Argon blocks the expression of locomotor sensitization to amphetamine through antagonism at the vesicular monoamine transporter-2 and mu-opioid receptor in the nucleus accumbens

We investigated the effects of the noble gas argon on the expression of locomotor sensitization to amphetamine and amphetamine-induced changes in dopamine release and mu-opioid neurotransmission in the nucleus accumbens. We found (1) argon blocked the increase in carrier-mediated dopamine release induced by amphetamine in brain slices, but, in contrast, potentiated the decrease in KCl-evoked dopamine release induced by amphetamine, thereby suggesting that argon inhibited the vesicular monoamine transporter-2; (2) argon blocked the expression of locomotor and mu-opioid neurotransmission sensitization induced by repeated amphetamine administration in a short-term model of sensitization in rats; (3) argon decreased the maximal number of binding sites and increased the dissociation constant of mu-receptors in membrane preparations, thereby indicating that argon is a mu-receptor antagonist; (4) argon blocked the expression of locomotor sensitization and context-dependent locomotor activity induced by repeated administration of amphetamine in a long-term model of sensitization. Taken together, these data indicate that argon could be of potential interest for treating drug addiction and dependence.     

Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis.

Although surgical lung resection could improve prognosis in some patients with multidrug-resistant tuberculosis (MDR-TB), there are no reports on the optimal candidates for this surgery. The aim of the present study was to elucidate the prognostic factors for surgery in patients with MDR-TB. Patients who underwent lung resection for the treatment of MDR-TB between March 1993 and December 2004 were included in the present study. Treatment failure was defined as greater than or equal to two of the five cultures recorded in the final 12 months of treatment being positive, any one of the final three cultures being positive, or the patient having died during treatment. The variables that affected treatment outcomes were identified through univariate and multivariate logistic regression analysis. In total, 79 patients with MDR-TB were included in the present study. The treatment outcomes of 22 (27.8%) patients were classified as failure. A body mass index <18.5 kg x m(-2), primary resistance, resistance to ofloxacin and the presence of a cavitary lesion beyond the range of the surgical resection were associated with treatment failure. Low body mass index, primary resistance, resistance to ofloxacin and cavitary lesions beyond the range of resection are possible poor prognostic factors for surgical lung resection in multidrug-resistant tuberculosis patients.     

Brachytherapy in France in 2002: results of the ESTRO-PCBE questionnaire]

The authors report the results of the Patterns of Care for Brachytherapy in Europe (PCBE) throughout France. Responses were obtained for 91% of the Radiation Oncology departments, which have declared using brachytherapy for 67, and gave detailed data for 49 ones. The equipments and treated tumours were recorded. LDR brachytherapy remained the most often used (53.5%), followed by HDR (28%). PDR represented 5.5% and permanent implants 11%. The authors discuss the development of new equipment, with an aggregation of the structures, and an increase of the PDR and prostate implants use.     

What is the place of electroneuromyographic studies in the diagnosis and management of pudendal neuralgia related to entrapment syndrome?

Entrapment of the pudendal nerve may be at the origin of chronic perineal pain. This syndrome must be diagnosed because this can result in the indication of surgical decompression of the entrapped nerve for pain relief. Electroneuromyographic (ENMG) investigation is often performed in this context, based on needle electromyography and the study of sacral reflex and pudendal nerve motor latencies. The limits of ENMG investigation, owing to various pathophysiological and technical considerations, should be known. The employed techniques do not assess directly the pathophysiological mechanisms of pain but rather correlate to structural alterations of the pudendal nerve (demyelination or axonal loss). In addition, only direct or reflex motor innervation is investigated, whereas sensory nerve conduction studies should be more sensitive to detect nerve compression. Finally, ENMG cannot differentiate entrapment from other causes of pudendal nerve lesion (stretch induced by surgical procedures, obstetrical damage, chronic constipation...). Thus, perineal ENMG has a limited sensitivity and specificity in the diagnosis of pudendal nerve entrapment syndrome and does not give direct information about pain mechanisms. Pudendal neuralgia related to nerve entrapment is mainly suspected on specific clinical features and perineal ENMG examination provides additional, but no definitive clues, for the diagnosis or the localization of the site of compression. In fact, the main value of ENMG is to assess objectively pudendal motor innervation when a surgical decompression is considered. Perineal ENMG might predict the outcome of surgery but is of no value for intraoperative monitoring.     

Effects of Carbetimer, a new antineoplastic drug, on bone metabolism

Carbetimer is a new antineoplastic agent whose main side effects consist of neurotoxicity and long-term dose-dependent hypercalcemia. We previously showed that Carbetimer is a potent calcium chelator responsible for an acute decrease in ionized Ca levels observed in vivo. However, the mechanism of the progressive increase in serum Ca remains unknown. We have evaluated the bone-resorbing effects of Carbetimer on 45Ca-prelabelled neonatal mouse calvariae. Carbetimer induced a dose-dependent increase in 45Ca release which started at a concentration of 1 mg/ml and reached a mean of 3.3 times the control values at 10 mg/ml. This marked increase in 45Ca release was similar on previously killed bones and could not be inhibited by calcitonin. Such concentrations are probably therapeutically relevant given the known affinity of Carbetimer for bone and the large daily doses administered to cancer patients (10-15 g). Since Carbetimer could exert its antineoplastic action through immunomodulation, we also studied its effects on the production of TNF-alpha and IFN-gamma which are also known to affect bone metabolism. Carbetimer did not stimulate TNF-alpha release from isolated normal human monocytes or lymphocytes, but it markedly inhibited T-lymphocyte production of IFN-gamma, which became undetectable at a concentration of 1 mg of Carbetimer/ml. In summary, Carbetimer-induced hypercalcemia appears to be due to a direct stimulation of osteolysis, but possibly also to an inhibition of IFN-gamma production.     

Septicemias in cancer patients during parenteral nutrition: contributing factors and detection by weekly blood cultures

Infections constitute the main complication of parenteral nutrition, particularly in cancer patients, but prediction of catheter-related septicemias (CRS) has been little investigated. We have evaluated, in 200 consecutive episodes of parenteral nutrition (PN) in cancer patients, the factors contributing to infectious complications, and the predictive value of weekly blood cultures performed through the nutrition catheter. The median duration of PN was 22 days with a total of 5816 patient-days of PN, neutropenia (neutrophils < 1,000/mul) being present in 872 (15%). Catheters were placed either in a jugular vein (71% single-lumen silicone catheters, 18.5% double-lumen Hickman-Broviac catheters) or in a femoral vein (10.5%). We observed 62 episodes of septicemia of which 22 were CRS (11% incidence for the 200 cycles) and 40 were non-CRS (20% incidence); CRS were mostly due to Staphylococcus epidermidis (14 22 ). Neutropenic patients as a group did not suffer more CRS than non-neutropenic patients, but the risk of CRS was slightly increased when expressed per day of neutropenia (8 CRS/872 days vs 14 CRS/4942 days without neutropenia, P < 0.05). On the other hand, a femoral insertion site was associated with a much higher incidence of CRS (9 CRS/21 femoral catheters vs 13 CRS/179 jugular catheters, P < 0.0001). It was possible to evaluate 20 episodes of CRS for their predictability by weekly blood cultures: the sensitivity for detecting CRS due to Staphylococcus epidermidis was 67%, the specificity 92%, the negative predictive value 98% and the positive predictive value 36%. The simple and widely available procedure of routine surveillance blood cultures performed through the PN catheter should be further investigated, because it could help the clinician to determine the origin of recent fever, particularly to exclude CRS and avoid unnecessary removal of PN catheters.