Biomedical subjects
Publications and source records attributed to G Fischer.
The authors describe a technique of percutaneous insertion of the distal catheter during ventriculo-atrial shunting procedure for hydrocephalus. This technique avoids surgical approach of the internal jugular vein and allows its preservation.
To determine the influence of weak magnetic field on the development of inflammations, a non-specific acute inflammation was induced in rats by subcutaneous injection of sterile SEPHADEX-gel in the lower dorsal quadrants. The magnetic field applied had a strength of 10 Gauss (equivalent to 20 times the magnetic field of the earth), rectangular curve and a frequency of 10 Hz. Following a field exposure of 2 and 3 days, cytological and biochemical analyses of the blood and inflammatory exudate were performed. Parameters were leucocytes and proteins in the blood and in the focus of inflammation as well as blood electrolytes. The protein values in the focus of inflammation of the control animals remained unchanged on the second and third day whereas in the animals exposed to the magnetic field, they increased from the second to the third day. In the blood similar effects could be seen, but they were not as pronounced. We conclude from these data that the magnetic field causes an increased exudation of serum proteins in the focus of inflammation. The cellular component remains unchanged.
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Proline-containing dipeptidyl-4-nitroanilides have been synthesised and subjected to dipeptidyl peptidase IV-catalysed hydrolysis at high enzyme concentrations to collect information on the conformational specificity of the enzyme active site for a nonscissile bond. Descriptions of the biphasic kinetics were carried out in terms of cis/trans interconversion of the substrates. The results show that the enzyme can cleave only the trans-conformation of the substrate. The competitive inhibition by Gly-Pro-OH and Ala-Pro-OH is also specific for the trans form of the dipeptides. The interpretation of the results obtained from these kinetic studies has led to proposals for the stepwise cleavage of biologically active peptides like substance P and beta-casomorphine by dipeptidyl peptidase IV.
Several N-peptidyl-O(4-nitrobenzoyl)-hydroxylamines were synthesized and their inhibitory action against dipeptidyl-peptidase IV, alpha-chymotrypsin, elastase and thermitase was investigated. If the petidyl residue can be recognized by the enzyme as a substrate, a time dependent irreversible inactivation occurs. The mechanism of inhibition by N,O-diacylhydroxylamines as enzyme activated inhibitors is discussed.
The antihistaminic drug methapyrilene hydrochloride, which induces liver tumors in rats, was administrated orally to female Wistar rats. The animals were killed after 21, 38, 77, 119, 181, and 196 days. The activities of adenosine-5-triphosphatase (ATPase) and gamma-glutamyltranspeptidase (gamma-GT) in the liver were investigated histochemically. At 21 days, a homogeneous decrease of ATPase activity as well as a slight increase of gamma-GT activity was found in the periportal zone. Additionally, after 38 days hepatocellular foci with reappearance of gamma-GT occurred mainly in the periportal zone. After 119 days, foci with increased gamma-GT activity as well as a significant reduction of ATPase activity could be observed predominantly in the periportal region. The size and number of these putative preneoplastic foci were increased according to the time of administration of methapyrilene hydrochloride. After 181 days of methapyrilene hydrochloride treatment three of five animals developed hyperplastic nodules with corresponding alterations of enzyme activities. Methapyrilene hydrochloride-a carcinogen with an unknown mechanism of reaction-produces preneoplastic changes that are analogous to the well known preneoplastic lesions in the liver observed after administration of other carcinogenic agents.
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An early fetal case of cloverleaf skull anomaly associated with thanatophoric chondrodystrophy is described. Localized ventricular diverticula are a peculiar finding. In addition there are previously described malformations limited to the temporal lobes and comprising plump gyri with abnormal deep sulci, thick periventricular heterotopias, dysgenesis of the parahippocampal gyrus, agenesis of the Ammon's horn, and small micropolygyria. The skull deformity is not dependent on hydrocephalus, demonstrating inconsistencies in previous pathogenetic concepts.
Preneoplastic liver foci were produced in female Wistar rats by the administration of 2-acetylaminofluorene (0.03% w/w) in the diet for 174 days. Increased UDP-glucuronyltransferase (UDP-GT) could be visualized immunohistochemically in the same focal areas which were ATPase-negative and gamma-glutamyltranspeptidase-positive. Immunohistochemical detection was possible using rabbit anti-UDP-GT and peroxidase-labeled swine anti-rabbit immunoglobulins. The results of immunohistochemistry were substantiated by enzyme determination in microdissected material. UDP-GT activity was 5-fold higher in focal areas in comparison with the surrounding liver tissue. Increased UDP-GT activity in conjunction with the altered pattern of other drug-metabolizing enzymes is consistent with increased resistance of preneoplastic cells to the cytotoxicity of carcinogens. Immunohistochemical detection of UDP-GT may provide a new marker for preneoplastic lesions which, in conjunction with other markers, may prove useful in analyzing the various stages of liver carcinogenesis and the remodeling of preneoplastic lesions after cessation of carcinogenic stimuli.
Treatment with the antihistaminic agent methapyrilene led to a decrease of glucose-6-phosphatase activity and to an increase of glucose phosphorylating activity in the periportal zone of the liver acinus. However, the glucogenic capacity was maintained by a compensatory elevation of glucose-6-phosphatase and simultaneous reduction of hexokinase and glucokinase in the perivenous zone. The normal metabolic zonation with a glucogenic periportal and a glycolytic perivenous zone was not abolished but inverted by these alterations.
Group B streptococci remain a serious cause of morbidity and mortality in neonates. GBS vaccine or immunoglobulin administered iv may enhance neonatal GBS immunity. Likewise, intrapartum antibiotic therapy of colonized mothers appears to reduce vertical transmission of group B streptococci and to prevent both maternal and neonatal GBS disease. However, the safety and effectiveness of routine penicillin prophylaxis less than or equal to 1 hr after birth remain in question. For example, penicillin prophylaxis appears to be of little value in infants with low birth weights (less than 2,000 g) who become symptomatic shortly after birth; however, it may reduce the incidence of disease in larger, full-term infants who acquire the group B streptococci at delivery or in the few hours immediately thereafter. The potential harm of administering penicillin to all neonates must also be considered, since routine antibiotic therapy may alter the incidence of both neonatal infections due to penicillin-resistant pathogens and possible later penicillin allergy. Theoretically, a single injection of penicillin at birth may suppress GBS disease in some neonates but not effectively treat it, allowing the disease to progress prior to diagnosis and therapy. The decision to use penicillin routinely in neonates to prevent GBS disease must therefore be made with caution. Presently, this decision must be made on a situational basis, with institutions having a high incidence of early-onset GBS disease electing to use penicillin only if the potential benefits outweigh the risks.
A considerable reduction in number of livebirths for mothers over 35 was observed in Denmark from 1960 to 1980. Birthrates for those aged 35-39 fell by 58.8%, for those aged 40-44 by 78%. In 1979-1980 100 infants with Down syndrome were born among 116757 newborns, a birth prevalence of 0.86 per 1000, which was significantly lower than the incidence of 1.17 per 1000 when the prenatally diagnosed cases were included. The reduction was noticeable for the age group over 35 where it fell to 1.89 per 1000 for mothers 35-39 and 6.48 per 1000 for mothers over 40. The utilization of prenatal diagnosis was 72 per 100 livebirths for women 35 and older in the Copenhagen area and 56 per 100 livebirths for the rest of the country, with differences in different areas. The number of induced abortions for women 35 years and older was 9265 against 6597 livebirths. The estimated number of Down syndrome cases averted by unrestricted abortion was 61, twice the number prevented by amniocentesis (31), with the greatest impact for mothers over 40. An increased risk of Down syndrome for the age group 35-39 was observed when liveborn and prenatal cases were considered together showing an incidence of 6.89 per 1000, with the highest incidence in the Copenhagen area, 8.70 per 1000, more than double the incidence of 3.04 observed in Copenhagen from 1960 to 1971, for the same age group.
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In the course of chemically induced liver carcinogenesis as one of the earliest changes, the histochemically demonstrable focal loss of nucleoside 5'-triphosphatase activities (ATPase) is detectable. The exact quantitation and differentiation of these alterations can be achieved by biochemical analysis in microdissected preneoplastic foci. The preparation of focal tissue was facilitated using a microscopic-microdissecting apparatus [1]. By microanalytic determination of hydrolytic cleavage of 32P from gamma 32P-ATP a decrease of total ATPase activity to about 70% was found. Furthermore, the alteration of ATPase activities in course of chemically induced liver carcinogenesis in rats will be described.
A male child was born with internal hydrocephalus due to aqueductal stenosis requiring a ventriculo-peritoneal shunt on the first postnatal day. Subsequently, the hydrocephalus did not subside but increased. Autopsy at the age of 15 months disclosed the peritoneal tip of the catheter located inside the transverse colon, the cerebral tip of the catheter within a huge abscess of the right cerebral hemisphere. Penetration of the intestine by a ventriculo-peritoneal catheter seems to be a rare event, occasionally resulting in early death due ascending infection.
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Female Sprague-Dawley rats kept on a standard chow or on a magnesium (Mg)-deficient diet during 6 days received s.c. injections of 0, 25, 50, 100 and 200 micrograms of epinephrine (Ep). 1 h before, they were orally treated with 0, 125 or 250 mg of Mg/kg b.w. given as magnesium aspartate hydrochloride. Drug-induced changes were studied by analyzing serum and cardiac tissue samples (Mg, Ca, K, Na and in addition glucose, FFA, cholesterol and creatine kinase in serum) taken at 7 different times (15 to 420 min) after treatment with Ep; effects were evaluated by considering the respective areas under the concentration-time curves (AUC). AUCs were calculated with linear and logarithmic graduation of the time-scale and were also transformed into logarithms. In additional experiments, animals of both diet groups were treated with Mg and Ep as described above and the hearts, excised after 420 min, were prepared for histological examination. Cardiotoxic effects induced by adrenergic overstimulation were aggravated by Mg deficiency. Most pronounced electrolyte alterations and histologically detectable cardiac necroses were observed in the Mg-deficient animals at 420 min following the s. c. injection of 200 micrograms of Ep. On the other hand, oral Mg treatment induced hypermagnesemia and reduced toxic effects of Ep--especially Ca overload of the heart muscle--in controls and in Mg-deficient rats.