Renin, (pro)renin and receptor: an update

PRR [(pro)renin receptor] was named after its biological characteristics, namely the binding of renin and of its inactive precursor prorenin, that triggers intracellular signalling involving ERK (extracellular-signal-regulated kinase) 1/2. However the gene encoding for PRR is named ATP6ap2 (ATPase 6 accessory protein 2) because PRR was initially found as a truncated form co-purifying with V-ATPase (vacuolar H+-ATPase). There are now data showing that this interaction is not only physical, but also functional in the kidney and the heart. However, the newest and most fascinating development of PRR is its involvement in both the canonical Wnt/β-catenin and non-canonical Wnt/PCP (planar cell polarity) pathways, which are essential for adult and embryonic stem cell biology, embryonic development and disease, including cancer. In the Wnt/β-catenin pathway, it has been shown that PRR acts as an adaptor between the Wnt receptor LRP5/6 (low-density lipoprotein receptor-related protein 5/6) and Fz (frizzled) and that the proton gradient generated by the V-ATPase in endosomes is necessary for LRP5/6 phosphorylation and β-catenin activation. In the Wnt/PCP pathway, PRR binds to Fz and controls its asymetrical subcellular distribution and therefore the polarization of the cells in a plane of a tissue. These essential cellular functions of PRR are independent of renin and open new avenues on the pathophysiological role of PRR. The present review will summarize our knowledge of (pro)renin-dependent functions of PRR and will discuss the newly recognized functions of PRR related to the V-ATPase and to Wnt signalling.     

The role of attachment avoidance in extradyadic sex

The purposes of the present research were to examine the relationship between attachment and extradyadic sex and to investigate a mediator of this relationship. Study 1 showed that attachment avoidance was positively associated with extradyadic sex, while attachment anxiety was unrelated to it. These results were maintained after controlling for sexual satisfaction, sexual desire, gender, and age. Study 2 replicated the results from Study 1, while also controlling for couple adjustment. Study 3 used a prospective design and further showed that concerns with the partner's desire for engagement mediated the relationship between attachment avoidance and extradyadic sex. Overall, the findings suggest that attachment avoidance increases people's irritation relative to their partner's desire for engagement which, in turn, increases their likelihood to engage in extradyadic sex. The possibility that individuals characterized by attachment avoidance might use extradyadic sex as a way to distance themselves from their partner is discussed.     

Identifying combinations of risk and protective factors predicting physical activity change in high school students

Research sought to identify combinations of risk and protective factors predicting change in physical activity (PA) over one year in high school students. Adolescents (N = 344; M = 15.7 years) participated in a longitudinal study with assessment of demographics, substance use/smoking exposure, height and weight, psychological factors, and PA in 10th and 11th grade. PA participation in 11th grade was greatest for adolescents who engaged in PA and had high sports competence (78%), and least for adolescents who did not engage in or enjoy PA (13%) in 10th grade. Identifying adolescent subgroups at risk for decreasing PA can inform the development of tailored interventions.     

A phase 1 study of nifurtimox in patients with relapsed/refractory neuroblastoma

The primary aim of this phase 1 study was to determine the maximum tolerated dose (MTD) and evaluate the safety of nifurtimox alone and in combination with cyclophosphamide and topotecan in multiple relapsed/refractory neuroblastoma pediatric patients. The secondary aim was to evaluate the pharmacokinetics of nifurtimox and the treatment response. To these ends, we performed a phase 1 dose escalation trial of daily oral nifurtimox with toxicity monitoring to determine the MTD, followed by 3 cycles of nifurtimox in combination with cyclophosphamide and topotecan. Samples were collected to determine the pharmacokinetic parameters maximum concentration, time at which maximum concentration is reached, and area under the curve between 0 and 8 hours. Treatment response was evaluated by radiographic and radionuclide (I-metaiodobenzylguanidine) imaging, measurement of urinary catecholamines, and clearance of bone marrow disease. We determined the MTD of nifurtimox to be 30 mg/kg/d. The non-dose-limiting toxicities were mainly nausea and neuropathy. The dose-limiting toxicities of 2 patients at 40 mg/kg/d were a grade 3 pulmonary hemorrhage and a grade 3 neuropathy (reversible). Overall, nifurtimox was well tolerated by pediatric patients at a dose of 30 mg/kg/d, and tumor responses were seen both as a single agent and in combination with chemotherapy. A Phase 2 study to determine the antitumor efficacy of nifurtimox is currently underway.     

Does neuraxial anesthesia reduce intraoperative blood loss?: A meta-analysis

STUDY OBJECTIVE: To perform a meta-analysis of available randomized controlled trials to determine if neuraxial anesthesia would decrease blood loss, compared with general anesthesia. DESIGN: Retrospective analysis. SETTING: University medical center. MEASUREMENTS: The National Library of Medicine's PubMed database was searched from the period of 1966 to December 10, 2003 for all abstracts containing words related to neuraxial anesthesia and general anesthesia. The search was limited to randomized controlled trials and the English language and yielded 667 articles. MAIN RESULTS: A total of 66 articles met inclusion criteria and were used for the analysis. Overall, the use of spinal anesthesia resulted in significantly less estimated blood loss (EBL) (P < 0.0001), compared with epidural anesthesia (EA), which, in turn, resulted in significantly less EBL compared with general anesthesia (GA) or combined GA-EA (P < 0.0001). No significant difference between GA and GA-EA was noted when analysis was limited to studies directly comparing GA-EA and GA. CONCLUSIONS: Use of spinal anesthesia or EA is associated with a significant decrease in EBL when compared with that for GA or combined GA-EA.     

Plantarflexion strength of the toes: age and gender differences and evaluation of a clinical screening test

BACKGROUND: The toes play an important stabilizing role in weightbearing activities. However, the factors that influence toe plantarflexion strength are poorly understood, and there are no validated measures for assessing toe weakness in the clinical setting. Therefore, the objectives of this study were to determine whether plantarflexion strength of the toes differs according to age and gender and to evaluate the validity of a clinical screening test for assessing toe plantarflexor weakness (the paper grip test). METHODS: Plantarflexion strength of the hallux and lesser toes was measured in 40 young participants (20 men and 20 women, mean age 20.8 +/- 2.2 years) and 40 older participants (20 men and 20 women, mean age 74.6 +/- 5.7 years) using a pressure platform in conjunction with clinical assessment using the paper grip test. RESULTS: Older participants exhibited 32% less plantarflexion strength of the hallux and 27% less plantarflexion strength of the lesser toes compared to younger participants, and women exhibited 42% less hallux plantarflexor strength than men. Gender did not influence lesser toe plantarflexor strength. Participants who failed the paper grip test exhibited significantly reduced plantarflexion strength for both the hallux and lesser toes. The sensitivity and specificity of the paper grip test of the hallux to predict plantarflexor strength less than 2.6 kg was 80% and 79%, respectively, and the sensitivity and specificity of the paper grip test of the lesser toes to predict plantarflexor strength less than 2.2 kg was 75% and 74%, respectively. CONCLUSIONS: These findings indicate that aging is associated with reduced plantarflexion strength of the toes. The paper grip test may be a useful screening tool to detect toe weakness in the clinical setting.     

General practitioners' experiences of managing patients with chronic leg ulceration

OBJECTIVE: To understand general practitioners' experiences of managing patients with chronic leg ulceration, thus informing future strategies to improve leg ulcer care in general practice, Australia. DESIGN: Qualitative study using phenomenology and in-depth interviewing. PARTICIPANTS AND SETTING: Maximum variation sample of 12 GPs working in the Perth and Hills Division of General Practice between September and December 2004. MAIN OUTCOME MEASURE: Themes in participants' experiences of leg ulcer care. FINDINGS: Participants regarded leg ulcer management as an integral part of general practice. They expressed a desire to maintain their involvement, yet relied on nursing assistance. They perceived that ulcer care was usually straightforward and successful. Approaches to management appeared to differ significantly from that outlined in current guidelines. Instead, participants valued accessibility of care for the patient, awareness of patient context and regular review. Occasional problems with non-healing ulcers were experienced, and, in these situations, specialist opinion was appreciated. CONCLUSION: This study highlights fundamental differences between GP and specialist conceptualisation of leg ulcer care. For GPs, it identifies key areas of ulcer management that could be improved. For specialists, it suggests that widespread implementation of traditional guidelines may not be appropriate or acceptable. New approaches to leg ulcer management in general practice are likely to need a combination of education, human resources and practical support.     

Tension faecopneumothorax as the rare presenting feature of a traumatic diaphragmatic hernia

A traumatic diaphragmatic hernia is a well-known complication following abdominal trauma. It occurs in approximately 3% of abdominal injuries with a 2/1 ratio of penetrating trauma. These injuries remain undiagnosed in nearly half of the patients in the acute phase. Hence, delayed presentation, days or even years after the onset of the initial trauma, are not uncommon. Indeed, they are often revealed by a complication. It's exactly what happened with our patient who presented with an acute tension fecopneumothorax, resulting from diaphragmatic herniation and perforation of the colon in the pleural cavity. This presentation is rarely reported. In a search of the literature, only 11 cases could be found.     

Abortion training in Canadian obstetrics and gynecology residency programs

OBJECTIVE: To study abortion training in Canadian obstetrics and gynecology (ob-gyn) residency programs. METHODS: An anonymous questionnaire was sent to all postgraduate year (PGY)-4 and PGY-5 ob-gyn residents (n=130) and residency program directors (n=16) in Canada. The questionnaires inquired about demographic information, details of abortion training, resident participation in training, and intention to provide abortions after residency. RESULTS: Ninety-two of 130 residents (71%) and 15 of 16 program directors (94%) responded. Abortion training is considered routine in approximately half of programs and elective in half. The majority of residents (71%) participated in abortion training, and half plan to do elective abortions after residency. More than half of residents felt competent after training to perform first-trimester aspiration and second-trimester inductions but did not feel competent in first-trimester medical abortions or dilation and evacuation (D&E). Residents were more likely to participate in training if the program arranged the training for residents (P=.04) and were more likely to intend to provide abortions if the training was considered routine (P=.02), while controlling for all significant demographic and training variables. CONCLUSION: Most Canadian ob-gyn programs offer some training in elective abortion, but only half include it routinely in training, and the minority of residents feels competent in D&E and medical abortion. Integrated abortion training was associated with greater resident participation in training and increased likelihood of intention to provide abortions after residency.