Ventricular fibrillation related to reversal of the neuromuscular blockade in a patient with long QT syndrome

The long QT syndrome (LQTS) is associated with syncopal attacks or even sudden death at a young age due to ventricular fibrillation. We report a patient with an undiagnosed LQTS who had an episode of cardiac arrest during the final part of general anesthesia, immediately after the drugs for reversal of the neuromuscular blockade were given. We suggest that the administration of glycopyrronium might have been the provoking factor in this patient.     

Preparing Older People to Cope after a Fall

Clinical experience and previous research show that older people at risk of falling can become anxious at the thought of being on the floor, therefore physiotherapists and occupational therapists may be reluctant to teach them how to get up.Old people's reactions to two different methods of teaching them this skill are compared (three groups, mean age 84 years). The conventional method requires people to be helped down to the floor and then to learn how to get on to their knees prior to getting up with the help of furniture. An alternative method, based on backward-chaining principles, does not require that people start from the floor and reduces the likelihood of them experiencing failure. The activity is broken down into small steps — the last step in the chain being taught first.It is concluded that:

1 The backward-chaining method of teaching elderly people how to get up from the floor is much less stressful to older people and to staff than the conventional method.

2 Older people are slightly more likely to learn successfully how to get up from the floor by the backward-chaining method which, even if they are not successful, provides them with functionally relevant exercise.

3 Older people who cannot learn to get up from the floor should be helped to develop alternative strategies for summoning help and for preventing the consequences of the long lie.

Plasma level monitoring of mitotane (o,p'-DDD) and its metabolite (o,p'-DDE) during long-term treatment of cushing's disease with low doses

Summary. Mitotane (o,p'-DDD) can be used for the treatment of various adrenocortical diseases such as Cushing's syndrome, but the usual doses of 6–8 g per day are often associated with severe adverse effects.This paper reports the results of much lower doses of o,p'-DDD (0.5–2 g per day) in two patients with Cushing's disease over periods of 8 and 5 years, respectively, under concomitant monitoring of the plasma levels of the parent drug and its major metabolite, o,p'-DDE.It became apparent that o,p'-DDD and o,p'-DDE have a strong tendency to accumulate in the body due to their high lipophilicity. As a consequence, changes in dose regimens had long lag times before they were reflected in plasma levels and once an increase or decrease had started one had to be careful not to cause overshoot.Steady state plasma levels of o,p'-DDD between 5–10 g/ml appeared sufficient to induce and to maintain remission of the disease, which was accompanied with normal cortisol levels in plasma and urine. DDD-levels below 5 g/ml for several weeks may lead to relapses, whereas DDD-levels over 10 g/ml gave rise to side effects. On the other hand, o,p'-DDE seemed inactive at levels up to 4 g/ml in plasma.     

Ventricular arrhythmia and torsade de pointe: Dose limiting toxicities of the MDR-modulator S9788 in a phase I trial

Background: S9788 is a triazineaminopiperidine derivative capable of reversing multidrug resistance (MDR) in vitro. In preclinical models S9788 was several fold more potent MDR inhibitor than verapamil or cyclosporine. At P-glycoprotein (Pgp) blocking concentrations, S9788 appeared to have only very little toxicity.Patients and methods: In a two step phase I trial we treated 39 patients with refractory cancer with S9788 and bolus doxorubicin. The steps differed mainly in the S9788 infusion duration; in the first part 23 patients received the MDR-reversing drug S9788 over 30 minutes, in the second step of the study 16 patients were administered S9788 over 150 minutes. The doses of S9788 were escalated in cohorts of three patients up to a dose level (DL) of 96 mg/m2 on the 30 minutes infusion, and to 144 mg/m2 on the 150 minutes infusion. The pharmacokinetics of S9788 were determined.Results: With the 30-minute infusion schedule symptomatic cardiac arrhythmia were found to be dose limiting. In all patients at the highest DL transient cardiac repolarization prolongation with a long QT-interval on ECG was demonstrated. With the 150-minute administration schedule, S9788 could be escalated up to 144 mg/m2 without subjective toxicity. However, transient QT prolongation was present in all patients. A third degree AV-block and a QT increase of about 40% occurred at the highest DL. Asymptomatic torsade de pointe (DL 96 mg/m2) was demonstrated on Holter recording in one patient. Theses repolarization disturbances with QT increase were considered dose limiting toxicity and the trial was closed. No arrhythmia related death was noted. Pharmacokinetics were similar with both infusion schedules with a mean alpha half life of 11.3 and 13.2 minutes, for the 30-minute and 150-minute infusion, and a terminal half life of 13.5 and 15 hours, respectively. QTc prolongation duration appeared to be dose-dependent.Conclusions: With the tested infusion schedules, cardiac toxicity, in particular AV-blocks and QT prolongation, leading to ventricular arrhythmia and torsade de pointe, are the dose limiting toxicities of S9788. Our experience together with the observation of asymptomatic torsade de pointe in two other phase I trials of S9788 infused over six hours precluded the further clinical development of S9788.     

市售中长链脂肪乳注射液的质量评价

目的对市售2厂家产20％，的中长链脂肪乳注射液各3批进行质量比较。方法参考国内外同类产品质量标准，从性状、pH值、乳粒大小、游离脂肪酸、过氧化值、甘油、大豆油、中链甘油三酯、卵磷脂含量、溶血磷脂量、甲氧基苯胺值和细菌内毒素等方面进行比较。结果外观均为白色乳状液，pH值在7．83～8．37间，没有大于5μm的乳粒，大于1μm的乳粒在0．58％～1．67％间，游离脂肪酸在0．69～0．78mmol／L间，过氧化值在0．05～0．31mmol／L间，甘油在24，50～25．20mg／ml间，大豆油、中链甘油三酯和卵磷脂的含量均在标示量的97%以上，溶血磷脂在0．325～0．715mg／ml间，甲氧基苯胺值在0．90～2．86间，细菌内毒素均小于0．3EU／ml。结论有必要提高对脂肪乳的质控标准，以提高临床用药的安全性。     

长学制临床药学专业的开设

就我国临床药学教育现状提出了开展临床药学教育的重要性和必要性 ,针对该专业的特殊性提出开设长学制临床药学专业的设想 ,并对其培养目标、课程设置、实施方法、须解决的问题等方面进行了探讨     

柴黄益肾方提取物的长期毒性实验研究

目的：观察柴黄益肾方提取物（CYE）对大鼠的长期毒性,为临床安全用药提供依据.方法：将大鼠随机分为4个组,3个剂量组分别按8.8g/kg、4.4g/kg、2.2g/kg连续灌胃给予CYE 6个月,对照组给予同体积生理盐水.停药后继续观察4周,测试大鼠体重、血液学指标、血液生化学指标、脏器指数及病理组织学变化.结果：高剂量组大鼠体重增长缓慢,3个剂量组与红细胞相关指标与对照组比较小幅下降,尿素氮与对照组比较小幅上升,高中剂量组肝脏指数小幅上升,与对照组比较有显著性差异,以上改变均在正常生理范围之内.结论：CYE在临床推荐剂量下有一定的安全性.     

四肢长骨病理性骨折的治疗

目的分析石膏托和交锁髓内钉治疗股骨、胫骨、肱骨、桡骨病理性骨折的疗效。方法30例病理骨折(26例骨折、4例临界骨折)采用交锁髓内钉治疗,9例采用石膏托外固定。6例良性病变行病灶刮除、自体和(或)异体骨移植;15例转移癌13例行病灶姑息切除、骨水泥填充加强,2例单纯闭合穿钉固定。结果6例良性病变患者获随访,骨折首次术后平均4.5个月愈合;因复发或内固定失败需再手术2例。15例转移癌获随访,疼痛缓解功能恢复满意。结论交锁髓内钉是治疗股骨、胫骨、肱骨病理性骨折理想的内固定物,外固定可缓解疼痛,但有关节僵硬等并发症。     

饮用天然矿泉水人群健康调查

目的 调查了解湖南省天然矿泉水饮用人群的健康状况。方法选择长期饮用天然矿泉水人群为观察组，条件相近不饮用矿泉水人群为对照组，对比两组间健康指标的差异。结果 长期饮用天然矿泉水人群平均期望寿命(e^9)为72．04岁，比不饮用天然矿泉水的对照组人群e^0高出2．99岁，平均死亡年龄要高4．15岁，总患病率要低14．3％，人均医疗费用开支要少28．6％；男女小学生生长发育：男生身高高3．06cm，女生身高高4．26cm；男生体重重2．51kg，女生体重重3．40kg；男生胸围大1．62cm，女生胸围大1．81cm。结论长期饮用天然矿泉水人群的健康状况要优于条件相近不饮用矿泉水人群。