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Biomedical subjects

L Balant

Publications and source records attributed to L Balant.

At least 91 records · Page 5Linked to original sources
PubMed1977

Behaviour of glibenclamide on repeated administration to diabetic patients.

Six maturity onset diabetic patients took glibenclamide 5 mg by mouth, every morning 10 min before a standard breakfast. Serum levels of immunoreactive glibenclamide, glucose and immunoreactive insulin were measured repeatedly on the first and 15th days of treatment. Measured glibenclamide blood levels were in close agreement with an analogue computer simulation of data obtained from healthy volunteers: there was no accumulation of drug in the blood, but there was strong evidence for the existence of a slowly equilibrating "deep" compartment. Considerable insulin release and correction of the breakfast-induced hyperglycaemia were observed immediately after administration of the drug, as well as 5 h later, at lunch time. The clinical significance of blood levels of glibenclamide, as well as the correlation of pharmacokinetics with pharmacodynamics, are discussed in the light of these results.

Administration, Oral↗
PubMed1976

[Electrocardiograms of digitalis intoxication. Reevaluation].

Serum digoxin concentration and ECG were recorded 111 times in 96 patients taking digoxin. The generally accepted ECG criteria of digoxin concentration seem greatly to overestimate the incidence of toxic cases. According to these criteria 63 ECGs in this study would have been regarded as toxic, whereas toxicity (defined by the association of serum digoxin elevation and clinical symptoms of toxicity) was actually present in only 11 cases.

Adult↗
PubMed1976

[Pharmacokinetics of two beta blocking drugs: detection of a pharmacogenetic abnormality].

10 healthy male volunteers received orally either 100 mg tolamolol or 20 mg bufuralol. These experiments were repeated by intravenous administration of 10 and 5 mg respectively of these two drugs. Plasma levels of the parent drugs and their main metabolite were measured. In one subject, the apparent half-life of elimination was increased from 2.5 h (normal subjects) to 5 h for both drugs. This prolongation of the half-life is associated with low plasma levels of the metabolites, a peculiarity which can be explanined by a decreased rate of metabolism for these two drugs. This anomaly may explain the marked orthostatic hypotension observed only in this subject. The likelihood of a pharmacogenetic defect is discussed.

Administration, Oral↗
PubMed1976

[Clinical pharmacokinetics].

The action of a drug depends on the quantity which reaches the site of its pharmacological action and how long it remains there. The necessary vital processes of the body dilute the active principle into different compartments of distribution, transform it into metabolites, and excrete it. Since a time duration of drug presence at the site of action is vital for the cure of disease, a comprehensive and quantitative expression of these time courses of drug distribution as a function of dose and route of administration is necessary for the establishment of proper dosage regimens for the treatment of disease and the avoidance of toxicities. The purpose of pharmacokinetics is to study these phenomena and to construct models suitable to explain them and to predict the behavior of drugs in conditions not yet studied. In this review some basic principles of pharmacokinetics (i.e. the compartment, the volume of distribution, the elimination half-life, etc.) are explained. Their clinical implications are shown in the case of multiple dose administration and in the study of the relations existing between blood levels of digoxin and the pharmacological action of this drug.

Body Weight↗
PubMed1976

Renal failure, drug pharmacokinetics and drug action.

Patients with renal insufficiency often react abnormally to a number of drugs. Small doses that are safe under normal conditions may cause severe and even fatal side-effects. As a consequence, modification of the usual drug dosage of these drugs in required in renal insufficiency. Since the risk of retention concerns only those drugs which are mainly excreted by the kidney, it is possible to establish a mathematical relationship between glomerular filtration rate and the rate of drug elimination. These relationships serve as a basis for the determination of the proper dosage regimen for the individual patient. Such dosage adaptation for intermitten drug administration can be obtained by two methods and a series of compromises between them: (1) increase of the dosage interval without changing the dose, and (2) reduction of the does without changing the frequency of administration. One must however, not only consider inadequate drug elimination but also a number of other factors. Some of these modify the behaviour of the drug, such as hypoalbumineamia, which causes an increase of the unbound portion of the drug; anomalies of the volume of distribution, as found in patients with oedema; metabolic disturbance; alteration of absorption from the gastro-intestinal tract, etc. Other factors are related only indirectly to the pharmacokinetic behaviour of the drug. Frequently, there is an increased sensitivity to the undesirable side-effects of certain drugs in patients with renal insufficiency, causing the level of tolerance to be lowered compared with normal patients. Such an effect probably involves functional or morphological modifications of the drug receptors, or interaction with substance retained in renal insufficiency. Furthermore, drugs may accentuate the consequences of the nephropathy or have increased nephrotoxicity for those with diseased kidneys. It is with these important reservations that a critical analysis of the proposed methods of adapting drug dosage in renal insufficiency is presented. An appendix tabulates the effects of renal insufficiency on the behaviour of 117 drugs. Irrespective of the method used to calculate drug dosage, all patients with renal disease must be monitored closely, particularly for signs of unexpected drug toxicity.

Drug Administration Schedule↗
PubMed1975

[Proceedings: Alkaline phosphatases in patients in chronic hemodialysis].

The alkaline phosphatases (AP) have been studied in 28 patients on chronic hemodialysis. Total AP averaged 49 IU/1 while 4 out of the 28 patients exhibited pathologic values (above 60 IU/1). Determination of iso-AP by acrylamide gel electrophoresis revealed the existence of an intestinal band in 50% of cases, thought this is not observable in a control population. The only relationship seen between the presence of the intestinal iso-AP and different parameters concerned the blood groups O and B. Significant increase of total AP is in all cases due to a bone iso-AP. During a hemodialysis session a mean increase of 30% in total AP has been noted. An increase in total AP is observed in only 2 cases out of 17.

Alkaline Phosphatase↗
PubMed1975

[Proteinuria in mature diabetic patients. Quantitative and qualitative analysis].

Proteinuria has been analysed in 334 maturity-onset diabetics and 80 matched controls. Proteinuria measured in the recumbent position exceeded 100 mug/min in 53% of the diabetic population. The percentage of excessive proteinuria increased with duration of the disease. Sex and age had no influence. Out of 55 first year diabetics, 49% had abnormal quantitative proteinuria; this is in contrast to 76 longterm diabetics (over 12 years) of whom 38% had proteinuria under 100 mug/min. Electrophoresis and immuno-electrophoresis showed a glomerular pattern in 40%, a tubular pattern in 15% and a mixed pattern in 8% of all the diabetics. 32% of the diabetics with quantitatively normal proteinuria were abnormal qualitatively, and this may be the first manifestation of diabetic nephropathy. Thirty-eight other patients had a normal electrophoretic pattern in spite of increased proteinuria. Proteinuria levels were significantly associated with hematuria, bacteriuria and reduced GFR, but not with leukocyturia, insulin dependence and hypertension. Upright position increased the proteinuria to a greater degree amongst the patients with normal proteinuria. We discuss the role of increased filtration pressure and glomerular permeability in modifying proteinuria in diabetes. Sensitive quantitative and qualitative proteinuria determinations are important tools both in early diagnosis of diabetic nephropathy in clinical practice and in epidemiological studies.

Adult↗
PubMed1975

[Alkaline phosphatase isoenzymes. Selection of the seperation methods and their diagnostic value].

Polyacrylamide gel electrophoresis (PAGE) of alkaline phosphatase (AP) was performed in 116 patients with elevated AP and in 36 controls. Results were compared with clinical data and with the heat inactivation techniques for AP isoenzyme separation. This latter method is simple but approximate; it is without value in the case of coexistent bone and liver pathology. PAGE gave a clear separation of liver, bile, bone, and intestinal AP isoenzymes. Disagreement with clinical data was rare (6 out of 86) and occurred in cases of associated bone and liver pathology (with 1 exception only), where one of these two abnormalities was not detected. Heat inactivation is useful as a screening test. If the cause of the elevated AP remains unknown after a few simple examinations, PAGE should then be utilized. Although more time-consuming, it is certainly more effective in the separation of AP isoenzymes.

Adult↗
PubMed1975

[Physiological proteinuria. Data of acrylamide-SDS gel electrophoresis and other methods of qualitative and quantitative analysis].

Since detection of the first stage of nephropathies requires an exact definition of physiological proteinuria, this has been sought in 97 healthy individuals. Measured by a modification of the biuret reaction, physiological proteinuria did not exceed 100 mug/min in the recumbent position (average of 24.5 mug/min) and 150 mg/24 h (average of 51 mg/24 h). No significant differences were seen with respect to age or sex. Qualitative analysis of urinary proteins was done by cellulose acetate electrophoresis, immunoelectrophoresis and polyacrylamide-SDS electrophoresis. This latter method has the great advantage of classifying the proteins according to their molecular weight, wtihout electrostatic interference. Its graphic representation delineates a normal zone allowing an objective distinction between physiological and pathological proteinurias. In the majority of cases, the proportion of albumin is between 25 and 55%. The orthostatic position increases proteinuria (average of 41 mug/min) with a tendency to a distribution which erroneously suggests a glomerulopathy. Accordingly, investigation for small changes in proteinuria should always be carried out on urine formed in the recumbent position.

Adult↗
PubMed1975

Comparison of the pharmacokinetics of glipizide and glibenclamide in man.

Four subjects received 5 mg 14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg 14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-lives increased steadily with time. The two sulfonylureas were extensively metabolized and were excreted in the urine as hydroxylated or conjugated metabolites. The effects of both drugs on blood glucose and immunoreactive insulin were comparable. The findings are compared with other published results.

Administration, Oral↗
PubMed1975

Catabolism physical, and immunologic properties of endocytosed isologous and heterologous iota-globulins by mouse macrophages.

The catabolism of completely endocytosed isologous and heterologous gamma-globulins by mouse macrophages was studied in vitro. Mouse, human, and rabbit 125-I-IgG were coupled to mouse, human, or sheep erythrocytes either as antibodies or by covalent binding. They were exposed to macrophages for 1 hr and the non-endocytosed erythrocytes were then removed with a Ficoll gradient centrifugation. Catabolism was evaluated after 2, 5, and 18 hr in culture by measuring the radioactivity released into the culture medium as well as the radioactivity that remained associated with cells. It was found that all iota-globulins were catabolized in a similar fashion, and that the type of carrier erythrocytes (isologous or heterologous) had no influence on catabolism. Some of the material that remained associated with macrophages was on the cell membrane and could be removed by trypsin. Some of the material that was released by macrophages was completely degraded but some was either not degraded or only partially degraded. Sucrose density gradient analysis and SDS-polyacrylamide gel electrophoresis showed that this material had kept some physical properties of native iota-globulins. It was also found with the antigen-binding inhibition test and incubation with erythrocytes that the released material contained molecules carrying Fab determinants and was able to bind specifically to erythrocytic antigens. Taken together, these observations show that iota-globulins phagocytosed in the form of antigen-antibody complexes are only incompletely degraded and that the material associated with plasma membrane of macrophages or found in the culture medium is a product of cell catabolism.

Animals↗