Urodynamic findings in men operated on for an undescended testicle.

OBJECTIVE: To test the hypothesis that men with a history of undescended testicle have voiding problems similar to those in rodents exposed to excessive amounts of oestrogens during development, although the role of oestrogen in the failure of the human testicle to descend remains controversial. PATIENTS AND METHODS: Thirteen men (mean age 45 years) previously operated on for an undescended testicle (testis-retention, TR group) and 12 age-matched men operated on for inguinal hernia or appendicitis (control group) participated in a urodynamic examination, transrectal ultrasonography (TRUS) of the prostate, and blood tests for hormones and prostate-specific protein. They also completed a questionnaire on urinary symptoms. RESULTS: The free maximum flow rate was significantly lower and the detrusor pressure at maximum flow (P(det)Q(max)) slightly higher in the TR than the control group. Three men in the TR group (and none of the controls) had bladder outlet obstruction (BOO), whereas voiding was not obstructed among 11 control men (and five men in the TR group). The hormone concentrations of the groups did not differ significantly but the prostates were significantly smaller in the TR group. The testosterone concentrations and the ratio between 17beta-oestradiol (E2) and free testosterone (E2/fT) influenced prostate size significantly. An exploratory analysis suggested that E2/fT may influence the maximum detrusor pressure and P(det)Q(max). CONCLUSION: Men born with an undescended testicle had smaller prostates but more often had BOO than did the controls. The results suggest that an imbalance between the actions of oestrogen and testosterone may influence the initiation and continuance of BOO among cryptorchid men.

Withdrawal time estimation of veterinary drugs: extending the range of statistical methods.

In order to use a drug in a food producing animal, evidence has to be provided that after a certain withdrawal time, drug residues in tissues, such as muscle meat, fat, liver, kidney etc., are below a given maximum residue limit (MRL), for a majority of animals. Several statistical methods, both regression based and nonparametric based methods, have been proposed, each relying on different sets of assumptions, which may or may not hold for the specific data situation. The purpose of this paper is to enrich the range of methods, i.e. to provide approaches for situations where current methods are inappropriate. Bayesian methods, using Markov chain Monte Carlo, are proposed to derive inference on the parameters of interest.

Pharmacokinetics of clomipramine in dogs following single-dose intravenous and oral administration.

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. ANIMALS: 6 male and 6 female Beagles. PROCEDURES: Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food.

Efficacy of nitenpyram as a systemic flea adulticide in dogs and cats.

In a clinical trial involving 123 cats and 88 dogs, the efficacy of tablets containing nitenpyram against natural flea infestations was investigated. The animals were selected from the routine cases of nine veterinary clinics in the UK and 143 were treated with the tablets and 68 control animals were treated with placebo tablets. Each animal was maintained in an individual cage. The time when the first fleas fell off each animal was recorded between 30 minutes and five hours after treatment, and six hours after treatment the numbers of live, moribund or dead fleas on each animal were determined, and the flea survival rate was calculated. The drug's efficacy was assessed by comparing the mean survival rates of fleas on the treated and control animals. Fleas started to fall from the animals 30 minutes after treatment and two hours after treatment some fleas had detached from 81 per cent of the treated animals. After six hours the efficacy of the drug reached 96.7 per cent on dogs and 95.2 per cent on cats, and 85.9 per cent of the fleas were found off the treated animals, compared with 1.8 per cent in the controls. No adverse drug reactions were recorded during the trial.

A generalization of the mixture model in the mapping of quantitative trait loci for progeny from a biparental cross of inbred lines.

The recent advent of molecular markers has created a great potential for the understanding of quantitative inheritance. In parallel to rapid developments and improvements in molecular marker technologies, biometrical models have been constructed, refined and generalized for the mapping of quantitative trait loci (QTL). However, current models present restrictions in terms of breeding designs to which they apply. In this paper, we develop an approach for the generalization of the mixture model for progeny from a single bi-parental cross of inbred lines. Detailed derivations are given for genetic designs involving populations developed by selfing, i.e., where marker genotypes are obtained from Fx (x > or = 2) individuals and where phenotypes are measured on Fy (y > or = x) individuals or families. Extensions to designs involving doubled-haploids, backcross-derived individuals and random matings are outlined. The derivations presented here can easily be combined with current QTL mapping approaches.