Subfertility among parents of men diagnosed with testicular cancer

It is well known that men with testicular cancer also have reduced fertility before diagnosis. It is unclear, however, whether their parents also have reduced fertility. We performed a population-based record linkage study comparing parental fertility among 3711 testicular cancer cases and 371 100 control males. The cases were diagnosed from 1961 to 2001, and the data were analysed by logistic regression. Included indicators of parental fertility were number of children, rate of unlike-sex twins as a proxy for dizygotic twinning rate, and proportion of boys. The number of children was reduced across increasing sibship size among both mothers [odds ratio (OR) = 0.95, p(trend) = 0.003] and fathers [OR = 0.97, p(trend) = 0.057] of subjects with testicular cancer. The proportion of unlike-sex twins was also reduced among their mothers [(OR = 0.56, p = 0.049 (adjusted for year of birth)] and fathers [(OR = 0.56, p = 0.049 (adjusted for year of birth)]. The results were only marginally changed when also adjusting for respective parental age. Our study indicates that parents of testicular cancer cases have reduced fertility. This suggests that genetic factors are important in the association between testicular cancer and reduced fertility.     

A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia

The study's objective was to identify HPA 1a-negative women and to offer them an intervention program aimed to reduce morbidity and mortality of neonatal alloimmune thrombocytopenia (NAIT). HPA 1 typing was performed in 100 448 pregnant women. The HPA 1a-negative women were screened for anti-HPA 1a. In immunized women, delivery was performed by Cesarean section 2 to 4 weeks prior to term, with platelets from HPA 1a-negative donors reserved for immediate transfusion if petechiae were present and/or if platelet count was less than 35 x 10(9)/L. Of the women screened, 2.1% were HPA 1a negative, and anti-HPA 1a was detected in 10.6% of these. One hundred seventy pregnancies were managed according to the intervention program, resulting in 161 HPA 1a-positive children. Of these, 55 had severe thrombocytopenia (< 50 x 10(9)/L), including 2 with intracranial hemorrhage (ICH). One woman with a twin pregnancy missed the follow-up and had one stillborn and one severely thrombocytopenic live child. In 15 previous prospective studies (136 814 women) there were 51 cases of severe NAIT (3 intrauterine deaths and 7 with ICH). Acknowledging the limitation of comparing with historic controls, implementation of our screening and intervention program seemed to reduce the number of cases of severe NAIT-related complications from 10 of 51 to 3 of 57.     

Psychological distress after recent detection of fetal malformation: short-term effect on second-trimester uteroplacental and fetoplacental circulation

We examined the short-term effect of severe maternal psychological distress on the placental circulation in second trimester in a prospective observational study. In 86 pregnant women with a newly detected fetal malformation, and 98 women with normal ultrasound findings, distress was assessed using the Impact of Event Scale and the General Health Questionnaire-28. Uterine and umbilical artery pulsatility indices, notching and heart rates were measured by Doppler ultrasound. Psychological distress was high in the anomaly group, but circulatory outcome measures did not differ between groups. Multiple regression analyses did not show an increase in circulatory resistance measures even at high distress levels.     

Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers

Human papillomaviruses (HPV) are associated with nearly all cervical cancers, 20% to 30% of head and neck cancers (HNC), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, cervical cancers, and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV(+) HNCs and cervical cancers differed in their patterns of gene expression yet shared many changes compared with HPV(-) HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV(+) HNCs and cervical cancers were found to be up-regulated in their expression of a distinct and larger subset of cell cycle genes than that observed in HPV(-) HNC. Moreover, HPV(+) cancers overexpressed testis-specific genes that are normally expressed only in meiotic cells. Many, although not all, of the hallmark differences between HPV(+) HNC and HPV(-) HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testis-specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV(+) and HPV(-) cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV(+) cancers.     

Mean arterial pressure about 40 mmHg during CPB is associated with cerebral ischemia in piglets

Objective. To investigate if a mean arterial pressure below 50 mmHg during CPB may lead to cerebral ischemia. Material and methods. Piglets with low mean arterial pressure by nitroprusside (LP-group) (n?=?6) were compared with piglets given norepinephrine to obtain high pressure (HP-group) (n?=?6) during normothermic and hypothermic CPB. Intracranial pressure, flow and markers of cerebral energy metabolism (microdialysis) were recorded. Results. Mean arterial pressure differed significantly between the groups and stabilized about 40–45 mmHg in the LP-group. Cerebral perfusion pressure decreased to 21.3 (7.7) mmHg in the LP-group and increased to 51.8 (11.2) mmHg in the HP-group at 150 min of CPB (P?<?0.001, between groups). During bypass the intracerebral glucose concentration decreased significantly in the LP-group. In this group the lactate/pyruvate ratio increased from 15.5 (5.3) to 64.5 (87.6) at 90 min and 45.0 (36.5) at 150 min (P?<?0.05) with no such changes in the HP-group. Similarly the cerebral glycerol concentration increased significantly in the LP-group, whereas glycerol remained stable in the HP-group. Conclusion. Mean arterial pressure about 40 mmHg during CPB is associated with cerebral ischemia.