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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.

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A study was performed to test the effect of sensitization to flea antigen, followed by exposure to fleas on mast cells (MCs), their subtypes, and IgE+ cells. Biopsies were taken from flea-sensitized dogs (n=28) and non-sensitized dogs (n=5) that had been exposed to fleas. Control groups consisted of flea-sensitized (n=12) and non-sensitized dogs (n=9) that were not exposed to fleas. Biopsies, taken before, 24 and 72 h after local flea exposure, were stained with haematoxylin and eosin (H&E), toluidine blue, a double labelling technique for MC chymase and tryptase and anti-IgE. An intradermal test for flea antigen was performed and serum titres of allergen-specific IgE and IgG were measured. Significantly higher numbers (P<0.001) of double labelled MCs compared to toluidine blue stained MCs were detectable in flea-sensitized dogs independent of flea exposure. In contrast, in non-sensitized dogs, the number of toluidine blue stained MCs and the number of double labelled MCs did not differ. In flea-sensitized dogs after flea exposure the percentage of C-MC was significantly increased at day 1 (P<0.001) and day 3 (P<0.001), whereas the percentage of TC-MCs decreased significantly at day 1 (P<0.001) and day 3 (P<0.05). The percentage of T-MCs decreased (P<0.05 day 0 versus day 1; P<0.05 day 0 versus day 3). No significant difference was detectable after toluidine blue staining and staining for IgE+ cells between the groups nor between the MC density and the number of IgE+ cells. All flea-sensitized dogs had positive skin tests to flea antigen and high serum titres of flea-specific serum IgE and IgG antibodies. In non-sensitized dogs, these results were negative. Our data provide strong evidence for an upregulation of MC proteases during the process of sensitization and a generalized selective release of mast cell tryptase after exposure to the antigen.

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Rate-response toxicity tests on Aphidius rhopalosiphi were carried out with seven plant protection products using three different test systems. The first type of test system conformed to the standard laboratory testing guidelines and consisted of two treated glass plates fitted into a metal frame, which created an enclosure for the wasps. In the second type of test system, the plant protection products were applied to two bean-leaf disks mounted on agar filled dishes, which were fitted to a transparent plastic frame. The third type of test system consisted of potted barley plants, which were treated and covered with an acrylic cylinder. Adult wasps were exposed to the dried residues of the products for 48 h before wasp mortality was assessed. For each product and test system, the LR50 value (application rate at which 50% mortality of the wasps occurs) was determined with a Bayesian Probit analysis. Technically, rate-response testing was feasible with all three test systems, and rate-response relationships could be established. The results support a sequential testing scheme, as the LR50 values increased from 'glass plate test' to 'excised leaf test' to 'whole plant test' with all tested products. The LR50 values were 7.8-340 times higher on whole plants than on glass plates. Because of the variability of this factor, a numerical safety factor cannot be used to substitute extended laboratory testing for regulatory purposes.

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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.

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OBJECTIVE: To examine the social, cultural and religious factors underlying postpartum depression within a cultural cross-section of Jewish Jerusalem women. STUDY DESIGN: A prospective, repeated-measures study of 327 women. The Edinburgh Postpartum Depression Scale (EPDS) was administered immediately postpartum and 6-10 weeks later. Detailed sociodemographic information included perceptions of the pregnancy, community supports and religious affiliation. Odds ratios, 95% confidence interval and P values were calculated for all covariates. Multiple logistic regression was performed to estimate the degree of independent association between religiosity and postpartum depression. RESULTS: Postpartum depressive symptoms significantly associated with secular affiliation (odds ratio [OR] 2.9 [1.3-6.3] and tended toward an inverse association with orthodox affiliation (OR 0.6 [0.3-1.3]). Across secular, traditional, religious and orthodox groups, there was a decreasing trend in EPDS mean scores. Other predictors of depressive symptoms were psychiatric history, immigrant status and poor support with newborn care. CONCLUSION: Our study sample was particularly suitable for the assessment of cultural and religious elements of postpartum depression. We found religiosity, with its associated social and community structuring and well-defined social roles, to be significantly associated with self-reported postpartum depressive symptoms. These findings suggest that cultural factors, including role definitions, community support and rituals, may explain discrepancies found in the incidence of postpartum depression.

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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.

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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.

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OBJECTIVE: A survey of treatment centers for phenylketonuria (PKU) in the United States and Canada was undertaken regarding current practices of dietary treatment of PKU. METHODS: A total of 111 centers, who follow more than 6,950 patients with PKU responded to the survey. RESULTS: The majority of the centers, 87%, favor life-long dietary control of phenylalanine intake. The survey found lack of uniformity regarding acceptable range of blood phenylalanine levels. The frequency of clinic visits varied and became less frequent as patients got older. Although most of the clinics recommend diet for life, only one-third of the clinics follow patients beyond the age of 18 years, therefore, it is unclear who manages these patients beyond that age. The survey also showed a high number of families with children who were reported for medical neglect (3.0% compared to < 0.06% in the general population). Because of dietary noncompliance, 1% of the children were removed from the home. DISCUSSION: The survey points to the common treatment goal of diet for life for patients with PKU and underscores the need for uniform guidelines for achieving this goal.

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OBJECTIVE: To assess the prevalence and incidence of postnatal depression and its relation to certain psychosocial factors. METHOD: A questionnaire was administered to 327 randomly selected pregnant women on the first or second postpartum day A and again 6 to 12 weeks later B. The questionnaire comprised a psychosocial and demographic self-report, and the 10-item Edinburgh Postnatal Depression Scale (EPDS). RESULTS: At time A the prevalence of postnatal depression was 9.9-22.3%, and at time B it was 5.2-12.4% (p < 0.0001). Four of the psychosocial determinants examined correlated significantly with depression at times A and B. These factors were: a positive psychiatric history, Oriental ethnic origin, being foreign born, inconvenient timing of pregnancy. CONCLUSION: Postnatal depression was less common than in most reported series. It was related to marital and social support, the circumstances of the pregnancy, and the degree of religious observance. Postnatal depression is a specific disorder, not equivalent to depression in the prenatal period.

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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.

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Nineteen early-treated phenylketonuric patients, whose diet was discontinued between 4.5 and 13 years of age, and who have been off the diet for 12-28 years, were reassessed in 1992-93. There was little change in mean IQ between end of diet and follow-up, less than one IQ point on the average, with no change for any individual exceeding 12 IQ points. Both prior and current IQ correlated slightly negatively with mean phenylalanine (Phe) concentration, and positively with parents' education. The phenylalanine level at follow-up was significantly lower on average by about 900 mumol/L. Five of the subjects (26%) have evidence of mental disease. However, the data suggest that the discontinuation of the diet did not cause intellectual deterioration. Nonetheless, the patients' intellect cannot be the only consideration for maintenance of diet. The occurrence of psychopathology among phenylketonuric patients and the possible unknown effects of toxic elevation of phenylalanine during their lifetime suggest the need to maintain the diet. The use of DNA for diagnostic and prognostic purposes might assist in decisions about dietary quality and duration, and in anticipation of psychopathology.

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