cells derived from human iPS cells.

Congratulations to Dr. Takahashi for the great and well-deserved honor of the Ogawa-Yamanaka Prize.

As readers of this blog likely recall, Dr. Takahashi received our blogsStem Cell Person of the Year Award last year in honor of her pioneering work and that included a $2,000 prize.

Otherpast winners of our Stem Cell Person of the Year Award have gone on to get additional awards too.

The 2013 Stem Cell Person of the Year, Dr. Elena Cattaneo, went on to win the ISSCR Public Service Award in 2014 along with colleagues.

And our 2012 Stem Cell Person of the Year Award winner, stellar patient advocateRoman Reed, went on in 2013 to receive the GPI Stem Cell Inspiration Award.

The more we can recognize the pioneers and outside-the-box thinkers in the stem cell field, the better.

I recently ran a poll on my blog about how the FDA is doing on handling stem cell clinics.

There is substantial debate in the stem cell arena about how the FDA handles stem cell clinics ranging from the view that the agency is far too strict to excessively lenient.

The results of the poll reflect a great deal of dissatisfaction with the job that the FDA is doing on stem cell clinics.

Only 9% of respondents felt that the FDA is currently do things just about right.

While the top 2 answers were polar extremes, by a large margin the top answer was that the FDA was much too lenient.

Although Internet polls of this kind are not scientific, they can reflect sentiments of a community.

Science can come in various forms ranging from numbers to words to images.

In the stem cell field, some of the images can be particularly striking. One of my own favorites is the one above that I took some years ago of differentiation of neural stem cells that ended up on the cover of my first book.

Do you have a favorite stem cell-related image?

Im doing a stem cell image contest.

The winner receives a $100 prize and their image will be posted here along with a blurb on their research.

If more than one entry is particularly amazing, I may give out more than one prize.

The rules are straightforward. Anyone can enter whether you are in academia or industry.

Email me your favorite stem cell-related image (knoepflerATucdavisDOTedu). The image must be your own. Team entries are allowed.

By entering the contest you agree that the image may be posted on this stem cell blog.

The deadline is September 30th at midnight USA PDT.

As readers of this blog may recall, I have a garden where I grow a variety of plants every year. One year I had quite a few sunflowers and ever since I have volunteer sunflowers popping up that have all kinds of interesting traits. The neighborhood squirrels collected hundreds of sunflower seeds and buried some as a cache. Some of those survived and sprouted new sunflowers.and so on every year.

Ive noticed that each of the sunflowers becomes its own microcosm with thousands of bugs.

Predominantly each sunflower is colonized by ants, which farm aphids on them. However, other bugs live there too including some amazing praying mantises that hunt bees once they grow large enough.

You can see one at left from a past year. I thought to myself, Youre never going to catch a bee, but that mantis was big and fearless and there were a lot of bees.

This year Ive been following an interesting, very large yellow-green spider (anyone know what type it is?) who lives on a sunflower in the garden.

The spider hung out on the flower head too just like the mantises of past years. See below and look at the top of the sunflower. The spider almost looks like a crab. On the opposite side is a ladybug down around 6 oclock.

I wondered if the spider was hunting some insect attracted to the sunflower. Bees like the mantis? It isa very big spider so I was guessing it was eating well on something.

A few days later I took a look again and was impressed to see that the spider had caught a big bee.

What a meal!

Im still not sure on how the spider did it since it doesnt seem to be a web spinner. It must have been an ambush attack with maybe a quick loop of silk around the bee and some powerful venom.

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Knoepfler Lab Stem Cell Blog | Building innovative ...

Recommendation and review posted by simmons

Top 10 list of important, easy to understand facts for patients about stem cell treatments

For better or worse, I am in the unique position of being a stem cell scientist and also a patient. Looking on the bright side this gives me a unique perspective on things.

I know there are thousands of people out there looking for more practical information about stem cell therapies and treatments. These folks understandably are using the Internet to look for some clear, good info on stem cell treatments either for themselves or their loved ones. Too often the info that is out there is either wrong, misleading, or overly complex.

So in this post I want to address this need speaking as a scientist, patient advocate and cancer survivor in the form of 10 key facts to help you guide your way through the jungle of stuff out there about stem cells.

1) Stem cells are essentially a type of drug or biological and possibly permanent in nature. Yeah, they are extremely unusual drugs, but they are drugs. The FDA considers them drugs. Unlike other drugs, once a patient receives a stem cell drug, it will not necessarily simply go away like other drugs because a stem cell drug consists of living cells that often behave in unpredictable ways. What this means is if the stem cells are doing bad things your doctor has no way to stop it.

2) Like any medical product, even aspirin, stem cells treatments will have side effects. Not maybe. Definitely. Our hope is the side effects will be relatively mild.

3) The only stem cell treatment explicitly approved by the FDA for use in the U.S. is bone marrow transplantation. What this means is that any other stem cell treatment you see advertised on Facebook or Google or elsewhere that indicates it will be given to you inside the U.S. may in fact be illegal and unsafe. The exception to this is if it is part of an FDA-approved clinical trial.

4) If you venture outside the U.S. for a stem cell treatment, use extra caution and have a knowledgeable physician inside the U.S. guiding you. We have to avoid the trap of thinking that only the U.S. can offer advanced medical treatments, but on the other hand within the U.S. you have the added safety of the FDA, which is trying to protect you. In the vast majority of other countries regulatory agencies are practically non-existent or are far less strict than the FDA.

5) Stem cells are not a cure all. I am as excited as anybody about the potential of stem cells to treat a whole bunch of diseases and injuries, but they are not some kind of miracle cure for everything. When a doctor offers to inject some kind of stem cells or a stem cell-derived product into a patient either into the bloodstream or into a specific place that is injured such as a shoulder, we just do not know at this point if it will do any good with the exception of bone marrow transplant.

6) Dont let celebrities be your guide to medical care. The number of famous people getting stem cell treatments is increasing including sports stars and politicians. Dont let what these folks do influence what you decide to do about your health. Just because they are famous do not believe for one minute that they are any more informed than you or your personal doctor about medical treatments or stem cells. If anything I think sometimes famous people are more reckless with their health than average people like you and me.

7) Reach out to scientists as a source of info. As a scientist I am always happy to hear from people outside the scientific community with questions about stem cells and other research. I cant speak for all stem cell scientists but you might be surprised at how likely it is that if you send them a very short, clear email with one or two questions that they will respond and be helpful. We cant or shouldnt offer medical advice, but we can give our perspectives on stem cell research and its clinical potential, etc. Just do not cold call scientists as you are unlikely to find them that way and even if you do, they may be cranky. Email.

8 )The people selling you non-FDA approved stem cell treatments want your money. Unlike stem cell researchers, the people out there advertising stem cell treatments that are not FDA approved are only really after one thing: your money. As such they will do their best to convince you that their treatment is safe and effective. They may offer patient testimonials either from patients who truly believe they were helped or from people who are paid to say the treatment helped them. The bottom line is that the sellers of dubious stem cell treatments simply want your money.

9) There is no such thing as completely proven safe and if something sounds too good to be true, it probably is. I am contacted fairly regularly by patients or their families and they often mention that the doctors offering stem cell treatments told them that the treatments are proven safeor that umbilical cord blood cannot harm you.or that your own stem cells cannot harm you..or that adult stem cells are harmless. Ill believe it when the FDA says it is so and you should be skeptical too.

10) The most important thing is data and you have a right to see it before treatment.Before you or a loved one get a stem cell treatment, ask two key questions. First, is the treatment FDA approved and if not, why not? Second, can you please show me the data that proves your treatment is safe and effective. See what kind of answer you get. If they criticize the FDA then that is a warning flag. If they refuse to show you data, then that is a big red warning flag. They may say it is confidential or that it is not published yet, but as a patient you have a right to see the data, assuming they have any data at all.

These facts will hopefully change over the coming years, but right now I think they represent reality. I know as patients we need hope, but these unapproved stem cell treatments will at best take your money for nothing, and at worst will endanger you or your loved ones.

The post above is for information only and is not medical advice. All medical decisions should be made by patients in consultation with their personal physicians.

More here:
Patients guide to treatments | Knoepfler Lab Stem Cell Blog

Recommendation and review posted by sam

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Life Extension

Recommendation and review posted by Bethany Smith

The Orthopaedics and Sports Medicine clinics at UWMC-Rooseveltand the UW Medicine Eastside Specialty Center offer subspecialized surgical care for arthritis patients. UW surgeons provide the most current approaches for patients with arthritis affecting:

The Orthopaedics and Sports Medicine clinicsat UWMC-Roosevelt offer a specialty program for rheumatoid arthritis. The Rheumatoid Arthritis Service provides health care, support, and information to optimize the health, comfort, and productivity for individuals with:

Physicians in the Department of Orthopedics and Sports Medicine and on the Rheumatoid Arthritis Service work closely with the Arthritis Foundation's Washington/Alaska Chapter and with other UW specialists to provide information on the latest medical and surgical treatment methods.

You may make your own appointment with an arthritis surgeon in the Department of Orthopedics and Sports Medicine or with a physician on the Rheumatoid Arthritis Service or you may be referred by your physician or other specialist.

To make an appointment, please call: 206-520-5000 or Toll Free 877-520-5000.

The Hip and Knee Center at UWMC - Roosevelt, The Hand, Elbow & Shoulder Center at UWMC - Roosevelt, and The Foot and Ankle Center at UWMC - Roosevelt are locatedat UWMC-Roosevelt, an outpatient facility at 4245 Roosevelt Way N.E. in Seattle's University District. There is an underground parking garage in the building. A number of bus lines stop right outside or nearby, and there also is a free shuttle bus service from UW Medical Center.

The Eastside Specialty Center is located in Bellevue at 3100 Northup Way. Free parking is available on site.

Please be aware that many insurance programs will not pay for you to see a specialist without prior authorization, so check with your health insurance plan first.

Link:
Arthritis | UW Orthopaedics and Sports Medicine, Seattle

Recommendation and review posted by simmons

The word "arthritis" makes many people think of painful, stiff joints. But, there are many kinds of arthritis, each with different symptoms and treatments. Most types of arthritis are chronic. That means they can go on for a long period of time.

Arthritis can attack joints in almost any part of the body. Some types of arthritis cause changes you can see and feelswelling, warmth, and redness in your joints. In some kinds of arthritis, the pain and swelling last only a short time, but are very uncomfortable. Other types of arthritis might be less painful, but still slowly cause damage to your joints.

Arthritis is one of the most common diseases in the United States. Older people most often have osteoarthritis, rheumatoid arthritis, or gout.

Osteoarthritis (OA) is the most common type of arthritis in older people. OA starts when tissue, called cartilage, that pads bones in a joint begins to wear away. When the cartilage has worn away, your bones rub against each other. OA most often happens in your hands, neck, lower back, or the large weight-bearing joints of your body, such as knees and hips.

OA symptoms range from stiffness and mild pain that comes and goes to pain that doesn't stop, even when you are resting or sleeping. Sometimes OA causes your joints to feel stiff after you haven't moved them for a while, like after riding in the car. The stiffness goes away when you move the joint. Over time, OA can make it hard to move your joints. It can cause a disability if your back, knees, or hips are affected.

Why do you get OA? Growing older is what most often puts you at risk for OA, possibly because your joints and the cartilage around them become less able to recover from stress and damage. Also, OA in the hands may run in families. Or, OA in the knees can be linked with being overweight. Injuries or overuse may cause OA in joints such as knees, hips, or hands.

Rheumatoid arthritis (RA) is an autoimmune disease, a type of illness that makes your body attack itself. RA causes pain, swelling, and stiffness that lasts for hours. RA can happen in many different joints at the same time. People with RA often feel tired or run a fever. RA is more common in women than men.

RA can damage almost any joint. It often happens in the same joint on both sides of your body. RA can also cause problems with your heart, muscles, blood vessels, nervous system, and eyes.

Gout is one of the most painful kinds of arthritis. It most often happens in the big toe, but other joints can also be affected. Swelling may cause the skin to pull tightly around the joint and make the area red or purple and very tender.

Eating foods rich in purines like liver, dried beans, peas, anchovies, or gravy can lead to a gout attack in people with the disease. Using alcohol, being overweight, and taking certain medications may make gout worse. In older people, some blood pressure medicines can also increase the chance of a gout attack. To decide if you have gout, your doctor might do blood tests and x-rays.

You might have some type of arthritis if you have:

If any one of these symptoms lasts more than 2 weeks, see your regular doctor or one who specializes in treating arthritis, called a rheumatologist. If you have a fever, feel physically ill, suddenly have a swollen joint, or have problems using your joint, see your doctor right away.

Getting enough rest, doing the right exercise, eating a healthy, well-balanced diet, and learning the right way to use and protect your joints are keys to living with any kind of arthritis. The right shoes and a cane can help with pain in the feet, knees, and hips when walking. But make sure the cane is fitted by a professional. Dont borrow one from a friend or neighbor. There are also gadgets to help you open jars and bottles or to turn the doorknobs in your house.

Some medicines can help with pain and swelling. Acetaminophen might ease arthritis pain. Some people find NSAIDs (nonsteroidal anti-inflammatory drugs), like ibuprofen, naproxen, and ketoprofen, helpful. Some NSAIDs are sold without a prescription, while others must be prescribed by a doctor. Be very careful about possible side effects of some NSAIDs, whether sold with or without a prescription. Read the warnings on the package or insert that comes with the drug. Talk to your doctor about if and how you should use acetaminophen or NSAIDs for your arthritis pain. The U.S. Food and Drug Administration has more information about drugs such as those mentioned here.

Osteoarthritis (OA). Medicines can help you control the pain. Rest and exercisemay make it easier to move your joints. Keeping your weight down is a good idea. If pain from OA is very bad, there are shots your doctor can give you.

Rheumatoid arthritis (RA). Treatment can help the pain and swelling. This might slow down or stop joint damage. You may feel better and find it easier to move around. Your doctor might also suggest anti-rheumatic drugs called DMARDs (disease-modifying antirheumatic drugs). These can slow damage from the disease. Other medicines known as corticosteroids (like prednisone) can ease swelling. These are strong medicine and should only be taken with a doctors prescription. Another kind of drug, called a biologic response modifier, blocks the damage done by the immune system. These may help people with mild-to-moderate RA when other treatments have not worked.

Gout. The most common treatment for an acute attack of gout is NSAIDs or corticosteroids. They can bring down the swelling, so you may start to feel better within a few hours after treatment. The pain usually goes away within a few days. If you have had an attack of gout, talk to your doctor to learn why you had the attack and how to prevent future attacks. If you have had several attacks, your doctor might prescribe medicines to prevent future ones.

Along with taking the right medicine and properly resting your joints, exercise might help with arthritis symptoms. Daily exercise, such as walking or swimming, helps keep joints moving, lessens pain, and makes muscles around the joints stronger.

Three types of exercise are best if you have arthritis:

The National Institute on Aging (NIA) has created the Go4Life campaign to help you start and stick with a safe exercise program. You can learn all about it by going to http://www.nia.nih.gov/Go4Life. There youll find exercises, tip sheets, personal success stories, and more! You can even keep track of progress in your exercise program. You can also order Go4Life materials in English and Spanish by calling the NIA at 1-800-222-2225 (toll-free).

Along with exercise and weight control, there are other ways to ease the pain around joints. You might find comfort by using a heating pad or a cold pack, soaking in a warm bath, or swimming in a heated pool.

Your doctor may suggest surgerywhen damage to your joints becomes disabling or when other treatments do not help with pain. Surgeons can repair or replace some joints with artificial (man-made) ones.

Recent studies suggest that acupuncture may ease OA pain for some people. Research also shows that two dietary supplements, glucosamine and chondroitin, may help lessen moderate to severe OA pain, but they seem to have no effect on changes to cartilage in the knee. Scientists continue to study these kinds of alternative treatments. Always check with your doctor before trying any new treatment for arthritis.

Many people with arthritis try remedies that have not been tested or proven helpful. Some of these, such as snake venom, are harmful. Others, such as copper bracelets, are harmless, but also unproven.

How can you tell that a remedy may be unproven?

See below for more information about getting NIA's AgePage called Beware of Health Scams.

Pain and arthritis do not have to be part of growing older. You can work with your doctor to safely lessen the pain and stiffness and to prevent more serious damage to your joints.

Here are some helpful resources:

American College of Rheumatology/Association of Rheumatology Health Professionals 2200 Lake Boulevard, NE Atlanta, GA 30319 1-404-633-3777 http://www.rheumatology.org

Arthritis Foundation P.O. Box 7669 Atlanta, GA 30357-0669 1-800-283-7800 (toll-free) or check the telephone directory for your local chapter http://www.arthritis.org

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 1-888-463-6332 http://www.fda.gov

National Center for Complementary and Alternative Medicine NCCAM Clearinghouse P.O. Box 7923 Gaithersburg, MD 20898 1-888-644-6226 (toll-free) 1-866-464-3615 (TTY/toll-free) http://www.nccam.nih.gov

National Institute of Arthritis and Musculoskeletal and Skin Diseases NIAMS Information Clearinghouse 1 AMS Circle Bethesda, MD 20892-3675 1-877-226-4267 (toll-free) 1-301-565-2966 (TTY) http://www.niams.nih.gov

To get the NIA's exercise guide or Beware of Health Scams or for more information on health and aging, contact:

National Institute on Aging Information Center P.O. Box 8057 Gaithersburg, MD 20898-8057 1-800-222-2225 (toll-free) 1-800-222-4225 (TTY/toll-free) http://www.nia.nih.gov http://www.nia.nih.gov/espanol

Sign up for regular email alerts about new publications and find other information from the NIA.

Visit http://www.nihseniorhealth.gov, a senior-friendly website from the National Institute on Aging and the National Library of Medicine. This website has health and wellness information for older adults. Special features make it simple to use. For example, you can click on a button to make the type larger.

National Institute on Aging National Institutes of Health NIH...Turning Discovery into Health U.S. Department of Health and Human Services

July 2009 Updated February 2012

Read the original here:
Arthritis Advice | National Institute on Aging

Recommendation and review posted by simmons

Last Modified on Sep 07, 2015

Arthritis is defined as inflammation of one or more joints. The primary symptoms of the condition include joint stiffness and pain. The condition is typically considered progressive and worsens with age; however, the specific type of arthritis determines the rate and direction of progression.

The two main forms of arthritis are osteoarthritis and rheumatoid arthritis. Osteoarthritis is caused by wear and tear while rheumatoid arthritis is considered an autoimmune disorder.

Pain and stiffness are the most characteristic symptoms of the condition; however, additional symptoms are common. Swelling, redness, and decreased range of motion are other indicative symptoms.

While the exact type of medical treatment for arthritis depends on the type of arthritis, several medications are common. Analgesics, nonsteroidal anti-inflammatory drugs or NSAIDs, counterirritants, and biologics are among the most common treatment options. However, many of these treatments are limited at best and harmful at worst.

Treatments such as analgesics only treat pain and do nothing to reduce inflammation. Likewise, NSAIDs can cause stomach irritation and increase the risk of heart attack and stroke. Biologics put you at risk for more serious immune diseases and debilitate the immune system altogether.

As limited as traditional medical treatments are, we suggest treating arthritis from a natural perspective. This approach relies on natural remedies, such as apple cider vinegar, baking soda, and blackstrap molasses, as well as noninvasive practices, like weight loss, exercise, and acupuncture.

Apple cider vinegar is an effective treatment option for a variety of reasons. The treatment contains beta-carotene, which serves as an antioxidant, as well as acetic acid. The combination of these two helps relieve arthritis pain and reduce inflammation.

As an imbalance in the bodys natural pH level is one of the primary causes of arthritis, baking soda is an effective treatment option. Baking soda helps neutralize the bodys acidic state and return the body to alkalinity. As it does so, baking soda helps relieve arthritis pain and inflammation.

Blackstrap molasses is a nutrient-rich syrup with powerful healing qualities. The syrup contains a variety of nutrients including magnesium and calcium that regulate the nerve impulses in the body and relieve pain.

While no one likes to hear the W word, consider the fact that a single 1 pound loss takes 4 pounds of pressure off of your joints. When you look at it that way, it makes sense that losing weight would help effectively treat arthritis, a joint disease. Consider your current weight compared to you suggested weight and see if you need to make any changes.

Exercise helps strengthen the body, including the muscles and the bones. It also helps promote effective circulation. As such, it can help relieve inflammation and even pain associated with arthritis.

An ancient Chinese practice, acupuncture utilizes specific pressure points to relieve pain. This treatment can relieve pain and promote general movement.

Understanding your condition is one of the most important forms of treatment, but aside from that utilizing natural treatment options or at least support is vital as well. Give one of our suggestions a try or add your favorite remedy to a reader-contributed list below!

Additional Pages of Interest: Rheumatoid Arthritis Osteoarthritis Pain Remedies

Here is the original post:
Natural Cures for Arthritis - Earth Clinic

Recommendation and review posted by simmons

Welcome to the Mostoslavsky Lab!

Mission Statement

The Mostoslavsky Lab is a basic science laboratory in the Section of Gastroenterology in the Department of Medicine at Boston University, affiliated with the Boston University Center for Regenerative Medicine (CReM). Our goal is to advance our understanding of stem cell biology with a focus on their genetic manipulation via gene transfer and their potential use for stem cell-based therapy. We believe that by discovering the mechanisms involved in stem cell self-renewal and differentiation we will be able to manipulate stem cell fate and use it as the basis for the correction of several diseases. Project areas in the lab focuses on the use of different stem cell populations, including embryonic stem cells, induced Pluripotent Stem (iPS) cells, hematopoietic stem cells and intestinal stem cells and their genetic manipulation by lentiviral vectors.

Specific Areas of Research

Embryonic Stem Cell Modeling of Intestinal Differentiation Embryonic Stem Cells (ESC) are pluripotent undifferentiated cells capable of giving rise to cells from all three germ layers. This unique ability makes them ideal candidates to model early development allowing us to study the basic signaling mechanisms involved in stem cell fate determination. At the same time, manipulating ESC differentiation toward a specific developmental pathway holds a great promise for their use in regenerative medicine. One focus of our lab is differentiating mouse ESC into intestinal epithelial cells in order to understand the complex signaling pathways involved in intestinal commitment from endodermal progenitors and undifferentiated stem cells.

iPS cells Our lab has a major interest in the study of induced Pluripotent Stem cells or iPS cells and the development of tools for their generation and characterization. Pioneering work by the laboratory of Dr. Yamanaka showed that fibroblasts transduced with retroviral vectors expressing four transcription factors, Oct4, Klf4, Sox2 and cMyc can be reprogrammed to become pluripotent stem cells that appear almost indistinguishable from ESC. In contrast to ESC, iPS cells are genetically identical to the individual from whom they are derived, raising the prospect of utilizing iPS cells for autologous cell based therapies without risk of rejection. We have previously developed a single lentiviral vector expressing a stem cell cassette, named STEMCCA, capable of generating iPS cells from post-natal fibroblasts with the highest efficiency reported to date. We have recently modified it to make it excisable and have used it to generate mouse and human iPS cells free of exogenous transgenes. We aimed at using iPS cells in parallel to ESC for the study of endoderm/intestinal lineage specification, as well as for disease modeling and their potential for regenerative medicine. We are currently establishing and characterizing iPSC lines from several GI tract related diseases, including Familial Adenomatous Polyposis (FAP), Crohns disease and Hemochromatosis.

Hematopoietic Stem Cell Manipulation for the Study of Stem Cell Self-Renewal and Differentiation Hematopoietic Stem Cells (HSCs) are the most thoroughly characterized stem cell population in the body and their study has resulted in well established methods for their isolation, purification and reliable assays of HSC function. During the last few years we have substantially improved our ability to genetically manipulate HSCs using viral vectors for gene transfer. Despite these efforts, few genes are known to play a role in the processes of stem cell self-renewal and differentiation. Understanding the molecular mechanisms that govern those unique functions are crucial for developing the promise that stem cells hold for developmental biology and regenerative medicine. In our lab, we use lentiviral viral gene transfer to study the role of several molecules in long-term HSC self-renewal and differentiation.

Read more from the original source:
Stem Cell Biology & Gene Therapy: Mostoslavsky Lab BUMC

Recommendation and review posted by sam