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Biomedical subjects

J F Blickle

Publications and source records attributed to J F Blickle.

At least 55 records · Page 3Linked to original sources

[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↗

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↗

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↗

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↗

[Treatment of severe hyperthyroidism by plasma exchange. Clinical and biological efficacy. 8 cases].

The effectiveness of plasmapheresis was evaluated in 8 patients with severe thyrotoxicosis of diverse origin and clinical manifestations, who underwent a total of 22 plasma exchanges. The method proved rapidly effective in controlling the symptoms in 6 cases. No adverse reaction was noted. In all patients plasma exchanges significantly reduced plasma concentrations of total thyroxine and triiodothyronine and of thyroxine-binding globulin, without effect on free thyroxine and triiodothyronine fractions. The satisfactory clinical results obtained can only be explained by displacement of thyroid hormones from the intracellular compartment. The hormonal variations observed were proportional to the initial hormone concentrations, to the amount of thyroxine-binding globulin removed and to the plasma volume purified. It is concluded that plasmapheresis rapidly extracts thyroid hormones and is therefore useful in the treatment of acute severe thyrotoxicosis.

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↗

Genetically engineered insulin: five years of experience.

Genetically engineered insulin is the first application of recombinant DNA technology which has gone into industrial production and wide clinical use. Four years after the first clinical trials, it appears that there are only minor pharmacokinetic differences from purified pork insulin; in particular, a faster subcutaneous absorption for both regular and NPH forms. The hypoglycaemic potency of genetically engineered insulin is identical to that of purified pork insulin but a weaker effect on counterregulatory hormones has been reported. However, the main advantage of biosynthetic human insulin is its species specificity, which reduces its immunogenicity. Convincing results were obtained in patients suffering from insulin-produced adverse reactions such as insulin resistance or allergy, although biosynthetic human insulin does have some immunological properties and crossreacts with beef or pork insulin antibodies.

Animals↗

[Biosynthetic human insulin. Pharmacokinetic characteristics and activity in normal subjects].

The pharmacokinetics and pharmacodynamic effects of intravenously injected (0.06 U/kg) human biosynthetic insulin of recombinant DNA origin and purified porcine insulin, both regular, were compared in 10 healthy volunteers. Both had identical immunological properties. Some of their pharmacokinetic features, such as total plasma clearance and bioavailability, were similar, but they appeared to differ in biological half-life, elimination rate constant and apparent volume of distribution. No appreciable difference was found between their hypoglycaemic activity and their inhibitory effect on endogenous insulin secretion. However, hyperglucagonaemia seemed to be less pronounced after human biosynthetic insulin than after purified porcine insulin. These findings are discussed by comparison with the results of other studies on human biosynthetic insulin.

Adult↗

The role of insulin, glucagon and growth hormone in the regulation of plasma glucose and free fatty acid levels in anorexia nervosa.

It is well established that glucagon plays an important role in the regulation of fuel supplies as its plasma level increases during the first days of a complete fast. However, it is not certain that glucagon is involved in the adaptation to chronic starvation. In the present study, this problem was investigated by the determination of the changes in the plasma glucagon level elicited by an i.v. glucose tolerance test followed by an i.v. arginine perfusion in 26 self starved patients suffering from anorexia nervosa (AN) and 14 control patients having only minor neurotic disorders. The basal plasma glucagon level tended to be higher in the AN patients than in the controls; but the difference was not statistically significant. Glucagon responses to glucose and arginine observed in the AN patients were not significantly different from those seen in the control patients. In the AN patients, the insulin response to both loads was reduced and the plasma GH level increased paradoxically after the glucose load, whereas it rose normally after the arginine load. It may be concluded that in chronic starvation by AN the regulation of fuel supplies depends mainly on decreased insulin and increased growth hormone secretion. The role of glucagon seems to be of minor importance in this condition.

Adolescent↗