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Biomedical subjects

J Schulz

Publications and source records attributed to J Schulz.

At least 19 recordsLinked to original sources

Alterations in the disposition of differently cleared drugs in patients with cirrhosis.

We have compared the disposition of antipyrine orally (15 mg/kg) and the new antiarrhythmic drug lorcainide intravenously (1.5 mg/kg) in 8 patients with alcoholic cirrhosis. Antipyrine (AP) serves as a model drug for drugs which are eliminated independently of liver blood flow and lorcainide (L) elimination as a model for drugs which depend on liver blood flow. Since in healthy subjects elimination half-life (t 1/2) of L increased with age (r = 0.68, p less than 0.01) due to parallel change in the volume of distribution (r = 0.52, p less than 0.05), its disposition had to be compared to age-matched controls. Elimination of both AP and L was impaired in cirrhotic patients, expressed either in terms (mean +/- SD) of t 1/2 (AP = 26.8 +/- 15.0 hr and 12.3 +/- 1.8; L = 12.5 +/- 4.5 hr and 7.7 +/- 2.2 hr, p = 0.002) or of clearance (Cl) (AP = 21.9 +/- 7.9 ml/min and 41.7 +/- 5.5 ml/min; L = 814 +/- 144 and 1002 +/- 304 ml/min, p = 0.06). While the alterations in plasma Cl were great for AP, they were smaller for L. This suggests that elimination of drugs in cirrhotic patients is associated with relatively more impairment of enzyme activity than of hepatic blood flow. The slightly decreased Cl of L in patients with alcoholic cirrhosis would suggest that L should be carefully handled in patients with dysfunction of the liver.

Acetanilides

Restoration of impaired immune functions of aged animals by chronic bestatin treatment.

An attempt to correct the state of immunodeficiency in old age was made by repeatedly injecting a chemically defined immunostimulating agent, bestatin, to 16 month old (C57Bl/6 x BALB/c) F1 mice. Aged mice were found to have depressed T-cell and B-cell responses but increased ADCC activity. Weekly injections of bestatin over a period of 6 months resulted in varying effects depending on the dose administered. Small doses (10 microgram per injection) were more effective in restoring humoral responses to SRBC rather than delayed-type hypersensitivity reactions, whereas large doses (100 microgram per injection) acted in the opposite way. Macrophage activation was only obtained after the administration of the high doses of bestatin. Continuous treatment with bestatin did not prevent the appearance of suppressor cells induced by ageing. It led to a significant reduction of ADCC activity in aged animals near to the base line value of young animals. Animals were examined for the presence of spontaneous tumours from the end of the treatment until the age of 28 months. A significant reduction of spontaneous tumour incidence was observed in mice given repeated injections of 100 microgram bestatin when compared to untreated aged mice and to mice given the low doses of bestatin.

Aging

[Immunofluorescence tests for the detection of antibodies against Corynebacterium pyogenes and streptococci in blood serum and vaginal mucus of cattle].

Bacteriological tests were applied to cattle with endometritis and vaginitis. Included were cervical mucus samples and immunofluorescence tests to detect in that mucus as well as in blood serum antibody to Corynebacterium pyogenes and Streptococcus haemolyticus. The results pointed at intensive contact of the animals with the above pathogens and to their frequent occurrence in cervical mucus of cattle afflicted with endometritis and vaginitis. They also supported the assumption of localised antibody formation in the sexual organs or female cattle.

Animals

[Diagnostic significance of lactose level in milk. 1. Lactose level in first quarter milk samples following artificial udder irritation and infection].

Studies were conducted into lactose levels of milk in response to experimentally irritated or artificially infected udder quarters. Milk lactose was found to be suitable as a model parameter by which to objectivate pathophysiological processes in the udder in the context of research, such as experiments on artificial udder infection or testing of udder tolerance of certain medicaments.

Animals

[Diagnostic significance of lactose level of milk. 2. Lactose level in first quarter milk samples in various udder disorders].

The behaviour of lactose levels in first quarter milk was studied in the context of a large dairy herd in the presence of various udder health defects. The results were related to other criteria generally used in mastitis diagnosis. The lactose level in first quarter milk was found to be a diagnostic criterion which was properly applicable to detecting and identifying clinical and subclinical mastitis. A limit value of 4.6 per cent has been commonly assumed in literature and proved to be a sound basis for udder health assessment, provided that the given phase of lactation is taken into due consideration (exclusion of cows in the first month post partum as well as of aged milking cows from the seventh month of lactation). Also reported in this paper are results regarding milk lactose and its correlations with other criteria for mastitis diagnosis. A close correlation was found to exist between lactose level and electric conductivity of first quarter milk.

Animals

[Filling of the Circle of Willis in carotid angiography using halothane anesthesia].

A comparative study of 150 carotid angiographies carried out under local anaesthesia and the same number under halothane anaesthesia did not show any great deviation from the well-known filling rates of the counter-lateral carotid region and the ipsilateral A. cerebri posterior nor any striking differences in the two methods of anaesthesia which could convince of a favourable influence of halothane on the demonstration of the vessels. The causative factors of the filling of adjacent vascularisation regions can certainly only be explained from the complex co-action of physiological and any external factors in cerebral angiography.

Adolescent

[Cardiovascular changes of the foetal circulation during deceleration in acute foetal hypoxia (author's transl)].

Acute foetal hypoxia trials were conducted in 11 foetuses of sheep. The following parameters were determined continuously besides heart rate, art. pO2, arterial and venous blood pressure: cardiac output, stroke volume and system resistance. Acute foetal hypoxia was produced in two ways: 1) Compression of the maternal vena cava The arterial blood pressure in the foetus is increased. This is reflected mainly by the systolic blood pressure. This increase is provoked by the increase in stroke volume (up to 100%). This increase in stroke volume is so great that the cardiac output is increased despite the onset of deceleration. The system resistance remains unchanged. 2) Maternal hypoxia In contrast to foetal hypoxia as described above, the increase of stroke volume is not so pronounced at the onset of deceleration, and the system resistance is increased. After termination of maternal hypoxia there is an abrupt change of system resistance back to the original value. Both types of foetal hypoxia will subsequently not differ significantly from each other.

Acute Disease

Pharmacologic factors and manipulation of immunity systemic adjuvants in cancer therapy.

Because of the experimental and clinical studies which have been extensively conducted with bacillus Calmette-Guérin (BCG) as a systemic adjuvant in cancer immunotherapy, we have analyzed the main factors and conditions which determine its beneficial action and have underlined some of these (eg, the dose factor which controls the amplification of suppressor cells which is probably responsible for failures and even the possible tumor-enhancing effect of immunotherapy). Knowing those factors and conditions, we have been able to establish a systematic immunopharmacologic study of systemic immunity adjuvants, which has resulted in the discovery of agents whose actions are more rapid than that of BCG on one or a few populations of cells involved in immunity and which, unlike BCG, do not induce suppressor cell amplification. This amplification may explain the difference in the results obtained with this mycobacterium in various clinical immunotherapy trials in which it was applied differently. It is proposed to combine these mono- or pauc-functional adjuvants in order to try to obtain all of the beneficial effects of BCG without the amplification of suppressor cells.

Adjuvants, Immunologic

Regulation of anaerobic glycolysis in Ehrlich ascites tumour cells.

1) In intact Ehrlich ascites tumour cells the anaerobic glycolytic flux rate and pattern of intermediates have been investigated at different pH values of the extracellular medium. 2) As predicted from the dependence of the lactic acid dehydrogenase equilibrium on pH a strong negative correlation between log ([lactate]/[pyruvate]) and pH has been found. 3) The steady state fluxes of glycolysis at pH 8.0 and 7.4 are rather equal, despite significant differences in the intracellular concentrations of glycolytic intermediates. At pH 8.0 the concentrations of ATP, glucose 6-phosphate, and fructose 6-phosphate are lower, and the concentrations of ADP, AMP, fructose 1,6-bisphosphate, triose phosphates, phosphoglycerates, and phosphoenolpyruvate are higher than at pH 7.4. 4) From the analysis of the pH dependent changes of metabolites it follows that different mechanisms are responsible for maintaining equal actual activities of hexokinase, phosphofructokinase and pyruvate kinase at pH 7.4 and 8.0. 5) From an application of the linear theory of enzymatic chains and a calculation of the control strength of the regulatory important enzymes results that hexokinase is evidently rate-limiting for glycolysis, and phosphofructokinase is also significantly influencing the glycolytic flux. Pyruvate kinase and glyceraldehyde phosphate dehydrogenase, on the other hand, do not significantly affect the rate of the overall glycolytic flux in ascites.

Anaerobiosis