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J Auzerie

Publications and source records attributed to J Auzerie.

18 recordsLinked to original sources

[Treatment of growth hormone deficiencies with growth hormone releasing hormone. Current status and perspectives].

Results of clinical trials performed with human hypothalamic growth hormone releasing factor (GRF) are conflicting, but rather disappointing for most of them. Pulsatile administration of GRF has been found to increase growth hormone secretion as well as growth velocity, but is not convenient for practical use. All other routes and rhythms of administration lead only to sub-optimal results, and generally does not seem to procure an appropriate GRF bio-availability. Improvements are possible, particularly the development of agonists and new galenic forms with sustained release. Therapeutic approach with hexapeptides, or hexapeptides analogs, looks promising, but could be more complementary than competitive.

Child↗

Discontinuation of growth hormone therapy in growth-hormone-deficient patients: assessment of body fat mass using bioelectrical impedance.

The changes in body composition evaluated by the mean of bioelectrical impedance analysis (BIA) have been observed in a group of 16 male adolescents at the time of discontinuation of growth hormone (GH) therapy as well as at 6 and 12 weeks later. After reevaluation of their endocrine function, 6 patients (3 craniopharyngioma, 1 irradiation, 1 malformative, 1 idiopathic) had a profound persistent GH deficiency (maximum peak of GH under provocative tests < 5 ng/ml and low IGF-1 levels), while 10 patients had a normal somatotropic function. Both groups were comparable as far as age, weight and body mass index are concerned. Fat weight is significantly higher in the GH-deficient patients (9.9 +/- 2.6 kg) than in boys with a normal somatotropic function (6.0 +/- 1.1 kg) at the time of the discontinuation of GH therapy (p < 0.01). 3 months later, the increase in fat weight is significant only in the group of patients with severe GH deficiency (+4.1 +/- 2.2 kg; p < 0.05), the difference between the 2 groups (14.0 +/- 3.5 and 7.3 +/- 1.0 kg) becoming highly significant (p < 0.001). Lean body mass is lower in the GH-deficient patients and decreases slightly after GH discontinuation, while no significant variation is observed in the group of non GH-deficient boys. Although BIA assessment of body composition may be discussed when applied to GH-deficient subjects, these results show that such patients should be reevaluated after the discontinuation of GH therapy, including examination of the possible metabolic consequences of GH deficiency.

Adipose Tissue↗

A placebo-controlled trial of intranasal growth hormone-releasing hormone [GHRH(1-44)-NH2] administration in normal young adults.

Growth hormone-releasing hormone, GHRH(1-44), was administered intranasally to 16 healthy young adult male volunteers in a placebo-controlled study using a dose of 1,000 micrograms dissolved in two different solvent vehicles: water alone and water with the surface tension-lowering agent Tween 80 (0.12%). The growth hormone (GH)-releasing effects of intranasal GHRH as well as that of the vehicle were established and compared to the effects of 80 micrograms intravenous GHRH. Plasma GH response was assessed by frequent blood sampling over an 180-min period, using both peak response and area under the curve (AUC). The results show that the GH-release effects of intranasal GHRH are comparable whichever vehicle is used, and are similar, with the dose of 1,000 micrograms, to the response obtained following the administration of 80 micrograms intravenous GHRH. Peak GH responses to GHRH (means +/- SEM) were 25.6 +/- 4.2 ng/ml (1,000 micrograms GHRH with water), 32.9 +/- 9.1 ng/ml (1,000 micrograms with water plus Tween 80) and 36.3 +/- 7.8 ng/ml (80 micrograms i.v. administration) (not significant). There was no significant GH response to placebo. Mean peak GH responses occurred after approximately 30 min in all three active treatments (29.2 +/- 2.7, 33.9 +/- 3.2 and 30.9 +/- 3.9 min, respectively). The AUC values (ng.min.ml-1) were not statistically different: 1,914.4 +/- 386.7 (water), 2,176.2 +/- 599.9 (water plus Tween 80) and 2,419.2 +/- 506.9 (i.v.) (not significant). Intranasal GHRH administration was well tolerated in all subjects. Occasional local reactions consisted of a prickly sensation in the nostrils or sneezing irrespective of the vehicle used.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Growth response to growth-hormone administration during the decelerating phase of the pubertal growth spurt in short normal children.

In order to investigate the value of growth hormone (GH) treatment during late puberty, we studied the effect of human GH (hGH) administration (0.85 +/- 0.30 IU/kg/week; range: 0.44-1.28) on height velocity (HV) after the peak of the pubertal growth spurt in a group of 10 (4 girls and 6 boys) short normal children (GH peak after pharmacological stimulation: 15.5 +/- 2.3 ng/ml) with growth retardation (height: 2.6 +/- 0.3 SD) and puberty Tanner stage 4. A group of 10 untreated children, observed prior to the study, served as controls. The children were regularly measured during their pubertal growth spurt, and HV (cm/year) was calculated every 6 months. The pretreatment evaluation consisted of 2 consecutive 6-month periods characterized by a decrease in HV of at least 25%. In the group of selected children, hGH administration was then initiated and growth variables were evaluated after 6 and 12 months of therapy. Skeletal maturation was evaluated at the beginning as well as after 6 months and 12 months of hGH therapy. In the controls, HV (mean +/- SD) had decreased from 8.8 +/- 1.8 to 4.9 +/- 1.4 cm/year during the pretreatment period (in girls from 7.9 +/- 1.4 to 4.1 +/- 0.6 cm/year and in boys from 9.6 +/- 1.6 to 5.8 +/- 1.2 cm/year). During the following semester, HV was 3.3 +/- 0.8 cm/year (girls: 3.4 +/- 1.0 and boys: 3.2 +/- 0.2 cm/year).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Plasma prolactin, sex steroids and gastrin in human volunteers treated for 2 weeks with therapeutic doses of cimetidine or the new histamine H2-receptor antagonist ramixotidine (CM 57755A).

Three groups of eight healthy male volunteers received placebo for 2 days, then daily morning doses either of cimetidine 800 mg, ramixotidine 750 mg (CM 57755A), or placebo, for 14 days, and then were all returned to placebo for one more day. Plasma levels of prolactin, testosterone and 17 beta-estradiol were measured on Days 2, 3, 16 and 17 in blood samples taken 30 and 15 min before and 0, 60, 120, 180, 240 and 300 min after treatment. Gastrin was assayed in blood collected on the same days 180 min after treatment. Mean pre- and post-treatment areas under the time-concentration curves of the first three hormones were not significantly different in the three groups on any test day, or within the same group throughout the four test days. Mean plasma gastrin levels ranged between 27 and 42 pg/ml, respectively, in the placebo and cimetidine treated groups on test day 3, and intermediate values were found in the group receiving CM 57755A. There was no statistically significant difference in gastrin level between the groups on any test day or within the same group throughout the four test days. No subjective side-effects attributable to the treatments were reported, and there were no abnormalities in blood pressure, heart rate or standard laboratory tests.

Adult↗

Meningeal penetration of apalcillin in man.

We have used high performance liquid chromatography to evaluate the meningeal penetration of apalcillin. In subjects without meningitis the penetration was poor and the levels obtained did not exceed 1.75 mg/l. In cases of meningitis, when the spinal fluid albumin level was greater than 0.60 g/l, the levels varied from 5 to 30 mg/l. These figures are in accord with those obtained in cases of experimental meningitis. A dosage of 200 mg/kg/day should allow the treatment of meningitis due to sensitive bacteria and in particular due to Pseudomonas aeruginosa.

Adult↗

[Transplacental transfer of 5 antibiotics by in vitro human placental perfusion].

Transplacental transfer of 5 semi-synthetic penicillins which act on Gram + and Gram - bacteria were studied by in vitro perfusion of the human placenta. These penicillins were: amoxicillin, apalcillin, mezlocillin, piperacillin and ticarcillin. Placental transfer of these 5 antibiotics varies between 5 and 7% of the maternal concentration. Amoxicillin 7,62% - apalcillin 5,66% - mezlocillin 5,4% - piperacillin 7,37% - ticarcillin 4,86%. The reasons for such low transfer and the clinical repercussions of these results are discussed by the authors.

Amoxicillin↗

Treatment of adult asthma: controlled double-blind clinical trial of oxitropium bromide.

Sixteen young adult sufferers from extrinsic paroxysmal asthma with pollen hypersensitivity took part in a therapeutic trial of the synthetic anticholinergic agent oxitropium bromide administered by a metered dose inhaler. The study comprised three 3-week periods. The first, run-in period was carried out to confirm the ability of the patients to maintain a daily record of symptoms. During the second and third periods, the patient received 3 X 2 inhalations of drug or placebo in a cross-over design. The medical staff was blind to the nature of the aerosol (drug or placebo), which was given in random order. The run-in clinical score was high. Asymptomatic days were relatively infrequent and daily drug consumption was high. Functional studies between the cross-over periods showed flow-rate values close to normal, with an increase in residual volume and functional residual capacity. During treatment either with placebo or oxitropium, there was a statistically significant decrease in clinical scores. Results for oxitropium bromide treatment were significantly better than the run-in values (p less than 0.005) and the placebo period (p less than 0.02). There was no significant change in non-trial drug consumption. Functional values showed no difference in terms of flow rate, although oxitropium did cause a significant improvement in the RV/TLC ratio (p less than 0.05). No adverse reactions were reported.

Administration, Intranasal↗

[Bacteriostatic activity of apalcillin on Gram-negative bacilli and strict anaerobic bacteria. Multicenter study].

This work reports a multicenter study of the bacteriostatic activity of apalcillin, a new N-acyl-penicillin, against 1 827 clinical isolates of Gram-negative bacilli and obligate anaerobes. The modal minimal inhibitory concentrations (MICs) for susceptible strains are (mg/l) : Salmonella-Shigella : 1 ; E. coli : 0.5-2 ; Klebsiella : 4 ; Citrobacter : 1-2 ; Enterobacter : 2 ; Serratia : 8 ; Proteus-Providencia : 1 ; Acinetobacter : 1-4 ; P. aeruginosa : 2 ; H. influenzae : 0.06 ; C. perfringens : 0.03-01 ; Peptococcus : 0.2 ; B. fragilis : 16. Against Enterobacteriaceae and Acinetobacter, apalcillin is as active as mezlocillin and piperacillin, and much more than carbenicillin. Against P. aeruginosa, apalcillin is the most active penicillin : 2 to 16 fold more active than azlocillin and piperacillin, and 2 to 128 fold more active than ticarcillin. Against H. influenzae, C. perfringens and Peptococcus, apalcillin has MICs similar to those of other N-acyl penicillins, and inferior to those of carboxypenicillins . Apalcillin, as other penicillins, is poorly active against B. fragilis.

Ampicillin↗

[Pharmacokinetics of apalcillin. Study of linearity].

Apalcillin is a new semi-synthetic penicillin active on the positive Gram bacteria, and on the enterobacteria, with a particular activity on Pseudomonas and Acinetobacter. The linearity study of the pharmacokinetic was carried out on 26 subjects who were given increasing doses (500, 1 000, 2 000, 3 000 mg) of apalcillin by the venous route. The dosages carried out by the HPLC and bacteriological methods, show a good correlation between the two methods. The serum concentrations, 5 mn. after injection, were respectively 72 micrograms/ml (500 mg); 145 micrograms/ml (1 g) ; 221 micrograms/ml (2 g) ; 290 micrograms/ml (3 g). Urinary excretion is around 20 %, and this, regardless of the dose. The dose increase seems to have no effect on the pharmacokinetic parameters, calculated on the basis of a bi- compartmental model. The areas under the time serum concentrations, increase proportionally, to the dose : 61 (500 mg) ; 146 (1 g) ; 285 (2 g) ; 367 (3 g) - micrograms/ml X h. the linear regression between the AUC (y) and the applied doses (X) is : y = 0,12 X + 14,27 ; r = 0,9046 ; n = 69. The correlation between the AUC and the doses is significant (p less than 0,001). The results obtained show that increasing the dosage has no effect on apalcillin pharmacokinetics, which appear linear.

Adult↗

[Effect of a new synthetic anticholinergic (oxytropium bromide) on acetylcholine-induced bronchospasm].

Oxytropium bromide, a new synthetic anticholinergic agent, delivered by a dose inhaler, was compared to a placebo in a cross-over double-blind trial. The drop in FEV1 after administration of increasing doses of acetylcholine aerosol spray was measured 45 min after administration of the test drug, and the dose-response curve was determined. The placebo modified neither acetylcholine threshold dose (bronchial sensitivity) nor the slope of the curve (bronchial reactivity). Oxytropium bromide elevated the response threshold and decreased bronchial reactivity to vagal stimuli.

Acetylcholine↗

[Pharmacokinetic study of apalcillin after infusion].

Apalcillin is a new semi-synthetic penicillin of the uridino-penicillin group. The study comprises two groups of 6 subjects receiving 1 g and 2 g respectively of apalcilline by a two-hour infusion. The assays done by HPLC and microbiology show a good correlation between the two methods. The serum concentrations at the end of the infusion are: 32,2 micrograms/ml-1 (1 g) and 62,7 micrograms/ml-1 (2 g). The modelisation of the serum curves has been realized according to an open model with two compartments. A phase of rapid distribution is observed: t 1/2 alpha of 19.5 mn (1 g), 8.96 mn (2 g) followed by a phase of longer elimination: t 1/2 beta of 1.17 h (1 g), 1.15 h (2 g). The distribution volume at the steady-state is: 14.19 l (1 g), 14.76 l (2 g). This volume, much greater than the plasmatic volume, allows to suppose a good tissular diffusion of apalcilline. The urinary concentrations of the twelve first hours are: 182.64 micrograms/ml (1 g), 323 micrograms/ml (2 g). The urinary elimination during the 24 hours following the administration is: 18.58% (1 g), 16.47% (2 g).

Adult↗

[Renal vein thrombosis in the newborn infant].

In a child born with traumatism to a diabetic mother, an acute thrombosis of the left renal vein occurred. An arteriography performed at the acute stage, established the diagnosis. The newborn received urokinase and heparin administered through an arterial catheterism. An arteriography, repeated at the 3rd day, showed an improvement in the vascularization of the kidney, which returned to normal functions. The radiological symptons of renal vein thrombosis are reviewed including the arteriography which is never used for the diagnosis in newborns. The interest of the use of urokinase and its efficiency in this disorder are discussed. This therapy harmless and efficient seems of interest. Such a therapy has to be tried because of the failure of isolated heparin-therapy and of the sequellae which may be observed after spontaneous recovery or after anticoagulant treatment.

Female↗