Characterization of the tetanus toxin model of refractory focal neocortical epilepsy in the rat

PURPOSE: To characterize in detail a model of focal neocortical epilepsy. METHODS: Chronic focal epilepsy was induced by injecting 25-50 ng of tetanus toxin or vehicle alone (controls) into the motor neocortex of rats. EEG activity was recorded from electrodes implanted at the injection site, along with facial muscle electromyographic (EMG) activity and behavioral monitoring intermittently for up to 5 months in some animals. Drug responsiveness was assessed by using the antiepileptic drugs (AEDs) diazepam (DZP) and phenytoin (PHT) delivered systemically, while 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), a competitive antagonist at AMPA receptors, was administered directly to the brain to investigate the potential benefits of focal drug delivery. RESULTS: Tetanus toxin induced mild behavioral seizures that persisted indefinitely in all animals. EEG spiking activity, occurring up to 80% of the time, correlated with clinical seizures consisting of interrupted behavioral activity, rhythmic bilateral facial twitching, and periods of abrupt motor arrest. Seizures were refractory to systemic administration of DZP and PHT. However, focal delivery of NBQX to the seizure site reversibly reduced EEG and behavioral seizure activity without detectable side effects. CONCLUSIONS: This study provides a long-term detailed characterisation of the tetanus toxin model. Spontaneous, almost continuous, well-tolerated seizures occur and persist, resembling those seen in neocortical epilepsy, including cortical myoclonus and epilepsia partialis continua. The seizures appear to be similarly resistant to conventional AEDs. The consistency, frequency, and clinical similarity of the seizures to refractory epilepsy in humans make this an ideal model for investigation of both mechanisms of seizure activity and new therapeutic approaches.     

Tetanus immunization in pregnant women. Serum levels of antitetanus antibodies at time of delivery

The objective of this study was to determine the tetanus immunity status of pregnant women at the time of delivery according to tetanus toxoid (TT) vaccination coverage during their most pregnancy. The serum anti-tetanus antibody levels of 493 mothers who had live births at a hospital in Ankara were determined by enzyme-linked immunosorbent assay (ELISA). Protected women were defined as those with serum antibody levels 0.6 IU/ml. Overall, 69.0% of mothers had protective tetanus antibody titers at the time of delivery. The rates of protection for mothers who had received no vaccination, one TT dose, or two TT doses during pregnancy were 46.4, 93.5, and 95.6%, respectively. Vaccinating every pregnant woman with at least one dose of TT would be an affordable and effective way to protect against neonatal tetanus, and would be a step toward eliminating the deaths that continue to occur due to this preventable disease in Turkey.     

履行项目承诺 促进“两纲”目标落实

“降低孕产妇死亡率和消除新生儿破伤风”项目 (“降消”项目 )实施一年半时间 ,初见成效。“降消”项目工作思路清晰 ,启动快 ,可操作性强 ,影响大 ,带动范围广 ,注重对供方的支持和对需方的救助。这个项目只剩半年时间 ,还存在一些困难和问题。因此 ,要增强实现项目目标的紧迫感 ,进一步加强领导 ;加大督查力度 ,及时解决项目实施中的困难与问题 ;深入进行技术培训和健康教育工作 ,发挥急救“绿色通道”的作用 ;巩固和发展项目成果 ,坚持不懈地抓好“降消”工作 ,带动农村的妇幼卫生工作。     

内蒙古自治区消除新生儿破伤风项目工作评价

目的落实卫生部和澳大利亚政府国际发展局援助内蒙古自治区开展消除新生儿破伤风(NT)项目,评价乌拉特中旗、乌拉特后旗、乌审旗、鄂托克前旗NT高危旗所有18~35岁的育龄期妇女开展破伤风疫苗(TV)接种效果。方法按照0、1、7个月程序开展突击接种3剂TV,每剂次0.5ml。结果4个旗应种35 138人,报告接种率TV192.79%,TV291.43%,TV390.30%,12个项目旗2003~2005年无NT病例报告。结论应在保证清洁接生的基础上,对NT高危旗育龄期妇女开展TV常规免疫接种,加强NT监测。     

Seroprotection associated with infant vitamin A supplementation given with vaccines is not related to antibody affinity to Hepatitis B and Haemophilus influenzae type b vaccines

Vaccines are usually assessed by analyses of their safety and immunogenicity to determine the effectiveness of eliciting antibody responses against target organisms. However, it is equally important to establish antibody affinity because of its specific role in protection from infection. Antibody affinity can be determined by comparisons of various antibody concentrations in dose–response curves. During a study on the immunogenicity of a pentavalent vaccine in 888 infants, antibody affinity analyses of the hepatitis B and Haemophilus influenzae type b components were investigated in infants given 15 mg RE vitamin A with their vaccination and those who were not given vitamin A. In this paper we present the results of 222 infants; a 25% sub-sample of the original study. Analyses were carried out using dilutions of serum samples from fitted values corresponding to optical densities from antibody detection assays. These were obtained from the ligand binding equation and mid point titres in dose–response curves were then calculated. Vitamin A supplementation had no effect on the midpoint titres of Hepatitis B and H. influenzae type b vaccine derived antibodies. The significant effect of vitamin A supplementation on the Hepatitis B vaccine component observed in a previous seroprotection analysis is probably due to the amount of antibodies since affinity was unaffected.     

Restoration of anti-tetanus toxoid responses in patients initiating highly active antiretroviral therapy with or without a boost immunization: an INITIO substudy

INITIO is an open-labelled randomized trial evaluating first-line therapeutic strategies for human immunodeficiency virus-1 (HIV-1) infection. In an immunology substudy a tetanus toxoid booster (TTB) immunization was planned for 24 weeks after initiation of highly active antiretroviral therapy (HAART). All patients had received tetanus toxoid immunization in childhood. Generation of proliferative responses to tetanus toxoid was compared in two groups of patients, those receiving a protease inhibitor (PI)-sparing regimen (n = 21) and those receiving a PI-containing (n = 54) regimen. Fifty-two participants received a TTB immunization [PI-sparing (n = 15), PI-containing (n = 37)] and 23 participants did not [PI-sparing (n = 6) or PI-containing (n = 17)]. Cellular responses to tetanus antigen were monitored by lymphoproliferation at time of immunization and every 24 weeks to week 156. Proportions with a positive response (defined as stimulation index ≥ 3 and Δ counts per minute ≥ 3000) were compared at weeks 96 and 156. All analyses were intent-to-treat. Fifty-two participants had a TTB immunization at median 25 weeks; 23 patients did not. At weeks 96 and 156 there was no evidence of a difference in tetanus-specific responses, between those with or without TTB immunization (P = 0·2, P = 0·4). There was no difference in the proportion with response between those with PI-sparing or PI-containing regimens at both time-points (P = 0·8, P = 0·7). The proliferative response to tetanus toxoid was unaffected by initial HAART regimen. Anti-tetanus responses appear to reconstitute eventually in most patients over 156 weeks when treated successfully with HAART, irrespective of whether or not a TTB immunization has been administered.     

Year of birth,sex and residence,as ≪ determinants ≫ of tetanus incidence and immunity in Italy

Regional results of a seroepidemiological study and official notification data are evaluated to describe the situation of tetanus in Italy. Tetanus incidence has been decreasing during the past years. Vaccination has been the principal means of tetanus prevention. Trend analyses for sex- and age-specific rates suggest a change of exposure, presumably linked to the transformation of the Italian society after the World War II, a higher incidence among the elderly as a function of poor coverage and vanishing immunity. Regional data show remarkable variability in prevalence of susceptible population. Reported rates by region are different. Different degrees of regional underreporting in case notification is suggested.     

Leucocyte migration inhibition in diphtheria toxoid hypersensitivity

A donor who was highly reactive to diphtheria toxoid (DT) in delayed hypersensitivity and in lymphocyte transformation showed scant evidence of antigen-induced inhibition in the direct leucocyte migration agarose test. Other donors, weak or negative to DT in skin test and transformation, did show evidence of inhibition. Although the migration test is useful in assessing cellular reactivity to tubercular antigen, these results question its suitability for DT.     

Pancuronium blood level monitoring in patients with tetanus

Overdosage of muscle relaxant has been given as a possible explanation for the hypotensive episodes occurring during the management of tetanus. The aim of the present work was to study the pharmacokinetics of pancuronium during long term infusion. Pancuronium was administered to eight patients with severe tetanus for a period varying from 8 to 24 days. The concentration of pancuronium was measured daily in plasma and urine using a fluorimetric method. The plasma concentration varied from 0.27 to 0.48 g/ml. No tendency to accumulation was observed. The plasma concentration fell rapidly below the level associated with muscle relaxation when pancuronium was discontinued. This absence of accumulation can be explained by a rapid elimination of pancuronium through the kidney according to a process of ultrafiltration.This work was supported by grants from Faculté de Médecine Xavier-Bichat (Université Paris VII). This work was presented in part at the Second World Congress on Intensive Care, September 1977, Paris, France     

Evaluation of left ventricular performance during sympathetic nervous storm in a case with severe tetanus by transesophageal M-mode echocardiography

Transesophageal M-mode echocardiography was applied for the evaluation of left ventricular performance in a case of severe tetanus with labile hypertension due to sympathetic nervous ‘torm’. When systemic blood pressure was elevated, increases in pulmonary arterial pressure, cardiac output, left ventricular enddiastolic diameter, fractional shortening and mean velocity of circumferential fiber shortening were noted. No changes were found in total peripheral vascular resistance or left ventricular endsystolic diameter. Positive pressure ventilation, rendered standard transthoracic echocardiography ineffective.