Obese adolescents have the same risk of premature death in adulthood as people who smoke more than 10 cigarettes a day, while those who are overweight have the same risk as less heavy smokers, according to research published on http://www.bmj.com today.

Smoking and obesity are two of the most important behavioural risk factors for premature death in the western world, but it is not known whether smoking and weight have combined effects on the risk of death.

The authors, led by Dr Martin Neovius at Karolinska Institute in Sweden, analysed the cause of death of over 45,000 men who underwent mandatory military conscription tests in Sweden. The participants all had their body mass index (BMI) measured and reported their smoking status at the age of 18 and were followed up for an average of 38 years. In total, the authors assessed 1.7 million person-years of follow-up in relation to the health and mortality of all the participants.

During the follow-up period 2,897 subjects died, the incidence of death was lowest for people with normal weight and highest in obese subjects.

Compared to normal weight adolescents, being overweight at the age of 18 increased the risk of premature death by just over a third, while being obese more than doubled the risk.

Being underweight carried no increased risk, irrespective of smoking status. However, being seriously underweight (a body mass index of less than 17) carried the same risk of premature death as being overweight.

Early death was also linked to the number of cigarettes participants smoked per day. This risk gradually increased the more participants smoked, with heavy smokers at more than double the risk of premature death compared to non-smokers.

But, interestingly, when the effects of weight and smoking were combined, the researchers found no significant change in the results. The combination of obesity and heavy smoking was associated with a large excess risk of early death (almost five times greater than normal weight non-smokers). However, there was no statistically significant interaction between these two factors.

This means that being overweight or obese at the age of 18 increases the risk of premature death, regardless of smoking status, they explain.

The authors note that since the baseline measurements for this study were carried out, the number of adolescent men who are overweight in Sweden has tripled and those who are obese has increased five-fold. However, the number of men who smoke and are underweight in Sweden has halved. Internationally, there have been marked increases in overweight and obesity, but also in adolescent smoking in some countries.

Dr Neovius and his colleagues therefore conclude that “overweight, obesity and smoking among adolescents remain important targets for intensified public health initiatives.”

“Research: Combined effects of overweight and smoking in late adolescence on subsequent mortality: nationwide cohort study.”

US scientists reviewing 20 years of research and expert opinion on generic versus brand name drugs in the treatment of cardiovascular diseases found no clinical evidence showing brand names were superior to generic versions even though a substantial number of experts writing editorials advised against interchanging them.

The study was the work of Dr Aaron S Kesselheim, of Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues, and is published online in the 3rd December issue of the Journal of the American Medical Association, JAMA.

When two drugs are bioequivalent it means that to all intents and purposes after they have been given to the patient they are biologically equivalent to each other, for example the composition, rate and extent to which their active ingredients are present at the target site inside the body are so similar that you can’t tell the difference between them.

And yet there appears to be a general opinion among doctors and patients that despite the fact generic drugs are bioequivalent to brand name drugs, the brand names are clinically superior. But generic drugs are much cheaper, so Kesselheim and colleagues decided to investigate the available clinical evidence on generics versus brand names and the views of editorial writers on the subject with respect to cardiovascular treatments.

For the study, the researchers systematically searched for peer reviewed studies published between 1984 and 2008 and listed in a number of well known databases, including MEDLINE, EMBASE, and International Pharmaceutical Abstracts.

They selected those studies that compared the clinical effectiveness and safety of generic versus brand name cardiovascular drugs. In a separate exercise they also identified editorials that wrote about substituting brand names with generic versions.

Kesselheim and colleagues then used techniques commonly used in research that reviews other studies, whereby the design, setting, participants, results and funding of each study is extracted and put through a test that assesses the quality of the trial, whilst the results are pooled in such a way that they can then be viewed as if they had come from one giant trial (meta-analysis).

As a separate exercise they reviewed the editorials and classified them as negative, positive or neutral, depending on the authors’ view on generic substitution.

They found a total of 47 clinical trials covering 9 subclasses of cardiovascular drugs, and established the following results:

* 38 of the 47 (81 per cent) trials were randomized controlled trials (considered to be higher quality).

* For beta-blockers, 7 out of 7 randomized controlled trials (100 per cent) found generics to be clinically equivalent to brand names.

* For diuretics, the figure was 10 out of 11 (91 per cent).

* For calcium channel blockers it was 5 out of 7 (71 per cent).

* For antiplatelet agents it was 3 of 3 (100 per cent).

* For statins it was 2 out of 2 (100 per cent).

* For angiotensin-converting enzyme inhibitors it was 1 out of 1 (100 per cent).

* And for alpha-blockers, 1 out 1 randomized controlled trial (100 per cent) found generics to be clinically equivalent to brand names.

* In drugs that have a narrow therapeutic index (where you have to be really careful to give the right dose so as not to injure the patient), clinical equivalence was found in 1 out of 1 randomized controlled trial (100 per cent) for class 1 antiarrhythmic agents, and in 5 out of 5 (100 per cent) for warfarin.

* Pooling the results of all the trials gave a total of 837 participants and an aggregate effect size of -0.03 (95 per cent confidence interval of -0.15 to 0.08), meaning that across the studies as a whole, there was no statistically significant evidence that brand names were superior to generic drugs.

Reviewing the material from 43 editorials, the researchers found that:

* 23 of them (53 per cent), expressed a negative view about whether generic drugs could replace or be used instead of brand names.

* This compared with 12 (28 per cent) that encouraged substitution.

* The other 8 editorials did not reach a conclusion on interchangeability.

* Among editorials covering narrow therapeutic index drugs, 12 (67 per cent) expressed a negative view compared with 4 (22 per cent) in favour generic substitution.

Kesselheim and colleagues concluded that:

“Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.”

They wrote that the rising cost of prescription drugs is a critical policy issue: it strains the budgets of patients and insurance providers, and leads to poorer health as it works against helping everyone to make sure patients can complete their medication schedules.

“The primary drivers of elevated drug costs are brand-name drugs, which are sold at high prices during a period of patent protection and market exclusivity after approval by the Food and Drug Administration (FDA),” they added.

The idea of generics is to help people afford drugs, and these become available after the brand names have had their period of being the only ones on the market, the so called exclusivity period. Many doctors and payers encourage this.

However, some patients and doctors have been concerned that the generic versions may not be as effective. As Kesselheim and colleagues explained:

“Brand-name manufacturers have suggested that generic drugs may be less effective and safe than their brand-name counterparts. Anecdotes have appeared in the lay press raising doubts about the efficacy and safety of certain generic drugs.”

Kesselheim and colleagues suggested that one explanation for the discordance between the clinical evidence and the opinion expressed by experts in the editorials could be that:

“Commentaries may be more likely to highlight physicians’ concerns based on anecdotal experience or other nonclinical trial settings.”

Another explanation they suggested was that the:

“Conclusions may be skewed by financial relationships of editorialists with brand-name pharmaceutical companies, which are not always disclosed.”

Nearly half the trials (23 out of 47) and nearly all the editorials and commentaries they reviewed did not reveal where the funding came from, noted Kesselheim and colleagues, who also wrote that:

“We identified numerous studies that evaluated differences in clinical outcomes with generic and brand-name medications. Our results suggest that it is reasonable for physicians and patients to rely on FDA bioequivalence rating as a proxy for clinical equivalence among a number of important cardiovascular drugs, even in higher-risk contexts such as the NTI drug warfarin.”

“These findings also support the use of formulary designs aimed at stimulating appropriate generic drug use. To limit unfounded distrust of generic medications, popular media and scientific journals could choose to be more selective about publishing perspective pieces based on anecdotal evidence of diminished clinical efficacy or greater risk of adverse effects with generic medications. Such publications may enhance barriers to appropriate generic drug use that increase unnecessary spending without improving clinical outcomes,” they added.

“Clinical Equivalence of Generic and Brand-Name Drugs Used in Cardiovascular Disease: A Systematic Review and Meta- analysis.”
Aaron S. Kesselheim; Alexander S. Misono; Joy L. Lee; Margaret R. Stedman; M. Alan Brookhart; Niteesh K. Choudhry; William H. Shrank.
JAMA. Vol 300, No 21, pp 2514-2526, December 3, 2008

Some experts and doctors recently have voiced concerns that people who were diagnosed with HIV/AIDS in the early years of the epidemic are experiencing “prematur[e]” or “disproportionate numbers” of ailments associated with aging, the New York Times reports. CDC estimates show that the number of people ages 50 and older living with HIV increased by 77% between 2001 and 2005 and that this population now represents more than 25% of all HIV/AIDS cases in the U.S. The “graying of the AIDS epidemic” has raised interest in the link between AIDS and cardiovascular disease, certain cancers, diabetes, osteoporosis and depression, the Times reports.

Cardiovascular disease and diabetes are associated with lipodystrophy, which results in fat redistribution that can leave the face and lower limbs gaunt, the stomach swollen and the back humped. Lipodystrophy also raises cholesterol levels and causes glucose intolerance, which could be particularly harmful to black people, who are predisposed to heart disease and diabetes. According to the Times, there are no data that compare the incidence, age of onset and cause of aging-related diseases in the general population with long-term survivors of HIV. However, experts say they do not see HIV-negative people in their mid-50s with hip replacements associated with vascular necrosis, heart disease or diabetes related to lipodystrophy, or osteoporosis without the usual risk factors.

The most comprehensive research has come from the AIDS Community Research Initiative of America, which has studied 1,000 long-term survivors in New York City. The ACRIA study, published in 2006, found unusual rates of depression and isolation among older people living with HIV.

The NIH-funded Multi-Site AIDS Cohort Study — which has followed 2,000 subjects nationwide for the past 25 years — will examine the effects of HIV/AIDS and aging over the next five years. MACS investigators and other researchers say the slow pace of research on HIV/AIDS and aging is a result of numbers. They note that the first generation of people diagnosed with HIV/AIDS in the mid-1980s had no effective treatments for 10 years and died in large numbers, leaving few people to participate in studies.

Charles Emlet — an associate professor at the University of Washington-Tacoma and a leading HIV and aging researcher — said HIV/AIDS and aging research has been slow to start because of “the rapid increase in numbers.” CDC’s most recent data, from 33 states that meet certain reporting criteria, showed that the number of people age 50 and older with HIV or AIDS was 115,871 in 2005, compared with 64,445 in 2001. In addition, the “routine exclusion” of older people from drug trials by large pharmaceutical companies has undermined such research, the Times reports. The studies are designed to measure safety and efficacy but not long-term side effects of drugs. The lack of research also limits a patient’s care, the Times reports.

“AIDS is a very serious disease, but longtime survivors have come to grips with it,” Emlet said, noting that although some patients experience unpleasant side effects from the antiretroviral drugs, a vast majority find a regimen they can tolerate. “Then all of a sudden they are bombarded with a whole new round of insults, which complicate their medical regime and have the potential of being life threatening. That undermines their sense of stability and makes it much more difficult to adjust,” he added (Gross, New York Times, 1/6).

Reprinted with kind permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

The same vitamin D deficiency that can result in weak bones now has been associated with an increased risk of cardiovascular disease, Framingham Heart Study researchers report in Circulation: Journal of the American Heart Association.

“Vitamin D deficiency is associated with increased cardiovascular risk, above and beyond established cardiovascular risk factors,” said Thomas J. Wang, M.D., assistant professor of medicine at Harvard Medical School in Boston, Mass. “The higher risk associated with vitamin D deficiency was particularly evident among individuals with high blood pressure.”

In a study of 1,739 offspring from Framingham Heart Study participants (average age 59, all Caucasian), researchers found that those with blood levels of vitamin D below15 nanograms per milliliter (ng/mL) had twice the risk of a cardiovascular event such as a heart attack, heart failure or stroke in the next five years compared to those with higher levels of vitamin D.

When researchers adjusted for traditional cardiovascular risk factors such as high cholesterol, diabetes and high blood pressure, the risk remained significant with a 62 percent higher risk of a cardiovascular event in participants with low levels of vitamin D compared to those with higher levels.

Researchers observed the highest rate of cardiovascular disease events in subset analyses dividing 688 participants according to high blood pressure status. After researchers adjusted for conventional cardiovascular risk factors, participants with hypertension and a vitamin D deficiency had about 2 times the risk of having a cardiovascular disease event in five years.

Researchers also found an increase in cardiovascular risk with each level of vitamin D deficiency.

“We found that people with low vitamin D levels had a higher rate of cardiovascular events over the five-year follow-up period,” Wang said. “These results are intriguing and suggestive but need to be followed up with further study.”

Study participants had no prior cardiovascular disease and were tested for vitamin D status and then followed for an average of 5.4 years.

The participants attended the offspring examinations between 1996 and 2001. Researchers obtained medical history, physical examinations and laboratory assessments of vascular risk factors. They also obtained medical records related to cardiovascular disease.

Overall, 28 percent of individuals had levels of vitamin D below15 ng/mL and 9 percent had levels below10 ng/mL. Although levels above 30 ng/mL are considered optimal for bone metabolism, only 10 percent of the study sample had levels in this range, researchers said.

During follow-up:

* 120 participants developed a first cardiovascular event including fatal and nonfatal coronary heart disease;

* 28 participants had fatal or nonfatal cerebrovascular events such as nonhemorrhagic stroke;

* 19 participants were diagnosed with heart failure; and

* 8 had occurrences of claudication, fatigue in the legs during activity.

“Low levels of vitamin D are highly prevalent in the United States, especially in areas without much sunshine,” Wang said. “Twenty to 30 percent of the population in many areas has moderate to severe vitamin D deficiency.”

Most of this is attributed to lack of sun exposure, pigmented skin that prevents penetration of the sun’s rays and inadequate dietary intake of vitamin D enriched foods, researchers said.

“A growing body of evidence suggests that low levels of vitamin D may adversely affect the cardiovascular system,” Wang said. “Vitamin D receptors have a broad tissue distribution that includes vascular smooth muscle and endothelium, the inner lining of the body’s vessels. Our data raise the possibility that treating vitamin D deficiency, via supplementation or lifestyle measures, could reduce cardiovascular risk.

“What hasn’t been proven yet is that vitamin D deficiency actually causes increased risk of cardiovascular disease. This would require a large randomized trial to show whether correcting the vitamin D deficiency would result in a reduction in cardiovascular risk.”

Therfore, Wang doesn’t recommend physicians check for vitamin D deficiency or that those with a known vitamin D deficiency be treated to prevent heart disease at this time.

During the past decade, researchers have studied several other vitamins that initially showed promise in reducing heart disease. But the vitamins didn’t reduce heart disease in subsequent large randomized trials.

“On the flip side, just because other vitamins haven’t succeeded doesn’t preclude the possibility of finding vitamins that might prevent cardiovascular disease,” Wang said. “This is always an area of great interest. Vitamins are easy to administer and in general have few toxic effects.”

The American Heart Association recommends that healthy people get adequate nutrients by eating a variety of foods in moderation, rather than by taking supplements. Food sources of vitamin D include milk, salmon, mackerel, sardines, cod liver oil and some fortified cereals. Vitamin or mineral supplements aren’t a substitute for a balanced, nutritious diet that limits excess calories, saturated fat, trans fat, sodium and dietary cholesterol. This dietary approach has been shown to reduce coronary heart disease risk in healthy people and those with coronary disease.

CryoCor, Inc. (Nasdaq: CRYO), a medical device company focused on the treatment of cardiac arrhythmias, announced the publication of a European study of atrial fibrillation patients treated with CryoCor’s Cardiac Cryoablation System. The purpose of the study was to evaluate the role of atrial flutter in the recurrence of atrial fibrillation and the effectiveness of an ablation strategy focused on isolating the pulmonary veins to treat the atrial fibrillation. The study was published in the December 11, 2007 issue of Circulation.

The 98-patient study was conducted by Dr. Wendel Moreira, Dr. Luz-Maria Rodriguez, Dr. Carl Timmermans and others in Academic Hospital Maastricht using CryoCor’s Cardiac Cryoablation System. The study prospectively evaluated the best catheter ablation strategy in patients with paroxysmal atrial fibrillation with and without concomitant right atrial flutter. During follow-up averaging 26 months, the authors found that electrical isolation of the pulmonary veins by catheter ablation was successful in patients without concomitant atrial flutter at an 82% success rate. In patients with concomitant atrial flutter, the combination of ablation for atrial flutter and pulmonary vein isolation alone to treat atrial fibrillation was frequently insufficient in preventing recurrences of atrial fibrillation (recurrence rate of 67%). The authors concluded that those patients with atrial flutter and atrial fibrillation may require additional sites of ablation to effectively treat their atrial fibrillation.

Dr. Rodriguez, senior author of the study, stated, “This is the first time that an ablation strategy for paroxysmal atrial filbrillation and atrial flutter has been systematically studied. This has implications for the tools that a clinician may use to treat these atrial arrhythmias. Based on this study, we do not believe that it will be sufficient to simply isolate the pulmonary veins in a significant proportion of patients.”

About CryoCor

CryoCor is a medical technology company that has developed and manufactures a disposable catheter system based on its proprietary cryoablation technology for the minimally invasive treatment of cardiac arrhythmias. The Company’s product, the CryoCor Cardiac Cryoablation System, or the Cryoablation System, is designed to treat cardiac arrhythmias through the use of cryoenergy, or extreme cold, to destroy targeted cardiac tissue. The Cryoablation System has been approved in Europe for the treatment of atrial fibrillation, and atrial flutter, the two most common and difficult to treat arrhythmias, since 2002. In the United States, CryoCor is conducting a pivotal trial to evaluate the safety and efficacy of the Cryoablation System for the treatment of atrial fibrillation and the Cryoablation System has been approved for the treatment of right atrial flutter. For more information please visit the Company’s website at http://www.cryocor.com

Forward Looking Statements

The statements in this press release that are not descriptions of historical facts are forward-looking statements that are subject to risks and uncertainties. These include statements related to the study’s results and conclusions drawn from the study’s results, all of which are prospective. Such statements are only predictions and reflect CryoCor’s expectations and assumptions as of the date of this press release based on currently available operating, financial, and competitive information. The actual events or results may differ materially from those projected in such forward-looking statements due to a number of factors, including risks involved with CryoCor’s technology and the diagnosis and treatment of atrial arrhythmias; risks associated with the Company’s dependence on patents and proprietary rights; risks associated with the Company’s protection and enforcement of its patents and proprietary rights; risks associated with the development or availability of competitive products or technologies; risks associated with the Company’s ability to maintain and achieve milestones under collaborative agreements and the other risks and uncertainties identified in the Company’s filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof. The Company expressly disclaims any intent or obligation to update any of these forward-looking statements.

CryoCor, Inc

http://www.cryocor.com

When cholesterol-clogged plaque narrows an artery that feeds the heart, the body responds by trying to bulk up tiny blood vessels in the heart. As these so-called collateral vessels grow more muscular and interconnected, they begin to reroute some of the blood flow around the blockage. Scientists have been trying for years to nudge collateral blood vessels to develop and prosper, but without great success. However, you can do it at home without anything more high-tech than a comfortable pair of shoes, reports the Harvard Heart Letter in its January 2008 issue.

Growing new collateral blood vessels can ease chest pain (angina), limit heart attack damage, improve survival, and perhaps even offer extra time for emergency therapy in the case of a heart attack. And exercise can boost these blood vessels.

Exercise dramatically increases blood flow through the coronary arteries. The inner lining of the arteries responds to this “stress” much as it does to the stress of atherosclerosis, by stimulating collateral blood vessels to elongate, widen, and form new connections.

The Heart Letter notes that a little bit of exercise won’t do the trick. You need to push your heart. If you aren’t used to exercising, that may mean brisk walking. Any activity that gets your heart beating faster will do as long as you keep it up for 20 to 30 minutes at a time and do it several times a week.

Exercise is a great way to prevent heart disease, and a host of studies show that it can help some people with narrowed coronary arteries safely avoid bypass surgery or angioplasty. The Harvard Heart Letter asks: Why not give yourself a natural bypass before you need a surgeon to perform a more painful and hazardous one?

Harvard Heart Letter
Harvard Health Publications Harvard Medical School 10 Shattuck St., Ste. 612
Cambridge, MA 02115
United States

http://www.health.harvard.edu

Since the year 2000, much has been learned about the potential for using transplanted cells in therapeutic efforts to treat varieties of cardiac disorders. With many questions remaining, the current issue of CELL TRANSPLANTATION (Vol.16 No. 9), The Proceedings of the Third Annual Conference on Cell Therapy for Cardiovascular Disease, presents research aimed at answering some of them. Eleven papers were included in this issue; the four below represent a sample.

Bench to Bedside

“Cardiac stem cell therapy involves delivering a variety of cells into hearts following myocardial infarction or chronic cardiomyopathy,” says Amit N. Patel, MD, MS, director of cardiac cell therapy at the University of Pittsburgh Medical Center and lead author of an overview and introductory article, Cardiac Stem Cell Therapy from Bench to Bedside. “Many questions remain, such as what types of cells may be most efficacious. Questions about dose, delivery method, and how to follow transplanted cells once they are in the body and questions about safety issues need answers. The following studies, contribute to the growing body of data that will move cell transplantation for heart patients closer to reality.”

According to Patel, special editor for this issue, suitable sources of cells for cardiac transplant will depend on the types of diseases to be treated. For acute myocardial infarction, a cell that reduces myocardial necrosis and augments vascular blood flow will be desirable. For heart failure, cells that replace or promote myogenesis, reverse apoptopic mechanisms and reactivate dormant cell processes will be useful.

“Very little data is available to guide cell dosing in clinical studies,” says Patel. “Pre-clinical data suggests that there is a dose-dependent improvement in function.”

Patel notes that the availability of autologous (patient self-donated) cells may fall short.

Determining optimal delivery methods raise issues not only of dose, but also of timing. Also, assessing the fate of injected cells is “critical to understanding mechanisms of action.”

Will cells home to the site of injury” Labeling stem cells with durable markers will be necessary and new tracking markers may need to be developed.

Improved cell survival drugs

Adult bone marrow-derived mensenchymal stem cells (MSCs) have shown great signaling and regenerative properties when delivered to heart tissues following a myocardial infarction (MI). However, the poor survival of grafted cells has been a concern of researchers. Given the poor vascular supply after a heart attack and an active inflammatory process, grafted cells survive with difficulty. Transmyocardial revasularization (TMR), a process by which channels are created in heart tissues by laser or other means, can enhance oxygenated blood supply.

“We hypothesized that using TMR as a scar pretreatment to cell therapy might improve the microenvironment to enhance cell retention and long-term graft success,” said Amit N. Patel, lead author of a study titled Improved Cell Survival in Infarcted Myocardium Using a Novel Combination Transmyocardial Laser and Cell Delivery System. “TMR may act synergistically with signaling factors to have a more potent effect on myocardial remodeling.”

Patel and colleagues, who used a novel delivery system to disperse cells in the TMR-generated channels in an animal model, report significant cell survival in the TMR+Cell group versus Cells or TMR alone. The researchers speculated that there was an increase in local production of growth factors that may have improved the survival of transplanted cells.

Stem cells depolarize

Recent studies have suggested that there are stem cells in the heart. In this study, researchers engineered mesenchymal stem cells (MSC) to over express stromal cell-derived factor-1 (SDF-1), a chemokine.

“Our study suggests that the prolongation of SDF-1 expression at the time of an acute myocardial infarction (AMI) leads to the recruitment of what may be an endogenous stem cell in the heart,” says Marc Penn, MD, PhD, director of the Skirball Laboratory for Cardiovascular Cellular Therapeutics at the Cleveland Clinic Foundation. “These cells may contribute to increased contractile function even in their immature stage.”

In the study titled SDF-1 Recruits Cardiac Stem Cell Like Cells that Depolarize in Vivo, researchers concluded that there is a natural but inefficient stem cell-based repair process following an AMI that can be manipulated through the expression of key molecular pathways. The outcome of this inefficient repair can have a significant impact on the electrical and mechanical functions of the surviving myocardium.

Grafting bioartifical myocardium for myocardial assistance

While the object of cell transplantation is to improve ventricular function, cardiac cell transplantation has had limited success because of poor graft viability and low cell retention. In a study carried out by a team of researchers from the Department of Cardiovascular Surgery, Pompidou Hospital, a matrix seeded with bone marrow cells (BMC) was grafted onto the infarcted ventricle to help support and regenerate post-ischemic lesions.

“Our study demonstrated that bone marrow cell therapy associated with the surgical implantation onto the epicardium of a cell-seeded collagen type 1 matrix prevented myocardial wall thinning, limited post-ischemic remodeling and improved diastolic function,” says Juan Chachques, MD, PhD, lead author for Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Clinical Trial): One year follow-up.

“The use of the biomaterial appears to create a micro atmosphere where both exogenous and endogenous cells find an optimal microenvironment to repair tissues and maintain low scar production,” explains Chachques.

According to Chachques, the favorable effects may be attributed to several mechanisms. The BMC seeded in the collagen matrix may be incorporated into the myocardium through epicardial channels created at the injection sites. Too, the cell-seeded matrix may help prevent apoptosis.

“This biological approach is attractive because of its potential for aiding myocardial regeneration with a variety of cell types,” concluded Chachques.

Those cell types include skeletal myoblasts, bone marrow-derived mensenchymal stem cells, circulating blood-derived progenitor cells, endothelial and mesothelial cells, adipose tissue stem cells and, potentially, embryonic stem cells.

“Cardiac stem cell repair is one of the most important new areas of research today,” says Cell Transplantation editor Paul Sanberg, PhD, DSc. “This special issue illustrates important new findings and the significant efforts being taken to develop these therapies and move them from the scientist’s bench to the bedside where in clinical practice they can make a difference in the lives of patients.”

CELL TRANSPLANTATION – The Regenerative Medical Journal

http://www.cognizantcommunication.com/filecabinet/Cell/ct.htm

Josh Bristow was in the late stages of heart failure when he came to the Emergency Department at Cedars-Sinai Medical Center on Aug. 25, 2007. Medications and the earlier implantation of a pacemaker had given him some time, but the 51 year old Studio City man’s heart could no longer supply the blood and oxygen his body needed, and he was running out of options.

Bristow is a long-term survivor of AIDS, which probably led to the deteriorating function of his heart (HIV-associated cardiomyopathy). The immune compromising nature of the illness virtually excluded him as a candidate for heart transplantation because of the increased risk of infection and the inability to undergo immunosuppression to prevent organ rejection.

But on Aug. 30, in an operation led by Sinan A. Simsir, M.D., surgical director of the Heart Transplant and Ventricular Assist Device Program at Cedars-Sinai’s Heart Institute, Bristow became one of a very few patients with AIDS to have a left ventricular assist device (LVAD) implanted as “destination therapy.” His heart remains in place, as does the previously implanted pacemaker, but the LVAD has taken on most of the organ’s workload.

Left ventricular assist devices are often used as a “bridge to transplant,” prolonging a patient’s survival until a donor heart becomes available. But for certain patients with AIDS, cancer and other conditions that preclude immunosuppressive therapy, an LVAD can now be considered a permanent solution, replacing the function of the left ventricle, the heart’s main pumping chamber, to return oxygenated blood into circulation.

“This option has not been considered frequently in patients with HIV or AIDS because of the associated infections, pneumonias and other considerations that are common with the illness. In this case, Mr. Bristow was here at just the right time, when no other infections were going on. I think it was a timing issue as well as a recognition among our team members that this therapy may be possible for him,” said Lawrence Czer, M.D., medical director of the Heart Transplant Program and director of Transplantation Cardiology.

According to cardiologist Ernst R. Schwarz, M.D., Ph.D., members of the LVAD team are making an effort to provide information in community settings on heart failure and treatment options. “Patients and even many physicians are not familiar with left ventricular assist devices. They may think of them as a research tool or a useful device for very special cases, but they are not aware that they may be considered a routine option for an end-stage heart failure patient,” he said.

Only a few hospitals in the nation maybe about three dozen, estimates Simsir are approved to offer LVADs for destination therapy. The treatment is generally covered by Medicare, Medicaid and insurance plans for appropriate patients.

The device is placed on top of the stomach, under the muscles of the abdomen. One tube is attached to the heart’s left ventricle and another goes to the aorta. Thin electrical cords exit the body through an opening in the skin and connect to an external “fanny pack” of rechargeable batteries, giving the patient the freedom to live at home with few limitations.

“Although the operation is relatively straightforward, there is risk with this or any other surgical procedure,” Simsir said, adding that possible complications include stroke, post-operative bleeding and device malfunction. Risk of infection, especially in patients with compromised immune systems, is one of the greatest concerns.

“Artificial devices do not have the natural defenses of white blood cells and mechanisms in the tissues to prevent infection, which means we have to be meticulous in surgery and post-operatively, with the use of antibiotics and other measures to keep the device from becoming infected,” said Czer. “Judgment is needed in deciding whether to proceed with this therapy. It is not for everyone with HIV or AIDS, but in a selected population, this does offer some hope to patients who would be in an otherwise hopeless situation.”

Schwarz said that because the device is mechanical with electronic components, members of the LVAD team, including coordinators, electrical technicians and sometimes physicians, visit patients’ homes to be sure electrical systems are adequate and there is always a power backup. They also teach patients, family members and others the steps to take in an emergency.

Like most patients reaching end-stage heart failure, Bristow was extremely sick, with numerous systems shutting down from lack of oxygen. Considering his poor health going in, the doctors have been more than satisfied with his progress. He was discharged from Cedars-Sinai on Oct. 8 and is continuing to regain his strength at home.

“The sickness continues after you put the pump in, and that’s when the patient needs very good medical care. But with the pump completely emptying the heart and getting the blood flowing, gradually the liver gets better and the kidneys get better. The changes in Josh have been really dramatic,” Simsir said.

Bristow worked for an information technology company for 27 years before going on disability a year and a half ago. He looks forward to being able to return to his hobbies of candle-making and working in his patio garden, which, he adds, clearly needs attention.

When he and his domestic partner, Don, moved from Florida to Southern California in the mid-1990s, Bristow thought AIDS would take his life in just a few years. But with improvements in medical treatment, his expectations changed. “Here I am, 11 years later, still around, and I want to say fighting, because I don’t want to go. I hate not working but I’m happy to be alive,” he said.

The first in Southern California and one of only 10 hospitals in the state whose nurses have been honored with the prestigious Magnet designation, Cedars-Sinai Medical Center is one of the largest nonprofit academic medical centers in the Western United States. For 19 consecutive years, it has been named Los Angeles’ most preferred hospital for all health needs in an independent survey of area residents. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities as well as breakthroughs in biomedical research and superlative medical education. It ranks among the top 10 non-university hospitals in the nation for its research activities and is fully accredited by the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP). Additional information is available at http://www.cedars-sinai.edu.

Cedars Sinai Medical Center
8700 Beverly Blvd., Rm 2429A
Los Angeles, CA 90048
United States

http://www.cedars-sinai.edu

A University of Leicester academic has given evidence to the House of Lords’ Science and Technology Committee.

Dr William Toff, Senior Lecturer in Cardiology, gave expert evidence to the inquiry on Air Travel and Health. He told the committee that, “for the average traveller, the use of aspirin is a relatively ineffective intervention” in the prevention of DVT. Whilst it undoubtely has a role in reducing the risk of arterial thrombosis it has only a modest effect in the prevention of venous thrombosis. Indeed, in some cases the use of aspirin may be counterproductive.

Dr Toff went on to say that “you have to treat a lot of people to prevent one thrombosis and the estimate would be something in the region of treating 24,000 people to prevent one thrombosis. On the other hand, the number that you need to treat for harm from aspirin is in the region of one in 17,000″ . In other words, on the balance of probabilities, and for the population as a whole, taking aspirin as prophylaxis may be more likely to do harm than good.

Dr Toff is a member of the Scientific Executive Committee responsible for the design and implementation of the WRIGHT project into the health risks of long haul flights.

His team also led the studies to investigate the possible effects of low pressure and low oxygen in the aeroplane cabin on the risk of thrombosis. The research found no evidence of such effects.

Dr Toff said: “The first phase of the WRIGHT Project has improved our understanding of the scale of the problem of travellers’ thrombosis and its underlying causes. For most people, the risk is very low but they should regularly exercise their legs when seated for prolonged periods and get up or interrupt long journeys to take a walk from time to time. That applies not just to air travel but to long journeys by car, bus or train. For people with known risk factors for thrombosis, the risk from long-distance travel may be much greater and they should discuss the need for other preventive measures with their doctor.”

The study did not investigate effective preventive measures against DVT and VTE. However, experts recognize that blood circulation can be promoted by exercising the calf muscles with up-and-down movements of the feet at the ankle joints. Moving the feet in this manner encourages blood flow in the calf muscle veins, thus reducing blood stagnation. People should also avoid wearing tight clothing during travel, as such garments may restrict blood flow.

Phase I of the WRIGHT project concludes that there is a need for travellers to be given appropriate information regarding the risk of VTE by transport authorities, airlines, and medical professionals. Further studies are needed to identify effective preventive measures. This will comprise Phase II of the project, which requires additional funding before it can begin.

Individuals with questions regarding prevention of VTE should consult their physicians before travelling.

Background on the WRIGHT project:

In 2000, media and public attention was focused on the risk of thrombosis in long-haul travellers, following the death from pulmonary embolism of a young English woman who returned on a long-haul flight from Australia. In the same year, a report from the Select Committee on Science and Technology of the United Kingdom House of Lords recommended research into the risk of DVT. Following a consultation of experts convened by WHO in March 2001, the WRIGHT Project was initiated. Phase 1 was funded by the UK Government (Department for Transport and Department of Health) and the European Commission.

The objectives of Phase I were to confirm whether the risk of venous thromboembolism (VTE) is increased by air travel and to determine the magnitude of risk.

The studies were conducted under the auspices of WHO and performed by an international collaboration of researchers from the Universities of Leiden, Amsterdam, Leicester, Newcastle, Aberdeen and Lausanne. There were five studies: a population based case control study to investigate the risk factors of VTE; two retrospective cohort studies among employees of international organizations and Dutch commercial pilots to investigate the actual risk of VTE related to air travel; two pathophysiological studies to investigate the influence of immobility on VTE related to travel and the influence if any of low oxygen and low pressure in the cabin of air crafts on VTE related to travel.

University of Leicester

http://www.le.ac.uk

Otsuka Pharmaceutical Development & Commercialization, Inc. announced recently that the U.S. Food and Drug Administration has accepted a new drug application (NDA) for the company’s investigational oral once-daily medication tolvaptan, a selective V2-vasopressin receptor antagonist, for two indications: treatment of adults with worsening heart failure and treatment of hyponatremia1. These indications are based on data from three phase 3 pivotal trials2.

OPDC was established in 2007 by Otsuka America, Inc. (OAI). OPDC is wholly owned by OAI, which is the holding company for Otsuka Pharmaceutical Co., Ltd. (OPC) interests in the U.S. OAI is wholly owned by OPC.

Tolvaptan is a novel, investigational small molecule designed to be an antagonist of the vasopressin V2 receptor, which plays a role in the kidney’s regulation of fluid excretion. The majority of patients hospitalized for worsening heart failure have edema or excess body fluid, which is treated with diuretics to excrete the fluid. In contrast to diuretics, tolvaptan is designed to promote aquaresis, the excretion of electrolyte-free water. In clinical trials, the most common adverse reactions in patients with worsening heart failure (incidence greater than or equal to 5% in patients treated with tolvaptan and double the incidence of patients treated with placebo) were thirst, dry mouth and polyuria. In patients with hyponatremia, the most common adverse reactions in clinical trials (incidence greater than or equal to 5% in patients treated with tolvaptan and double the incidence of patients treated with placebo) were thirst, dry mouth, asthenia, constipation, pollakiuria and hyperglycemia. The most serious adverse events were cardiogenic shock (1.7% in patients receiving tolvaptan vs. 1.2% of patients receiving placebo), pulmonary embolism (1.3% in patients receiving tolvaptan vs. 0.8% for patients receiving placebo,) and gout (4.7% in patients receiving tolvaptan vs. 3.9% in patients receiving placebo). For all of these, the number of patients that received tolvaptan was 2063 and for placebo was 2055 in addition to standard of care.