Fixed-interval schedules for drug self-administration in the rat

The practicality of using second-order fixed-interval schedules in studies of heroin reinforcement with rats was examined. Optimum rates of responding were obtained with a dose of 0.03 mg/kg/infusion and an interval duration of 3 min. In addition, schedules consisting of a only a single interval were shown to be practical, leading to response rates comparable to those obtained with cocaine or food as reinforcer.The views expressed in this publication are those of the author and do not necessarily represent those of the Addiction Research Foundation     

Radical prostatectomy for adenocarcinoma of the prostate: The influence of preoperative and pathologic findings on biochemical disease-free outcome

Objective. This retrospective study evaluated the outcome for a cohort of men undergoing radical retropubic prostatectomy alone as primary treatment for clinical T1–2 prostate adenocarcinoma.Methods. Sixty-two patients treated at Boston University Medical Center between 1987 and 1992 underwent radical prostatectomy alone without adjuvant or neoadjuvant endocrine therapy. Actuarial and multivariate analyses were made of disease-free outcome according to preoperative tumor T stage, prostate-specific antigen (PSA), and biopsy grade, and according to the pathologic findings at surgery. Recurrence was defined as the persistence or recurrence of detectable serum PSA four or more weeks following surgery.Results. Of all patients judged clinically to have localized disease (T1–2), 52 percent proved to have pathologic T3 tumors. Of these, 81 percent had positive surgical margins. The strongest preoperative predictors of pT3 disease were the biopsy Gleason grade and the initial serum PSA value. Actuarial analysis showed the overall likelihood of remaining free from detectable PSA at four years to be 43 percent (75% for those with organ-confined disease and 27% for those who were pT3). The poorest prognosis was seen in those with seminal vesicle involvement. Biopsy Gleason grade and initial PSA were independent preoperative predictors of biochemical failure in a Cox regression analysis but clinical T stage was not.Conclusions. The biopsy Gleason grade and initial PSA were identified as strong preoperative predictors of disease-free outcome. We confirmed the favorable prognosis of men with organ-confined disease, but emphasize the high likelihood of relapse in those with positive surgical margins or seminal vesicle invasion.     

Lethal Congenital Muscular Dystrophy with Arthrogryposis Multiplex Congenita: Three New Cases and Review of the Literature

Congenital muscular dystrophy (CMD) comprises a heterogeneous group of muscle disorders. We report on two stillborn sibs with early lethal CMD and a prematurely born boy who died within minutes after birth. The pregnancies were complicated by polyhydramnios. All presented with arthrogryposis multiplex congenita, severe muscle wasting, lung hypoplasia, and hydrops. The muscle biopsies showed fibrosis, variation in fiber size, and extensive fat replacement compatible with muscular dystrophy. Fatal CMD seems to be distinct from CMD with survival after birth and is probably autosomal recessively inherited.     

Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia.

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is capable of inhibiting nitric oxide synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. The potential role of inflammation in the metabolism of ADMA has been elucidated in an in vitro model using tumour necrosis factor-alpha, resulting in a decreased activity of the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH). The kidney probably plays a crucial role in the metabolism of ADMA by both urinary excretion and degradation by DDAH. We aimed to further elucidate the role of the kidney in a rat model under basal conditions and during endotoxaemia. METHODS: Twenty-five male Wistar rats weighing 275-300 g were used for this study. The combination of arteriovenous concentration differences and kidney blood flow allowed calculation of net organ fluxes. Blood flow was measured using radiolabelled microspheres according to the reference sample method. Concentrations of ADMA, SDMA and arginine were measured by high-performance liquid chromatography. RESULTS: The kidney showed net uptake of both ADMA and SDMA and fractional extraction rates were 35% and 31%, respectively. Endotoxaemia resulted in a lower systemic ADMA concentration (P = 0.01), which was not explained by an increased net renal uptake. Systemic SDMA concentrations increased during endotoxaemia (P = 0.007), which was accompanied by increased creatinine concentrations. CONCLUSIONS: The rat kidney plays a crucial role in the regulation of concentrations of dimethylarginines, as both ADMA and SDMA were eliminated from the systemic circulation in substantial amounts. Furthermore, evidence for the role of endotoxaemia in the metabolism of dimethylarginines was obtained as plasma levels of ADMA were significantly lower in endotoxaemic rats.     

Isochromosome 18q in a girl with holoprosencephaly,DiGeorge anomaly,and streak ovaries

We report on the clinical and pathologic findings in a girl with isochromosome 18q (46, XX,i(18q)) who had combined manifestations of monosomy 18p and trisomy 18q. Major congenital anomalies included premaxillary agenesis, alobar holoprosenphaly, double Outlet right ventricle, DiGeorge anomaly and streak ovaries. The clinical spectrum in i(18q) is very broad. © 1993 Wiley-Liss, Inc.