Transient association between semen exposure and biomarkers of genital inflammation in South African women at risk of HIV infection

IntroductionSemen induces mucosal changes in the female reproductive tract to improve pregnancy outcomes. Since semen‐induced alterations are likely short‐lived and genital inflammation is linked to HIV acquisition in women, we investigated the contribution of recent semen exposure on biomarkers of genital inflammation in women at high HIV risk and the persistence of these associations.MethodsWe assessed stored genital specimens from 152 HIV‐negative KwaZulu‐Natal women who participated in the CAPRISA 008 trial between November 2012 and October 2014. During the two‐year study period, 651 vaginal specimens were collected biannually (mean five samples per woman). Cervicovaginal lavage (CVL) was screened for prostate‐specific antigen (PSA) by ELISA, whereas Y‐chromosome DNA (YcDNA) detection and quantification were conducted by RT‐PCR, representing semen exposure within 48 hours (PSA+YcDNA+) and semen exposure within three to fifteen days (PSA−YcDNA+). Soluble protein concentrations were measured in CVLs by multiplexed ELISA. T‐cell frequencies were assessed in cytobrushes by flow‐cytometry, and vulvovaginal swabs were used to detect common vaginal microbes by PCR. Linear mixed models adjusting for factors associated with genital inflammation and HIV risk were used to assess the impact of semen exposure on biomarkers of inflammation over multiple visits.ResultsHere, 19% (125/651) of CVLs were PSA+YcDNA+, 14% (93/651) were PSA−YcDNA+ and 67% (433/651) were PSA−YcDNA−. Semen exposure was associated with how often women saw their partners, the frequency of vaginal sex in the past month, HSV‐2 antibody detection, current gonorrhoea infection and Nugent Score. Both PSA detection (PSA+YcDNA+) and higher cervicovaginal YcDNA concentrations predicted increases in several cytokines, barrier‐related proteins (MMP‐2, TIMP‐1 and TIMP‐4) and activated CD4+CCR5+HLA‐DR+ T cells (β = 0.050; CI 0.001 to 0.098; p = 0.046) and CD4+HLA‐DR+ T cells (β = 0.177; CI 0.016 to 0.339; p = 0.032) respectively. PSA detection was specifically associated with raised pro‐inflammatory cytokines (including IL‐6, TNF‐α, IP‐10 and RANTES), and with the detection of BVAB2 (OR = 1.755; CI 1.116 to 2.760; p = 0.015), P. bivia (OR = 1.886; CI 1.102 to 3.228; p = 0.021) and Gardnerella vaginalis (OR = 1.815; CI 1.093 to 3.015; p = 0.021).ConclusionsMore recent semen exposure was associated with raised levels of inflammatory biomarkers and the detection of BV‐associated microbes, which declined by three to fifteen days of post‐exposure. Although transient, semen‐induced alterations may have implications for HIV susceptibility in women.     

Increased levels of nm23 H1/nucleoside diphosphate kinase A mRNA associated with adenocarcinoma of the prostate

Summary Overexpression of the nm23H1 gene has been associated with the suppression of metastasis in several solid tumors. However, in colorectal carcinoma and neuroblastoma, increased levels of nm23 H1 nucleoside diphosphate kinase A (NDPKA) mRNA are associated with tumorigenesis. To determine the role of nm23 H1/NDPKA in the prostate, normal and/or malignant tissue samples from 29 consecutive patients were studied. Levels of nm23 H1/NDPKA mRNA and nm23 H1/NDPKA mRNA protein were determined in tissue from 18 and 27 patients, respectively. In all, 16 of the 18 tumor samples expressed increased levels of nm23 H1/NDPKA mRNA as compared with those measured in normal tissue. The level of nm23 H1/NDPKA mRNA was >10-fold higher in a metastatic lymph node than in normal prostate tissue. All cancer specimens and areas of prostatic intraepithelial neoplasia showed immunoreactivity with the nm23 H1/NDPKA antibody; however, normal prostatic tissue was unreactive. These findings suggest that overexpression of the nm23 H1/NDPKA gene occurs frequently in adenocarcinomas of the prostate and may be an early event in prostate cancer tumorigenesis.     

Long-term durability of resection and end-to-end anastomosis for ascending aortic aneurysms

BACKGROUND: Ascending aortic aneurysms with normal sized sinotubular junction are generally treated by resection of the dilated aorta and replacement with tubular graft. Aortic resection and direct end-to-end anastomosis has been applied to repair aortic coarctation, interrupted aortic arch, and traumatic aortic rupture. No data exist regarding the long-term durability of this approach in ascending aortic aneurysms. The aim of this case-control study was to illustrate the durability of this operation by presenting our entire experience and the long-term follow up of a cohort of 34 patients who underwent ascending aortic aneurysm resection and primary end-to-end anastomosis between January 1990 and March 2003 in Caen University Hospital (Caen, France). METHODS: The mean age of patients was 61.5 +/- 12.5 years, and there were 18 male and 16 female patients. The operative technique included extensive mobilization of the arch, supra-aortic trunks, and inferior vena cava to enable approximation of the aortic ends, thus avoiding tension on the suture lines. Associated aortic valve replacement was performed in 27 patients; mechanical valves were used in 19. A bicuspid aortic valve was present in 9 patients; in 3 cases the valve was regurgitant. Aortic valve regurgitation was present in a total of 7 patients. Patients were followed up at regular intervals; total follow-up was 2187 patient-months, with a median follow-up time of 72 months per patient (25th-75th percentile 10.5-102.7 months). RESULTS: One patient died 10 days after the operation of aortic rupture related to suture infection caused by mediastinitis. Late deaths occurred in 3 patients, who died 12, 62, and 71 months after the operation, but none of these deaths were attributable to late aortic repair failure. No patient in this series required reoperation, including patients with aortic regurgitation or bicuspid aortic valve. Follow-up was 91.1% complete at the closing date of April 1, 2003. The Kaplan-Meier estimate of survival for all patients was 120.4 months (95% confidence interval 105.1-135.7 months). The median of preoperative maximal aortic diameter was 55.1 mm (range 50.3 to 67.5 mm, 25th-75th percentile 50.5-56.8 mm). The median immediate postoperative diameter was 40.3 mm (range 33.4-46.4 mm, 25th-75th percentile 37.2-42.0 mm, P <.0001 relative to preoperative diameter), and the median length of the resected aortic segment was 52 mm (range 48-76 mm, 25th-75th percentile 50.1-66.4 mm). The median decrease of aortic diameter was 24.9 mm (range 8.9-32.6 mm, 25th-75th percentile 18.2-26.6 mm).The median aortic diameter at the end of the follow-up was 41.0 mm (range 34.6-46.1 mm, 25th-75th percentile 37.0-43.2 mm, P =.6 relative to immediate postoperative diameter). CONCLUSIONS: Ascending aorta aneurysm resection and primary end-to-end anastomosis provides effective long-term outcome and in selected cases represents a good alternative to aortic interposition grafting. Aortic regurgitation and bicuspid aortic valve do not represent a contraindication for this treatment.     

The first 2 years of a palliative care consultation team in the Netherlands

In January 1999 an integrated multidisciplinary palliative care consultation (PCC) team was established in Maastricht in the Netherlands. The team included experts in palliative care who had extensive experience in a variety of settings. One of the major tasks of the PCC team was to give support, information and advice to healthcare professionals caring for terminally ill patients. The PCC team was asked by the government to consecutively register and evaluate all consultations. This article describes these consultations, including information on the requesting caregivers, the patients, the questions asked and the recommendations given in the first 26 months. The results show that the PCC team served the needs of professional caregivers in a variety of settings. Most consultations concerned physical and pharmacological problems and the majority of recommendations were evaluated as positive.     

Activity of cefapirin against bacterial strains isolated from acute otitis media in children

The antibacterial activity of cefapirin was tested against 210 strains isolated from the auricular exudate of childrens' acute otitis media. For 112 strains of Haemophilus studied (20% secreted a beta-lactamase), the MIC 50 and 90 of cefapirin were 2 and 4 mg/l respectively. Ten strains of Branhamella catarrhalis were tested (9 secreted a beta-lactamase) and the MIC ranged from 0.25 to 4 mg/l. Against Streptococcus pneumoniae, cefapirin has an extremely high activity with MIC 50 and 90 less than 0.06 mg/l. Of the strains of Staphylococcus aureus sensitive to meticillin, one had a MIC less than 0.06 mg/l, and 11 had a MIC = 0.25 mg/l. For 14 strains of Enterobacteriaceae studied, we obtained a MIC 50 of 8 mg/l and a MIC 90 of 32 mg/l. The results show that cefapirin is an antibiotic particularly suitable for the treatment of acute otitis media.