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PERSONALIZED MEDICINE: GENE MUTATION IMPROVES DRUG’S EFFECT ON LEUKEMIA PATIENTS
A study led by cancer researchers at Ohio State University shows that a mutation present in some cases of acute leukemia makes the disease more susceptible to high doses of a particular anticancer drug. The findings, published online in the Journal of Clinical Oncology, could change how doctors manage these patients, the researchers said. The retrospective study shows that people with acute myeloid leukemia (AML) whose leukemic cells have mutations in the RAS gene are more likely to be cured when treated after remission with high doses of the drug cytarabine. It also suggests that testing for RAS mutations might help doctors identify which AML patients should receive high-dose cytarabine as their post-remission therapy.

 

While levels of the so-called “hunger hormone” ghrelin are known to increase when a person doesn’t eat, findings by UT Southwestern scientists suggest that the hormone might also help defend against symptoms of stress-induced depression and anxiety. Researchers said they found in mice that chronic stress causes ghrelin levels to go up and that behaviors associated with depression and anxiety decrease when ghrelin levels rise. The resulting side effect is increased food intake and body weight. To determine how ghrelin affects mood, researchers restricted the food intake of laboratory mice for 10 days. This caused their ghrelin levels to quadruple. As compared to the control mice, which were allowed free access to food, the calorie-restricted mice displayed decreased levels of anxiety and depression when subjected to mazes and other standard behavior tests for depression and anxiety. Researchers said they plan to look at whether ghrelin treatment could help people with anorexia nervosa, with the idea being that in a certain population, calorie restriction and weight loss could have an antidepressant effect and could be reinforcing for the illness.

 

PERSONALIZED MEDICINE: COMMON GENE VARIENTS LINKED TO INCREASED RISK OF METABOLIC SYNDROME
Nutrition researchers at Washington University School of Medicine in St. Louis have identified five common genetic variations that increase the risk of metabolic syndrome, a group of factors linked to heart disease and diabetes. Another variant they found appeared to protect against the condition. People with metabolic syndrome have at least three of the following symptoms: abdominal obesity, high blood triglyceride levels, lower good cholesterol (HDL), elevated blood pressure and elevated fasting blood glucose. They are four times as likely to develop heart disease and at least seven times more likely to develop diabetes as individuals without metabolic syndrome. The findings, published in the journal Human Molecular Genetics, looked for changes in the CD36 gene, which is located in a region of chromosome 7 that has been linked to metabolic syndrome in several genome-wide studies. The researchers say linking changes in the CD36 gene to the risk for metabolic syndrome and abnormal levels of good cholesterol is important because as more people in the United States become obese, they also become susceptible to these problems. Better understanding of the relationships between obesity, the gene and disease risk may allow for earlier identification of individuals who are more susceptible to develop metabolic syndrome. Treatments such as medication or lifestyle changes could begin earlier, perhaps preventing or delaying future problems with diabetes or heart disease.

 

Researchers are cutting the time and cost it normally takes to develop radiopharmaceuticals by taking advantage of an FDA-sanctioned procedure that enhances post-discovery drug development while observing scientific and patient safety standards. In January 2006, the FDA issued a guidance that cleared the path for drug developers in the United States to obtain important pharmacokinetic information at a much earlier stage of clinical development by using an approach called Exploratory Investigational New Drug. In the case of Avid Radiopharmaceuticals, the Philadelphia-based company tested four imaging agents labeled with a radiotracer (18F-flourine) in 100 patients at 10 clinical sites. Researchers have been using new imaging agents to detect amyloid plaque deposits—abnormal deposits that pile up in the brain and are thought to be a cause of Alzheimer's disease. Evaluation of the first agent ended after distribution to only eight subjects, allowing the researchers to concentrate on the remaining agents. After one year, a tracer was identified as the best detector of plaque deposits. Designed to determine a drug's pharmacokinetics ExpINDs are conducted prior to early-stage tolerance and dose escalation studies.

 

Leading scientists are calling on Europe to invest more funds into the study of lipids—the “fatty” molecules that play a crucial role in the function of human cells and which are implicated in a range of diseases from obesity and diabetes to Alzheimer’s. Common lipids such as cholesterol are known to play an important part in the normal functioning of cells and tissues, but human cells contain thousands of different lipids, which are also vital for functions that include storing energy, maintaining the structure of the cell and sending biochemical signals. Scientists are discovering that if the biochemical pathways that regulate the metabolism and transport of these lipids become disturbed, this can result in disease. Researchers said a concerted research effort in lipidomics would help shed light on conditions ranging from obesity and heart disease to cancer and Alzheimer’s. They added that the number of European researchers with expertise in lipidomics is low and that increased funding is needed to help Europe to catch up with the level of research in countries such as Japan and the US.

 

Patients diagnosed with colon cancer who had abundant vitamin D in their blood were less likely to die during a follow-up period than those who were deficient in the vitamin, according to researchers at the Dana-Farber Cancer Institute and the Harvard School of Public Health researchers. The study looked at the level of vitamin D by quartiles in a group of 304 participants diagnosed with colorectal cancer between 1991 and 2002. The results showed that individuals with the vitamin D levels in the highest quartile were 48 percent less likely to die (from any cause, including colon cancer) than those with the lowest vitamin D measurements. The odds of dying from colon cancer specifically were 39 percent lower, the scientists found. The results were published in the June 20 issue of the Journal of Clinical Oncology. Researchers said the findings of the study—the first to examine the effect of vitamin D among colorectal cancer patients—merit further research but added that it is too early to recommend supplements as a part of treatment.

 

Measuring and diagnosis of high blood pressure (hypertension) should be done using systolic blood pressure only in patients aged over 50 years, rather than using both systolic and diastolic as is current practice, European hypertension researchers said. Because of aging populations, systolic hypertension is becoming much more common and important due to its high prevalence in patients over 50, compared with diastolic hypertension, said the researchers from the United Kingdom’s University of Leicester and Leicester Royal Infirmary, Umea University Hospital, Sweden, and the International Centre for Circulatory Health, Imperial College London. Systolic blood pressure is the peak pressure in the arteries at the beginning of the heart’s pumping cycle, while diastolic blood pressure is the lowest pressure in the rest phase of the cycle. Systolic blood pressure rises with age; but diastolic blood pressure only rises until age 50 years and falls thereafter, at a time when risk of cardiovascular disease begins to rise. Thus there is an increased prevalence of systolic hypertension over age 50 years and an almost total disappearance of diastolic hypertension.

 

Patients with depression have an increased risk of developing type-2 diabetes, and patients with type-2 diabetes have an increased risk of developing depression, according to researchers at Johns Hopkins. Results of the study showed that patients with elevated depressive symptoms were 42 percent more likely overall to develop diabetes by the end of the study than those without these symptoms. The study was published in the June 18 Journal of the American Medical Association and examined data in the Multi-Ethnic Study of Atherosclerosis (MESA) looking at risk factors for atherosclerosis, or hardening of the arteries, in an ethnically diverse group of 6,814 men and women between ages 45 to 84. The researchers found that when patients were treated for diabetes, about 9 percent of the group, they were about 54 percent more likely to develop elevated depressive symptoms than those without diabetes. They speculate that depression may lead patients to develop behaviors that trigger diabetes or make it worse, such as overeating, not exercising or smoking. Similarly, keeping up with the often extensive treatment regimens to care for their diabetes may make patients’ depression worse, researchers said.

MORTALITY: LOW TESTOSTERONE APPEARS TO INCREASE LONG-TERM RISK

Men may not live as long if they have low testosterone, regardless of their age, according to researchers with the Ernst-Moritz-Arndt University of Greifswald, Institute for Community Medicine in Germany. Men with low testosterone levels had more than 2.5 times greater risk of dying during the next 10 years compared to men with higher testosterone, according to the study, which looked at nearly 2,000 men aged 20 to 79 years, who were living in northeast Germany and who participated in the Study of Health in Pomerania. The new study, which is to be presented at The Endocrine Society's 90th Annual Meeting in San Francisco, adds to the scientific evidence linking deficiency of this sex hormone with increased death from all causes over time. Researchers said the

results should serve as a warning for men with low testosterone to have a healthier lifestyle, including weight control, regular exercise and a healthy diet.

A new computer-based method of analyzing cellular activity has correctly predicted the anti-tumor activity of several molecules, according to researchers at the Georgia Institute of Technology. CoMet, as the system is named, compares the gene expression levels of cancer cells relative to normal cells and converts that information into the enzymes that produce metabolites. Metabolites are the small molecules that are naturally produced in cells. CoMet then predicts metabolites that have lower concentrations in cancer relative to normal cells. Researchers said the system opens up the possibility of novel therapeutics for cancer and develops the understanding of why such metabolites work. The research was published in BioMed Central’s open access journal Molecular Cancer.

 

Scientists at the University of Texas Health Science Center at Houston have discovered a novel compound that might lead to an inexpensive, easy-to-take treatment for diarrhea, in a development that may lessen the epidemic of diarrhea-related deaths among children in developing countries. The compound targets acute secretory diarrhea caused by E. coli and other enterotoxigenic strains of bacteria, which produce toxins that stimulate the linings of the intestines, causing them to secrete excessive fluid, thereby producing diarrhea. During pre-clinical tests, the compound, a derivative of Pyridopyrimidine,was associated with a significant reduction in intestinal fluid secretion in an animal model of bacterial diarrhea. It was also linked to reduced fluid build up during laboratory tests on human colon cells. Diarrhea kills an estimated 1.6 to 2.5 million children every year. The results of pre-clinical tests appear in the June 16 online edition of the journal Proceedings of the National Academy of Sciences of the United States of America.

 

A drug commonly used to treat alcohol addiction has a similar effect on pathological gamblers by curbing the urge to gamble and participate in gambling-related behavior, according to a new research at the University of Minnesota. Forty percent of the 49 participants who took the drug naltrexone (sold under the brand names Revia and Depade) and completed the study quit gambling for at least one month. Their urge to gamble also significantly dropped in intensity and frequency. Only 10.5 percent of the 19 others who took the placebo were able to abstain from gambling. Study participants were aged 18 to 75 and reported gambling for 6 to 32 hours each week. The research was published in the June issue of the Journal of Clinical Psychiatry. Researchers estimate between 1 to 3 percent of the population has a gambling problem.

 

Intake of oily fish is associated with a reduced risk of developing rheumatoid arthritis, whereas psychosocial work stress and smoking can increase the risk of developing the condition, according to a study in Sweden called the Epidemiological Investigation of Rheumatoid Arthritis or RA. For the first time, the intake of oily fish has been demonstrated to have a protective effect against the development of RA, reducing an individual’s risk by 20 percent to 30 percent, the research found. The study looked at 1,899 subjects with a confirmed diagnosis of RA as well as 2,145 controls. The study found that work stress and tobacco smoking are established risk factors for RA. But the investigators discovered that there is a dose dependency for the level of smoking (i.e. the number of cigarettes smoked across a given period) on the odds ratio of developing anti-citrulline (anti-CCP) positive RA.

Ohio University researchers said they have found potential new biomarkers for growth hormone, which they say could help the sports community in detecting growth hormone abuse. The results of the animal study, presented at The Endocrine Society’s 90th Annual Meeting in San Francisco, could overcome the challenge of detecting growth hormone, which only briefly appears in blood and is identical to naturally occurring growth hormone in the body. Many athletes are misusing recombinant human growth hormone, a drug intended for people who are growth hormone deficient, because of its supposed ability to decrease fat and increase muscle. The researchers found several proteins, or variants of them, greatly increased or decreased in the growth hormone-treated mice, compared with controls. They included transthyretin, clusterin, albumin, and apolipoprotein A-1 (apoA1). If the results translate to humans, these proteins have the potential to be new biomarkers for growth hormone action

 

HERPES: PRESENCE OF CERTAIN VIRUS ANTIBODIES LINKED WITH FORM OF DIABETES IN SUB-SAHARAN AFRICANS
Researchers at the Hôpital Saint-Louis, Paris have found an association between the presence of antibodies for the virus human herpesvirus 8 and an atypical form of type 2 diabetes in persons from sub-Saharan Africa. In the preliminary study, published in JAMA, the researchers found human herpesvirus 8 is common in sub-Saharan Africa in patients with a form of diabetes known as ketosis-prone type 2 diabetes mellitus (DM-2). An atypical type of diabetes has emerged as one of the most frequent forms of diabetes in populations of African origin. Ketosis is the condition of having ketone bodies (byproducts of fat metabolism) build up in body tissues and fluids. This type of diabetes is characterized by sudden onset, suggesting there may be triggering factors. The virus was six times more likely to be found in DM-2 patients than the general population.

 

ALCOHOLISM: ABUSE CAN DAMAGE BRAIN BY DECREASING INSULIN AND INSULIN-LIKE GROWTH FACTOR RECEPTORS
Too much alcohol can cause permanent brain damage, such as Wernicke-Korsakoff syndrome, which is largely related to thiamine deficiency, researchers at Rhode Island Hospital and the Warren Alpert School of Medicine at Brown University report. Previous animal studies have shown that alcohol can also cause brain injury and degeneration by inhibiting insulin and insulin-like growth factor or IGF. The study using postmortem human brain tissue has found that chronic alcohol abuse can decrease levels of genes needed for brain cells to respond to insulin/IGF, leading to neurodegeneration similar to that caused by Type 2 diabetes mellitus. They study was published in the online edition of Alcoholism: Clinical & Experimental Research.

 

MORTALITY: PEOPLE WITH LOWER INCOMES, LOWER EDUCATION LEVELS HAVE HIGHER RATES OF DEATH
Mayo Clinic researchers present new data suggesting that people with lower incomes and education levels are more likely to die after heart attack than more affluent, educated people. Over the past several decades, medical research has helped identify a list of factors that increase a person’s risk for heart attack. These factors include behaviors such as smoking or inactivity, and a variety of physical characteristics, including high blood pressure, high blood cholesterol, and obesity. In a report published in the Mayo Clinic Proceedings, researchers studied 705 patients in Olmstead County, Minnesota, where the Mayo Clinic is based. The researchers found that among the 155 deaths recorded during the study period, one-year survival estimates across income groups were lowest for people with the lowest income. Seventy-five percent were survivors among people earning $28,732 to $44,665; 83 percent survived among people earning $49,435 to $53,561; and 86 percent survived among people earning $56,992 to $74,034. Similarly, the survival rates were lowest for participants with less education. Sixty-seven percent were survivors among those who had fewer than 12 years of education; 81 percent survived among people with 12 years of education; and 85 percent survived among people with greater than 12 years of education. Mayo researchers believe that the association observed for education could be related to education’s positive effect on factors that include job opportunities, income, housing, access to nutritious foods and health insurance.

By 2025, the wait to see a doctor could get a lot longer if the current number of students training to be primary care physicians doesn’t increase soon, according to a new University of Missouri study. Researchers at the MU School of Medicine warn that the United States could face a shortage of up to 44,000 family physicians and general internists in less than 20 years, due to a skewed compensation system that rewards specialists increasingly more than primary care practitioners. Today, generalist physicians are a third of the U.S. physician workforce and are responsible for more than half of all patient visits at doctors’ offices. During the past decade, the number of generalist graduates has fallen by 22 percent and declines continue as medical school graduates enter other specialties. At the same time, the U.S. population is increasing by about 1 percent each year, and the baby boomer generation will significantly increase the number of Americans older than 65 by 2025. The study, published in Health Affairs, used data from the National Ambulatory Medical Care Survey to estimate the future demand for generalist care. The Census Bureau predicts that the number of adults will increase 21 percent by 2025, and the number of Americans older than 65 will rise by 73 percent.