Fomepizole as an Adjunctive Treatment in Severe Acetaminophen Toxicity

A 33-year-old male presented to the emergency department with a chief complaint of abdominal pain after taking #50 500 mg acetaminophen tablets over the preceding two days. He was tachycardic and tachypneic, and the initial labs were notable for acetaminophen level, 337 mg/L; AST, 137 IU/L; ALT, 194 IU/L; ABG pH, 7.24; and lactate, 4.1 mmol/L. The patient was started on IV N-Acetylcysteine (NAC) as well as given a single dose of 15 mg/kg fomepizole. The patient did remarkably well, with a peak AST of 198 IU/L, peak ALT of 301 IU/L, and peak INR of 3.1. Biochemical and animal data support fomepizole having hepatoprotective effects in acetaminophen poisoning. To our knowledge, this is the first human case of an intentional dual NAC/fomepizole regimen for severe acetaminophen toxicity.     

中药辅助治疗孔源性视网膜脱离的临床研究

目的评价中药辅助治疗孔源性视网膜脱离（rhegmatogenous retinal detachment,RRD）的临床疗效。方法将52例（52眼）RRD患者按随机数字表法分为观察组和对照组,每组26例（26眼）。对照组采用单纯视网膜脱离复位术;观察组在视网膜脱离复位术基础上采用中药辨证论治治疗,对2组患者视网膜下液吸收的情况及术后视力恢复情况进行比较。结果①视网膜下积液吸收情况：观察组总有效率92.3%;对照组总有效率为61.5%,2组比较差异有统计学意义（P〈0.01）。②视力改善情况：观察组总有效率为73.1%。对照组总有效率为46.2%,2组较差异有统计学意义（P〈0.05）。结论中药能促进视网膜下积液的吸收及视功能的恢复,是辅助治疗RRD的一个重要举措。     

连续性肾脏替代治疗治疗急性重度有机磷农药中毒伴重度脑病

目的探讨急性重度有机磷农药中毒伴重度脑病采取连续性肾脏替代治疗(CRRT)治疗的疗效。方法选取2011年5月~2016年5月我院收治的72例急性重度有机磷农药中毒伴重度脑病患者。随机分为CRRT组和非CRRT组各36例。两组均给予盐酸戊乙奎醚+氯磷定治疗,CRRT组在此基础上联合CRRT治疗,观察对比两组疗效。结果 CRRT组苏醒时间、机械通气时间、CHE恢复时间、住院时间、盐酸戊乙奎醚用量、氯磷定用量均显著低于非CRRT组,差异有统计学意义(P<0.05);治疗24h后,CRRT组IL-4、TNF-α含量及APACHEⅡ评分均显著优于非CRRT组,差异有统计学意义(P<0.05);CRRT组治愈率显著高于非CRRT组,病死率显著低于非CRRT组,差异有统计学意义(P<0.05)。结论采取CRRT联合解毒药物治疗伴有重度脑病的急性重度有机磷农药中毒患者,临床疗效显著,具有推广价值。     

Combined Initial Cyclophosphamide with Repeated Methylprednisolone Pulse Therapy for Severe Paraquat Poisoning from Dermal Exposure

Abstract

The article presents a patient with severe paraquat poisoning from dermal exposure, who had chemical burns to more than 10% of his body surface area, serum paraquat level 0.13 µg/mL 60 hr after exposure, and severe hypoxemia (PaO₂ 41.6 mmHg). The patient was successfully treated with combined initial megadoses of cyclophosphamide (15 mg/kg/day, total 2 days) with repeated methylprednisolone pulse therapy (15 mg/kg/day, total 6 days) and continuous dexamethasone administration (5 mg every 8 hr), and recovered completely without sequelae 3 months later. This treatment deserves further investigation in future clinical trials.     

Nasal Sumatriptan as Adjunctive Therapy for idiopathic Trigeminal Neuralgia: Report of Three Cases

We examine the effect of nasal sumatriptan as an adjunctive therapy in 3 patients with idiopathic trigeminal neuralgia refractory to carbamazepine (CBZ) and found that this therapy might be suitable for patients for whom the CBZ dose cannot be increased, who are under poor pain control, and who are not candidates for nerve blocks or surgery.     

Calcium and Digoxin vs Calcium Alone for Severe Verapamil Toxicity

Calcium chloride (CaCl(2)) is ineffective in severe calcium channel antagonist overdoses. Digoxin increases intracellular calcium by inhibiting the sodium-potassium adenosine triphosphatase enzymes. OBJECTIVE: To examine the effect of calcium and digoxin on the treatment of verapamil toxicity. METHODS: Sixteen dogs were instrumented to monitor hemodynamics. Verapamil toxicity (50% decrease in mean arterial pressure) was induced with verapamil (VER) at 6 mg/kg/hr and maintained for 30 minutes by titrating the VER rate. Following toxicity, the dogs received either digoxin (0.018 mg/kg) (DIG) (n = 8) or saline (No-DIG) (n = 8). Both groups received VER at three sequential rates (1 mg/kg/hr from 0 to 90 min, 6 mg/kg/hr from 90 to 130 min, and 18 mg/kg/hr from 130 to 170 min). Calcium boluses were given (500 mg at 0 and 15 min; 1 g at 140, 150, and 160 min). Data were analyzed using a repeated-measures analysis of covariance comparing DIG vs No-DIG across the infusion rates and time. Animal weight, does of VER administered during the toxicity phase, and baseline values were included as covariates. Mortality rates were compared at 230 minutes following a total dose of 500 mg of VER. RESULTS: The DIG group had a higher systolic blood pressure (SBP) than the No-DIG group during the 1-mg/kg/hr (early p = 0.028, late p = 0.01), 6-mg/kg/hr (p = 0.051), and 18-mg/kg/hr (p = 0.038) VER infusion rates. There were no deaths in the DIG group and four deaths in the No-DIG group (Fisher = 0.08). Neither ventricular tachycardia nor ventricular fibrillation developed in either group. Other hemodynamic parameters did not show significant changes. CONCLUSIONS: In a model of severe verapamil toxicity, digoxin plus calcium raised SBP and did not result in ventricular arrhythmias when compared with calcium alone.     

钙拮抗剂对重症急性胰腺炎肾损害保护作用的实验研究

【目的】探讨钙拮抗剂对重症急性胰腺炎（SAP）大鼠肾损害的影响。【方法】Wistar大鼠45只,随机分为假手术组（A组）、SAP组（B组）和钙拮抗剂治疗组（C组）,观察各组动物肾功能、炎性细胞因子IL-1、IL-6、TNF-α和肾脏组织病理学改变。【结果】SAP时血清中炎性细胞因子IL-1、IL-6、TNF-α升高,肾功能下降,肾组织损害严重。钙拮抗剂治疗组炎性因子水平降低,肾组织损害减轻,肾功能明显改善。【结论】钙拮抗剂可抑制SAP某些细胞因子的产生和释放,对肾损害具有保护作用。     

Mutant Sodium Channel for Tumor Therapy

Viral vectors have been used to deliver a wide range of therapeutic genes to tumors. In this study, a novel tumor therapy was achieved by the delivery of a mammalian brain sodium channel, ASIC2a, carrying a mutation that renders it constitutively open. This channel was delivered to tumor cells using a herpes simplex virus-1/Epstein–Barr virus (HSV/EBV) hybrid amplicon vector in which gene expression was controlled by a tetracycline regulatory system (tet-on) with silencer elements. Upon infection and doxycycline induction of mutant channel expression in tumor cells, the open channel led to amiloride-sensitive sodium influx as assessed by patch clamp recording and sodium imaging in culture. Within hours, tumor cells swelled and died. In addition to cells expressing the mutant channel, adjacent, noninfected cells connected by gap junctions also died. Intratumoral injection of HSV/EBV amplicon vector encoding the mutant sodium channel and systemic administration of doxycycline led to regression of subcutaneous tumors in nude mice as assessed by in vivo bioluminescence imaging. The advantage of this direct mode of tumor therapy is that all types of tumor cells become susceptible and death is rapid with no time for the tumor cells to become resistant.     

Chronic Renal Disease Patients with Severe Star Fruit Poisoning: Hemoperfusion May Be an Effective Alternative Therapy

We report a case of star fruit intoxication in a 60-yr-old male patient with a past medical history of diabetes mellitus and chronic renal failure. Clinical effects included hiccups, hearing impairment, urine retention, and disturbed consciousness. Star fruit intoxication was also the suspected cause of hypothermia, an unusual symptom. The patient remained comatose after receiving two sessions of hemodialysis. However, after a 6 h session of charcoal hemoperfusion following the second hemodialysis treatment, his consciousness returned to normal within 1 day. While no previous study on hemoperfusion therapy in star fruit intoxication has been reported, in view of the fatal outcome of star fruit intoxication in uremic patients, hemoperfusion may be an alternative therapy if intensified hemodialysis fails.     

不同途径给予氨溴索针剂辅助治疗小儿肺炎临床观察

目的:评价不同途径给予氨溴索(沐舒坦)针剂辅助治疗小儿肺炎的临床疗效及安全性。方法:将同期住院的300例肺炎患儿随机分为观察组与对照组,每组150例。观察组除按所感染病原的不同常规给予合理的抗感染、对症支持治疗外,均辅以沐舒坦针剂治疗,其中观察组再随机分为沐舒坦空气压缩泵雾化吸入组(A组)、沐舒坦静脉滴注组(B组)、联合应用沐舒坦针剂雾化吸入及沐舒坦静脉滴注组(C组);对照组仅按常规方法根据感染病原的不同给予抗感染、对症支持治疗。临床观察患儿体温恢复正常时间,咳嗽气促、喉中痰鸣缓解和肺部罗音吸收等好转情况及可能的药物不良反应,并进行住院日比较。结果:观察组除A、B两组惠儿体温恢复正常时间与对照组无显著差异外,咳嗽消失时间、喉中痰鸣缓解、肺部罗音吸收等好转情况均优于对照组,住院日较对照组缩短,经统计学处理两者有显著差异(P<0.05),尤其是联合应用沐舒坦针剂雾化吸入和静脉滴注组(C组)效果更明显(P<0.01),且临床上未发现任何不良反应。A、B、C 3个观察组的治疗总有效率均比对照组明显提高,但各观察组之间临床疗效比较,并无统计学差异(P>0.05)。结论:多种途径使用沐舒坦针剂辅助治疗小儿肺炎均有较好疗效,联合使用沐舒坦雾化吸入及静脉滴注治疗效果更显著,且非常安全。     

黄芪注射液辅助治疗原发性肾病综合征的系统评价

目的:系统评价黄芪注射液辅助治疗原发性肾病综合征的疗效及安全性。方法:计算机检索维普中文科技期刊数据库(VIP)、中国知网数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库(Wangfang)、Pubmed、Cochrane图书馆、Embase(自建库起至2018年5月),全面收集黄芪注射液辅助治疗原发性肾病综合征的临床随机对照试验,然后由2名研究者遵循Cochrane手册的要求独立地进行文献筛选、数据提取及文献质量评价。运用RevMan5.3软件进行数据处理。结果:一共纳入17篇文献,包含975例患者,其中试验组511例,对照组464例,Meta分析结果显示,黄芪注射液辅助治疗原发性肾病综合征在提高总缓解率[OR=3.11,95%CI(1.93,5.01),P<0.00001]、升高血清白蛋白[MD=5.08,95%CI(3.92,6.25),P<0.00001]、减少24h尿蛋白定量[MD=-1.11,95%CI(-1.46,-0.77),P<0.00001]、降低总胆固醇[MD=-1.71,95%CI(-1.90,-1.51),P<0.00001]、降低甘油三酯[MD=-0.13,95%CI(-0.22,-0.04),P=0.0004]均明显优于单纯西药治疗,其差异具有统计学意义。结论:黄芪注射液辅助治疗原发性肾病综合征较单纯西药治疗具有明显优势,但受纳入文献的数量和质量的限制,以上结论仍需更多高质量的研究予以验证。     

Mibefradil: A New Selective T-Channel Calcium Antagonist for Hypertension and Angina Pectoris

Calcium antagonists are an established therapy for patients with hypertension and angina pectoris, but their current usage is often limited by their pharmacologic profilers and side effects. Mibefradil is a recently developed calcium antagonist with a unique chemical structure, site of action, and set of pharmacologic effects. Unlike currently available calcium channels as well as L-type channels. It is further distinguished from the other calcium antagonists in that it is the first member of a new class of calcium antagonists, the tetralol derivatives. With chronic oral dosing, mibefradil attains steady-state plasma concentrations within 3-4 days, has a bioavailability of approximately 90%, and a plasma half-life of 17-25 hours. It has a gradual onset of action and can be administered once daily without regard to food intake. It increases coronary blood flow and lowers peripheral vascular resistance. The vasodilatory effects of mibefradil are associated with a lack of inotropic effect on myocardium, lack of neurohormonal activation, and a reduction in heart rate. In clinical trials it has been demonstrated to be an effective agent in the treatment of patients with hypertension and angina pectoris, with a good safety and tolerability profile regardless of age, gender, or race.     

重度有机磷中毒患者阿托品化观察指标的探讨

目的：探讨重度有机磷中毒患阿托品化的观察指标。方法：在救治145例重度有机磷农药中毒患中，对常用的阿托品化指标及股动脉抢击音、体温等7项指标进行观察。结果：瞳孔散大和肺部湿罗音显减少两项指标在阿托品化前后无显差异(P>0．05)，而其他指标则差异非常显(P<0．01）。结论：瞳孔散大和肺部湿罗音显减少仅可作为辅助观寨指标或应用阿托品后有效的一般指征，而体温升高在37．5～38．8℃和股动脉枪击音对阿托品化的判断价值大。轻度躁动不安是判断阿托品化比较可靠的指标。     

血液净化救治急性重症中毒并急性肾功能衰竭30例的临床分析

目的：总结急性重症中毒并急性肾功能衰竭（ARF）的临床特点并探讨多种血液净化（BP）模式抢救急性重症中毒的临床疗效。方法：回顾性分析我院30例急性中毒并ARF患者,其中9例行血液透析（HD）治疗,11例行HD串联血液灌流（HD＋HP）治疗,10例采用连续性静脉-静脉血液透析滤过（CVVHDF）治疗,各组均给予综合性治疗,比较单纯HD组、HD＋HP组、CVVHDF组之间治疗效果。结果：CVVHDF组治愈率高,肾功能恢复优于其他血液净化组（P〈0．05）,昏迷者的清醒时间快,住院时间缩短（P〈0．05）,无明显毒副作用。结论：CVVHDF、HD＋HP血液净化治疗抢救各种急性中毒并ARF患者成功率高,对急性重症中毒伴多器官功能障碍者,提倡早期行CV—VHDF治疗,同时重视洗胃、营养支持、水电解质酸碱平衡、抗感染等综合治疗,以利于急危重症中毒患者的救治。     

白介素-Ⅱ辅助治疗空洞型肺结核的疗效及护理

目的 探讨白介素-Ⅱ辅助治疗空洞型肺结核的疗效及护理.方法 将50例空洞型肺结核病者随机分为2组,实验组采用白介素-Ⅱ联用链霉素 利福平 异烟肼 对氨水杨酸(SRHP)方案治疗空洞型肺结核1个月,对照组单用SRHP方案常规治疗.观察空洞病灶愈合的程度和痰菌阴转率.结果 实验组患者的空洞病灶各有不同程度的愈合,痰找抗酸杆菌呈阴性;而对照组空洞病灶无明显改变,痰菌阴转率较低.结论 白介素-Ⅱ安全可靠.做好心理护理和病情观察对提高空洞型肺结核的疗效具有重要意义.     

Nephrotoxicity After Acute Severe Acetaminophen Poisoning in Adolescents

Objective: To determine the rate of acetaminophen related nephrotoxicity in adolescents who present after acute severe acetaminophen intoxication and to identify potential predictors of this outcome. Study Design: Retrospective analysis of consecutive patients between the ages of 12 and 18 years who were admitted at a tertiary care children's hospital for treatment of acute severe acetaminophen intoxication with N-acetylcysteine. The main outcome measure was the frequency of acetaminophen-related nephrotoxicity, defined as abnormal blood urea nitrogen (> 6.4 mmol/L or >18 mg/dL) and/or elevated creatinine (97.2 μmol/L or >1.1 mg/dL) in association with one or both of the following: elevated blood pressure (systolic blood pressure >140 mm Hg/diastolic blood pressure >85) or abnormal urinalysis (urinalysis with hematuria or proteinuria). Statistical analyses used were measures of central tendency, Student's t-test, Mann-Whitney, and multivariate logistic regression. Results: Fourty-five patients were included. Acetaminophen-related nephrotoxicity occurred in 4 (8.9%) cases. One victim developed severe renal injury in association with elevated hepatic transaminases. Intergroup analyses revealed no statistically significant association between acetaminophen-related nephrotoxicity and amount/kg of acute severe acetaminophen ingested, delay in treatment with N-acetylcysteine, or measures of hepatic function. Conclusions: Acetaminophen-related nephrotoxicity occurred in 8.9% [95% CI: 4.52, 20.48] of children with severe overdose. There are no obvious predictors of this complication of acetaminophen overdose. Because the occurrence of renal injury can not be predicted, serial blood pressure, blood urea nitrogen/creatinine, and urinalysis should be considered an integral part of the management of children with acute, severe acetaminophen intoxication.     

Fulranumab as Adjunctive Therapy for Cancer-Related Pain: A Phase 2, Randomized,Double-Blind,Placebo-Controlled,Multicenter Study

This randomized, double-blind (DB), placebo-controlled, phase 2 study assessed the efficacy and safety of fulranumab as a pain therapy adjunctive to opioids in terminally ill cancer patients. Ninety-eight patients were randomized (2:1) to receive one subcutaneous injection of fulranumab (9 mg) or placebo in the 4-week DB phase. Seventy-one (72%) patients entered the 48-week open-label extension phase and were administered 9 mg of fulranumab every 4 weeks. The study failed to demonstrated efficacy at the end of the DB phase (primary endpoint, mean [SD] change in average cancer-related pain intensity was ?.8 (1.26) for fulranumab and ?.7 (1.56) for placebo; P?=?.592). However, potential benefit is suggested based on secondary endpoints (30% responder rate [P?=?.020], Brief Pain Inventory-Short Form [BPI-SF] pain intensity subscale [P?=?.003], and pain interference subscale [P?=?.006]). The most commonly reported treatment-emergent adverse events were (fulranumab vs placebo): asthenia (16% vs 10%), decreased appetite (12% vs 6%), fatigue (10% vs 0%), and malignant neoplasm progression (10% vs 0%). Although no differences were seen between fulranumab and placebo groups on the primary endpoint, improvements in BPI-SF pain subscale scores and responder rates support further research of anti-nerve growth factor therapy in cancer-related pain.