Treatment of acute decompensation of maple syrup urine disease in adult patients with a new parenteral amino-acid mixture.

BACKGROUND: Acute decompensation of maple syrup urine disease (MSUD) is usually treated by enteral feeding with an amino-acid mixture without leucine (Leu), valine or isoleucine. However, its administration is ineffective in cases of gastric intolerance and some adult patients refuse enteral feeding via a nasogastric tube. We developed a new parenteral amino-acid mixture for patients with MSUD. METHODS: Seventeen decompensation episodes in four adult patients with MSUD treated with a parenteral amino-acid mixture (group P) were compared to 18 previous episodes in the same patients treated by enteral feeding (group E). RESULTS: The mean Leu concentration at presentation was similar in the groups P and E (1196.9 µmol/L and 1212.2 µmol/L, respectively). The mean decrease in the Leu concentration during the first 3 days of hospitalisation was significantly higher in group P than group E (p = 0.0026); there were no side effects. The mean duration of hospitalisation was similar (4 vs. 4.5 days, p = NS). No patient in group P deteriorated whereas one patient in group E required dialysis. CONCLUSION: This new parenteral amino-acid mixture is safe and allows efficient Leu concentration decrease during acute MSUD decompensation episodes in adults. Its use avoids the need for nasogastric tube insertion.

[Review of cases of prolonged QTC and wave burst arrhythmia in patients treated with methadone]. / Revue des cas d'allongements du QTC et de torsades de pointe chez des patients traités par méthadone.

INTRODUCTION: For the past 40 years, methadone has been known to be an efficient treatment of substitution. Its use allowed a significant reduction in the mortality related to opioid addiction. Since 2001, many articles have reported some cases of syncope, wave burst arrhythmia, ventricular tachycardia due to prolonged QT interval and sudden death secondary to cardiac arrest, with a risk of prolongation of the QT interval above 440 ms (men) and 460 ms (women). Many explorations have helped in understanding the physiopathology by showing that opioids, including methadone, cause a blockage of the potassium channels of the gene HERG K+P. This event could slow the repolarisation and the atrioventricular cardiac synchronization and could induce ventricular arrhythmia. LITERATURE FINDINGS: Nearly 20 studies showed a prolonged QT interval secondary to methadone in patients exhibiting the following features: (1) patients with cardiac pathologies, notably bradycardia, congenital long QT interval, myocardial pathologies related to AIDS and electrolyte disturbances; (2) patients receiving concomitant treatment with substances known to prolong QT interval, such as psychoactive stimulants, narcoleptics, tricyclic antidepressants, antiarrhythmic agents, macrolids, quinolones, non diuretic hypokalemiants and certain corticoids; (3) patients receiving treatments that inhibit methadone's metabolism, particularly those that act on the cytochrome P450 3A4 such as SSRI, antifungal agents, some macrolids and some retroviral agents. Many recent studies, while evaluating the dose-dependent effect of methadone on the QT prolongation, showed a tendency to a prolonged QT when using higher doses of methadone. CONCLUSION: Screening for these risk factors should be carried out before prescribing methadone. EKG should not be systematically performed unless the conditions described above are present or if a higher dose of methadone is needed.

Perioperative infusions in paediatric patients: rationale for using Ringer-lactate solution with low dextrose concentration.

To assess the usefulness of Ringer-lactate solution with 0.9% dextrose, fluid therapy during surgery in paediatric patients was reviewed. From the literature, the need for intravenous (i.v.) infusion and water could be established. The need for sodium was also evident and use of normonatraemic i.v. solutions should be recommended to avoid hyponatraemia. Little data were found about the value of the other electrolytes. Dextrose requirements have been the subject of debate for the last two decades. The choice of dextrose concentration is a compromise between avoiding hypoglycaemia and hyperglycaemia. Four clinical trials assessing the use of Ringer-lactate solution with 0.9 or 1% dextrose in paediatric patients suggest that it is appropriate for routine infusion in paediatric patients during the perioperative period. However, fluid therapy during surgery has rarely been studied, probably because it is inexpensive, rarely leads to problems and is used in very different clinical settings. Development of consensus clinical guidelines on the use of electrolyte infusions in paediatric surgery would be helpful.

The role of chemical, physical, or viral exposures and health factors in neurocarcinogenesis: implications for epidemiologic studies of brain tumors.

This review highlights some future prospects and implications for epidemiologic research on the etiology of nervous system tumors. It reviews some points regarding physiology of the nervous system, in connection with mechanisms of neurocarcinogenesis, and experimental studies in animals. The results of epidemiologic studies are summarized in the light of the biological and experimental observations. The following aspects are particularly emphasized: (i) higher susceptibility of the developing nervous system to neurocarcinogenic agents (in the fetus and after birth); (ii) possible implications of knowledge about mechanisms of neurocarcinogenesis regarding crossing of the blood-brain barrier, activation of oncogenes and inactivation of anti-oncogenes, relationship between chemical structure and neurocarcinogenic action; (iii) necessity of further investigation concerning the occurrence of nitrosoureas and their precursors in the environment, and the potential role of nitroso compounds in the development of human brain tumors; (iv) lack of information about promoting or inhibiting neurocarcinogenic effects, and co-carcinogenesis--among others, interaction between X-irradiation and exposure to neurocarcinogenic nitrosoureas; (v) need for studying the potential neurocarcinogenic risk of polyomaviruses BKV, JCV, and SV40 to humans.

Occupational paternal exposure to benzene and risk of spontaneous abortion.

OBJECTIVE: The purpose of this study was to evaluate the risk of spontaneous abortion among the wives of male workers occupationally exposed to benzene. METHODS: The wives of 823 men working in two chemical plants at the time of the study were asked to complete a questionnaire describing their pregnancies. The analysis of the 1739 pregnancies that ended in a spontaneous abortion or a birth is presented. The firms' payroll records provided all workers' employment history, including dates. Benzene exposure, graded at two levels (< 5, > or = 5 ppm), was determined for every job, so that benzene exposure for each worker's entire professional life (at these companies) could be assessed. This information was linked to the dates of the pregnancies reported in the questionnaires to enable the exposure status of each pregnancy to be defined (1270 non-exposed and 274 exposed). The frequency of spontaneous abortion, defined as the number of spontaneous abortions divided by the total of spontaneous abortions and births was evaluated. RESULTS: When adjusted for tobacco consumption, mother's age and pregnancy order, the odds ratio of the association between paternal exposure to approximately 5 ppm of benzene and the risk of spontaneous abortion was close to and statistically not different from unity (OR = 1.1; 95% CI (0.7-1.8). CONCLUSION: In this study paternal exposure to benzene did not increase the risk of spontaneous abortion.

[Study of the association of bladder cancer and phenacetin use. Problems set by a pharmaco-epidemiological study]. / Etude de l'association entre le cancer de la vessie et la consommation de phénacétine. Problèmes posés par une étude de pharmacoépidémiologie.

In a survey of the literature, phenacetin appears to be responsible for an increased risk of urothelial tumours in humans, especially renal pelvis tumour. Few observations have suggested an association between bladder cancer and phenacetin containing analgesics however. To assess this association in France, a case-control study of bladder cancer (143 cases, 120 controls) was undertaken. We point at some methodological difficulties, such as difficulties of recall, definition of a control group, non-responses, possible French distinctive features of analgesics use. Results are not able to confirm the suspected relationship between bladder cancer and phenacetin use.