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In the present study we have examined the levels and phosphorylation state of the insulin receptor and insulin receptor substrate 1 (IRS-1) as well as the association between IRS-1 and phosphatidylinositol 3-kinase (PI 3-kinase) in the liver and muscle of rats treated with glucagon. There was a decrease in the insulin-stimulated receptor and IRS-1 phosphorylation levels which was paralleled by a reduced association between IRS-1 and PI 3-kinase in vivo in the liver and muscle of glucagon-treated rats. These observations suggest that glucagon, probably acting through cAMP, may impair insulin signaling in the three early steps in insulin action after binding.

A sensitive, selective and rapid reverse-phase high-performance liquid chromatographic method was developed for the simultaneous analysis of imipramine, desipramine, amitriptyline and nortriptyline in human plasma. The procedure consisted of extracting the drugs and the internal standard (clomipramine) from 1 ml plasma with hexane:isoamyl alcohol (99:1, v/v) in alkaline medium. A newly marketed column, LiChrospher 60 RP-select B (dp 5 microns) of Merck was employed. The mobile phase, consisting of acetonitrile/0.25 N sodium acetate buffer at pH 5.5 (50:50, v/v), was delivered at a flow rate of 1.0 ml/min, and detection at 254 nm. The precision, linearity and limit of quantification of the method were within acceptable limits. The method was considered adequate and has, therefore, been used in routine analysis for the therapeutic control of depressed patients.

In a cohort of 79 febrile episodes in 50 consecutive neutropenic patients seen at the University Hospital, Federal University of Rio de Janeiro, Brazil, between 1987 and 1991, it was observed that the cumulative incidence of disseminated fungal infections rose from 3% to 19% after the introduction of a new empirical antibiotic regimen. In order to identify risk factors, as well as to assess the impact of the new antibiotic regimen on the emergence of fungal infections, a nested case-control study was undertaken, in which 10 cases of disseminated fungal infections were compared with 30 randomly chosen controls, drawn from the same cohort. In a multiple logistic regression analysis, the predictive factors for disseminated fungal infection were younger age (odds ratio 0.85, 95% confidence interval 0.75-0.97) and use of the new antibiotic regimen (odds ratio 14.18, 95% confidence interval 1.05-191.80) The probable explanation for the emergence of fungal infections is that the new antibiotic regimen, by lowering the incidence of bacteraemia-related deaths, allowed patients to be at risk for the development of disseminated fungal infections.

Thyroid peroxidase (TPO) iodide and guaiacol oxidation activities were evaluated in eight dyshormonogenetic goiters. Two of these had a defective thyroglobulin; the TPO iodide oxidation (431 and 316 U/g ptn) and iodination (31 and 8.6 nmol I/mg ptn) activities were within the normal ranges. The goiters from two siblings with positive perchlorate iodide discharge tests also had normal TPO iodide oxidation (602 and 299 U/g ptn) and iodination activities (44 and 11 nmol I/mg ptn). No TPO iodide oxidation activity was found in the goiters from the other four patients with positive perchlorate iodide discharge tests, and TPO iodide oxidation inhibitory activities were detected in both their TPO and thyroglobulin preparations. Three of them had some TPO guaiacol oxidation activity and did not inhibit normal guaiacol oxidation. The TPO preparation immunoblot of these three goiters showed a faintly visible band of normal 100 kDa TPO. However, in the other patient no guaiacol oxidation activity was detected, and only two bands of low-molecular-weight TPO (72 and 43 kDa) were found, again showing that iodine organification defects in dyshormonogenetic goiters can be due to either qualitative or quantitative TPO defects. The TPO inhibition diminished when iodide was increased in the assay, but was not altered by increasing cofactor (H2O2). Our results, so far, suggest that the TPO-inhibitory substance may interact reversibly with a specific iodide site on the enzyme or with the oxidized form of iodide, and/or could bind free iodide, making it unavailable for enzymatic oxidation.

We compared three chromatographic methods for the therapeutic control of clonazepam. The first method analyzes the underivatized benzodiazepine, direct gas chromatography (GC) method, using nitrazepam as internal standard and GC with an electron-capture detector (63Ni). This method was compared with a second one, in which the same compounds were converted to the respective methylated derivatives (GC of derivatized samples) and also quantified by GC. The two methods were then compared with a third procedure for clonazepam quantification, using high-performance liquid chromatography (HPLC). Statistical analysis of clonazepam concentrations detected in the plasma of 37 patients, treated with Rivotril, indicated that HPLC is the most precise method, showed just significant correlations among the three methods, and suggested that plasma concentrations of clonazepam, estimated by the direct GC method, are significantly lower than those determined by the other two methods. The direct GC method and HPLC have been proposed as reference methods for the therapeutic control of clonazepam, with options for use left to the resources available in various laboratories.

The authors studied the prevalence of HBV markers among health care personnel of the University Hospital of the Federal University of Rio de Janeiro. The aim of study was to identify the high risk groups, in order to counsel vaccination of those groups, in order to counsel vaccination of those groups at risk as a routine. As a control group, a group of office workers of the hospital were chosen. A significant difference of incidence of HBV markers, mainly in surgeons (40%) and hemodialysis unit personnel (36.4%) when compared to the control group, was observed (p less than 0.05). The incidence increased with age and the time spent in the profession. The authors concluded that vaccination is indicated in surgeons hemodialysis personnel, dentists and laboratory personnel.

The Dubin-Johnson syndrome (DJS), a hereditary conjugated hyperbilirubinemia, is associated with an impairment of porphyrin metabolism. Total urinary coproporphyrin (CP) excretion and the urinary CP isomer I and III constellation were examined in 15 patients with DJS and 12 unaffected family members, and then compared with 50 unrelated control persons (55 +/- 15 nmol/24 h of total CP: 27 +/- 3% of isomer I; +/- SD). The patients with DJS excreted 80 +/- 7% (+/- SD) of CP isomer I (p less than 0.001). The isomer relation in two young children, 3 and 5 years old, shows an isomer reversal, with isomer I of about 95%. Studies done on four families from our patients with DJS indicate and confirm the autosomal recessive mode of inheritance. Total urinary CP was found to be elevated in subjects with DJS, reaching a mean value of 164 +/- 123 nmol/24 h (upper limit 120 nmol/24 h). Fecal CP isomers I and III were found to be in the usual physiological proportion to each other, but total fecal CP excretion had declined to the lower normal level (10 +/- nmol/g, n = 8). The pathogenetic mechanisms in DJS have not yet been fully worked out. Four possible explanations are currently under discussion: 1. an impaired hepatic excretory function: 2. a uroporphyrinogen III synthase defect; 3. an increase in porphobilinogen deaminase (uroporphyrinogen synthase) activity, or 4. a membrane-associated transport disorder with secondary metabolic changes of the isomer pool and enzyme activities.

Twenty achlorhydric patients and five controls were submitted to gastric endoscopic biopsies in order to study the histological pattern of the gastric mucosa and the number of enterochromaffin (EC) and gastrin (G) cells of the antral mucosa. The histological changes of the oxyntic mucosa of achlorhydric patients were variable being the predominant pattern the severe chronic atrophic gastritis. The antral mucosa was normal in appearance or revealed mild degree of gastritis. In the most achlorhydric patients the antral EC cell number was decreased when compared to the controls and the G cell number were relatively numerous. The results of the present work are suggestive of an increased G:EC cell ratio in achlorhydric patients.

The use of a reduced solution of phosphomolybdic acid for the precipitation of phenothiazine derivatives offers excellent conditions for the assay of these compounds. The quantitative assay range for each of the phenothiazine derivatives was determined by the precipitation, proportionality, in accordance with the procedure used for chlorpromazine. The conditions offered by the new method make it possible to assay 12 phenothiazine derivatives.

A prospective study of the effects of maximal doses of betazol hydrochloride ( Histalog ) on the endoscopic and histologic findings of the gastric mucosa of volunteers was made. Of the 11 patients examined, no alteration was seen on gastroscopic examination after Histalog in three, slight to moderate congestion of the mucosa in six and scattered oozing bleeding points in two. The study of the histologic findings revealed no statistical significant difference in the recurrence of erosion, hemorrhage and edema in the antrum and body gastric mucosa, before and after the administration of Histalog . It was concluded that maximal doses of Histalog cause no significant hemorrhage in the mucosa of the stomach and that the brown colour frequently seen in the gastric secretions of the final portions of a Histalog test is to be attributed to trauma to the mucosa by the nasogastric tube and to Histalog induced congestion of the mucosa.

The histological study of four cases and one by electron microscopy of subependyomomas allowed us to obtain morphostructural characteristics of ependymocytes and astrocytes. Comparing these findings to those of the present day literature, we propose to name these tumours ependymal astrocytomas.