SEARCHLIGHT Navigating the Global Medical Network Of Sexual Health Issues for Sexual Health Matters

Mr Ibrahim Bolaji, MD, FRCPI, FRCOG.
Consultant Obstetrician and Gynaecologist, Diana Princess of Wales Hospital, Grimsby, DN3 2BA
Honorary Senior Clinical lecturer, Section of Reproductive and Developmental Medicine, University of Sheffield.

You are welcome to this column in Sexual Health Matters that will regularly navigate the medical world to flag recent development in Sexual Health issues. There will be opportunity to take par in regular problem based searchlight medical exercises. The columnist welcomes regular feedback from readers through the feedback email. Enjoy your reading.

 

Germ cells inheritance: alternative pathway

Germ cells have the unique capacity to start a new life upon fertilization. They are generated during a sex-specific differentiation programme called gametogenesis The production of germ cells is a unique process involving a cell division that halves the size of the genome. The genetic code in the resulting DNA is however not the only influence on the maturation of the sperm and egg. A series of heritable 'epigenetic' modifications is also involved; these control gene expression via changes in chromatin and histone structures and DNA methylation, but leave the DNA code intact. The epigenetics of germ cells are the subject of a recent review article by Sarah Kimmins and Paolo Sassone-Corsi from Strasbourg in France1. An understanding of the enzymes and signal molecules involved could contribute to new reproductive technologies and the prevention of heritable diseases.
1Kimmins S and Sassone-Corsi P ;
Chromatin remodelling and epigenetic features of germ cells. Nature 434, 583 - 589 (31 March 2005.



Low –dose aspirin in the primary prevention of cardiovascular disease in women: a randomised control trial

Although aspirin is effective in the treatment of acute myocardial infarction and in the secondary prevention of cardiovascular disease among men and women, its use in primary prevention remains controversial. To date, five randomized trials involving 55,580 participants have evaluated aspirin in the primary prevention of cardiovascular disease. In men, low-dose aspirin prevents myocardial infarction but not stroke. In a recent paper1 from Boston (Mass) involving a large study of healthy women, the opposite was found.
A total of 39,876 healthy women 45 years of age or older were assigned randomly to receive 100 mg of aspirin on alternate days or placebo and they were monitored for 10 years for a first major cardiovascular event (non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes).
During follow-up, 477 major cardiovascular events were confirmed in the aspirin group, as compared with 522 in the placebo group, for a non-significant reduction in risk with aspirin of 9% (RR, 0.91; 95 % CI, 0.80-1.03; P=0.13).
With regard to individual end points, there was a 17 % reduction in the risk of stroke in the aspirin group, as compared with the placebo group (RR, 0.83; 95 % CI, 0.69 - 0.99; P=0.04), owing to a 24 % reduction in the risk of ischaemic stroke (RR, 0.76; 95 % CI, 0.63 -0.93; P=0.009) and a non-significant increase in the risk of hemorrhagic stroke (RR, 1.24; 95 % CI, 0.82-1.87; P=0.31).
As compared with placebo, aspirin had no significant effect on the risk of fatal or nonfatal myocardial infarction (RR, 1.02; 95 % CI, 0.84-1.25; P=0.83) or death from cardiovascular causes (RR, 0.95; 95% CI, 0.74-1.22; P=0.68). Gastrointestinal bleeding requiring transfusion was more frequent in the aspirin group than in the placebo group (RR, 1.40; 95 % CI, 1.07-1.83; P=0.02). Subgroup analyses showed that aspirin significantly reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction among women 65 years of age or older.
In this large, primary-prevention trial among women, aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a non-significant finding with respect to the primary end point.
1Paul M Ridker, M.D., Nancy R. Cook et al.
A Randomized Trial of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease in Women. NEJM Volume 352:1293-1304.

Treatment exhaustion in HIV drug management

A multicentre cohort study (1) involving six large HIV centres in Southeast England published in the BMJ in March 2005. It evaluated the evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options.
The study involved individuals 16 593 of which 13 378 (80.6%) were male patients. 10 340 (62.3%) were infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex. The median age was 34 years. They were seen for care between 1 January 1996 and 31 December 2002. The main outcome measures were exposure to highly active antiretroviral therapy (HAART) and drug classes, CD4 count, plasma HIV RNA burden.
Overall, 10 207 of the 16 593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm3 and 4.34 log10 copies/ml in 1996 to 408 cells/mm3 and 1.89 log10 copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, about one quarter had evidence of "viral load failure" with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden > 2.7 log10 copies/ml and a CD4 count < 200 cells/mm3.
The study concludes that the proportion of individuals with HIV infection in the UK who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients.

1Sabin A, Lampe F,Matthias R, Bhagani S, Gilson R, Youle, M Johnson M et al.
Treatment exhaustion of highly active antiretroviral therapy (HAART) among individuals infected with HIV in the United Kingdom: multicentre cohort study . BMJ 2005; 330:695 (26 March).

Preconception folic acid therapy in preventing neural tube defect: how effective is the recommendation in Europe?

Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects. Unambiguous evidence of the effectiveness of periconceptional folic acid in preventing neural tube defects has been available since early nineties, and improving folate status sufficiently could result in the prevention of more than two thirds of all neural tube defects (NTD). A report on trends in the prevalence of neural tube defects from 1990 to 2001, in the context of a survey in 16 European countries of periconceptional folic acid policies and their implementation was published recently1. The effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of NTD was published in a retrospective cohort study of births monitored by birth defect registries (Eurocat)2.
Thirteen birth defects registries monitored the rates of neural tube defects from 1988 to 1998 in Norway, Finland, Northern Netherlands, England and Wales, Ireland, France (Paris, Strasbourg, and Central East), Hungary, Italy (Emilia Romagna and Campania), Portugal, and Israel. Cases of neural tube defects were ascertained among live born infants, stillbirths, and pregnancy terminations (where legal). Policies and recommendations were ascertained by interview and literature review.
The main outcome measures consists of incidences and trends in rates of NTDs before and after 1992 (the year of the first recommendations) and before and after the year of local recommendations (when applicable).
The surprising result was that the issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of neural tube defects.
The study concludes that recommendations alone did not seem to influence trends in NTDs up to six years after the confirmation of the effectiveness of folic acid in clinical trials. New cases of NTDs preventable by folic acid continue to accumulate. A reasonable strategy would be to quickly integrate food fortification with fuller implementation of recommendations on supplements.

1Busby A, Abramsky L, Dolk H et al,
Preventing neural tube defects in Europe: Population based study. BMJ 2005; 330: 574-575 (12 March).
2Botto L, Lisi A, Robert-Gnansia E, Erickson D , Vollset S, and Mastroiacovo P,
International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? BMJ 2005; 330:571.

Recurrent Bacterial Vaginosis treatment update - life in the littoral zone: lactobacilli losing the plot

Bacterial vaginosis is a clinical condition caused by replacement of the normal hydrogen peroxide producing Lactobacillus sp. in the vagina with high concentrations of characteristic sets of aerobic and anaerobic bacteria. Bacterial vaginosis is the most prevalent cause of vaginal discharge or malodour, although 50 percent of women who meet the criteria for this condition are asymptomatic.
Bacterial vaginosis is reported in 10 to 41 percent of women, and new evidence has shown association with maternal and fetal morbidity.
Studies have shown that spontaneous abortion, preterm labour, premature birth, preterm premature rupture of the membranes, amniotic fluid infection, postpartum endometritis, and post caesarean wound infections are increased because of infection with bacterial vaginosis during pregnancy. Clinical trials demonstrated important reductions in many of these adverse events with appropriate screening and antimicrobial treatment protocols.
Recurrent bacterial vaginosis is a great challenge not only for the healthcare professionals but also by for those affected by it. The inability to maintain remission after treatment may be because of the flawed approach of using antibiotics to treat a condition that is an imbalance rather than an infection. The maintenance of a healthy lactobacillus population offers an approach to preventing relapse: the problem is how best to do this. Physiological approaches such as the use of hydrogen peroxide, lactic acid, and exogenous lactobacilli require further exploration.
The role of bacterial vaginosis as a risk factor for acquisition of HIV and other sexually transmitted diseases is a further impetus in attempting to prevent recurrent bacterial vaginosis. This topic is discussed in detail in a very interesting review article by Peter Hay (1).

1Hay P.
Life in the littoral zone: lactobacilli losing the plot. Sex Transm Infect.2005; 81: 100-102.

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