Balding gene

A variant of the androgen receptor gene could be responsible for hair loss in men, according to a study headed by Professor Markus Nöthen of the Life & Brain Centre of the Bonn University Clinic and Dr Roland Kruse of the Skin Clinic at Düsseldorf University Clinic.

The findings are also interesting in terms of how hair loss is inherited. The gene for the androgen receptor lies on the X chromosome. Men always inherit the X chromosome from their mother. In many cases men therefore take after their grandfather on their mother's side rather than their father.

However, this defect is not simply caused by one gene: "We have indications that other genes are involved which are independent of the parents' sex," Prof. Nöthen stressed. The hereditary defect can sometimes be passed on directly from father to son. For several years the researchers searched nationwide for families in which several men were affected by hair loss.

In blood samples taken from the volunteers they then looked for candidate genes. Initially they succeeded in narrowing down the search to a series of areas on various chromosomes. In an area where the largest contribution was suspected lay the gene for the androgen receptor. "One variant of this gene was found among men who suffered from premature balding at a very early stage very much more often than among men who still had a full head of hair when over 60," said Professor Nöthen. The genetic variant probably results in more androgen receptors in the scalp.

"Our findings permit two explanations," explained Axel Hillmer from Prof Nöthen's team. "Either more androgen receptors are formed among the men affected, or the variant of the receptor which develops as a result of the genetic change is more stable and is not broken down so quickly. Both mechanisms can lead to the effect of the androgens becoming greater, which in turn brings about hair loss."



Pertussis vaccine

The US Food and Drug Administration (FDA) has approved the first combination vaccine for adolescents that provides a booster immunisation against pertussis (whooping cough) in combination with tetanus and diphtheria.

The vaccine will be marketed as Boostrix by GlaxoSmithKline. Pertussis is a highly communicable disease of the respiratory tract that can be especially serious for infants less than one year old; it may even be fatal. Pertussis can cause spells of coughing and choking that make breathing difficult.

The disease is generally less severe in adolescents, but it is thought that they might transmit the disease to susceptible infants and other family members. In the past 20 years, rates of pertussis infection have been increasing in very young infants who have not received all their immunisations as well as in adolescents and adults.

Boostrix is a Tetanus Toxoid (T), Reduced Diphtheria Toxoid (d) and Acellular Pertussis vaccine (ap), Adsorbed. Although booster vaccines for adolescents containing T and d are currently licensed and marketed for use in this age group, none contain a pertussis component. Boostrix has the same components as Infanrix, a DTaP vaccine for infants and young children, but in reduced quantities.

Boostrix is indicated for use as a single booster dose to adolescents 10-18 years of age.



Breast cancer test

A test that measures how quickly cells are dividing is an accurate way for doctors to predict the aggressiveness of breast cancer tumours, even among women with very early stages of the disease, researchers told the second ESMO Scientific & Educational Conference (ESEC) in Budapest, Hungary, recently.

The findings will help clinicians decide which patients will benefit most from treatment with more intensive chemotherapy. For most women whose invasive breast cancer is detected early prognosis is generally excellent. But the group includes dramatically different subgroups of patients who need to be identified in order to perform the most effective treatment.

Clinicians know that the molecule Ki67 is a good indicator of cell proliferation rate and the marker is already used to define the aggressiveness of later stages of breast cancer. Dr Monica Giovannini and colleagues from the University of Verona in Italy analysed 4,250 patients with early invasive breast cancer and correlated Ki67 levels with tumour size, nodal status and other parameters.

"We found that high cell proliferation rate, measured as Ki67 levels, correlates with larger tumour size, axillary nodal involvement, higher grading, lymphovascular invasion, ER and PgR negativity, c-erbB2 overexpression, p53 mutation, younger age at diagnosis and symptomatic presentation," Dr Giovannini said. "All these factors are well-known markers of poor prognosis."

The same findings were also valid when the 'pT1' subgroup of the very earliest stage cancers was considered. "This means that very early invasive breast cancer gathers very different tumours in terms of prognosis. Ki67 could be a reliable and easily obtainable marker in order to identify which pT1s have worse prognoses," Dr Giovannini said. Commenting on the data, Dr Ahmad Awada from Jules Bordet Institute, Brussels, Belgium, said it confirmed that Ki67 is a prognostic indicator in early breast cancer.

"In clinical practice, tumours with a pathological size of <1cm are a true challenge in term of therapeutic decision (mainly chemotherapy indication). Consequently, it will be important to correlate Ki67 expression and prognostic in these very small tumours, which ultimately could help us to use this 'easy-to-perform' parameter in the selection of therapeutic approach."



Ebola, Marburg vaccines

Scientists from the Public Health Agency of Canada (PHAC) – with assistance from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) – have developed vaccines against the Ebola and Marburg viruses in nonhuman primates.

In a study published recently in Nature Medicine, Canadian researchers Dr Heinz Feldmann and Dr Steven Jones of PHAC's National Microbiology Laboratory and Dr Thomas Geisbert of USAMRIID report that the vaccines have proven 100% effective in protecting monkeys against infection from these often deadly viruses.

Monkeys are known to develop haemorrhagic fever symptoms similar to those observed in humans infected by the viruses. Demonstrating that these vaccines are safe and effective in monkeys is a promising indicator of their real potential for use in humans.

"When you see the tragedies these viruses cause, it's very frustrating that we can't do more to help people," said Dr Feldmann who, along with Dr Jones and others from PHAC, has been providing on-site rapid diagnostic support to the current Marburg outbreak in Angola.

"It'll be some time before we can use these vaccines in the field, but it's satisfying to know that we're getting closer." According to Dr Geisbert, this is the first vaccine system, or platform, that has protected non-human primates from both Ebola and Marburg. "In addition, the vaccine targets dendritic cells, which are the same cells that Ebola and Marburg attack," said Dr Geisbert.

"These cells are also important in generating a protective immune response. So the vaccine goes exactly where we want it to go." PHAC's National Microbiology Laboratory in Winnipeg is Canada's only Containment Level 4 laboratory, where pathogens such as Ebola and Marburg can be worked with safely. The laboratory has been at the forefront of research into SARS, West Nile virus, anthrax and other dangerous pathogens.



New heart failure guide

New ESC Guidelines for the Diagnosis and Treatment of Chronic Heart Failure have been released by the European Society of Cardiology (ESC). The guidelines offer up-todate practical recommendations on the diagnosis, assessment and treatment of chronic heart failure.

They have been specifically formulated for use in clinical practice, as well as in epidemiological surveys and clinical trials, and feature a new chapter on the diagnosis of heart failure with preserved ejection fraction (diastolic heart failure). “These updated guidelines are more user-friendly and tailored to the needs of practising physicians,” said Professor Kenneth Dickstein of Stavanger University Hospital, Norway, member of the Committee for Practice Guidelines of the ESC and President-Elect of the Heart Failure Association of the European Society of Cardiology.

“Since the last Guidelines on Chronic Heart Failure were issued in 2001, there have been substantial developments in the area of heart failure overall. The whole approach has also become more multidisciplinary. We are increasingly seeing a trend towards hospital-based heart failure management programmes and recognising the multifaceted role of natriuretic peptides in heart failure.

“The last Guidelines were not particularly deviceoriented, but since then there have been important advances with strong trial evidence, most specifically in Cardiac Resynchronisation Therapy (CRT) and Implantable Cardiac Defibrillation (ICD), which are appropriately represented in the update with practical recommendations.”

Furthermore, studies such as CHARM and VALIANT have demonstrated the efficacy of Angiotensin Receptor Blockers (ARB). ARBs are increasingly used in routine management and reflect the impact of the newer documentation. “These Guidelines also recognise the impact of the extensive co-morbidity in this population, the importance of the large geriatric population and the special needs of patients with advanced heart failure”.

The ESC Guidelines for the Diagnosis and Treatment of Chronic Heart Failure are available in a variety of formats which can be accessed and/or ordered from www.escardio.org



Insulin pill

Moscow chemists have found a way to produce insulin in pill-form instead of injections.

To control blood sugar levels diabetics have to inject insulin up to several times a day. The lack of timely injection may have fatal results.

The pills would significantly simplify their lives, however the fact that insulin is quickly destroyed when in contact with stomach acid significantly complicates the creation of pilled insulin.

Researchers at the Chemical Faculty, Lomonosov Moscow State University, have overcome this problem by developing a multi-layered polymeric capsule using positive protamin and negative dextransulphate. These polymeric capsules are stable and remain intact in both an acid and neutral medium but gradually excrete insulin at pH +5, accelerating at pH +8.

Such pH-dependent protection means the insulin pill is stable in the stomach but will excrete insulin as it moves to the small intestine and ileum where the pH reaches 6 to 8 units. The polymers used to create the capsules are naturally biodegradable and are easily destroyed by enzymes once their job is done.



Metabolic Syndrome

A May workshop in Brussels aimed to highlight among industry professionals the prevalence and economic impact of the metabolic syndrome as part of the wider Lipgene project.

Estimates suggest that adult obesity across the EU ranges from 10-25% and may be as high as 30%. Many more people are overweight and the prevalence continues to rise. The storage of excess fat increases an individual’s risk of developing risk factors for life-threatening diseases such as cardiovascular disease (CVD).

A number of these risk factors, including abdominal obesity, insulin resistance, low HDL cholesterol, high blood triglycerides and raised blood pressure, are now recognised as manifestations of the metabolic syndrome when they occur together. The metabolic syndrome, in turn, poses a risk to health:

- people with metabolic syndrome have a five-fold greater risk of developing type two diabetes, which is becoming more common in line with obesity trends

- people with metabolic syndrome are twice as likely to die from CVD and three times as likely to have a heart attack or stroke compared to people without the syndrome.

Several of these symptoms usually require treatment with prescription drugs. With an estimated 25% of the adult population in some EU member states being affected by the metabolic syndrome, this is resulting in huge costs to the healthcare system, or to individuals themselves in those countries with a healthcare system that is not free to the user. These costs are set to rise as an estimated 31 million people across Europe will need treatment for diabetes and related complications by 2010 – just one of the conditions associated with the metabolic syndrome.

No single treatment for the metabolic syndrome exists yet but lifestyle changes, for example changes in diet and an increase in physical activity, form the underlying strategy for both prevention and treatment.

Specific approaches to managing the metabolic syndrome are being considered within the Lipgene project, including ways in which to make it easier for people to eat a diet which can benefit cardiovascular health, and therefore reduce their risk of developing the metabolic syndrome, type two diabetes and cardiovascular disease (CVD).

For further information on the metabolic syndrome and the Lipgene project visit: www.nutrition.org.uk/lipgene



Foam for varicose veins

Injecting patients with a foam that expands in the blood vessels can successfully treat troublesome varicose veins, say doctors. Between 20% and 30% of adults develop varicose veins, usually later in life or during pregnancy.

As well as looking unpleasant, varicose veins can ache, throb and itch. More than 50 patients at Ealing Hospital in London have received the foam therapy with good results, says consultant George Geroulakos. While small varicose veins may be controlled with compression bandages or stockings, larger or more complicated cases will need surgical stripping, tying off or sclerotherapy (injecting an agent to close the vein).

Sclerotherapy, which doctors have performed with liquid for years, can be done under local anaesthetic, leaves only one small scar in the groin and requires a much shorter hospital stay. However, in contrast to liquid, foam is not diluted once injected, so less is needed and it remains in the vein for a longer time.

The foam works by pushing the blood out of the way and is able to make better contact with the inside of the vein walls. All of these factors mean it could work better than liquid sclerotherapy, according to Geroulakos. "Sometimes the liquid can leak out of the vein and cause a chemical sore or ulcer.

We think complications should be less common with the foam. Plus you can see exactly where the foam is using ultrasound, is a major advantage," he said. Geroulakos has been treating patients with the foam technique for two years. "The early and interim results are really promising, but we have not been doing it long enough to know about the long-term results," he said.


 

                                  
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