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.     

Results of the tension-free vaginal tape procedure for stress incontinence: Patient''s perspective

BACKGROUND: To evaluate the results of the tension-free vaginal tape procedure (TVT) from a patient's perspective. METHODS: Between May 1999 and January 2002, 90 patients underwent a TVT for genuine stress incontinence (GSI) and mixed incontinence. Prior to the procedure, GSI was confirmed by clinical examination and urodynamic studies. Results were then audited from patient notes and the same patients were sent questionnaires to examine results from a patient perspective. RESULTS: Overall response rate to the questionnaire was 70 (77%). The mean age of the patients was 50.4 years (range 31-83 years). Sixty-one patients had spinal anesthesia, seven had general anesthesia and two had local anesthesia. Mean hospital stay was 3.36 days (range 2-14 days) and mean period from the operation to the time of the survey and audit was 16.34 months (range 3-28; SD 6.92). Thirty-nine (56%) of the 70 patients who answered said that the operation had cured their incontinence, 16 (23%) had an improvement in their symptoms, 7 (10%) had worsening of their symptoms and 8 (11%) felt that the operation did not make any difference. The overall success rate according to the patients' perspective was 79%, whereas our audit showed an overall success rate of 86% (77% and 82%, respectively, when we compared only the 66 patients who had both notes and replies available for analysis). CONCLUSION: Although a patient's perception regarding the success of TVT tends to differ from that of a clinician, it was not found to be statistically significant (P = 0.22, McNemar test). The TVT is a very successful operation, but realistic cure rates should be offered to patients.     

Hodgkin disease: CT of the thymus

The computed tomography (CT) scans in two groups of patients with Hodgkin disease were reviewed to determine the frequency of thymic enlargement. In 50 CT scans from 50 patients with evidence of thoracic disease on CT scans who were examined for primary staging, the thymus was enlarged in 15 of 50 (30%). Fifty CT scans were obtained from 44 patients at the time of 50 separate episodes of known or suspected relapse. Relapse occurred in the mediastinum in 12 episodes, lung parenchyma in five, and both sites in one. Thymic enlargement thought to be due to involvement by disease was present in seven of 18 (38%). Mediastinal disease was associated with thymic enlargement in all but one patient in whom a thymic cyst developed after radiation therapy. Differentiation of thymic enlargement from enlarged superior mediastinal lymph nodes was easily made in all but two patients. Thymic enlargement in the absence of lymph node enlargement may indicate a different disease, since isolated Hodgkin disease of the thymus is uncommon. Primary thymic tumor should be considered initially, whereas after treatment, rebound hyperplasia of the thymus may be the cause of enlargement.     

Solid and papillary epithelial neoplasms of the pancreas: CT findings

Five female patients and one male patient with solid and papillary epithelial neoplasms of the pancreas were examined with computed tomography (CT). The mean age of the patients was 27 years (range, 13-46 years). All cases showed well-encapsulated, round or lobulated masses consisting of both cystic and solid areas. Cystic portions showed CT numbers that suggested hemorrhagic necrosis. There were no internal septations within the masses. In three tumors located in the head of the pancreas, dilatation of the biliary tree was absent or minimal, although the masses were large. Two tumors contained calcifications. One tumor demonstrated metastatic deposits in liver and lymph nodes. Metastatic masses appeared similar to the primary pancreatic mass. Solid and papillary neoplasm of the pancreas should be the primary diagnostic consideration when characteristic CT findings are detected in a young female patient.     

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.     

Comparative genomic hybridization of 49 primary retinoblastoma tumors identifies chromosomal regions associated with histopathology,progression, and patient outcome

Forty-nine primary retinoblastoma (Rb) tumors were analyzed by the use of comparative genomic hybridization (CGH), and clinical/histological correlations were performed. Adverse histological factors were present in 13 patients. Chromosomal imbalance was a frequent phenomenon, seen in 96% of the tumors. Gain of 6p represented the most frequent event (69% of the tumors), whereas +1q was observed in 57%, confirming that these abnormalities are key secondary events in retinoblastoma tumor progression. Loss of 13q and 16 was significantly associated with tumors displaying adverse histo-prognostic factors, whereas -16q was significantly associated with tumors without adverse features. In three patients who developed an extra-ocular relapse, the tumors showed -13q and 2/3 had -5q, suggesting that these abnormalities may be associated with metastasis. Children >or= 36 months of age at enucleation tended to have more CGH abnormalities per tumor than children < 12 months (median numbers 11 vs. 3). In addition, +1q, +13q, -16, and -16q were more frequent in children with an older age at enucleation. Identical CGH changes were found in both tumors from one patient with bilateral tumors, suggesting a common origin. It is possible that tumors displaying loss of 13q and 5q indicate those patients who may suffer an adverse outcome and who would require alternative or more intensive therapy. CGH analysis on larger cohorts and in prospective clinical trials will be invaluable in determining whether a genetic classification of retinoblastoma represents a reliable measure of prognosis.     

Interactions of γ-immunoglobulins with lipid mono- or bilayers and liposomes. Existence of two conformations of γ-immunoglobulins of different hydrophobicities

Interactions between rabbit-γ-immunoglobulins and model membranes (lipid monalayers, planar lipid bilayers, liposomes) have been investigated. No significant interaction was observed with immunoglobulins. However, immunoglobulins dialysed first vs aqueous buffer having pH 2 or 3 and then dialysed against pH 7 buffer presumably adopt a new conformation which allows their bindings to model membranes. This binding is hydrophobic and the immunoglobulin region interacting with the lipid acyl chains is probably located in the heavy chain, as suggested by labelling in this region by a photosensitive probe previously incorporated into the lipid hydrophobic core. Cleavage at the hinge region by papain or pepsin, or heating above 38°C, induces the loss of the hydrophobic conformation responsible for hydrophobic bindings. The binding capacity of immunoglobulins heated above 38°C is restored after momentary dialysis at pH 2. The possible existence of two Ig isomers is discussed in relation to the mechanism of γ-immunoglobulin passage through the endoplasmic membrane and fixation into the plasma membrane.