The total package: A skillful, compassionate doctor

INDIANAPOLIS, 26 jan 2009 – Patients and their families want physicians who are gifted in diagnosis and treatment and who are caring individuals with the interpersonal skills needed to communicate complex information in stressful circumstances.

A new study in the January 2009 issue of Academic Medicine shows training physicians to be humanistic is feasible and produces measurably better communicators.

"Humanism in medicine isn't about sitting and singing Kumbaya, it is about taking the individual patient's concerns and values into account in his or her treatment," said study co-author Richard Frankel, Ph.D. "Those values are clearly linked to higher quality of care and reduction of medical errors yielding safety improvement." Dr. Frankel is a professor of medicine at the Indiana University School of Medicine and a Regenstrief Institute research scientist.

The study was conducted at five very different medical schools – Emory University School of Medicine, Indiana University School of Medicine, the University of Rochester School of Medicine, Baylor College of Medicine and the University of Minnesota Medical School – rather than only one institution. The authors believe their findings are generalizeable throughout American medical education.

The 2001 Institute of Medicine report, "Crossing the Quality Chasm: A New Health System for the 21st Century," highlighted the benefits of patient-centered humane care that is respectful of and responsive to patients' needs, values and concerns.

The concept of humanism in medicine and patient-centered care predates the 21st century. In the 1920's Francis Peabody, M.D., wrote that "the secret of care of the patient is caring for the patient" a humanistic concept that in the intervening years has become overshadowed by a preoccupation with technological advances in medicine, the same technology that resulted in the development of antibiotics and thousands of other life-saving drugs, sophisticated scanning devices and untold number of vital therapies.

"Traditionally medical school curricula have focused on the pathophysiology of disease while neglecting the very real impact of disease on the patient's social and psychological experience, that is, their illness experience. It is in this intersection that humanism plays a profound role," said Dr. Frankel, who is a medical sociologist.

"As educators, we aim to foster the development of future physicians who are competent both technically and interpersonally. Patients, their families, and the public expect no less of us. This study suggests there are various faculty development processes that will allow us all to pursue these aims more effectively," said study co-author Thomas Inui, M.D., I.U. School of Medicine associate dean for health care research and Sam Regenstrief Professor of Health Services Research. Dr. Inui also is president and CEO of the Regenstrief Institute.

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Other authors of the study, which was funded by the Arthur Vining Davis Foundations, are William T. Branch, Jr., M.D., of Emory University; Catherine F. Gracey, M.D., of the University of Rochester; Paul M. Haidet, M.D., M.P.H., of Baylor College of Medicine; Peter F. Weissmann, M.D., of the University of Minnesota Medical School; Paul Cantey, M.D, M.P.H., formerly of Emory and now of the Centers for Disease Control and Prevention; and Gary A. Mitchell, M.D., formerly at the IU School of Medicine, now with the American University of the Caribbean School of Medicine.

Avoiding Hypoglycemia After Bariatric Surgery

26 jan 2009--A review in Annals of Internal Medicine suggests that clinicians caring for diabetic patients after bariatric surgery should be aware of the changes the procedures cause to patients' glucose metabolism.

The analysts remind clinicians that about a third of patients undergoing bariatric surgery have type 2 diabetes and that the condition resolves for over 80% undergoing bypass procedures and in about two thirds of those having restrictive procedures.

They advise that "patients may require only long-acting basal insulin in the immediate postoperative period, with rapid-acting insulin for correction of hyperglycemia as necessary." When patients resume eating, the authors advise use of rapid-acting insulin after prandial coverage because "its short action reduces the risk for dose-stacking and subsequent hypoglycemia."

LINK(S):

Annals of Internal Medicine article (Free abstract; full text requires subscription)

Personality and dementia risk

Keeping active, both mentally and physically, reduces dementia risk

26 jan 2009--“Being laid-back and outgoing makes you 50% less likely to develop Alzheimer's disease”, the Daily Mail reported. The newspaper said that people who are anxious, shy and prone to stress are more likely to go on to develop dementia. It said a study looked at the personalities and lifestyles of 506 older people and followed them for six years. Those who were calm had a 50% lower risk of dementia, even if they were not socially active, than those who were isolated and prone to stress.

This study found that people with low levels of neuroticism and high levels of extroversion (calm, relaxed types with outgoing personalities) had less risk of dementia than those with high neuroticism (those prone to distress and poor coping responses) and high extroversion.

However, the study cannot prove that these personality factors themselves affected the risk of dementia, as early dementia-related changes could themselves have affected personality. This study has not looked at whether changing your personality, which may not be possible, can affect your risk of dementia. For elderly people, maintaining social contact with others is likely to have benefits, but whether or not it reduces dementia risk remains to be proven.

Where did the story come from?

Dr Hui-Xin Wang and colleagues from the Karolinska Institutet and other research institutes in Sweden and the US carried out this research. The work was funded by the Swedish Council for Working Life and Social Research, and various other charitable organisations in Sweden and the US. The study was published in the peer-reviewed medical journal: Neurology.

What kind of scientific study was this?

This prospective cohort study looked at the relationship between personality traits (neuroticism and extroversion), lifestyle and dementia. Previous studies have found that stress is associated with degenerative changes in the brain. It has also been found that people’s personality traits and their level of social interaction may affect their ability to cope with stress. Therefore, the researchers wanted to investigate whether these factors might affect risk of dementia, which is a result of degenerative changes in the brain.

The participants were obtained from a previous cohort study of ageing and dementia in Sweden. The researchers excluded anyone from that study who met criteria for probable dementia at the time of assessment, and those who were unable to complete a personality questionnaire that assessed neuroticism and extroversion. This neuroticism part of the questionnaire is designed to identify people prone to ‘psychological distress, unrealistic ideas, excessive cravings or urges, and maladaptive coping responses’. Low scores indicate people to be ‘calmer, more relaxed, unemotional, and self-satisfied’. The extroversion part of the questionnaire assesses ‘quantity and intensity of interpersonal interaction, activity level, need for stimulation, and capacity for joy’. People who score lower on extraversion are identified as being ‘more reserved, sober, task-oriented, and quiet’.
Those who met inclusion criteria were asked to take part in a personal interview in which they were asked about their lifestyle, including their social interactions and leisure activities.

Of the people who were asked, 544 completed the questionnaire, and 506 (average age 83 years) were successfully followed up for an average of six years. The participants were given a full clinical assessment at three and six years, including medical history and psychological assessment. If an individual could not answer questions, the researchers identified a person close to them who could provide the relevant information.

Diagnoses of dementia were based on standard criteria. Two physicians made independent diagnoses, and if they agreed then this was the final diagnosis. If they disagreed then a third opinion was obtained. If a person died, their medical history and diagnoses were assessed using hospital records and death certificates.

The researchers then looked at whether levels of neuroticism or extroversion were individually associated with dementia. They also looked at the effects of these two personality traits together, and at how this association was affected by social interaction. They compared the proportion of people who developed dementia among those with low levels of neuroticism, extroversion or both with those who had high levels of both. The researchers adjusted their analyses for factors that could affect the results, such as whether the participants had the form of the ApoE gene which has been associated with a higher risk of Alzheimer’s disease. They also took into account the participants’ age, cognitive function, gender, level of education, depressive symptoms or diagnoses, vascular disease, and whether they had died or were still alive at follow up.

What were the results of the study?

Of the 506 participants, 144 (28%) developed dementia during the six years of follow up. When they looked at each personality trait individually, the researchers found no association between the participants’ neuroticism or extroversion and their risk of developing dementia. However, when the two traits were assessed together some associations with dementia were found. People who had low neuroticism but high extroversion were about half as likely to develop dementia as those with high neuroticism and high extroversion (hazard ratio 0.51, 95% CI 0.28 to 0.94). Risk of dementia among people with low neuroticism and extroversion, or high neuroticism and low extroversion did not differ from those with high levels of both traits.

The researchers then split the participants into those with different social lifestyles. Among those who had an inactive and socially isolated lifestyle, people who were less neurotic had a lower risk of dementia than those who were more neurotic, but this was not the case among people with an active and socially integrated lifestyle. Extroversion was not associated with risk of dementia in either socially inactive or socially integrated groups.

What interpretations did the researchers draw from these results?

The researchers concluded that people with low neuroticism and high extroversion have the lowest risk of dementia. They say that low neuroticism alone can reduce the risk of dementia in people with an inactive and socially isolated lifestyle.

What does the NHS Knowledge Service make of this study?

The prospective design of this study is one of its strengths; however, there are some limitations to consider:

• Even though this study followed people over time, it is difficult to determine the sequence of events. People who did not have detectable dementia may have had very early brain changes associated with this condition, and these changes may have affected their personality rather than the other way around. However, the authors feel they reduced this possibility by testing for cognitive performance at the beginning of the study, and adjusting their analyses accordingly.
• Even if the personality traits preceded the brain changes, it does not necessarily mean that the personality traits themselves increased the risk of dementia. There may be another factor or factors that affect both personality and risk of dementia.
• About a third of the people asked did not complete the personality questionnaire, and this may have affected the results if they differed from those who chose to complete it.
• Personality was only assessed once, and may not have been indicative of personality at other times during the participants’ lives.
• It is not possible to say from this study whether attempting to change one’s social life would have an effect on risk of dementia.
• The results may not be applicable to other countries, where social customs and interactions may differ.

Further replication of the findings of this study in other settings would increase confidence in the results. By objectively measuring dementia over time, by using a series of brain scans for example, it may be possible to avoid the criticism that this study is a “chicken and egg scenario”. These could help to determine whether it is the personality traits that increase the risk of dementia or if they are simply an early sign of the disease.

Heart Risk Linked to Metabolic Syndrome and Smoking

Chinese study of older adults shows an increased risk of cardiovascular disease

26 jan 2009-- In China, older adults with metabolic syndrome who are exposed to either active or passing smoking have an increased risk of cardiovascular disease, according to a report published in the Jan. 27 issue of the Journal of the American College of Cardiology.

Yao He, M.D., of the Chinese PLA General Hospital in Beijing, China, and colleagues surveyed 2,334 Chinese subjects (943 men and 1,391 women) aged 60 and older. Among men, 58.1 percent were identified as ever smokers and 34.8 percent had metabolic syndrome. Among women, 13.1 percent were identified as ever smokers and 54.1 percent had metabolic syndrome. Women were more likely than men to have been exposed to secondhand smoke (42.3 percent versus 19.9 percent).

Compared to never-smokers without metabolic syndrome, the researchers found subjects with metabolic syndrome who were exposed to active or passive smoking had an increased cardiovascular disease risk of 48 to 193 percent. They also calculated that smoking cessation could reduce the risk by 37 percent in male smokers with metabolic syndrome.

"Considering that both tobacco use and metabolic syndrome are the two leading causes of preventable death in China, our findings have important public health implications," the authors write. "Our results emphasize that public health policies are needed to control smoking, secondhand smoke and metabolic syndrome. In terms of the implications for clinical practice, smokers or those exposed to passive smoke with metabolic syndrome have very high cardiovascular disease risk and should be targeted for intensive interventions."

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ISET: For Angioplasty, Wrist Entry May Be Safer Than Groin

Less bleeding, less overall risk, especially in obese patients

26 jan 2009 -- For most patients undergoing angioplasty to treat blocked heart arteries, entry through the wrist is safer and cheaper than entry through the groin, according to research presented at the 21st Annual International Symposium on Endovascular Therapy, held from Jan. 18 to 22 in Miami.

Ramon Quesada, M.D., of the Baptist Cardiac & Vascular Institute in Miami, and colleagues analyzed data from over 5,000 angioplasty procedures, predominantly via the femoral artery as only 2 percent of minimally invasive heart treatments are currently performed via the wrist.

Whereas studies suggest that angioplasty via the femoral artery has a 2.8 percent risk of bleeding or nerve damage, radial approach angioplasty conducted at the Baptist Cardiac & Vascular Institute had a 0.3 percent risk of bleeding complications and none of the patients had nerve damage, the authors note. Although wrist access angioplasty would be suitable for up to 75 percent of patients, those with very small or twisted arteries, and those who are extremely thin would not be suitable candidates, the researchers found.

"Using the radial approach results in lower cost, less time before the patient can get up and walk around and fewer complications," Quesada explained in a statement. "Patients who are ideal candidates for the radial approach are those who are obese or have severe peripheral arterial disease."

Many Alzheimer's Caregivers Admit to Abusive Behavior

By Ed Edelson
25 jan 2009-- More than half of family members looking after people with dementia admit they have behaved abusively toward their relative, a new British study finds.

Actual physical abuse was rare, being reported by only three of the 220 caretakers in the study. But the researchers, who published their findings in the Jan. 23 online issue of BMJ, say that 115 (52.3 percent) of those surveyed acknowledged some abusive behavior toward the relative under care, with "significant" abusive behavior described by 74 (33.6 percent) of caregivers.

The results indicate "the extreme difficulty of caring for persons with dementia," said study author Dr. Claudia Cooper, a psychiatrist and research training fellow in health sciences research with the Medical Research Council, the British equivalent of the U.S. National Institutes of Health.

The most common form of abuse (26 percent) was screaming or yelling at the person with dementia. Insults or swearing accounted for 18 percent of reports, with threats of sending the person to a nursing home happening in 4.4 percent of cases.

"Mostly people said they wished it hadn't happened," Cooper said. "People with dementia can act aggressively. They [the caretakers] were reacting to being the subject of aggression or being in a difficult situation."

The British government is considering a revision of its policies for safeguarding vulnerable adults, focusing on paid caretakers. The newly reported study of family caretakers was done, because "previous smaller studies that asked about abusive behaviors reported high rates," Cooper said. "Given those studies, which indicated that about a third of family carers reported significant abuse, we needed to know more about it."

Cooper and her colleagues interviewed family members of people living at home with dementia in London and in Essex, a borough near London. The results were pretty much as expected, she said. "We predicted that a third of family carers would report significant abuse. We also expected few cases of physical abuse or frequent abuse."

The study is part of a larger program aimed at reducing abusive behavior in such families, Cooper said. "We need to know exactly what is going on before looking for ways to reduce it," she said.

The incidence of such abuse in the United States is not known, since comparable studies have not been done here, said Beth A. Kallmyer, director of client services at the Alzheimer's Association. But the association "gets a lot of questions about it," Kallmyer said, enough so that it maintains a 24-hour telephone service, at 800-272-3900.

"One of our messages is that people can't do this alone," Kallmyer said. "It is a progressive disease, so that the ability of the person being cared for diminishes with time. That creates great stress."

To help caretakers determine whether the stress has grown too great, the association has provided a caregiver stress test, at www.alz.org/stresscheck, she said.

"We want them to reach out, because if they don't reach out they get burnt out," Kallmyer said.

Another report in the same issue of BMJ dealt with a different matter of concern for the elderly: the effectiveness of specialized geriatric hospital units.

Older people who are cared for in such units have a better chance of returning home after discharge than those treated in conventional hospital facilities, said a report by physicians at the University Hospital of Getafe in Madrid.

A review of 11 studies that compared care provided by acute geriatric units run by specialists with conventional hospital units found elderly patients had a better ability to function back at home and a reduced risk of returning to the units in the three months after discharge.

But further studies are needed to determine if the benefits persist over the longer term, the report said.

More information

For more on elder abuse, go to the The AGS Foundation for Health in Aging.

Impaired Kidney Function Linked to Mortality in Elderly

Statins benefit high-risk patients with impaired function

25 jan 2009-- Impaired kidney function is associated with a higher risk of death and cardiovascular disease in elderly individuals at risk of vascular disease, while statins reduce the risk of death and heart attack in patients with impaired kidney function, according to the results of a study published online Jan. 20 in PLoS Medicine.

Ian Ford, Ph.D., from the University of Glasgow in Scotland, and colleagues determined whether estimated glomerular filtration rate (eGFR) could be used to predict cardiovascular disease and mortality using data from 5,804 older individuals (aged 70 to 82 years) at risk of vascular disease who had received pravastatin or placebo as part of a randomized clinical trial.

After adjusting for cardiovascular risk factors, the researchers found that a low eGFR (less than 40 compared with 60 mL/min/1.73 m² or more) was associated with a higher risk of all-cause mortality (hazard ratio, 2.04), vascular mortality (HR, 2.37), other non-cancer mortality (HR, 3.52), coronary heart disease death or non-fatal myocardial infarction (HR, 1.64), and fatal or non-fatal heart failure (HR, 3.31). Statin treatment was associated with reduced coronary heart disease death or non-fatal myocardial infarction in patients with low eGFR, the authors report.

"Impaired GFR is independently associated with significant levels of increased risk of all-cause mortality and fatal vascular events and with composite fatal and non-fatal coronary and heart failure outcomes," Ford and colleagues conclude. "Our analyses of the benefits of statin treatment in relation to baseline GFR suggest that there is no reason to exclude elderly patients with impaired renal function from treatment with a statin."

Full Text

Novel Biomarkers Predict Death, Myocardial Infarction

H-FABP, NT-pro-BNP are predictors in patients with ischemic-type chest pain

25 jan 2009-- When patients are admitted to the hospital with ischemic-type chest pain, two novel biomarkers can provide useful prognostic information, according to research published in the Jan. 1 issue of the American Journal of Cardiology.

Conor J. McCann, M.D., of Royal Victoria Hospital in Belfast, United Kingdom, and colleagues studied 664 patients presenting to two coronary care units with ischemic-type chest pain over a three-year period starting in 2003. Patients were followed-up for a year.

The researchers found that heart fatty acid-binding protein (H-FABP) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) -- in addition to age, left ventricular hypertrophy on initial electrocardiography and peak cardiac troponin T (cTnT) -- were significant independent predictors of death or myocardial infarction within one year. Patients without elevated H-FABP, NT-pro-BNP or peak cTnT were at very low risk of death or myocardial infarction within one year. Patients with high levels of all three were at very high risk, however, the report indicates.

"In conclusion, the measurement of H-FABP and NT-pro-BNP at the time of hospital admission for patients with ischemic-type chest pain adds useful prognostic information to that provided by the measurement of baseline and 12-hour cTnT," the authors write.

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Increased Mortality Linked to Topical Retinoid Usage

Rise in mortality among individuals receiving topical tretinoin cream causes discontinuation of study

25 jan 2009-- Topical tretinoin, a frequently prescribed retinoid cream, is associated with increased all-cause mortality, according to study results published in the January issue of the Archives of Dermatology.

Martin A. Weinstock, MD, PhD, of the VA Medical Center in Providence, RI, and colleagues initiated the Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) study, a randomized chemoprevention trial designed to test whether topical tretinoin could reduce the risk of keratinocyte cancers. A total of 1,131 veterans (mean age 71 years) were randomized to receive twice-daily application of either topical tretinoin cream (0.1 percent) or a vehicle control.

An excessive number of deaths in the tretinoin cream treatment arm led to a premature halt of the VATTC study. The excess deaths in the intervention group versus the control group (82 versus 53) were determined to be statistically significant. A post hoc analysis found age, presence of comorbidities, and smoking were all important predictors of mortality. No specific cause of death was associated with tretinoin use.

"Debate will continue regarding whether the association between topical tretinoin and death found in the VATTC resulted from chance or a real biological effect," the authors of an accompanying editorial write, adding practitioners "may wish to discuss the results of the VATTC with all patients using topical tretinoin."

Several of the study authors report financial relationships with the pharmaceutical industry. OrthoNeutrogena, a division of Ortho-McNeil Pharmaceutical Inc., provided the tretinoin and vehicle creams for the study.

Abstract
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Editorial

Many of China's 140 million old people find the crowd to be lonely

24 jan 2009--IT has 20 per cent of the world's population with 1.4bn people – but China's rapid economic and social change has caused its pensioners to feel lonely and alienated, a new study suggests.

Although capitalism has brought prosperity and increased political power to China, it has also caused the weakening of a traditional society that had collectivism and strong family ties at its heart.

The study by Durham University and the University of Reading, published in Ageing and Society, examined in detail two surveys of Chinese people aged 60 years and over in 1992 and 2000 (1). The percentage of older people who said they were lonely has doubled from about 16% in 1992 to 30% in 2000.

While loneliness can severely impact a person's quality of life, it can also be a triggering factor for mental health issues. The findings suggest that policy makers in China need to take urgent action to assess what is needed to improve the quality of life for its 140 million older people, who collectively amount to the largest older population in the world.

The Durham and Reading University study suggests potential causes for loneliness include a widespread move since the late1970s from highly collectivised communities, where several generations lived under one roof in close proximity to their neighbours, to communities dominated by the nuclear family, many living in impersonal city apartment blocks.

Under the collectivised system in rural areas, communes, brigades and teams were not only responsible for agricultural production but many other community affairs, meaning a high level of social interaction for all.

In today's economic climate, sons and daughters are more likely to have moved long distances from the country to the city or from one city to another in search of work, often leaving their parents behind. They can work long hours, juggling childcare with the demands of full-time work, and although they send money home, visits can be infrequent. The single-child policy means that older people are increasingly left without a selection of offspring for company and care in their old age.

Lead study author Dr Keming Yang, a Durham University sociologist who hails from China's third largest city, Tianjin, said: "While economic development has brought many benefits for China, such as money, increased political power and better standards of living, loneliness is one of its negative effects.

"Mao has been roundly criticised for many aspects of his leadership but - like it or not - the way the society was structured at the time effectively provided opportunities for a high level of social interaction, either good or bad.

"There was a lack of competition and a slower pace of life where people had more control over their schedule. Members of the community tended to attend long meetings where they would talk to others about not merely business but personal issues as well."

But the study authors point out that more detailed research is needed to obtain a more accurate picture outlining the extent of the loneliness problem: Dr Yang added: "While concentrating on economic advancement it is easy to ignore the wider social effects of a richer but more competitive society.

"Experience of capitalist societies to date suggests it is very likely that many other sections of the population, especially young people who are under huge amounts of pressure at school and home, are feeling the same sense of isolation."

Co-author Professor Christina Victor, of the University of Reading, said: "Levels of loneliness in China are now comparable, or higher than, those observed in Western Europe; therefore, this is not just a problem seen in developed countries."

Dr Yang said a potential solution for the Chinese authorities to tackle loneliness in the old was to ensure the local community played a greater role in engaging older people in social and group activities, although this would require some financial support.

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Footnote:

(1) The surveys used for the study were the Survey of the Support System for the Elderly in China (1992) and the Survey of the Aged Population in China (2,000). Differences in the design of the two studies mean they can not be used as an exact comparison but they are the best statistical indication to date of the problem of loneliness.

MEDIA INFORMATION

INTERVIEWS:

Dr Keming Yang, lecturer in Durham University's School of Applied Social Sciences, is available for interviews in English or Mandarin Chinese. Tel: +44(0) 191 334 6822 or, out of hours, +44(0) 7951 907888.

Note to broadcasters: An ISDN radio line is available on campus for interviews, for use free of charge. Contact Durham University Media Relations Office for more information/to arrange use.

PHOTOGRAPH:

A headshot of Dr Keming Yang is available from Durham University Media Relations Office.

SOURCE MATERIAL:

The Prevalence of and risk factors for loneliness among older people in China: Yang, K and Victor, Christina R; Ageing and Society 28, 305-327.

Professor Christina Victor is a co-author of 'The Social World of Older People: Understanding Loneliness and Social Isolation in Later Life', published by Open University Press in January 2009.

New study provides further evidence that apple juice can delay onset of Alzheimer's disease

Amsterdam, The Netherlands, 24 jan 2009– A growing body of evidence demonstrates that we can take steps to delay age-related cognitive decline, including in some cases that which accompanies Alzheimer's disease, according to a study published in the January 2009 issue of the Journal of Alzheimer's Disease.

Thomas B. Shea, PhD, of the Center for Cellular Neurobiology; Neurodegeneration Research University of Massachusetts, Lowell and his research team have carried out a number of laboratory studies demonstrating that drinking apple juice helped mice perform better than normal in maze trials, and prevented the decline in performance that was otherwise observed as these mice aged.

In the most recent study Shea and his team demonstrated that mice receiving the human equivalent of 2 glasses of apple juice per day for 1 month produced less of a small protein fragment, called "beta-amyloid" that is responsible for forming the "senile plaques" that are commonly found in brains of individuals suffering from Alzheimer's disease.

Dr. Shea commented that "These findings provide further evidence linking nutritional and genetic risk factors for age-related neurodegeneration and suggest that regular consumption of apple juice can not only help to keep one's mind functioning at its best, but may also be able to delay key aspects of Alzheimer's disease and augment therapeutic approaches."

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The article is "Dietary Supplementation with Apple Juice Decreases Endogenous Amyloid-β Levels in Murine Brain" by Amy Chan and Thomas B. Shea. It is published in the Journal of Alzheimer's Disease 16:1 (January 2009).

Eating less may not extend life

Caloric restriction only benefits obese mice: The Journal of Nutrition

24 jan 2009--If you are a mouse on the chubby side, then eating less may help you live longer.

For lean mice – and possibly for lean humans, the authors of a new study predict – the anti-aging strategy known as caloric restriction may be a pointless, frustrating and even dangerous exercise.

"Today there are a lot of very healthy people who look like skeletons because they bought into this," said Raj Sohal, professor at the University of Southern California's School of Pharmacy.

He and Michael Forster, of the University of North Texas Health Science Center, compared the life span and caloric intake of two genetically engineered strains of mice.

The "fat" strain, known as C57BL/6, roughly doubles in weight over its adult life. That strain benefited from caloric restriction, Sohal said.

The "lean" strain, DBA/2, does not become obese. Caloric restriction did not extend the life of these mice, confirming previous work by Forster and Sohal.

The results appeared online Jan. 13 in advance of print publication in the Journal of Nutrition.

"Our study questions the paradigm that caloric restriction is universally beneficial," Sohal said. "Contrary to what is widely believed, caloric restriction does not extend (the) life span of all strains of mice."

By measuring the animals' metabolic rate, Sohal and his colleagues came to a deceptively simple conclusion: Caloric restriction is only useful when, as in the case of the obese mice, an animal eats more than it can burn off.

"Your energy expenditure and your energy intake should be in balance," Sohal said. "It's as simple as that. And how do you know that? By gain or loss of weight.

"The whole thing is very commonsensical."

For humans of normal weight, Sohal strongly cautions against caloric restriction. In a 2003 study, he and Forster found that caloric restriction begun in older mice – both in DBA and leaner C57 individuals – actually shortened life span.

However, Sohal said that obese individuals are probably better off cutting calories than increasing their exercise to make up for overeating. Overly vigorous exercise can lead to injuries and long-term wear and tear.

In other words, it is better to skip the double cheeseburger than to turn up the treadmill after binging at Carl's Jr.

Sohal's study is not the first to question the allegedly universal benefits of caloric restriction. A study by Ross et al. published in Nature in 1976 ("Dietary practices and growth responses as predictors of longevity") found that caloric restriction works best in mice that gain weight rapidly in early adulthood, Sohal said.

Studies of caloric restriction in wild types of mouse strains have shown minimal life span extension, he added.

Next, the researchers want to understand why the obese mice have a lower metabolic rate that promotes weight gain.

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The other members of the research team were Melissa Ferguson and Barbara Sohal of the USC School of Pharmacy.

Funding for the study came from the National Institute on Aging, part of the National Institutes of Health.

Read the study at http://jn.nutrition.org/cgi/content/abstract/jn.108.100313v1

Scientists unlock possible aging secret in genetically altered fruit fly

PROVIDENCE, R.I., 24 jan 2009— Brown University researchers have identified a cellular mechanism that could someday help fight the aging process.

The finding by Stephen Helfand and Nicola Neretti and others adds another piece to the puzzle that Helfand, a professor of biology, molecular biology, cell biology and biochemistry, first discovered in 2000. Back then, he identified a mutation in the Indy ("I'm Not Dead Yet") gene that can extend the life span of fruit flies.

Subsequent studies of the Indy flies have led to the new finding that a mechanism in those genetically altered fruit flies appears to reduce significantly the production of free radicals, a cellular byproduct that can contribute to the aging process. This intervention takes place with few or no side effects on the quality of life for the fruit fly. The discovery could lead to the development of new anti-aging treatments.

"There are very few, if any, interventions that are known to dramatically extend healthy lifespan," Helfand said. "Understanding how … the Indy mutation alters the metabolic state of the fruit fly would allow someone to come up with pharmacological interventions that could mimic it and give you the benefit of genetic manipulation without having to do genetics."

The findings are detailed in new research published Jan. 21 in the online Early Edition of the Proceedings of the National Academy of Sciences. Titled "Long-lived Indy reduced mitochondrial reactive oxygen species production and oxidative damage," the piece includes a number of collaborators. Helfand served as senior author and Neretti, assistant professor (research) in Brown's Institute for Brain and Neural Systems, served as lead author. Other researchers collaborated from the University of Chicago and the University of Connecticut Health Center.

With Helfand having established that the mutated Indy gene helped fruit flies live longer, he now wanted to explore what mechanisms lead to the longer life of the fruit fly. (Indy flies' life span increased from an average life span of about 35 days to 70 days.

The researchers decided the best way to try to understand how the Indy mutation might extend life span would be to study the differences in molecular changes between the Indy flies and normal flies throughout their entire life. By comparing the expression level of all genes in the Indy flies to that of normal flies, they made an important finding. Some of the genes involved in generating the power necessary for normal cell life were expressed at lower levels in the Indy flies.

This led to a decrease in free radicals and the damage they normally cause in the cell, but it surprisingly did not decrease the overall amount of energy in the cell. These studies provide evidence for possible interventions that can alter metabolism in a way that reduces free-radical or oxidative damage and extends life span, without some of the negative consequences normally associated with a change in metabolism.

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Research funding came from National Institute on Aging grants and an Ellison Medical Foundation New Scholar Award.

F.D.A. Approves a Stem Cell Trial

By ANDREW POLLACK

24 jan 2009--In a research milestone, the federal government will allow the world’s first test in people of a therapy derived from human embryonic stem cells.

Federal drug regulators said that political considerations had no role in the decision. Nevertheless, the move coincided with the inauguration of President Obama, who has pledged to remove some of the financing restrictions placed on the field by President George W. Bush.

The clearance of the clinical trial — of a treatment for spinal cord injury — is to be announced Friday by Geron, the biotechnology company that first applied to the Food and Drug Administration to conduct the trial last March. The F.D.A. had first said no, asking for more data.

Thomas B. Okarma, Geron’s chief executive, said Thursday that he did not think that the Bush administration’s objections to embryonic stem cell research played a role in the F.D.A.’s delaying approval.

“We really have no evidence,” Dr. Okarma said, “that there was any political overhang.”

But others said they suspected it was more than a coincidence that approval was granted right after the new administration took office.

“I think this approval is directly tied to the change in administration,” said Robert N. Klein, the chairman of California’s $3 billion stem cell research program. He said he thought the Bush administration had pressured the F.D.A. to delay the trial.

Mr. Klein called the approval of the first human trial of this sort “an extraordinary benchmark.”

Stem cells derived from adults and fetuses are already being used in some clinical trials, but they generally have less versatility than embryonic stem cells in terms of what tissue types they can form.

The F.D.A. approval comes a little more than 10 years after the first human embryonic stem cells were isolated at the University of Wisconsin, in work financed by Geron.

Because the cells can turn into any type of cell in the body, the theory is they may one day be able to provide tissues to replace worn-out organs or nonfunctioning cells to treat diabetes, heart attacks and other diseases. The field is known as regenerative medicine.

The Bush administration restricted federal financing for research on embryonic stem cells because creation of the cells entails the destruction of human embryos.

Geron’s trial will involve 8 to 10 people with severe spinal cord injuries. The cells will be injected into the spinal cord at the injury site 7 to 14 days after the injury occurs, because there is evidence the therapy will not work for much older injuries.

The study is a so-called Phase I trial, aimed mainly at testing the safety of the therapy. There would still be years of testing and many hurdles to overcome before the treatment would become routinely available to patients.

Geron, which is based in Menlo Park, Calif., said that it had identified up to seven medical centers for the trial but that those sites must first get permission from their own internal review boards to participate.

Even as some researchers hailed the onset of clinical trials, others expressed trepidation that if the therapy proves unsafe — or even if it is safe but does not work — it could cause a backlash that would set the field back for years.

“It would be a disaster, a nightmare, if we ran into these kinds of problems in this very first trial,” said Dr. John A. Kessler, the chairman of neurology and director of the stem cell institute at Northwestern University.

Dr. Kessler, whose own daughter was paralyzed from the waist down in a skiing accident, said he thought Geron’s therapy was not the ideal candidate for the first trial. He said results showing the therapy worked in moderately injured animals might not apply to more seriously injured people.

“We really want the best trial to be done for this first trial, and this might not be it,” he said.

Dr. Okarma of Geron emphasized that the purpose of the first trial was safety, so that lack of efficacy should not be a problem. While researchers will also look for signs the treatment works, he said, the best that could be hoped for would be some slight restoration of function that could then be enhanced through physical therapy.

“We don’t expect to take someone who is completely paralyzed from the waist down and have them dance six months later,” he said. If the first trial shows safety, the company would then hope to test higher doses of cells and treat patients with less severe injuries, he said.

Geron’s therapy involves using various growth factors to turn embryonic stem cells into precursors of neural support cells called oligodendrocytes, which are then injected into the spinal cord at the site of the injury.

The hope is that the injected cells will help repair the insulation, known as myelin, around nerve cells, restoring the ability of some nerve cells to carry signals. There is also some hope that growth factors produced by the injected cells will spur damaged nerve cells to regenerate.

The therapy was developed in collaboration with Hans Keirstead of the University of California, Irvine. He has shown videos of paralyzed rats that were able to walk again, albeit imperfectly, after receiving the therapy. Those videos helped persuade California voters to approve the $3 billion stem cell research program in 2004.

The main safety concern is that if raw embryonic cells are put into the body, they can form tumors. Even though most such tumors do not spread like other cancers, any unwanted growth in the spinal cord can further damage nerves.

“It’s not ready for prime time, at least not in my mind, until we can be assured that the transplanted stem cells have completely lost the capacity for tumorogenicity,” said Dr. Steven Goldman, chairman of neurology at the University of Rochester. He was a member a committee convened by the F.D.A. last April to examine the safety aspects of trials using therapies from embryonic stem cells.

Dr. Okarma said Geron had done numerous studies showing that its cells did not contain residual embryonic cells and did not form tumors in animals even after a year. It submitted 22,000 pages of data to the F.D.A., perhaps the largest application ever for permission to begin a clinical trial.

The embryonic stem cell line used by Geron is one of the oldest ones and was therefore eligible for federal financing under the Bush administration’s policy, Dr. Okarma said.

Nevertheless, Geron paid for its own work, spending $45 million to prepare its F.D.A. application.

Geron, which was formed in 1990 as an antiaging company, is still in the development stage and is not yet profitable, having lost about $500 million since its inception. Besides working on stem cells, it is testing drugs for cancer that influence telomeres, the caps on the ends of chromosomes that help control the aging of cells. Geron’s market value is about $400 million.

While the Bush administration’s policy did not impede the company’s application at the F.D.A., Dr. Okarma said, it did slow progress for the field in general by making it hard for academics to do research.

“It is the private sector that has kept the technology alive so that it can see the light of day in a clinical trial,” he said.

Mr. Klein of the California stem cell program said he thought the next trial might be of a treatment for macular degeneration, an eye disease, that is being developed in Britain.

In the last couple of years, some attention has turned away from embryonic stem cells to a newer technique that allows a patient’s own skin cells to be turned into a cell resembling such embryonic cells.

That might do away with the need for embryos. And the resulting tissue made from those cells would match the patient, doing away with the need for immune suppression to prevent rejection of the transplant. Geron said its trial would require only temporary use of low doses of immune-suppressing drugs.

But the newer technique involves putting genes into the skin cells using viruses, which also raises a risk of cancer.

Moderate Alcohol Consumption May Protect Against Disabilities

By Carolyn Colwell
23 jan 2009-- Healthy people 50 and older who drink alcohol moderately are less likely to suffer physical disabilities that cause so many seniors to lose their independence, a new study says.

The study authors said their research showed that healthy older adults who were light-to-moderate drinkers had 25 percent lower odds of being unable to carry out daily activities such as walking, dressing, eating, running errands or doing chores.

Conversely, heavy drinkers and abstainers had higher risks of disabilities that would limit such activities.

"What it's really telling light-to-moderate drinkers is don't worry, you're probably in good company, and you're probably going to get good benefits from this," said lead researcher Dr. Arun S. Karlamangla, an associate professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles.

But, the study should also serve as a warning to older adults who aren't in good health, Karlamangla added. For the participants who reported that their overall health was fair or worse, alcohol offered no benefit at all.

"If you're health is not good, you probably should not be drinking," he said.

Study co-author Dr. Alison A. Moore, an associate professor of medicine in the geriatrics division at the David Geffen School of Medicine, said there were two possible reasons why the unhealthy didn't benefit. Alcohol may have negatively interacted with their medications, or their health may have been so poor it wasn't reversible, she said.

The researchers defined light-to-moderate drinking as less than 15 drinks a week with a daily maximum of five for men and four for women. Moore said the study included the number of drinks a day to eliminate people who binge drink. The daily consumption may be part of the protective mechanism, she explained.

Moore said that a common recommendation for older adults is consuming about one drink a day. This study and other new data may change that standard. "There are healthy 65- to 70-year-olds who can take more than a drink a day," she added.

The UCLA researchers said their study was the first to follow a large, nationally representative sample over a period of years to look at the relationship between alcohol and physical disabilities. The findings were published online Jan. 15 in the American Journal of Epidemiology.

Dr. Kenneth J. Mukamal, an associate professor of medicine at Harvard Medical School, said the new research "adds to quite a substantial body of evidence that suggests in people who can demonstrate they can drink safely, there is no inherent medical reason not to drink." Studies by Mukamal and others have suggested that moderate drinking is associated with a lower risk of heart attacks and strokes.

Alcohol isn't the only adult beverage that may offer health benefits. Drinking coffee daily in midlife may decrease the chance of Alzheimer's and dementia in later years, according to a new Finnish study.

Ths study, published in the January issue of the Journal of Alzheimer's Disease, found that people who drank three to five cups of coffee a day had the lowest risk. Their risk was decreased by 65 percent compared to those who drank no or little coffee, the study found.

More information

For more on the benefits and risks of moderate drinking, visit the University of North Carolina at Chapel Hill.

New treatment option for latent tuberculosis

MUHC researchers are studying a shorter treatment with fewer side effects

Montreal,23 jan 2009– Patients who are infected with the latent form of tuberculosis (TB) show no symptoms and are not contagious, yet they pose the biggest challenge when it comes to controlling the disease. The latest study by Dr. Dick Menzies of the Research Institute of the McGill University Health Centre (MUHC) describes a new potential treatment for this particular form of TB. The paper based on this study was recently published in the Annals of Internal Medicine.

"Our results show that a four-month treatment with a drug called rifampin is better tolerated than the traditional nine-month treatment with a drug called isoniazid," explained Dr. Menzies. "The side effects with rifampin are much less frequent, particularly liver toxicity - which is the most serious risk of the traditional therapy with isoniazid. In addition patients are much more likely to complete this treatment - another big drawback to the nine month standard therapy."

Patients who currently receive a diagnosis of latent TB are treated for nine months with daily doses of isoniazid. Although effective, this treatment is very long and has major side effects on the liver. It is therefore common that patients do not complete treatment. Of course, this reduces the treatment's efficacy.

The new therapeutic option studied by Dr. Menzies lasts only four months and causes a lot less liver damage. Patients therefore adhere better to their treatment regimens, which is a critical first step towards ensuring the efficacy of the medication. This study was conducted on 847 patients in Canada, Brazil and Saudi Arabia. The results can therefore be generalized to a very broad population.

Currently, rifampin is most often used to treat the active form of TB. More in-depth studies will be necessary to test the effectiveness of this medication against latent TB, but the study researchers consider this treatment option to be very promising.

This study was funded by the Canadian Institutes of Health Research (CIHR) and the Fonds de la recherche en santé du Québec (FRSQ).

Dr. Dick Menzies is the Director of Respiratory Medicine at the MUHC and a researcher in the Respiratory Health Axis and Health Outcomes Axis at the Research Institute of the MUHC. He is also a Professor in Medicine, Epidemiology and Biostatistics - in the Faculty of Medicine of McGill University.

The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge.

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The Research Institute of the MUHC is supported in part by the Fonds de la recherche en santé du Québec. For further details visit: www.muhc.ca/research.

Find this press release, with the original article and a short audio document by following this link : http://www.muhc.ca/media/news/

'Sunshine vitamin' link to cognitive problems in older people

Vitamin D linked to cognitive impairment

23 jan 2009--Researchers from the Peninsula Medical School, the University of Cambridge and the University of Michigan, have for the first time identified a relationship between Vitamin D, the "sunshine vitamin", and cognitive impairment in a large-scale study of older people. The importance of these findings lies in the connection between cognitive function and dementia: people who have impaired cognitive function are more likely to develop dementia. The paper will appear in a forthcoming issue of the Journal of Geriatric Psychology and Neurology.

The study was based on data on almost 2000 adults aged 65 and over who participated in the Health Survey for England in 2000 and whose levels of cognitive function were assessed. The study found that as levels of Vitamin D went down, levels of cognitive impairment went up. Compared to those with optimum levels of Vitamin D, those with the lowest levels were more than twice as likely to be cognitively impaired.

Vitamin D is important in maintaining bone health, in the absorption of calcium and phosphorus, and in helping our immune system. In humans, Vitamin D comes from three main sources – exposure to sunlight, foods such as oily fish, and foods that are fortified with vitamin D (such as milk, cereals, and soya drinks). One problem faced by older people is that the capacity of the skin to absorb Vitamin D from sunlight decreases as the body ages, so they are more reliant on obtaining Vitamin D from other sources.

According to the Alzheimer's Society, dementia affects 700,000 people in the UK and it is predicted that this figure will rise to over 1 million by 2025. Two-thirds of sufferers are women, and 60,000 deaths a year are attributable to the condition. It is believed that the financial cost of dementia to the UK is over £17 billion a year.

Dr. Iain Lang from the Peninsula Medical School, who worked on the study, commented: "This is the first large-scale study to identify a relationship between Vitamin D and cognitive impairment in later life. Dementia is a growing problem for health services everywhere, and people who have cognitive impairment are at higher risk of going on to develop dementia. That means identifying ways in which we can reduce levels of dementia is a key challenge for health services."

Dr Lang added: "For those of us who live in countries where there are dark winters without much sunlight, like the UK, getting enough Vitamin D can be a real problem – particularly for older people, who absorb less Vitamin D from sunlight. One way to address this might be to provide older adults with Vitamin D supplements. This has been proposed in the past as a way of improving bone health in older people, but our results suggest it might also have other benefits. We need to investigate whether vitamin D supplementation is a cost-effective and low-risk way of reducing older people's risks of developing cognitive impairment and dementia."

Decline in health among older adults affected by Hurricane Katrina

23 jan 2009--In the year following Hurricane Katrina, the health of survivors 65 and over declined nearly 4 times that of a national sample of older adults not affected by the disaster, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health. The August 2005 storm was one of the most powerful and deadliest hurricanes in U.S. history. Hurricane Katrina displaced thousands and severely disrupted access to health care. Researchers monitored enrollees of a New Orleans-area managed care organization and found morbidity rates increased 12.6 percent compared with 3.4 percent nationwide. The results are published in the January issue of The American Journal of Managed Care.

"In the year following Hurricane Katrina, morbidity rates increased substantially," said Lynda Burton, ScD, lead author of the study and adjunct associate professor with the Bloomberg School's Department of Health Policy and Management. "Morbidity rates among non-white Orleans residents were the highest when compared to other parishes and there was a significant increase in the prevalence of patients with cardiac diagnoses, congestive heart failure and sleep problems. Survivors displaced out-of-state experienced higher morbidity rates than those not displaced. In the month following the disaster, mortality spiked, but during the remainder of the year returned to a level consistent with the previous year."

Researchers examined the managed care organization claims of 20,612 white and non-white residents of Orleans, Jefferson, St. Tammany and Plaquemines parishes who were over the age of 65 and enrolled in Peoples Health, a provider-owned managed care organization. Burton, along with colleagues from the Bloomberg School, Health Data Essentials, Inc. and the Johns Hopkins School of Medicine, conducted an observational study to compare mortality, morbidity and services used for one year before and after Hurricane Katrina. The researchers found that emergency department visits increased 100 percent in the month following Katrina, and by 21 percent over the next year compared to the pre-Katrina year. Hospitalization rates increased 66 percent in the first month after Katrina and maintained an increase of 23 percent over the ensuing year. Using a telephone survey, the study also examined the health of a random sample of enrollees after the hurricane. Researchers believe displacement played a major role in health outcomes. Sixty-nine percent reported moderate or severe damage to their home, or that their home was destroyed. At the end of the year, 28 percent reported their residence remained unlivable and another 28 percent reported a worse financial situation.

"The enormous health burden experienced by older individuals and the disruptions in service utilization reveal the long-term effects of Hurricane Katrina on this vulnerable population," said Jonathan Weiner, DrPH, senior author of the study and director of the Bloomberg School's PhD Program in Health Services Research and Policy. "Although quick rebuilding of the provider network may have attenuated more severe health outcomes for this managed care population, new policies must be introduced to deal with the health consequences of a major disaster."

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"Health of Medicare Advantage Plan Enrollees at 1 Year After Hurricane Katrina" was written by Lynda C. Burton, Elizabeth A. Skinner, Lori Uscher-Pines, Richard Lieberman, Bruce Leff, Rebecca Clark, Qilu Yu, Klaus Lemke, and Jonathan P. Weiner.

The research was funded by Peoples Health.

Studies point to novel target for treating arrhythmias

23 jan 2009--Abnormal heart rhythms – arrhythmias – are killers. They strike without warning, causing sudden cardiac death, which accounts for about 10 percent of all deaths in the United States.

Vanderbilt investigators have discovered a new molecular mechanism associated with arrhythmias. Their findings, reported in The Journal of Clinical Investigation, could lead to novel arrhythmia treatments.

"The current antiarrhythmic drugs do not prolong life," said Björn Knollmann, M.D., Ph.D., associate professor of Medicine and Pharmacology and the senior author of the current report. "There's a large need for new approaches to antiarrhythmic therapy."

In their quest to understand how irregular heart rhythms arise – as a way to find new molecular targets for treatment – Knollmann and his colleagues have focused on the role of calcium inside heart muscle cells.

Calcium is central to the contractile cycle. After it is released from its storage sites in heart muscle cells, it interacts with proteins called troponins, part of the cell's myofilament contractile apparatus. The interaction of calcium with troponins regulates myofilament activation and contraction.

Mutations in troponin genes had been linked to inherited forms of hypertrophic cardiomyopathy (HCM), which carries a high risk of sudden cardiac death. HCM is perhaps most famous as a cause of sudden cardiac death in young athletes, but it can affect individuals of any age.

In previous studies, Knollmann's team demonstrated that troponin mutations associated with HCM increase the sensitivity of the troponins to calcium – they bind calcium more readily, which activates the myofilaments more easily and results in stronger contractions.

Increased myofilament calcium sensitivity has also been found in acquired heart diseases, such as heart failure, that have a high incidence of sudden cardiac death, Knollmann said. He and his colleagues proposed that increased myofilament calcium sensitivity contributes to arrhythmia susceptibility.

The researchers examined the heart rhythms of mice expressing various troponin mutants that cause HCM and showed that the mice develop ventricular tachycardia (a particular arrhythmia). The risk for this arrhythmia was directly related to the degree of calcium sensitization caused by the troponin mutation: the higher the calcium sensitivity, the greater the arrhythmia risk.

The investigators then tested whether or not a calcium-sensitizing drug – infused into the mouse heart – would cause arrhythmias. It did.

"We could make a normal heart prone to arrhythmias simply by changing the sensitivity of the myofilaments to calcium," Knollmann said.

Calcium-sensitizing drugs are used clinically in Europe and Japan to treat heart failure (because they increase the strength of contraction), but they have not been approved for use in the United States. The current studies suggest that these agents would increase the risk of arrhythmias.

In addition to demonstrating that a calcium-sensitizing drug could cause arrhythmias, Knollmann and colleagues showed that an agent that desensitizes the myofilaments – makes them less "willing" to bind calcium – prevented arrhythmias. The drug they used is limited to in vitro testing, but the studies validate the concept of calcium desensitization as a way to prevent or block arrhythmias.

"The next step is to look for agents that have a desensitizing effect and then try them therapeutically, first in our mouse models, and then potentially further along to patients," Knollmann said.

"We're excited about these studies because we believe that we have identified a novel mechanism that renders the heart susceptible to arrhythmias and a new therapeutic target for familial hypertrophic cardiomyopathy and other arrhythmia syndromes."

The first author of the current report, Franz Baudenbacher, Ph.D., assistant professor of Biomedical Engineering and Physics, played a key role in studying the electrical changes that caused the arrhythmias. Using optical imaging, he and colleagues in the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) measured how electrical excitation traveled across the hearts expressing troponin mutants or treated with calcium-sensitizing agents. These experiments defined the electrical underpinnings of the arrhythmias.

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The National Institutes of Health, the American Heart Association and VIIBRE supported the research.

Excessive weight loss can be a bad thing

Saint Louis University doctor helps draft new guidelines for wasting disease

ST. LOUIS, 23 jan 2009 -- Doctors are not doing enough to pick up on problems with excessive weight loss, says a Saint Louis University physician who helped draft recent guidelines to diagnose the condition called "cachexia" (kuh-kex-ee-uh).

"In sick people, weight loss is an important indicator of disease and potentially impending death," said John Morley, M.D., an endocrinologist and director of the division of geriatric medicine at Saint Louis University School of Medicine.

"Cachexia is an extraordinary problem for people who are having other health problems, yet this is something that many physicians don't pay attention to."

A group of physicians and scientists agreed on a definition of cachexia, which was published in the December edition of the medical journal, Clinical Nutrition.

"The definition is important because it gives physicians the guidelines to make a diagnosis and treat the condition," Morley said. "A definition of cachexia also makes it easier for scientists to conduct research and potentially develop new therapies for the problem."

About half of hospitalized patients and between 10 and 15 percent of sick patients who see a doctor have cachexia. The condition accompanies diseases such as cancer, congestive heart failure, HIV, diabetes, kidney failure and COPD (chronic obstructive pulmonary disease).

Adults with cachexia lose weight and children don't grow. Muscle mass melts away, and those with cachexia also may lose fat.

Those who traditionally have had difficulty taking off weight and suddenly find the pounds melting off should beware, Morley said. They may be ill and could get even sicker as they become weaker and weaker.

"Cachexia should be seen as a wasting disease that requires specialized treatment from a physician who is familiar with the problem," Morley said.

The researchers clarified the definition of cachexia by noting it is always linked to an underlying disease. They differentiated it from starvation; loss of muscle mass that comes with aging; depression; thyroid problems; and the body's difficulty in absorbing nutrients. Rather, cachexia is a complicated metabolic syndrome that is often associated with anorexia, inflammation, insulin resistance and increased muscle protein breakdown.

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Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first M.D. degree west of the Mississippi River. Saint Louis University School of Medicine is a pioneer in geriatric medicine, organ transplantation, chronic disease prevention, cardiovascular disease, neurosciences and vaccine research, among others. The School of Medicine trains physicians and biomedical scientists, conducts medical research, and provides health services on a local, national and international level.