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Biomedical subjects

J M Brogard

Publications and source records attributed to J M Brogard.

At least 73 records · Page 4Linked to original sources

Semisynthetic human insulin: biological and pharmacokinetic effects in normal subjects.

The assessment of pharmacokinetic and pharmacodynamic properties of semisynthetic human insulin produced by enzymatic conversion was done in normal subjects, and compared to those of highly purified pork insulin. Ten healthy volunteers were submitted to an intravenous injection of 0.06 U/kg of regular insulin, semisynthetic (Actrapid HM) and monocomponent pork insulin (Actrapid MC) in succession. No significant differences were pointed out as far as the pharmacokinetic parameters, immunoreactivity and hypoglycemic effect of both types of insulin are concerned. Only a stronger inhibition of endogenous insulin secretion, expressed by a significantly lower plasma-C-peptide levels, was observed after PPI. Stimulation of glucagon secretion was similar with both types of insulin.

Adult↗

[Experimental evaluation of the biliary tract passage of ceftriaxone and its hepatic disposition].

The biliary elimination of ceftriaxone was studied by an isolated perfused rabbit liver model (n = 5). After adding of 10 mg of this antibiotic to the circulating blood of this preparation, a mean biliary peak level reaching 120.5 +/- 24.6 micrograms/ml was obtained between the 30th and 60th minutes. The total amount of ceftriaxone eliminated unchanged in the bile collected during a 3h period represents 8.8 +/- 2.6% of the administered dose. At the end of this study period, 32.7 +/- 3.3% of the initial dose remained in the circulating blood. The hepatic tissue concentrated 3.7% of the whole dose. At last, control experiments proved that 36.4% of the added antibiotic has been degraded by the experimental system itself. Thus the remaining 18.4% can be attributed to a hepatic biotransformation of ceftriaxone.

Animals↗

[Direct determination of clavulanic acid in biological fluids using HPLC].

The so far described HPLC methods for clavulanic acid (CA) monitoring needed post-column derivatization with imidazole, resulting in poorly practicable methods. We propose here a direct determination of CA in human biological fluids with a ion-pairing technology using the bathochromic shift of tetrabutylammonium bromide (TBAB). The separation is performed on a reversed phase analytical column (250 X 4.6 mm) with the following mobile phase: 10% acetonitrile in 1 mM TAB and 20 mM ammonium acetate (pH = 5). The U.V. detection is at 214 nm. Serum and bile are prepared with acetonitrile and methylene chloride, and urines are diluted 1/10 prior the analysis. Retention time of CA is 8.4 min. Detection limit for bile and serum is 0.1 mg/l and 5 mg/l for urines. Within and between-day reproducibility is respectively 5.4% and 7.2% for serum and bile, and 4.7% and 6.8% for urine. This method may be suitable for clinical routine analysis and pharmacokinetic studies.

Bile↗

Ceftazidime: experimental and clinical evaluation of biliary elimination.

During a 3-h perfusion of five isolated rabbit liver preparations, 1.4% of 10 mg of ceftazidime added to the circulating blood was eliminated in the bile and 0.9% was metabolized or inactivated in the liver. Five normal subjects were given 2 g of ceftazidime intravenously; antibiotic concentration in the aspirated duodenal fluid rose progressively during the 4 h of the investigational period to a maximal mean level of 21.3 +/- s.e.m. 9.2 micrograms/ml and 0.05% of the dose given was recovered during this period. The same dose was given to 12 cholecystectomized patients fitted with a Kehr drain. An average peak value of 36.3 +/- 4.0 micrograms/ml was reached in the collected bile during the second hour after drug administration. The 12-h biliary recovery was 0.21% of the dose given. Ceftazidime concentrations in choledochal and gallbladder bile sampled peroperatively in 10 patients 1 h after intravenous administration of 2 g of ceftazidime were 78.3 +/- 12.0 and 17.9 +/- 7.5 micrograms/ml respectively. These data compare favourably with the results of the authors' studies on the biliary elimination of 15 other beta-lactams and are consistent with a possible beneficial effect of ceftazidime in the treatment of biliary tract infections.

Adult↗

[Evaluation of bile diffusion of piperacillin].

In 10 patients undergoing cholecystectomy peroperative samples of serum, bile and gall bladder tissue were obtained one hour after intravenous injection of 2 g of piperacillin. Measurements were made by high performance liquid chromatography. Mean concentrations of piperacillin were 81.7 +/- 13.6 micrograms/ml in serum (S), 382 +/- 110 micrograms/ml in choledochal bile (CB), 30.8 +/- 8.5 micrograms/ml in gall bladder bile and 10.5 +/- 2.6 micrograms/g of gall bladder tissue. With a CB/S ratio of 4.7, piperacillin may be classified among beta-lactams showing good distribution in the biliary tract. This property would make piperacillin useful against the pathogens usually responsible for biliary tract infections.

Adult↗

[Current trends in dietetics in diabetology and their experimental bases].

The last decade has witnessed drastic changes in our views on diet for diabetics, whether insulin-dependent or not. To bring blood glucose levels down to normal values, thereby preventing diabetic microangiopathy or alleviating its course, remains the compelling purpose of treatment, but the modalities and constraints of the dietetic measures which contribute to this result have been radically revised. Leaving aside fashions and controversies, three tendencies have emerged: the low carbohydrate diet does not improve the glycaemic balance but implies an excessive fat intake which may aggravate the microangiopathy. Of course, an hypocaloric diet remains fundamental in the management of obese non-insulin dependent diabetics; the effects on glycaemia of the carbohydrate ration constituents must be reconsidered. The classical distinction between "fast" and "slow" sugars seems to be excessive and insufficient, if not erroneous. Food replacements must take into account the glycaemic index; a minimal dietary fibre intake has a favourable effect on post-prandial glycaemia and lipid metabolism and is to be recommended, notably to diabetics.

Diabetes Mellitus↗

Biliary elimination of cefotiam, an experimental and clinical study.

Five isolated rabbit livers were in vitro perfused over a 3-hour period. After addition of 10 mg of cefotiam to the circulating blood, a biliary peak concentration of 76.2 +/- 14.2 micrograms/ml (mean +/- SEM) was reached between the 90th and 120th min; 3.1 +/- 0.4% of the dose given was excreted in the bile during the 3-hour period. In 10 recently cholecystectomized patients provided with a T-tube drain, 1 g of cefotiam was given intravenously. A biliary peak concentration of 340 +/- 81 micrograms/ml was observed 2 h later. 1.8 +/- 0.7% of the administered dose was recovered in the bile during the 12-hour period. In 5 clinically normal subjects given intravenously 1 g of cefotiam, 0.5 +/- 0.2% of the administered dose was found in the duodenal fluid aspirated over a 4-hour period. Cefotiam concentrations measured in choledochal and gallbladder bile collected simultaneously during operation 1 h after intravenous administration of 1 g of the drug to 10 patients were 502 +/- 102 micrograms/ml and 143 +/- 39 micrograms/ml, respectively; they exceeded significantly the concentration determined in the serum sampled at the same time (17.9 +/- 2.6 micrograms/ml). The biliary parameters of cefotiam were compared with those of 14 other beta-lactam antibiotics previously studied by the same procedure. The results of the present study are consistent with a possible beneficial effect of cefotiam in the treatment of biliary tract infections.

Animals↗

[Malnutrition and deficiency of insulin secretion in alcoholic cirrhosis. Study by the assay of urinary C-peptide].

In order to evaluate the relationship between nutritional status and insulin secretion in cirrhosis, the following parameters of caloric (tricipital skin fold, prealbumin) and proteic (arm muscle size, transferrin, 24 h-urinary creatinine excretion) nutritional status were compared in 20 alcoholic cirrhotics and 10 normal subjects. Insulin secretion was evaluated in both groups by insulin and C-peptide response to an intravenous glucose tolerance test and by 24 h urinary excretion of C-peptide. When compared to normals, cirrhotics have lower values for all nutritional status parameters and individually for at least three of those in 14 (70 p. 100) patients. In cirrhotics there is a significant decrease of the 4-min poststimulative response of insulin and C-peptide, contrasting with higher basal and late poststimulative values than in normals. This contrast could be explained by a reduced metabolic clearance rate of insulin (consistent with insulin resistance) and of C-peptide (the urinary clearance of which is 2.5 times lower in cirrhotics than in normals). The 24-h urinary excretion of C-peptide, probably weakly dependent of this reduced clearance, is 50 p. 100 lower in cirrhotics: 12.9 +/- 1.6 nM/24 h than in normals: 26.0 +/- 2.4 nM/24 h (p less than 0.001). In cirrhotics there is a significant linear correlation between 24 h urinary C-peptide excretion and all the nutritional status parameters but one (prealbumin). These results indicate that in cirrhosis: 1) urinary C-peptide excretion rate is a good index of insulin secretion; 2) urinary C-peptide indicates a marked deficit in insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Experimental and clinical evaluation of the biliary elimination of ceftazidime].

After adding 10 mg of ceftazidime to the circulating blood of five isolated rabbit liver perfusions, total antibiotic excretion over a 3 hours period accounted for 1.4% of the administered dose; only 0.9% was found to be metabolized by the liver. In five healthy subjects given 2 g ceftazidime intravenously, 0.05% (102 +/- 576 micrograms) was recovered in the duodenal fluid over a four-hour period. In 10 patients with a T-tube inserted following cholecystectomy, 0.21% of a 2 g dose of ceftazidime injected intravenously was found in the bile collected over a 12-hour period (4 161 +/- 489 micrograms); a mean biliary peak of 36.3 +/- 4.0 micrograms/ml was recorded during the second hour. In 10 patients in whom serum, choledochal bile and gallbladder bile were sampled simultaneously during surgery 1 hour after IV administration of ceftazidime, the concentrations found were 40.6/e 2.1, 78.3 +/- 12.0 and 17.9 +/- 7.5 micrograms/ml respectively. Our results suggests that ceftazidime may be suitable in the treatment of biliary tract infections.

Adult↗

Biliary elimination of apalcillin: an experimental and clinical study.

After adding 10 mg of apalcillin to the circulating blood of five isolated rabbit liver perfusion preparations, total apalcillin biliary recovery over a 3 h-period accounted for 30.7% of the administered dose; the biliary peak level averaged 686.0 +/- 135.9 micrograms/ml. In five healthy subjects, a maximum level of 1088 +/- 582 micrograms/ml was measured in the duodenal fluid collected during 4 h following intravenous injection of 1 g of apalcillin. In 10 cholecystectomized patients provided with T-tube drainage, after the same dosage, a biliary peak of 2093 +/- 859 micrograms/ml was attained in the 3rd hour and cumulative biliary recovery over a 12 h-period amounted to 12.1% of the injected dose. In 20 patients undergoing biliary surgery, intra-operative simultaneous sampling performed 1 h after intravenous injection of 1 g of apalcillin showed antibiotic levels of 65.5 +/- 5.0 micrograms/ml in serum, 3860 +/- 551 micrograms/ml in common bile duct bile and 2552 +/- 627 micrograms/ml in gallbladder bile. The results of these investigations were compared with data previously obtained with 13 other beta-lactam derivatives.

Ampicillin↗

Diagnosis and treatment of heart failure in different European countries: a young AEMIE questionnaire.

To compare diagnosis and treatment of heart failure among different European countries, an anonymous questionnaire was developed and sent to young AEMIE members all over Europe. 159 filled-in questionnaires were received: 30 p. 100 from France (F), 25 p. 100 from Great Britain (GB), 21 p. 100 from the Benelux countries (NL), 13 p. 100 from Italy (I) and 11 p. 100 from West-Germany (D). Baseline characteristics of the participating physicians (age, years of hospital training, available equipment, etc.) were comparable among the different countries. There was good agreement in the value of history, clinical examination, ECG and chest X-ray for the diagnosis of heart failure. In all countries breathlessness, basal crepitations and gallop rhythm were counted among the most important signs of left heart failure. Whereas the value of gated-blood-pool scanning and Holter monitoring as a first diagnostic approach was unanimously denied, the value of 2D-echocardiography in heart failure was discussed controversially: in I, F and D 50-80 p. 100 of the physicians thought echocardiography a first-hand diagnostic tool, whereas only 20-30 p. 100 of the physicians in GB and NL recommended echocardiography in the first place. Diuretics, sodium reduced diet and afterload reduction (in GB only) are the first therapeutic measures in GB, NL and F. However, in I and D digitalis is still the cornerstone of therapy (greater than or equal to 50 p. 100!). Physicians of all European countries with the exception of the physicians in D prefer pure digoxin as the first digitalis preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lack of correlation of glycosylated haemoglobin level with the duration of diabetes or diabetic angiopathy.

Patients with severe diabetic angiopathy show an increased physiologic haemolysis. The aim of the present study was to evaluate the practical influence of the resulting reduced red cells half-life on the glycosylated haemoglobin (GHb) level as determined by a routine method. 168 diabetics, aged 55.7 +/- 1.3 years, were studied. The duration of disease ranged from 3 months to 34 years; 66 patients were insulin-treated and 87 had clinical features of arteritis and/or patent microangiopathy. A highly significant correlation was found between the mean plasma glucose level determined on the first day after admission and the GHb value. The slopes of regression curves of diabetics with and without angiopathies were similar. For a given mean glucose level there was no correlation between the GHb value and the duration of diabetes. So, in clinical practice, it is not necessary to take into account the duration of diabetes or the presence of angiopathies for explaining the GHb results.

Adult↗

High-performance liquid chromatographic method for determination of ciprofloxacin in biological fluids.

A simple and precise high-performance liquid chromatographic procedure has been developed for the determination in biological fluids of ciprofloxacin, a new, with extended antibacterial spectrum, quinoline carboxylic acid. The work-up procedure involves a chemical extraction step followed by isocratic chromatography on a reversed-phase analytical column, with ultraviolet detection. The detection limit for blood levels is 10 ng/ml. The calibration curve is linear from this detection limit to 10 microgram/ml. The statistical analysis of the correlation made between this assay and an agar diffusion procedure during a pharmacokinetic study suggests the existence of one or more active metabolites which could be mainly excreted in the bile.

Anti-Infective Agents↗

[Ciprofloxacine: evaluation of its biliary elimination in man].

To investigate the possibility of therapeutic use of ciprofloxacin in infections of the biliary tract, the serum and bile kinetics, and the biliary, urinary and fecal elimination of this new broad-spectrum quinolone were studied in 12 recently cholecystectomized patients with T-tube drainage. Ciprofloxacin concentrations were determined by simultaneously performed HPLC and microbiological assay in serum, urine, and bile over a 24-hour period following oral administration of a single dose of 500 mg of the drug. The two methods yielded similar values both in the serum and in the urine. Average peak serum concentrations were 0.97 +/- SEM 0.17 microgram/ml (HPLC) and 1.08 +/- 0.19 microgram/ml (microbiological assay) (NS). The respective mean urinary concentrations in the first 6-hour sample were 267 +/- 74 micrograms/ml and 241 +/- 58 micrograms/ml (NS). In bile, however, the microbiological assay gave higher values than HPLC:average peak concentrations of 10.3 +/- 3.4 micrograms/ml and 7.5 +/- 2.8 micrograms/ml (p less than 0.02) respectively, reached during the 2nd hour after drug administration, and mean total 24-hour biliary ciprofloxacin output of 2167 +/- 288 micrograms and 1587 +/- 222 micrograms (p less than 0.01) respectively. This may point to hepatic transformation of ciprofloxacin to more active metabolite(s) than the parent compound. The significantly higher concentrations of ciprofloxacin in bile than in serum exceeded the minimum inhibitory concentration for organisms usually responsible for biliary infections. These infections may, therefore, be favorably affected by ciprofloxacin.

Adult↗

Biliary elimination of beta-lactam antibiotics by the isolated perfused rabbit liver.

Biliary elimination of 15 beta-lactams was studied using a model of isolated perfused rabbit liver. During the perfusion period, the main liver functions were well preserved. The highest biliary concentrations were reached by antibiotics of the penicillin group, and the highest biliary recovery was observed with metampicillin, apalcillin and mezlocillin (46.5, 30.7 and 20.3%, respectively, of the dose administered). This technique was also suitable for estimating the degree of bio-transformation in the liver of the antibiotics studied.

Animals↗

Comparison of high-pressure liquid chromatography and microbiological assay for the determination of biliary elimination of ciprofloxacin in humans.

Serum kinetics and biliary, urinary, and fecal elimination of ciprofloxacin, a new quinolone derivative, were studied in 12 recently cholecystectomized patients provided with T-tube drainage during 24 h after oral administration of a single 500-mg dose of this substance. Drug concentrations were measured by both high-pressure liquid chromatography (HPLC) and microbiological assay. The results were comparable for the concentrations in serum (average of peaks, 2.0 +/- 0.2 micrograms/ml by HPLC and 2.3 +/- 0.3 micrograms/ml by the microbiological method) and urine (0 to 6 h, 267 +/- 74 and 241 +/- 58 micrograms/ml, respectively). This was not the case for biliary values, for which the microbiological assay yielded significantly higher concentrations than did HPLC (average of peak concentrations, 21.2 +/- 2.6 and 16.0 +/- 2.5 micrograms/ml, respectively [P less than 0.02]), nor for total 24-h biliary output (2,167 +/- 288 and 1,587 +/- 222 micrograms, respectively [P less than 0.01]). This suggests hepatic biotransformation of ciprofloxacin into microbiologically active metabolites. The apparent broad antibacterial spectrum of ciprofloxacin and its higher biliary levels than simultaneously determined serum concentrations suggest that this derivative is suitable for the treatment of biliary tract infections.

Adult↗