Study shows heart attack disparity between men & women

A Middle East regional study by researchers from the Gulf Heart Association shows that 70% of female heart attack victims suffer from hypertension, compared to 43% of males.

Their findings come from an analysis of Gulf Race – the Gulf Registry for Acute Coronary Events, which looked at the death-rate of 8,166 males and females hospitalised for acute coronary syndrome (ACS) in Bahrain, Kuwait, Qatar, Oman, UAE and Yemen.

ACS includes heart attack and unstable angina.

As part of the study it was revealed that on average women were nine years older than men when they suffered from ACS, and were more likely to have hypertension (70% vs 43%), diabetes (55% vs 36%), high cholesterol (44% vs 28%), and to be obese than their male counterparts.

The study also found that female patients who had suffered a certain type of heart attack were 1.75 times more likely to die while in hospital than males, in part because cardiovascular drugs and post- ACS interventions were underused in the women’s group – findings that have been previously documented in eight similar studies across the world.

Dr Wael Mahmeed, President of the Emirates Cardiac Society and one of the principal investigators of Gulf Race, commented: “The study confirms that hypertension is a major risk factor for ACS among women in the Gulf, alongside diabetes, dyslipidemia and obesity.

This underscores the importance of regular blood pressure checks for women, especially as they get older, and making sure females are prescribed the correct cardiovascular medications to treat hypertension. “Higher in-hospital death rates among women with ACS compared to men is also very worrying.

It shows that greater emphasis must be put on diagnosing ACS in women, and may indicate a greater need for training among medical personnel in spotting the signs and symptoms of the disease in women which are different to those in men. Speedy diagnosis is essential for ACS treatments to be effective.”

In an effort to promote awareness among doctors about the diagnosis and treatment of hypertension, the drug company Novartis sponsored a regional lecture tour by Professor Bjorn Dahlof, a renowned specialist in cardiovascular medicine and hypertension. In January he gave talks in Dubai, Abu Dhabi, Beirut, Kuwait City, and Doha.

HIV enzyme discovery could be treatment key

Scientists have finally discovered the structure of a key enzyme found in HIV and similar viruses, a breakthrough that has crucial implications for HIV treatment. Researchers from Imperial College London, in the UK, and Harvard University, in the US, developed a crystal that could reveal the structure of integrase – an enzyme used by HIV to integrate its genetic material into a host cell.

Many researchers had tried and failed to unravel the threedimensional structure of integrase, which is bound to viral DNA. When someone is infected with HIV, the virus uses integrase to paste a copy of its genetic information into the person’s DNA.

The new study, published in the latest edition of Nature, revealed how a class of lifeprolonging antiretroviral drugs – integrase inhibitors – functions. The drugs work by blocking integrase, but for a long time scientists did not understand fully how the medicines managed to do this, or how to improve them.

“We now know how drugs that target integrase – such as Isentress [an integrase inhibitor produced by pharmaceutical company Merck & Co] – bind to and block integrase, meaning it is now possible to improve the drugs on the market,” Dr Peter Cherepanov, of Imperial College London, one of the study’s lead authors, told IRIN/PlusNews.

“Now we have this information, drug developers can modify the available drugs to work better – for instance, to bind tighter to integrase,” he said. “We will also be able to better understand and explain HIV drug resistance, since we now know how these HIV drugs work.”

Using a version of integrase borrowed from a retrovirus similar to HIV, the researchers were able to grow a crystal after more than 40,000 unsuccessful attempts. “This is the holy grail of HIV research,” said Dr Matilu Mwau, a virus researcher at the Kenya Medical Research Institute.

“It has the potential to increase the repertoire of drugs to treat HIV; it opens a whole new door for manufacturers of HIV medication.” “In the developing world we do not tailor-make drug combinations for HIV patients – we treat HIV from a public health perspective, where most people are put on a similar combination,” he said.

“More drugs available mean better chances for people to be put on secondand third-line treatment regimens where first-line drugs don’t work.”

Some morbidly obese people are missing part of their DNA

According to a new study published in Nature, around 7 in every 1,000 morbidly obese people are missing a part of their DNA, containing approximately 30 genes.

This genetic variation was not found in normal weight people. The researchers from 11 European centres believe the missing DNA may have a dramatic effect in some people’s weight.

Researchers believe that the weight problems of around one in twenty morbidly obese people are due to known genetic variations, including mutations and missing DNA. Many more similar obesitycausing mutations, such as the one in this study, remain to be found, says the team. Previous research had identified several genetic variations that contribute to obesity, most of which are single mutations in a person’s DNA that change the function of a gene.

This research is the first to clearly demonstrate that obesity in otherwise physically healthy individuals can be caused by a rare genetic variation in which a section of a person’s DNA is missing.

The researchers do not yet know the function of the missing genes, but previous research has suggested that some of them may be associated with delayed development, autism and schizophrenia.

Professor Philippe Froguel, lead author of the study from the School of Public Health at Imperial College London, said: “Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic.

It is becoming increasingly clear that for some morbidly obese people, their weight gain has an underlying genetic cause. If we can identify these individuals through genetic testing, we can then offer them appropriate support and medical interventions, such as the option of weight loss surgery, to improve their long-term health.”

● Citation: “A new highly penetrant form of obesity due to deletions on chromosome 16p11.2”, P. Froguel et al. Nature 463, 671-675 (4 February 2010), doi:10.1038/ nature08727

Cancer stem cells suppress immune system

Cancer-initiating cells that launch glioblastoma multiforme, the most lethal type of brain tumor, also suppress an immune system attack on the disease, scientists from the University of Texas M. D. Anderson Cancer Center report in a paper published 15 January 2010 in Clinical Cancer Research.

The researchers demonstrate that this subset of tumor cells, also known as cancer stem cells, stifles the immune response in a variety of ways, but that the effect can be greatly diminished by encouraging the stem cells to differentiate into other types of brain cell.

“We’ve known for years that glioblastoma and cancer patients in general have impaired immune responses,” said senior author Amy Heimberger, MD, an associate professor in M. D. Anderson’s Department of Neurosurgery. “Our research uncovers an important mechanism that shows how that happens.

The cancer stem cells inhibit T cell response, and it is these T cells that recognise and eradicate cancer.” She explained that there were multiple research groups around the US, including hers, trying to develop vaccines or other immunotherapeutics against glioma stem cells.

These findings that show that “the stem cell may deliver a fatal blow back to the immune system will help us understand how to design immune-based therapies".

Could two be tipping point for childhood obesity?

Research published in the February 2010 issue of Clinical Pediatrics suggests that the “tipping point” in obesity often occurs before two years of age, and sometimes as early as three months, when the child is learning how much and what to eat.

Often obese infants grow up to be obese teens saddling them with type-2 diabetes, elevated cholesterol and high blood pressure, according to the article.

“I really think this should be a wake up call for doctors,” said principal investigator Dr John Harrington, a paediatrician at Children’s Hospital of The King’s Daughters and an assistant professor at Eastern Virginia Medical School in the US. “Too often, doctors wait until medical complications arise before they begin treatment. What this study suggests is that prevention of obesity should begin far, far earlier.” This US-based study comes in the midst of alarming rates of childhood obesity in many countries around the world, including several in the Middle East.

The researchers examined records from a paediatric practice of 111 children whose body mass index (BMI) exceeded 85% of the general population. Researchers determined that these children had started gaining weight in infancy at an average rate of .08 excess BMI units per month. On average, this progression began when the children were three months old. Over half the children became overweight at or before age 2 and 90% before reaching their 5th birthday.

The Clinical Pediatrics study suggests obesity prevention efforts should begin before age two, when children reach a “tipping point” in a progression that leads to obesity later in life. “Our study suggests that doctors may want to start reviewing the diet of children during early well-child visits,” said Harrington.

“Getting parents and children to change habits that have already taken hold is a monumental challenge fraught with road blocks and disappointments. This study indicates that we may need to discuss inappropriate weight gain early in infancy to affect meaningful changes in the current trend of obesity.”

● Citation: “Identifying the “Tipping Point” Age for Overweight Pediatric Patients” CLIN PEDIATR OnlineFirst, published on 11 February 2010 as doi:10.1177/ 0009922809359418

● The article is available free for a limited time at: dpdf/0009922809359418v1

HMGB1 protein triggers islet cell rejection

Researchers at RIKEN and Fukuoka University have pinpointed the mechanism responsible for early rejection of transplanted pancreatic islet cells in the treatment of type 1 diabetes, also known as juvenile diabetes.

A new system based on this mechanism has been shown to vastly increase transplant efficiency, setting the stage for the development of powerful new treatment techniques.

Currently, the most widelyused treatment for type 1 diabetes is the regular injection of insulin, a burdensome task for patients. Islet cell transplantation, whereby insulinproducing cells from a donor pancreas are transplanted into the patient’s liver, is a promising alternative approach. However, it has achieved limited success due to a strong and rapid immune-mediated rejection of the transplanted islets.

With their discovery, the researchers have demonstrated that HMGB1 (high-mobility group box 1), a nuclear protein whose precise function has heretofore remained elusive, is in fact produced by the islet cells and directly triggers their early rejection.

Based on this finding, they developed a system to measure the level of HMGB1 in the blood and determine the onset of rejection, information which they used to establish a treatment four times more effective than earlier islet transplantation protocols.

While shedding light on a previously-unknown function of a major nuclear protein, the discovery of the HMGB1- mediated pathway also represents a breakthrough in diabetes research. For millions of diabetes sufferers around the world, its application to islet transplantation promises great improvements in this technique, bringing dreams of insulin independence one step closer to reality.

● This paper is published in the February 2010 issue of The Journal of Clinical Investigation. Read the paper here: 0?key=82f6533c5783a48c4c6c

Ambidextrous kids more likely to have learning problems

Children who are mixedhanded, or ambidextrous, are more likely to have mental health, language and scholastic problems in childhood than right- or left-handed children, according to a new study published 25 January 2010 in the journal Pediatrics.

The researchers behind the study, from Imperial College London and other European institutions, suggest that their findings may help teachers and health professionals to identify children who are particularly at risk of developing certain problems. Around one in every 100 people is mixed-handed.

The study looked at nearly 8,000 children, 87 of whom were mixed-handed, and found that mixed-handed 7 and 8-year old children were twice as likely as their right-handed peers to have difficulties with language and to perform poorly in school.

When they reached 15 or 16, mixed-handed adolescents were also at twice the risk of having symptoms of attention deficit/hyperactivity disorder (ADHD).

They were also likely to have more severe symptoms of ADHD than their right-handed counterparts. The adolescents also reported having greater difficulties with language than those who were left- or righthanded.

This is in line with earlier studies that have linked mixed-handedness with dyslexia. Little is known about what makes people mixed-handed, but it is known that handedness is linked to the hemispheres in the brain.

Researchers take first steps to new class of antibiotics

Researchers have made the first step towards creating a new class of antibiotics by revealing the structure of a protein called Gp2.

This protein is produced by the T7 virus, which only targets bacteria and which infects and kills them by interfering with the way in which they express genes.

The research is published in the 19 January 2010 issue of Proceedings of the National Academy of Sciences. Gp2 works by interfering with RNA Polymerase, which represents the central machinery that enables information contained in their genes to be “read”.

If the RNA Polymerase is unable to function, the bacteria cannot survive. This is the first study to look at the shape of a protein that is able to strongly inhibit RNA Polymerase and is derived from a virus.

There is already a group of clinically used antibiotics, known as rifamycin, which interfere with the RNA polymerase from bacteria, but against which many bacteria have developed resistance. Accordingly, the researchers hope that if new drugs can be devised that mimic Gp2, these will be less susceptible than existing antibiotics to antibiotic resistance, because they will work in a different way to the antibiotics that are currently available.

The next step for this research will be for scientists to identify small molecule mimics of Gp2 that can be used to create these drugs.

Dr Sivaramesh Wigneshweraraj, who conducted the analyses of how Gp2 interferes with the intricate functionalities of the bacterial RNA polymerase, said: “This work is at a very early stage, but knowing the shape of viral proteins like Gp2 and how they operate represents an important first step towards creating new drugs against bacteria from viruses that infect and kill bacteria.”

New radiotracer dose for paediatric PET

Researchers in the United States have shown that PET (positron emission tomography) scans are safe for use as a diagnostic tool in paediatric conditions and have developed a new radiotracer dose regimen based on body weight.

In a study published in the February issue of The Journal of Nuclear Medicine (JNM), researchers at the Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania (Penn) gathered data that may provide clinicians with new formulas – specific to paediatrics – to calculate the amount of radiotracer that should be injected based on the patient’s weight.

Researchers report in their study that when following an injection protocol proportional to weight, the data quality of PET images was found to improve with decreasing weight. The study provides practical injection protocols to trade this advantage for decreased scan time or dose at constant image quality.

“These findings mean that PET can be used in children with methods that are even more patient-specific than those currently employed,” said Roberto Accorsi, PhD, former research assistant professor of radiology at CHOP-Penn and lead author of the study. In nuclear medicine, there are well-established guidelines for administering radiopharmaceutical doses for adults; however, there is little guidance for administering paediatric doses.

Thus, the CHOPPenn study sets out to examine how nuclear medicine physicians can take into consideration a child’s lighter weight and body size and adjust the dose and scan time accordingly, while maintaining highquality imaging for the best diagnosis possible.

“The results of this study show that, due to children’s relatively small size and light weight, it is possible to reduce radiological dose (or scan time) while preserving image quality as compared to PET imaging in adults,” said Dr Accorsi.

● Citation: “Improved Dose Regimen in Pediatric PET” , R. Accorsi et al, J Nucl Med 2010, doi:10.2967/jnumed. 109.066332

Physicians mum on end-oflife talks with cancer patients

Despite guidelines recommending that physicians discuss end-of-life options with terminally-ill patients who have less than a year to live, most who see cancer patients would not do so as long as their patients are feeling well, according to a new study published online in Cancer in January this year.

According to a survey of physicians in the United States, most of them opted to wait for symptoms to develop or until there are no more treatments to offer before discussing end-of-life options.

US guidelines recommend discussions of end-of-life issues when patients have limited time left so that patients’ preferences can be met. Some evidence suggests that when these discussions occur, individuals have better experiences with death.

To determine the extent to which physicians follow these recommendations, Nancy Keating, MD, MPH, of the Brigham and Women’s Hospital and Harvard Medical School in Boston and colleagues surveyed a national sample of 4,074 physicians who care for cancer patients.

The survey questioned physicians about end of life issue discussions – prognosis, preferences for resuscitation, hospice care, etc. – with patients who had four to six months to live but who were currently feeling well. While 65% of physicians would discuss prognosis now, fewer would discuss patients’ preferences for resuscitation (44%), hospice (26%), or where patients would like to die (21%). Instead, most would wait until patients felt worse or until no more treatment options were available.

The survey also found that younger physicians and physicians who were not cancer specialists would discuss endof- life options sooner than older doctors and cancer specialists. Dr Keating noted that research was needed to understand doctors’ reasons for putting off end-of-life discussions with terminally-ill cancer patients who are feeling well. “Most physicians may delay end-of-life discussions because they are difficult and time consuming,” she said, and added that it is also possible that physicians disagree with the guidelines, which are based primarily on expert consensus because data are limited.

● Citation: “Physician factors associated with discussions about end-of-life care.” Nancy L. Keating, Mary Beth Landrum, Selwyn O. Rogers, Jr., Susan K. Baum, Beth A. Virnig, Haiden A. Huskamp, Craig C. Earle, and Katherine L. Kahn. CANCER; Published Online: January 11, 2010 (DOI: 10.1002/cncr.24761).

Serotonin may have role to play in SIDS

The brains of infants who die of sudden infant death syndrome (SIDS) produce low levels of serotonin, a brain chemical that conveys messages between cells and plays a vital role in regulating breathing, heart rate, and sleep, reported researchers in the United States.

SIDS is the death of an infant before his or her first birthday that cannot be explained after a complete autopsy, an investigation of the scene and circumstances of the death, and a review of the medical history of the infant and of his or her family. According to the US National Center for Health Statistics, SIDS is the third leading cause of infant death, claiming more than 2,300 lives in 2006.

The researchers theorise that this newly discovered serotonin abnormality may reduce infants’ capacity to respond to breathing challenges, such as low oxygen levels or high levels of carbon dioxide. These high levels may result from rebreathing exhaled carbon dioxide that accumulates in bedding while sleeping face down.

The findings appear in the 3 February issue of The Journal of the American Medical Association.

“We have known for many years that placing infants to sleep on their backs is the single most effective way to reduce the risk of SIDS,” said Alan E. Guttmacher, MD, acting director of the US-based Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

“The current findings provide important clues to the biological basis of SIDS and may ultimately lead to ways to identify infants most at risk as well as additional strategies for reducing the risk of SIDS.”

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