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Biomedical subjects

A Leroy

Publications and source records attributed to A Leroy.

At least 91 records · Page 5Linked to original sources

Dipeptidyl-amino-peptidase IV activity in stored buffy coat smears from human blood.

The stability of dipeptidyl-amino-peptidase IV (DAP IV) activity in lymphoid cells of buffy coat smears from human blood was studied during storage for 40 days. Fixed or unfixed smears may be stored at 20 C for up to 24 hr before a decrease in activity occurs. Storage of either fixed or unfixed smears at 4 C, -10 C and -80 C results in a significant loss of activity within 24 hr. However, the cells retain more than 85% of their DAP IV activity for up to 10 days when stored fixed at -80 C. These data underscore the importance of proper processing of slides for DAP IV staining to avoid misinterpretation of results.

Adult↗

[Coronary intramural ruptures caused by transluminal angioplasty. Incidence, significance and development controlled by coronary angiography].

The authors report their experience of coronary intimal rupture (CIR) observed at control angiography performed at the end of transluminal angioplasty in a series of 150 cases. This lesion was observed in 34 p. 100 of cases. Two subgroups were established according to the presence (Group I: 51 cases) or absence of CIR (Group II: 99 cases) in order to try and identify any predisposing factor. The following features were compared in each group: age, sex, number of risk factors, duration of the disease, its severity, the site and morphology of the lesions (calcification, length, excentric or concentric) on the artery dilated and the technique used (number of inflations, maximal pressure, guidable catheter). The only significant feature associated with CIR was the morphology of the stenosis. Intimal rupture was statistically more frequent when the stenosis was long, calcific and excentric (p less than 0.05). The excentric character was highly predictive of CIR +/- 0.02) and even of complicated CIR (p less than 0.01). The CIR was complicated in 10 cases (19.6 p. 100) with a higher incidence than in the rest of the population (p less than 0.05). These complications were immediate presenting as attacks of angina leading on to 4 myocardial infarctions (7.8 p. 100) but no deaths. The treatment consisted in an attempt to redilate the artery with effective angioplasty in 3 out of 4 cases. Medical therapy alone was sufficient in 2 cases and 4 patients underwent coronary bypass. There were no complications in cases of initially asymptomatic intimal rupture. The 6 months outcome was controlled by coronary angiography in 131 angioplasties.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

Uptake of platinum compounds in human tumors. In vitro study.

The kinetics of intratumoral uptake of cisplatin, carboplatin (CBDCA) and TNO-6 were studied in vitro in fragments of tumors of the head and neck maintained in culture medium under conditions simulating therapeutic conditions of chemo-embolization. Cisplatin and TNO-6 are more rapidly taken up than CBDCA (carboplatin). With each of these compounds, after 24 hours a fraction of the platinum taken up is not irreversibly bound to the tissue. The rate of uptake and the proportion of platinum irreversibly bound depends a great deal on the tumor under study. The characteristics of the diffusion indicate that TNO-6 is better used with chemo-embolization than with systemic injection. The opposite finding is seen with carboplatin. Cisplatin appears to to be about equally well-suited for either method of injection.

Aged↗

[Factors of meningeal diffusion of amoxicillin and ampicillin at the acute phase of purulent meningitis in children].

Amoxicillin and ampicillin levels were comparatively studied in blood and CSF of children with purulent meningitis. Thirty one children aged 2 months to 11 years were treated by one of two beta lactams by monotherapy in a daily dose of 200 mg/kg (Group 1: amoxicillin, n = 17; group 2: ampicillin, n = 14). Samples were collected on day 2 one hour after administration of 50 mg/kg IV of the chosen antibiotic. The mean levels observed in serum (69.5 and 53.4 micrograms/ml) and in CSF (7.74 and 7.96) were not significantly different. Beyond these levels we studied different biologic parameters in CSF: leucocytes, polymorphonuclears, protein, glucose and lactic acid. Multiple linear correlations were found, for the two groups and for the whole population between the CSF antibiotic level and the 6 other parameters (group 1: R1 = 0.82; group 2: R2 = 0.88; group 1 + 2: R3 = 0.78). The best correlated parameters with antibiotic CSF level are serum antibiotic level and CSF lactic acid. With these two parameters we can also estimate antibiotic level in CSF with good correlations (R1 = 0.78; R2 = 0.72 and R3 = 0.72).

Amoxicillin↗

[Pharmacokinetics of azlocillin in chronic renal failure and hemodialysis patients].

The pharmacokinetics of azlocillin were studied in 16 patients with varying degrees of renal impairment (creatinine clearance Ccr ranging from 0 to 52 ml/min/1.73 m2) and on and off sessions in 4 of these patients on periodical haemodialysis. A single dose of azlocillin 80 mg/kg was given by intravenous infusion over 30 min. Maximum concentrations in the sera of patients with renal impairment were the same as in normal subjects, ranging from 300 to 400 micrograms/ml. The elimination half-life (t 1/2) increased as renal function deteriorated, with values of 1.11 h in subjects with healthy kidneys to 5.66 h in patients with Ccr less than 15 ml/min (maximum 8.38 h). The apparent volume of distribution (Vd) was unchanged in patients with renal impairment but was significantly increased in patients on haemodialysis. The mean percentage of the dose administered excreted in the urines decreased from 60-70% in normal subjects to about 11% in patients with severe renal failure, but urinary concentrations remained above therapeutic levels. The extra-renal elimination of azlocillin was unmodified by renal impairment. Azlocillin is easily removed by dialysis: t 1/2 values between and during 6 h sessions of haemodialysis were 6.55 h and 2.81 h respectively, corresponding to a 45.8% extraction on the dialyser. These results are comparable to those found in the literature and can be used as a basis for adjusting azlocillin dosage to the degree of renal function.

Adolescent↗

Concentrations of cefotaxime and the desacetyl metabolite in serum and CSF of patients with meningitis.

Thirty-two cases of meningitis (20 caused by Gram-positive or -negative cocci, 7 by Gram-negative bacilli or listeria, and 5 with aseptic meningitis) received cefotaxime, 2 g 8-hourly, in addition to routine therapy. The concentrations of cefotaxime and its desacetyl metabolite in serum and CSF were determined by a high pressure liquid chromotography. Mean concentration of cefotaxime in CSF ranged from 0.8 mg/l (aseptic meningitis), to 6.4 mg/l (Gram-negative and listeria meningitis), and from 0.5 to 5.4 mg/l for the metabolite. The concentrations of both cefotaxime and the derivative demonstrated a correlation with the degree of inflammation (i.e., cell count and protein concentration) and were higher at 3 h after an infusion of antibiotic than at one and two hours. The concentration showed no marked decline on day 10 when signs of inflammation had largely resolved. The concentrations of both the parent compound and the metabolite 3 h after the infusion suggest that, considering the activity and half life of both the dosing might be spaced at 6-8 h intervals.

Cefotaxime↗

Pharmacokinetics of ceftazidime in normal and uremic subjects.

The pharmacokinetics of ceftazidime, administered as a single intravenous dose of 15 mg/kg given in a bolus injection over 3 min, were investigated in 5 normal subjects and in 19 uremic patients. The subjects studied were divided into five groups according to values for endogenous creatinine clearance (CLCR): group I, five subjects with CLCR greater than 80 ml/min; group II, five patients with CLCR = 30 to 80 ml/min; group III, six patients with CLCR = 10 to 30 ml/min; group IV, four patients with CLCR = 2 to 10 ml/min; and group V, four anuric patients on hemodialysis. A two-compartment open model was used to calculate the pharmacokinetic parameters. In normal subjects, the mean apparent elimination half-life was 1.57 +/- 0.13 h. The central distribution volume and the apparent volume of distribution were 0.127 +/- 0.023 and 0.230 +/- 0.015 liter/kg, respectively. Of the injected dose, 83.6 +/- 3.6% was eliminated in the urine as parent drug within 24 h. The terminal half-life increased with impairment of renal function to about 25 h in severely uremic patients. Impairment of function did not significantly modify the half-life at alpha phase, central distribution volume, or apparent distribution volume. A 6- to 8-h hemodialysis procedure reduced concentrations of ceftazidime in plasma by approximately 88%, and the elimination half-life was 2.8 +/- 0.2 h. There was no evidence of accumulation of ceftazidime in four patients with severe and chronic impairment of function who received doses of 0.5 to 1.0 g every 24 h for 10 days.

Adult↗

[Pharmacokinetics of moxalactam in adults].

Specific characteristics of Moxalactam, a new beta-lactam antibiotic, are high serum concentrations, prolonged half-life and good tissular diffusion. After IM injection of a single dose of 0.25, 0.5 and 1 g, the maximum serum concentration, achieved at one hour, averages 13, 16-21 and 30-50 micrograms/ml. After rapid IV injection of 0.5 and 1 g, the average maximum serum concentrations are 90 and 150 micrograms/ml; after an IV infusion of 2 g over 20 minutes, maximum concentrations are 150 to 180 micrograms/ml. Moxalactam elimination kinetics are linear, independent from the dose and route of administration, with a distribution half-life (T 1/2 alpha) between 0.20 and 0.60 hours and an elimination half-life (T 1/2 beta) between 2 and 2.5 hours (range: 1.9 and 3.1 hours). The apparent distribution volume is between 15 and 18 liters, i.e. 20 to 25% of the body weight. Serum or total clearances and renal clearances are respectively 80 to 100 and 50 to 90 ml/mn, with wide variations from one author to another. Approximately 70 to 90% of the administered dose are eliminated in the urine over 24 hours, without any tubular secretion. Renal failure results in a progressive increase of the elimination half-life, which can reach 20 hours in patients with anuria; approximately 50% of the injected dose are recovered by hemodialysis. Many pharmacokinetic studies have demonstrated the excellent diffusion of the agent in the various tissues and body fluids, particularly in the CSF. From the collation of bacteriologic and pharmacokinetic data, dosage regimens adjusted to the renal function can be proposed.

Adult↗

RBC membrane adenosine triphosphatase activities in patients with major affective disorders.

Red blood cell Na+, K+-, Mg2+-, and Ca2+-adenosine triphosphatase (ATPase) activities were studied longitudinally in eight patients with affective disorders and 12 healthy volunteers. The patients had a higher mean Ca2+-ATPase activity than the volunteers, and the fluctuations in all three ATPase activities were greater in the patients than in the volunteers. Even though the mean Ca2+-ATPase activity was higher during manias and euthymic periods than during depressions, mood and ATPase activities did not correlate with each other in all patients. Lithium carbonate treatment did not alter the ATPase activities, and the quantity of vanadium present in the membranes could not account for the variations in the enzyme activities observed. We suggest that either the RBCs of manic-depressive patients are very sensitive to fluctuations of a lipophilic ATPase activity--regulating factor present in plasma or the patients have at times high levels of such a factor. In some patients, the level of this hypothesized regulator may fluctuate in synchrony with mood changes.

Adenosine Triphosphatases↗

Pharmacokinetics of temocillin (BRL 17421) in subjects with normal and impaired renal function.

The pharmacokinetics of temocillin were investigated in five normal subjects and in 20 uraemic patients. Normal subjects were given single intravenous doses of 3.75, 7.5 and 15 mg/kg of temocillin and a single intramuscular dose of 7.5 mg/kg. Patients with renal impairment were given 7.5 mg/kg of the antibiotic intravenously. A three-compartment open model was used to calculate kinetic data after iv administration. Pharmacokinetic parameters of temocillin were similar both for the three iv doses and for the im dose. The terminal serum half-lives (T1/2 beta) averaged 4.75-5.88 h. The central distribution volume (Vc) and the apparent volume of distribution (Vd area) were 0.093-0.111 and 0.268-0.303 l/kg, respectively. Renal and total body clearances were within 27.4-34.1 and 40.2-47.8 ml/min/1.73 m2, respectively. 67.4-71.5% of the dose was recovered unchanged in urine over 24 h. Intramuscular dosing of 7.5 mg/kg gave a mean peak level of 26.71 mg/l at 1.67 h. In uraemic patients, similar maximum serum concentrations were found after a single 7.5 mg/kg iv dose. The terminal half-life increased according to the degree of renal failure, from 5 h in normal subjects to about 30 h in severe uraemic patients. Renal impairment did not significantly modify Vd area, fractional clearance (Cr/GFR) and non renal clearance. 65.2% of the antibiotic was removed during haemodialysis. Dosage adjustments of temocillin in uraemic patients are proposed.

Adult↗

[Pharmacokinetics of dibekacin in subjects with normal renal function].

The principal pharmacokinetic parameters of dibekacin were studied in five adult subjects with normal renal function after IM and IV injection of a single dose of 1 mg/kg. The results obtained showed that the pharmacokinetics of dibekacine were independent of the dose (T1/2: 2.1 h; distribution volume: 14-161; renal clearance: congruent to 70 ml/min; urinary excretion in 24 hours congruent to 80%) and very similar to those of other aminoglycosides of the deoxystreptamine group.

Adult↗

[Pharmacokinetics of dibekacin in patients with chronic renal impairment].

The pharmacokinetics of dibekacin were studied in 23 patients with varying degrees of renal insufficiency. Creatinine clearance was between 4 and 51 ml/min. Chronic renal insufficiency did not affect maximum serum concentrations, nor the time required to reach a peak level after an intramuscular injection of 1 mg/kg of dibekacin. The maximum concentration was 4 to 5 mcg/ml and the peak obtained within the first hour. Renal insufficiency caused a very marked prolongation in the serum half-life of elimination. This rose from 6 hours in moderate renal insufficiency to 50 hours in a patient with a clearance of a few millilitres. Whatever the degree of renal insufficiency, it should be noted that urinary concentrations remained markedly higher than the MIC of organisms sensitive to the aminoglycoside. Dibekacin is highly dialysable, being virtually totally extracted during a 6 hours dialysis session using a membrane of 1 m2 surface area. An outline of dose adaptations in relation to the degree of renal insufficiency is suggested on the basis of these pharmacokinetic data.

Adult↗

[Pharmacokinetics of cefotaxime and metabolites in uremic patients (author's transl)].

The study was done after a single dose in 6 normal subjects and 24 patients with varying degrees of renal insufficiency. In normal subjects, the results are similar whatever the assays are used. In uremic patients, the half-life for the terminal phase increased with renal failure with the microbioassay, but it is demonstrated that deacetyl cefotaxime has only a prolonged half - life with a more specific assay = HPLC method. After repetitive doses, the tendency for accumulation was only noted in patients with very severe renal failure (creatinine clearance less than 5 ml.min-1).

Adult↗

[Pharmacokinetics of cefotaxime in patients with chronic renal impairment (author's transl)].

The pharmacokinetics of cefotaxime were investigated in 6 healthy subjects and in 22 uraemic patients with various degrees of renal insufficiency. After i.v. bolus injection of a single 15 mg/kg dose, pharmacokinetic data were calculated using a two compartment model. Serum and urine concentrations were determined by microbiological (M.A.) and HPLC assays. With microbiological assay, the elimination serum half-life (T 1/2) increased in patients according to their degree of renal insufficiency and reached 10 hours when creatinine clearance fell below 10 ml.min-1. When concentrations of cefotaxime and its derivatives (desacetyl cefotaxime, M2 and M3) were determined by HPLC assay, the elimination serum half-life of cefotaxime (T 1/2) was not modified in severe uraemic patients; however the elimination half-life of the metabolites increased when creatinine clearance decreased. Cefotaxime can be administered at a dose of 1 g i.v., twice daily in patients with stable chronic renal insufficiency when creatinine clearance is above 5 ml min-1. In cases of more severe renal failure, the dose should be halved and given i.v. every 12 hours.

Adult↗