Influence of sampling on the reproducibility of ovarian follicle counts in mouse toxicity studies

Different ovarian follicle counting procedures were investigated to reduce labor while retaining statistical power. Intact ovaries of untreated CD-1 mice (20/group) from National Toxicology Program Reproductive Assessment by Continuous Breeding (RACB) studies were serially sectioned at 6 microm. Mean numbers of small and growing follicles were used to assess sampling efficiency. In 10 mice per group, comparisons were made between 10% nonrandom samples from every 10th section starting at either the first or sixth section having follicles (approximately 40 sections per ovary). These 10% counts were compared with 5% (20 sections) and 20% (80 sections) nonrandom samples and with 1% (4 sections), 5%, or 10% random samples from the same 10 animals. For two studies, a 10% nonrandom sample was analyzed from 20 mice per group. Follicle counts for each group were comparable regardless of the sampling paradigm. Four to 10 animals provided 90% confidence that a 20% difference in mean counts would be detected. The 1% sample had a larger error term and, thus, slightly reduced statistical power. These data suggest that follicle counts from 1% or 5% random samples may provide a suitable screen for ovarian toxicity.     

Stimulation of insulin release from the MIN6 cell line by a new imidazoline compound, S-21663: evidence for the existence of a novel imidazoline site in beta cells

1. The MIN6 cell line derived from in vivo immortalized insulin-secreting pancreatic beta cells was used to study the insulin-releasing capacity and the cellular mode of action of S-21663, a newly synthesized imadizoline compound known for its antidiabetic effect in vivo and its ability to release insulin from perfused pancreas. 2. S-21663, at concentrations ranging from 10(-5) M to 10(-3) M was able to release insulin from MIN6 cells; its activity peaked at 10(-4) M, a drop in the stimulant factor being noted between 10(-4) and 10(-3) M. Its efficacy, which did not differ whatever the glucose concentration (stimulant or not), was higher than that of the other secretagogues tested, glucose, sulphonylureas or the peptide tGLP-1. 3. In contrast to tGLP-1, S-21663 did not change the cyclic AMP content, whereas it increased Ca2+ influx via verapamil- and nifedipine-sensitive voltage-dependent calcium channels, the insulin release being a direct consequence of this Ca2+ entry. The S-21663-induced Ca2+ influx appears to be essentially the consequence of closure of K+ channels which differ from the ATP-dependent K+ (K-ATP) channels as determined by measurement of 86Rb efflux and use of a K-ATP channel opener. 4. Comparison of the effects of S-21663 to that of efaroxan, another imidazoline compound shown to act on insulin release in a glucose-dependent way via binding sites distinct from the imidazoline I1 and I2 sites, suggested that S-21663 acts through a novel site which displays a remarkably stable expression along the cell culture. 5. It is concluded that S-21663 is a very efficient, glucose-independent insulin secretagogue acting through a novel imidazoline site, linked to K+ channels, distinct from the I1, I2 and 'efaroxan' binding sites. In vitro and in vivo features of S-21663 indicate that this compound, or new drugs derived from it, might be the basis for a new pharmacological approach to the mangement of type II (non insulin-dependent) diabetes.     

Do vaginal lactobacilli prevent preterm labour?

OBJECTIVE: To determine the prevalence of Lactobacillus spp. in vaginal flora during pregnancy and to assess the protective effects of lactobacilli against preterm labour. DESIGN: Cross-sectional analysis of Lactobacillus spp. in the vaginal flora of the pregnant coloured population of the Western Cape. PARTICIPANTS: A total of 480 consecutive pregnant women, aged 13-48 years, seen at their first visit to the Tygerberg Hospital antenatal clinic. MAIN OUTCOME MEASURES: Preterm labour, i.e. before 34 and 37 weeks' gestation, premature rupture of membranes, intra-uterine growth retardation and perinatal deaths. RESULTS: A total of 163 patients had negative cultures and 317 positive cultures for lactobacilli, aerobes or both. Delivery before 37 weeks occurred in 18% and 20% of the two groups, respectively. Lactobacillus only was cultured from 116 patients and Lactobacillus and/or other aerobes from 201 patients. Preterm labour occurred in 20% of the first group and in 19% of the second group. The perinatal outcome in patients from whom lactobacilli only were cultivated did not differ from patients from whom other aerobes and lactobacilli or other aerobes only were cultured. CONCLUSION: In patients at high risk for preterm labour, the presence of lactobacilli in the vagina does not seem to play a protective role.     

Hepatitis C virus genotypes in liver transplant recipients: impact on posttransplant recurrence, infections, response to interferon-alpha therapy and outcome

BACKGROUND: End-stage liver disease due to hepatitis C virus (HCV) is the most common indication for liver transplantation in U.S. veterans. We investigated the influence of HCV genotypes on the incidence and timing of recurrent HCV hepatitis, survival, infectious morbidity, and response to interferon-alpha therapy in this unique patient population. METHODS: HCV genotype was determined by direct sequencing of the NS5 region of HCV with type-specific primers. RESULTS: Genotype 1a (66%, 32/47) was the predominant genotype. Type 1b was found in 25% (12/47) of patients and type 2b was found in 9% (4/47). Histopathologically recurrent HCV hepatitis developed in 53% (25/47) of the patients after transplantation. This group included 45% (14/31) of the patients with type 1a, 67% (8/12) of the patients with type 1b, and 25% (1/4) of the patients with type 2b (P>0.5). The time to recurrence and the severity of HCV recurrence as defined by aminotransferase levels or Knodell scores were not different among the three genotypes. There was a trend toward a higher incidence of major infections in patients with type 1b (75%) versus type 1a (48%) and type 2b (50%) (P=0.11). The response to interferon-a therapy did not differ significantly among the genotypes. Mortality at 5 years was 16% (5/31) in patients with genotype 1a, 42% (5/12) in patients with genotype 1b, and 50% (2/4) in patients with genotype 2b (P=0.06). CONCLUSIONS: The incidence, time to recurrence, and response to interferon-alpha therapy did not differ between the various genotypes in our liver transplant recipients. However, there was a trend toward higher infectious morbidity and overall mortality in patients with genotype 1b after transplantation.     

Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasia. A serial intravascular ultrasound study

Hepatic hydrothorax is a rare complication of portal hypertension. Conservative therapy may be successful but refractory hepatic hydrothorax is not uncommon. Management of refractory hydrothorax is usually ineffective and can result in a worsened clinical status. Transjugular intrahepatic portosystemic shunts (TIPS) lower portal pressure and have been used in the treatment of refractory ascites. The aim of this study was to determine the efficacy of TIPS in the treatment of symptomatic refractory hepatic hydrothorax. A TIPS was placed in 24 consecutive cirrhotic patients with symptomatic refractory hepatic hydrothorax. Five patients (20.8%) were Child's/Pugh class B and 19 (79.2%) were class C. All had undergone multiple thoracenteses and were hypoalbuminemic. Mean follow-up was 7.2 months (range, 0.25-49 months). Fourteen (58.3%) of 24 patients had complete relief of symptoms after shunt placement and did not require further thoracentesis. Five (20.8%) additional patients required fewer thoracenteses. Five (20.8%) patients developed worsening liver function and died within 45 days. In eight (66.7%) of 12 patients with > or = 60 days of follow-up, the serum albumin increased by a mean of 1.2 g/dL (range, 0.1-2.2 g/dL). The Child's-Pugh score improved in 7 (58.3%) of these 12 patients and two patients improved from class C to class A. These two patients no longer require liver transplantation. This study shows that TIPS can be effective in the management of symptomatic, refractory hepatic hydrothorax. Clinical and laboratory improvement may be seen and liver transplantation may become unnecessary.     

Options for diabetic patients with chronic heel ulcers

Which are the determinants of return to work in middle aged myocardial infarction patients? This question was analysed by means of a follow-up study on men between 1986 and 1992 (group 1: n = 64, age = 46.6 (+/- 5.4), 5-6 years follow-up; group 2: n = 36, age = 51.2 (+/- 7.5), 2 years follow up), all of whom underwent a cardiac rehabilitation program in our hospital. Our aim was to determine the predictive power of social and psychological as compared to cardiologic factors. These factors were operating under two relevant conditions: 1. relative social homogeneity of the samples; 2. rehabilitation including qualified cardiologic diagnostic and an interdisciplinary therapeutic program. As a result we found age--at the same time a biologic and a social variable--to be the best independent predictor in logistic regression as in discriminant analysis. Age was followed by hopelessness in the year before MI, ST segment depression in physical stress test and, with restriction, marital status. Thus our study points to three factors limiting employment status: age as a biological and social limit for achievement, ST segment depression as a coronary and ongoing hopelessness as a psychological limit, with a social background of living alone in some cases. It is important for cardiac rehabilitation to take into account not only biological but also social and psychological limits of work capacity. Comprehensive care tries to modify these limits but cannot remove them.     

Obstructed nasolacrimal duct system in epiphora: long-term results of dacryocystoplasty by means of balloon dilation

PURPOSE: To evaluate the long-term results of balloon dacryocystoplasty in the treatment of epiphora due to obstruction of the nasolacrimal ducts. MATERIALS AND METHODS: One hundred eyes in 84 patients with complete or incomplete obstruction of the lacrimal sac and duct were selected for dacryocystoplasty. A catheter with a balloon diameter of 3 mm was used. Follow-up was 5-48 months. No stents were placed. A Kaplan-Meier analysis was used to evaluate patency. RESULTS: The long-term primary patency rate was 70% +/- 7 (+/- standard error). Repeat dacryocystoplasty was successful in 10 of the 11 cases with initial failure or reobstruction during follow-up, which yielded a long-term secondary patency rate of 81% +/- 7. There was no association between the length of the obstruction or the duration of symptoms before dacryocystoplasty and the initial and long-term success. Initial and long-term success was statistically significantly higher in dacryocystoplasty for an incomplete obstruction rather than for a complete obstruction. CONCLUSION: The long-term results of dacryocystoplasty, followed if necessary by repeat dacryocystoplasty, are good. Dacryocystoplasty is a safe and simple procedure and could become the treatment of choice for epiphora due to obstruction of the nasolacrimal ducts. Dacryocystorhinostomy is indicated when dacryocystoplasty or repeat dacryocystoplasty fails or when dacryocystoplasty is contraindicated (e.g., in anatomic malformations in the lacrimal duct or bony canal).