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.     

Sequential bilateral adnexal torsion after a single cycle of gonadotropin ovulation induction with intrauterine insemination

As part of a programme for the implementation of a Smoking Control Policy in our hospital, an open study, without randomization, of 65 hospital workers, who wanted to give up smoking, was carried out. The characteristics of smoking in each subject were recorded. The Fagerstrom Questionnaire was used to measure the degree of dependence on nicotine. The treatment consisted of the daily use of 16 h nicotine patches for 12 weeks. During the first 4 weeks, the patches contained 15 mg of nicotine, for the second 4 weeks, 10 mg, and for the last 4 weeks 5 mg (per patch and day). Five visits were scheduled during the 26 week study period: at the start of the study and after 4, 8, 12 and 26 weeks. The abstinence was checked by measuring carbon monoxide in end-expiratory air. The success rate was 31% after 12 weeks, and decreased to 29% after 26 weeks. In conclusion, the nicotine patches appeared safe and effective in this study.     

Metabolic consequences of alcohol dependency

Alcohol dependency leads to a variety of biochemical adaptations and morphological changes which may be considered as either adaptive or destructive. This ranges from the utilization of ethanol as a metabolic fuel, to overt tissue and cellular damage, and may lead to increases in morbidity and mortality. Virtually every organ system is affected by either acute and chronic ethanol exposure and numerous metabolic pathways are altered. As a consequence of these wide ranging effects, it is extremely difficult to cover every aspect of alcohol toxicity in a single review. Instead, attention is focussed on selected areas, such as nutrition and protein metabolism in the liver and bone (and to a lesser extent, skeletal muscle and the gastrointestinal tract). The aim is to illustrate the numerous ways in which alcohol affects the body.     

Effects of ligand priming and multiple-dose injection on tissue uptake of 111In-pentetreotide in rats

In patients undergoing somatostatin receptor scintigraphy, treatment with octreotide (Sandostatin) is usually discontinued 24-48 h before and after injection with the radioligand 111In-pentetreotide ([111In-DTPA(O)]octreotide) (Octreoscan) because octreotide competes with radioligand for the same receptors. However, D?rr et al. and Soresi et al. reported improved visualization of carcinoid and small cell lung cancer lesions, respectively, during continued octreotide treatment. We found that intravenous administration of unlabeled octreotide to rats inhibited the binding of an optimal dose (0.5 microg) of 111In-pentetreotide to somatostatin receptors in pancreas and adrenals in a mass- and time-dependent way. Pretreatment with unlabeled octreotide never increased receptor binding of 111In-pentetreotide. Administration of 100 microg of octreotide decreased receptor-bound radioactivity if given simultaneously with or 10 or 20 min after injection of the radioligand, but had no effect if given 30 min after the radioligand. These findings indicate rapid processing of receptor-bound octreotide and suggest that octreotide treatment of patients undergoing 111In-pentetreotide scintigraphy may be reinitiated as soon as 1 h after radioligand administration.     

Mortality studies of machining fluid exposure in the automobile industry. V: A case-control study of pancreatic cancer

MANOVA and repeated measures ANOVA approaches have provided evidence of a number of limitations in several event-related potential (ERP) studies due to violations of their statistical assumptions and the typically moderate size of the available sample. Alternative, computer-intensive methods based on permutation principles have recently been developed. Up to now this methodology has focused mostly on magnitude differences between scalp distributions as measured by t statistics. In this paper the scope of permutation techniques in ERP analysis was widened. A new statistic (D statistic) is introduced to compare the shapes of scalp distributions of ERPs. Additionally a general non-parametric combinatory technique is introduced to evaluate, by means of multivariate permutation tests, several time points and/or recording sites in ERP data. The methodology described here was used to test if two ERP components elicited during word-pair matching tasks to semantic or phonological incongruences had different scalp distributions.     

Catalytic activity of phospholipase A2 in serum in experimental fat embolism in pigs

In a population-based epidemiological study, 991 Pima Indians with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 288 without diabetes aged > or =15 years were examined for retinopathy by fundus photography with a 45 degrees fundus camera after mydriasis. The photographs were graded using a modified Airlie-House classification scheme. The associations of several factors with retinopathy were studied by logistic regression. Non-proliferative retinopathy was present in 11.2 % (19/169) subjects at the time of diagnosis of diabetes and in 8.3% (4/48) in newly diagnosed subjects who had a documented non-diabetic oral glucose tolerance test within 4 years prior to diagnosis of diabetes. The prevalence of retinopathy in subjects with impaired glucose tolerance was 12% (8/68). Retinopathy at the time of diagnosis of diabetes was significantly associated with lower body mass index and higher systolic blood pressure but not glycaemia. Retinopathy was present in 375 (37.8 %) diabetic subjects and 14 (5.2 %) non-diabetic subjects. Among all subjects with diabetes (duration 0-37 years), stepwise multivariate analysis showed non-proliferative retinopathy to be associated with duration of diabetes, mean blood pressure, fasting plasma glucose, treatment with insulin and albuminuria. Proliferative retinopathy was seen in 34 (2.7%) of diabetic and none of the non-diabetic subjects, and was associated with 2 h post-load glucose concentrations, as well as albuminuria, insulin treatment, younger age, and diastolic blood pressure. These data confirm the need for fundus examination at the time of diagnosis of diabetes and during long-term follow-up. Albuminuria and blood pressure are potentially modifiable risk factors and the impact of treating these on incidence and progression of diabetic retinopathy need to be assessed.     

Activation of thromboxane receptors and the induction of vasomotion in the hamster cheek pouch microcirculation

1. The present study was designed to investigate a possible role of thromboxane A2 (TXA2) on arteriolar vasomotion (spontaneous rhythmic variations of the vessel diameter). Therefore the microcirculatory effects of the thromboxane-receptor (TP-receptor) agonist, U 46619, as well as the effects of the TP-receptor antagonists S 17733 and Bay U3405 were evaluated in the hamster cheek pouch microcirculation. For comparison some effects of angiotensin II were also investigated. 2. For microcirculatory measurements, the cheek pouch preparation was placed under an intravital microscope coupled to a closed circuit TV system. The TV monitor display was used to obtain arteriolar internal diameter measurements by means of an image shearing device. 3. Superfusion (0.1 nM to 1 microM) or bolus application (1 pmol to 10 nmol) of U 46619 concentration- or dose-dependently decreased the arteriolar diameter and induced vasomotion in arterioles with a mean initial diameter of 24+/-2 microm. Both the vasoconstriction and the vasomotion induced by U 46619 were inhibited by the TP-receptor antagonists S 17733 (100 mg kg(-1), i.v.) and Bay U3405 (10 mg kg(-1), i.v.). 4. Bolus applications of angiotensin II (0.1 pmol to 1 nmol) induced transient vasoconstriction followed by vasodilatation in the cheek pouch arterioles. The dilatation but not the constriction, was sensitive to treatment with the NO-synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG; 100 microM). Angiotensin II did not induce vasomotion in control conditions or in the presence of L-NOARG. 5. Bolus application of phenylephrine (10 pmol) induced vasoconstriction but no vasomotion in previously quiescent hamster cheek pouch arterioles. 6. These results indicate that activation of TP-receptors causes vasomotion in the hamster cheek pouch arterioles. These spontaneous rhythmic variations in arteriolar diameter are not observed with equipotent doses of angiotensin II and phenylephrine. Thus, the vasoconstriction by itself cannot explain the occurrence of vasomotion observed with the TP-receptor agonist.     

Adhesion properties of mutants of Staphylococcus aureus defective in fibronectin-binding proteins and studies on the expression of fnb genes

Staphylococcus aureus 8325-4 has the potential to express two distinct cell wall-associated fibronectin-binding proteins called FnBPA and FnBPB. In order to test if both proteins are expressed in S. aureus and if both are required for promoting bacterial adhesion to fibronectin-coated surfaces, insertion mutations were isolated in each gene. A DNA fragment encoding tetracycline resistance was inserted into fnbA and a fragment encoding erythromycin resistance was inserted into fnbB. A double fnbAfnbB mutant was also constructed. The fnbA and fnbB single mutants showed no significant reduction in their adhesion to polymethylmethacrylate coverslips that had been coated in vitro with fibronectin. However, the double mutant was completely defective in adhesion. Monospecific antibodies directed against the non-conserved N-terminal regions of both proteins confirmed the lack of expression of FnBPs in the mutant strains. Wild-type fnbA and fnbB genes cloned seperately on a multicopy plasmid were each able to restore fully the adhesion-defective phenotype of the 8325-4 fnbAfnbB mutant. This demonstrates that both fnb genes are expressed in S. aureus and that both contribute to the ability of strain 8325-4 to adhere to fibronectin-coated surfaces. The double mutant was also defective in adhesion to coverslips that had been removed from tissue cages implanted subcutaneously in guinea-pigs, which suggests that fibronectin is important in promoting attachment of S. aureus to biomaterial in vivo.     

Exacerbation of atopic dermatitis after bacillus Calmette-Guérin vaccination

In two children with atopic dermatitis, routine vaccination with bacillus Calmette-Guérin (BCG) was followed by severe exacerbation of skin disease. If the sequence is cause and effect, a possible mechanism is stimulation of a Th2 lymphocyte cytokine profile by the vaccine, with migration of activated lymphocytes to inflamed skin. In children with active atopic dermatitis, BCG vaccination is best deferred until remission.