[Diagnostic and prognostic value of additional neurologic diagnosis in alcohol withdrawal delirium]. / Diagnostischer und prognostischer Wert neurologischer Zusatzdiagnostik beim Alkoholdelir.

A severe course of alcohol withdrawal has been observed in 28% of patients in a neurological intensive care unit due to complicating central nerve system (CNS) diseases. In any atypical alcoholic delirium, especially with focal neurological signs, partial seizures, or decreased level of consciousness, CNS diseases like meningoencephalitis, intracranial hemorrhage, or central pontine myelinolysis must be diagnosed by computed tomography (CT) scan and cerebral spinal fluid (CSF) tap. The diagnostic and prognostic value of CT scan and CSF analysis was examined in 32 persons with alcohol withdrawal syndrome or delirium tremens. Neurological complications and cerebral convulsions at the beginning of delirium tremens appear to predispose the patient to a protracted clinical course and necessary mechanical ventilation. Blood-CSF barrier permeability is increased in 70% of alcohol withdrawal patients and that also seems to be a marker of a prolonged clinical course. Cerebral atrophy as shown in CT scan does not play a role in predicting clinical course. In our experience, CT examination or lumbar puncture is not necessarily recommended if clinical signs are typical for alcohol delirium.

Lobular--but not periovular--inhibition of collagen deposition in the liver of S. mansoni infected mice using interferon-gamma.

BACKGROUND/AIMS: Interferon-gamma (IFNgamma) elicits antiproliferative and antifibrogenic activity in a variety of mesenchymal cells, including hepatic stellate cells (Ito cells), and therefore represents a possible drug for liver fibrosis. However, IFNgamma binds to heparan sulfate, and is localized by these molecules in a restricted area within the tissue. For example, in rat liver, it has been shown that following injection, IFNgamma was concentrated in a restricted area by heparan sulfate. The aim of this study was to analyze, at the tissular level in the liver, the antifibrogenic activity of IFNgamma. METHODS: Chronic inflammation due to Schistosoma infection induces hepatic fibrogenesis around the parasite eggs (portal fibrosis) and in the parenchyma (lobular fibrosis). Infected mice were treated with recombinant IFNgamma, and the collagen content of the liver was evaluated by means of biochemical dosages, histologic and morphometric examination of liver tissue, and electron microscopic analysis. RESULTS: IFNgamma reduced the whole liver collagen content by 28% compared to control mice. In control mice, collagen was found around eggs and infiltrating the parenchyma, associated with a diffuse array of inflammatory cells, while in treated mice the collagen was present only around eggs and surrounded by a dense layer of inflammatory cells. Therefore, collagen was measured in isolated granulomas and in the remaining parenchyma. We found that IFNgamma strongly reduced the parenchymal collagen (74%), but had no effect on the granuloma collagen content. CONCLUSIONS: Together these data demonstrate that IFNgamma did not act in a homogeneous manner in the liver. Since granulomas are almost completely devoid of heparan sulfate, these data could suggest, among others hypotheses, that heparan sulfate which binds IFNgamma either localizes or mediates the cytokine activity outside the granulomas.

Heparin decreases the blood clearance of interferon-gamma and increases its activity by limiting the processing of its carboxyl-terminal sequence.

Interferon-gamma (IFN-gamma) binds with high affinity to heparan sulfate and heparin molecules through its carboxyl-terminal domain. In vivo, IFN-gamma is eliminated from the bloodstream with a half-life (t1/2) of 1.1 min, due to binding to heparan sulfate. Unbound IFN-gamma is cleaved rapidly at the carboxyl-terminal side, a process that removes at least 18 amino acids and inactivates the cytokine. When bound to heparin, the plasma clearance of IFN-gamma is decreased greatly (t1/2 = 99 min), and the area under the curve obtained with IFN-gamma alone represented only 15% of that obtained with injected IFN-gamma bound to heparin. Furthermore, the binding of heparin to IFN-gamma limits the extent of its carboxyl-terminal domain degradation to less than 10 amino acids. Importantly, this process increases the cytokine activity by as much as 600%. These data demonstrate that the blood clearance of the cytokine is a non-receptor-mediated process and that in vivo the local concentration of heparan sulfate/heparin-like molecules regulates IFN-gamma activity by a unique mechanism involving a controlled processing of its carboxyl-terminal sequence.

Distribution of hepatic glycosaminoglycans during acute schistosomiasis: modulation by IFN gamma treatment.

An important pathological outcome of schistosomiasis is hepatic fibrosis, with a significant deposit of collagens and proteoglycans. In this study, hepatic and granuloma-associated glycosaminoglycans (GAGs) were analyzed both quantitatively and qualitatively at the acute stage of murine infection with Schistosoma mansoni. The effects of IFN gamma, which has been successfully used for reducing collagen deposition in the liver during schistosomiasis, were also analyzed in granulomas and the surrounding liver parenchyma. Acute schistosomiasis resulted in a 4.4-fold increase in total hepatic GAG content, from which granulomatous GAGs--mainly chondroitin sulfates A/C and B--represented only one sixth of total GAGs amount. Therefore, the increase was found predominantly in the parenchyma. In this compartment, qualitative changes were also induced with a marked increase in the proportion of chondroitin sulfates A/C balanced by a decrease in the proportion of heparan sulfate and dermatan sulfate. IFN gamma reduced parenchymal GAG content by 47%. Qualitatively, the cytokine increased the proportion of heparan sulfate and reduced the quantity of chondroitin sulfates A/C by half in this compartment. By contrast, IFN gamma had neither quantitative nor qualitative effect on fibroinflammatory granulomas. In these structures, the absence of heparan sulfate--which is suspected to mediate IFN gamma activity--might explain these observations.

Molecular and biochemical study of the presence and synthesis sites of methionine enkephalin-like substances in the circumoesophageal ganglia, the ovotestis and the tentacles of the snail.

In situ hybridization with an oligonucleotidic 35S-labelled probe complementary to the 388-435 coding region of rat proenkephalin mRNA seems to show a colocalization between synthesis and storage sites of methionine-enkephalin(MK)-like substances only in young cellular stages of the ovotestis and in several neurons of cerebral, parietal and pleural ganglia. No positive signal can be detected neither in pedal and visceral ganglia nor in the tentacular collar cells, in spite of previous immunocytochemical data. Radioimmunoassays carried out on acidic extracts of the same organs confirm the molecular results and lead us to conclude to the presence of substances strongly related to MK in the ovotestis as well as in the circumoesophageal ganglia (COG), and to ascertain that the MK-positive tentacular collar cells do not contain authentic MK.

[Pregnancy in a representative Swiss population (study of pregnancy and newborn infants in Aarau). 3. Diseases and drugs in pregnancy]. / Schwangerschaftsverlauf in einem repräsentativen Schweizer Kollektiv (Aarauer Schwangerschafts- und Neugeborenenstudie). III. Krankheiten und Medikamente in der Schwangerschaft.

As part of an overall study, a cohort of 996 Swiss mothers was interviewed upon admission to the labour ward regarding illnesses, disorders and the use of drugs during pregnancy. The data are presented and compared with analogous data on the entire female population of the same age group in Switzerland, and with epidemiologic reviews of pregnancy events from other countries. Somatic illness, particularly the common cold, were reported by 55%, and complaints of a more psychosomatic character by 47%. Illness related to pregnancy was found in more than 40% of the women. Only 16% reported no illnesses or complaints during the course of pregnancy. On the other hand, 33% of the mothers had taken no medication during pregnancy. Compared with studies from other countries the use of medication in this group of women was lower, particularly self-medication for minor complaints. The women reported an average intake of 1.6 drugs. In the offspring of these mothers only a few minor somatic effects were demonstrable. The Brazelton behavioral assessment did, however, reveal some significant correlations.