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Biomedical subjects

R Gross

Publications and source records attributed to R Gross.

At least 325 records · Page 18Linked to original sources

Cardiovascular effects of the calcium-agonistic dihydropyridine BAY K 8644 in conscious dogs.

The hemodynamic effects of the dihydropyridine-derivative BAY K 8644 (methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoro-methylphenyl)-pyridine-5-carboxylate), a chemical analogue of Nifedipine, were evaluated in 9 conscious, chronically instrumented dogs. Compared to Nifedipine, BAY K 8644 displays an opposite pharmacological profile. Dose-dependent hemodynamic effects are observed at doses of 4 micrograms/kg i.v. and above. With 32 micrograms/kg i.v. BAY K 8644 increases total peripheral vascular resistance by 100%. It causes a rise of both, systolic and diastolic, blood pressure up to 196/138 mm Hg at spontaneous sinus rhythm and up to 216/162 mm Hg when keeping heart rate constant at 150 beats/minute. Spontaneous heart rate reflexly drops to 52 beats/minute. Cardiac contractility as indicated by LV(dP/dt)max markedly increases from 2800 to 5600 mm Hg/s at spontaneous sinus rhythm and from 2900 to 6100 mm Hg/s while pacing at 150 beats/minute. These effects are apparently neither affected by alpha-adrenergic blockade with Phenoxybenzamine (5 mg/kg i.v.) nor by beta-blockade with Propranolol (0.5 mg/kg i.v.) but can be reserved by equivalent doses of Nifedipine. In conclusion, the Calcium-agonistic dihydropyridine BAY K 8644 due to its novel mechanism of action could be the precursor of a new class of positive inotropic or antihypotensive drugs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

[Dilator effects of adenosine on rat pancreatic vessels].

The effect of adenosine (an agonist of the P1 purinoceptors) alone or in presence of a specific blocker of these receptors, theophylline, was studied on the vascular flow of the isolated perfused rat pancreas. Adenosine alone at a low concentration (1.65 microM) induced a rapid increase in vascular flow (+ 17%) which lasted throughout the perfusion of the nucleoside. This effect was suppressed by theophylline (50 microM). Our results show that adenosine provokes a dilator effect on the vessels of the rat pancreas and suggest that this effect is due to an action on purinergic receptors of the P1 type.

Adenosine↗

[The pneumonias].

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Anti-Infective Agents↗

Genetic and biochemical characterization of the aerobactin synthesis operon on pColV.

Certain ColV plasmids of Escherichia coli contain genes that specify functions for the acquisition of iron(III) via aerobactin. The locus for aerobactin synthesis of pColV-K311 was cloned into pBR322. Mutagenesis with the transposon Tn1000, and the generation of deletions with restriction enzymes resulted in multicopy plasmids which complemented pColV mutants impaired in various steps of aerobactin synthesis. The insertion and deletion mutants were mapped and assigned to three loci termed aerA, aerB, and aerC. It is proposed that these genes mediate the synthesis of aerobactin by specifying functions for hydroxylation (aerA), acetylation of the 6-amino group of 6-hydroxylysine (aerB), and the coupling of N-acetyl-N-hydroxy-lysine with citrate (aerC). The order and transcription polarity of the structural genes was found to be aerB, aerC, aerA.

Bacteriocin Plasmids↗

[What is a safe principle for therapeutic decision?].

In surgery (as in other disciplines of medicine) a causal therapy is connected with a causal diagnosis. Many physicians confine themselves to symptomatic measures which are useless beyond self-healing or introduce some kind of poly-pragmasia. Sometimes between those extreme positions there is a need of deliberations "as if" or primarily diagnostic operations. Diagnostics as a whole consist of logical as well as of psychological elements. Approximation is made either by some kind of hypothetico-deductive calculations or using some kind of pattern recognition. Anamnesis and immediate personal examination yield a preliminary diagnosis in about 80%. Yet a diagnosis of this sort has to be verified or falsified by scientific methods. The final decision is a function of both the theory of probability and the theory of utility. The combination is demonstrated by the so-called decision matrix and the so-called decision tree, going from simple models to complicated ones.

Computers↗

[Gastrointestinal complications in children with hemolytic-uremic syndrome].

Eight children out of 106 with haemolytic-uraemic syndrome (HUS) had marked gastrointestinal complications requiring close cooperation between the paediatrician and paediatric surgeon. These children showed signs of ileus and peritonitis. Six children hat these complications in the prodromal stage, whereas the other two children showed them in the anuria stage. The complications were closely connected with multiple erosions of the mucosa and ulcerations of the intestinal wall which resulted in perforation of the intestinal wall in two cases. In two further cases, intestinal vagination was seen which was limited toward the small intestine. All operated children died. The authors are of the opinion that prognosis in HUS with severe gastrointestinal complications is very infaust.

Abdomen, Acute↗

Effect of insulin on free fatty acid uptake by hepatocytes in the duck.

To elucidate the hypolipacidaemic effect of insulin in ducks, its action on the uptake of free fatty acids (FFA) by duck hepatocytes was determined. At low doses (10 mu./l) insulin stimulated FFA uptake. This effect was not observed with higher doses of insulin (20, 30 and 50 mu./l). Growth hormone at physiological concentrations and corticosterone (14.4 nmol/l) decreased basal activity, probably by reducing glucose metabolism and consequently alpha-glycerophosphate (alpha-GP) supply. Insulin was able to reverse the inhibition induced by GH and corticosterone on both FFA uptake and alpha-GP production. These results therefore suggest that the hypolipacidaemic effect of insulin may be partly mediated by its action on hepatic FFA uptake.

Animals↗

Plasmid and chromosomal mutants in the iron(III)-aerobactin transport system of Escherichia coli. Use of streptonigrin for selection.

Assimilation of iron via aerobactin by Escherichia coli requires functions encoded by certain ColV plasmids and by the chromosomal fhu region. Mutants obtained by insertion of the transposons Mu d1 (Ap lac) and Tn5 into ColV-K311 revealed that the aerobactin genes are transcribed from the locus that determines aerobactin synthesis to the gene encoding the outer membrane receptor protein for ferric aerobactin uptake. The antibiotic streptonigrin was used for selection of mutants impaired in iron assimilation. A simple assay was devised to identify mutants devoid of aerobactin synthesis. In addition, we performed complementation studies between fhu mutants and fhu genes cloned into pBR322. The genes fhuC,D,B were required for uptake of ferric aerobactin. Mutations in the fhuA gene usually decreased expression of the subsequent fhuC,D,B genes to such an extent that growth on ferric aerobactin as sole iron source was abolished. The results suggest that the genes on the chromosome and on the ColV plasmid are organized in two operons.

Biological Transport, Active↗

Threshold pressure for the pressure-dependent renin release in the autoregulating kidney of conscious dogs.

The effect of varying renal artery pressure between 160 and 40 mm Hg on renal blood flow and renin release was studied in seven conscious foxhounds under beta-adrenergic blockade receiving a normal sodium diet (4.1 mmol/kg/day). Pressure was either increased by bilateral common carotid occlusion or reduced in steps and maintained constant by a control-system using an inflatable renal artery cuff. Carotid occlusion itself had no influence on renal blood flow and renin release when renal artery pressure was kept constant and the beta-receptors in the kidney were blocked. Between 160 mm Hg and resting pressure there was no change in renal blood flow; between resting blood pressure and the lower limit of autoregulation (average 63.9 mm Hg) renal blood flow increased slightly (average 7%) indicating a high efficiency of renal blood flow autoregulation. The relationship between renal artery pressure and renin release could be approximated by two linear sections: a low sensitivity to a pressure change (average slope: -0.69 +/- 0.26 ng AI/min/mm Hg) was found above a threshold pressure (average: 89.8 +/- 3.3 mm Hg) and a high sensitivity to a pressure change (average slope: -64.4 +/- 20.8 ng AI/min/mm Hg) was observed between threshold pressure and 60 mm Hg. There was no further increase of renin release between 60 and 40 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

High-dose MTX/5-FU and adriamycin for gastric cancer.

In a phase II trial we tried to evaluate the efficacy of a sequential combination of high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (ADM). In a pilot study we had found high-dose MTX effective as a single agent in gastric cancer. MTX and 5-FU were combined sequentially because Cadman et al had shown synergism for this combination. The therapy protocol consisted of high-dose MTX, 1.5 g/m2 of body surface, and high-dose 5-FU, 1.5 g/m2. MTX was administered 1 hr prior to 5-FU. Both drugs were given as a bolus. Twenty-four hours after MTX administration, citrovorum factor rescue was started, 15 mg/m2, q.6h. X 12, orally. Forty-eight hours after MTX administration, serum concentration of the drug was measured by high performance liquid chromatography (HPLC). Fourteen days after MTX was given, ADM, 30 mg/m2, was injected as a bolus. This protocol was repeated every 28 days. Patients eligible for this treatment should have a creatinine clearance of greater than 60 ml/min. The study included 30 patients with metastasizing gastric cancer and performance status between 40% and 70%. The response rate was 63% (19 of 30 patients). Two of 30 patients had complete remissions, which are still maintained. The median survival for responders is not yet evaluable: 68% are living after 17+ mo. The median survival for nonresponders was only 5 mo. The difference in survival curves is significant at a level of p less than 0.05. Cytostatic treatment was well tolerated. Fifty percent of the patients could be treated on an outpatient basis. Total alopecia was observed in only 10% of the patients. Severe leukopenia, thrombocytopenia, and kidney disorders were not observed.

Adult↗