Apoptosis: a key effector mechanism of lymphocyte action in human nonseminomatous testicular carcinoma?

OBJECTIVE: To correlate the number of tumour-infiltrating T lymphocytes (TILs) with the extent of apoptosis in testicular germ cell tumours, as TILs are considered to be a favourable prognostic factor of human testicular tumours, especially of seminomas, but the mechanism by which TIL contribute to an improved outcome is unclear. MATERIALS AND METHODS: Tissue samples from 47 patients with nonseminomatous germ cell tumour (NSGCT) and 15 with seminomatous GCT were investigated immunohistochemically for lymphocyte infiltration and apoptosis. The apoptotic index (AI) was assessed in various categories (DNA condensation and fragmentation) using in-situ end-labelling to identify typical apoptotic DNA strand breaks, and nuclear staining to identify typical apoptotic morphology. RESULTS: In seminomatous GCT there was no correlation between the number of TILs and any AI. In NSGCT there was only a relationship between lymphoid infiltration and those AIs showing morphological criteria of apoptosis in a small subgroup of NSGCT, i.e. metastasized embryonal cell carcinomas. Only 1.2% (AI, chromatin condensation) and 0.8% (AI, fragmentation and condensation) of all tumour cells showed these features of apoptosis. The overall AI in NSGCT was 7.9%. CONCLUSIONS: TILs do not seem to induce apoptosis in testicular tumours. Embryonal cell carcinomas might be susceptible to lymphocyte attack, resulting in apoptosis of the tumour cell. The mechanisms of interaction between lymphocytes and testis tumour cells need further investigation.     

The effects of temperature and acute alcohol intoxication on brain stem auditory evoked potentials in the cat

The effects of core temperature changes (less than 1 degree C) and acute ethanol intoxication (100-400 mg%) on brain stem auditory evoked potentials in cats were studied independently--then together--to distinguish between a putative direct pharmacological action of ethanol on brain stem auditory neurons, as reflected in reported BAEP latency changes, and in indirect action of ethanol mediated through slight changes in central temperatures. The results suggest that the reported BAEP latency effects are attributable, largely if not entirely, to the second mechanism above. No significant temperature-independent BAEP latency alterations occurred at any sublethal blood ethanol concentration or in one dosage that subsequently proved fatal. These findings do not exclude a direct ethanol effect on brain stem auditory neurons but provide no evidence for a temperature-independent effect. Knowledge of secondary BAEP temperature effects associated with drug administration is crucial to proper interpretation of BAEPs in both experimental and clinical applications.     

Age-related complaints in women and their determinants based on a representative community study

OBJECTIVES: To determine (a) the relationship between physical and somatoform complaints, distress, life satisfaction and ageing in the female community and (b) to identify their psychosocial determinants. METHODS: Two stratified random samples of the German female population (total of 2771 women) were investigated by standardised questionnaires of complaints (MFI-20, GBB), distress (HADS) and life satisfaction (LSQ). RESULTS: When participants were divided into six age groups (18-30, 31-40, 41-50, 51-60, 61-70, >70 years), we found a continuous increase of physical, mental and general fatigue, inactivity and reduced motivation. Age-associated increases were also observed for exhaustion, cardiovascular and musculoskeletal complaints, but not for gastrointestinal complaints. This was accompanied by a reduced satisfaction with health and sexuality and increased depression and anxiety scores. Marked increases of complaints were mostly found in the sixth decade. However, depression already increased in the fourth decade, musculoskeletal complaints and reduced motivation peaked in the fifth decade, whereas mental fatigue did not increase significantly before the seventh decade followed by a rise of anxiety in women over 70 years. Most consistently, complaints were predicted by a combination of negative subjective health, higher age, lack of a partnership, and additional sociodemographic vulnerability (unemployment, low income, residence) and protective (religion) factors. CONCLUSIONS: Community data provide important reference points in evaluating the ageing female. Based on regression analyses, we could also demonstrate the contribution of psychosocial vulnerability and protective factors to the development of age-related symptoms.     

Basic science and translational research in female pelvic floor disorders: proceedings of an NIH-sponsored meeting

AIMS: To report the findings of a multidisciplinary group of scientists focusing on issues in basic science and translational research related to female pelvic floor disorders, and to produce recommendations for a research agenda for investigators studying female pelvic floor disorders. METHODS: A National Institutes of Health (NIH)-sponsored meeting was held on November 14-15, 2002, bringing together scientists in diverse fields including obstetrics, gynecology, urogynecology, urology, gastroenterology, biomechanical engineering, neuroscience, endocrinology, and molecular biology. Recent and ongoing studies were presented and discussed, key gaps in knowledge were identified, and recommendations were made for research that would have the highest impact in making advances in the field of female pelvic floor disorders. RESULTS: The meeting included presentations and discussion on the use of animal models to better understand physiology and pathophysiology; neuromuscular injury (such as at childbirth) as a possible pathogenetic factor and mechanisms for recovery of function after injury; the use of biomechanical concepts and imaging to better understand the relationship between structure and function; and molecular and biochemical mechanisms that may underlie the development of female pelvic floor disorders. CONCLUSIONS: While the findings of current research will help elucidate the pathophysiologic pathways leading to the development of female pelvic floor disorders, much more research is needed for full understanding that will result in better care for patients through specific rather than empiric therapy, and lead to the potential for prevention on primary and secondary levels.     

Spinal anesthesia for cesarean section following inadequate labor epidural analgesia: a retrospective audit

BACKGROUND: High blocks have been reported when spinal anesthesia is used for cesarean section following inadequate labor epidural analgesia. We have therefore modified the practice at our institution to minimize this risk and conducted a retrospective observational study of outcome following the change of practice. METHOD: The records of 115 women with inadequate epidural labor analgesia who required cesarean section between July 1998 and January 2002 were studied. No epidural boluses were administered in the 30 min preceding spinal anesthesia and a reduced spinal dose, median (range) 9.38 mg (7.5-11.3 mg) of 0.75% hyperbaric bupivacaine and fentanyl 15 microg (10-25 microg) was used. Patients were left sitting for 2 min and then positioned supine with left uterine displacement and were closely monitored for symptoms or signs that would suggest a high block. RESULTS: No parturient developed a high spinal necessitating intubation, and there was no adverse neonatal outcome. CONCLUSION: These findings do not conclusively establish this method as safe, but should spinal anesthesia for cesarean section following suboptimal labor epidural analgesia be considered, avoiding epidural boluses immediately preceding spinal injection, using a lower spinal dose, and delayed supine positioning following spinal injection may be advisable.