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Biomedical subjects

E Richter

Publications and source records attributed to E Richter.

At least 235 records · Page 13Linked to original sources

Extrahepatic microsomal metabolism of N-nitrosodi-n-butylamine in rats.

The omega- and omega-1-hydroxylation of N-nitrosodi-n-butylamine (NDBA) has been studied in microsomes from rat liver, lung, intestine and kidney. Both reactions followed at least two enzyme kinetics with low (2-10 microM) and high (1 mM) Km values. Whereas omega-1-hydroxylation was the predominant pathway in liver, omega-hydroxylation was more important in extrahepatic tissues. First-pass metabolism of NDBA in lungs and intestinal mucosa may be of importance in the development of urinary bladder tumours in rats.

Animals↗

Hydroxylation of dibutylnitrosamine in the human liver and intestinal microsomal fractions.

The metabolism of the bladder carcinogen N-nitroso-di-n-butylamine (NDBA) was studied in microsomal preparations of tissues of patients of both sexes, aged 59-69 years undergoing abdominal surgery. Samples of liver, ileum, and colon were of normal histological appearance. For comparison, samples of rat liver and small intestinal mucosa microsomes were included in the study. Using 1-14C-labeled NDBA, the biotransformation to hydroxylation products retaining the nitroso group, NDBA-2-OH, NDBA-3-OH, and NDBA-4-OH, respectively, was investigated by reversed phase HPLC. In order to separate these metabolites, pooled samples were analysed by normal phase HPLC. The rate of hydroxylation of NDBA was found to be 5.5 times higher in rat liver microsomes compared to those from human liver (2.86 +/- 0.29 vs 0.52 +/- 0.03 nM X min-1 X mg-1). NDBA-3-OH proved to be the major metabolite formed (greater than 80% of total metabolites). The metabolism of NDBA was low but detectable in seven out of nine specimens of human gut, 0.1-0.5 nM X mg-1 in 1 h of incubation, and of the same order of magnitude in rat intestinal tissue (0.4-0.6 nM X mg-1).

Aged↗

[Double-contrast pharyngography in surgically treated and/or irradiated oro- and hypopharyngeal malignant tumors].

The use of a double contrast technique in the oropharynx and hypopharynx is described and its diagnostic value following treatment is defined. By means of the double contrast pharyngogram, it is possible to demonstrate the pharyngeal mucosa and, post-operatively, the anastomosis. It is the only imaging method which demonstrates the course of swallowing and passage through the pharynx. By paying attention to physiological changes following treatment and taking account of early post-therapeutic appearances, it is possible to form a judgement concerning the peripharyngeal tissue. CT, however, is the method of choice for demonstrating an extraluminal tumour. In view of the ease of the method, double contrast pharyngography is the ideal radiological procedure for close follow-up of patients with malignant tumours of the pharynx.

Barium Sulfate↗

Intestinal metabolism of nitrosamines. 1. Transport and metabolism of six nitrosamines in isolated perfused rat small intestinal segments.

Possible relationships between structure and metabolism of nitrosamines have been investigated in the rat small intestine. Isolated segments of jejunum and ileum were perfused from the luminal side for 2 h with a Tyrode solution containing one of four symmetrical dialkylnitrosamines with 2-5 carbon atoms per side chain, all 14C-labeled at the alpha position, or one of two unsymmetrical nitrosamines, N-nitroso-tert-butylmethylamine and N-nitrosomethylbenzylamine, 14C-labeled in the methyl group. Besides measurement of 14CO2 production and covalent binding of 14C to intestinal tissue, the absorbed fluid (absorbate) as well as the perfusion medium and tissue homogenates were analysed by h.p.l.c. for the presence of polar metabolites to assess the intestinal metabolism of nitrosamines. Neither N-nitrosodiethylamine nor the two unsymmetrical nitrosamines were metabolized to any significant extent. With increasing chain length of symmetrical dialkylnitrosamines small intestinal metabolism increased dramatically. At a concentration of 1 microM up to 60% and 30% of N-nitrosodipropylamine (NDPA) in jejunal and ileal segments, respectively, and greater than 90% of N-nitrosodibutylamine (NDBA) and N-nitrosodipentylamine (NDAA) in both intestinal segments were metabolized during absorption. Metabolites were found also in perfusate and tissue homogenate but generally at lower percentages as compared with the absorbate. With increasing concentrations the percentage of metabolites decreased, the decrease being more pronounced in ileal as compared with jejunal segments. CO2 production and covalent binding were negligible in ileal segments but amounted up to 5-8% and 0.1-0.4% of the dose in jejunal segments perfused with NDPA, NDBA or NDAA. With NDBA and NDAA no concentration-dependent decrease could be observed, the highest amounts of 14CO2 and bound 14C being found at intermediate concentrations. At concentrations below 10 microM metabolic pathways other than alpha-hydroxylation seem to be of greater importance. The toxicological evaluation of the high intestinal first-pass metabolism of NDPA, NDBA and NDAA must await the identification and quantitation of the metabolites formed.

Animals↗

Primary non-Hodgkin's lymphomas of the CNS.

This paper reports on 10 patients (4 male, 6 female) with primary non-Hodgkin's lymphomas of the brain (CNS-NHL--mean age 46.8 years, mean postdiagnostic survival 10 months). Pathological CSF (cerebrospinal fluid) was found in all 8 patients examined (positive cytology in 7/8 cases). Solitary tumors, diffuse periventricular infiltration or diffuse cerebral infiltration were demonstrated in cerebral computer-assisted tomography (CAT). Angiographical findings were unspecific. The histologic subtypes were lymphoplasmacytoid immunocytoma (4), unclassified low grade (1), centroblastic (1), B-immunoblastic (1), T-immunoblastic (1), lymphoblastic convoluted T-cell type (1), unclassified high grade (1) NHL. Patients who had received radiotherapy (+/- surgery) in this group had a mean survival of 15.66 months (sigma = 7.63). In addition, an overview of 83 well-documented, cases of the literature tries to characterize main histological and topographical distributions, histology-, patient's age-, and therapy-related survival. Patients with primary CNS-NHL have a 5-year survival expectancy of 30% compared with 2.3% in secondary CNS-manifestations of systemic non-Hodgkin's lymphomas. In this report, the beneficial effect of radiotherapy (mean survival 30.3 months) compared to surgery or symptomatic treatment (3.6 or 3.3 months) could be confirmed. It is concluded that primary CNS-NHL frequently present with atypical neuropsychiatric syndromes; diagnosis should be established preferentially with CAT and CSF-examinations or stereotactic biopsies, whereas open surgery should be avoided. An approach to exact classification should be attempted, as survival is clearly related to histological subtypes.

Adult↗

[Galactosamine-induced acute liver failure in the guinea pig--spontaneous course and controlled study conditions].

The spontaneous course of the galactosamine-hepatitis in the guinea-pig (750 and 1000 mg/kg GalN iv respectively) is characterized by a terminal hypoglycemia together with hypothermia and arterial hypotension fifty-nine hours on average after GalN-application. Preventing hypoglycemia and hypothermia by continuous intravenous infusion of a glucose solution and by increasing room temperature, the animals do not develop hepatic coma, but show an increasing disturbance of the righting reflex and survive at least seventy-two hours. Plasma biochemical tests and liver histology reflect severe hepatic damage. A twofold increase of the liver weight is caused by raised water and lipid content combined with a concomitant depletion of liver glycogen. Pharmacological studies with 14C-Pentobarbital result in a distinctly diminished clearance and in a prolonged half life while the cytochrome P-450 content of the liver shows a moderate decrease. In animal models of acute liver failure the possible incidence of hypoglycemia, arterial hypotension and hypothermia should be considered.

Acute Disease↗

[Dose-response relationship and serum concentrations of methohexital and hydroxymethohexital following rectal anesthesia induction with 1% and 5% methohexital solutions in children].

Dose-response-curves for rectal induction of anaesthesia in children with 1%- or 5%-methohexitone-solutions and dosages of 5, 10, 15, 20 and 25 mg/kg body wt. were obtained in 10 groups of 20 children. Methohexitone and hydroxy-methohexitone serum-levels were compared in another 23 children after application of 1%- or 5%-methohexitone-solutions at dosages of 15 and 20 mg/kg body wt. The sleep induction quota after 1%-methohexitone-solution in the 20 and 25 mg/kg body wt.-dosages was significantly higher, 20% and 25% respectively, and the mean sleep induction time shorter, 37% and 45% respectively compared with results after 5%. The change after 15 mg/kg body wt. was not significant. A study of dosages 5 and 10 mg/kg body wt. was discontinued due to insufficient effect. Methohexitone serum-levels ranged from 0.7-8 mg/l. All of the children after the use of 1%-methohexitone-solution, and only 60% after 5%-methohexitone had serum concentrations above the sleep inducing "borderline" concentration of 2 mg/l. The differences between mean methohexitone and hydroxy-methohexitone-serum-levels were not significant due to the small groups and the wide range of results. We conclude that individual dosages of 15 or 20 mg/kg body wt. 1%-methohexitone-solution should be applied according to clinical criteria such as physical and psychic status of the child.

Anesthesia, Rectal↗

[Computed tomographic determination of the target volume of tumors in the pharyngeal and laryngeal areas].

Computed tomography plays an important role in radiotherapy, especially in the delimitation of a target volume. For the oncologist, tumor and lymph node regions form a therapeutic unity. A direct imaging of the normal lymph node regions is not possible by CT. A method is described which allows an indirect presentation of lymph nodes in the head and neck area and, consequently, a better delimitation of the target volume. A three-dimensional presentation of the target volume is obtained by a certain quantity of CT scans which show various irregular forms making evident that a two-dimensional consideration of a single scan is no longer justified. Therefore five to seven scans are required for a more precise, three-dimensional determination of a target volume in the head and neck area.

Humans↗

[Double infection with Yersinia enterocolitica 0:3 and 0:9].

An unusual case of Yersiniosis was observed in a 20-year-old woman. Except for an extraordinarily severe onset the clinical course was not remarkable. But two different strains of Yersinia were repeatedly isolated. While strain serotype 0:9 was demonstrated only transiently and gave an only weak immune reaction, serotype 0:3 persisted longer and stimulated a strong immune reaction. But both strains had similar virulence characteristics in different tests, such as plasmid demonstration, autoagglutination, growth on Ca-deficient agar, and in mice.

Adult↗

Seleno-DL-methionine and the protection of human platelets against freezing injury.

The effect of seleno-DL-methionine, which has antioxidative properties, on the recovery of human platelets after freezing with 0.5 mol/liter glycerol or 0.7 mol/liter (5% v/v) dimethyl sulfoxide was investigated. Incubation of platelets with 2 mumol/liter seleno-DL-methionine for 30 min at room temperature before equilibration with the protective additives improved the post-thaw uptake of 5-hydroxytryptamine and the percentage reversal in the hypotonic stress test. The effect was small, but in view of the ability of seleno-DL-methionine to inhibit lipid peroxidation in membranes, the results suggest that oxidative damage is implicated in freezing injury. The dimethyl sulfoxide protocol apparently afforded greater protection to the platelets than the glycerol protocol. But, if the platelets were incubated for 24 hr at 37 degrees C after thawing, there was a marked improvement in the response of cells in the hypotonic stress test, particularly in the samples frozen with glycerol, and there was no longer any difference between the two additives. There was, however, a concomitant loss of almost half the number of cells in the thawed suspensions during the prolonged incubation at 37 degrees C.

Biological Transport, Active↗

[The Currarino triad. An autosomal-dominant inherited complex of anorectal malformation, sacrococcygeal defect and presacral tumor. Observation of 9 further cases].

Nine cases of a syndrome are described, which is known as the "Currarino triad" and which belongs to the group of malformations in which there is a persistent neurenteric communication. The features of the triad consist of ano-rectal anomalies (particularly ano-rectal stenoses), a curved, but limited, sacro-coccygeal defect ("scimitar sacrum") and a presacral tumour, which may be an anterior sacral meningocoele, a teratoma, a cyst (dermoid or neurenteric a cyst (dermoid or neurenteric cyst) or a mixture of these. In at least 50% of cases, the triad is familial and autosomal dominant. Of our nine cases, seven were familial. A dangerous complication is meningitis due to infection of the cystic component, or fistula formation between the colon and spinal canal (one of our cases). Other complications are a fixed filum terminale ("tethered cord") and malformations of the urogenital tract. The risk of malignancy in a teratoma is low, but exists. When considering the indications for surgery, this must be kept in mind, as must the risk of infection, and damage to neural structures during operation. In all cases of early obstipation the sacrum should be x-rayed in order to exclude a Currarino triad. The finding of a sacral defect and a presacral mass makes it essential to obtain CT of the pelvis with contrast in the distal gut and in the meningeal sac. The same is true for screening of the family (including views of the sacrum).

Abnormalities, Multiple↗