Selenium diet-supplementation improves cocaine-induced myocardial oxidative stress and prevents cardiac dysfunction in rats

Chronic cocaine abuse causes cardiac dysfunction and induces oxidative stress. The goal of this study was to evaluate whether an enhanced antioxidant pool, induced by the administration of selenium, may prevent the myocardial dysfunction induced by cocaine. Cocaine was administered for 7 days (15 mg/kg/day, i.p.) to rats pretreated for 4 weeks with selenium (1.16 mg/L/day, p.o.). Cardiac function was evaluated by cardiac index and left ventricular (LV) fractional shortening (FS) measured by echocardiography. The redox ratio and enzymatic activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured in the LV myocardium. Cocaine administration induced a cardiac dysfunction, as evidenced by a decrease in cardiac index and LV FS as well as by an increase in LV diameters. Moreover, antioxidant markers and redox ratio were altered in rats after cocaine exposure. Selenite supplementation induced a significant limitation of cardiac index and FS alterations observed after cocaine administration. This improvement in cardiac function was associated with a redox ratio recovery while SOD and GPX activities remained unchanged. Thus, selenite reversed both the oxidative stress and the contractile dysfunction induced by cocaine administration. These results suggest a major role of oxidative stress in the cocaine-induced cardiotoxicity.     

Detecting life-threatening lactic acidosis related to nucleoside-analog treatment of human immunodeficiency virus-infected patients,and treatment with L-carnitine

OBJECTIVE: Our first objective was to determine a blood lactate threshold predictive of survival in human immunodeficiency virus patients experiencing lactic acidosis related to nucleoside analogs, and second, to test l-carnitine for the treatment of patients exceeding that threshold. DESIGN: a) Retrospective study using data from personal and published observations to determine the lactate threshold between survivors and nonsurvivors in human immunodeficiency virus patients being treated with nucleoside analogs. b) Prospective multicenter open trial to test l-carnitine treatment of human immunodeficiency virus patients receiving nucleoside analogs. SETTING: Medical intensive care units of four teaching hospitals and one general hospital. PATIENTS: Retrospective analysis of data from 39 human immunodeficiency virus patients (five personal cases and 34 patients from the literature) receiving nucleoside-analog treatment from which lactate values were available. An additional six patients with high lactate values were included as a pilot study testing the use of l-carnitine therapy. MEASUREMENTS AND MAIN RESULTS: An initial lactate level of 9 mmol/L, which gave good positive and negative predictive values, was determined as a threshold between survivors and nonsurvivors for the patients receiving nucleoside-analog treatment. Six patients with initial lactate levels >10 mmol/L were prospectively treated with l-carnitine; three survived beyond the end of the study. CONCLUSIONS: The blood lactate levels in human immunodeficiency virus patients receiving nucleoside-analog therapy can predict mortality in these patients. The preliminary data from this pilot study suggest that l-carnitine may be helpful for patients who have nucleoside-analog-related lactic acidosis with blood lactate levels >10 mmol/L. Further studies will be necessary to affirm the therapeutic efficacy of l-carnitine in this setting.     

Limitations of current Parkinson's disease therapy

Levodopa and other dopaminergic medications drastically improve the motor symptoms and quality of life of patients with Parkinson's disease in the early stages of the disease. However, once the "honeymoon" period has waned, usually after a few years of dopaminergic therapy, patients become progressively more disabled despite an ever more complex combination of available antiparkinsonian treatments. Sooner or later, they suffer from "dopa-resistant" motor symptoms (speech impairment, abnormal posture, gait and balance problems), "dopa-resistant" nonmotor signs (autonomic dysfunction, mood and cognitive impairment, sleep problems, pain) and/or drug-related side effects (especially psychosis, motor fluctuations, and dyskinesias). Therefore, the current antiparkinsonian therapy cannot be considered as ideal with regard to both efficacy and safety.     

Phonological short-term memory networks following recovery from Landau and Kleffner syndrome

Landau-Kleffner syndrome (LKS) is a rare acquired aphasia occurring in otherwise healthy children, together with spike-wave discharges predominating over superior temporal regions and activated by sleep. Although the outcome of language abilities is variable, a residual impairment in verbal short-term memory (STM) is frequent. This STM deficit might be related to the persistent dysfunction of those temporal lobe regions where epileptic discharges were observed during the active phase of the disorder. We tested this hypothesis by measuring brain activation during immediate serial recall of lists of 4 words, compared to single word repetition, using H(2) (15)O positron emission tomography (PET), in 3 LKS patients after recovery and in 14 healthy controls. The patients (TG, JPH, and DC) had shown abnormally increased or decreased glucose metabolism in left or right superior temporal gyrus (STG) at different stages during the active phase of their disease. At the time of this study, the patients were 6-10 years from the active phase of LKS. Results showed that Patients JPH and DC had impaired performance in the STM condition, whereas TG showed near normal performance. PET data showed that JPH and DC activated significantly less than controls left and right posterior STG. TG, having near normal STM performance, showed increased activity in the posterior part of the right STG. These data suggest that impaired verbal STM at late outcome of LKS might indeed be related to a persistent decrease of activity in those posterior superior temporal gyri that were involved in the epileptic focus during the active phase.     

Pharmacokinetic interaction between high-dose methotrexate and oxacillin

An 18-year-old man received two high-dose methotrexate cycles for the treatment of an osteosarcoma. Fifteen grams of methotrexate were infused over 6 hours. During the second cycle, co-administration of oxacillin (1g/8h) resulted in prolonged and marked elevation of methotrexate plasma concentrations. The patient experienced acute toxicity with renal failure, myelosuppression, mucitis, fever, and dermatologic abnormalities. After an initial improvement with folinic acid rescue and hemodialysis, the patient died. Oxacillin may thus inhibit the elimination of methotrexate.     

Conservative management of malignant and borderline ovarian tumor

Conservative management of at least a part of one ovary and the uterus, in order to preserve fertility-potential, could be propose in most of patients with nonepithelial and borderline ovarian tumor. This conservative management could be performed even in patients with borderline ovarian tumor associated with noninvasive peritoneal implants (if complete resection of peritoneal disease). A removal of the preserved ovary after completion of the pregnancy(ies) is not necessary if patients agree to a careful follow-up procedure. In patient with epithelial ovarian cancer, conservative management could be performed only in case of young patients who desire to preserve fertility function with: unilateral tumor (stage IA), grade 1 (and 2?), who underwent an adequate staging surgery (including peritoneal washings, omentectomy, multiple peritoneal biopsies, uterine curettage and complete pelvic and paraaortic lymphadenectomy) and with a careful follow-up. A conservative management should not be performed in patients with tumor stage > IA and/or grade 3. Removal of preserved ovary should be performed after completion of pregnancy(ies) in order to reduce the risk of ovarian recurrence.     

Ion channel variation causes epilepsies

The discovery of genetically transmissible form of epilepsy associated with a mutation in a gene that codes for a subunit of a ligand-gated channel shined a new light in this field of neurological diseases. Because this gene (CHRNA4) codes for a neuronal nicotinic acetylcholine receptor subunit, functional studies could be designed to evaluate the alterations caused by this mutation. Since this initial observation, five mutations were identified and determination of their functional properties initiated. These experiments were extended to pairwise expression of the control and mutated allele to mimic the heterozygote human genotype. The first common functional trait identified so far, in four of these mutants, is an increased sensitivity to the acetylcholine, suggesting that these mutations may cause a gain of function. An alternative possibility that cannot be excluded is that conditions in the brain are such that these higher responding receptors may be more prone to desensitization. The importance of ionic channels as cause of epilepsies was further demonstrated with the identification of the association between the benign neonatal epilepsy and mutations in genes coding for potassium channel subunits (KCNQ2, KCNQ3). Additional evidences were brought by the identification of mutations in voltage-dependent sodium channels (SCN1A, SCN1B) in a form of generalized epilepsy with febrile seizures.     

Laparoscopic appendectomy: indications and controversies

The introduction of laparoscopic appendectomy has been more controversial than that of laparoscopic cholecystectomy. Randomized trials have been performed, as well as meta-analysis, with equivocal results regarding effectiveness. The further expansion of the technique for interval appendectomy and in cases of complicated appendicitis has introduced new controversies and success stories. We hope to review the current application of laparoscopic appendectomy in adults based on the available literature and discuss some current controversies.