Multicenter study of a slow-release theophylline: armophylline

In a co-operative study involving 10 centres, 95 asthmatic patients were treated with Armophylline, a new slow-release theophylline for a period of 1 to 3 months. Eighty per cent of the patients receiving the drug in doses of 11 to 15 mg/kg/day immediately had adequate blood theophylline levels (7-20 mcg/ml). There was a significant decrease in dyspnoea and number of asthmatic attacks and a significant increase in FEV1 and FEV1/VC ratio. The drug was usually well tolerated. Side-effects, such as insomnia, headache or digestive disorders were, as a rule, mild.     

Inhibition by phospholipids of haemolytic action of asbestos.

Haemolysis by asbestos fibres results from an increase in membrane permeability and not from rupture of red blood cells (RBC). The effect of chrysotile asbestos on RBC is at least partly, if not completely, attributable to lipid extraction and adsorption on to the fibres. This was suggested by the hyperbolic relationship between the haemolytic activity of chrysotile and the relative concentration of both chrysotile and RBC. Moreover, it was shown that pre-incubation of chrysotile with lipids, either as RBC membranes or with pure lipids in the form of liposomes, prevents haemolysis.     

Significant contribution of large BRCA1 gene rearrangements in 120 French breast and ovarian cancer families

Genetic linkage data have shown that alterations of the BRCA1 gene are responsible for the majority of hereditary breast-ovarian cancers. However, BRCA1 germline mutations are found much less frequently than expected, especially as standard PCR-based mutation detection approaches focus on point and small gene alterations. In order to estimate the contribution of large gene rearrangements to the BRCA1 mutation spectrum, we have extensively analysed a series of 120 French breast-ovarian cancer cases. Thirty-eight were previously found carrier of a BRCA1 point mutation, 14 of a BRCA2 point mutation and one case has previously been reported as carrier of a large BRCA1 deletion. The remaining 67 cases were studied using the BRCA1 bar code approach on combed DNA which allows a panoramic view of the BRCA1 region. Three additional rearrangements were detected: a recurrent 23.8 kb deletion of exons 8-13, a 17.2 kb duplication of exons 3-8 and a 8.6 kb duplication of exons 18-20. Thus, in our series, BRCA1 large rearrangements accounted for 3.3% (4/120) of breast-ovarian cancer cases and 9.5% (4/42) of the BRCA1 gene mutation spectrum, suggesting that their screening is an important step that should be now systematically included in genetic testing surveys.     

Evaluation of Breast Cancer Risk in a Multigenic Model Including Low Penetrance Genes Involved in Xenobiotic and Estrogen Metabolisms

Breast cancer has become the most frequent cancer among women in Westernized countries. The majority of breast cancers are due to low penetrance genes, which can act with environmental factors, particularly nutrition. Polymorphisms in gene coding for xenobiotic and estrogen metabolic pathways could increase individual cancer susceptibility and lead to the indication of individuals at higher cancer risk. A population-based, case-control study consisting of 911 breast cancer cases and 1,000 healthy control cases was performed. The association between 11 single nucleotide polymorphisms (SNP) in 7 genes and breast cancer risk was investigated in a multigenic model. The CYP1B1-432 Leu-Val and Val-Val genotypes significantly increased risk [odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.08–1.39; OR = 1.51, 95% CI = 1.17–1.94, respectively] similarly as observed with CYP1B1-453 (Asn-Ser genotype: OR = 1.17, 95% CI = 1.00–1.37; Ser-Ser genotype: OR = 1.38, 95% CI = 1.00–1.89). We showed that catechol-O-methyltransferase (COMT) could modulate the risk conferred by CYP1B1, ESR, GSTP1, and NAT2 acetylation phenotype. Additionally, a higher risk conferred by the variant for COMT was noted only for individuals presenting a high waist-to-hip ratio (COMT Val-Met, OR = 1.60, 95% CI = 1.04–2.44; COMT Met-Met, OR = 1.57, 95% CI = 0.98–2.53), suggesting a relationship with abdominal adiposity. In conclusion, COMT constitutes a crucial element in estrogen metabolism by regulating carcinogen metabolites elimination and, consequently, is a major factor in breast cancer risk.     

Left main coronary stenting in a non surgical octogenarian population: a possible approach

Coronary artery bypass grafting is conventionally considered the standard treatment for significant left main coronary artery (LMCA) disease. The management of LMCA disease in octogenarians is however still debated. The aim of this study was to appreciate the safety and effectiveness of percutaneous coronary intervention (PCI) for LMCA disease in octogenarians who were denied for surgical revascularization. The study included 70 consecutive patients ≥80 years of age who had undergone PCI for the treatment of LMCA and who were primary denied by our center's heart team for surgical revascularization. Mean age was 83.4±2.6 years. Mean Euroscore was 21.1±16.7 and mean Syntax score was 28.6±8.7. Overall in-hospital mortality was 11%. Mean follow-up time was 30.5±24.2 months. Overall mortality at the end of follow-up was 28%. Cardiac death was found in 18 patients and 2 patients died from terminal renal insufficiency. One patient (2%) presented with a new STEMI, 7 (11.3%) with a new non-STEMI, 13 (21%) with heart failure, and 2 (3.2%) had minor hemorrhage. There was a percutaneous target vessel revascularization in 6 (10%) patients. During follow-up, the total major adverse cerebral and cardiovascular event (MACCE including death, non-fatal acute myocardial infarction (AMI), target lesion revascularization (TLR), or stroke) was 27.4%. Stent implantation was relatively safely applied for the treatment of LMCA disease in octogenarians who were refused for surgery and who represented a high risk population. Despite a non-negligible rate of MACCE, the clinical long term outcome seems correct for this specific population with heavy basal status.     

Ovarian carcinogenesis: recent and past hypotheses

Ovarian carcinogenesis and the early stages of malignant transformation are limited because of the lack of a candidate precursor. There have been several proposed hypotheses: first, ovary and the ovarian surface epithelium and more recently observations have increasingly focused attention of the Fallopian tube. Moreover, molecular genetic analysis has designed two main pathways of tumorogenesis. In this review, we discuss the different and perhaps complementary hypotheses about ovarian carcinogenesis.     

Peripheral blood DNA methylation detected in the BRCA1 or BRCA2 promoter for sporadic ovarian cancer patients and controls

BackgroundOvarian cancer is located at the fifth rank of female cancers. Different risk factors including genetic factors with BRCA1 and BRCA2 genes played an important role in the etiology of the ovarian cancer. In most of sporadic ovarian cancer, variation in the expression of BRCA1 and BRCA2 genes was observed and it could be a consequence of epigenetic modifications. This work aimed to study methylation at CpG islands within the promoter of the BRCA1 and BRCA2 genes in sporadic ovarian cancers.MethodsFor this, we conducted a case-control study consisted of 51 ovarian cancer cases with no BRCA mutation and 349 healthy women. All participants came from the Auvergne region in France. Genomic DNA was extracted from peripheral blood cells (PBCs) and we used the Quantitative Analysis of Methylated Alleles (QAMA) to estimate the per cent of methylation in the BRCA1 and BRCA2 promoters.ResultsBRCA1 methylation is significantly decreased in ovarian cancer by comparison with the control group. The comparison between the two different populations did not show any significant difference regarding BRCA2 methylation but exhibited a trend in the decrease of BRCA2 promoter methylation in peripheral blood DNA of sporadic ovarian cancer.ConclusionsThese results may have implications in better understanding the underlying epigenetic mechanisms in BRCA1 and BRCA2 oncosuppressors in sporadic ovarian cancer.     

Assessment of preventive measures for accidental blood exposure in operating theaters: a survey of 20 hospitals in Northern France

BACKGROUND: Accidental exposures to blood of body fluids (ABE) expose health care workers (HCW) to the risk of occupational infection. OBJECTIVES: Our aim was to assess the prevention equipment available in the operating theater (OT) with reference to guidelines or recommendations and its use by the staff in that OT on that day and past history of ABE. METHODS: Correspondents of the Centre de Coordination de la Lutte contre les Infections Nosocomiales (CCLIN) Paris-Nord ABE Surveillance Taskforce carried out an observational multicenter survey in 20 volunteer French hospitals. RESULTS: In total, 260 operating staff (including 151 surgeons) were investigated. Forty-nine of the 260 (18.8%) staff said they double-gloved for all patients and procedures, changing gloves hourly. Blunt-tipped suture needles were available in 49.1% of OT; 42 of 76 (55.3%) of the surgeons in these OT said they never used them. Overall, 60% and 64% of surgeons had never self-tested for HIV and hepatitis C virus (HCV), respectively. Fifty-five surgeons said they had sustained a total of 96 needlestick injuries during the month preceding the survey. Ten of these surgeons had notified of 1 needlestick injury each to the occupational health department of their hospital (notification rate, 10.4%). CONCLUSION: The occurrence of needlestick injury remained high in operating personnel in France in 2000. Although hospitals may improve access to protective devices, operating staff mindful of safety in the OT should increase their use of available devices, their knowledge of their own serostatus, and their ABE notification rate to guide well-targeted prevention efforts.