Biomedical subjects
M Dorner
Publications and source records attributed to M Dorner.
[Essential labile diabetes (author's transl)].
"Essential labile diabetes" is an insulin-dependent diabetes, in the course of which irregular and unpredictable hyperglycemias, frequently with ketosis, and sometimes serious hypoglycemias alternate. In spite of careful treatment with insulin, diet and suitable hygienic measures, this form of diabetes cannot be influenced. Fortunately, it seldom occurs, not more frequently than in 1 to 2% of diabetics. Various attempts have been made to explain the pathogenesis of this form of the disease. The most probable explanation is that there is an almost complete exhaustion of insulin secretion. This hypothesis is based on the extremely low level of the C peptide below 0.60 ng/ml, whereas in non-labile insulin-dependent diabetics the C peptide amounts to more than 2.2 ng/ml
[Radiologic study of arterial calcifications of the lower extremities in diabetic patients].
The authors analyse the frequency of arterial calcifications in the lower limbs in diabetics. These calcifications were found in the thighs and legs and also in the feet. They were more frequent in diabetics than in normal subjects and occurred earlier in life. Their presence showed the existence of a severe microangiopathic process.
Biliary excretion of ampicillin: experimental and clinical study.
The biliary excretion of ampicillin was studied in various conditions. Using an isolated perfused rabbit liver preparation, 4.1% of the amount of ampicillin added to the circulating blood (10 mg) was recovered in the bile where the maximum antibiotic activity (mean: 104 +/- microng/ml) was 4 times higher than in the serum (mean: 24.1 +/- 3.4 microng/ml). In man, provided with T-tube drain, the oral or intravenous administration of 500 mg ampicillin resulted in a biliary excretion of 0.10% of the administered dose. The biliary concentrations thus obtained equalled or exceeded for several hours the minimal inhibitory concentration of the organisms included in the antibacterila spectrum of ampicillin justifying thus the use of this antibiotic in the treatment of biliary tract infections. Per-operatory assays showed that in patients with gallbladder disease or with cystic duct obstruction, ampicillin levels in the gallbladder bile were markedly lower than in the common duct bile.
[Parodontopathy revealing insulin-dependant diabetes].
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[Present concepts of treatment of diabetes during pregnancy].
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[Biliary transport, bile levels and entero-hepatic cycle of antibiotics. Personal study of the biliary elimination of beta-lactamines].
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Experimental and clinical pharmacology of metampicillin in the biliary tract.
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Characteristics of intestinal phase of gastric secretion.
In four dogs provided with special gastroduodenal fistulas allowing for the complete separation of stomach and duodenum without interrupting the vagal connections between them, the magnitude of the gastric and intestinal phases was compared and their contribution to the total gastric response to a meal was established. A liver extract (LE) meal, confined to the stomach and maintained at pH 5.0 by an intragastric titration technique, produced acid output reaching 66% of the maximal response to histamine (MRH). Perfusion of the LE meal into the duodenum resulted in acid secretion amounting to 57% of MRH. The combination of the gastric and intestinal phases caused the highest acid output, amounting to about 90% of MRH. Gastric and intestinal phases induced separately were accompanied by a significant elevation in serum gastrin concentrations which reached the highest values when both phases were evoked simultaneously. Acidification of the intestinal meal resulted in pH-dependent inhibition of gastric secretion falling to the basal values at pH 1.0. These secretory changes were mimicked by exogenous secretin. Serum gastrin levels remained essentially unaffected by the acidification of the intestinal meal while exogenous secretin significantly lowered them. In conclusion, in the intact stomach with undisturbed nervous connections between the stomach and duodenum, a peptone meal in the intestine is capable of evoking a potent gastric acid and pepsin stimulation by a mechanism involving the release of antral hormone.
Adjustment of cephaloridine (Keflodin): dosage according to its pharmacokinetics.
The determination of the serum and urine concentrations of cephaloridine permitted calculation of the pharmacokinetic constants of this antibiotic: after administration of a 1-gram intravenous dose in five normal subjects; after administration of a 1-gram intramuscular dose in five normal subjects, five patients with renal impairment and five patients on maintenance hemodialysis. In normal subjects, serum half-life averaged 1.56 h (Ke=0.4445) after intravenous administration and 1.63 h (Ke=0.4254) after intramuscular administration of a 1-gram dose of the antibiotic. The urinary excretion of cephaloridine over the 6 h following its intramuscular administration in normal subjects amounted to 56.4% of the administered dose. The renal clearance of cephaloridine was 194 ml/min. A linear correlation (Ke=0.0670+0.0028 CrCl) was established between overall elimination rate-constant values and the creatinine clearances of the patients under investigation. These data were used to calculate the maintenance and loading doses and intervals adjusted to creatinine clearance values. Accurate dosage regimens adjusted to the renal status of each individual patient were derived from the calculated values.
Cephacetrile--application of pharmacokinetic data to dosage determination.
This pharmacokinetic investigation was based on the determination of serum and urinary levles of cephacetrile in 50 subjects given single intramuscular or intravenous doses of 0.5 or 1 gm of the antibiotic; 30 normal subjects, 10 patients with renal insufficiency, and 10 patients with chronic nephritis undergoing maintenance haemodialysis were included in this study. In normal subjects, mean serum half-life was 1.09 hours (Ke = 0.6337) after intramuscular injection of 0.5 gm cephacetrile, 1.31 hours (Ke = 0.5276) after intramuscular injection of 1 gm, and 0.89 hours (Ke = 0.7806) after intravenous injection of 1 gm. Absorption half-life was 0.45 hours after intramuscular injection of 1 gm cephacetrile. The urinary elimination of cephacetrile over the first 6 hours after injection was on the average 72.7% of the administered dose. After intravenous injection of 1 gm of the antibiotic, the plasma clearance of cephacetrile was 407 ml/min., and its renal clearance 313 ml/min. A linear correlation was found between the values of overall elimination rate constant (Ke) and creatinine clearance in the subjects under investigation (Ke = 0.0080 + 0.0061 ClCr). The established pharmacokinetic characteristics were used to calculate the maintenance and loading doses as well as the intervals between injections adjusted to creatinine clearance. These data constitute true dosage schemes adapted to the particular case of each patient according to his kidney function.
Determination of cefalexin pharmacokinetics and dosage adjustments in relation to renal function.
Following oral administration of a single 500-mg dose of cefalexin, serum and urine levels of the antibiotic were determined comparatively in ten normal subjects, ten patients with renal impairment, and ten patients with chronic nephritis on maintenance hemodialysis. In normal subjects, mean serum peak levels (12.0 +/- 0.8 mcg/ml) were observed 2 hours after drug administration. Absorption half-time (Ta1/2) averaged 0.82 hour and mean serum half-life (T 1/2) was 1.03 hours. Urinary recovery of cefalexin over a 6-hour period amounted to 64 per cent of the ingested dose. The renal clearance of the drug was 214 ml/min. In patients with renal impairment and in patients on maintenance hemodialysis, total elimination rate constant (Ke) was markedly lower (CrCl=0; Ke=Km=0.0766), whereas serum half-life (T 1/2) was significantly increased, reaching theoretically 8.47 hours in patinets with creatinine clearance of 0 ml/min. A correlation was established between Ke values and the creatinine clearances of the patients under study (Ke=0.0766 + 0.0060 CrCl). Initial loading doses, maintenance doses, and intervals adjusted to creatinine clearances were calculated from these data; accurate dosage schedules well adjusted to the renal status of each individual patient were derived from the calculated values.
The biliary excretion of cefazolin.
The biliary excretion of cefazolin was studied by perfusion of isolated rabbit livers. Under these conditions, 6.7 percent of the amount of cefazolin added to the circulating blood was excreted in bile, and concentrations of drug in bile were significantly higher than concentrations in serum. Biliary excretion of cefazolin was also studied in humans after the intravenous administration of 500 mg of the drug. In 10 normal subjects, maximal concentrations of cefazolin (17.10 plus or minus 8.5 mug/ml) in the fluid obtained by duodenal tubing were attained 1-2 hr after administration of cefazolin. Concentrations were similar in bile collected by external drainage from five cholecystectomized patients (maximal levels, 14.0 plus or minus 4.7 mug/ml) 1-2 hr after injection. Assays during cholecystectomy showed that 1 hr after injection, cefazolin levels were much higher in common duct bile (31 plus or minus 11 mug/ml) than in gallbladder bile (5 plus or minus 2 mug/ml).
[Diffusion of cephazolin in the biliary tract].
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[Hypoglycemic accidents during treatment with antidiabetic sulfamides. Apropos of 5 cases of hypoglycemic coma in aged subjects].
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Biliary excretion of a new semisynthetic cephalosporin, cephacetrile.
The biliary excretion of a new derivative of cephalosporin, cephacetrile (CIBA 36 278 Ba), was studied (i) in the isolated perfused rabbit liver, (ii) in humans with a duodenal tube, and (iii) in patients after cholecystectomy with a Kehr's drain in the common bile duct. The biliary excretion of the antibiotic was very low in the perfused liver, and no antibiotic activity was found in liver tissue at the end of the experiment. This observation, together with the finding of a rapid decline of the antibiotic concentration in the circulating blood serum, favors the assumption that a metabolic transformation of CIBA 36 278 Ba in liver tissue takes place. In humans, the antibiotic concentration was found to be low both in the duodenal juice and in the bile obtained by external drainage. The biliary concentrations found in these subjects seem to be inferior to those required for the inhibition of the common bacteria of biliary infections. In renal failure, however, the biliary excretion of CIBA 36 278 Ba increased considerably.
The biliary excretion of cephalothin.
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[In what framework should internal medicine be taught?].
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