Trizivir^TM治疗80例HIV／AIDS患者临床研究

目的1．评估Trizivir^TM（AZT＋3TC＋ABC，TZV）治疗中国HIV／AIDS患者的疗效和安全性；2．HIV／AIDS患者的依从性；3．考察中国社区内HIV／AIDS患者服用固定剂量三联片治疗的可行性。方法80例HIV／AIDS患者进入治疗组。是一项单中心、开放式、无对照的临床试验。患者接受36个月的治疗，在治疗1，2，3，4，5，6，9，12，18，24，30和36个月按时到门诊随访。结果57例（71．3％）患者完成36个月治疗随访，23例（28．7％）在治疗过程中因药物不良反应、机会性感染复发、依从性不好或治疗失败而退出。57例治疗36个月后，CD4＋ T淋巴细胞计数平均增加252／μL，93．0％的患者显示病毒载量〈400拷贝／mL。在36个月的治疗期间，有4例患者出现耐药。结论TZV抗病毒效果显著，对于病毒载量〉500000拷贝／mL的患者也有很好的效果，CD4＋T淋巴细胞计数均显示明显增加。TZV不良反应较少，与其他药物的相互作用较少，服用方便，患者服药依从性好，对某些患者尤其有毒瘾者不失为一种可以选用的治疗方案。     

Hemodynamic Effects and Clinical Determinants of Defibrillation Threshold for Transvenous Atrial Defibrillation Using Biatrial Biphasic Shocks in Patients with Chronic Atrial Fibrillation

We assessed the relationship between the hemodynamic changes and shock intensity in transvenous atrial defibrillation for chronic AF. The correlation between the clinical profile and atrial DFT and the factors predicting maintenance of SR after successful defibrillation were also investigated. Atrial defibrillation using entirely transvenoas leads has been investigated as an alternative means of managing patients with AF. However, the hemodynamic consequence of this technique and the clinical factors predicting defibrillation efficacy have not been evaluated. Thirty-seven patients with chronic AF (4 weeks to 60 months) underwent transvenoas atrial defibrillation. Defibrillation was performed by delivering R wave synchronized, biphasic (3/3 ms) shocks with step-up voltages (20–400 V) between defibrillation catheters in the anterolateral right atrium and the distal coronary sinus. Clinical profile of the patients, the DFT, arterial blood pressure, and RH interval during defibrillation and the 6-month recurrence rate were determined. SR was restored in 33 (89%) of 37 patients and the DFT was 3.7 ± 1.4 J (317 ± 58 V). Transvenous atrial defibrillation resulted in a mild reduction in blood pressure (6 ± 10 mmHg), but substantial prolongation of longest postshock RR intervals (507 ± 546 ms), which were significantly related to the shock intensity (r = 0.5, P < 0.001). There was no ventricular proarrhythmia. The patients'age, body weight, duration of AF, left atrial diameter, and ejection fraction were not related to the success of defibrillation, not the 6-month maintenance rate of SR (39%). However, the patients'age was related to DFT. Apart from transient reduction in blood pressure and shock related pauses that may require backup pacing, transvenous biatrial defibrillation was a highly effective and well-tolerated technique. The absence of clinical determinant for successful defibrillation suggests that restoring SR by transvenous atrial defibrillation could be attempted in most patients with chronic AF.     

GADD45β基因表达诱导对不同p53状态的肝癌细胞作用

目的：体外合成GADD45β基因全序列表达质粒后，研究GADD45β基因表达诱导对呈不同p53状态的肝癌细胞的作用及可能机制。方法：采用RT-PCR法获得GADD45β基因全序列，插入pDrive穿梭克隆载体和pIRES2-EGFP荧光表达载体后大量扩增获得DNA，结合p53全基因表达质粒pp53-EGFP转染HepG2、Hep3B细胞后，以[^3H]胸腺嘧啶脱氧核苷掺入法(^3H—Tdr)和细胞克隆形成法分析DNA合成变化及细胞生长能力；以双抗体夹心ELISA法测定TGF-β1表达变化。结果：成功合成GADD45β基因全序列和表达质粒，通过流式细胞仪收集转染阳性的荧光表达细胞能显著提高转染效率；转染GADD45β后．具有野生型p53基因的HepG2细胞的细胞克隆形成能力和DNA合成能力明显受到抑制，细胞凋亡明显增加，TGF-β1的表达亦明显受抑。与之相反，缺失p53基因的Hep3B需要同时共转染p53基因后，方出现抑制效应。结论：GADD45β基因能够有效抑制肝癌细胞的生长．其功能需要完整p53基因的辅助和(或)调控。GADD45表达和（或)功能异常，导致p53介导的DNA损伤修复途径异常或阻断，是肝脏细胞恶性转化及形成肿瘤的可能机制。     

High Density Endocardial Mapping of Shifts in the Site of Earliest Depolarization During Sinus Rhythm and Sinus Tachycardia

BETTS, T.R., et al. : High Density Endocardial Mapping of Shifts in the Site of Earliest Depolarization During Sinus Rhythm and Sinus Tachycardia. Previous mapping studies of sinus rhythm suggest faster rates arise from more cranial sites within the lateral right atrium. In the intact, beating heart, mapping has been limited to epicardial plaques or single endocardial catheters. The present study was designed to examine shifts in the site of the earliest endocardial depolarization during sinus rhythm and sinus tachycardia using high density activation mapping. Noncontact mapping of the right atrium during sinus rhythm was performed on ten anesthetized swine. Recordings were made during sinus rhythm, phenylephrine infusion, and isoproterenol infusion. The hearts were then excised and the histological sinus node identified. The mean minimum and maximum cycle lengths recorded were   355 ± 43   and   717 ± 108 ms   . A median of three (range two to five) sites of earliest endocardial depolarization were documented in each animal. With increasing heart rate the site of earliest endocardial depolarization remained stationary until a sudden shift in a cranial or caudal direction, often to sites beyond the histological sinoatrial node. The endocardial shift was unpredictable with considerable variation between animals; however, faster rates arose from more cranial sites   (r = 0.46, P = 0.023)   . There was no difference in the mean cycle length of sinus rhythm originating from specific positions on the terminal crest   (r = 0.44, P = 0.17)   . Cranial sites displayed a more diffuse pattern of early depolarization than caudal sites. In the porcine heart the relationship between heart rate and site of earliest endocardial depolarization shows considerable variation between individual animals. These findings may have implications for clinical mapping and ablation procedures. (PACE 2003; 26[Pt. I]:874–882)     

Factors affecting mortality of critical care trauma patients

Background

Critically-ill trauma patients have a high mortality.

Objective

To study the factors affecting the mortality of ICU trauma patients treated at Al-Ain Hospital, United Arab Emirates (UAE).

Methods

All trauma patients who were admitted to the ICU were prospectively collected over three years (2003–2006). Univariate and multivariate analysis were used to compare patients who died and who did not. Gender, age, nationality, mechanism of injury, systolic blood pressure and GCS on arrival, the need for ventilation, presence of head or chest injuries, AIS for the chest and head injuries and the ISS were studied.

Results

There were 202 patients (181 males). The most common mechanism of injury was road traffic collisions (72.3 %). The overall mortality was 13.9%. A direct logistic regression model has shown that factors that affected mortality were decreased GCS (p < 0.0001), mechanism of injury (p = 0.004) with burns having the highest mortality, increased age (p = 0.004), and increased ISS (p = 0.02). The best GCS that predicted mortality was 5.5 while the best ISS that predicted mortality was 13.5.

Conclusion

Road traffic collision is the most common cause of serious trauma in UAE followed by falls. Decreased GCS was the most significant factor that predicted mortality in the ICU trauma patients.     

Multiple spinal intramedullary cavernous angioma: case report

Spinal cavernous angiomas frequently accompany to cranial cavernous angiomas. Multiple spinal cord cavernous angiomas are very rare and to authors knowledge, only one case has been described having multiple intramedullary cavernous angiomas without cranial involvement until now. In this report, we present a case with acute paraplegia who had thoracic and cervical intramedullary cavernous angiomas and normal cranial magnetic resonance imaging.     

Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers

Park SW, Chung NG, Hur SY, Kim HS, Yoo NJ, Lee SH. Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers. APMIS 2009; 117: 880–5. Hypoxia is a general feature of solid cancer tissues. Hypoxia upregulates hypoxia‐inducible factor 1α (HIF1α) that transactivates downstream genes and contributes to cancer pathogenesis. HIF1α is upregulated not only by hypoxia but also by genetic alterations in HIF1α‐related genes, including VHL. Cullin 2 (CUL2) interacts with the trimeric VHL‐elongin B‐elongin C complex and plays an essential role in the ubiquitinated degradation of HIF1α. The aim of this study was to explore whether HIF1α and CUL2 genes are somatically mutated, and contribute to HIF1α activation in common human cancers. For this, we have analyzed the coding region of oxygen‐dependent degradation domain of HIF1α in 47 colon, 47 gastric, 47 breast, 47 lung, and 47 hepatocellular carcinomas, and 47 acute leukemias by a single‐strand conformation polymorphism assay. In addition, we analyzed mononucleotide repeat sequences (A8) in CUL2 in 55 colorectal and 45 gastric carcinomas with microsatellite instability (MSI). We found one HIF1α mutation (p.Ala593Pro) in the hepatocellular carcinomas (1/47; 2.1%), but none in other cancers. We found two CUL2 frameshift mutations in colon cancers (p.Asn292MetfsX20), which were exclusively detected in high MSI cancers (4.9%; 2/41). Our data indicate that somatic mutation of HIF1α is rare in common cancers, and somatic mutation of CUL2 occurs in a fraction of colorectal cancers (colorectal cancers with high MSI). The data suggest that neither HIF1α nor CUL2 mutation may play a central role in HIF1α activation in gastric, colorectal, breast, lung and hepatocellular carcinomas, and acute leukemias.     

Arthritis Susceptibility in Mice Expressing Human Type II Collagen in Cartilage

Collagen type II (CII) induced arthritis (CIA) in mice is an experimental model for rheumatoid arthritis. Induction with non-self (e.g. human) CII induces severe arthritis whereas the mice are less susceptible to induction with self CII (i.e. mouse). To analyse whether an autoimmune response to human CII can develop and is pathogenic the authors have established transgenic mice expressing human CII in cartilage and backcrossed them into two different gene backgrounds susceptible to CIA (DBA/1 and C3H.Q). The transgenic human CII expression was restricted to cartilage and did not disturb cartilage morphology or lead to chondrodystrophy. In addition, development of stress-induced arthritis was not affected by the transgene. The cartilage specific expression of human CII reduced, but did not eliminate, the susceptibility to CIA irrespective of the species source (human, bovine, chick, rat) of CII used for immunization. A common denominator between these heterologous CII in comparison with mouse CII is the previously defined CII 256–270 epitope. An expression level dependent T-cell tolerance was seen in this epitope as well as to the entire CII. However, all human transgenic mouse lines could still mount significant autoreactive T- and B-cell responses. Approximately 10% of the transgenic mice developed arthritis after immunization with human CII. These findings show, therefore, that cartilage-located human CII induce tolerance but can nevertheless be a target for development of arthritis.