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Biomedical subjects

M Dorner

Publications and source records attributed to M Dorner.

At least 55 records · Page 3Linked to original sources

[Pharmacokinetics of intramuscular mezlocillin in patients with normal and impaired renal function (author's transl)].

Pharmacokinetic values of mezlocillin were determined after a single intramuscular injection of 1 g to 10 subject with normal renal function, 10 patients with stable renal insufficiency and 5 patients with chronic renal failure under long-term haemodialysis. The values obtained in normal subjects were : biological half-life Tb 1/2 0.9 hour; elimination constant Ke 0.790 (h-1); total clearance Ct 449 ml/min/1.73 m2; renal clearance Cr 263 ml/min/1.73 m2. Twelve hours after the injection 72.2 % of the dose administered were recovered in the urine. Theoretical values after repeated injection were calculated from the values obtained in subjects with normal renal function. The loading doses providing steady state serum concentrations were determined for various dosage intervals (2, 3, 4, 6 and 8 hours). In patients with renal insufficiency or treated with haemodialysis, serum levels decreased more slowly. The theoretical Tb 1/2 for zero creatinine clearance was 4.7 hours. Sixty-two percent of the amount of mezlocillin present in the central compartment at the onset of haemodialysis were removed after a 6-hour dialysis session. In all 25 subjects investigated, a significant correlation was found between Ke and Ccr (Ke = 0.1973 + 0.0046 Ccr). This correlation was used to calculate the loading and maintenance doses (and sometimes also the intervals between injections) adjusted to renal function values. Dosage guidelines in relation to the renal function were established from these data.

Humans↗

[Comparative biliary excretion of mezlocillin and 12 other beta-lactam antibiotics (author's transl)].

The biliary excretion of mezlocillin was studied on an experimental in vitro model (perfused rabbit liver) and by various methods in man. After addition of 10 mg mezlocillin to blood perfusing isolated rabbit lever preparations (n = 5) during 3 hours, a mean biliary peak of 758 +/- 129 micrograms/ml was recorded between 30 and 60 minutes. The 0-3 h cumulative biliary excretion was 20.3 % of the dose administered. Following a 30 min intravenous infusion of 5 g mezlocillin to 5 healthy subjects, the mean maximal antibiotic activity in the duodenal aspiration fluid was 626.0 +/- 115.0 microgram/ml during the first hour. In 10 cholecystectomized patients with T-tube drainage who received 1 g mezlocillin intramuscularly, a mean biliary peak of 296 +/- 58 micrograms/ml was recorded. The 0-12 h cumulative biliary excretion of the antibiotic was 2.6 % of the dose injected. After intravenous infusion of 5 g mezlocillin, the corresponding values were 505 +/- 118 micrograms/ml and 1.3 % respectively. One hour after rapid intravenous injection of 2 g mezlocillin, the antibiotic activities in samples of serum, common bile duct bile and gallbladder bile collected during cholecystectomy were 28.9 +/- 5.3, 895 +/- 196.1 and 402 +/- 133.2 micrograms/ml respectively. These results were compared with those obtained in similar conditions with 12 other beta-lactam antibiotics.

Animals↗

[Infertility and carbohydrate metabolism. A study of 93 cases (author's transl)].

An oral glucose tolerance test was performed in 93 women with unexplained infertility (sterility or repeated abortions). An abnormal carbohydrate metabolism was found in 1/3 of the cases (32 patients). Advice on diet control, provided to all of these patients, was followed only by 13.9 of these, who conceived less than 6 months after initiation of the low carbohydrate diet, achieved full-term pregnancy. These results suggest a relationship between infertility and glucose intolerance. A glucose tolerance test should be performed in all women presenting unexplained infertility.

Abortion, Habitual↗

[Maternal glucose tolerance along pregnancy (author's transl)].

The development of the foetal and placental unit induces large changes in maternal glucose tolerance along pregnancy. Oestrogen-induced hyperinsulinism is responsible for facilitated anabolism which take place during the first part of pregnancy. Accelerated catabolism occurring during the second part is due to the direct action of placental hormones, mainly of human placental lactogen. The latter is responsible for diminution of peripheral insulin activity. Hyperinsulinism, which is very important at this stage, facilitates from where nutrients can be easily removed. Glucose and amino-acide uptake by placental and foetus are greatly increased by all these changes.

Amino Acids↗

[Juvenile diabetes of recent onset. Sustained insulin remission by means of preprogrammed insulin infusion (author's transl)].

Seven young insulin-dependent diabetic patients were treated within 45 days at the latest from the onset of the disease by programmed insulin infusions delivered with an insulin pump. In every case normal serum glucose levels were obtained. At the end of each 84-hour infusion, an attempt was made to institute oral antidiabetic treatment. This was successful in 6 patients after 2 or 3 infusions and in one patient after 3 infusions followed by 2 months' conventional insulin therapy and a 4th infusion. In 5 patients (71%), oral treatment could be continued for more than 3 months, which indicates sustained remission of insulin-dependence. These results are comparable to those achieved with an artificial pancreas and can be explained by optimal diabetes control during the programmed infusions. The method has the advantages of being simple and relatively inexpensive.

Administration, Oral↗

Biliary excretion of cefuroxime. Experimental and human study.

The biliary excretion of cefuroxime was studied experimentally, using a preparation of isolated rabbit liver (n = 5) perfused in vitro during 3 h; 0.92% of the cefuroxime (10 mg) added to the circulating blood was found in the bile, while peak antibiotic activity reached a mean value of 8.0 +/- 1.1 microgram/ml. In man, 1 h after a single intravenous injection of cefuroxime (0.5 g), a maximum concentration of 4.0 +/- 1.6 microgram/ml was found in the duodenal aspiration fluid collected from 5 healthy subjects. In 10 patients with T-tube drainage, a mean biliary peak of 10.3 +/- 2.4 microgram/ml was observed 2 h after intravenous injection of the same dose; the biliary excretion of cefuroxime during the 12-hour experiment corresponded to 0.13% of the administered dose. Assays performed during cholecystectomy in 10 patients 1 h after cefuroxime intravenous injection of 0.5 g showed concentrations of 11.9 +/- 0.8 microgram/ml in the serum, 12.0 +/- 1.5 microgram/ml in the common duct bile and 7.4 +/- 1.1 microgram/ml in the gallbladder bile. These results were compared with those observed after administration of 11 other beta-lactam antibiotics in identical experimental and clinical conditions.

Animals↗

[Experimental and clinical study of the biliary elimination of mezlocillin (author's transl)].

The biliary elimination of mezlocillin was studied in 5 perfused rabbit liver preparations. After adding 10 mg of mezlocillin to the perfusion medium, the biliary peak averaged 758 +/- 129 microgram/ml and total mezlocillin recovery within 3hr amounted to 20.3% of the administered dose. In 5 healthy subjects, the mean levels in the duodenal fluid collected during the 4 hrs following an infusion of 5 g of mezlocillin ranged from 440 to 637 microgram/ml. In cholecystectomized patients provided with a T-tube drainage, the maximal concentration after the same dosage (n = 10) was 505 +/- 158 microgram/ml and cumulative biliary excretion of mezlocillin over a 12 hr period corresponded to 1.3% of the administered dose. Under the same conditions, after intra-muscular injection of 1 g of mezlocillin to 10 subjects, the biliary peak averaged 292 +/- 58 microgram/ml and the total biliary recovery 2.6% of the administered dose. In 10 patients undergoing biliary tract surgery, the levels determined 1 hr after IV injection of 2 g of mezlocillin reached 896 +/- 196 microgram/ml and 402 +/- 133 microgram/ml in the main duct and in the gallbladder bile, respectively. These results were compared with the values obtained under identical conditions with 12 other beta-lactam antibiotics.

Animals↗

[Experimental and clinical study of the biliary excretion of cefamandole (author's transl)].

Using the isolated rabbit liver perfusion model, it could be shown that 11.1% of 10 mg of cefamandole added to the circulating blood were recovered in the 3 hours collected bile. The maximal biliary antibiotic activity averaged 214 +/- 37 microgram/ml. In humans a peak concentration of 19.0 +/- 6.1 microgram/ml could be measured in the aspirated duodenal fluid (n = 5) 1 hour after a single intravenous injection of 1 g of cefamandole. In 10 patients provided with a Kehr's drainage, a mean biliary peak of 141.4 +/- 86.4 microgram/ml was observed at the 2nd hour after administration of the same dose of cefamandole. Assays performed during cholecystectomy showed 1 after the intravenous injection of 1 g of cefamandole mean values of 64.0 +/- 18.0 microgram/ml in the gallbladder bile and 87.2 +/- 16.1 microgram/ml in the common duct bile. These data are compared with those obtained by administration of 11 other beta-lactamines under similar experimental and clinical conditions.

Animals↗

Biliary elimination of mezlocillin: an experimental and clinical study.

The biliary elimination of mezlocillin, a new semisynthetic penicillin of the acyl-ureido-penicillin group, was investigated in vitro in rabbit liver preparations and in vivo in humans. Experimentally, mezlocillin recovery in the bile during perfusion of isolted rabbit liver (3 h; n = 5) averaged 20.3% of the administrered dose (10 mg). The mean peak concentration in the bile (758 +/- 129.3 micrograms/ml) was reached between 0.5 and 1 h. Biliary clearance was 169 ml/h. In healthy subjects (n = 5), the concentrations of antibiotic measured in the duodenal fluid during a period of 4 h after intravenous administration of 5 g of mezlocillin ranged between 440 and 637 micrograms/ml. In 10 cholecystectomized patients provided with a T-tube, intramuscular injection of 1 g of mezlocillin resulted in a biliary peak concentration of 295.7 +/- 58.1 micrograms/ml. Mean total amount of antibiotic eliminated in the bile over 12 h corresponded to 2.6% of the administered dose. Assays performed during surgery after intravenous administration of 2 g of mezlocillin (n = 10) showed antibiotic activity of 895 +/- 196 micrograms/ml in the common duct bile and 402 +/- 133 micrograms/ml in the gallbladder bile. These data were compared with the values determined for 11 other beta-lactamines studied under identical conditions.

Animals↗

[Variations of the coefficient of glucose assimilation in normal pregnancy].

Three hundred eleven intravenous glucose tolerance tests were performed in normal pregnant women between the 8th and the 40th week, and compared with similar tests performed in two groups of non-pregnant women, one group on oral contraceptives, the other not. There was a relative improvement in glucose tolerance at the beginning of pregnancy followed by marked loss of tolerance after the 24th week. This evolution is due to the physiologic adaptation of the maternal pancreas to fetal and placental metabolism. The range of normality for the glucose disappearance rate differs before and after the 24th week of pregnancy, and this must be recognised in setting diagnostic criteria for gestational diabetes. Consideration of simultaneous studies of glucose tolerance and insulin secretion at various periods of pregnancy suggests that changes in K value are more closely correlated with variations in peripheral insulin effects than with changes in insulin secretory function of the maternal pancreas.

Female↗

[The oral glucose tolerance test during normal pregnancy (author's transl)].

Physiological changes in carbohydrate tolerance were studied between the beginning and end of pregnancy. Amongst 145 oral glucose tolerance tests performed between the 9th and 40th weeks, results indicated that carbohydrate tolerance evolved throughout pregnancy. The first 24 weeks were characterised by a change in the shape of the glucose tolerance curve, in the form of horizontalisation of the terminal part, but with no increase in early blood glucose figures. It was only after the 24th week that mean blood glucose levels were seen to be increased. The interpretation of glucose tolerance tests during pregnancy should take these physiological changes into account. Critical values, above which diabetes must be suspected, are different at the beginning and end of pregnancy. The critical point would appear to be around the 24th week.

Adult↗

[Screening for diabetes during pregnancy (author's transl)].

Screening for diabetes, or more commonly the study of maternal glucose tolerance, a routine procedure during pregnancy. The first step consists of assessing the diabetic risk for the patient. Screening tests should be applied early if risk factors for diabetes are present, and/or at a later stage in all pregnant women. The initial test should always be provoked hyperglycemia by the intravenous route. According to the value of the glucose assimilation coefficient K, the test will be repeated using the oral route. Screening can only be effective if applied to all pregnant women.

Administration, Oral↗