Effects of Lidocaine on Shock-Induced Vulnerability

Introduction: Lidocaine is known to increase the defibrillation threshold (DFT) of monophasic shocks (MS) and have no effect on DFT of biphasic shocks (BS). The aim of this study was to enhance our understanding of the mechanisms of vulnerability and defibrillation through the investigation of this difference.
Methods and Results: We studied the effect of 15 μM lidocaine on shock-induced vulnerability using fluorescent imaging of Langendorff-perfused rabbit hearts. Vulnerability was assessed as vulnerable window with shock strengths of 15 to 150 V and vulnerable period (VP) with shock delivery phase of 0% to 100% of action potential duration (% APD). With MS, lidocaine caused a significant increase in both the upper limit of vulnerability (ULV, 71 ± 17 V vs 120 ± 1.5 V, P < 0.01) and upper limit of VP (91 ± 8.0% APD vs 110 ± 4.2% APD, P < 0.01). With BS, lidocaine had no effect on ULV (40 ± 3.4 V vs 45 ± 4.5 V) and did not increase the upper limit of VP (78 ± 8.9% APD vs 96 ± 12% APD, P < 0.01). Lidocaine caused reduction of the conduction velocity during pacing (0.58 ± 0.08 m/s vs 0.44 ± 0.05 m/s, P < 0.01), shock-induced break excitation (0.82 ± 0.17 m/s vs 0.30 ± 0.07 m/s, P < 0.01), and postshock reentry (0.34 ± 0.07 m/s vs 0.19 ± 0.08 m/s, P < 0.01). Lidocaine had no effect on shock-induced virtual electrode polarization.
Conclusion: Lidocaine increased MS ULV due to slowing of shock-induced break-excitation wavefronts, which resulted in enhanced probability of survival of virtual electrode induced phase singularity. Lidocaine had no effect on BS ULV because no break excitation was induced by BS. Reduction of conduction velocity by lidocaine resulted in increased dispersion of repolarization and led to upper limit of VP increase for both MS and BS. (J Cardiovasc Electrophysiol, Vol. 14, pp. S237-S248, October 2003, Suppl.)     

Prophylactic diclofenac infusions in major orthopedic surgery: effects on analgesia and acute phase proteins

The influence of diclofenac, given by continuous i.v. infusion starting preoperatively, on postoperative pain and inflammation was assessed in a double-blind, randomized, placebo-controlled study in 40 patients scheduled for major orthopedic surgery. Starting 30 min before induction the patients received either diclofenac (0.35 mg.kg-1 bolus followed by a constant-rate infusion of 90 micrograms.min-1) or placebo for 24 h. The pain intensity (VAS) and the amount of rescue narcotic (piritramide on demand) were significantly lower in the diclofenac group from 4 and 6 h postsurgery, respectively, till end of infusion. Acute phase proteins used as inflammation markers (C-reactive protein, alpha 1-chymotrypsin, alpha 1-acid glycoprotein, haptoglobin and coeruloplasmin) showed similar variations in both groups for 24 h. The diclofenac treatment had no influence on hematological and coagulation profiles, nor on muscle and liver enzymes in comparison with placebo. Both patients and observer rated the diclofenac treatment as significantly superior to the placebo treatment.     

Phase II study of low dose cyclophosphamide and intravenous interleukin-2 in metastatic renal cancer

Thirteen patients with metastatic renal cancer were treated in a phase II trial with interleukin-2, 21.6 million IU/m² intravenously daily for five days on two consecutive weeks, starting 3 days after the administration of low dose cyclophosphamide 350 mg/m² intravenously. Treatment cycles were repeated every 21 days. No responses were seen (95% Confidence Interval: 0–22%). The most common toxicities were fever, fatigue, hypotension, nausea/emesis, and myalgia/arthralgia. There were 11 episodes of Grade III toxicity including Grade III hypotension in 7 patients. Because of the significant toxicity and the lack of observed response, the study was discontinued. Cyclophosphamide and interleukin-2 at the dose and schedule used in this study has considerable toxicity and is unlikely to improve on response rates previously seen with other IL-2-based regimens in metastatic renal cancer.     

A phase I study of sulofenur in refractory pediatric malignant solid tumors

Summary The diarylsulfonylureas have shown promise in xenograft models of childhood cancer. Sulofenur has been evaluated in phase I and II trials in adults with a variety of solid tumors, but the toxicity and maximum tolerated dose of sulofenur in children and adolescents have not been determined. In a phase I study, sulofenur was administered to 13 patients with refractory pediatric malignant solid tumors. Daily dosages of 640, 800, and 960 mg/M² in two divided oral doses were given for 5 consecutive days each week for 3 weeks. The primary and dose-limiting toxicity was methemoglobinemia, which occurred at all dose levels and required transfusions of packed red blood cells, administration of methylene blue, or both. Anemia and, less frequently, leukopenia and thrombocytopenia were also observed. A maximum tolerated daily dosage was not defined, as methemoglobinemia was noted with each dosage level. There were no measurable tumor responses. The toxicity of this agent makes it unattractive for further investigation in pediatric patients.     

A phase II trial of paclitaxel (Taxol®) as first line treatment in advanced breast cancer

Summary Paclitaxel (Taxol®) is a natural product with a broad spectrum of activity against various solid tumors. This report includes nineteen patients with advanced breast cancer who have not previously received chemotherapy for metastatic disease. Fifteen patients had received adjuvant chemotherapy, eight of which were doxorubicin based. Patients were treated with 135 mg/m² over 24 hours by continuous infusion given every 21 days. There were 2 complete and 4 partial responses for an objective response rate of 32% (95% C.I.: 14%, 57%) and eight patients or 42% with stable disease. Three of eight patients (38%) who had received adjuvant doxorubicin did respond to paclitaxel. Responses occurred in lung, liver, and soft tissue. The primary toxicity was hematologic with 13 hospitalizations for febrile neutropenia in 180 cycles (7%). Paclitaxel has moderate activity in a small number of patients with metastatic breast cancer at the dose of 135 mg/m² over 24 hours in this study.     

导纳血液循环自动检测仪检测结果的数据处理

利用HD-3181型导纳血液循环自动检测仪分别对心肌缺血前、后的家兔进行采集，为使采集到的导纳微分环波形数据进行量化分析，本文介绍了使用计算机技术定位导纳微分图上的特征点，并按时相将形成导纳微分环的导纳、导纳微分原始数据，以及各项参数的计算结果输出到数据文件中，对导纳微分环数据进行更深入的研究，为临床更好地应用导纳微分环技术提供理论依据。     

头颈部鳞状细胞癌DNA含量与临床生物学行为的关系

目的：研究头颈部鳞状细胞癌（HNSCC）DNA倍体的变化与临床生物学行为的关系。方法：选择40例未经治疗的HNSCC患术后新鲜肿瘤标本，采用流式细胞仪（FCM）测定DNA含量的3个主要参数，异倍体（aneuploid),DNA指数（DNA Index,DI)和S期细胞比例（S－phase fraction,SPF)，探索3个参数与肿瘤组织学分级，临床分期以及淋巴结转移之间的关系。结果：40例未经治疗的HNSCC中，异倍体检出率为62．5％（25／40）。DI与淋巴结转移无关，与肿瘤组织学分级和肿瘤临床分期有关（P＜0．01）。SPF与肿瘤组织分级无关，与临床分期及淋巴结转移有关（P＜0．01）。结论：DNA异倍体是HNSCC的重要特征之一；DI和SPF可作为预测头颈部鳞状细胞癌生物学特性的重要指标。     

Multishot partial-k-space EPI for high-resolution fMRI demonstrated in a rat whisker barrel stimulation model at 3T.

A multishot partial-k-space EPI technique is presented and validated by fMRI at high spatial resolution. High-resolution phase maps corrected by phase-encoded reference scans have less off-resonance effects. Phantom studies demonstrate that this method can substantially improve partial-k-space EPI image formation. BOLD fMRI at submillimeter spatial resolution (156 x 156 x 2000 microm(3), 0.049 microl) was achieved in a rat whisker barrel stimulation model using this technique. The study included eight rats, five of which were administered an intravascular contrast agent (monocrystalline iron oxide nanocolloid (MION)) after the BOLD experiments. In two rats the highest BOLD responses were in the deep layers (IV-VI), and in six rats the highest responses were on the surface and in the deep cortical layers. Most of the pixels that exhibited high BOLD responses had high blood volume weightings. The benefits of this technique are expected to increase for high-resolution fMRI at higher magnetic fields, where T(2) (*) is shorter.