Are Central Eastern European countries involved in clinical trials of supportive care?

Clinical trials are the most widely accepted tools in the search for more effective supportive care drugs/interventions. The aim of our study was to determine Central Eastern European countries' (CEEC) involvement and future interest in conducting supportive care clinical trials. Our study was a part of an ESMO/MASCC program launched to support the development of supportive care in CEEC. The study was designed as a mailed questionnaire survey within the ESMO CEE Task Force. It involves national representatives from 18 countries. The purpose of the questionnaire was to assess the involvement and interest in conducting clinical trials in 13 representative supportive care fields: antiemetic therapy, cancer pain control, infections/febrile neutropenia, mucositis, fatigue, hypercalcemia, dyspnea, anorexia/cachexia, psychosocial support, toxicity reducing agents, hematopoietic growth factors, communication/education and quality of life. A total of 15 completed questionnaires were returned (83.3%). CEEC were mainly involved in clinical trials of hematopoietic growth factors (7/15), quality of life (6/15), antiemetic therapy (5/15), and cancer pain control (4/15). Increased interest was observed in the trials of fatigue, dyspnea, psychosocial support, infections / febrile neutropenia, communication / education and toxicity reducing agents. Clusters of CEEC that are similar in terms of their previous involvement and future interest in supportive care trials were identified. Our survey may prove to be a significant first step for CEEC active involvement in multinational clinical trials, which are crucial for improving supportive care standards.     

Conformational State-dependent Effects of Halothane on Cardiac Na sup + Current

Background: The Na sup + channel is voltage gated and characterized by three distinct states: closed, open, and inactivated. To identify the effects of halothane on the cardiac Na sup + current (INa) at various membrane potentials, the effects of 1.2 mm halothane at different holding potentials (VH) on INa were examined in single, enzymatically isolated guinea pig ventricular myocytes.

Methods: The INa was recorded using the whole-cell configuration of the patch-clamp technique. Currents were generated from resting VH s of -110, -80, or -65 mV. State-dependent block was characterized by monitoring frequency dependence, tonic block, and removal of inactivation by veratridine.

Results: Halothane produced significant (P < 0.05) VH -dependent depressions of peak INa (mean +/- SEM): 24.4 +/- 4.1% (VH = -110 mV), 42.1 +/- 3.4% (VH = -80 mV), and 75.2 +/- 1.5% (VH = -65 mV). Recovery from inactivation was significantly increased when cells were held at -80 mV (control, tau = 6.0 +/- 0.3 ms; halothane, tau = 7.1 +/- 0.4 ms), but not at -110 mV. When using a VH of -80 mV, halothane exhibited a use-dependent block, with block of INa increasing from 8.6 +/- 1.4% to 30.7 +/- 3.5% at test pulse rates of 2 and 11 Hz, respectively. Use-dependent inhibition was not apparent at VH of -110 mV. When inactivation of INa was removed by exposure to 100 micro Meter veratridine, no significant difference was observed in the depressant effect of halothane at both VH s: 26.6 +/- 4.5% (VH = -80 mV) and 26.4 +/- 5.6% (VH = -110 mV).     

Loss of T-type Calcium Current in Sensory Neurons of Rats with Neuropathic Pain

Background: Pathophysiology in the primary sensory neuron may contribute to chronic neuropathic pain. Ca channels play a central role in neuronal processes, and sensory neurons are rich in low-voltage-activated calcium channels (LVACCs). However, the physiologic function of these channels is unknown. Their possible role in rebound burst firing makes them a candidate for increased excitability after neuropathic injury.

Methods: This study uses pharmacological methods to isolate LVACC in cells from the dorsal root ganglia of neuropathic and sham-operated rats, including the blockade of high-voltage-activated Ca channels with fluoride and selective toxins. LVACCs were examined with conventional whole cell patch clamp electrophysiology techniques.

Results: After chronic constriction injury of the peripheral axon, LVACC was significantly reduced compared to sham rats as shown by a 60% reduction in peak current density and an 80% reduction in total calcium influx. A depolarizing shift in the voltage dependence of activation and an increase in the rate of deactivation and inactivation appear to cause this reduction of LVACC. Either Ni2+ or mibefradil, blockers of LVACC, applied in the bath to normal dorsal root ganglion cells during current clamp significantly and reversibly increased excitability.     

冠状动脉粥样硬化性心脏病的当代治疗

0　引言冠状动脉粥样硬化性心脏病(简称冠心病)治疗在20世纪60年代以前是药物治疗为主,到了20世纪70年代,外科采用冠状动脉旁路术开辟了冠心病治疗的新途径.进入20世纪80年代,冠状动脉旁路术在西方发达国家已经非常成熟,非常普遍.同时期,内科介入治疗也迅速发展起来,下面就各种治疗方法的进展分别进行讨论.1　内科治疗1.1　药物治疗　冠心病的药物治疗随着患者病情不同而不同.对一般常有心绞痛发作的患者常用药物主要有两类,一类是扩张冠状动脉血管,减轻心脏缺血,缓解或预防心绞痛.这类药物主要有硝酸盐制剂,如硝酸甘油、亚硝酸异戊酯、四硝…     

急诊体外循环抢救急性心脏损伤8例

0　引言　体外循环技术已越来越普及,为了推广该项技术,我们介绍体外循环技术在急诊室的应用.1　临床资料　1993-03/1999-05我们遇到急性心脏损伤8例,全部为男性,年龄23～78(平均44.5)岁;急诊体外循环下行手术治疗,存活5例,死亡3例,成活率62%.1例老年患者,因急性心梗发作,心肌破裂5min来院,急诊开胸手术.见左室壁3处大面积梗死,后壁破裂,急建体外循环,,行修补术.但复温过程中前壁及后壁均发生破裂,无法修补而至手术失败.1例工人,施工中不慎被高压电击伤,从右肩至左踝穿出.来院后行急诊开胸心脏按摩,左室呈石头心样改变,急诊体外循环进行辅助…     

肢端型系统性硬皮病误诊1例

1　病例报告　女 ,45岁 ,因吞咽困难 16 mo伴发热 15 d,于1999- 0 7- 12入院 .于 16 mo前与人争吵后出现吞咽困难 ,以进食馒头、面条为著 ,剑突下有时出现梗噎感 ,随即呕吐 ,呕出所进食物及粘液 ,情绪波动可诱发症状加重 ,伴食欲减退、返酸 .15 d前无诱因出现不规则发热 ,T38～ 39℃ ,上腹痛加重 ,全身酸困不适 ,乏力、头晕、消瘦 .追问病史 ,患者 5 a前双手、足疼痛麻木 ,尤以受凉、精神刺激后明显 ,手指初发白 ,继而发紫 ,变红 ,且麻木疼痛加重 ,手足小关节渐僵硬、畸形 .曾到多家医院就诊 ,诊断 :“雷诺病、类风湿性关节炎”.2 a前出现…     

The effects of the new antiarrhythmic E 047/1 on postoperative ischemia-induced arrhythmias in dogs

Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens. IMPLICATIONS: Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.     

Electrical thresholds for biomechanical response in the ankle to direct stimulation of spinal roots L4, L5, and S1. Implications for intraoperative pedicle screw testing

STUDY DESIGN: A comparison of electrical thresholds for biomechanical response in the ankle and for evoked electromyographic signals from specific leg muscles during intraoperative extradural direct stimulation of roots L4, L5, and S1. OBJECTIVE: To determine whether a biomechanical response in the ankle to direct root stimulation occurs before evoked electromyographic signals and to determine differences in electrical excitability of the roots circumferentially. SUMMARY OF BACKGROUND DATA: Stimulus intensities of 1.2-5.7 mA are reported to evoke electromyographic response in corresponding muscles to direct stimulation of normal roots. Stimulus intensities of 6-8 mA were suggested to detect bony pedicular compromise by stimulation of a hole or a screw during pedicle instrumentation. Electrical thresholds of three-dimensional torque response in the ankle to direct root stimulation have not yet been evaluated and compared with thresholds of evoked electromyogram. METHODS: Direct monopolar stimulation of the surgically exposed roots L4, L5, and S1 was performed from different sites around the root by a cuff multielectrode. Biomechanical response was measured as an isometric torque in the ankle at each of three orthogonal axes. Compound muscle action potentials (CMAPs) from root-specific muscles were detected by a pair of surface or wire electrodes. RESULTS: Mean threshold for biomechanical response in the ankle to stimulation of roots L4, L5, and S1 was 0.72 +/- 0.39 mA and for CMAP response was 1.09 mA +/- 0.36 (N = 13). Thresholds for biomechanical responses were significantly lower than for CMAP responses (P = 0.0004; paired t test). Nerve roots were electrically most excitable on their ventral aspects. CONCLUSION: The biomechanical response in the joint to root stimulation can be used to test all root-related muscles crossing that joint at their individual innervation pattern and their residual innervation and to detect electrical excitation of the root at electric thresholds lower than those for detecting CMAP from single standard root-specific muscle. However, this method does not provide sufficient root specificity. It will be valuable in conjunction with multimodality neurophysiologic monitoring of the roots for earlier and more reliable detection of pedicle bone breakthrough or integrity. Further clinical investigations are suggested.     

Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.     

Expression and characterization of Gag protein of HIV-1（CN） in Pichia pastoris

To express the core protein of HIV-1 of Chinese prevalent strain （HIV-1 （CN）） in Pichia pastoris, the fulllength gag gene was inserted into the secretory expression vector pHILS1. Linearized recombinant plasmid pHILGAG by Sail was electrotransformed into the yeast strain GS115, and the yeast transformants were identified by PCR. To induce the interest protein to be expressed, the PCR positive transformants were inoculated in the medium of BMGY and BMMY, mRNA of the strain was detected by RT-PCR, and the expressed protein was analyzed by SDS-PAGE, Western blotting and thin layer scanning. mRNA （1.3 kb） was amplified by RT-PCR. SDS-PAGE and Western blotting analysis showed that the molecular mass of the expressed protein was 55 kD, which was similar to the expected value, and the expressed protein could react with McAb to HIV-1 p24. Thin layer scanning analysis demonstrated that the whole amount of the expressed protein was approximately 13 % of the soluble protein in the supernatant. The recombinant yeast had good genetic stability. The optimal expression conditions of the engineering yeast were as follows： BMMY medium, 80-90% of dissolved oxygen, 1% methanol, and 3-day-cultivation course. Gag proteins were expressed under the optimal expression condition and purified via gel filtration chromatography. The purity of the interest protein was up to 85 %. After the purified proteins were inoculated into BALB/c mice, the anti-HIV-1 antibodies in the immunized mice could be detected by Western blotting.