Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation

In somatic cells phosphoinositide 3-kinase (PI 3-kinase) is activated upon interaction with both receptor tyrosine kinases (RTK) and G- proteins resulting in the production of moieties involved in the inositol phospholipid signalling pathway. As G proteins, RTK and the inositol phospholipids have all been implicated in the human sperm acrosome reaction, experiments were carried out to determine whether PI 3-kinase was also involved in this phenomenon. Wortmannin is a selective inhibitor of PI 3-kinase and was shown to significantly inhibit the acrosome reaction induced by both mannose-bovine serum albumin (mannose-BSA) (10, 50 and 100 nM) and a polyclonal antibody raised against an extracellular region of the sperm zona receptor kinase (ZRK, at 100 nM only). Wortmannin did not inhibit the A23187- or progesterone-induced acrosome reaction. These results suggest that PI 3- kinase is involved in the human sperm acrosome reaction. The levels of tyrosine phosphorylation of sperm proteins as detected by Western blotting using antiphosphotyrosine antibodies was not affected by wortmannin in agonist (A23187 and mannose-BSA)-stimulated spermatozoa. This indicated that PI 3-kinase operates downstream of tyrosine phosphorylation in the signal transduction cascade which leads to the human sperm acrosome reaction.      

Impact of the learning curve on term delivery rates following laparoscopic salpingostomy for infertility associated with distal tubal occlusive disease

The objective of this study was to determine the impact of the learning curve of one surgeon on the term delivery rate following laparoscopic salpingostomy for tubal infertility. This was a retrospective audit of ongoing clinical practice, undertaken in two tertiary level infertility programmes. Subjects in this study were women undergoing surgery for total occlusion of the distal Fallopian tube. The main outcome measure was cumulative term delivery rates. On stepwise life-table analysis the length of infertility, primary and secondary infertility, tubal diameter and whether surgery was performed in the first or second half of the series were significantly associated with outcome. These data suggest that there is a learning curve in obtaining skills to perform laparoscopic salpingostomy, that patient selection may improve with experience, and that selection criteria should be emphasized during didactic teaching and the preceptorship process.      

The vasoconstrictor and angiotonin-neutralizing properties of renal venous plasma

Our experiments showed that blood from a kidney in which the arterial flow and pressure had been markedly reduced possessed a greater vasoconstrictor effect and a lesser ability to neutralize angiotonin than did normal kidney blood.     

Investigation of rectal bleeding in children

Rectal bleeding is a common symptom in children, however the range of diagnoses is large and varied, with most being non-life threatening. Occasionally, however, this symptom is a sign of major morbidity, which, if not diagnosed urgently, may lead to either death or long-term morbidity. Major factors in respect of diagnosis are that of age and mode of presentation. This review will look at the surgical differential diagnoses based on age, ranging from prematurity to teenager, presentation and the investigations that are appropriate. The article will then finish with an algorithm to help direct the clinician towards the appropriate investigation.     

Manifestations of sepsis

The clinical manifestations of sepsis may be flagrant or subtle. Awareness of the signs and symptoms of sepsis allows early recognition and prompt, appropriate management. The clinical presentation, relative frequency, and current pathophysiologic understanding of the manifestations of sepsis are reviewed. Special emphasis is placed on the cardiopulmonary manifestations, which are examined in a temporal sequence of preshock, early shock, and late shock states. While therapy for the underlying infection (such as antibiotics and drainage of abscesses) is often sufficient, therapy for the specific manifestations of sepsis may also be necessary. Guidelines for therapy for these manifestations of sepsis are given.     

Educational approaches to the responsible conduct of clinical research: an exploratory study.

PURPOSE: To identify best practices in education related to the responsible conduct of clinical research (RCCR). METHOD: American Society for Bioethics and Humanities (ASBH) members involved with teaching RCCR were asked to complete an online survey, followed by an in-depth telephone interview. The online survey asked about respondents' RCCR teaching, trainees, and institutional context. The phone interview involved discussions about teaching strategies, institutional context, and needs. The study was conducted between 2003 and 2005. RESULTS: Forty-eight respondents to the online survey indicated a breadth of topics being covered in RCCR curricula; 35 respondents indicated that their RCCR teaching applied toward institutional RCCR requirements. Among the 21 instructors interviewed, many described a wide variety of teaching responsibilities. Recommended teaching strategies included fostering interactive discussion, using skills-based exercises such as designing IRB applications, accommodating students' individual interests in curriculum design, involving experienced researchers, involving trainees early in their careers as well as requiring continuing education, and designing a curriculum with a clear view of educational objectives. Interviewees described the institutional supports they needed, and they noted that insufficient support sometimes undermines RCCR teaching goals. Participants generally agreed that RCCR education should be required. CONCLUSIONS: Strong agreement among participants concerning recommended strategies for teaching RCCR provides useful, if provisional, guidance to instructors and institutions charged with providing such training. The study suggests a need for substantial investments in RCCR training, studying outcomes, and developing mechanisms to ensure the quality of instruction.     

The parent interview for child symptoms: a situation-specific clinical research interview for attention-deficit hyperactivity and related disorders.

OBJECTIVE: To describe the properties of a semistructured research interview of parents designed to evaluate attention-deficit hyperactivity disorder (ADHD) and related psychopathology. METHOD: We examined interrater reliability in 48 videotaped interviews randomly selected from a large clinic sample. We examined convergence of the Parent Interview for Child Symptoms (PICS) and Conners' Parent Rating Scale (CPRS) scores in 594 clinic-referred cases and 26 control subjects, comparing the groups generated by cross-tabulation on measures of intelligence, academic achievement, and inhibitory control. RESULTS: Intraclass correlation coefficients for symptom scores of ADHD, oppositional defiant disorder (ODD), and conduct disorder (CD) were excellent. We found good reliability for diagnoses of ADHD (e = 0.73) and CD (kappa = 0.73) and excellent reliability for the diagnosis of ODD (kappa = 0.80). Two-thirds of cases were classified similarly on the PICS and the CPRS. Greater impairment in inhibitory control was observed in cases identified as ADHD by the PICS, compared with those identified by the CPRS-ADHD index. CONCLUSIONS: The PICS displays good reliability and validity, indicating that a balance between clinical applicability and reliability can be achieved in the development of clinical research instruments.