Use of neuroendocrine effects in discrimination between CNS-active drugs in the rat

Different psychotropic drugs were investigated in order to determine their effect on the release of prolactin and corticosterone and their influence on the tuberoinfundibular dopamine (TIDA) neuron activity. The results were used in a principal component analysis, which grouped the psychotropic drugs into different clusters. In the plot showing these clusters the anxiolytic drugs were found to be grouped together and differ from the antidepressant drugs by their potent ability to increase plasma corticosterone. The antipsychotic drugs formed a separate group being clustered together. Typical neuroleptic and atypical antipsychotic drugs could be separated within the cluster by their different effects on plasma prolactin and corticosterone and on TIDA neuron activity. The results indicate that the neuroendocrine profiles of antidepressant and anxiolytic drugs are different from those of antipsychotic drugs and that the neuroendocrine measurements could be a useful tool in the early classification of psychotropic drugs. © 1993 Wiley-Liss, Inc.     

Factors related to renal haemodynamics in young type-1 diabetes mellitus patients

The influence of metabolic control (HbA_1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11–17 years. Renal function was evaluated in terms of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal size was determined as renal parenchymal volume (RPV) by ultrasonography. The patients' HbA_1c values ranged from 8.2% to 12.9% (normal range 5.5–8.5%) and their GFR and ERPF were higher than normal. Their IGF-II values were higher, and NA and IGF-I levels were lower than those of healthy controls. Inverse correlations between NA and GFR (r=–0.66) and NA and ERPF (r=–0.63) were found. No correlation was found between serum IGF-I and renal functional parameters. The IGF-II values correlated with GFR and HbA_1c (r=0.63,r=0.70 respectively). There were linear correlations between RPV and GFR, RPV and ERPF, HbA_1c and GFR, and ERPF and RPV. Decreased NA concentrations and increased IGF-II values appear to be factors contributing to renal hyperfunction in these patients.     

Sexual risk behavior in women with cervical human papillomavirus infection

In a study of 972 women, sexual characteristics of 66 women with a cervical human papillomavirus infection (CHPI) were compared to the remaining study population. Among a number of sexual variables that were significantly correlated with CHPI were number of lifetime sexual partners, short partnerships, many recent partners, infidelity, casual travel sex, sexual début abroad, oral and anal sex, and sexual abuse. In multifactorial analyses four variables remained significantly correlated with CHPI, i.e., number of lifetime sexual partners, casual travel sex, sexual début abroad, and infidelity. It is concluded that CHPI shows most of the epidemiological characteristics of a sexually transmitted disease.     

Lithotripsy of urinary bladder stones with a mechanical lithotriptor inserted through a narrow introducer. An experimental study in pigs.

Mechanical lithotripsy of urinary bladder stones was performed with the RotoLith lithotriptor in 8 pigs with implanted human stones or artificial stones after open cystotomy. The effect of the treatment on the urinary bladder was investigated macro- and microscopically immediately after the lithotripsy in 4 animals and 4 weeks after the lithotripsy in the other 4 animals. The stones were fragmented into very small pieces which would have been possible to pass with the urine. The histopathologic examination immediately after the procedure showed slight mucosal edema, patches of erosions in the mucosa, and minor submucosal bleeding. Microscopic examination of the bladders removed 4 weeks after lithotripsy showed slight chronic inflammation. The experimental results have encouraged us to plan to use this lithotripsy procedure in selected patients with bladder stones.     

Epirubicin as a single agent therapy for the treatment of breast cancer — A pharmacokinetic and clinical study

Sixty women with breast cancer (mean age: 61 years; range 36-78 years) were treated with Epirubicin (4’epi-Dox-orubicin), 60 mg m^-2 , as single drug therapy. The drug was administered as 2 hours’ constant rate infusions. The pharmacokinetics of the drug during the first course of treatment was evaluated by measurements of the plasma concentration of Epirubicin at the end of the infusion period. There was a five-fold inter-individual variation of the dose-normalized maximum plasma concentration, which increased with increasing age of the patients. There was no correlation between this pharmacokinetic parameter and degree of obesity.     

Determinants of survival in liver resection for colorectal secondaries

All 72 resections for colorectal liver secondaries during the period 1971-1984 were analysed retrospectively. Liver tumours were single in 35 (49 per cent), unilateral in 55 (76 per cent) and associated with extrahepatic disease in 12 (18 per cent) patients. Operative mortality was 5.6 per cent. With respect to the disease in the liver, the presence or absence of four or more metastases was the predominant prognostic determinant with a 5 year survival rate of 20 per cent in patients with less than four liver tumours, and no 3 year survivor among patients with four or more tumours. When the number of liver tumours was less than four, the prognosis in patients with unilateral disease was not significantly better than in patients with bilateral disease (P = 0.19). No other liver disease variable seemed to play any role in the prognosis. Extrahepatic disease was associated with a poor prognosis and no 5 year survivor. The length of the tumour-free resection margin was the only treatment variable that varied with the outcome: a resection margin of less than 10 mm was followed by a poor survival. Variables that did not influence survival included uni- or bilateral disease, liver tumour volume, tumour size, type of liver resection, Dukes' classification, differentiation of the primary tumour and synchronous or metachronous disease. It is concluded that resection for liver colorectal secondaries is indicated when there are less than four liver tumours, even if bilateral, no extrahepatic disease is present, and a resection margin of at least 10 mm can be obtained. It should not be performed unless all of these requirements are met.     

Gene expression of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in skeletal muscle from type 2 diabetic subjects

The gene of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase gives rise to several splice variants. We hypothesized that the expression of p85alpha splice variants may be altered in skeletal muscle from subjects with type 2 diabetes mellitus. Skeletal muscle biopsies were obtained from nine type 2 diabetic and eight healthy men, matched for age, body mass index (BMI) and physical fitness. PI 3-kinase activity in skeletal muscle following in vitro insulin stimulation was reduced in subjects with type 2 diabetes. p85alpha mRNA was elevated fourfold in type 2 diabetic as compared to healthy control subjects ( P<0.05). p85alpha mRNA abundance was positively correlated with plasma insulin concentration ( P<0.01) and serum glucose concentration ( P<0.01). Despite this, protein levels of p85alpha, p55alpha, and the novel human p50alpha were not altered in type 2 diabetic subjects. Thus, although gene expression of full-length p85alpha is increased in skeletal muscle from type 2 diabetics, this is not reflected by increased protein levels. Therefore, defects in PI 3-kinase activity are likely due to impaired activation of the enzyme rather than changes in protein expression of the isoforms of the regulatory subunit.