Smoking and female infertility: a systematic review and meta-analysis

The high prevalence of smoking among women in their reproductive years continues to be a matter of concern. The negative effects of smoking on general health are well known, but smoking may also affect fertility. The objective of the present study was to perform a systematic review of the literature to determine whether there is an association between smoking and risk of infertility in women of reproductive age, and to assess the size of this effect. In the 12 studies used for this meta- analysis, the overall value of the odds ratio (OR) for risk of infertility in women smokers versus non-smokers was 1.60 [95% confidence interval (CI) 1.34-1.91]. Studies of subfertile women undergoing in-vitro fertilization (IVF) treatment also show a reduction in fecundity among women smokers. A meta-analysis of nine studies found an OR of 0.66 (95% CI 0.49-0.88) for pregnancies per number of IVF- treated cycles in smokers versus non-smokers. Despite the potential limitations of meta-analyses of observational studies, the evidence presented in this review is compelling because of the consistency of effect across different study designs, sample size and types of outcome. However, continued reassurance is needed that the calculated overall effect is not in fact due to confounding variables.      

Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X- linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.      

Falloposcopy in conjunction with laparoscopy: possibilities and limitations

Falloposcopy is a transvaginal microendoscopic technique to explore the human Fallopian tube from the uterotubal ostium to the fimbrial end. Falloposcopy provides a unique possibility to visualize endotubal disease and may be used therapeutically for removal of debris and for cutting down filmy intraluminal adhesions. To assess the clinical performance of falloposcopy as part of an infertility investigation, a total of 43 women scheduled for laparoscopy as part of an investigation of infertility had a falloposcopy performed in conjunction with the laparoscopy. All women were investigated at Danderyd Hospital, Stockholm and Akademiska Hospital, Uppsala, during 1995 and 1996. Images from the endosalpinx were obtained in 26 of 43 women (60.5%). In 10 women (23.3%), it was possible to obtain images from both tubes. No images were of sufficient quality to describe the entire tubal mucosa in detail. Falloposcopy represents a unique tool for visualization of endotubal disease and may provide a valuable instrument for in-vivo exploration of tubal physiology. However, certain technical problems limit the usefulness of this method in routine clinical practice. These technical problems have to be solved before falloposcopy can achieve a central position in investigation and treatment of tubal disease.      

High level of unequal meiotic crossovers at the origin of the 22q11. 2 and 7q11.23 deletions

Interstitial chromosomal deletions at 22q11.2 and 7q11.23 are detected in the vast majority of patients affected by CATCH 22 syndromes and the Williams-Beuren syndrome, respectively. In a group of 15 Williams- Beuren patients, we have shown previously that a large number of 7q11.23 deletions occur in association with an interchromosomal rearrangement, indicative of an unequal crossing-over event between the two homologous chromosomes 7. In this study, we show that a similar mechanism also underlies the formation of the 22q11.2 deletions associated with CATCH 22. In eight out of 10 families with a proband affected by CATCH 22, we were able to show that a meiotic recombination had occurred at the critical deleted region based on segregation analysis of grandparental haplotypes. The incidences of crossovers observed between the closest informative markers, proximal and distal to the deletion, were compared with the expected recombination frequencies between the markers. A significant number of recombination events occur at the breakpoint of deletions in CATCH 22 patients (P = 2.99x10(-7)). The segregation analysis of haplotypes in three- generation families was also performed on an extended number of Williams-Beuren cases (22 cases in all). The statistically significant occurrence of meiotic crossovers (P = 4.45x10(-9)) further supports the previous findings. Thus, unequal meiotic crossover events appear to play a relevant role in the formation of the two interstitial deletions. The recurrence risk for healthy parents in cases where such meiotic recombinations can be demonstrated is probably negligible. Such a finding is in agreement with the predominantly sporadic occurrence of the 22q11.2 and 7q11. 23 deletions. No parent-of-origin bias was observed in the two groups of patients with regard to the origin of the deletion and to the occurrence of inter- versus intrachromosomal rearrangements.      

CD4 responses to conserved HIV-1 T helper epitopes show both negative and positive associations with virus load in chronically infected subjects

Characterization of immune responses to immunodominant CD4 epitopes in HIV-1 that are associated with control of HIV infection could be used to strengthen the efficacy of polyepitope HIV vaccines. We measured both the proliferative and the CD4 interferon (IFN)-gamma and interleukin (IL)-2 cytokine responses specific for 11 previously identified HIV-1 T helper epitopes in 10 HIV-infected non-progressors (LTNPs) (infected for a median of 15 years with a stable CD4 count of >500 cells x 10(6)/l), and seven slow progressors (SPs) (infected for a median of 15 years with a CD4 count that had declined to <500 cells x 10(6)/l). Both groups were antiretroviral treatment-naive at the time of evaluation. The median virus load of SP group was higher than that of the LTNP group (P = 0.0002). The CD4 response to a peptide pool representing all potential CD4 Gag epitopes and to Gag p24 protein was also studied. Compared to SPs, LTNPs had higher numbers of Gag-specific IFN-gamma+IL-2+ CD4s (P = 0.0059). The Gag-specific cytokine and proliferative responses correlated inversely with virus load (P = 0.03 and 0.0002, respectively), highlighting the potential importance of this response in immunity to HIV. A direct correlation was noted between proliferation and the Gag-specific IL-2 (P = 0.0053) rather than IFN-gamma response (P = 0.1336), demonstrating that the proliferation assay reflected the IL-2 rather than the IFN-gamma secreting capacity of CD4 cells. Several subjects with diverse class II DRB1 alleles responded, confirming the 11 selected peptides to be both antigenic and conserved. CD4 cytokine responses to one Gag and two conserved Pol peptides correlated negatively with virus load. The cytokine response to two additional Pol peptides correlated positively with virus load. The data indicate that there is not an absolute correlation between the CD4 immune response to conserved and broadly antigenic helper T cell epitopes in HIV non-progression.     

Rectal cancer in the Kingdom of Saudi Arabia: the King Faisal Specialist Hospital experience

BACKGROUND: No survival data have yet been published from the Kingdom of Saudi Arabia for patients with rectal cancer. The present paper reports experience with these patients over an 8-year period. METHODS: All patients referred to the King Faisal Specialist Hospital (KFSH) between March 1990 and February 1998 for the primary management of rectal cancer were entered into a computerized database. Prior to 1993 patients did not receive adjuvant therapy. Kaplan-Meier survival curves and the log-rank test were used to compare outcome data. RESULTS: There were 70 men (average age: 55.6 years) and 75 women (average age: 52.8 years). Twelve per cent of patients admitted a family history of colorectal carcinoma (CRC). Twenty-seven per cent of tumours were circumferential. Most tumours were larger than 4 cm and the lowest edge of the majority of tumours was less than 6 cm from the anal verge. Fifty-four per cent of tumours were fixed; 69% of patients received either pre-operative or postoperative radiotherapy. A total of 106 patients underwent 'curative' surgery. Equal numbers of patients had abdomino-perineal resection (APR) and anterior resection (AR) of the rectum. Thirty-five patients received blood peri-operatively (APR, 34%; AR, 12%). Major anastomotic leakage following AR occurred in two patients. Two patients died within 30 days of surgery. Ten patients were lost to follow-up. Following curative AR, eight patients had a distal resection margin of < 2 cm and two patients (Dukes' C) developed local recurrence (25%); 37 patients had a margin > 2 cm and seven developed local recurrence (18.9%). A total of 48 patients underwent curative APR, and four patients developed local recurrence (8.3%). Overall local recurrence was tumour stage-dependent (Dukes' B, 8.8%; Dukes' C, 29.3%). Recurrence was local in 13 patients. Pre-operative radiotherapy seemed to reduce average tumour size (3.6 vs 4.3 cm). The crude overall 5-year survival rate was 39%. The 5-year survival rate for patients with Dukes' stage C cancers following 'curative' surgery was 25%. CONCLUSION: Curative surgery can be performed with a relatively low requirement for blood transfusion, a low mortality and morbidity, and comparable outcomes to Western studies in spite of the large, low and often advanced stage of the tumours managed. Local recurrence rates following curative resection and re-anastomosis for low rectal cancers may be reduced by resisting patient pressure to avoid stomata.     

Diagnosis of pulmonary embolism: Ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography

The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses.     

颈动脉粥样硬化疾病的处理——美国血管外科学会临床实践指南

美国血管外科学会（SVS）任命了一个专家委员会制定颈动脉狭窄处理的循证临床指南。在制定临床实践推荐意见过程中，该委员会使用系统评价对当前最佳的证据进行了总结，采用GRADE标准对推荐意见的强度（强烈推荐为GRADEI级，一般推荐为GRADEⅡ级）和证据的质量（高、中、低和极低）进行了分级。对于轻度颈动脉狭窄患者（有症状患者狭窄程度〈50％和无症状患者狭窄程度〈60％），推荐进行最佳的内科治疗而非血管重建术（I级推荐，高质量证据）。对于有症状中到重度狭窄患者（狭窄程度〉150％），推荐行颈动脉内膜切除术（CEA）＋最佳的内科治疗（I级推荐，高质量证据）。对于围手术期风险高的有症状中到重度狭窄患者（狭窄程度≥50％），建议采用颈动脉支架置入术作为其替代治疗手段（Ⅱ级推荐，低质量证据）。对于中到重度狭窄的无症状患者（狭窄程度≥60％），只要围手术期风险较低，就推荐行CEA＋内科治疗（I级推荐，高质量证据）。对于中到重度狭窄的无症状患者（狭窄程度≥60％），不推荐行颈动脉支架置入术（I级推荐，低质量证据）。颈动脉狭窄≥80％但存在CEA高危解剖学风险的患者可能是一个例外。