Differential immunoreactivity of her-2/neu oncoprotein in prostatic tissues.

To investigate HER-2/neu oncoprotein immunoreactivity, monoclonal antibody TA1 immunohistochemical examination of flash-frozen radical prostatectomy specimens was performed (n = 35). All prostatic specimens contained benign prostatic hyperplasia (BPH) and/or prostatic intraepithelial neoplasia (PIN), as well as prostatic carcinoma (CaP). HER-2/neu oncoprotein immunoreactivity in BPH tissues was not significantly different than that for the PIN basal cell layer (P = 0.10) or for the PIN luminal cells (P = 0.17). There was significantly more HER-2/neu oncoprotein immunoreactivity in BPH than in areas of CaP (P < 0.001). There was no significant difference in the amount of immunoreactivity present in PIN basal cells when compared to the PIN luminal cells (P = 0.49). Both the PIN basal cells and luminal cells stained for the HER-2/neu oncoprotein to a higher degree than cells in the CaP areas (P < 0.001 in both cases). HER-2/neu oncoprotein immunoreactivity is present at a significantly higher degree in BPH and PIN than in malignant prostatic epithelium.     

Differential effects of octreotide on motor responses to nicotine in rats.

We tested the hypothesis that brain somatostatin levels modify two motor behaviors evoked by ICV infusions of nicotine. Unrestrained, awake rats were given fixed-concentration infusions of nicotine until the prostration/immobility (PI) syndrome and convulsions were produced. Infusion duration ranged from 0.9 to 1.2 min for the PI syndrome and 2.5 to 4.9 min for the convulsions. Octreotide, a stable somatostatin analog (4.5 micrograms, ICV), significantly raised the threshold for nicotine convulsions 1.0 and 5.5 h after pretreatment but not at 24 or 48 h. Cysteamine, a somatostatin releaser and depletor (0.35-0.75 mg/rat, ICV), also caused a dose-dependent increase in seizure threshold. Similarities in the response to octreotide and cysteamine suggest that depression of nicotine convulsions by cysteamine may be mediated by release of endogenous somatostatin. Neither octreotide nor cysteamine altered the threshold for the PI syndrome. These results support the view that one motor behavior evoked by nicotine is subject to control by somatostatin whereas another is not.     

Risperidone exerts potent anti-aggressive effects in a developmentally immature animal model of escalated aggression.

BACKGROUND: Risperidone has been shown to be clinically effective for the treatment of aggressive behavior in children, yet no information is available regarding whether risperidone exhibits aggression-specific suppression in preclinical studies that use validated developmentally immature animal models of escalated aggression. Previously, we have shown that exposure to low doses of the psychostimulant cocaine-hydrochloride (.5 mg/kg intraperitoneally) during the majority of pubertal development (postnatal days [P]27-57) generates animals that exhibit a high level of offensive aggression. This study examined whether risperidone exerts selective aggression-suppressing effects by using this pharmacologic animal model of highly escalated offensive aggression. METHODS: Experimental hamsters were tested for offensive aggression after the acute administration of risperidone (.05-1.0 mg/kg, intraperitoneally). RESULTS: Risperidone dose-dependently reduced the highly aggressive phenotype, with a significant reduction observed at .1-.2 mg/kg for most aggressive responses measured. Experimental animals treated with higher doses of risperidone (.3-1.0 mg/kg) showed significant reductions in aggression and social interest toward intruders, indicating more general behavioral inhibition. CONCLUSIONS: These studies provide evidence that risperidone exerts specific aggression-suppressing effects in a developmentally immature animal model of escalated aggression.     

Mortality risk associated with ejection fraction differs across resting nuclear perfusion findings

Background  Left ventricular ejection fraction (LVEF) is a significant predictor of morbidity and death. The nuclear summed rest score (SRS) measures myocardial perfusion defects and provides prognostic information, but its effects on long-term outcomes are not fully established. Moreover, information regarding the potential interaction between these 2 covariates is limited. The purpose of this study was to determine whether the mortality risk associated with LVEF is the same across all values of SRS in a population undergoing evaluation for ischemic heart disease. Methods and Results  We examined 3,187 patients who underwent cardiac catheterization and perfusion single photon emission computed tomography imaging with a maximum follow-up of 8.1 years and median follow-up of 3.1 years. Cox proportional hazards modeling showed that increasing nuclear SRS and decreasing LVEF were independently associated with a higher long-term mortality rate, with a clinically significant interaction between them (P=.032). Patients with a normal LVEF and a high SRS (greater perfusion abnormality) have a prognosis similar to those with a reduced LVEF. Conclusions  Resting perfusion studies provide prognostic information for long-term survival and significantly impact the interpretition of mortality risk associated with changes in LVEF. Patient prognostication, risk stratification, and future research using these variables should take this interaction into account. Supported by a grant from the Tom & Lynn Royster Foundation. Durham, NC, and a National Institutes of Health Research Fellowship Grant (T5 GM08679-04), Bethesda, Md.     

Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome

Ribavirin is a broad-spectrum antiviral drug that has in vitro activity against human immunodeficiency virus. To determine the kinetics of ribavirin, 17 symptom-free homosexual men with lymphadenopathy were studied. Single doses of ribavirin, 600, 1200, or 2400 mg, were given orally or intravenously. The plasma ribavirin concentration-time profiles were well fitted by a three-compartment open model. Ribavirin followed linear kinetics over the dose range studied. The mean 1-hour postinfusion concentrations after intravenous ribavirin, 600, 1200, and 2400 mg, were 8.0, 19.7, and 37.1 mumol/L, respectively. The mean +/- SD plasma beta-phase half-life, terminal-phase (gamma) half-life, and volume of distribution at steady state were 2.0 +/- 1.1 hours, 35.5 +/- 14.0 hours, and 647 +/- 258 L, respectively. The mean ribavirin renal clearance and total body clearance were 99 +/- 30 and 283 +/- 37 ml/min, respectively. After an oral dose of 600, 1200, and 2400 mg, the mean peak plasma ribavirin concentrations (which occurred 1.5 hours after administration) were 5.1, 9.9, and 12.6 mumol/L, respectively. The mean absorption half-life and bioavailability of ribavirin were 0.5 hour and 45%. Ribavirin had no plasma protein binding and the drug accumulated within red blood cells. In conclusion, ribavirin is incompletely absorbed from the gastrointestinal tract, its renal excretion accounts for approximately one third of the drug's elimination, and drug accumulation (greater than threefold) will result with repetitive dosing at the 6- to 8-hour dosing interval currently used.     

Comparison of salivary calmodulin binding proteins in Sjögren''s syndrome and healthy individuals

Background: Reduction in salivary secretion is the hallmark of Sjögren's syndrome (SS). Calmodulin (CaM) and calmodulin binding proteins (CaMBPs) play a key role in the secretory process of saliva. Recent studies have suggested that SS‐B, an autoantibody associated with SS, is a CaMBP. This finding suggests that CaMBP may contribute to the loss of saliva in SS. To better understand the role(s) of these proteins in SS, the purpose of this study was to compare salivary CaMBPs in Sjögren's patients and controls. Methods: Saliva samples were collected from 20 patients and 20 age‐, race‐, and gender‐matched controls. CaM overlay was used to identify CaMBPs in saliva of patients and controls. Results: Higher number of salivary CaMBPs was observed among patients than controls. Conclusions: The increased number of salivary CaMBPs in SS may suggest a potential role for these proteins in the pathogenesis of the disease.     

Sex differences in spatial ability in children

There is considerable evidence that sex differences in spatial ability exist in adults, with males outperforming females at every age after puberty. It is difficult, however, to find sex differences in children younger than 13. This is due in part to the lack of adequate measures of spatial ability for use with children. We report the use of spatial tests for children that are similar to those that have shown large sex differences in adults and may be measuring ability comparable to adult spatial ability. Four tests of mental rotation and spatial visualization were given to two samples of children. The first sample consisted of 81 children (39 males and 42 females) aged 9 to 12 years. The second sample consisted of 42 children (21 males and 21 females) aged 9 to 13 years. Sex differences of .4–.6 standard deviations were found on three tests in both samples. These results indicate that sex differences in spatial ability can be found in preadolescents if appropriate tests are used. Measurement of these abilities in children facilitates the investigation of possible biological and sociocultural contributors to the sex differences in spatial ability.This study was supported by National Institutes of Health Grant HD19644 and NIH Biomedical Research Support Grant S07 RR05366-24.     

Children and the ingestion of alcohol: a statistical analysis of children attending an A & E department

The results of a survey of children attending an Accident and Emergency (A & E) Department following ingestion of alcohol are reported. Data were analysed to indicate age and sex of children, date and time of attendance, method of transport to hospital, whether accompanied to hospital and if so by whom, and whether admitted or discharged. Trends in children's consumption of alcohol, as observed by the author, are discussed.