Tiny gene mutations increase risk of autism

Tiny gene mutations, each individually rare, pose more risk for autism than had been previously thought, suggests a study funded in part by the National Institute of Mental Health, a component of the National Institutes of Health.
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These spontaneous deletions and duplications of genetic mater...

Tiny gene mutations, each individually rare, pose more risk for autism than had been previously thought, suggests a study funded in part by the National Institute of Mental Health, a component of the National Institutes of Health.

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These spontaneous deletions and duplications of genetic material were found to be ten times more prevalent in sporadic cases of autism spectrum disorders than in healthy control subjects %26#8211; but only twice as prevalent in autism cases from families with more than one affected member. The results implicate the anomalies as primary, rather than just contributory, causes of the disorder in most cases when they are present, according to the researchers. Although they might share similar symptoms, different cases of autism could thus be traceable to any of 100 or more genes, alone or in combination.

Drs. Jonathan Sebat, Michael Wigler, Cold Spring Harbor Laboratory (CSHL), and 30 colleagues from several institutions, report on their discovery online, March 16, 2007 in Science Express.

"These structural variations are emerging as a different kind of genetic risk for autism than the more common sequence changes in letters of the genetic code that we%26#8217;ve been looking for," explained NIMH director Thomas Insel, M.D. "The best evidence yet that such deletions and duplications are linked to the disorder, these findings certainly complicate the search for genes contributing to autism. These are rare changes, dispersed across the genome, and they tell us that autism may be the final common path for many different genetic abnormalities."

"Our results show conclusively that these tiny glitches are frequent in autism, occurring in at least ten percent of cases, and primarily in the sporadic form of the disease, which accounts for 90 percent of affected individuals," added Sebat. "Understanding such sporadic autism will require different genetic approaches and stepped-up recruitment of families in which only one individual has the disease."

Sebat and colleagues used new high resolution array technology to detect mutations that were present in a child but not in either parent. They screened genetic material from 264 families drawn, in part, from the Autism Genetic Resource Exchange (AGRE) and the NIMH Center for Collaborative Genetic Studies of Mental Disorders.

They found the spontaneous mutations in 14 of 195 people with autism spectrum disorders compared to two of 196 unaffected individuals. Among the 14 autism patients with mutations, 12 were the only affected members of their family, while two were in families with other affected individuals.

Since the rate of mutations was much lower in families with more than one affected member, the researchers propose that "two different genetic mechanisms contribute to risk: spontaneous mutation and inheritance, with the latter being more frequent in families that have multiple affected children."

The two mutations detected in 196 healthy controls were duplications, while 12 of those in people with autism were deletions of genetic material. Relatively more females had the mutations, suggesting that the anomalies may contribute to disease more equally across the sexes than other causes of autism. Boys with autism outnumber girls 4 to 1.

Since each mutation is individually rare %26#8211; few were seen more than once %26#8211; the results suggest that many different sites in the genome likely contribute to autism.

"Failure to develop social skills and repetitive and obsessive behavior may in fact be the consequence of a reaction to many different cognitive impairments," note the researchers.

Source: National Institute of Mental Health

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New approach kills bacteria by interfering with a key bacterial nutrient

A new antimicrobial approach can kill bacteria in laboratory experiments and eliminate life-threatening infections in mice by interfering with a key bacterial nutrient, according to research led by a University of Washington scientist. The joint project, conducted at the UW, the University of Iowa, ...

A new antimicrobial approach can kill bacteria in laboratory experiments and eliminate life-threatening infections in mice by interfering with a key bacterial nutrient, according to research led by a University of Washington scientist. The joint project, conducted at the UW, the University of Iowa, and the University of Cincinnati, will be featured in the April 2 issue of the Journal of Clinical Investigation.

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Bacteria are increasingly resistant to antibiotics, and existing drugs work poorly against chronic infections like those that occur in wounds, on medical devices and in the lungs of people with cystic fibrosis. For these reasons, a great deal of research is focused on finding new antibiotic compounds.

In this study, researchers took a different approach. Rather than trying to find agents that best killed bacteria in test tubes, they sought to intensify the stress imposed on microbes by one of the body's own defense mechanisms.

"The competition for iron is critical in the struggle between bacteria and host," explained the study's senior author, Pradeep Singh, associate professor of medicine and microbiology at the UW. "The body has potent defense mechanisms to keep iron away from infecting organisms, and invaders must steal some if they are to survive."

Iron is critical for the growth of bacteria and for their ability to form biofilms, slime-encased colonies of microbes that cause many chronic infections. "Because iron is so important in infection, we thought infecting bacteria might be vulnerable to interventions that target iron," explained Yukihiro Kaneko, senior fellow in microbiology at the UW and the study's lead author.

To accomplish this, the researchers used gallium, a metal very similar to iron.

"Gallium acts as a Trojan horse to iron-seeking bacteria," said Singh. "Because gallium looks like iron, invading bacteria are tricked, in a way, into taking it up. Unfortunately for the bacteria, gallium can't function like iron once it's inside bacterial cells."

The researchers showed that gallium killed microbes, and prevented the formation of biofilms. Importantly, gallium's action was intensified in low iron condition, like those that exist in the human body. Gallium was even effective against strains of Pseudomonas aeruginosa from cystic fibrosis patients that were resistant to multiple antibiotics. In mice, gallium treatment blocked both chronic and acute infections caused by this bacterium.

The idea of using gallium as a substitute for iron was developed by a group led by Bradley Britigan, a researcher at the University of Cincinnati and a co-author on this study. The general approach of targeting stresses already applied by natural defense mechanisms could be a promising new way to treat infections.

"We badly need new approaches to fight bacteria," said Singh. "The gallium strategy isn't ready for clinical use yet," he added. "However, we think this approach is promising, and we can't afford to leave any stone unturned."

Source: University of Washington

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Small molecule plays key role in preventing embryonic stem cells from differentiating into one or more specific cell types

A newly discovered small molecule called IQ-1 plays a key role in preventing embryonic stem cells from differentiating into one or more specific cell types, allowing them to instead continue growing and dividing indefinitely, according to research performed by a team of scientists who have recently ...

A newly discovered small molecule called IQ-1 plays a key role in preventing embryonic stem cells from differentiating into one or more specific cell types, allowing them to instead continue growing and dividing indefinitely, according to research performed by a team of scientists who have recently joined the stem-cell research efforts at the Keck School of Medicine of the University of Southern California. Their findings are being published today in an early online edition of the Proceedings of the National Academy of Sciences.

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This discovery takes scientists another step closer to being able to grow embryonic stem cells without the %26#8220;feeder layer%26#8221; of mouse fibroblast cells that is essential for maintaining the pluripotency of embryonic stem cells, says the study%26#8217;s primary investigator, Michael Kahn, Ph.D., who was recently named the first Provost%26#8217;s Professor of Medicine and Pharmacy at USC. Such a layer is needed because it is currently the only proven method to provide the stem cells with the necessary chemical signals that prompt them to stay undifferentiated and to continue dividing over and over.

Still, growing human embryonic stem cells on a layer of mouse fibroblasts has never made much sense to the scientists forced to do just that. %26#8220;Stem cells that grow on feeders are contaminated with mouse glycoproteins markers,%26#8221; Kahn says. %26#8220;If you use them into humans, you%26#8217;d potentially have a horrible immune response.%26#8221;

And so, in order to take any eventual stem cell-based treatments from the laboratory to the clinic, there needs to be a way to keep the cells growing and dividing without the use of mouse fibroblasts. The discovery of IQ-1, says Kahn, is a significant step in that direction.

What IQ-1 does, Kahn explains, is to block one arm of a cell-signaling pathway called the Wnt pathway, while enhancing the signal coming from the other arm of the Wnt pathway. The Wnt pathway is known to have dichotomous effects on stem cells i.e. both proliferative and differentiative. More specifically, IQ-1 blocks the coactivator p300 from interacting with the protein %26#223;-catenin; this prevents the stem cells from being %26#8216;told%26#8217; to differentiate into a more specific cell type. At the same time, IQ-1 enhances the interaction between the coactivator CBP and %26#223;-catenin, which signals the cells to keep dividing and to remain as fully potent stem cells. %26#8220;This way, you can essentially maintain the stem cell%26#8217;s growth and potency for as long as you want,%26#8221; Kahn says.

The studies of IQ-1 and its effects reported in the newly published PNAS paper were performed at the University of Washington in Seattle by Kahn and his colleagues (along with collaborators from the Asahi Kasei Corporation in Shizuoka, Japan) using mouse embryonic stem cells, but Kahn notes that subsequent pilot studies using human embryonic stem cells, in collaboration with Dr. Qilong Ying at the Center for Stem Cell and Regenerative Medicine at the Keck School of Medicine, have confirmed that IQ-1 plays a similar role in that system as well.

Source: University of Southern California

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Saliva test detects breast cancer

Sebastian Z. Paige and Charles F. Streckfus, DDS, MA, the authors of the study, "Salivary analysis in the diagnosis and treatment of breast cancer," published in the March/April 2007 issue of General Dentistry, the Academy of General Dentistry"s (AGD) clinical, peer-reviewed journal, researched a ne...

Sebastian Z. Paige and Charles F. Streckfus, DDS, MA, the authors of the study, "Salivary analysis in the diagnosis and treatment of breast cancer," published in the March/April 2007 issue of General Dentistry, the Academy of General Dentistry"s (AGD) clinical, peer-reviewed journal, researched a new method of diagnosis.

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They found that the protein levels in saliva have great potential to assist in the diagnosis, treatment, and follow-up care of breast cancer. And general dentists are perfect candidates to assist with this diagnosis samples because they can easily remove saliva samples from a patient"s mouth during routine visits. As the AGD"s Vice-President Paula Jones, DDS, FAGD says, "Since a patient visits the dentist more frequently than their physician, it makes sense that this diagnostic tool could be very effective in the hands of the general dentist."

Salivary testing has some advantages over blood testing. The authors of the study argue that saliva is a clear, colorless liquid, while blood undergoes changes in color, which might affect test results. The authors also say that saliva collection is safe (no needle punctures), non-invasive, and can be collected without causing a patient any pain.

This method of early diagnosis is not yet approved by the Food and Drug Administration (FDA). If it does receive approval, dentists and physicians could use it to collaboratively diagnose breast cancer.

But Dr. Jones also warns that this is not the only means for diagnosis. "It would not eliminate the need for regular mammogram screening or blood analysis; it would just be a first line of defense for women," she says. "For example, if the salivary screening did show a positive result, a mammogram or other imaging test would be necessary to determine in which breast the cancer was located."

Advantages of salivary testing:

-- Salivary testing is safe (no needle punctures) and can be collected without causing the patient any pain.

-- Salivary testing does not require any special training or equipment.

-- Patients who may not have access to or money for preventive care could easily be tested through saliva.

Source: Academy of General Dentistry

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Notorious cancer gene may contribute to tumor growth

A new study suggests how a notorious cancer gene may contribute to tumor growth.The insight emerged from a long-running study of a protein called PMR1, the key player in an unusual mechanism that cells use to quickly stop production of certain important proteins.Researchers discovered that PMR1 is a...

A new study suggests how a notorious cancer gene may contribute to tumor growth.The insight emerged from a long-running study of a protein called PMR1, the key player in an unusual mechanism that cells use to quickly stop production of certain important proteins.

Researchers discovered that PMR1 is activated %26#8211; or %26#8220;turned on %26#8211; by another molecule, an energy-packing protein called Src (pronounced %26#8220;sark%26#8221;).

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Discovered in 1977, Src became the first %26#8220;oncogene%26#8221; %26#8211; mutated genes that help make cells cancerous. Oncogenes are altered forms of genes that control cell growth and cell division.

These findings provide insight into how Src might contribute to cancer development.

The study by researchers with the Ohio State University Comprehensive Cancer Center is published in the March 9 issue of the journal Molecular Cell.

%26#8220;The link between Src and cancer was discovered 30 years ago, but to this day, we still don't know its exact role in tumor development,%26#8221; says principal investigator Daniel R. Schoenberg, professor of molecular and cellular biochemistry.

%26#8220;Our data suggest that Src may promote cancer by causing PMR1 to halt production of proteins that normally put the brakes on cell growth %26#8211; tumor-suppressor proteins, for example, or other growth-regulating proteins.%26#8221;

In healthy cells, Src helps control cell proliferation, differentiation, survival and movement. Mutated Src is found in about half of all colon, liver, lung, breast and pancreatic tumors, and the amount of Src can be significantly higher in cancer cells compared to normal cells.

Earlier research led by Schoenberg found that PMR1 helps control protein production by destroying particular messenger RNAs (mRNAs), molecules that carry the information used to assemble a protein.

That work showed that PMR1 attaches to the mRNAs and remains there as a silent passenger. If it receives the proper signal, however, the protein chops up and destroys the mRNA, which instantly stops production of that protein.

Cells use that mechanism to control the production of proteins such as growth factors, which activate genes in response to a hormone or other signal.

PMR1 also plays a key role in Cooley's anemia, which causes the loss of red blood cells in infants and children.

For the present study, Schoenberg and coauthor Yong Peng, a research associate in Schoenberg's laboratory, wanted to learn how PMR1 is activated to attach to mRNAs.

They found that activation occurs when PMR1 is momentarily joined by an unidentified enzyme. Contact with this enzyme changes the properties of PMR1, and this enables it to join with, or bind to, its target mRNA.

Peng then used monoclonal antibodies to isolate PMR1 and the enzyme while the two were bound together, capturing both. After separating the two, the investigators identified the enzyme as Src, which is a member of a large family of molecules called tyrosine kinases. These molecules act like switches that turn other molecules on and off, including PMR1.

%26#8220;That's the real excitement about this paper,%26#8221; Schoenberg says. %26#8220;We came at this with an interest in mRNA decay, and we may have stumbled across a fundamental mechanism of cancer.%26#8221;

Next, Schoenberg and his associates Xiaoqiang Liu and Elizabeth Murray will use three cancer-cell lines to try to identify what messenger RNAs %26#8211; which will also tell them what proteins %26#8211; are targeted and destroyed by PMR1.

%26#8220;That will help tell us whether Src works through PMR1 to contribute to cancer,%26#8221; Schoenberg says.

Funding from the National Institute for General Medical Sciences supported this research.

Source: Ohio State University

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New gene appears to increase risk of developing schizophrenia

Psychiatric researchers at The Zucker Hillside Hospital campus of The Feinstein Institute for Medical Research have uncovered evidence of a new gene that appears to increase the risk of developing schizophrenia, a disorder characterized by distorted thinking, hallucinations and a reduced ability to ...

Psychiatric researchers at The Zucker Hillside Hospital campus of The Feinstein Institute for Medical Research have uncovered evidence of a new gene that appears to increase the risk of developing schizophrenia, a disorder characterized by distorted thinking, hallucinations and a reduced ability to feel normal emotions.

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Working in conjunction with researchers at the Harvard Medical School Partners Center for Genetics and Genomics in Boston, MA, the Zucker Hillside team utilized a cutting-edge technology called whole genome association (WGA) to search the entire human genome in 178 patients with schizophrenia and 144 healthy individuals. WGA technology was used to examine over 500,000 genetic markers in each individual, the largest number of such markers examined to date, and the first published study to utilize WGA technology in a psychiatric illness. Previous studies have been much more limited in scope, often incorporating less than 10 markers.

The study results are scheduled to be published online Tuesday in Molecular Psychiatry, which can be accessed at http://www.nature.com/mp/journal/vaop/ncurrent/index.html.

Of the 500,000 genetic markers, the researchers found that the most significant link with schizophrenia came from a marker located in a chromosomal region called the pseudoautosomal region 1 (PAR1), which is on both the X and Y chromosomes. The marker was located adjacent to two genes, CSF2RA and IL3RA, which previously were thought to play a role in inflammation and autoimmune disorders. Those two genes produce receptors for two cytokines, GM-CSF and interleukin-3. Cytokines are involved in the body%26#8217;s response to infection, and may play a role in the brain%26#8217;s response to injury.

By then examining the DNA sequence of those genes in a separate group of patients with schizophrenia and healthy individuals, the research team %26#8211; working in conjunction with PGx Health in New Haven, CT -- observed multiple gene abnormalities in patients with schizophrenia that were not found, or were found much less commonly, in healthy individuals.

%26#8220;WGA technology allowed us to shine a light across virtually the entire genome, rather than looking at just one gene at a time,%26#8221; said Todd Lencz, PhD, the first author of the study, and an investigator at Zucker Hillside and The Feinstein Institute. %26#8220;Using WGA, we found genes that had not been previously considered in studies of schizophrenia.%26#8221; Dr. Lencz added that %26#8220;the critical next step is confirming these results in independent datasets.%26#8221;

Source: The Feinstein Institute for Medical Research

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Brucellosis: The fact sheet

Brucellosis is a contagious, costly disease of ruminant animals which also affects humans. Although brucellosis can attack other animals, its main threat is to swine, cattle, and bison. This disease is also known as contagious abortion or Bang’s disease.In humans, it's known as undulant fever ...
Brucellosis is a contagious, costly disease of ruminant animals which also affects humans. Although brucellosis can attack other animals, its main threat is to swine, cattle, and bison. This disease is also known as contagious abortion or Bang%26rsquo;s disease. In humans, it's known as undulant fever because of the severe intermittent fever it causes. This fever is accompanying human infection, also known as Malta fever because it was first recognized as a human disease on the island of Malta.

Should we be afraid of brucellosis?

Considering the damage done by the infections in animals, this must be considered as one of the most serious livestock diseases. In animals, brucellosis can cause a decreased milk production, weight loss, loss of young, infertility, and lameness. This disease can spread very rapidly, and is transmissible to humans. These facts make it all the more serious.

What can cause brucellosis?

Brucellosis is caused by a group of bacteria known scientifically as the genus Brucella. There are three species of Brucella that cause the most concern. Those are B. abortus, principally affecting cattle and bison, B. suis, principally affecting swine and reindeer but also cattle and bison, and B. melitensis, principally affecting goats. In cattle and bison, the disease currently localizes in the reproductive organs. Bacteria are shed in milk or via the aborted fetus, afterbirth, or other reproductive tract discharges of the affected animal.

Signs and symptoms of brucellosis

There is no effective way to detect infected animals by symptoms of brucellosis. The most obvious signs in pregnant animals are abortion or birth of weak calves. Milk production may be reduced from changes in the normal lactation period. This is caused by abortions and delayed conceptions. It is not true that all infected cows abort.
However, those that do abort, usually abort between the fifth and seventh month of pregnancy.





Infected cows usually abort once, but a percentage will abort during additional pregnancies too. Calves born from later pregnancies may be weak and unhealthy due to brucellosis. Even though their calves may appear healthy, infected cows continue to harbor and discharge infectious organisms. Those animals should be regarded as dangerous sources of the disease. Other symptoms of brucellosis include an apparent lowering of fertility with poor conception rates. It is retained after births with consequential uterine infections and occasionally enlarged, arthritic joints.

How does brucellosis spread?

Brucellosis is commonly transmitted onto susceptible animals by direct contact with infected animals. It can also transmit through an environment that has been contaminated with discharges from infected animals. Aborted fetuses, placental membranes or fluids, and other vaginal discharges present after an infected animal has aborted or calved are all highly contaminating as well. These discharges and fluids have a lot of Brucella organisms. Cows commonly lick those materials or the genital area of other cows. Cows could also ingest the disease-causing organisms with contaminated food or water. Despite occasional exceptions, the general rule is that brucellosis is carried from one herd to another by an infected animal. This mode of transmission occurs when a herd owner buys replacement cattle or bison that are infected. It could also happen when the owner%26rsquo;s animals were exposed to infection prior to purchase. The disease may also be spread when wild animals or animals from an affected herd mingle with brucellosis-free animals.

How to fight brucellosis?

In the past, brucellosis control was limited mainly to individual herds. These days there is a Cooperative State Federal Brucellosis Eradication Program working to eliminate the disease from the entire country. Like other animal disease-eradication efforts, the success of the program depends on the support and participation of each livestock producer. States are designated brucellosis-free when none of their cattle or bison is found to be infected for 12 consecutive months. The question is, how do epidemiologists help fight brucellosis? Epidemiologists are specially trained veterinarians who investigate disease sources and the means of eliminating infection in affected herds and areas. They are concerned with diseases in a group or population of animals, and evaluate circumstances connected with the occurrence of brucellosis. These veterinarians help eliminate brucellosis by identifying factors essential to its control and prevention in their region.

How does the brucellosis ring test surveillance work?

The BRT procedure, or brucellosis ring test procedure, makes it possible to perform surveillance on whole dairy herds quickly and economically. Milk or cream from each cow in the herd is pooled, and a sample is taken for testing for brucellosis. Then a suspension of stained, destroyed Brucella organisms is added to a small quantity of milk. If the milk from one or more infected animals is present in the sample, a bluish ring forms at the cream line as the cream rises, which is good sign the animals could have brucellosis. With certain exceptions, herd tests must include all cattle and bison over 6 months of age.

What is the incubation period of brucellosis?

An incubation period is the interval of time between exposure to an infectious dose of organism and the first appearance of disease signs for that animal. The incubation period of brucellosis in cattle, bison, and other animals is quite variable, ranging from about 2 weeks to a full year, and even longer in certain instances. When abortion is the first sign observed, the minimum incubation period is about 30 days in most animals. Some animals abort before developing a positive reaction to the brucellosis diagnostic test. Other infected animals may never abort. There are also infected animals that do not abort but develop a positive reaction to the diagnostic test within 30 to 60 days after infection. Some animals may not develop a positive reaction for several months to over a year after exposed to brucellosis.

Can brucellosis in animals be cured?

Put simply %26ndash; no, brucellosis cannot be cured. Repeated attempts to develop a cure for brucellosis in animals have failed. Occasionally, animals may recover after a period of time but it is more common that only the signs disappear and the animals remain diseased. Such animals are dangerous sources of infection for other animals with which they associate.

Can brucellosis be prevented?

The disease may be avoided by employing good sanitation and management practices for each animal. In fact, for cattle and bison in heavily infected areas or replacement animals added to such herds, officials recommend vaccinating heifers with an approved Brucella vaccine as the best prevention. The vaccine is a live product and must be administered only by an accredited veterinarian. It is important is that tattoo identifies the year in which vaccination took place. Brucella abortus vaccine produces a bodily response that increases the animal%26rsquo;s resistance to this disease. However, vaccination is not 100% effective in preventing brucellosis. The vaccine typically protects about 65% of the vaccinated cattle from becoming infected by an average exposure to Brucella.

How does brucellosis affect humans?

People infected with the brucellosis organism usually develop symptoms similar to a severe influenza. However, this disease (called undulant fever) persists for several weeks or months and may get progressively worse. Farmers, ranchers, veterinarians, and packing plant workers are infected most frequently, because they come into direct contact with infected animals. The initial symptoms of brucellosis are fatigue and headaches, followed by high fever, chills, drenching sweats, joint pains, backache, and loss of weight and appetite. Undulant fever usually does not kill its victims, but the disease is too serious to be dealt with lightly.

What are the main sources of human infection?

In years past, prior to pasteurization, raw milk was considered the prime source of brucellosis in humans, but today most humans contract the disease by coming in direct contact with infected material. Those are aborted fetuses, afterbirth, and uterine discharges of diseased animals, or infected carcasses at slaughter.

Can people get brucellosis by eating meat?

There is no danger from eating cooked meat products, because the disease-causing bacteria are not normally found in muscle tissue. Besides, these bacteria are killed by normal cooking temperatures. The disease could only be transmitted to humans while slaughtering infected animals or processing contaminated organs from freshly killed animals.

How to protect against brucellosis?

Ranchers, farmers, or animal managers should clean and disinfect calving areas and other places likely to become contaminated. Each individual should wear sturdy rubber or plastic gloves when assisting calving or aborting animals. They should also scrub hands well with soap and water afterward. Precautions against drinking raw milk or eating un-pasteurized milk products are also important. Ultimately, the best prevention for brucellosis is to eliminate brucellosis from all animals in the area.

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Wegener's Granulomatosis: Diagnosis & Treatment

Wegener’s granulomatosis is not a contagious disease as many people believe. There is no evidence suggesting that it is hereditary either. It is a very rare disease, affecting only 1 in every 30,000-50,000 people which is probably why most of us are not aware of this problem. About 500 new cas...
Wegener%26rsquo;s granulomatosis is not a contagious disease as many people believe. There is no evidence suggesting that it is hereditary either. It is a very rare disease, affecting only 1 in every 30,000-50,000 people which is probably why most of us are not aware of this problem. About 500 new cases are diagnosed each year, with the disease occurring at any age. However, it mostly affects individuals in their 30s and 40s. It affects males and females equally, but 97% of all patients are Caucasian, 2% are Negroid and 1% are of another race. With Wegener%26rsquo;s granulomatosis it is extremely important to know more about diagnosis and its treatment once it is diagnosed.

What is Wegener%26rsquo;s granulomatosis?

Wegener%26rsquo;s granulomatosis is a rare disorder that causes blood vessels in the upper respiratory tract (nose, sinuses, and ears), followed by lungs, and kidneys, to become swollen and inflamed. The eyes, skin, and joints may also be affected with arthritis occurring in about half the cases. Wegener's granulomatosis is thought to be an autoimmune disorder. This uncommon disease usually begins as a localized granulomatous inflammation of upper or lower respiratory tract mucosa, and may progress into generalized necrotizing granulomatous vasculitis and glomerulonephritis. The cause of Wegener%26rsquo;s granulomatosis is unknown. Although the disease resembles an infectious process, no causative agent has been isolated yet. Because of the characteristic histological changes, hypersensitivity has been postulated as the basis of the disease.

Symptoms of Wegener%26rsquo;s granulomatosis

Frequent sinusitis is the most common symptom for Wegener%26rsquo;s granulomatosis.






Other early symptoms include persistent fever without an obvious cause, night sweats, fatigue, and malaise (an %26ldquo;ill feeling%26rdquo;). Chronic ear infections may preclude a diagnosis of Wegener%26rsquo;s granulomatosis.







Other upper respiratory symptoms include nose bleeds, pain, and sores around the opening of the patient%26rsquo;s nose. Loss of appetite and weight loss are common as well. Skin lesions typically occur, but there is no one typical lesion associated with this disease. Symptoms of kidney disease may be present, but this does not always happen. The urine may be bloody, and usually it first appears as red or smoky urine. Eye problems develop in a significant number of patients, which may range from mild conjunctivitis to severe swelling of the eye. Other symptoms include weakness, cough, or coughing up blood, as well as bloody sputum. The patient commonly complains about shortness of breath, wheezing, chest pain, rashes, and joint pains.

Diagnosis of Wegener%26rsquo;s granulomatosis

Wegener's granulomatosis is diagnosed by characteristic clinical, serologic, and pathologic findings. Wegener%26rsquo;s granulomatosis must be diagnosed and treated early to prevent complications. Common complications include kidney disease, lung disease, heart attacks, and brain damage. A doctor can usually recognize the distinctive pattern of symptoms, although blood test results cannot specifically identify Wegener%26rsquo;s granulomatosis.





However, these blood tests can strongly support the diagnosis. A blood test can detect antineutrophil cytoplasmic antibodies in the blood, which suggest this disease. If the nose, throat, or skin is not affected, a diagnosis can be difficult. This is because the symptoms and x-rays can resemble those of several lung diseases. Chest x-ray may show cavities or dense areas in the lungs similar to cancer. To definitely diagnose Wegener%26rsquo;s granulomatosis a variety of tests may be performed, including a biopsy of abnormal tissue. The doctor could chose to have open lung biopsy, upper airway biopsy, nasal mucosal biopsy, bronchoscopy with transtracheal biopsy, or kidney biopsy. Urinalysis is helpful to look for signs of kidney disease such as protein and blood in the urine. In fact, the presence of kidney disease is necessary to make a definitive diagnosis of Wegener%26rsquo;s granulomatosis.

Treatment of Wegener%26rsquo;s granulomatosis

Corticosteroids may be used alone to treat the early symptoms. However, most people also need another immunosuppressive drug, such as cyclophosphamide to treat Wegener%26rsquo;s granulomatosis.





Imuran is a common choice. This drug is able to control the disease by reducing the body%26rsquo;s inappropriate immune reaction, which improves the prognosis significantly. Without treatment, this form of the disorder is fatal. Treatment is usually continued for at least a year after the symptoms for Wegener%26rsquo;s granulomatosis disappear.

Corticosteroids, given at the same time to suppress inflammation, can usually be tapered off and discontinued during other treatment still last. For people receiving immunosuppressive drugs, a doctor treats any suspected infection as early as possible. This is because of the body%26rsquo;s decreased ability to fight infections during this therapy. Pneumonia is particularly common when the lungs are affected by Wegener%26rsquo;s. Moreover, antibiotic may be used to prevent infections in people who have been taking immunosuppressive drugs for years. Treatment with corticosteroids, cyclophosphamide, methotrexate, or azathioprine produces a long-term remission in over 90% of patients afflicted by Wegener%26rsquo;s granulomatosis.







With treatment, most people recover within months although some may develop chronic renal failure. Without treatment, patients can die within a few months, which is why complications usually result from lack of treatment. Possible complications include chronic kidney failure, hemoptysis (coughing up blood), respiratory failure, or inflammation of the eyes. Common complications are also nasal septum perforation and rash. Moreover, medications used to treat the disease can cause side effects. These side effects may also lead to complications.

It is important to know when to call the health care provider. Anyone who experiences chest pain, coughing up blood, blood in the urine, or other symptoms of this disorder should call their health care provider. The problem is that no preventive measures are currently known.

Prognosis of Wegener%26rsquo;s granulomatosis

With proper treatment, most people diagnosed with Wegener%26rsquo;s granulomatosis recover within months. However, some may develop chronic renal failure. The complete syndrome usually progresses rapidly to renal failure once the diffuse vascular phase begins due to Wegener%26rsquo;s granulomatosis.







Patients with limited disease may have nasal and pulmonary lesions, with little or no systemic involvement, where pulmonary manifestations may improve or worsen spontaneously. A previously fatal prognosis can be been dramatically improved by treatment with immunosuppressive cytotoxic drugs. Early diagnosis and treatment are crucial, because a high remission rate is now possible. In fact, critical renal complications can be avoided or reduced. Cyclophosphamide, 1 to 2 mg/kg/day with oral hydration, or by initial rapid IV infusion as a single dose q 2 to 3 weeks is the drug of choice for Wegener%26rsquo;s granulomatosis.







Corticosteroids, which reduce the vasculitic edema, are given concurrently. It could be prednisone 1 mg/kg/day. After 2 to 3 mo, prednisone is tapered until the patient is maintained solely on cyclophosphamide. This means long-term IV dosing appears to be less efficacious.

In Wegener%26rsquo;s granulomatosis treatment, Azathioprine is less effective. However, this drug may be an alternative or adjunct to cyclophosphamide for patients who cannot tolerate cyclophosphamide. Pulse treatment with methotrexate seems to be a better alternative. Long-term prophylactic trimethoprim-sulfamethoxazole seems to be highly effective for upper respiratory tract lesions and may suffice as the sole long-term treatment once all systemic features have been ablated by cyclophosphamide and corticosteroids. Occasionally, the associated anemia may be so profound that blood transfusions are required due to this therapy.

Long-term complete remission can be achieved with proper therapy, even in the case of advanced disease. Kidney transplantation has been successful in renal failure, although a report of one patient who received a cadaver kidney implant showed that typical renal lesions of Wegener's granulomatosis developed at the end. An increased incidence of solid tumors after many years may reflect high-dose cyclophosphamide use as a therapy of choice. The high incidence of bladder cancer many years after treatment is an alarming consequence of the hemorrhagic cystitis associated with excreted cyclophosphamide breakdown products. It is often unmitigated by high fluid output during initial therapy. Kidney lesions cause glomerulonephritis, which may result in blood in the urine and kidney failure at the end as serious consequences of Wegener%26rsquo;s granulomatosis.







Kidney disease can quickly worsen, and if left untreated, kidney failure and death occur in more than 90% of patients. Wegener's granulomatosis is most common in middle-aged adults and some doctors think that men are affected twice as often as women. It is rare in children, but the disease has been seen in infants as young as 3 months of age.

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Biceps Tendinitis

Tendinitis is also known as tendonitis. This is an inflammation of a tendon, which is a band of fibrous tissue connecting muscle to bone. The inflammation causes pain, tenderness, and occasionally restricted movement of the muscle attached to the tendon. When we talk about biceps tendonitis, it is a...
Tendinitis is also known as tendonitis. This is an inflammation of a tendon, which is a band of fibrous tissue connecting muscle to bone. The inflammation causes pain, tenderness, and occasionally restricted movement of the muscle attached to the tendon. When we talk about biceps tendonitis, it is an inflammation of the biceps muscle tendon.

What is tendinitis?

Tendinitis can cause permanent damage to the tendons where a natural tendency to favor the painful area can also lead to stiffness. A vague discomfort at the age of 30, if overuse is continued for years, can lead to a loss of flexibility. Most commonly, this is due to scarring of the tissues. Sometimes the discomfort of tendinitis disappears within weeks, especially if you rest the affected area. In elderly people and those who continue to use the affected area, tendinitis often heals more slowly, and could even progresses to a chronic condition. Almost any tendon in the body can be affected. However, those located around the knee, foot, elbow and shoulder are most frequently affected.

Knee tendonitis is a common location for this inflammation type. Actually, there are three types of knee tendonitis %26ndash; patellar tendinitis, quadriceps tendinitis, and popliteus tendinitis. Patellar tendinitis is also called %26ldquo;jumper%26rsquo;s knee%26rdquo;. It affects the patellar tendon just below the patella (kneecap). The patient complains of pain during an activity such as landing from a jump and going downstairs, or during a lack of activity - for example sitting for long periods of time. Quadriceps tendinitis affects the patellar tendon just above the kneecap; this condition is likely to be found in athletes who do a lot of rapid acceleration and deceleration. Popliteus tendinitis affects the site of insertion of the popliteus tendon on the lateral epicondyle of the femur, so runners, particularly those who run down hills or along sloping surfaces, are likely to complain of this type of tendinitis.







Reducing the symptoms is the first step in alleviating the tendonitis and establishing a diagnosis. The doctor may tell you to use ice or heat, take certain medications, and limit physical activity. This might help control the pain and swelling along with self-massaging the area. Ice helps prevent swelling and reduces pain, so placing ice on the painful area for 10 minutes at a time, several times a day, may be a good idea. If you already have a swelling, heat may help; apply a heating pad or hot towels to the tendon for 30 minutes at a time, two or three times a day. Pain relievers and anti-inflammatory drugs are used to ease immediate symptoms. However, this is not going to cure the condition or keep it from recurring. Injecting cortisone and a local anesthetic into the area surrounding the tendon usually provides substantial relief. However, this relief only lasts for 24-72 hours. In rare cases, surgery is necessary to repair damage. Rest allows the tissues to heal after the surgery. On the other hand, returning to activity too soon may cause the symptoms to reoccur.

Self-massage using a heat-inducing cream or oil may also help with tendonitis. Physical therapists suggest rubbing the ointment in semicircles in all directions away from the knotted tissue three times a day. You should continue with this process until healed.

Shoulder tendinitis has three types, which are rotator cuff tendinitis, calcific tendinitis and biceps tendinitis. The rotator cuff consists of four muscles around the shoulder joint that help control the shoulder%26rsquo;s position. This tendon keeps it stable. With rotator cuff tendinitis the pain is located about three inches below the top of the shoulder. This pain is felt when reaching overhead or behind the back. Rotator cuff tendinitis will usually resolve with rest, anti-inflammatory medications, or an injection of cortisone and a local anesthetic into the area surrounding the tendon. Patients with rotator cuff tendonitis should also exercise using light weights. If pain is not relieved with exercise and medication alone, an x-ray of the shoulder may reveal bony anatomy. This occurs between a bone at the top of the shoulder and the ball at the top of the arm bone. A procedure called an acromioplasty is performed to make more room for the rotator cuff tendons and relieve this problem. Using an arthroscope it is inserted into the shoulder and the surgeon is able to remove some of the bone from the acromion through two or three small 1/4%26quot; incisions.

Calcific tendinitis is caused by calcium deposits in the rotator cuff region, and symptoms include excruciating pain and severe restriction of shoulder motion. X-rays reveal calcium deposits within the rotator cuff or overlying the head of the humerus and treatment includes injection of cortisone and a local anesthetic into the area surrounding the tendon. Multiple needle punctures into the calcium deposit may break it up and relieve the symptoms of tendinitis. If conservative treatment is ineffective, arthroscopic calcium removal and subacromial bursectomy are viable alternatives.

Biceps tendinitis is an inflammation of the biceps tendons that attach to the shoulder, usually affecting individuals whose occupations involve repetitive biceps flexion against resistance, or whose activities include forceful throwing of a ball. Biceps tendinitis will resolve with rest, anti-inflammatory medications or an injection of cortisone and a local anesthetic. All this is placed into the area surrounding the tendon, as well as a sling to immobilize the shoulder. With biceps tendinitis surgery is occasionally required to stabilize a displaced tendon.

More on biceps tendinitis

The biceps muscle is a large, strong muscle in the front of the upper arm. This muscle divides into two major sections. The larger section of the bicep, called the long head of the muscle, is connected to the shoulder by a long tendon that passes through a groove in the upper end of the arm bone, called the bicepital groove. That is the point where tendinitis strikes, and beyond the groove, the tendon enters the shoulder joint and attaches to the top of the shoulder socket. Biceps tendon is held in the groove of the upper arm bone by the inter-tubercular ligament. If this ligament is injured or stretched, the tendon slides in the groove causing problems. This is because sliding irritates the tendon, and the result is biceps tendinitis. A second cause of biceps tendinitis may be a deformity in the groove itself that can be too shallow or have rough edges. In any overhead position, the tendon is forced to curve, but the groove is fixed, so if the tendon is not firmly held down, it will slide out.

Signs and symptoms of biceps tendinitis

Injuries to the biceps tendons are commonly caused by repetitive overhead activity, so symptoms include pain when the arm is overhead or bent. It could also appear as localized tenderness as the tendon passes over the groove in the upper arm bone. Occasionally, a snapping sound or sensation in the shoulder area could also be a sign of biceps tendinitis. If you notice anything similar, it would be good to have doctor%26rsquo;s exam.

Diagnosis and treatment of biceps tendinitis

Like most shoulder ailments, biceps tendinitis is painful, especially in the throwing or serving position. The pain is focused on the front of patient%26rsquo;s shoulder, so for simple cases of biceps tendinitis, it is recommended to apply ice and rest. This means initial treatment is conservative. A patient should also start pendulum exercises as soon as the pain decreases.

Usually, the irritation disappears in a week, but you should know if you put too much pressure on the tendon too soon, the tendinitis will flare up again. For the more severe cases of biceps tendinitis, the doctor could prescribe oral anti-inflammatory medication and two weeks of rest. The icing should continue twice a day and patient should also perform pendulum exercises if they are not too painful. Very rarely does biceps tendinitis require surgery as the only treatment option that works. It only happens when the tendon will not stay in the bicipital groove and the irritation is chronic; the operation procedure involves surgically detaching the tendon from the shoulder joint. It is reattached to the coracoid process, a lip in the front of the shoulder, so this operation alleviates the pain and, almost unbelievably, there is very little loss of strength or mobility.

Surgical options for biceps tendinitis

If the pain results from shoulder instability or from pressure on the tendon from the shoulder bones, your orthopaedist may recommend arthroscopic surgery as the best treatment. Using fiber optic technology and miniature instruments inserted through a small incision, the surgeon can examine the shoulder joint. This way he will also be able to anchor the tendon properly. After surgery, your orthopaedist will prescribe a rehabilitation program. This program includes stretching and strengthening exercises. Early movement is important, but patient should wait for physician%26rsquo;s approval before doing any heavy lifting or returning to sports. However, once diagnosed with biceps tendonitis, the doctor will examine you and see which treatment options is the best choice in your case. Every patient might require different treatment, depending on many variable factors of this disease.

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Morton's Neuroma: Symptoms & Treatment

A neuroma is a thickening of nerve tissue. This problem may develop in various parts of the body. The most common neuroma in the foot is a Morton’s neuroma. It occurs at the base of the third and fourth toe. It is sometimes referred to as an inter-metatarsal neuroma, where inter-metatarsal des...

A neuroma is a thickening of nerve tissue. This problem may develop in various parts of the body. The most common neuroma in the foot is a Morton%26rsquo;s neuroma. It occurs at the base of the third and fourth toe. It is sometimes referred to as an inter-metatarsal neuroma, where inter-metatarsal describes its location (in the ball of the foot between the metatarsal bones, extending from the toes to mid-foot). Neuromas may also occur in other locations in the foot. The thickening or enlargement of the nerve that defines a neuroma is the result of nerve compression and irritation. This compression creates a swelling, eventually leading to permanent nerve damage as a serious consequence of Morton%26rsquo;s neuroma.

What is Morton%26rsquo;s neuroma?

Morton's neuroma is an enlarged nerve that usually occurs in the third inter-space. This inter-space is between the third and fourth toe. Problems often develop in this area because a part of the lateral plantar nerve combines with a part of the medial plantar nerve here. When the two nerves combine, they are typically larger in diameter than nerves going to the other toes. Moreover, the nerve lies in subcutaneous tissue, just above the fat pad of the foot, close to arteries and veins. Above the nerve, there is a structure called the deep transverse metatarsal ligament. This ligament is very strong, holding the metatarsal bones together. This ligament also creates the ceiling of the nerve compartment. With each step, the ground pushes up on the enlarged nerve and the deep transverse metatarsal ligament pushes down, which causes compression in a confined space. The reason the nerve enlarges has not been determined yet. Flat feet can cause the nerve to be pulled toward the middle more than normal. This could lead to irritation and possibly enlargement of the nerve. The syndrome is more common in women than men, possibly because women wear confining shoes more often.

High heels cause more weight to be transferred to the front of the foot, and tight toe boxes create lateral compression.





Because of this, more force is being applied in the area and the nerve compartment is squeezed from all sides. Under such conditions, even a minimal enlargement in the nerve can elicit pain as one of the symptoms.

Signs and symptoms of Morton%26rsquo;s neuroma

The most common symptom of Morton's neuroma is a localized pain in the inter-space between the third and fourth toe. The pain could be sharp or dull, and is worsened by wearing shoes and by walking. However, the pain is usually less severe when the foot is not bearing weight. Patient diagnosed with Morton%26rsquo;s neuroma will probably have one or more of these symptoms where the nerve damage occurs. These symptoms are tingling, burning, or numbness, pain, and a feeling that something is inside the ball of the foot, or that there is a rise in the shoe or a sock is bunched up. The progression of a Morton%26rsquo;s neuroma often follows the same pattern. The symptoms begin gradually, and at first they occur only occasionally, when wearing narrow-toed shoes or performing certain aggravating activities. Symptoms may be suppressed temporarily by massaging the foot or by avoiding aggravating shoes or activities. Over time the symptoms progressively worsen and may persist for several days or weeks even when you avoid walking. The symptoms become more intense as the neuroma enlarges and the temporary changes in nerve become permanent.

What causes Morton%26rsquo;s neuroma?

Anything that causes compression or irritation of the nerve can lead to neuroma. One of the most common offenders is wearing shoes that have a tapered toe box. High-heeled shoes that cause the toes to be forced into the toe box could also cause Morton%26rsquo;s neuroma. People with certain foot deformities, such as bunions, hammertoes, flatfeet, or more flexible feet are at higher risk for developing Morton%26rsquo;s neuroma. Other potential causes are activities that involve repetitive irritation to the ball of the foot, such as running or racquet sports. An injury or other type of trauma to the area may also lead to Morton%26rsquo;s neuroma.

Diagnosing Morton%26rsquo;s neuroma

To diagnose Morton%26rsquo;s neuroma the podiatrist commonly palpates the area to elicit pain. He will try to diagnose you by squeezing the toes from the side. Next he or she may try to feel the neuroma by pressing a thumb into the third interspace of the foot. The podiatrist then tries to elicit Mulder%26rsquo;s sign. He or she will do this by holding the patient%26rsquo;s first, second, and third metatarsal heads with one hand and the fourth and fifth metatarsal heads in the other and pushing half the foot up and half the foot down slightly, where in many cases of Morton%26rsquo;s neuroma, this causes an audible click. This click is known as Mulder%26rsquo;s sign, which can help with Morton%26rsquo;s neuroma diagnosis. An x-ray should be taken to ensure that there is not a fracture of the foot. X-rays also can be used to examine the joints and bone density, ruling out arthritis and osteoarthritis. An MRI scan or magnetic resonance imaging is used to ensure that the compression is not caused by a tumor. An MRI also determines the size of the neuroma and how the syndrome should be treated - whether conservatively or aggressively. If surgery is indicated, the podiatrist can determine how much of nerve must be resected. This is important because there are different surgical techniques available, depending on the size and the position of the neuroma. However, MRIs are expensive, which is why some insurance companies are reluctant to pay for them. If the podiatrist believes an MRI is necessary, he or she can persuade the insurance company to pay for it. To establish a diagnosis, the foot and ankle surgeon will also need to obtain a thorough history of your symptoms and examine your foot. The best time to see a foot and ankle surgeon is early in the development of symptoms. This is because early diagnosis of a Morton%26rsquo;s neuroma greatly lessens the need for more invasive treatments and may avoid surgery.

Treatment of Morton%26rsquo;s neuroma

In most cases, initial treatment consists of padding and taping. The goal is to disperse weight away from the neuroma. If the patient has flat feet, an arch support is incorporated so the patient will be instructed to wear shoes with wide toe boxes and avoid shoes with high heels. The doctor could recommend an injection of a local anesthetic to relieve pain and a corticosteroid to reduce inflammation. The patient is advised to return in a week or two sothat the progress of the disease could be monitored. If the pain has been relieved, the neuroma is probably small and caused by the structure of the patient%26rsquo;s foot and the type of the patient%26rsquo;s shoes. It can be relieved by a custom-fitted orthotic that helps keep the foot in a better position to prevent further damage. Conservative treatment does not work for most of patients and minor surgery usually is necessary to treat Morton%26rsquo;s neuroma.

There are two surgical procedures available in Morton%26rsquo;s neuroma treatment. The dorsal approach involves making an incision on the top of the foot, which permits the patient to walk soon after surgery. This is because the stitches are not on the weight-bearing side of the foot. The podiatrist maneuvers the instruments carefully through many structures and cuts the deep transverse metatarsal ligament. This ligament typically causes most of the nerve compression. This procedure can lead to instability in the forefoot that may require attention after treatment. The second procedure involves a plantar approach. In this procedure the incision is made on the sole of the foot. The patient must use crutches for about three weeks and the scar that forms can make walking uncomfortable as a side effect of this approach.

The advantage of the plantar approach is that the neuroma can be reached easily and resected without cutting any structures in the foot. However, before surgery, while developing a treatment plan, the foot and ankle surgeon will first determine how long the patient has had the neuroma. He will also need to evaluate its stage of development, because treatment approaches vary according to the severity of the problem. For mild to moderate cases of neuroma, treatment options include padding, which are techniques that provide support for the metatarsal arch, thereby lessening the pressure on the nerve and decreasing the compression when walking. Icing mean placing an icepack on the affected area helps reduce swelling. Orthotic devices issued by a foot and ankle surgeon provide the support needed to reduce pressure and compression on the nerve. Activity modifications are important to reduce especially those that put repetitive pressure on the neuroma. You should avoid these activities until the condition improves.

Changes in shoe wear could help, because it is important to wear shoes with a wide toe box and avoid narrow-toed shoes or shoes with high heels. Non-steroidal anti-inflammatory drugs such as Ibuprofen help reduce the pain and inflammation. If there is no significant improvement after the initial treatment, injection therapy may be tried as a treatment option for Morton%26rsquo;s neuroma. Surgery may be considered in patients who have not received adequate relief from other treatment options. The foot and ankle surgeon will determine which approach is optimal for your condition. The length of the recovery period after surgery will vary depending on the procedure or procedures performed. Regardless of whether you've undergone surgical or non-surgical treatment, your foot and ankle surgeon will recommend long-term measures, since it is important to help keep your symptoms from returning.

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