Can parturients distinguish between intravenous and epidural fentanyl?

We tested the hypothesis that the sedative, euphoric, and analgesic effects of intravenous fentanyl would distinguish intravenous from epidural administration. One hundred ASA I and II labouring parturients received 100 μg fentanyl either iv or via an epidural catheter in a double-blind, randomized, crossover fashion. Nineteen anaesthetists (8 staff and 11 residents) participated and correctly guessed the route of administration of the fentanyl in 61/66 intravenous doses and in 69/75 epidural doses yielding a sensitivity of 92.4%, a specificity of 92.0%, a positive predictive value of 91.0%, and a negative predictive value of 93.2%. Of the 41 patients that were crossed over, 38 (92.7%) were able to detect a difference between the routes of administration. Most patients experienced prompt, short-lived symptoms with iv fentanyl but no important differences in fetal heart rate pattern or in maternal desaturation were seen between the groups. This study suggests that subjective symptoms will accurately distinguish intravenous from epidural fentanyl administration in labouring parturients (P < 0.001), and should serve as a safe and reliable intravenous test dose for epidural anaesthesia in the obstetric population.     

Use of psychoactive substances in three medical specialties: anaesthesia,medicine and surgery

In order to determine the prevalence of psychoactive substance use in three specialty groupings, 1,624 questionnaires were sent to physicians in medicine, surgery and anaesthesia; all had trained at the same academic institution. A response rate of 57.8% was achieved. Comparison of prevalence of impairment rates showed no differences between Surgery (14.4%), Medicine (19.9%) and Anaesthesia (16.8%). Substance abuse was clearly associated with a family history of abuse; 32.1% of the abusers had a family history of such abuse compared with 11.7% of the non-abusers. Increased stress at various career stages did not appear to increase substance abuse; problem areas during medical life times were similar for each specialty. Substances most frequently used were marijuana (54.7%), amphetamines (32.9%); and benzodiazepines (25.1%). Seventy-three used psychoactive drugs which were non-prescribed. Drug counselling programmes were judged inadequate by most. Use of alcohol and drugs by faculty members was reported by a number of respondents.     

Proteolysis and invasiveness of brain tumors: Role of urokinase-type plasminogen activator receptor

Summary The cellular receptor for urokinase-type plasminogen activator (uPAR) in glioblastoma cell lines has been identified and found to be similar to the uPAR expressed by other tumor cell lines. Increased levels of uPAR have been found in primary malignant brain tumor tissues, especially highly malignant glioblastoma, and, to a lesser degree, in malignant astrocytomas, suggesting that this receptor might be involved in efficient activation of pro-uPA and confinement of uPA activity on the cell surface of invading brain tumors. The cell surface uPARs in gliomas could constitute an optimum environment for the generation and activity of plasmin, which is known to play a crucial role in the dissolution of the extracellular matrix during tumor cell invasion.In situ hybridization studies have shown that uPAR mRNA is expressed abundantly in tumor cells and is consistently present at the invasive edges of malignant gliomas. These results imply that uPAR is involved in plasmincatalyzed proteolysis during glioma invasion and that interference with the uPAuPAR interactions could constitute a novel approach for developing therapeutic strategies to counteract invasion of brain tumors.     

Excitatory amino acid release from astrocytes during energy failure by reversal of sodium-dependent uptake

Non-synaptic release may be the major route of excitatory amino acid (EAA) efflux during cerebral ischemia. Possible routes of non-synaptic release include non-specific anion channels, reversal of Na⁺-, CI^?-, or Ca²⁺-dependent uptake, and cell lysis. In the present study we employ a novel approach to show reversal of Na⁺-dependent uptake as a major route of EAA efflux from astrocyte cultures under conditions of energy failure. Primary rat astrocyte cultures were subjected to combined blockade of glycolytic and oxidative metabolism after incubation with [³H]-D-aspartate (D-ASP). Energy failure produced an efflux of D-ASP that was maximal by 90 minutes. The efflux over this period was reduced by more than 50% in cells that had been pre-loaded with PDC (L-transpyrrolidine-2,4-dicarboxylic acid) or TBHA (threo-β-hydroxyaspartic acid), compounds that are competitive inhibitors of Na⁺-dependent glutamate uptake. The effect of pre-loading with the inhibitors was concentration dependent. No effect was seen if the inhibitors were added after induction of energy failure, suggesting that the attenuation of D-ASP efflux resulted from binding of the inhibitors to an intracellular site. These results provide strong evidence that EAA efflux from astrocytes under conditions of energy failure occurs largely through reversal of Na⁺-dependent uptake. © 1995 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Effets de l’halothane sur la ventilation et les gaz du sang artériel chez le rat avec ou sans paralysie diaphragmatique

Certains patients atteints de paralysie diaphragmatique ou de dysfonctionnement diaphragmatique maintiennent leur ventilation par la mise en jeu d’autres muscles que le diaphragme. L’anesthésie, modifiant le fonctionnement de ces muscles, représente un risque potentiel chez ces patients. Afin d’évaluer ce risque, nous avons étudié les effets de l’halothane sur la ventilation et sur les gaz du sang artériel sur un modèle de paralysie diaphragmatique bilatérale, le rat phrénicectomisé. L’étude a été réalisée sur 43 rats. L’efficacité de la phrénicectomie a été contrôlée par l’observation directe, après laparotomie. La laparotomie n’entraine pas de modification des gaz du sang. Chez 23 rats, une laparotomie a été effectuée et une artère carotide a été cathétérisée. Chez 11 rats témoins, les nerfs phréniques ont été abordés, sans être sectionnés. Chez 12 rats, les phréniques ont été sectionnés. La ventilation a été mesurée par une technique pléthysmographique, chez les rats éveillés, avant et après l’opération, puis chez les mêmes rats anesthésiés avec 1,1%, d’halothane inspiré. Les gaz du sang ont été mesurés après l’opération chez les rats éveillés, puis anesthésiés. Chez les 23 rats opérés on observe, après l’opération, une diminution du poids et de la température centrale, plus importante chez les phrénicectomisés que chez les témoins. Chez les 11 rats témoins, après l’opération, la ventilation augmente, sans modification des gaz du sang. Chez ces rats, l’halothane provoque une diminution de la ventilation minute et de la PaO₂ et une augmentation de la PaCO₂. La phrénicectomie entraine chez les 12 rats, éveillés, une augmentation de la ventilation minute, une hypoxémie et une hypercapnie. Chez ces rats, l’halothane entraine le décès dans trois cas, une diminution de la ventilation minute et une hypercapnie et une hypoxémie importantes chez les neuf autres rats. Les modifications des gaz du sang sont plus importantes que chez les témoins anesthésiés. Chez le rat intact, l’halothane provoque des modifications des gaz du sang comparables à celles observées chez d’autres espèces et chez l’homme. La présente étude confirme les effets de l’halothane sur les muscles respiratoires autres que le diaphragme. Elle met en évidence le risque respiratoire majeur que l’anesthésie peut fair courir aux patients dont la ventilation est maintenue par d’autres muscles que le diaphragme.     

Influence of cycle variability and coital frequency on the risk of pregnancy

Researchers have cautioned against generalizing results from contraceptive trials because these studies rely on self-selected participants meeting strict selection criteria who may differ from typical users. Using information collected on daily diaries, we reanalyzed data from the recently completed Reality female condom clinical trial to evaluate factors that influence the probability of pregnancy. Noncompliant women, women with less variable menstrual cycles (17-43 days), and women engaging in intercourse frequently (> or = 11 acts per month) were more likely to conceive during this 6-month trial. The adjusted hazard ratios and 95% confidence intervals for these three covariates were 6.1 (2.0-18.7), 7.2 (1.0-54.3), and 2.0 (0.7-5.3), respectively. The strict selection criteria used in this study failed to recruit a homogeneous cohort with respect to factors that influence the risk of pregnancy. The overall pregnancy rate does not pertain to individual study participants, but rather represent average effects for a population with the particular mix of characteristics found in this study. In particular, we not only confirm the well known importance of compliance and the obvious role of frequency of intercourse, but also demonstrate that women with cycles outside the range of 17-43 days appear to be at a much lower risk of pregnancy.     

Antibodies against the beta subunit of voltage-dependent calcium channels in Lambert-Eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome is an autoimmune disease that impairs neuromuscular transmission. Several studies suggest that neurotransmitter release is reduced by an immune response directed against the calcium channel complex of nerve terminals. The immunoglobulin G fractions from Lambert-Eaton myasthenic syndrome patients immunoprecipitate solubilized neuronal N- and P/Q-type channels and in certain cases brain, skeletal and cardiac muscle L-type channels [El Far O. et al. (1995) J. Neurochem. 64, 1696-1702; Lennon V. A. and Lambert E. H. (1989) Mayo Clin. Proc. 64, 1498-1504; Sher E. et al. (1989) Lancet ii, 640-643; Suenaga A. et al. (1996) Muscle Nerve 19, 1166-1168]. These channel immunoprecipitation assays are considered as useful for the diagnosis of this syndrome. In this study, we demonstrate that two predominant neuronal voltage-dependent calcium channel beta subunits (beta3 and beta4, of mol. wt 58,000) are general targets of Lambert-Eaton myasthenic syndrome autoantibodies. Of 20 disease sera tested, 55% were able to immunoprecipitate 35S-labeled beta subunits. All five patients affected with small-cell lung carcinoma were positive for the beta-subunit immunoprecipitation assay. Interestingly, only a fraction of the beta-subunit-positive sera was also able to immunoprecipitate N- and P/Q-type channels, suggesting that several of the beta-subunit epitopes are masked in native channels. In accordance with this observation, we found that several beta-positive sera were able to prevent the interaction between calcium channel alpha1 and beta subunits in vitro. In cases where sera were able to immunoprecipitate beta subunits, N- and P/Q-type channels, the immunoprecipitation of both channel types was either partially or entirely mediated by beta-subunit antibodies. Our results suggest that assays based on the immunoprecipitation of beta subunits can be used as an additional test to assist in the diagnosis of Lambert-Eaton myasthenic syndrome.     

Endovascular treatment of hemifacial spasm associated with a cerebral arteriovenous malformation using transvenous embolization: case report

OBJECTIVE AND IMPORTANCE: To illustrate that decompression of the facial nerve by transvenous endovascular treatment may relieve hemifacial spasm (HFS) caused by dilated veins. CLINICAL PRESENTATION: A 35-year-old man suffered severe chronic right HFS associated with a dilated right lateral mesencephalic vein lying in the vicinity of the facial nerve. This nonessential vein was recruited as a secondary collateral drainage from an inoperable left temporo-occipital arteriovenous malformation. INTERVENTION: The lateral mesencephalic vein was reached through the superior petrosal sinus using a transfemoral venous approach and was occluded with interlocking detachable coils (Target Therapeutics, Freemont, CA). There was complete remission of HFS without recurrence after 2.5 years of follow-up. CONCLUSION: This case report supports vascular compression in the pathogenesis of HFS and suggests that facial nerve injury is not essential for the therapeutic effect of surgical decompression.     

A risk-benefit assessment of amifostine in cytoprotection.

Recent advances in chemotherapy have focused on the benefit of high dose regimens, increasing the dose intensity of conventional chemotherapy and using intensified chemotherapy with or without autologous bone marrow rescue. Dose intensity usually increases objective response rates of antineoplastic drugs and might, in some circumstances, improves survival. However, unacceptable acute and/or cumulative toxicity often impairs the proper management of patients, leading to dose reduction or treatment delay, thus reducing the efficacy and potentially the quality of life of patients. Therefore, considerable efforts have been made to manage, to prevent, and to delay many acute and cumulative treatment-related toxicities. Amifostine (WR-2721 ) is a multiorgan cytoprotector which has demonstrated cytoprotective effects, in vitro and in vivo, against the most common cytotoxic drug-related toxicities and against radiation-induced adverse effects in healthy tissues. In vitro and in vivo, cytoprotection was observed in several organs including kidney, haematopoietic stem cells, myocardial cells, neural cells, and mucosa, without detectable protection of malignant cells. In addition, in preclinical studies, amifostine appeared to be able to reduce the risk of radiation-induced secondary neoplasms. Phase I studies showed that nausea/vomiting and hypotension are the dose-limiting toxicities of amifostine and these may be controlled by reducing the duration of injection of amifostine. Phase II and randomised studies have confirmed the efficacy of amifostine in protecting against radiotherapy-induced mucositis, cisplatin-induced nephrotoxicity, cyclophosphamide-induced neutropenia and carboplatin-induced thrombocytopenia. Importantly, the cytoprotection of healthy tissues occurred without any significant deleterious effect on response rate, time to progression, and survival of patients receiving amifostine. However, in addition to the potential quality of life benefit, the most important question of whether the use of a cytoprotective agent might translate into the possibility of maintaining the dose intensity of anticancer therapies has still to be answered. The real benefit of amifostine in the overall management of patients with cancer requires additional studies to determine whether this chemoprotective approach can be of benefit to patients by increasing response rate, time to progression, and long term survival in patients receiving the more recent combination therapies involving new drugs such as the taxanes and oxaliplatin.