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Biomedical subjects

R Bloch

Publications and source records attributed to R Bloch.

At least 73 records · Page 4Linked to original sources
PubMed1981

Central cardiovascular effects of taurine: comparison with homotaurine and muscimol.

The central cardiovascular effects of taurine were compared with those of homotaurine and muscimol. The drugs were injected i.c.v. in cumulative doses into pentobarbital-anesthetized cats. Muscimol (0.1-30 microgram/kg) produced dose-dependent hypotension and bradycardia, with a maximum effect of 70 +/- 5 mm Hg and 75 +/- 5 beats/min, respectively. Homotaurine led to a dose-related fall in blood pressure and heart rate; maximum effects were obtained with 300 microgram/kg and averaged 55 +/- 3 mm Hg and 73 +/- 3 beats/min. For both drugs, the dose-response curves were shifted to the right by pretreatment with 10 microgram/kg of bicuculline i.c.v. This antagonism confirms that the central cardiovascular effects of muscimol and homotaurine are mediated by a stimulation of gamma-aminobutyric acid receptors. Taurine produced dose-related hypotension and bradycardia. The depressive effects of taurine started at a dose of 10 microgram/kg; at a dose of 1000 microgram/kg, the maximum effects observed were a 55 +/- 7 mm Hg hypotension and a 53 +/- 8 beats/min bradycardia. These effects were not affected by bicuculline pretreatment, but strychnine (i.c.v) prevented the effects of taurine. These findings indicate that glycine-type receptors may be involved in the taurine effects rather than gamma-aminobutyric acid type receptors. However, these results do not exclude the involvement of taurine-type receptors for which the specific antagonists is not yet available.

Animals↗
PubMed1980

Medullary cardiovascular effects of tetrodotoxin in anaesthetized cats.

Tetrodotoxin injected in the cat nucleus tracus solitarii produced hypertension without bradycardia, whereas in the nucleus reticularis lateralis it led to hypotension and bradycardia. Tetrodotoxin acts by blocking neuronal activity; it is a useful tool for studying the central organization of cardiovascular regulation. The present data confirm that the nucleus reticularis lateralis is a vasopressive centre.

Anesthesia↗
PubMed1980

'MacDope': a simulation of drug disposition in the human body: applications in clinical pharmacokinetics.

1 We have described a novel approach to absorption, distribution, metabolism and elimination of drugs in which the patient is described using 23 Patient Factors and drugs by up to 50 Drug Factors. Kinetic behavior of a drug results from the interaction of patient and drug factors according to equations describing an eight compartment model. In this model non-linear processes (protein binding, hepatic drug metabolism and renal tubular transport) are handled by derivations of the law of mass action which have been generalised to permit the consequences of multiple drugs interacting at single macromolecular sites to be correctly calculated. 2 The mathematical description of this model is provided in a companion paper and solution of the equations is only possible using a digital computer. The computer programme is provided with an interactional format which makes operation independent of mathematical skills. Patients are defined by age, sex, height and weight with, or without, organ dysfunction; the programme then generates appropriate factors. Drug enters the system when a prescription is type on the keyboard and required Drug Factors are then retrieved from the disc flies. Drug concentrations in plasma or body fluids are given as simple graphs as a function of time, or in tabular form. 3 Any of the Patient or Drug Factors may be altered before, or during a run and up to three drugs may be simulated at one time thus permitting certain kinetic interactions to be examined. The scope of the simulator is illustrated using aspirin: pH dependent gastric absorption, first-order conversion of aspirin to salicylate, partly first order and partly saturable hepatic metabolism of salicylate, and the complex renal handling of this drug are all represented. Interaction of phenytoin with salicylate has been examined quantitatively to suggest limited clinical relevance for the observed displacement of phenytoin from serum albumin. The use of the simulator in a short course of pharmacokinetics is briefly described.

Aspirin↗
PubMed1980

[The significance of dietary fat and fiber for the aetiology of colon cancer (author's transl)].

Dietary habits of 49 patients with colorectal carcinoma or precancerous adematous polyps were investigated and compared with age- and sex matched, healthy controls. The dietary fiber intake of the tumor group was not significantly lower than control. Tumour patients were found to eat more animal fat than controls, the difference not reaching statistical significance. By contrast, we found a highly significant difference in the ratio of daily dietary fat/fiber intake (p less than 0.001). The ratio was 19.1 +/- 1.1 in tumour patients and 14.5 +/- 0.6 in controls. It is concluded that in the genesis of colorectal carcinoma, the relation of dietary fat to fiber might be more important than the intake of these two dietary constituents in absolute terms.

Cellulose↗
PubMed1979

[Importance of follow-up investigation in colonic carcinoma (author's transl)].

Extensive follow-up investigations were done in 1978 in 135 patients, most of whom had been operated for colo-rectal carcinoma of all stages in 1977. In 71% of the cases no or no sufficient postoperative control had been performed in the patients' own area. At the follow-up investigations 11 recurrences in the anastomosis, 10 of which were operable, 20 distant metastases, 1 simultaneous second carcinoma, 15 adenomas, partially with numerous atypical cells, 1 polyposis coli and 23 nonspecific granulomas of the anastomosis were detected. The Haemoccult test was positive in 3 of the 11 anastomotic recurrences. Only in cases of distant metastases were values of carcinoembryonic antigen clearly increased (greater than 5 ng/ml). These findings underline the necessity of intensifying the regular follow-up investigation in colo-rectal carcinoma.

Adult↗
PubMed1979

Degradation of junctional and extrajunctional acetylcholine receptors by developing rat skeletal muscle.

We have examined the rate of degradation of the total acetylcholine receptor content of diaphragm muscles of young rats and have found that even in muscles from 1-day-old rats some receptors are metabolically more stable than adult extrajunctional receptors. Further experiments have shown that acetylcholine receptors at junctional regions from young rats are degraded slowly, whereas those in extrajunctional regions are degraded rapidly. The results demonstrate that junctional acetylcholine receptors in rat diaphragm are degraded at a slow rate characteristic of adult junctional receptors at all ages after birth.

Acetylcholine↗
PubMed1979

Protection from gentamicin nephrotoxicity by cephalothin and carbenicillin.

In rats, cephalothin exerts a protective effect upon the nephrotoxicity of gentamicin. To examine the possibility that this effect is also observed with carbenicillin, we gave the following (milligrams per kilogram) to rats daily for 14 days: gentamicin alone, 60; gentamicin plus cephalothin, 100, 500, or 1,000; gentamicin plus carbenicillin, 50, 100, 250, 500, or 1,000. A 500-mg/kg dose of cephalothin afforded significant partial protection from gentamicin nephrotoxicity, as did a 100-mg/kg dose of carbenicillin. Increasing doses of either drug failed to increase protection. The data suggest that in rats not only does carbenicillin afford some protection from gentamicin nephrotoxicity, but also that it does so at a lower dose than cephalothin. These findings may in part explain the divergent observations regarding the nephrotoxicity of cephalothin-gentamicin combination therapy in rats and humans.

Animals↗
PubMed1978

Minoxidil treatment of malignant hypertension. Recovery of renal function.

We treated eight severely hypertensive, long-term hemodialysis patients who failed to respond to ultrafiltration or conventional medication with minoxidil rather than with bilateral nephrectomy. Control of blood pressure and relief of symptoms was achieved in all eight. In addition, three of the patients, who were all severely oliguric, recovered sufficient renal function to allow the discontinuation of dialysis. Two are presently doing well, while one died of causes unrelated to uremia or minoxidil therapy. We presently reserve bilateral nephrectomy for those hypertensive dialysis patients who are awaiting transplantation.

Acute Kidney Injury↗
PubMed1978

Comparative nephrotoxicity of aminoglycoside antibiotics in rats.

Netilmicin, gentamicin, tobramycin, amikacin, kanamycin, streptomycin, and sisomicin were given daily for 15 days to groups of rats at three dosage levels corresponding to 10, 15, or 25 times the dose recommended for humans on a weight basis. Decreased urinary osmolality and increased urinary excretion of protein and beta-N-acetyl hexosaminidase were dose-related features of nephrotoxicity. Decreased tubular resorption of glucose and phosphate were observed with the most toxic regimens after extensive renal damage had occurred. All aminoglycosides accumulated in renal tissue; however, the concentration of drug in the renal cortex at the time the rats were killed was not useful for the prediction of renal impairment. Streptomycin and netilmicin exhibited a flat dose-reponse curve with respect to histological damage, as compared with the curves for the other drugs. Results of studies of creatinine clearance and examination of renal tissue suggested the following order of increasing toxicity of the treatment regimens: (1) 0.9% NaCl and uninjected controls; (2) streptomycin; (3) netilmicin; (4) tobramycin; (5) sisomicin, amikacin, and kanamycin; and (6) gentamicin.

Amikacin↗
PubMed1978

[Ventrobulbular hypotensive action of muscimol].

Muscimol, a rigid analogue of GABA has been injected in the CNS of urethane anesthetized, normotensive cats. Injected either intracisternally (1 or 2 microgram/kg, 0.05 ml) or directly by microinjection in a restricted ventrolateral region of the brain stem (0.5 or 1 microgram/kg, 0.5 microliter), muscimol induced hypotension and bradycardia. These central cardiovascular effects of muscimol were antagonized by bicuculline, a "specific" GABA antagonist agent. These data emphasize the involvement of gabergic mechanisms in the central cardiovascular control, at least in the ventrolateral part of the medulla oblongata.

Animals↗