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Biomedical subjects

G Olive

Publications and source records attributed to G Olive.

At least 109 records · Page 6Linked to original sources

X-linked hypogammaglobulinemia and isolated growth hormone deficiency.

We undertook clinical, immunologic, and endocrinologic studies of a family in which two brothers and their two maternal uncles had a similar disorder characterized by hypogammaglobulinemia and isolated growth hormone deficiency. Recurrent sinopulmonary infections were a prominent feature in two patients. All patients had short stature and retarded bone age during childhood, and the adults had delayed onset of puberty. The immunodeficiency was characterized by absent specific antibody production in vivo and impaired immunoglobulin production in vitro. Three of the four patients lacked circulating B lymphocytes, even though tonsils were present in those patients. All patients had deficient growth hormone responses to insulin and arginine or levodopa. These patients have an X-linked recessive disorder, but their immunodeficiency differs from the X-linked immune disorders in the World Health Organization classification; their X-linked pattern of growth hormone deficiency, without other endocrine abnormality, is also unique.

Adolescent↗

Pharmacokinetics of buflomedil after intravenous and oral administration.

Pharmacokinetics studies were conducted in 4 patients who received buflomedil 100 mg intravenously and in 3 volunteers who received buflomedil 450 mg per os. Buflomedil concentrations were determined by a gas liquid chromatography method. Buflomedil levels declined multiphasically with a mean clearance after intravenous administration of -0,034 (1 h-1 kg-1). The decline appeared to be monophasic after oral administration. In both cases the overall half-life is short, mean 2.07 hrs (range, 1,47-2,6 hrs).

Administration, Oral↗

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↗

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↗

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↗

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↗

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↗

Plasma hypoxanthine in neonatal hypoxia: a comparison of two methods.

Hypoxanthine levels were determined in both venous and arterial cord blood of 42 neonates. Two methods were compared, a PO2 electrode determination and an HPLC (high-pressure liquid chromatography) method. A good correlation was found between the two methods. However, the HPLC method was more sensitive, more reproducible and easier to perform. Hypoxanthine levels in the umbilical artery were found to be higher than in the vein. A significant negative correlation between pH and hypoxanthine level was established. The studies showed that plasma hypoxanthine levels by themselves did not provide an absolute diagnosis of intrauterine hypoxia.

Blood Gas Analysis↗

[Determination of dipotassium clorazepate in the plasma by gas chromatography (author's transl)].

The authors present a method of estimation of dipotassium clorazepate by gas chromatography with a detector for electron capture. It requires 2 ml of blood. Two separate extractions are necessary, including one immediately after the sampling to determine the nordiazepam present at the time of the blood sample. The second extraction permits one to determine the total nordiazepam obtained by transformation of all the dipotassium clorazepate. This method is simple and rapid and permits one to determine with precision, specificity and good reproducibility (CV -- 3%) the therapeutic concentrations of this drug.

Anti-Anxiety Agents↗

[Pharmacologic bases of use of benzodiazepines in peréinatal medicine].

The pharmacokinetics of benzodiazepines have been studied because these drugs are often given to pregnant mothers and occasionally to neonates. The rate of absorbition is faster in the neonate than in the mother by all routes of administration but the drugs accumulate, the degree being related to gestational age, the more premature the greater the accumulation. There is preferential storage in some organs including the heart. Diazepam and chlordiazepoxide are metabolised to active compounds but oxazepam, nitrazepam and flurazepam are inactivated. Individual susceptibilities are important. These drugs readily pass across the placenta but the teratogenic risk is uncertain. They are also excreted in the breast milk in quantities which justify their withdrawal during breast feeding. On the basis of the findings therapeutic protocol is proposed.

Adult↗

Micromethod for determination of diazepam by electron-capture gas-liquid chromatography.

We used 100 microliters of plasma for the determination of diazepam. After the internal standard, prazepam, is added, the serum is directly extracted with diethyl ether, the extract is evaporated, the residue is dissolved in ethanol, and the drug is measured by gas-liquid chromatography, with use of an electron capture detector. With this procedure, 2.5 ng of diazepam in the sample can be speedily measured with specificity, accuracy, and reproducibility (CV = 4.5%).

Chromatography, Gas↗

Effect of 24 hour fast in obese children.

Effects of a 24 hour fast were studied in 21 obese children aged 7 to 14 and in 8 controls. Mean blood glucose (BG) during fast dropped more in controls (0.88 to 0.54 g/l) than in obese (0.90 to 0.63 g/l) Plasma cortisol changes were similar in the 2 groups, FFA increased (p less than 0.01) in the 2 groups, but the 24 hour mean level was higher in controls (4.0 mEq/l) than in obese (2.06 mEq/l). At the end of the fast, a ketonuria was present in all obese children except 2. Serum alanine dropped similarly in obese (28 to 24 muM p. cent ml) and in controls (30 to 22 muM p. cent ml). All obese exhibited at the end of the fast a significant rise (p less than 0.01) of branched chain aminoacids, not observed in controls. Responses to glucagon (0.03 mg/kg I.M.) were studied before and after fast. At time 0, BG response was higher and more prolonged in obese in spite of hyperinsulinism. At time 24 hours, BG raised from 0.50 to 0.74 g/1 and insulin from 8 to 35 muU/ml in controls, while in obese BG raised from 0.63 to 1.06 g/l and insulin from 25 to 88 muU/ml. Concomitant hyperinsulinsim and biological criteria of hypoinsulinism demonstrated in obese children the peripheral resistance to insulin. The contrast between a normal degree of protein gluconeogenesis and a reduced rate of fat mobilization during fast may be a major biological feature of obesity in childhood.

Adolescent↗

[Semi-micromethod for the assay of vitamin E. Use in neonatal pharmacology].

A micromethod using 250 mul of plasma was described for assaying vitamin E. The complete extraction of the plasmatic vitamin E was made possible. The sensitivity and occurency of this method are particularly suitable in pediatric determinations. The vitamin E plasmatic levels were measured in the low birth-weight newborn given or not a 10 mg vitamin E supply in the feeding.

Anemia, Hemolytic↗