Biomedical subjects

P d'Athis

Publications and source records attributed to P d'Athis.

18 recordsLinked to original sources

PubMed1979

[The pharmacokinetics of nalidixic acid administered parenterally. Towards rational use in severe infections (author's transl)].

Nalidixic acid is effective toward Gram negative infections but its short half-life and potential neurological toxicity explain that its parenteral use is hazardous. Interindividual variations of its pharmacokinetic parameters explain also the absolute necessity of a careful drug monitoring adapted to each patient. The study of plasma kinetics of a single dose of nalidixic acid injected by intravenous route, shows these metabolic variations. With this results, the predicted plasma drug concentrations show that classical dosage regimens are adapted only to a little number of patients. Advantages and inadequacies of a single daily intravenous infusion of nalidixic acid are next analysed.

Bacterial Infections↗

PubMed1979

Transfer in vitro of three benzodiazepines across the human placenta.

A comparative study of the placental transfer to the foetus of three benzodiazepines was performed using a dual perfusion system of the human placental lobule. A transport fraction was calculated for each benzodiazepine and was compared with reference substances. Relative to antipyrine, the transport fraction of diazepam was 85%, and that of nordiazepam was 84%. The transport fraction of clorazepate represented only 20% of that of tritiated water. The relatively high transfer of diazepam and nordiazepam can be attributed to their high lipid solubility, and the lower transfer of clorazepate is due to its polar nature. It is suggested that in certain instances this benzodiazepine may be of especial value to obstetricians.

Anti-Anxiety Agents↗

PubMed1979

Pharmacokinetics of clorazepate in pregnant and non-pregnant women.

A single dose of clorazepate 20 mg was injected i.m. in 7 pregnant and 7 non-pregnant women. Blood samples were collected for one week, and urine was collected for 24 h after the dose. The concentrations of clorazepate and its metabolite nordiazepam were determined by electron capture gas liquid chromatography. There was no difference between the two groups on physical examinations. Clorazepate was rapidly absorbed and the peak concentration was reached within 2 h. Mean pharmacokinetic parameters for clorazepate were absorption half life 0.77 h in pregnant women and 0.56 h in non-pregnant women; elimination half life 1.3 h in pregnant women and 2.0 h in non-pregnant women; volume of distribution: 0.43 1 . kg-1 in the pregnant women and 0.33 1 . kg-1 in non-pregnant women. Nordiazepam reached its peak concentration within 12 h after dosing; its mean half life of elimination was 180 h in pregnant women and 60 h in non-pregnant women. Within 24 h, 1.3% of the clorazepate was recovered in urine from pregnant women and 7% in urine from the non-pregnant women.

Adult↗

PubMed1979

Pharmacokinetics of the placental transfer and distribution of clorazepate and its metabolite nordiazepam in the feto-placental unit and in the neonate.

Clorazepate 20 mg was given i.m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. "Total nordiazepam", i.e. the sum of clorazepate and its metabolite nordiazepam, was determined by gas-liquid chromatography in maternal blood, umbilical cord blood (both arterial and venous), amniotic fluid and in milk. Clorazepate was found to cross the placental barrier slowly, but nordiazepam was transferred more rapidly. Nordiazepam was found in the milk and in the blood of neonates after breast-feeding had started.

Adult↗

PubMed1979

Placental transfer of atropine at the end of pregnancy.

In a first study, 28 pregnant women received a fast intravenous injection of atropine sulphate 12.5 microgram/kg, as in a classical atropine test. Fetal tachycardia resulted. The maternal venous blood concentration of atropine, determined by bioassay on guinea pig ileum, decreased rapidly in the first 3--5 min and very slowly therafter. In a second study, 45 women in labour received the same dose i.v., and at birth atropine was measured both in maternal and cord blood. Placental transfer of atropine had occurred in every case and was highly variable, depending on the maternal blood concentration of the drug. This suggests that the atropine test is not mainly dependent on placental function.

Adult↗

PubMed1979

Phenytoin binding to human albumin.

Binding of phenytoin to human plasma proteins and to human serum albumin is studied using equilibrium dialysis method at pH 7.4 and 37 degrees C. Phenytoin is mainly bound to albumin, the percentage of bound drug being constant over a wide range of total drug concentrations. Calculation of the drug binding parameters show a low affinity, k = 745 M-1, and a high number of binding sites, n = 8. Palmitic acid and some acidic drugs, warfarin and phenylbutazone added to human serum albumin, decreased phenytoin binding in a non competitive way. Basic and non-ionizable drugs, on the other hand, did not modify phenytoin binding.

Anilino Naphthalenesulfonates↗

PubMed1979

[Quantitative study of medullary adipocytes in marrow aplasia (author's transl)].

Quantification of adipocyte surface in relation to hematopoietic tissue was performed quantitatively with a classimat on 21 marrow biopsies from patients belonging to the Cooperative Marrow Aplasia Group. This analysis revealed two quantitative parameters, distribution and homogeneity, which permitted the classification of the biopsies into four groups. Each of these categories has been correlated with clinical and kinetic data.

Adipose Tissue↗

PubMed1979

[Quantitative study of the medullar fibrosis in 84 cases of idiopathic myeloid splenomegaly (author's transl)].

84 bone marrow biopsies were analysed by quantification methods with Classimat. The initial diagnosis was: idiopathic myelofibrosis with splenomegaly. A previous study divided the patients among three categories, according to the classification in three progressive stages of the bone marrow disease. The quantitative lecture was done after reticulin coloration, "in blind", and on several biopsies from the same patient. The results show good correlation with classical histologic methods. The quantitative measure of fibrosis is already important as soon as the first stages of the disease. Correlations with prognosis are more difficult to define.

Biopsy↗

PubMed1979

Pharmacokinetics of carbamazepine in the neonate and in the child.

1. Pharmacokinetic of carbamazepine were made in 7 new-borns and in 5 children. They were hospitalized for epilepsy and were receiving drugs such as phenobarbital alone or in association with other antiepileptic drugs, but not with carbamazepine. 2. The drug was given by oral route with a mean dose of 17.2 mg.kg-1. 3. The determination of carbamazepine concentration in serum was made by gas liquid chromatography on a 50 microliter sample. 4. A one compartment body model was used to determine the pharmacokinetic constants with first order rate constants for absorption and elimination. 5. Absorption was generally delayed by about half an hour, the maximum concentrations ranging from 3.14 to 10 microgram.ml-1 at 2 and 9 hr after administration. The mean half-life for absorption was 1.42 +/- 0.34 hr. The mean half-life for elimination was 8.76 +/- 0.85 hr. The half-life for elimination was much shorter than those already described even in multiple dosing epileptic adult patients. The pharmacokinetic parameters were used to predict blood levels in chronic treatment in 3 children. The predicted steady state concentrations disagreed with the concentrations measured.

Adult↗

PubMed1979

[Stabilisation of total hip arthroplasty. Hemodynamic and gasometric disturbances (author's transl)].

This work aims at studying the operative complications of the stabilisation of total hip arthroplasties with the help of 11 hemodynamic studies, 19 functional records of the epinephrines and 25 surveys of the impact of the stabilisation on arterial blood gas. 1) Within the few minutes following the implantation of bone cement one may remark: -- a drop in the average arterial pressure, -- greater lowering of the stroke index after a femoral implantation than after a cotyloïdal implantation, -- a constant and massive rise of pulmonary resistances which appears mainly after a femoral stabilisation. 2) The hemodynamic disturbances are accompanied by neither a significant rise nor a significant fall of the plasmatic and urinary levels of the epinephrines. 3) There appears with the insertion a massive hypoxemia which can be prevented by the inhalation of pure oxygen.

Aged↗

PubMed1978

[Comparative study of the peripheral lymphocyte count in controls and in patients with chronic lymphocytic leukemias 4 hours after injection of hydrocortisone (author's transl)].

The peripheral lymphocyte count was investigated prior to and 4 h after a single intravenous injection of 400 mg of hydrocortisone (HSHC) in 23 controls and 43 patients with chronic lymphocytic leukemia. A reduction in the peripheral lymphocyte count was observed in all normal controls, the mean decrease being 51.9%, with differences according to age.

Aged↗

PubMed1978

[A new parameter for chronic lymphocytic leukemia : determination of the large lymphocytes by means of Hemalog D (author's transl)].

The munber of large peripheral lymphoid cells and the ratio of these large unstained cells (LUC) to the total number of peripheral lymphocytes were determined by means of the Hemalog D in 57 patients with chronic lymphocytic leukemia (CLL) and in 100 controls. While the absolute number of LUC per mm3 is simply a reflection of peripheral lymphocytosis, the ratio LUC/total lymphocyte count was shown to correlate with clinical staging. In controls, this ratio ranged from 3.2% to 11.2%. In CLL is was less than 11.2% in 43 patients and less than 11.2% in 14 patients. This latter group corresponded statistically to patients with advanced disease in our clinical staging system (stages III and IV). An increase in the LUC/total lymphocyte ratio is therefore a statistical criterion of poor prognosis.

Autoanalysis↗

PubMed1978

[An approximate solution to the integral equation by using non serial cuts (author's transl)].

The problem formulated and resolved by WICKSELL is reformulated for a new technique of quantitative cytology utilizing non-serial cuts instead of serial sectioning. With a technique borrowed from numerical analysis an approximate solution can be obtained. Theoretical results are in agreement with experimental results obtained using a mixture of red blood cells from humans and rats.

Animals↗

PubMed1977

Investigation of a new parameter in chronic lymphocytic leukemia: the percentage of large peripheral lymphocytes determined by the Hemalog D. Prognostic significance.

The number of large peripheral lymphoid cells and the ratio of these large unstained cells to the total number of peripheral lymphocytes was determined by means of the Hemalog D in 57 patients with chronic lymphocytic leukemia (CLL) and in 100 control subjects. Although the absolute number of large unstained cells/mm3 is simply a reflection of peripheral lymphocytosis, the ratio large unstained cells to total lymphocyte count was shown to correlate with clinical staging. In control subjects, this ratio ranged from 3.2 per cent to 11¿per cent. In those with CLL it was less than 11.2 per cent in 43 patients and greater than 11.2 per cent in 14 patients. These 14 patients corresponded statistically to patients with advanced disease in our clinical staging system (stages III and IV). An increase in the large unstained cells to total lymphocyte ratio is therefore a statistical criterion of poor prognosis.

Humans↗

PubMed1977

[Comparative bioavailability of three pharmaceutical forms of digoxin].

The bioavailability single doses (0.5 mg) from three preparations of digoxin is compared in a crossover study in nine normal volunteers. Plasma digoxin concentrations from 0 to 72 hr and urinary glycoside excretion for 96 hr are measured by radioimmunoassay. Areas under the plasma concentration-time curves are assessed according to two different statistical methods, one comparing preparations, the other comparing subjects. With the first, bioavailabilities are similar; with the second, they significantly differ. On the other hand, urinary excretions do not differ. This discrepancy is probably related to different kinetics of digoxin release from the pharmaceutical preparations, the total amount absorbed being equivalent.

Administration, Oral↗

PubMed1977

Variations in lymphocyte counts four hours after administration of hydrocortisone in patients with chronic lymphocytic leukemia.

The peripheral lymphocyte count and the number of large unstained cells (LUC) were investigated prior to and 4 hr after a single intravenous injection of 400 mg of hydrocortisone in 23 controls and 51 patients with lymphoid disorders (43 chronic lymphocytic leukemia, 3 cases of Waldenström macroglobulinemia, 2 hairy cell leukemias, 1 Sézary syndrome, and 2 cases of infectious mononucleosis). A reduction in both the peripheral lymphocyte counts and the number of LUC was observed in all normal controls, the mean decrease being 54% and greater than 60%, respectively, with differences according to age. In chronic lymphocytic leukemia (CLL), the peripheral lymphocyte count showed a variable response: decrease, no change, or increase. A correlation was shown to exist between a decrease in peripheral lymphocyte counts and anatomical-clinical staging: patients with involvement restricted to blood and bone marrow very often exhibited a drop in their peripheral lymphocyte count (p less than 0.01). In addition, the percentage of circulating T lymphocytes was higher (54%) in CLL patients whose peripheral lymphocyte count dropped than in other CLL patients (p less than 0.001).

Age Factors↗

PubMed1976

Binding of four sulphonamides to human albumin.

The four sulphonamides studied--furosemide, tolbutamide, sulfafurazole and sulfonamidochlorobenzoic acid--bind to human albumin at the same sites but with decreasing affinity. These sites are also common to other drugs, namely acenocoumarin, chlorophenoxyisobutyric acid, phenylbutazone and warfarin. In plasma, the four sulphonamides considered bind mainly to albumin, but also, at higher concentrations, to globulins, to an extent that increases as their affinity for albumin lessens.

Acenocoumarol↗

PubMedDate not supplied

[Quantitative study of the medullar fibrosis in 84 cases of idiopathic myeloid splenomegaly (author's transl)].

Bone Marrow↗