Cefamandole pharmacokinetics and dosage adjustments in relation to renal function.

The pharmacokinetic characteristics of cefamandole were determined after intravenous administration of a 1-Gm dose to 10 subjects with normal renal function, 10 patients with stabilized renal failure, and five chronic nephritic patients included in a intermittent hemodialysis program. In normal subjects, biological half-life (t1/2) averaged 0.94 hour, the overall elimination rate constant (Ke) was 0.7378 (hr-1), total clearance (Ct) was 223 ml/min/1.73 m2, renal clearance (Cr) was 164 ml/min/1.73 m2, and urine recovery of cefamandole over the 6 hours following a dose amounted to 74 per cent of the administered dose. In patients with stabilized renal failure and in patients on hemodialysis, biological half-life was markedly increased, with a theoretical value of 10.4 hours in case of a creatinine clearance of zero. The amount of antibiotic extracted over a 6-hour dialysis period accounted for 29 per cent of the cefamandole present in the vascular compartment at the beginning of the dialysis procedure. A significant correlation was established between the values of Ke and creatinine clearances, Ccr: Ke = 0.0289 + 0.0063Ccr (r = 0.937). This relationship was used to calculate the loading dose (LD), maintenance doses (D), and dosage intervals (tau) with regard to renal function. From these data recommendations regarding the adjustment of cefamandole dosage to the renal status can be made.

[Sleep disorders and use of psychotropic drugs in 6-year-old children]. / Troubles du sommeil et consommation de médicaments psychotropes chez l'enfant de six ans.

The purpose of this prospective survey, conducted over a two years period, was to study the use of psychoactive drugs among six year-old children in the Bas-Rhin administrative "département", of eastern France. The factors analysed were family environment, after-school time, the child's sleep, the locality where the child lived and the drugs used. The child was examined by school doctors, in the presence of the parents, at the compulsory consultation at the start of first-year infant school. The study was exhaustive. Of the 11,274 children examined, 12.1% used a psychoactive drug, although only 1% were considered by their parents to be suffering from insomnia. Of the children using drugs, 32% had used them for more than a year, 24% for more than two years and 11% for more than three years. Consumption was also shown to vary greatly between different localities; in some areas the proportion of children using drugs was more than 50%.

[Implication of emergency departments in the regulation of public hospitalizations]. / Place des services d'urgences dans la régulation des hospitalisations publiques.

PURPOSE: Emergency departments become a useful way to access to hospital care. Since these last years difficulties of hospitalization, mainly of the elderly, after visit to the emergency department, are on the increase. CURRENT KNOWLEDGE AND KEY POINTS: Emergency departments are an important mode of recruitment for hospital units, 4 patients to 10 are hospitalized from emergency departments. The difficulties of hospitalization starting at the emergency department are more important for the elderly. Actually, there are 2 type of hospital care, planed and non planed care. The development of observation units specific to the emergency departments allowed to resolve some of these difficulties. But they are limited by their small number of beds and the duration of hospitalization below to 36 h. Some hospitals developed polyvalent emergency short stay unit to hospitalize patients who visited emergency department without necessity to give them a specialized care. FUTURE PROSPECTS AND PROJECTS: This situation must allow us to purpose a better regulation of hospitalizations which includes emergency departments in a network system including the different hospital ways of taking care. A downstream way of care adapted to the emergency hospitalizations would be developed. This could include the emergency department, the observation unit and the emergency short stay unit in interface with internal medicine and general medicine units, geriatric unit and specialized units, all of them will be included in a town-hospital care network.

[Slowly reversible central scotoma: iatrogenic effect of hyperbaric oxygenation in the treatment of multiple sclerosis]. / Le scotome central lentement réversible: un effet iatrogène de l'oxygénothérapie hyperbare dans le traitement de la sclérose en plaques.

Considerable enthusiasm has been raised in the past about the use of Hyperbaric Oxygen (HBO) in various diseases, usually otherwise untreatable. Recently, special attention has been drawn on its hypothetical beneficial effects on multiple sclerosis (MS). We have witnessed a rare, though known, side-effect of HBO on a patient suffering from MS. She developed an acute, bilateral, centro-caecal scotoma, from which she slowly recovered several days after. The forementioned case led us to a review of the literature concerning: Various attempts to employ HBO in ophthalmology Side-effects of oxygen on eye and vision Possible mechanisms of ocular toxicity of oxygen. It appears from this review that we should be extremely cautious about using HBO on MS patients, particularly able to develop such side-effects.

[Substitution therapy of drug addicts]. / Les traitements de substitution chez le toxicomane.

ANALYZING PROPOSED TREATMENTS: The large body of literature on substitution treatments for drug abusers describes a variety of social settings and an extremely heterogeneous set of protocols. Establishing correlations between protocols and practical applications is thus a difficult task. METHADONE: The most widely studied substance is methadone. With methadone treatment, there is a decline in the amount of heroin used and in the number of injections. But there is no response with other drugs, leading to a real risk of increasing cocaine abuse. Methadone is used as a tool to decrease the risk of HIV although its impact is difficult to quantify. The most significant effect of methadone treatment is the social effect with a decrease in delinquency and in the number of drug-abuse related incarcerations. The consequences in terms of employment are less clear and vary depending on the social setting. The therapeutic window is very narrow with methadone and results are highly dependent on practical applications. A multidisciplinary and individualized approach is required. BUPHRENORPHINE: There has been less work on buphrenorphine. Like methadone, there is a dose/efficacy relationship. The results of comparative studies between the two agents are quite similar with a possible advantage for buphrenorphine because of the wider prescription spectrum and the possibility of longer intervals between administrations. EXTRAPOLATING MODELS: The implications of applying models developed in other countries to the social context in France still have to be analyzed on a scientific basis. New trial methodologies are needed to evaluate the social and psychological impact of individualized management.

[Immunoallergic intravascular hemolysis and tubulointerstitial nephritis due to penicillin G]. / Hémolyse intravasculaire et néphrite tubulo-interstitielle immunoallergiques dues à la pénicilline G.

A 51-year old woman treated with high doses of penicillin G developed acute intravascular haemolysis and tubulointerstitial nephritis. Immunological investigations showed circulating immune complexes, decreased C3 and C4 components of complement, IgG deposits in the renal interstitium, positive direct Coombs test with anti-IgG sera and complement and circulating anti-penicillin antibodies demonstrated by indirect antiglobulin tests and IgG RAST. Plasma haemoglobin and anti-penicillin antibodies could be removed by an early exsanguino-transfusion. These findings suggest that the nephritis was due to immune complexes and the haemolysis, to a combined hapten-type and immune complex mechanism.

[Duodenal perforations by the hooks of a Kimray-Greenfield filter]. / Perforation duodénale par les crochets d'un filtre de Kimray-Greenfield.

A case is reported of a duodenal perforation by a Kimray-Greenfield filter hook in a 66-year-old female patient. This device had been inserted four years before, after a pulmonary embolism. The patient presented with epigastric pain, vomiting and extracellular dehydration with renal failure. A plain abdominal film showed the filter to be tilted 15 degrees to the left, with an opening 28 mm wide. Various investigations were carried out, none of which providing a satisfactory diagnosis. Steroid treatment (1 mg.kg-1 x day-1 of prednisone) was started before admission to intensive care. Only at that time gastroduodenoscopy showed on of the filter's hooks jutting through the duodenal wall. This perforation was located in the posterior wall of the third part of the duodenum, and was associated with an ulcer of the mucosa facing this hook. The diagnosis was confirmed by an abdominal CT scan. The hook was cut and the perforation sealed off during a first laparotomy. Twenty-six days later, the patient developed intestinal obstruction due to a haematoma of the jejunal wall. She later had a cerebrovascular accident, with status epilepticus and deep coma. She died four months after her admission. The late complications of vena caval filters are discussed. The position of these devices should be regularly checked by a plain abdominal film. Abdominal CT scanning is a useful investigation for the diagnosis of intra and extravascular complications.

[Acute poisoning during substitution therapy based on high-dosage buprenorphine. 29 clinical cases--20 fatal cases]. / Intoxications aiguës par traitement substitutif à base de buprénorphine haut dosage. 29 observations cliniques--20 cas mortels.

OBJECTIVES: Buprenorphine has been an important advance in care for drug abusers, but the toxic risk may be fatal. We report here two original series of buprenorphine poisoning in opiate abusers on substitution therapy. PATIENTS: The first series included 20 males and 9 females, aged 20-35 years (mean = 27.5) with non-fatal poisoning. The second series included 20 subjects (19 males, 1 female) aged 14-48 years (mean = 26.6) with a fatal outcome. All subjects were opiate addicts taking high-dosage sublingual buprenorphine formulation as substitution therapy. RESULTS: Blood concentrations of buprenorphine were found in all cases to remain at a low level (1.0-2.3 ng/ml, m = 1.4 ng/ml, and 1.1-29.0 ng/ml, m = 8.4 ng/ml in non-fatal and fatal cases respectively). Almost all cases involved concomitant intake of psychotropic medications, especially benzodiazepines (18 non-fatal and 17 fatal cases). DISCUSSION: These observations confirm previously reported data on the danger of buprenorphine-benzodiazepine combinations. Intravenous injection of crushed tablets also appears to be a risk factor (8 deaths and 10 non-fatal poisonings). This series highlights the need for improvement in the recently developed French program for substitution therapy with high-dosage buprenorphine in heroin addicts.

[Experimental and clinical study of the biliary elimination of mezlocillin (author's transl)]. / Détermination expérimentale et étude clinique de l'élimination bilaire de la mezlocilline.

The biliary elimination of mezlocillin was studied in 5 perfused rabbit liver preparations. After adding 10 mg of mezlocillin to the perfusion medium, the biliary peak averaged 758 +/- 129 microgram/ml and total mezlocillin recovery within 3hr amounted to 20.3% of the administered dose. In 5 healthy subjects, the mean levels in the duodenal fluid collected during the 4 hrs following an infusion of 5 g of mezlocillin ranged from 440 to 637 microgram/ml. In cholecystectomized patients provided with a T-tube drainage, the maximal concentration after the same dosage (n = 10) was 505 +/- 158 microgram/ml and cumulative biliary excretion of mezlocillin over a 12 hr period corresponded to 1.3% of the administered dose. Under the same conditions, after intra-muscular injection of 1 g of mezlocillin to 10 subjects, the biliary peak averaged 292 +/- 58 microgram/ml and the total biliary recovery 2.6% of the administered dose. In 10 patients undergoing biliary tract surgery, the levels determined 1 hr after IV injection of 2 g of mezlocillin reached 896 +/- 196 microgram/ml and 402 +/- 133 microgram/ml in the main duct and in the gallbladder bile, respectively. These results were compared with the values obtained under identical conditions with 12 other beta-lactam antibiotics.

[Toxicity of calcium inhibitors]. / Toxicité des inhibiteurs calciques.

Calcium antagonists decrease the intracellular concentration of calcium ions. They act essentially on the smooth vascular muscle, on the cardiac muscle and on the automatic and conducting cells in the heart. At toxic doses these effects induce hypotension, shock and disturbances of sinusal automatism and atrio-ventricular conduction. The toxicity of the different calcium antagonists varies according to their tissue specificity. The treatment of overdose includes gastric lavage, oral activated charcoal, cardiorespiratory support, especially alphamimetic vasopressors for shock or hypotension, adrenaline or cardiac pacing for atrio-ventricular block.

Toxicokinetics of lithium intoxication treated by hemodialysis.

A 66-year old female on long-term lithium therapy, developed neurologic toxicity with coma and convulsions. The treatment consisted artificial ventilation, fluid and electrolyte infusions and a six hour hemodialysis (HD) on days 2, 3 and 4. The convulsions disappeared on day 4; the patient regained consciousness on day l2 and recovered with slight sequelae. Toxicokinetic studies were conducted for a period of 12 days. The lithium (Li) serum concentration fell from 4.4 mmol/l on admission to 2.16 before HD and 0.35 after three HD. Li serum half life was 54 hours before HD, 25 hours during the three days on which HD was carried out and 106 hours thereafter. The Li cerebrospinal fluid/Li serum ratio ranged between 0.4 and 0.6 and was not influenced by HD. Mean renal clearance was 10.6 ml per min. During hemodialysis, Li serum half life decreased to 3.5 - 4.9 hours and clearance was 108 ml/min. A total amount of l28.6 mmol lithium was excreted; 84.3 mmol by HD and 44.3 mmol in urine. Patient's clinical course and electroencephalographic signs were correlated with the calculated cellular pool of Li but not with Li serum concentrations. This study confirms the effectiveness of HD to decrease the cellular pool of lithium. However, rather than considering only the absolute Li serum concentration, the presence of a rebound peak after HD may be viewed as indication for further hemodialysis.