The combination of prazosin and verapamil in the treatment of essential hypertension

An exaggerated fall in blood pressure has been reported with the combination of an alpha 1-blocker and a calcium antagonist. This study investigated, in a placebo-controlled, randomized crossover trial, the clinical usefulness of the combination of prazosin (2 mg b.i.d.) and verapamil (160 mg b.i.d.). Therapeutic efficacy was monitored at regular outpatient visits: average supine and erect blood pressures were, respectively, 175/99 and 176/103 mm Hg with placebo, 160/91 and 164/96 mm Hg with single drug treatment, and 152/84 and 152/89 mm Hg with combination therapy. This significant and clinically useful reduction in blood pressure had an overall magnitude of approximately 28/18 mm Hg (supine) and 29/19 mm Hg (erect). Further measurements were made during a series of intensive study days, and the most important additional finding was a pharmacokinetic interaction that resulted in increased peak concentrations and bioavailability of prazosin. In conclusion, the combination of prazosin and verapamil proved effective in the treatment of 12 patients with essential hypertension who had been poorly responsive to conventional treatment with a beta-blocker and thiazide diuretic.     

Regulation of NGF gene expression in CNS glia by cell-cell contact.

Nerve growth factor (NGF) gene expression in central nervous system (CNS) glia appears to be associated with active glial growth. To study the underlying molecular mechanisms, we examined the effects of a number of growth-related factors on NGF mRNA expression in glial cultures. Our results suggest that glial membrane interaction, as a consequence of growth, actively inhibits NGF gene expression in CNS glia.     

Systematic review of effectiveness of bisphosphonates in treatment of low bone mineral density and fragility fractures in juvenile idiopathic arthritis.

AIMS: To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated with juvenile idiopathic arthritis (JIA), and the safety of bisphosphonates in JIA and other conditions. METHODS: Literature databases were searched using a structured search strategy. The effectiveness review included any studies of children with JIA treated with bisphosphonates. The safety review also included studies of osteogenesis imperfecta. Quantitative data analysis was not undertaken because of the heterogeneity of the studies; findings were summarised using tables and narrative synthesis. RESULTS: Ninety four studies were identified. Sixteen studies (78 JIA children) were included in the effectiveness review: one randomised controlled trial, three controlled cohort studies, 11 case series, and one case report. At baseline, children had low BMD below the expected values for age and sex matched children. In all studies, treatment with bisphosphonates increased BMD compared with baseline: the mean percentage increase in spine BMD ranged from 4.5% to 19.1%. Overall, studies were heterogeneous and of variable quality. A total of 59 papers were included in the safety review; treatment durations were up to three years. The most common side effect was a flu-like reaction with intravenous treatment. This occurred during the first infusion and was transient; the symptoms were managed with paracetamol and did not occur during subsequent cycles. CONCLUSIONS: Bisphosphonates are a promising treatment for low BMD and fragility fractures in children with JIA. However, the quality of the current evidence is variable and better studies are needed to more clearly assess their role.     

A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.     

Assessment of the durability of robot-assisted laparoscopic sacrocolpopexy for treatment of vaginal vault prolapse

Transabdominal sacrocolpopexy has been shown, in multiple long-term studies of its success and durability, to be the definitive treatment option for post-hysterectomy vaginal vault prolapse. It is, however, associated with greater morbidity than vaginal repair. We describe a minimally invasive technique for vaginal vault prolapse repair and present our experience with a minimum of one-year follow-up. The surgical technique involves five laparoscopic ports—three for the da Vinci robot and two for the assistant. After appropriate dissection a polypropylene mesh is attached to the sacral promontory and to the vaginal apex by use of Gore-Tex sutures. The mesh material is then covered by the peritoneum. Patient analysis focused on complications, urinary continence, patient satisfaction, and morbidity, with a minimum of 12 months follow-up. Forty-two patients with post-hysterectomy vaginal vault prolapse underwent robot-assisted laparoscopic sacrocolpopexy at our institute and 35 have a minimum of 12 months follow-up, with a mean follow-up of 36 months (range 12–48) in the group. Mean age was 67 (47–83) years and mean operating time was 3.1 (2.15–4.75) h for the entire cohort. All but one patient were discharged home on postoperative day one; one patient left on postoperative day two. One developed recurrent grade three rectocele, one had recurrent vault prolapse, and two suffered from vaginal extrusion of mesh. All patients were satisfied with their outcome. The robot-assisted laparoscopic sacrocolpopexy is a minimally invasive technique for vaginal vault prolapse repair, combining the advantages of open sacrocolpopexy with the reduced morbidity of laparoscopy. We observed reduced hospital stay, low occurrence of complications, and high patient satisfaction, with a minimum of 1-year follow-up. Most importantly, the long-term results of the robotic repair are similar to those of open repair, but with significantly less morbidity.     

Relative incidence of Crohn's disease and ulcerative colitis in six Melbourne hospitals

Information on the relative incidence of Crohn's disease and ulcerative colitis was obtained by a prospective investigation at six Melbourne teaching hospitals. One hundred and eleven patients who presented with chronic inflammatory bowel diseases between 1980-1981 were admitted to the study. Forty (36%) patients were diagnosed as having Crohn's disease and 63 (57%) patients as having ulcerative colitis. The type of chronic inflammatory bowel disease could not be determined in eight (7%) patients. These findings suggest that the relative frequency of Crohn's disease and ulcerative colitis in Melbourne hospitals is within the range that is reported for northern Europe and the United States.