Biomedical subjects
Publications and source records attributed to G Humbert.
Temporal arteritis is one of the localisation of the giant cell arteritis. The involvement of the female genital tract had been rarely reported with only 16 cases in the literature. We report 3 cases revealed by a tumor of the genital tract. Histologic features are found in the vessels of ovaries, fallopian tubes and myometrium. Only one patient had symptoms suggestive of temporal arteritis.
This study investigates the morphological and molecular changes that occur in the inner hair cell area of the rat cochlea following aminoglycoside treatment. Rats were injected daily with 500 mg/kg of amikacin between postnatal day 9 (PND9) and PND16. Cochleae were examined at PND16 to PND120 using both scanning and transmission electron microscopy and molecular fluorescent labeling. The inner hair cells showed obvious signs of apoptosis in response to amikacin treatment and most of them were missing by one week after the end of the aminoglycoside exposure period. Concomitantly, the epithelium became scarred as the surrounding supporting cells expanded and filled the space vacated by the missing IHCs. The mid-basolateral region of these modified supporting cells was surrounded by many afferent and efferent terminals. However, these cells expressed neither calbindin nor SNAP25, proteins that are both expressed by IHCs in the normal, untreated organ of Corti in the rat. In addition, these supporting cells remained attached to the basal lamina by a thin cytoplasmic process. The supporting cells surrounding the inner hair cells therefore appear unable to convert directly into inner hair cells following aminoglycoside induced hair-cell loss but may be able to provide trophic support for the remaining afferent and efferent neurites.
The pharmacokinetics of a single intravenous dose of 30 mg of cefoxitin/kg given to normal subjects and to patients with various degrees of chronic renal insufficiency were studied. The serum half-life of cefoxitin was correlated inversely with the rate of creatinine clearance, and the half-life increased exponentially when the creatinine clearance rate fell below 30 ml/min per 1.73 m2. The elimination of cefoxitin into urine was rapid and extensive in patients whose creatinine clearance was greater than 30 ml/min per 1.73 m2. In patients with more severe degrees of renal impairment, renal clearance of drug was diminished markedly (less than 20% of the administered dose was excreted in 4 hr as compared with greater than 60% in the former group). The clearance of cefoxitin can be increased fivefold by hemodialysis in patients with end-stage renal disease.
A review of the world literature on the penetration (ratio of concentrations of cerebrospinal fluid to concentrations of serum) and attainable antibiotic concentrations in the cerebrospinal fluid in humans for cefuroxime, cefoxitin, cefotaxime, ceftizoxime, cefmenoxime, cefamandole, cefoperazone, moxalactam, ceftazidime, and ceftriaxone indicates that, with the exceptions of cefamandole and cefoperazone, all agents appear equivalent. We conclude that the choice of cephalosporin for the treatment of acute bacterial meningitis should depend mainly on the potency of the agent for the specific meningeal pathogens in question. For the treatment of common meningeal pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis) and for gram-negative bacilli, mainly Escherichia coli and Klebsiella (excluding Pseudomonas aeruginosa), the cefotaxime-ceftriaxone group of cephalosporins has accrued the most clinical experience and the most pharmacokinetic data, while for P. aeruginosa the major interest has centered on ceftazidime.
The pharmacokinetics of single doses (15 mg/kg) of cefotaxime and each of its metabolites were examined in six normal subjects and 24 patients who showed various degrees of renal insufficiency. An additional nine patients with renal failure were entered into a multiple-dose study in which cefotaxime (1 g) was given twice daily for five to seven days. After intravenous administration, the levels of cefotaxime in serum declined in two phases. The half-life for the terminal phase was 1.10 +/- 0.78 hr. Cefotaxime administered intramuscularly was well absorbed from the injection site (91% +/- 19%) and produced maximal levels of 25.5 +/- 3.5 microgram/ml in serum at approximately 0.5 hr after injection. The levels of the desacetyl metabolite in serum were comparatively low, and the half-life of this metabolite was 1.3 hr. Microbiologic measurements of cefotaxime showed that the half-life of the drug was lower in normal subjects (1.71 +/- 0.90 hr) than in patients with severe renal impairment (half-life, 10.20 +/- 3.43 hr). However, this difference was due primarily to desacetylcefotaxime. Specific measurement by high-performance liquid chromatography indicated only a slight increase in the half-life of cefotaxime, whereas the increase in half-life of desacetylcefotaxime was greater. The most pronounced increases in half-life of metabolites occurred when values for creatinine clearance in patients were below about 5 ml/min per 1.73 m2. When cefotaxime was administered repetitively, the ratio of maximal serum levels after the last dose to those after the first dose demonstrated minimal accumulation of intact drug. The average accumulation of desacetylcefotaxime in this group of patients was about twofold, and that for metabolites M2 and M3 was approximately fourfold. This accumulation of metabolites was observed only in those patients with severe renal impairment and was not excessive. Hemodialysis caused a significant reduction in the half-life of both cefotaxime and desacetylcefotaxime. Recommendations are made for the adjustment of dosing schedules in patients with renal failure.
Results of the treatment of gram-negative bacillary meningitis have been disappointing: mortality is extremely high, and treatment with chloramphenicol has shown a high failure rate. This failure rate for chloramphenicol is consistent with the wide gap between minimal inhibitory concentration and minimal bactericidal concentration of this drug for Escherichia coli, Klebsiella, and other Enterobacteriaceae. Cefotaxime, a new cephalosporin, is cidal for most gram-negative bacteria at concentrations of less than 0.25 microgram/ml. By late 1981, 137 patients with meningitis due to a variety of bacteria had been treated with this agent. Bacteriologic cure rates were 93% for meningitis due to Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae and 88% for meningitis due to gram-negative bacteria (94.4% for meningitis due to E. coli and Klebsiella). This new antibiotic shows considerable promise in the treatment of these forms of meningitis.
The elimination kinetics of aztreonam (SQ 26,776), a new, completely synthetic, monocyclic beta-lactam antibiotic, were studied after the administration of a single 1g intravenous dose. Five healthy volunteers and 20 patients with various degrees of renal insufficiency were enrolled in this study. Concentrations of aztreonam in serum and urine were determined by both microbiological and high pressure liquid chromatography (HPLC) assays. The pharmacokinetic parameters for aztreonam were calculated on the basis of a 2-compartment open model. Serum concentrations of aztreonam at 10 minutes after administration were approximately 100 micrograms/ml in all subjects, regardless of renal function (HPLC assay). The mean serum half-life during the alpha-phase showed no important variation with renal function. The mean serum half-life during the beta-phase was 1.8 hours in normal subjects and 8.4 hours in haemodialysis patients (HPLC assay). There was a linear correlation between the serum clearance of aztreonam and creatinine clearance. The mean cumulative urinary recovery of aztreonam in 48 hours was 60 to 70% of the administered dose in normal subjects but this was reduced in the presence of renal insufficiency. SQ 26,992, the microbiologically inactive metabolite of aztreonam resulting from hydrolytic opening of the beta-lactam ring, was undetectable in the serum of normal subjects but was found in low levels in uraemic patients. Half of a 1g intravenous dose of aztreonam was eliminated during 4 hours of haemodialysis. Guidelines for administration of aztreonam in the presence of renal failure are given.
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The authors report the retrospective study of 333 cases of pneumococcal infection recorded in in-patients at the Rouen CHU (University Hospital Centre) from january 1974 to december 1978. Pneumococcal infection involves mainly the lungs (210 cases) according to different features. Pleural involvement is found in 70 cases only. Extra-respiratory localizations are less frequently encountered; they are represented mainly by meningitis (43 cases). Prognosis depends more on diathesis factors such as age and associated pathology than on the site of infection (cases with isolated respiratory involvement being usually less severe). The authors insist on the necessity of prevention especially by vaccination, of which indication is discussed.
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