ATM gene and lymphoid malignancies.

Inherited biallelic mutations of the ATM (ataxia-telangiectasia mutated) gene cause ataxia-telangiectasia, a rare autosomal recessive disorder associated with a high incidence of childhood leukaemias and lymphomas, suggesting that ATM gene alterations may be involved in lymphomagenesis. Loss of heterozygosity at 11q22-23 (location of the ATM gene) is a frequent event in sporadic lymphoid tumours, and several studies have reported a high prevalence of ATM gene alterations in diverse sporadic lymphoproliferative disorders, adding evidence to the postulated contribution of ATM in the pathogenesis of these tumours. This mini-review will summarize the recently published data concerning the ATM gene in sporadic lymphoid malignancies and will discuss the apparent paradox between the predominance of nonsense mutations observed in patient with ataxia-telangiectasia and the high proportion of missense alterations found in sporadic lymphoid tumours.     

Probiotics and inflammatory bowel diseases

Enteric microflora profiles vary considerably between active inflammatory bowel diseases (IBD) and healthy conditions. Intestinal microflora may partake in the pathogenesis of IBD by one or some ways: specific pathogenic infection induces abnormal intestinal mucosal inflammation; aberrant microflora components trigger the onset of IBD; abnormal host immune response loses normal immune tolerance to luminal components; luminal antigens permeate through the defective mucosal barrier into mucosal lamina propria and induce abnormal inflammatory response. Preliminary studies suggest that administration of probiotics may be benefit for experimental colitis and clinical trials for IBD. Researches have been studying the function of probiotics. Introduction of probiotics can balance the aberrant enteric microflora in IBD patients, and reinforce the various lines of intestinal defence by inhibiting microbial pathogens growth, increasing intestinal epithelial tight junction and permeability, modulating immune response of intestinal epithelia and mucosal immune cells, secreting antimicrobial products, decomposing luminal pathogenic antigens.     

Insertion problems, removal problems, and contraception failures with Implanon

OBJECTIVE: Analysis of the results of a national pharmacovigilance study on Implanon, a contraceptive implant containing 68 mg of etonogestrel. PATIENTS AND METHODS: This survey concerns cases of pregnancies (contraception failures), of migrations and of insertion or removal problems with Implanon reported to French Regional Drug Pharmacovigilance Centres and to Organon SA between May 2001 and September 2002. RESULTS: In France, 39 unintended pregnancies were reported over 17 months. The pregnancies were in 77% of cases (N = 30) due to an insertion technique error (implant not found when pregnancy has been diagnosed). For 3 patients (7,6%), pregnancy was due to a failure of etonogestrel contraceptive effect, explained twice by its association with an enzymatic inductor drug. For 4 patients (10%), pregnancy was due to an untimely insertion (insertion after day 5 of menstrual cycle or woman already pregnant). For two patients, no information was available. The incidence of reported pregnancies in France is estimated at 0.359 / 10(3) implants [0.246-0.482], in accordance with a typical Pearl Index of 0.06 [0.04-0.08]. Twenty-eight suspected migrations (N = 11), problems or failures in removal of the implant (N = 11) and insertion difficulties (N = 6) were notified, corresponding to an incidence of 0.257/10(3) implants [0.162-0.363]. DISCUSSION AND CONCLUSION: Occurrence of pregnancy is possible with Implanon, due to errors in the insertion technique (device not really inserted) or to a non-respect of the SPC recommendations (drug-drug interaction or untimely insertion). Insertion problems can lead to localisation problems (implant not visible by X-ray) then needing further tests and even harmful practice (removal under general anaesthesia). That is why a real and strict training is highly recommended to physicians.     

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on survival in patients with lung cancer. Studies evaluating the survival impact of COX-2 in lung cancer, published until December 2005, were selected. Data for estimation of individual hazard ratios (HR) for survival were extracted from the publications and combined in a pooled HR. Among 14 eligible papers, all dealing with non-small-cell lung cancer, 10 provided results for meta-analysis of survival data (evaluable studies). Cyclooxygenase-2 positivity was associated with reduced survival, improved survival or no statistically significant impact in six, one and seven studies, respectively. Combined HR for the 10 evaluable studies (1236 patients) was 1.39 (95% confidence intervals (CI): 0.97-1.99). In stage I lung cancer (six evaluable studies, 554 patients), it was 1.64 (95% CI: 1.21-2.24). No significant impact was shown in ADC. A slight detrimental effect on survival in patients with lung cancer is associated with COX-2 expression, but the statistical significance is not reached. This effect is statistically significant in stage I, suggesting that COX-2 expression could be useful at early stages to distinguish those with a worse prognosis.     

Recent increase of breast cancer incidence among women under the age of forty

Using data from the Geneva Cancer Registry, we found that in 2002-2004, breast cancer incidence in women aged 25-39 years increased by 46.7% per year (95% CI: 7.1-74.0, P=0.015), which surveillance or detection bias may not fully explain.