[Good use of aminosides].
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Aminoglycosides↗
Biomedical subjects
A Leroy
Publications and source records attributed to A Leroy.
Relationship between renal function and disposition of oral cefixime.
The pharmacokinetics of cefixime following a single oral dose of 200 mg have been investigated in 6 normal subjects and in 22 patients with various degrees of renal insufficiency. Serum and urine samples were collected between 0 and 72 h and were subjected to two methods of analysis: bioassay and HPLC. There was a linear relationship between the two sets of results from 228 samples. This result suggests that none of the metabolites, which may accumulate in uraemic patients, has antibacterial activity. In normal subjects, the peak serum level (Cmax) was 2.50 micrograms.ml-1 at 2.83 h (tmax); the apparent elimination half-life (t1/2) was 3.73 h; the apparent total body clearance (CL.f-1) was 154 ml.min-1, the mean renal clearance (CLR) was 39.1 ml.min-1 and the apparent fraction of the dose recovered in 24 h urine was 0.22. In uraemic patients, Cmax and tmax were slightly increased and t1/2 was increased to 12-14 h in patients with an endogenous creatinine clearance below 20 ml.min-1. The apparent volume of distribution was decreased. Apparent total and renal clearances were lower in proportion to the degree of renal insufficiency. Linear relationships were found between CL/f, CLR and creatinine clearance (CLCR). The findings suggest that the dose of cefixime needs to be reduced only in patients with severe renal failure.
Administration, Oral↗
Penetration of lomefloxacin into human prostatic tissue.
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4-Quinolones↗
Optimal dose of lignocaine for preventing pain on injection of propofol.
The purpose of this study was to define the optimum dose of lignocaine required to reduce pain on injection of propofol. We conducted a prospective, randomized, double-blind trial on 310 patients undergoing anaesthesia. Patients were allocated to four groups according to the lignocaine dosage: group A (control), no lignocaine; group B, lignocaine 0.1 mg kg-1; group C, lignocaine 0.2 mg kg-1; group D, lignocaine 0.4 mg kg-1. Our results showed that a dose of lignocaine 0.1 mg kg-1 significantly reduced the incidence of pain and that there was no improvement when the dose was increased.
Adolescent↗
Minor hemisphere syndrome following left hemispheric lesion in a right handed patient.
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Aged↗
Apolipoprotein A-I-containing lipoproteins in human umbilical cord blood. Relation to proapolipoprotein A-I and lecithin:cholesterol acyltransferase.
Lipids, apolipoproteins, lipoproteins, as well as lipoproteins containing both apo A-I and apo A-II (Lp A-I:A-II) or apo A-I but no apo A-II (Lp A-I), proapolipoprotein (proapo) A-I and the activity of lecithin:cholesterol acyltransferase (LCAT), were investigated in umbilical cord sera of 67 term human neonates (30 females and 37 males). Lp A-I and Lp A-I:A-II were present in umbilical cord sera with levels of 0.26 +/- 0.1 and 0.33 +/- 0.15 g/l, respectively. Furthermore, the absolute amount of proapo A-I was lower in cord blood than in adult plasma, but in view of the lower apo A-I levels in umbilical cord sera it comprised 10.48 +/- 3.86% of total apo A-I and was thus significantly higher than in adult plasma (7.1 +/- 0.9%). Proapo A-I was highly correlated with HDL cholesterol and apo A-I. Total serum LCAT activity was about 50% of adult plasma and was highly correlated with Lp A-I, but not with Lp A-I:A-II. We conclude that human umbilical cord serum contains both Lp A-I and Lp A-I:A-II particles and that the LCAT activity is predominantly related with the Lp A-I subfraction. The higher percentage in umbilical cord sera of proapo A-I may indicate a higher turnover of apo A-I or a lower activity of the proapo A-I cleaving enzyme which is still not identified.
Apolipoprotein A-I↗
Use of unstable chromosome aberrations for biological dosimetry after the first postirradiation mitosis.
The loss of unstable chromosome aberrations after the first postirradiation mitosis makes their use difficult in radiation dosimetry. We describe here a method which, in a cell population observed at this stage, allows retrospective estimation of the frequencies of the unstable aberrations induced at the time of irradiation, and their use as a dosimeter. The laws controlling the behavior of unstable aberrations during mitosis were defined from a large-scale experiment on irradiated human lymphocytes. For cells undergoing the first, second, or third mitosis after irradiation, relationships were determined between the frequency, at irradiation time, of acentric fragments not arising from formation of dicentrics or rings, and the ratio of dicentrics and centric rings appearing without acentric fragments to the total number of dicentrics plus rings. On the basis of this ratio, the method described here provides an assessment of the postirradiation mitotic activity in a cell population. This assessment permitted estimation of the cell distribution and frequency of dicentrics plus centric rings, and of the frequency of acentric fragments at the time of irradiation. The use of this method for retrospective dosimetry after whole-body irradiation under various conditions of exposure is illustrated.
Animals↗
Comparison of the effects of purified human alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor on NK cytotoxicity: only alpha 1-proteinase inhibitor inhibits natural killing.
While an inhibitory effect on natural killer (NK) cell activity was demonstrated with partially purified alpha 1 Achy, neither highly purified alpha 1 Achy from two healthy donors nor from one patient with giant-cell arteritis, which carries more highly branched glycans, inhibited the NK cytotoxicity. Our purification procedure, based on immunoaffinity chromatography and gel filtration, was not in question since the pure alpha 1-proteinase inhibitor (alpha 1PI) prepared in our laboratory by using a similar procedure continued to inhibit the NK cytotoxicity. If an inhibitory effect not related to antiprotease activity occurs with alpha 1PI, it is surprising that it is not shared by alpha 1 Achy which, like alpha 1PI, belongs to the serpin family and which possesses a strong structural homology with alpha 1PI. Our finding that alpha 1PI is able to affect human NK cytotoxicity while alpha 1 Achy (even with more highly branched glycans) is unable to suggests that events controlling NK activity may involve other enzymes than chymotrypsin-like enzymes.
Arteritis↗
Genotoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. I. Chromosome aberrations induced in vivo.
Unstable chromosome aberrations were scored in peripheral blood lymphocytes (PBL) serially collected from 21 breast cancer patients before and after radiotherapy (RT), chemotherapy (CT) and combined treatments. Local radiotherapy as treatment for mammary cancer induced unstable chromosome aberrations in peripheral blood lymphocytes. Only a fraction of these lymphocytes were exposed to irradiation during treatment and the chromosomal damage observed in PBL was equivalent to that induced by irradiation in vitro with 2 Gy at high dose rate, i.e., about 4% of the total dose delivered locally. Chemotherapy alone did not induce such anomalies. Apart from the observed interindividual variations in either the level or the fate of dicentrics with time, different features of chromosome damage were found when chemotherapy was given before or after local cobaltotherapy: secondary chemotherapy did not alter the frequency and the overdispersed distribution of dicentrics observed after first-line radiotherapy; in contrast, when CT was given before radiotherapy, a lower dicentric frequency was scored, the distribution of dicentrics was not always found to be overdispersed and there was a time-dependent decrease in dicentrics after in vivo exposure.
Breast Neoplasms↗
Genotoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. II. Alteration of DNA repair and chromosome radiosensitivity.
Lymphocytes from 43 breast cancer patients were tested for their DNA-repair ability and in vitro chromosomal radiosensitivity. Lymphocytes were collected before and after treatment with radiotherapy or chemotherapy or both, and then irradiated in vitro. The aim was to detect alterations of these 2 indicators of radiosensitivity, in relation to cancer status or medical treatment. Patients before treatment were significantly deficient in DNA-repair ability but had a normal chromosomal radiosensitivity as compared to healthy donors. When assessed after treatment, DNA-repair ability and the frequency of in vitro-induced chromosome anomalies were modified according to the type of treatment. A reduced DNA-repair ability was observed for patients after radiotherapy but not after chemotherapy. In vitro-induced dicentrics and acentrics were not modified to the same extent according to the treatment. A decreased number of acentrics (the most frequently observed alteration) was preferentially associated with a more reduced DNA-repair ability. Interindividual differences of response to in vitro irradiation tested by both assays were observed between patients who had undergone similar treatments. The possibility that these assays could be used for predicting individual susceptibility to radiation or chemotherapy drug exposure is discussed.
Adult↗
Pharmacokinetics of quinolones in renal insufficiency.
The pharmacokinetics of the new fluoroquinolone derivatives have been extensively studied in patients with various degrees of chronic renal insufficiency during the last few years. Their kinetic profiles depend on the elimination pathways and on the degree of metabolic transformation. Renal insufficiency does not significantly modify pefloxacin kinetics. For the other new quinolones, a decrease in glomerular filtration rate below 20-30 ml/min induces an increase in terminal half-life and a decrease in plasma and renal clearance, related to the degree of renal impairment. These drugs are poorly removed by haemodialysis. Dosage adjustments are required, particularly in severe renal failure and for the drugs almost exclusively excreted, in unchanged form, via the renal route.
Anti-Infective Agents↗
Buspirone therapy in anxious elderly patients: a controlled clinical trial.
Forty patients over 65 years of age with anxiety symptoms due to an anxiety state (N = 20) or secondary to neurotic depression (N = 20) took part in a double-blind, placebo-controlled trial conducted in a primary care practice. All patients were receiving concomitant drug therapy for chronic medical conditions; 70% were receiving two or more nonpsychotropic drugs in addition to the study medication. Patients were randomly assigned to treatment with buspirone 5-30 mg/day or placebo for 4 weeks, with clinical evaluations made weekly. One buspirone-treated and two placebo-treated patients discontinued treatment after 2 weeks because of lack of efficacy. Buspirone treatment resulted in significantly greater (p less than or equal to 0.05) improvement on the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinical Global Impression assessment than did placebo. Mild adverse experiences were reported by five buspirone-treated and nine placebo-treated patients. Buspirone (mean dose, 18 mg/day) proved equally effective for elderly patients suffering anxiety states or neurotic depression at doses similar to those used in younger patients, and was well tolerated by elderly patients receiving treatment for other chronic medical conditions.
Aged↗
Lomefloxacin pharmacokinetics in subjects with normal and impaired renal function.
Lomefloxacin pharmacokinetics were investigated in 6 normal subjects and 24 uremic patients after a single oral dose of 400 mg. In subjects with normal renal function, the peak level in plasma averaged 3.5 +/- 0.9 micrograms/ml (mean +/- standard deviation) and was obtained at 1.3 +/- 0.9 h. The absorption rate constant was 3.8 +/- 1.6 h-1. The terminal half-life was 7.77 +/- 0.95 h. The apparent volume of distribution was 2.54 +/- 0.66 liters/kg. Total body and renal clearances were 259 +/- 83 and 200 +/- 55 ml/min per 1.73 m2, respectively. The percentage of the dose recovered unchanged in 48-h urine was 80.6 +/- 2.8. In uremic patients, the terminal half-life increased in relation to the degree of renal failure: from 8 h in normal subjects to 38 h in severely uremic patients (glomerular filtration rate, less than 10 ml/min). Renal insufficiency did not significantly modify the peak level in plasma, the time to peak, the apparent volume of distribution, or the nonrenal clearance of lomefloxacin. The dialysis clearance of lomefloxacin was 54 +/- 13 ml/min. Linear relationships were found between lomefloxacin pharmacokinetic parameters and glomerular filtration rate data. Dosage adjustments are necessary in uremic patients.
4-Quinolones↗
Disposition of fleroxacin, a new trifluoroquinolone, and its metabolites. Pharmacokinetics in renal failure and influence of haemodialysis.
The pharmacokinetics of fleroxacin and its metabolites following a single oral dose of fleroxacin 400mg were examined in 6 healthy subjects and 24 patients with various degrees of renal insufficiency. Plasma and urine samples, collected at various times after administration, were assayed by high performance liquid chromatography (HPLC). In healthy subjects, Cmax was 6.8 +/- 0.7 mg/L; tmax = about 1h, t1/2 = 14 +/- 2h, total clearance = 4.86 +/- 0.72 L/h and the percentage of unchanged fleroxacin excreted in urine in 48 hours was 48 +/- 4% (HPLC). Plasma concentrations of metabolites were very low and accounted for no more than 5% of the levels of unchanged fleroxacin. In uraemic patients Cmax did not change, whatever the degree of renal failure; tmax was increased in patients with a glomerular filtration rate below 0.6 L/h, and Vd/f was independent of the severity of renal failure. These data suggest that bioavailability of the drug is unchanged. In uraemic patients t1/2 was prolonged and AUC multiplied by a factor of 2 to 3. A linear relationship was found between total and renal clearances of fleroxacin and creatinine clearance. Accumulation of N-demethyl-fleroxacin and N-oxide-fleroxacin was very high in uraemic patients, due to slow formation of these metabolites and decreased urinary elimination. Dialysance of fleroxacin and of its metabolites was approximately 3.6 to 4.8 L/h. These findings suggest that fleroxacin dosage may need to be reduced in patients with severe renal disease; in haemodialysed patients, treated every 2 days, a single dose of fleroxacin 400mg is recommended at the end of each dialysis session.
Adult↗
Severe self-poisoning with oxetorone: report of one case.
The authors report a case of severe self-poisoning with oxetorone. Plasma concentration of the drug assessed by HPLC was a thousand times higher than therapeutic levels. Coma, convulsions, and cardiac conduction defects were observed, similar to those noted with tricyclic and tetracyclic antidepressant poisoning. Similar cardiac disorders consisting of conduction defects had not been previously described during oxetorone intoxication.
Adult↗
Characterization of two monoclonal antibodies to human apolipoprotein A-I that also bind to rabbit apolipoprotein A-I. Application to ELISA evaluation of rabbit serum apo A-I.
Two monoclonal antibodies against human apolipoprotein A-I were characterized to recognize rabbit apo A-I. By immunoblotting we determined that while neither antibody reacted with the other rabbit apolipoproteins they both recognized all rabbit apo A-I isoforms. Cotitration revealed that each antibody bound to different apo A-I epitopes. Then we developed a noncompetitive enzyme-linked immunosorbent assay (ELISA) to measure the concentration of total apolipoprotein A-I in rabbit serum. The ELISA curves of the different lipoprotein class and serum showed the similarity of the expression of the apo A-I epitopes recognized in each of them and in serum. This assay, as opposed to other techniques, offers several advantages such as sensitivity, specificity, and simplicity and avoids the use of radioisotope.
Animals↗
Expression, location and cross-reactivity of two antigenic sites on the amino terminal region of rabbit and human apolipoprotein A-I.
Rabbit apolipoprotein A-I (apo A-I) of molecular weight 27,612 contained 241 amino acids. In contrast to its human counterpart which has 3 methionine residues, the rabbit protein possesses only one and therefore produces 2 fragments after CNBr cleavage (CNBr I and II, NH2- and COOH-terminal, respectively). From a series of monoclonal antibodies raised against human apo A-I, 2 (A05 and A16) cross-reacted with rabbit apo A-I. In the present study, we show that A05 recognizes the rabbit CNBr I fragment while the integrity of the intermediate region between the 2 CNBr fragments (including the methionine residue) is required for the expression of the A16 antigenic determinant. Competition experiments were performed between human 125I-labelled high density lipoprotein (HDL) and a variety of preparations of human and rabbit apo A-I (including the purified and delipidated protein, complexes of dimyristoylphosphatidylcholine (DMPC) containing apo A-I, HDL subfractions and whole serum). The A05 antigenic determinant was expressed identically in all these fractions of both species. In contrast the A16 showed poor reactivity with delipidated apo A-I, the apparent affinity constant being about 100 times less than for HDL. These data suggest that phospholipids improve the recognition of apo A-I by the A16 antibody. The similar immunoreactivity of the human and rabbit proteins in the present study is consistent with the view that the NH2-terminal region contains the major portion activating lecithin:cholesterol acyltransferase.
Animals↗
[Postoperative peridural analgesia with clonidine].
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Clonidine↗