Is there an association between female circumcision and perinatal death?

OBJECTIVE: In Sweden, a country with high standards of obstetric care, the high rate of perinatal mortality among children of immigrant women from the Horn of Africa raises the question of whether there is an association between female circumcision and perinatal death. METHOD: To investigate this, we examined a cohort of 63 perinatal deaths of infants born in Sweden over the period 1990-96 to circumcised women. FINDINGS: We found no evidence that female circumcision was related to perinatal death. Obstructed or prolonged labour, caused by scar tissue from circumcision, was not found to have any impact on the number of perinatal deaths. CONCLUSION: The results do not support previous conclusions that genital circumcision is related to perinatal death, regardless of other circumstances, and suggest that other, suboptimal factors contribute to perinatal death among circumcised migrant women.     

Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy.

BACKGROUND: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. PATIENTS AND METHODS: Five hundred and twenty-five women below the age of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. RESULTS: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). CONCLUSION: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS.     

Can the Hazard Assessment and Critical Control Points (HACCP) system be used to design process-based hygiene concepts?

Recently, the HACCP (Hazard Analysis and Critical Control Points) concept was proposed as possible way to implement process-based hygiene concepts in clinical practice, but the extent to which this food safety concept can be transferred into the health care setting is unclear. We therefore discuss possible ways for a translation of the principles of the HACCP for health care settings. While a direct implementation of food processing concepts into health care is not very likely to be feasible and will probably not readily yield the intended results, the underlying principles of process-orientation, in-process safety control and hazard analysis based counter measures are transferable to clinical settings. In model projects the proposed concepts should be implemented, monitored, and evaluated under real world conditions.     

Clinical Use of the Antiseptic Polihexanide for Genital Tract Infections

Background: In clinical practice, treatment of genital tract infections is based on administration of either antibiotics or antiseptics. While antibiotics may be applied systemically or topically, antiseptics may be applied only topically. In case of bacterial vaginosis (BV), antibiotic therapy may often be limited and side effects due to systemic administration may develop. Polihexanide (PHMB) is a promising option for the topical treatment of genital tract infections, in particular BV and vaginitis. Method: A systematic search for publications on the use of PHMB for the treatment of genital infections in two electronic databases was performed. Titles, abstracts and citations were imported into a reference database. Duplicates were removed and two reviewers assessed each identified publication separately. Results: Among a total of 204 references, 3 prospective randomized trials were identified. Two trials treated BV infections with PHMB in comparison to clindamycin as antibiotic standard therapy with no significant differences either in safety or in efficacy. The third controlled trial investigated the clinical efficacy of PHMB compared to placebo in the treatment of human papilloma virus. Patients treated with PHMB daily for up to 16-weeks showed significantly higher (52%) clearance of genital warts as compared to patients treated with placebo (4%). Conclusion: PHMB may be a clinically effective alternative for the treatment of BV and human papilloma virus. Although PHMB-based antiseptics are available since the late 90s, controlled trials to investigate its clinical potential for antiseptic treatment are scant. Clinical use of antiseptics for the treatment of infectious diseases should be explored and supported further.     

The HLA system in the population of Mongolia

The frequencies of HLA-A, B, C and DRB1 alleles and haplotype frequencies for HLA-A, B, C and A, B, DR loci were studied in 201 healthy unrelated Khalkha-Mongolians. The most common class I antigens were A24 (25.8%), A2 (23.4%), B61 (12.6%), B51 (8.5%), Cw10 (14.2%), Cw9 (14.1%), Cw7 (13.3%), Cwl (11.8%) and Cw6 (10.2%). A total of 35 DRB1 alleles were identified in this group of samples. The most frequent DRB1 allele was DRB1*0301 (11.1%), followed by DRB 1*0701 (9.7%) and DRBl*H01 (8.5%). One novel DRB1 allele (14MV) and three rare types, DRB1*1111, DRB 1*1504 and DRB 1*1412, recently described in Jews, the Dai minority of China and Japanese, respectively, were identified in Mongolians. The phylo-genetic tree constructed by UPG method put Mongolians in the Northeast Asian cluster. A comparison of three locus haplotype distributions with world populations, revealed that Mongolians share several characteristics in common with other Mongoloids as well as with Caucasoids and Amerindians. The most common A, B and DR haplotype in Mongolians, A33-B58-DR3, was shared with Thai, Thai Chinese and Singapore Chinese. These data support that unique genetic background of Mongolians played a major role in ethnic formation and differentiation of Mongoloid populations.     

C-erbB-2 expression does not predict response to docetaxel or sequential methotrexate and 5-fluorouracil in advanced breast cancer

Breast cancer patients with c-erbB-2-positive tumours seem to benefit from anthracycline-based adjuvant chemotherapy. The predictive value of c-erbB-2 for taxane sensitivity is not yet clear. The purpose of this study was to assess whether c-erbB-2 expression is associated with clinical sensitivity to docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). A total of 283 patients with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel with sequential MF in advanced breast cancer. Paraffin-embedded blocks of the primary tumour were available for 131 patients (46%). c-erbB-2 status was determined by immunohistochemistry using a polyclonal antibody to the c-erbB-2 protein. C-erbB-2 expression was scored in a semi-quantitative fashion using a 0 to 3+ scale. Staining scores 2+ or greater were considered positive. Response evaluation was performed according to World Health Organization (WHO) recommendations. Overall 54 (42%) patients had c-erbB-2-positive tumours. There was no association between treatment outcome and c-erbB-2 overexpression. The overall response rates (RR) (n=128) among c-erbB-2-negative and -positive patients were 35 and 44%, respectively (P=0.359). In the MF arm (n=62), the RR was somewhat higher in the c-erbB-2 overexpressors (33% versus 18%, P=0.18). In the docetaxel arm the RRs were very similar, regardless of the c-erbB-2 expression (53% versus 53%). While several studies have suggested a prognostic and putative predictive significance of c-erbB-2 overexpression in early breast cancer, the significance of c-erbB-2 expression as a predictive factor for response to various cytotoxic treatments in advanced breast cancer is still controversial. In this study, c-erbB-2 expression could not predict response to either MF or T. Thus, tumours over-expressing c-erbB-2 are not uniformly more sensitive to taxanes and c-erbB-2 expression cannot yet be applied clinically as a predictive factor for response in advanced breast cancer.     

Serum levels of oestrogens, progesterone, follicle-stimulating hormone and sex-hormone-binding globulin during simultaneous vaginal administration of 17β-oestradiol and progesterone in the pre- and post-menopause

Serum concentrations of 17β-oestradiol (E₂), unconjugated oestrone (E₁), total oestrone (tE₁), progesterone (P), follicle-stimulating hormone (FSH) and sex-hormone-binding globulin (SHBG) were measured before and after daily intravaginal administration of 250 μg micronized E₂ and 10 mg micronized P for 14 days to 12 post-menopausal and for 1 day only (during cycle days 5–8) to 11 pre-menopausal women. In the post-menopausal women the levels of all steroids increased to maximum values on day 1, 8–10 h after administration and fell thereafter. In the pre-menopausal women the steroid concentrations rose slowly to a plateau level 10–15 h after administration. Significantly higher absorption of E₂ and E₁ (area under the curve increments) was noted in the post-menopausal than in the pre-menopausal women.

In the post-menopausal women the steroid levels measured on days 7 and 14 corresponded to those observed in the very early or late luteal phase. Area under the curve increments were usually smaller on days 7 and 14 than on day 1 and the absorption kinetics altered to a ‘pre-menopausal’ pattern. FSH levels were significantly reduced as from 12 h after administration on day 1 and onwards. A slight (10%) but significant increase in SHBG levels was noted on day 14. It was concluded that the combined E₂ and P treatment used in this investigation brings about a physiological response with only minimal side effects on the liver as judged from changes in SHBG concentrations.