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Researchers ID Brain Circuits Responsible for Hunger

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A team of researchers has identified the brain circuits controlling hunger that are influenced by a hormone called leptin. The research, published in Proceedings of the National Academy of Science, found that leptin reduced activation in regions of the brain linked to hunger, while enhancing activation in regions linked to inhibition and satiety. The study suggests possible new targets for the treatment of obesity.

Three Turkish adults who lacked the leptin (ob) hormone were used in the study, and magnetic resonance imaging (MRI) was used to measure brain activity before and after leptin supplementation in them. The subjects were shown images of food before and after leptin treatment, while MRI imaging was in progress.

After leptin replacement, the subjects had feelings of hunger induced by the images, and activity in brain regions associated with hunger—the insula, parietal and temporal cortex—were reduced, while brain activity increased in the prefrontal cortex, previously associated with feeling full.

Despite the limitations in having only three subjects with the ob mutation, Prof. London says, "We think knowing the mechanisms by which leptin alters brain function in congential leptin deficiency can provide understanding of normal leptin physiology. Ultimately, that may help identify new targets for the treatment of obesity and related metabolic disorders."

The research was conducted by Edythe London, a professor of psychiatry in the UCLA Semel Institute for Neuroscience & Human Behavior, and Kate Baicy, a graduate student in Professor London’s lab. Other authors involved with the study were ohn Monteroso, Tuncay Delibasi, and Anil Sharma from the Semel Institute and the UCLA David Geffen School of Medicine, and Ma-Li Wong and Julio Licinio of the University of Miami Miller School of Medicine. The research was supported in part by the National Institutes of Health and the UCLA General Clinical Research Center. During the course of this study Amgen, Inc. provided leptin; Amylin, Inc. now provides leptin to these patients. Neither Amgen, Inc., nor Amylin, Inc., contributed to the design, analysis, or writing of this study.

Source: Proceedings of the National Academy of Science,October 29, 2007

One in Seven Americans Over 70 Has Dementia

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A new analysis suggests that about 3.4 million Americans over 70 years of age—one in seven people in that age group—has dementia, and 2.4 million of them have Alzheimer’s disease (AD).

The study was published online this week in Neuroepidemiology, and is the first to estimate rates of dementia and AD using a nationally representative sample of older adults across the United States.

The study highlights the nationwide reach of dementia, which affects not only those with the disease, but their families and communities as well. "As the population ages during the next few decades, the prevalence of Alzheimer’s disease will increase several-fold unless effective interventions are discovered and implemented," said National Institute on Aging Director Richard J. Hodes, M.D. "These data underscore the urgency of research in this area."

The study included 856 HRS participants over the age of 70 from 42 states in 2001-2003. Aging, Demographics and Memory Study (ADAMS) interviewers from Duke University Medical School conducted at-home evaluations to gather information about each participant’s cognitive and functional status and symptoms, neuropsychiatric symptoms, current medications, medical history and family history of memory problems. Prior neuroimaging and laboratory results were also obtained.

A team of clinicians reviewed the evaluation information and made a preliminary assessment of each person’s cognitive status. A consensus panel of other medical experts then used well-accepted diagnostic criteria to determine if the participant had normal cognitive function, cognitive impairment without dementia, or dementia. Such criteria further were used to discern the type of dementia, including AD or vascular dementia, the second most common cause of dementia in older adults.

Based on the experts’ classifications, Drs. Plassman and Langa and co-authors estimated the national prevalence and total numbers of people age 71 and older, by age group, with any dementia and with AD or vascular dementia in 2002. According to their calculations, 13.9 percent of Americans age 71 and older have some type of dementia, 9.7 percent of Americans in that age group have AD, and 2.4 percent have vascular dementia. AD accounted for about 70 percent of all dementia cases among people 71 and older.

As in other studies, the ADAMS analysis showed that the prevalence of dementia increases significantly with age. Five percent of people ages 71 to 79, 24.2 percent of people 80 to 89, and 37.4 percent of those 90 years or older were estimated to have some type of dementia. The estimated rate of Alzheimer’s also rose greatly with older age — from 2.3 percent of people ages 71 to 79 to 18.1 percent of people 80 to 89 to 29.7 percent of those age 90 and older. The ADAMS investigators found fewer years of education and the presence of at least one APOE e4 allele, a genetic risk factor for AD, to be strong predictors of AD and other dementias.

Richard Suzman, Ph.D., director of NIA’s Behavioral and Social Research Program, which jointly directs the HRS, said the ADAMS data will prove particularly valuable not only in assessing the prevalence of dementia, but also its impact. "ADAMS, with its link to the data about the health, economic, and family resources of individuals in the study, will help us to characterize more fully the burden of dementia on individuals, caregivers and the nation’s health care system," he says.

The ADAMS report is the latest published study to estimate the prevalence of dementia and AD among older Americans. "These assessments have provided a range of estimates, based on differing methodologies and approaches," explains Dallas Anderson, Ph.D., program director for population studies in NIA’s Dementias of Aging Branch.

For example, some studies have included lower age ranges than ADAMS or broader characterizations of dementia, or have sampled participants in a specific community as a base for national extrapolations. A study reported in 1998 (Brookmeyer et al., 1998) combined incidence data from four community-based studies, estimating that national Alzheimer’s prevalence among individuals age 60 years or older would rise from 2.3 million in 1997 to 8.6 million in 2047. Widely cited estimates based on the prevalence of Alzheimer’s disease in a Chicago-based community (Hebert et al., 2003), and an earlier comparable study using data from East Boston (Evans et al., 1990) forecast the number of those age 65 or older with AD to be 5.1 million in 2010.

Despite the varied approaches and findings, however, NIA experts point out, the numbers of people with dementia, and Alzheimer’s specifically, will certainly increase until ways to delay the progression or prevent the dementia are found. Advancing age is the most common known risk factor for Alzheimer’s disease.

The HRS is an ongoing national survey of 22,000 adults age 51 and older that began in 1992, providing data that helps researchers, policy makers and others understand the life circumstances of older adults and help address the challenges of the nation’s rapidly aging population.

NIA leads the federal effort supporting and conducting research on aging and the medical, social and behavioral issues of older people, including AD and age-related cognitive change.

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.

Brenda L. Plassman, Ph.D., of Duke University Medical Center, with Kenneth M. Langa, M.D., Ph.D., and David R. Weir, Ph.D., of the University of Michigan, Robert B. Wallace, Ph.D., of the University of Iowa, and others, conducted the analysis as part of the Aging, Demographics and Memory Study (ADAMS). ADAMS is a sub-study of the larger Health and Retirement Study (HRS), the leading resource for data on the combined health and economic circumstances of Americans over age 50. ADAMS and the HRS are sponsored by the National Institute on Aging, a component of NIH, under a cooperative agreement with the University of Michigan.

Source: National Institutes of Health, October 30, 2007

Improved IMRT Cancer Treatment Reduces Radiation Exposure to Healthy Tissue

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Recent studies by researchers at Montefiore Medical Center have shown that improved IMRT (intensity modulated radiation therapy) treatment provides far better patient care than standard radiation procedures because it safeguards healthy tissue surrounding cancerous tumors.

"We compared treatment techniques for cancers of the lung, abdomen, pelvis and head and neck, and were able to quantify just how much better IMRT was for patients in the studies than conventional radiation therapy," said Shalom Kalnicki, MD, chairman of the Department of Radiation Oncology at Montefiore.

Using the new IMRT technology, oncologists can now deliver thousands of precisely focused beams of radiation that follow the exact contours of a cancerous tumor. Today’s standard therapy uses cross-firing X-ray beams, and is not nearly as accurate.

A study of lung cancer patients showed that the average dose of radiation to the esophagus is reduced by 20 percent, and reduced by 30 percent to the area of the lung most critical for breathing.

"By developing and carrying out a tailor-made IMRT treatment plan for each patient, we reduced significantly the chance of having radiation beams harm healthy lung tissue and therefore impaired breathing," said Dr. Kalnicki.

In another study, Montefiore researchers used IMRT technology to treat patients with pancreatic cancer. Radiation dosage to the nearby kidneys was reduced by 38 percent, and radiation dosage to the normal bowel was also reduced by 38 percent.

A third Montefiore study used image guided adoptive planning, another advanced form of IMRT, to treat complex-shaped head and neck cancers.

The salivary glands, mandible, nerves and oral cavity lining were dramatically safeguarded using this method, resulting in significant improvement of patient quality of life.

Source: Montefiore Medical Center

Some Hypertension Drugs May Also Treat Alzheimer’s

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Recent research points to the possibility that patients being treated with hypertension drugs may also benefit from the drug’s ability to treat or even prevent Alzheimer’s disease.

"If we can deliver certain anti-hypertensive drugs to patients at high risk to develop Alzheimer’s disease, at doses that do not affect blood pressure, these drugs could be made available for all members of the geriatric population identified as being at high
risk for developing Alzheimer’s disease", says Dr. Giulio Maria Pasinetti of Mount Sinai School of Medicine.

Under Dr. Pasinetti’s supervision, more than 1,500 drugs used to treat other disorders have been screened for their potential in treating Alzheimer’s disease, and 7 out of 55 drugs prescribed for the treatment of hypertension have been identified as significantly preventing beta-amyloid production, which plays a key role in Alzheimer’s disease pathogenesis.

Valsartan, an anti-hypertensive agent, was found to pharmacologically prevent beta-amyloid production in the brains of test mice even when administered to Alzheimer’s disease mice at 3-4 times lower than the minimal equivalent dose prescribed for the treatment of hypertension in humans.

Other hypertension drugs with positive results included Propranol HCI, Carvedilol, Losartan, Nicardipine HCI, Amiloride HCI and Hydralazine HCI.

"The use of these drugs for their potential anti-Alzheimer’s disease role is still highly experimental," said Dr. Pasinetti, "and at this stage we have no clinical data beyond phenomenological observation in humans. We need to complete preventive and therapeutic clinical trials in the near future if we are to identify certain anti-hypertensive drugs with anti beta-amyloid antiligomeric activities, which will need to be prescribed at dosages that do not interfere with blood pressure in normotensive Alzheimer’s patients."

The research was conducted by Dr.Giulio Maria Pasinetti, MD, Ph.D., Professor of Psychiatry and Neuroscience, Geriatrics and Adult Development , and Director of the Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer’s Disease at Mount Sinai School of Medicine, and published in the November, 2007 issue of the The Journal of Clinical Investigation.

Rate of Memory Loss Greater in Dementia Patients With More Education

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According to a recent study in the journal Neurology, while higher education levels initially delay the onset of dementia, once dementia starts, the rate of memory loss is more rapid than in less educated individuals.

According to study author Charles B. Hall, PhD of the Albert Einstein College of Medicine, "our study showed that a person with 16 years of formal education would experience a rate of memory decline that is 50% faster than someone with just four years of education."

The study started in the 1980s, and monitored 488 people born between 1894 and 1906, with study findings based on the 117 members of the sample who eventually developed Alzheimer’s or some other form of dementia. Study participants ranged from people with postgraduate education to people with less than three years of elementary school education.

Dr. Hall believes that this rapid decline in the more educated people might be explained by their having a greater cognitive reserve, or the brain’s ability to maintain function in spite of damage. This meant that while patients are often diagnosed with dementia at a later date, once the cognitive reserve is no longer able to compensate for the damage that has occurred, then the symptoms emerge.

The study is valuable, says Dr. Hall, because it examines memory loss before a formal diagnosis of Alzheimer’s.

The study was supported by the National Institute on Aging. Other researchers from the Einstein Aging Study involved in the research included Carol Derby, PhD; Aaron LeValley, MA; Mindy J. Katz, MPH; Joe Verghese, MD; and Richard B. Lipton, MD.

Source: Neurology, October 23, 2007

Charcot Foot Condition on the Increase Among Diabetics

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With the number of diabetes cases growing nationwide, more diabetes patients are developing a somewhat rare, but dangerous foot complication called Charcot foot, according to a number of physicians with the American College of Foot and Ankle Surgeons.

Charcot foot is a sudden softening of the foot’s bones caused by severe neuropathy, or nerve damage, a common diabetic foot complication. It can cause joint loss, fractures, collapse of the arch, massive deformity, ulcers, amputation and even death. It cannot be reversed, but early detection can arrest its effects.

Symptoms, which appear suddenly, include warm and red skin, swelling and pain. A diabetic with a red, swollen foot or ankle requires emergency medical care because these symptoms can also indicate deep vein thrombosis, or an infection.

"More people with diabetes, their families and their care providers need to know about Charcot foot," says J.T. Marcoux, DPM, one of a few Massachusetts foot and ankle surgeons who perform Charcot foot reconstructions. "When I diagnose a patient with this complication, I telephone their primary care doctor and educate them about it as well."

Apathy and diabetic denial are major factors in preventing the treatment of Charcot foot among diabetics, say Keith Jacobson, DPM, and Dr. Marcoux. "I’ve had patients who are literally blind, on dialysis and neuropathic, who refuse to admit they have diabetes," says Jacobson. "I’ve seen horrific deformities with this condition."

Meanwhile Kim Schraeder, one patient who was successfully treated for Charcot foot by Dr. Jacobson, is back walking on both feet and is carefully watched by her children for any reoccurrence of the condition. "They’re all like hawks now." she says. "If I’m sitting here with bare feet, they’ll look to make sure they’re not red, hot or swollen."

Source: American College of Foot and Ankle Surgeons

Simple and Cost Effective Treatment of Calcific Shoulder Tendinitis

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A simple and cost effective way of treating calcium tendinitis of the shoulder was revealed by Spanish researchers,led by Dr. Del Cura, publishing in the American Journal of Roentgenology.

Calcium tendinitis presents as small calcium deposits (1 – 2 cm) on the rotator cuff of the shoulder in individuals over 35 years old. Often painful, some resolve spontaneously, but others persist and become disabling.

Traditional treatment involves shockwave therapy to the shoulder, and in worst case scenarios, surgery.

Dr. del Cura’s treatments, in contrast to surgery, are relatively non-invasive, and involve percutaneous needle lavage (with lidocaine or saline solution) guided by sonography.

In a study of 67 shoulders, 91% were "substantially or completely improved." Of note is that "transitory" recurrences were observed 15 weeks after treatment in 44% of shoulders that had previously improved.

Source: American Journal of Roentgenology (AJR 2007; 189:W128-W134)

Can Viruses Increase Obesity Risk?

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According to an article published by Dr. Richard Atkinson in the journal Mayo Clinic Proceedings, "the growing body of evidence that viruses produce human obesity supports the concept that at least some of the worldwide epidemic of obesity in the past 25 years is due to viral infections."

Dr. Atkinson views the pattern of spread of obesity since 1980 as an epidemic compatible with "infectious origin." Although noting that lack of exercise and food intake were obviously of great importance to this epidemic, he has focused on various animal and human viruses that have been shown to increase obesity. For instance, the SMAN-1, an avian adenovirus from India, is the only animal virus "associated with human obesity."

The clinical implications of this research, if it stands up, would point to development of infection controls. "Ideally," Dr. Atkinson noted, "we could prevent infection and virus-induced obesity with a vaccine for the obesity viruses. Development of a human vaccine will take several years.” .

FDA Approves Bristol-Meyers Squibb’s Drug Ixempra for Breast Cancer Treatment

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The U.S. Food and Drug Administration has approved Ixempra (ixabepilone), a new anti-cancer treatment, for use in patients with metastatic or locally advanced breast cancer who have not responded to certain other cancer drugs.

Ixempra is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

"This approval is important because it provides certain patients with a new chemotherapy option in instances where other drugs have failed," said Douglas C. Throckmorton, M.D., deputy director of the FDA’s Center for Drug Evaluation and Research.

The FDA evaluated Ixempra under priority review, completing its assessment of the drug’s safety and effectiveness in six months.

Ixempra was approved for use in combination with another cancer drug, capecitabine, in patients who no longer benefit from two other chemotherapy treatments. These prior treatments included an anthracycline (such as doxorubicin or epirubicin) and a taxane (such as paclitaxel or docetaxel).

Ixempra was also approved for use alone in patients who no longer benefit from an anthracycline, a taxane and capecitabine.

According to the American Cancer Society, about 180,000 new cases of breast cancer are diagnosed each year in the United States. Metastatic breast cancer is the most advanced stage of breast cancer and has the potential to spread to almost any region of the body.

Ixempra has been shown to bind to cancer cell microtubules, which are structures within cells that help to support and shape them. Microtubules also play a role in cell division.

The safety and efficacy of Ixempra in combination with capecitabine were evaluated in 752 patients in a randomized clinical trial comparing the combination to capecitabine alone. This combination therapy demonstrated improvements in delaying cancer progression or death compared to capecitabine alone.

The safety and efficacy of Ixempra administered alone were evaluated in a study of 126 patients. Clinically significant tumor shrinkage occurred in 12 percent of the patients.

Ixempra’s significant side effects included peripheral neuropathy (numbness, tingling or burning in the hands or feet) and bone marrow suppression. Other commonly observed toxicities included constipation, nausea, vomiting, muscle paint, joint pain, fatigue and general weakness.

Women taking Ixempra should avoid taking drugs that are strong inhibitors of CYP3A4, one of the enzymes that metabolizes Ixempra.

Ixempra should not be taken by women who have had severe allergic reactions to drugs that contain Cremophor or its derivatives, or by women who have baseline bone marrow suppression determined by low white blood cell or platelet count.

The combination of Ixempra and capecitabine should not be given to patients with moderate or severe liver impairment due to the increased risk of toxicity and death.

Ixempra is administered by intravenous infusion. It is distributed by Bristol-Meyers Squibb Company, Princeton, New Jersey.

Source: FDA (October 22, 2007)

Pharma-Funded Studies Conclude Less Risk from Inhaled Corticosteroids Than Studies Funded by Other Organizations

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Concerns have been raised about the use of inhaled corticosteroids for long-term treatment of children or for milder cases of asthma and other respiratory problems. While many studies have been conducted on the adverse effects of inhaled corticosteroids, researchers have found that studies funded by pharmaceutical companies are less likely to find significant differences in adverse effects between individuals assigned to inhaled corticosteroid groups and those who were not when compared to results of studies funded by other groups.

Specifically, 34.5% of pharma-funded studies and 65.1% of studies funded by other groups, including non-profit organizations and government agencies, found a significant difference in adverse effects between the two groups of patients.

The study by Antonio Nieto, M.D., Ph.D., of the Children’s Hospital La Fe, Valencia, Spain and colleagues assessed the safety reporting of inhaled corticosteroids in 504 studies of the drugs published between 1993 and 2002. Of those, 275 were funded by pharmaceutical companies and 229 were funded by other sources.

The authors conclude that "having information on source of funding will help readers of these studies have a better informed and balanced judgment on the authors’ interpretations," and that "disclosure of conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs."

Source: Archives of Internal Medicine, October 22, 2007