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Knowing that a reduction in the amount of PRPP synthetase 1 is what causes deafness in DFN2, Liu and his colleagues are now exploring potential enzyme replacement therapies to either restore hearing or prevent further hearing loss in boys with DFN2. Since the PRPS1 mutations can be used as a genetic marker for DFN2, in the future at-risk boys could be tested at birth and immediately put on enzyme replacement therapy to reduce or prevent the hearing loss that would ordinarily come later in life.

In addition, the knowledge that scientists gather about the mechanisms of PRPS1 potentially could be used to develop treatments to combat acquired hearing loss, such as the hearing loss caused by drugs that are used in some chemotherapy regimens and treatments for HIV/AIDS. These are powerful and helpful medications, but they have the unfortunate side effect of damaging, even killing, hair cells in the inner ear. The results from this study open the possibility for improving these life-saving treatments by eliminating or reducing the disabling side effect of hearing loss.

In addition to NIDCD support, the following institutions collaborated in this study: Chinese PLA General Hospital, Beijing; University of Science and Technology of China, Hefei; Chinese Academy of Sciences, Hefei; Guizhou Provincial People’s Hospital, GuiYang, China; UCL Institute of Child Health, London; Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Second Medical University, Shanghai; Department of Genetics, Harvard Medical School, Boston; Massachusetts Eye and Ear Infirmary, Boston; and Howard Hughes Medical Institute, Boston.

NIDCD supports and conducts research and research training on the normal and disordered processes of hearing, balance, smell, taste, voice, speech and language and provides health information, based upon scientific discovery, to the public. For more information about NIDCD programs, see the Web site at www.nidcd.nih.gov.
The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

A gene associated with a rare form of progressive deafness in males has been identified by an international team of researchers funded by the National Institute on Deafness and Other Communication Disorders. The gene, PRPS1, appears to be crucial in inner ear development and maintenance. The findings are published in the December 17 early online issue of the American Journal of Human Genetics.

“This discovery offers exciting therapeutic implications,” said James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. “Not only does it give scientists a way to develop a targeted treatment for hearing loss in boys with this disorder, it may also open doors to the treatment of other types of deafness, including some forms of acquired hearing loss.”

The gene is associated with DFN2, a progressive form of deafness that primarily affects males. Boys with DFN2 begin to lose their hearing in both ears roughly between the ages of 5 and 15, and over the course of several decades will experience hearing loss that can range from severe to profound. Their mothers, who carry the defective PRPS1 gene, may experience hearing loss as well, but much later in life and in a milder form. Families with DFN2 have been identified in the United States, Great Britain, and China.

The NIDCD-funded researchers led by Xue Zhong Liu, M.D., Ph.D., of the University of Miami Miller School of Medicine, discovered that the PRPS1 gene encodes the enzyme phosphoribosylpyrophosphate (PRPP) synthetase 1, which produces and regulates PRPP (phospho-ribosylpyrophosphate), and appears to play a key role in inner ear development and maintenance. The four mutations identified in the PRPS1 gene cause a decrease in the production of the PRPP synthetase 1 protein that results in defects in sensory cells (called hair cells) in the inner ear, and eventually leads to progressive deafness.

“PRPS1 is an interesting example of a human disease gene in which gain of function or loss of function mutations cause several different and distinct hereditary disorders,” says Dr. Liu. “Our findings emphasize the body’s need for tight regulation of PRPP synthetase 1 since a drop in activity can lead to deafness.” Other mutations in the PRPS1 gene have been linked to neurodegenerative disorders such as Arts syndrome and a form of Charcot-Marie Tooth disease, both of which feature deafness in the constellation of symptoms.

Chronic renal failure is a serious condition that, over time, causes the kidneys to stop working properly.

The University of Virginia Health System offers this list of conditions that could lead to chronic renal failure:
Damage to the kidneys in people with diabetes.
Persistent high blood pressure.
The autoimmune disease lupus.
A lingering blockage in the urinary tract.
Hereditary conditions such as cystinosis or Alport syndrome.
Nephrotic syndrome.
Polycystic kidney disease.
Inflammation of structures inside the kidneys.

Replacing or adding wiring increases the risk of major complications for patients having surgery to replace a pacemaker or other heart rhythm-stabilizing device, a new study finds.

U.S. researchers analyzed complication rates among patients enrolled in the REPLACE prospective multicenter registry who underwent replacement of a pacemaker, implantable cardioverter defibrillator (ICD), or cardiac resynchronization (CRT) generator. One group of patients required no new wiring while the other group did.

Major complications occurred in 15.3 percent of the 713 patients who needed wiring. The highest rate of major complications occurred in patients whose replacement procedure required a lead to connect a CRT generator to the left ventricle. Minor complications occurred in 7.6 percent of the wiring patients, said the University of Washington, Seattle researchers.

The average age of the patients needing wiring was 69.5 years at the time of enrollment. Of that group, 75.9 percent were male, 40.1 percent had previously suffered a heart attack, 30.4 percent had diabetes, and 55.7 percent had serious congestive heart failure.

The study was to be presented Sunday at the American Heart Association’s meeting in Orlando, Fla.

A moderate-fat diet may work better than a low-fat regimen for people suffering from metabolic syndrome, a collection of conditions putting them at higher risk for cardiovascular disease, new research finds.

“This is a good study that essentially confirms that the current recommendations are appropriate,” said Alice Lichtenstein, a spokeswoman for the American Heart Association (AHA). “Since 2000, the AHA has been recommending not a low-fat diet, but one that is low in saturated fats and trans fatty acids.”

People with metabolic syndrome are glucose-intolerant, meaning they can’t process blood sugar well. Low-fat, high-carbohydrate diets exacerbate this condition, Lichtenstein explained.

To be diagnosed with metabolic syndrome, you must have three or more of the following risk factors for heart disease: belly fat, high triglycerides, low good cholesterol, high blood sugar and high blood pressure.

The study was among several to be presented Monday at the AHA’s annual meeting in Orlando, Fla. Researchers from the University of Washington in Seattle randomized 71 men and women with metabolic syndrome into one of two diet arms, the first made up of 40 percent fat, 45 percent carbohydrate and 15 percent protein (the moderate-fat diet) and the other, the low-fat diet, containing 20 percent fat, 65 percent carbs and 15 percent protein. Saturated fat content was about 8 percent in each, and each had about the same amount of fiber.

Levels of LDL (or “bad”) cholesterol fell 3.4 milligrams per deciliter (mg/dL) on the low-fat diet compared with 11.6 mg/dL on the moderate-fat plan. HDL (or “good”) cholesterol also fell, by 4.9 mg/dL on the low-fat plan and by 1.9 mg/dL on the other.

C-reactive protein (CRP), a marker of inflammation linked to heart disease, fell more in the low-fat group than in the moderate-fat group (0.82 mg/L versus 0.63 mg/L), but the authors considered it a good drop in both cases.

While triglycerides, another measure of heart health, increased 11.1 mg/dL on the low-fat diet, they dropped 28.6 mg/dL on the other plan.

Experts familiar with the study aren’t surprised by the findings. “This sort of falls within the boundaries of what we used to call the Atkins diet, which was a high-lipid and low-carb diet. Normally this kind of diet suppresses appetite, improves diabetes,” said Dr. Alfred Bove, president of the American College of Cardiology. “This diet looks like it does a good job of altering the negative metabolic effects of early diabetes or high carbohydrate stimulation,” he said.

“Much of this we’ve known before, but the idea is that a moderate-fat diet is something most people can tolerate,” Bove said. “It probably affects the way insulin is released because if you have a lot of carbohydrates in the diet, you tend to generate a lot of insulin, and insulin is the hormone that lowers blood sugar,” Bove explained. “In addition to lowering blood sugar, it also increases appetite so a lot of people on high-carb diets are restimulated to eat more.”

Another study found yet more evidence to recommend the famed DASH (Dietary Approaches to Stop Hypertension) diet, an eating plan that has been found to lower blood pressure. DASH calls for a diet high in fruits and veggies and low in total fat, saturated fat and cholesterol. Red meat and sweets are limited as well.

This study showed that the diet lowered coronary heart disease risk for a decade by 18 percent compared with people eating as usual and 11 percent compared with people in a fruit- and vegetable-rich program.

“We took our data and plugged it into the Framingham risk equation used to estimate heart disease risk and found a 20 percent reduction in risk of heart disease,” said study senior author Dr. Lawrence Appel, professor of medicine at Johns Hopkins Medical Institutions in Baltimore. “We don’t have a 40,000-person randomized trial but, next to that, this is probably one of the best analyses to show that the DASH diet should reduce heart disease as well as blood pressure.”

Although the DASH diet is recommended to reduce blood pressure, there had been some “quirks” in previous data leading people to question the program’s net effect, Appel said.

A third study confirmed that even small helpings of fruits and veggies can boost your health.

In a Columbia University Medical Center study of 501 patients, just one extra serving of fruits or vegetables was linked with lower levels of both CRP and cholesterol. And adding another gram per day of omega-3 fatty acids, found in fish as well as plant-based oils, also was associated with a drop in CRP levels.

Lowering intake of saturated and trans fats meant reductions in both total and LDL cholesterol, the researchers, led by Dr. Lori Mosca, found.

And more calories from alcohol seemed to move HDL cholesterol levels down, although other measures did not change.

Think that a drink or two a day help keep your mind sharp into older age? Researchers from the United Kingdom may have poked a hole into that idea.

Dr. Claudia Cooper, at University College London, and colleagues note in a study that moderate drinkers - generally that’s two drinks a day for men and one for women - tend to have less forgetfulness and better mental skills as they age.

However, moderate drinkers also tend to have social, economic, and educational advantages that help them amass greater thinking skills over time.

A report by Cooper’s team in the Journal of Neurology, Neurosurgery and Psychiatry, suggests that it’s these advantages - and not moderate drinking itself - that are responsible for the benefits.

Cooper’s team evaluated social, economic, and physical factors, plus thinking skills, in 1735 men and women 60 to 74 years old. Most - about 87 percent - of the participants reported drinking moderately or abstaining. The rest had histories that suggested problem drinking, and were excluded from the study.

They tested how well the participants could read words pronounced differently from how they are spelled, which indicates how much of their early-learned reading skills each retained into older age.

It’s also a skill that isn’t lost until mental function declines a great deal, Cooper told Reuters Health by email, which makes it a good indicator of previously obtained thinking skills.

When Cooper’s team only took social and economic factors into account, they saw an association between moderate alcohol consumption and greater thinking abilities, similar to findings reported in earlier studies.

But when they allowed for current thinking skills, and the fact that participants with greater physical health were also more likely to drink more, the association between moderate drinking and current thinking skills disappeared.

The authors note that the American Heart Association recently warned against putting too much stock in the link between moderate drinking and better thinking skills, and that more than three drinks per day are linked to a variety of medical conditions such as heart disease and stroke.

People who suffer migraines have more than double the risk of ischemic stroke, and the risk is especially high in women, a new study has found.

Ischemic stroke, the most common type of stroke, occurs when blood supply to the brain is cut off by plaque accumulation or a blood clot.

In this study, researchers from Johns Hopkins University School of Medicine reviewed the findings of 21 studies that included a total of 622,381 men and women, aged 18 to 70, in Europe and North America. Those with migraines were 2.3 times more likely than people without migraines to suffer ischemic stroke. The risk was 2.5 times higher for migraine sufferers who experienced aura (visual disturbances such as flashing lights, zigzag lines and blurred vision), and for women experiencing aura, 2.9 times higher.

The study was to be presented Monday at the American Heart Association’s annual meeting in Orlando, Fla.

The findings reinforce the link between migraine and stroke and also correct some discrepancies in previous analyses that yielded mixed results, according to Hopkins cardiologist and senior study investigator Dr. Saman Nazarian.

Nazarian said nearly 1,800 articles have been written about the relationship between migraine and stroke, but the Hopkins review is believed to be the largest of its kind and was more selective, including only studies that used similar designs and groups of people.

“Identifying people at highest risk is crucial to preventing disabling strokes. Based on this data, physicians should consider addressing stroke risk factors in patients with a history or signs of light flashes and blurry vision associated with severe headaches,” Nazarian said in a Hopkins news release.

There are a number of migraine prevention and treatment options, including smoking cessation, taking medications to lower blood pressure or taking blood-thinning drugs such as aspirin, Nazarian added. For women with migraines, additional options include discontinuing use of birth control pills or stopping hormone replacement therapy.

Eating white and oily fish regularly may provide protection against type 2 diabetes, but eating shellfish may have the opposite effect, a study from the UK hints.

The study team noted about 25 percent less risk type 2 diabetes among men and women who reported eating one or more, as opposed to fewer, servings of white or oily fish each week.

Unexpectedly, however, they found that men and women who ate similar amounts of shellfish — primarily prawns, crab, and mussels — had about 36 percent increased risk of developing type 2 diabetes.

But “it may not be the ’shellfish’ per se which increased the risk for diabetes,” Dr. Nita Forouhi, of Addenbrooke’s Hospital, University of Cambridge, noted in an email to Reuters Health.

Rather, the cooking and preparation methods used in the UK, for example, oils used when frying or butter- and mayonnaise-based sauces served with shellfish, may increase cholesterol intake which, in turn, may raise diabetes risk.

Forouhi and colleagues assessed the weekly intake of shellfish plus white fish such as cod, haddock, sole, and halibut, or oily fish such as mackerel, kippers, tuna, and salmon, reported by 9,801 men and 12,183 women. The study participants were 40 to 79 years old at the time and had no history of diabetes.

Over an average of 10 years, 725 of these men and women developed type 2 diabetes.

Both the lower risk linked with white and oily fish and the greater risk tied to shellfish intake remained when the investigators allowed for a range of diabetes risk factors including physical activity, obesity, alcohol use, and fruit and vegetable intake.

The investigators emphasize that the link between shellfish intake and diabetes risk requires further investigations in other populations. This observed link, Forouhi commented, “does not imply that one is the cause of the other.”

The findings on white and oily fish “reinforce the public health message to consume fish regularly,” the investigators conclude, while the shellfish findings should be studied further.

Tissue plasminogen activator (tPA) treatment benefits stroke patients when used up to 4.5 hours after a stroke, according to German researchers who said their findings provide further evidence to increase the tPA treatment window from the current three hours to 4.5 hours.

Previously published findings from the ECASS III study indicated that tPA treatment led to better outcomes than placebo in stroke patients treated from three hours to 4.5 hours post-stroke.

In this new study, Dr. Werner Hacke, of the University of Heidelberg, and colleagues conducted a secondary analysis of ECASS III data using different endpoints. They focused on the efficacy and safety of tPA treatment (using alteplase) and also looked for any factors or patient subgroups that might affect treatment outcome.

The study included 418 patients who received alteplase from three hours to 4.5 hours after a stroke, and 403 patients who received a placebo. The results showed a clear benefit from treatment with alteplase in all types of patients, including those younger and older than 65 years, men and women, and those with or without a history of diabetes, stroke or high blood pressure.

The researchers also found that alteplase was beneficial, regardless of the severity of the stroke.

“Our results support the use of this thrombolytic drug in the extended period across a broad range of patient subgroups who meet the requirements of the European product label but miss the approved treatment window of 0-3 hours,” Hacke and colleagues wrote. “Even with these encouraging findings, the most important principle of acute stroke intervention should, however, not be lost — i.e., time remains critical and fast treatment still provides the greatest chance of recovery.”

The study was released online Oct. 20 in advance of publication in the December print issue of The Lancet.

“Thrombolytic therapy benefits patients, should be given as early as possible, offers sustained benefit, and is cost-effective,” Dr. Patrick Lyden, of Cedars-Sinai Medical Center in Los Angeles, wrote in an accompanying editorial.

“The physician must, as always, diligently undertake a careful history and physical examination, look at the non-contrast brain CT scan carefully, and follow the appropriate protocol. All of these steps will result in substantial benefit to public health and will safely benefit many patients. But ‘time is brain,’ and therapy must be given as soon as possible after the patient arrives — there is indeed not a moment to lose.”

An international team led by a National Institutes of Health researcher has found that carriers of a rare, genetic condition called Gaucher disease face a risk of developing Parkinson’s disease more than five times greater than the general public. The findings were published today in the New England Journal of Medicine.

In previous studies, several genes have been linked to Parkinson’s disease. However, researchers say their work conclusively shows that mutations in the gene responsible for Gaucher disease are among the most significant risk factors found to date for Parkinson’s disease. The discovery was made by investigators from the National Human Genome Research Institute (NHGRI) and the National Institute on Aging (NIA), both parts of the National Institutes of Health, in collaboration with scientists from 16 research centers across four continents.

“This analysis illustrates how studying a rare but important disorder, like Gaucher disease, can provide powerful clues about more common disorders, such as Parkinson’s disease,” said NHGRI Scientific Director Eric Green, M.D., Ph.D. “Understanding the genetic basis of rare conditions can thus provide insights into normal cellular and biological processes, which in turn may lead to improved diagnostic and therapeutic strategies.”

Parkinson’s disease, a neurological condition that typically causes tremors and stiffness in movement, affects about 1 to 2 percent of people over the age of 60. The chance of developing Parkinson’s disease increases with age and involves a combination of environmental risk factors and genetic susceptibility.

Gaucher disease occurs when an individual inherits two defective copies of the GBA gene, which codes for an enzyme called glucocerebrosidase. This enzyme breaks down a fatty substance called glucocerebroside, which, when not properly disposed of, can harm the spleen, liver, lungs, bone marrow and, in some cases, the brain. The enzyme functions in a part of the cell called the lysosome, where cellular components are broken down, or metabolized, for recycling.

In the past, it was thought that people who carry just one altered GBA gene were unaffected. However, in recent years, research groups at NHGRI and elsewhere have completed small studies suggesting that carriers of GBA alterations may have an increased risk of developing Parkinson’s disease.

“The opportunity was right to amass the data into one powerful study,” said Ellen Sidransky, M.D., senior investigator in NHGRI’s Medical Genetics Branch, who is the lead author of the study and coordinated the effort. “Our analyses of the accumulated data provide a convincing association between GBA alterations and Parkinson’s disease.”

The research team examined the frequency of GBA alterations in 5,691 patients with Parkinson’s disease, including 780 Ashkenazi Jews, a population in which a particular type of Gaucher disease is more prevalent. Those data were matched against 4,898 unaffected volunteers, called controls, which included 387 Ashkenazi Jews.

At least one of the two common GBA alterations was found in 3.2 percent of Parkinson’s patients and 0.6 percent of controls. Among the Ashkenazi subjects, 15.3 percent of those with Parkinson’s disease carried a GBA alteration compared to 3.4 percent of Ashkenazi controls.

In addition to screening for the two common alterations, five of the research centers sequenced the entire GBA gene in 1,642 non-Ashkenazi patients with Parkinson’s disease and 609 non-Ashkenazi controls. Using this more thorough method, they found many additional alterations associated with Parkinson’s disease, and showed that 7 percent of patients carried an alteration, indicating that it is important to look beyond the two common alterations to gain a true picture of risk in the general population.

Besides significantly increasing the risk of Parkinson’s disease, GBA alterations also appear to increase the likelihood of early disease onset. According to the new study, Parkinson’s patients with GBA alterations developed symptoms an average of four years earlier than other Parkinson’s patients.

Overall, the researchers found that the association between GBA and Parkinson’s disease is not confined to any single ethnicity or to specific GBA mutations, though they did find that some gene alterations are seen more frequently in certain populations. Compared with the general population, in which GBA alterations occur in fewer than one out of 100 people, GBA alterations occur in at least one out of 16 people of Ashkenazi descent. However, many GBA mutation carriers as well as patients with Gaucher disease never develop Parkinson’s disease, so this appears to be only one of several risk factors involved.

Further research is in progress to understand the full spectrum GBA alterations, their biological significance and their association with both Parkinson’s and Gaucher disease. The researchers are also pursuing ways to provide more accurate guidance based on the findings for genetic counseling and for the development of new therapeutic strategies for these disorders.

Along with NIH, the study included research centers in New York City, Jacksonville, Fla. and Seattle, as well as in Brazil, Canada, France, Germany, Israel, Italy, Japan, Norway, Portugal Singapore and Taiwan. The data were collected and analyzed at NHGRI.