Massive strychnine intoxication: serial blood levels in a fatal case.

A fatal case of strychnine intoxication is reported. The patient expired despite early aggressive management and prevention of metabolic complications. Serial blood levels are reported. In contrast to a previous report describing first order elimination kinetics, our data suggest that strychnine follows Michaelis-Menton elimination kinetics. The case illustrates the rapid, dramatic course of severe strychnine ingestions. A review of the toxicokinetics, mechanism of action and treatment of strychnine intoxication follows.     

Fluid therapy for induced labour under epidural analgesia: biochemical consequences for mother and infant

Two types of fluid regimen were provided for patients having labour induced under epidural analgesia. Reasons for the infusion were to pre-load the circulation before the epidural, and subsequently to sustain maternal hydration. Both fluids were isotonic, one was predominantly saline based (Hartmann's solution) and the other contained both saline and dextrose. Blood glucose and serum sodium, lactate and beta-hydroxybutyrate were measured before the start of induction, at delivery and in the cord sample. Blood glucose and serum sodium were measured in the babies at 12 and 24 h of age. The dextrose-saline fluid caused small but significant changes in blood glucose and serum sodium which did not exceed the normal reference limits for either. The use of Hartmann's solution was associated with considerable rises in maternal serum beta-hydroxybutyrate at delivery. Neither fluid had any significant effect on the blood glucose or serum sodium in infants at 12 and 24 h of age.     

Liver transplantation for severe Amanita phalloides mushroom poisoning

Amanita phalloides mushroom poisoning is an increasingly common and potentially lethal problem for which liver transplantation offers definitive therapy in selected patients. When significant liver dysfunction appears, early transfer to a liver transplant center is important to identify appropriate candidates and to begin the search for a donor organ. The clinical course of five severely poisoned patients, four of whom underwent liver transplantation, is reviewed. Indications for transplantation included primarily a markedly prolonged prothrombin time that was only partially correctable and a constellation of findings including metabolic acidosis, hypoglycemia, hypofibrinogenemia, and increased serum ammonia, following a marked elevation in serum aminotransferase levels. Unlike viral fulminant hepatic failure, grade III or IV hepatic encephalopathy, marked elevation of the serum bilirubin level, and azotemia were not indications for transplantation. Resected livers demonstrated hepatocyte viability of 0% to 30%. Manifestations of Amanita poisoning complicating preoperative and/or postoperative care included severe diarrhea, gastrointestinal hemorrhage, hypophosphatemia, bowel edema, and marrow suppression with lymphopenia, thrombocytopenia, and neutropenia. All five patients are well 1 year later. This largest experience with liver transplantation for Amanita poisoning further defines the early clinical and laboratory indications for, and the unique complicating features of, transplantation in this setting.     

Lung surfactant gelation induced by epithelial cells exposed to air pollution or oxidative stress

Lung surfactant lowers surface tension and adjusts interfacial rheology to facilitate breathing. A novel instrument, the interfacial stress rheometer (ISR), uses an oscillating magnetic needle to measure the shear viscosity and elasticity of a surfactant monolayer at the air-water interface. The ISR reveals that calf lung surfactant, Infasurf, exhibits remarkable fluidity, even when exposed to air pollution residual oil fly ash (ROFA), hydrogen peroxide (H2O2), or conditioned media from resting A549 alveolar epithelial cells (AEC). However, when Infasurf is exposed to a subphase of the soluble fraction of ROFA- or H2O2-treated AEC conditioned media, there is a prominent increase in surfactant elasticity and viscosity, representing two-dimensional gelation. Surfactant gelation is decreased when ROFA-AEC are pretreated with inhibitors of cellular reactive oxygen species (ROS), or with a mitochondrial anion channel inhibitor, as well as when A549-rho0 cells that lack mitochondrial DNA and functional electron transport are investigated. These results implicate both mitochondrial and nonmitochondrial ROS generation in ROFA-AEC-induced surfactant gelation. A549 cells treated with H2O2 demonstrate a dose-dependent increase in lung surfactant gelation. The ISR is a unique and sensitive instrument to characterize surfactant gelation induced by oxidatively stressed AEC.     

Fine Structure of A: Autonomic Nerve Fibers and Terminals in Human Myocardium; and B: Myocardial Changes in Congenital Heart Disease

In a histological and fine structural study of right atrial biopsy specimens from 31 patients with rheumatic heart disease (RHD), aged 7 to 46 years, and 11 patients with congenital heart disease (CHD), aged 3 to 36 years, nerve fibers or endings were seen by electron microscopy in 11 specimens. There was concurrence of ordinary axons along with terminals bearing pale cholinergic or dark adrenergic synaptic vesicles. Smaller and denser cholinergic vesicles suggested proliferation followed by exhaustion of such nerve endings. The closest proximity of nerve terminal to muscle fiber was about 100 nm. In one RHD specimen a “specific terminal cell” was present between a nerve ending and muscle fiber; in another a possible neuromuscular contact was developing at the surface of a regenerating small muscle fiber with a few myofilaments. Unmyelinated axons amidst increased subendocardial and subepicardial collagen, with prominent fibroblasts and depleted muscle fibers, were seen more frequently in specimens of CHD. Loss of myofibrils and accumulation of mitochondria, with infrequent formation of lipofuscin bodies, characterized degenerating muscle fibers in CHD also, although to a lesser degree than in RHD (reported earlier, 1985). The myocardial blood vessels in CHD tended to have pale swollen endothelial cells and narrowed lumen. The most severely affected cases of CHD were those with (1) a very wide atrial septal defect (ASD), (2) ventricular septal defect (VSD) with vegetations near the defect, (3) 1 infundibular pulmonary stenosis, and (4) Fallot's tetralogy.     

地塞米松对儿童自身免疫病患者外周血淋巴细胞早期凋亡的影响

目的　为了观察儿童自身免疫病患者 (以SLE为代表 )在应用地塞米松 2 4h前后细胞凋亡情况 ,对其外周血淋巴细胞早期凋亡率进行了检测。方法　应用最新的AnnexinV检测试剂盒及流式细胞仪检测早期凋亡细胞。结果　儿童SLE初发活动期患者外周血淋巴细胞早期凋亡率 (2 .36 6± 1.5 34% )明显低于经静脉注射地塞米松 2 4h后的患儿 (10 .6 96±2 .830 % )及同年龄段正常儿童 (12 .4 95± 2 .4 78% ) ;而后两者相比则无明显差异。结论　儿童SLE活动期患者经过静脉注射地塞米松以后 ,外周血淋巴细胞凋亡率明显升高。其可能的机制为固醇类激素通过激活促进凋亡基因 ,从而促进大量淋巴细胞凋亡 ,使自身免疫病的发生受到控制。     

Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage

Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage An alloimmune abnormality is believed to be the cause of recurrent miscarriage in couples in whom no other cause can be identified. Because of its immunosuppressive properties, intravenous immunoglobulin (IVIG) is used as a treatment for this disorder. The purpose of this study was to determine whether IVIG improves the chance of successful pregnancy in women with recurrent miscarriage by using individual patient data from efficacy trials. Detailed information on each patient enrolled in these trials was obtained to evaluate the efficacy of IVIG and investigate the effect of clinical variability on pregnancy outcome. Data from 125 patients in the IVIG group and 115 patients in the placebo group were available for analysis. Although the number of previous miscarriages and female age were both negative prognostic factors for successful outcome, there was no significant improvement in successful pregnancy or live birth rate with IVIG. Subgroup analyses indicated that timing of IVIG administration may be important. The results of the present study highlight the importance of stratification for known confounders, so that the role of IVIG can be evaluated in more detail. The collective evidence thus far indicates that IVIG does not have a therapeutic effect that is clinically meaningful.     

Sociodemographic Patterns of Exclusive,Dual, and Polytobacco Use Among U.S. High School Students: A Comparison of Three Nationally Representative Surveys

PurposeThis study examines sociodemographic patterns of exclusive/dual/polytobacco use among U.S. high school students using multiple national surveys.MethodsUsing three national youth surveys (Population Assessment of Tobacco and Health [PATH] Wave 4 [2016–2017], 2017 Youth Risk Behavior Survey, and 2017 National Youth Tobacco Survey), we classified tobacco products into four groups: (1) electronic nicotine delivery systems (ENDS), (2) conventional cigarettes (CCs), (3) other combustible tobacco products, and (4) smokeless tobacco products. We created 16 categories of non/exclusive/dual/polytobacco use within the past 30 days using the four product groups and calculated weighted population prevalence by sex and race/ethnicity (all surveys) and parental education and income (PATH), based on variable availability.ResultsThe results from 9,331, 12,407, and 9,699 high school students in PATH, Youth Risk Behavior Survey, and National Youth Tobacco Survey, respectively, largely agreed and pointed to similar conclusions. ENDS was the most prevalent exclusive use product (3.8%–5.2% across surveys), with CCs falling to second or third (1.2%–2.0% across surveys). By sex, exclusive, dual, and poly smokeless tobacco product use were more common for males, whereas exclusive CC use was more common for females. By race/ethnicity, non-Hispanic Whites had a higher prevalence of exclusive ENDS use and ENDS/CC dual use than non-Hispanic Blacks. As income and parental education levels increased from low to high, the prevalence of exclusive CC use decreased, whereas the prevalence of exclusive ENDS use increased.ConclusionUnderstanding sociodemographic patterns of tobacco use can help identify groups who may be at greater risk for tobacco-related health outcomes.     

A framework for considering the risk‐benefit trade‐off in designing noninferiority trials using composite outcome approaches

When a new treatment regimen is expected to have comparable or slightly worse efficacy to that of the control regimen but has benefits in other domains such as safety and tolerability, a noninferiority (NI) trial may be appropriate but is fraught with difficulty in justifying an acceptable NI margin that is based on both clinical and statistical input. To overcome this, we propose to utilize composite risk‐benefit outcomes that combine elements from domains of importance (eg, efficacy, safety, and tolerability). The composite outcome itself may be analyzed using a superiority framework, or it can be used as a tool at the design stage of a NI trial for selecting an NI margin for efficacy that balances changes in risks and benefits. In the latter case, the choice of NI margin may be based on a novel quantity called the maximum allowable decrease in efficacy (MADE), defined as the marginal difference in efficacy between arms that would yield a null treatment effect for the composite outcome given an assumed distribution for the composite outcome. We observe that MADE: (1) is larger when the safety improvement for the experimental arm is larger, (2) depends on the association between the efficacy and safety outcomes, and (3) depends on the control arm efficacy rate. We use a numerical example for power comparisons between a superiority test for the composite outcome vs a noninferiority test for efficacy using the MADE as the NI margin, and apply the methods to a TB treatment trial.