Uncovering factors at the heart of muscle weakness

Sep. 25, 2013 — Prof. Tamai of Kanazawa University has been examining how orange, apple and grapefruit juices affect the absorption of certain prescription drugs into the body.

Ikumi Tamai, has dedicated his career to investigating the molecules and genes responsible for cardiomyopathy, muscle weakness, and Reye's syndrome. His key discoveries relate to human organic anion transporting polypeptides (OATPs), their associated genes and their roles in the body.

Muscle weakening diseases are known to be triggered by a deficiency of carnitine in the body -- a compound that helps to transport fatty acids for the generation of metabolic energy after the breakdown of lipids. Little was known about the mechanisms inherent in carnitine deficiency until Tamai's work in the late 1990s led to the discovery of carnitine transporter OCTN2.

OCTN2 is expressed strongly in the kidneys, skeletal muscle, and the heart. If OCTN2 expression is disrupted, the defective transport of carnitine across plasma membranes increases the chances of muscle weakness.

In 1999, Tamai uncovered the gene responsible for encoding OCTN2 -- SLC22A5 -- and showed that patients with mutations in SLC22A5 exhibit carnitine transportation deficiencies. This discovery helped "contribute to a better understanding of the molecular mechanism of systemic carnitine deficiency and normal lipid metabolism... allow[ing] genetic screening and gene therapy [for] families with disease history."

Following on from these successes, Tamai went on to categorize all OATPs present in the human body, including three novel polypeptides. In his most recent research, Tamai is investigating OATPs and their influence on drug absorption in the body. His newest papers examine the intake of fruit juices and their effects on the absorption of prescription drugs into the body. In particular, Tamai is focusing how sugars such as naringin and hesperidin in orange, apple and grapefruit juices affect how drugs are absorbed.

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Heart Infection Causing Fewer Hospitalizations, Researchers Say

THURSDAY, Sept. 19 (HealthDay News) -- Hospitalizations for a deadly heart infection that affects mainly older people have declined in recent years, a new study finds. This was seen even with recommendations for more limited use of antibiotics to prevent the illness, called endocarditis.

Specifically, endocarditis is inflammation of the inside living of the heart valve and chambers, according to the U.S. National Heart, Lung, and Blood Institute. The risk of endocarditis increases when people have surgery, and it's considered the most serious infection of the cardiovascular system.

There was a significant increase in rates of hospitalization for endocarditis in the 1990s, which led many doctors to prescribe antibiotics before dental procedures and certain types of surgery.

However, the American Heart Association has narrowed the recommended use of antibiotics to prevent endocarditis to only a subgroup of patients undergoing dental procedures.

In this study, Yale School of Medicine researchers looked at the annual rates of endocarditis-related hospitalizations and related outcomes among more than 262,000 Medicare patients 65 and older between 1999 and 2010.

An increase in hospitalizations for endocarditis occurred between 1999 and 2005, but there was a decline between 2006 and 2010, according to the study in the August Journal of the American College of Cardiology.

"We were surprised to see reduced rates of endocarditis hospitalizations during this time period," study first author Dr. Behnood Bikdeli, a postdoctoral associate in cardiovascular medicine, and an internal medicine resident, said in a Yale news release.

"This downward trend was consistent in all major study subgroups, but certain subgroups, including black participants, had higher hospitalization rates and worse outcomes in the study period," he added.

This racial disparity in outcomes, as well as reasons for the overall decline in hospitalizations, require further investigation, Bikdeli said.

"Clinicians should consider the risks and benefits of antibiotic use on a case-by-case basis and should share the information with their patients for appropriate decision making," he concluded.

More information

The U.S. National Heart, Lung, and Blood Institute has more about endocarditis.

Copyright c 2013?HealthDay. All rights reserved.

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Memory problems, emotional stress result in early readmissions of heart patients

Sep. 17, 2013 — Heart patients' mental state and thinking abilities may help predict whether costly and potentially dangerous early hospital readmission will follow their release after treatment, according to the results of a significant new study by Henry Ford Hospital researchers.

The findings have important implications for the health care industry as it struggles to contain unnecessary costs, according to the study's lead author, Mark W. Ketterer, Ph.D., a psychologist and administrator for Henry Ford.

The study is published online in Psychosomatics.

"Wasted resources have become a central concern in American health care, including readmission soon after a patient has been released from hospital care," Dr. Ketterer says.

"Because heart failure has one of the highest readmission rates of all conditions that have been studied in Medicare and Medicaid populations, we decided to focus on it and try to identify predictors for early readmission."

What was found, Ketterer explains, was that a psychiatric history of depression, anxiety and other mood disorders, as well as impairments in a patient's ability to think, remember and reason, may well be such predictors.

"Given both the exorbitant fiscal costs and known health risks of hospitalization, including exposure to drug-resistant infections and medical errors, it could be well worth further study to test our findings." he adds.

Currently, Medicare is penalizing hospitals for what it considers excessive readmission rates. Last month, Medicare said it will access $227 million in fines against hospitals in 49 states as part of an initiative to reduce the number of patients readmitted within a month. Medicare said that 2,225 hospitals will see payments reduced for a year. Henry Ford Hospital is one of hospitals that will see a reduction in payments starting Oct. 1.

In the study, the researchers chose 84 patients who were admitted to Henry Ford Hospital for treatment of acute congestive heart failure. Each was interviewed for basic clinical and demographic information and asked to complete several questionnaires measuring depression, anxiety and spirituality.

Their medical risk factors -- including other illnesses and their severity -- and behavioral risk factors -- including depression and such cognitive impairments as loss of reasoning, planning, forgetfulness and other reduced mental functions -- as well as admissions during the past year and readmissions during the previous 30 days were recorded.

The patient group was 62 percent male with an average age of 66. Central nervous system disorders -- including Alzheimer's, dementia, closed-head injury and others -- were present in 21 percent. Nearly 70 percent lived with a family member, 24 percent acknowledged a psychiatric history, 36 percent used or had used antidepressants, 40 percent had coronary artery disease, 43 percent had diabetes, 86 percent had hypertension, 20 percent had chronic obstructive pulmonary disease, 48 percent had chronic kidney disease and 24 percent were alcohol or drug abusers.

The researchers found that depression, a history of substance abuse, and a history of coronary artery disease were related to hospital admissions during the previous year. Factors in 30-day readmission rates included immediate memory problems and a history of psychiatric treatment and/or the use of an antidepressant. The severity of congestive heart failure, however, was not a factor in either admission or readmission rates.

"Our results agree with several recent studies in finding an adverse impact of depression on admission and readmission rates," Ketterer says. "In addition, substance abuse and chronic kidney disease may also adversely impact these rates in congestive heart failure patients.

"Even severe heart disease, except in the extreme, appears to be manageable after release from the hospital unless it's complicated by one or more of the behavioral factors."

But perhaps most important in these findings is the relationship between emotional stress and/or cognitive impairment and early readmission to the hospital. "Both suggest a possible way to predict readmission and avoid it," Ketterer says.

Educating patients about their mental illness, as well as involving live-in family members in helping with the patient's medications, and keeping medical appointments may also help reduce hospital readmissions, the study concluded.

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Heart technique 'could save lives'

11 September 2013 Last updated at 10:07 GMT By Eleanor Bradford BBC Scotland Health Correspondent Every year 25,000 people in the UK have the kind of heart attack which is treated with an angioplasty A new, relatively simple way of treating heart attacks could save thousands of lives, according to specialists at a Clydebank hospital.

It involves clearing all narrowed arteries when someone is admitted with a heart attack, rather than just the one which is completely blocked.

A trial, involving the Golden Jubilee National Hospital, was so successful that the research was stopped early.

Jubilee heart specialist Prof Colin Berry said the results were "striking".

Fatty deposits

Another cardiologist, Prof Keith Oldroyd, said: "At the moment when patients come in with a heart attack they have an emergency angiogram and we usually only treat the artery that has caused the heart attack.

"Many of these patients have additional narrowings in other arteries. We're treating all the narrowed arteries at the same time to see if that confers additional benefit."

Every year 25,000 people in the UK have the kind of heart attack which is treated with an angioplasty.

This involves inserting a stent, or thin tube, to open an artery and restore the blood flow.

Arteries become narrowed by fatty deposits, so although a blood clot may have only blocked one artery, other narrowed arteries are common.

Current UK recommendations advise specialists only to treat the artery which is completely blocked.

"Most cardiologists thought it wasn't safe to treat a second or third artery at the same time as the first artery," Prof Oldroyd said.

"Sometimes the patients would be brought back several weeks later or sometimes only medication would be used. The results of this trial suggest that this recommendation should be revisited."

Reducing costs

The trial involved 465 patients in five specialist heart centres around the UK. In addition to the Golden Jubilee, they were the London Chest Hospital, Morriston Hospital in Swansea, Freeman Hospital in Newcastle, and Norfolk and Norwich University Hospital.

Half of the trial participants had all their arteries cleared, the rest were treated in the conventional way.

Prof Keith Oldroyd said most patients had narrowings in more than one artery

The researchers found that the new technique reduced the combined risk of dying, having another heart attack or being left with angina by two-thirds - such a significant finding that the trial was stopped early.

It also only added an average of 20 minutes to each treatment.

The results have been published in the New England Journal of Medicine and were presented at an international conference in Amsterdam earlier this month.

Prof Colin Berry, heart specialist at the Golden Jubilee and the University of Glasgow, said: "They were some of the most striking results for a treatment that I have ever seen. The results of this trial really challenge clinical practice."

Heart specialists are now keen that even larger studies get under way as quickly as possible.

In the past, it has taken a decade or more for the latest evidence to be adopted into frontline medical care.

Prof Berry added: "It's appealing because it's a form of usual care that can be readily adopted across the UK.

"On the other hand there are logistical considerations and cost considerations. However, we would argue that reducing the likelihood of further cardiac events, potentially reducing the heart failure admissions to hospital, is going to reduce costs overall and this should be implemented as soon as possible."

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Smog Tied to Higher Risk of Lung Cancer, Heart Failure

WEDNESDAY, July 10 (HealthDay News) -- There's more evidence that smog boosts a person's risk of both lung cancer and heart failure, with even short exposures to small amounts of pollution harming the body.

A pair of newly published European studies found that regularly breathing in air tainted with even low levels of air pollution raises your long-term risk of lung cancer. That finding came from a review of data from nearly 313,000 people across nine European countries. The study was published online July 10 in The Lancet Oncology.

At the same time, short-term exposure to smog has also been linked to increased risk of hospitalization or death from heart failure, according to a study led by the University of Edinburgh that reviewed data from 12 countries worldwide, published the same day in The Lancet.

The findings of the two studies further corroborate the known health risks of air pollution, said Dr. Albert Rizzo, immediate past chair of the national board of directors of the American Lung Association. He was not involved with the new research.

"On a day-to-day basis, a lot of people who aren't diagnosed with a specific illness may not know the importance of protecting yourself against these pollutants. Insult to your airways on a repeated basis can lead to dire consequences," said Rizzo, section chief of pulmonary/critical care medicine at Christiana Care Health System, in Wilmington, Del.

The lung cancer study assessed the risk of long-term exposure to particulate matter in the air by comparing local air pollution levels to reported cases of cancer, in an effort led by the Danish Cancer Society Research Center.

Researchers found that the risk of lung cancer grew with even tiny increases in the amount of particulate pollution in the air. Particulate pollution is the sort of black sooty smoke produced by diesel trucks and buses and by coal-fired power plants.

For example, consider that a human hair is about 70 micrometers wide. Lung cancer risk rose 18 percent every time the amount of 2.5 micrometer-wide particulates increased by 5 micrograms per cubic meter of air, the study said. Risk rose 22 percent every time the amount of 10 micrometer-wide particulates increased by 10 micrograms per cubic meter of air.

"We found no threshold below which there was no risk; the results showed a picture that 'the more the worse, the less the better," the authors said in a journal news release.

The other study compared air quality conditions in specific areas with reports of heart failure hospitalization or death. Researchers found that smog concentration is closely associated with heart failure hospitalization and death.

More specifically, they calculated that the risk of being hospitalized or dying from heart failure rose by about 3.5 percent with every increase of 1 part per million of carbon monoxide and about 2.4 percent for every increase of 10 parts per billion of sulfur dioxide.

Risk also rose 1.7 percent for every 10 parts per billion increase in levels of nitrogen dioxide, and 2 percent for every increase of 10 micrograms per cubic meter of particulate matter.

The study estimates that a modest reduction in particulate levels in the United States could prevent roughly 8,000 heart failure hospitalizations and save more than $300 million annually.

The researchers speculate that smog causes inflammation of the lungs that spills over and creates stress on the heart.

"Even a healthy young athlete who jogs on a high ozone day is going to feel that exposure," Rizzo said. Less healthy people might end up suffering heart failure from the increased stress.

To protect themselves, people in areas with high levels of air pollution should consider installing HEPA (high-efficiency particulate air) filters in their homes, said Dr. Len Horovitz, a pulmonary specialist at Lenox Hill Hospital, in New York City.

"This is something that people can do in the home or office to filter the air and get some of the particular offenders trapped in filters," Horovitz said. "A toxic substance is going right into the lungs, and I don't think it's a leap of scientific understanding to know it's bad for you when you apply a toxic substance directly to tissue."

People also should avoid going outside during times of heavy concentrations of air pollution, particularly if they are performing strenuous tasks like mowing or exercising, Horovitz said.

For his part, Rizzo said people also should lobby the U.S. Environmental Protection Agency to tighten the nation's clean air regulations.

More information

To learn more about particulate pollution, visit the U.S. Environmental Protection Agency.

SOURCES: Albert A. Rizzo, M.D., immediate past chair, national board of directors, American Lung Association, and section chief, pulmonary/critical care medicine, Christiana Care Health System, Wilmington, Del.; Len Horovitz, pulmonary specialist, Lenox Hill Hospital, New York City; July 10, 2013, The Lancet Oncology and The Lancet, online

Copyright c 2013 HealthDay. All rights reserved.

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FDA staff say Edwards heart valve meets goals

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WASHINGTON (Reuters) - U.S. Food and Drug Administration staff said on Monday that Edwards Lifesciences Corp's Sapien heart valve met its primary safety and effectiveness goals in research, but expressed caution about the risk of stroke and aortic leakage.

The FDA released a staff review document that found "no significant difference in mortality" up to one year, between aortic stenosis patients who received the Sapien valve and a control group that had aortic valve replacement through open-heart surgery.

But the document said there was only limited data available beyond two years and cautioned that some of the findings were hard to assess partly because some patients in the study did not receive the intended treatments.

The Sapien heart valve, which is threaded to the heart through an incision in the groin or ribs, has already been approved by the FDA for aortic stenosis patients deemed to be too sick for open-heart surgery. A panel of outside advisers to the FDA will vote Wednesday on whether to recommend that the agency approve the product for use among patients whose cases are high-risk but not inoperable.

Wall Street analysts said the FDA staff's cautious comments suggest that Edwards Lifesciences will face a challenge advisory committee hearing on Wednesday, but ultimately win the panel's recommendation and the regulatory agency's approval.

Sapien is considered to be one of the most important future growth drivers for Edwards, whose shares were up about 13 cents at $88.30 in afternoon trading.

"We estimate there will be approximately 5,500 of these (high-risk) procedures performed in the United States in 2013, moving to nearly 40,000 by 2016," Goldman Sachs analyst David Roman said in a note to investors.

Roman added that his 2016 estimate would be double the number of procedures anticipated for patients ineligible for surgery during the same year. The procedure is estimated to cost about $30,000.

In pivotal clinical trials, the company said the Sapien led to a slightly lower death rate and dramatically shorter recovery times and hospital stays than chest-cracking open-heart surgery.

The FDA staff cited findings that showed patients treated with Sapien had a mortality rate of 24.27 percent when the device was inserted through the leg, and 22.24 percent when inserted between the ribs. The control group had mortality rates above 26 percent.

FDA staff also highlighted research showing a significantly higher incidence of stroke. Earlier research suggested a higher stroke risk could potentially make surgery preferable for some, especially younger, stronger patients.

In addition to strokes, the FDA staff pointed to data showing that 53 percent of patients treated with the Sapien system experienced leakage known as aortic regurgitation and said there was mounting evidence of a link between the condition and death among Sapien patients.

"These data also show that the amount of (aortic regurgitation) is appreciable and does not decrease over time," the staff said.

Up to 1.5 million people in the United States suffer from aortic stenosis, a progressive disease that affects the aortic valve of their hearts, according to Edwards.

The company said that approximately 250,000 people have severe symptoms. But only about two-thirds of them undergo surgery.

The federal government's Medicare healthcare program for the elderly and disabled and the joint federal-state Medicaid program for the poor announced last month that they would cover the procedure for patients who cannot have surgery.

(Reporting By David Morgan; editing by Sofina Mirza-Reid and Maureen Bavdek)

Health Tip: Help Prevent Heart Disease

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(HealthDay News) -- You can't control all risk factors for heart disease, but living a healthy lifestyle and taking medication prescribed by your doctor can help prevent many of its dangerous risk factors.

The Womenshealth.gov website suggests these steps to help reduce your risk of heart disease:

Maintain healthy cholesterol and blood pressure.Quit or avoid smoking and drinking too much alcohol.Take steps to control diabetes.Maintain a healthy body weight.Get plenty of regular exercise and adhere to a regular sleep schedule.Control conditions such as sleep apnea and metabolic syndrome.

Copyright c 2012?HealthDay. All rights reserved.

Sanofi's Lantus shows no cancer, heart risks: study

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PARIS (Reuters) - Sanofi's insulin Lantus does not put people at risk of cancer, heart attacks or strokes when taken over long periods, according to a major study in which the drug failed to prove it can prevent heart disease in early-stage diabetics.

Although a positive result on heart disease could have widened Lantus's use, the findings of the longest and largest study of its kind should help shake off safety concerns about the French group's top-selling drug after a 2009 cancer scare.

A number of studies at the time suggested a possible link between Lantus and a heightened risk of cancer, with conflicting results.

"We know what the risks are of taking insulin on a long-term basis, and they are low," said the principal investigator of the trial, Hertzel Gerstein of McMaster University in Ontario, Canada, in a telephone interview with Reuters.

The closely watched study also found that people with pre-diabetes who received daily Lantus injections had a 28 percent lower chance of developing diabetes, even after the injections stopped.

The study tested more than 12,500 people at risk or in the early stages of diabetes with either a daily injection of Lantus or standard therapy for an average of six years.

The results confirmed two known side effects of insulin - low blood sugar levels and modest weight gain. Researchers said these were minor reactions.

The study also discovered that daily doses of Lovaza, a prescription pill based on fish oil and sold by Pronova Biopharma and GlaxoSmithKline, did not prevent heart-related deaths in diabetics.

The findings were presented on Monday at the American Diabetes Association congress in Philadelphia, U.S., and published online in the New England Journal of Medicine.

STUDY EXTENDED

Paris-based Sanofi said it would extend the study by two years to gather further data on Lantus.

Worldwide, Lantus has 80 percent of the market for long-acting, or basal, insulin used to treat diabetes, generating sales of around 3.9 billion euros ($4.9 billion) last year, representing 12 percent of Sanofi's total sales.

Sanofi is particularly reliant on Lantus because it faces a wave of patent expirations on other blockbuster medicines.

Fresh competition is emerging as rival drugmakers, such as U.S. group Eli Lilly and Danish company Novo Nordisk, prepare to launch newer long-acting insulin, in addition to the threat of biosimilars.

The insulin market is also vulnerable to the growth of GLP-1 therapies, including Sanofi's own Lyxumia, which is in late stage development.

(Reporting by Elena Berton; Editing by Dan Lalor)