贝伐单抗联合放射方案的实验研究

目的 实时测定贝伐单抗和放射线作用人肺腺癌细胞系(NCI-H141)裸鼠移植瘤后活体乏氧调节蛋白(HIF-1α)水平变化,为优化贝伐单抗和放射线联合计划提供依据.方法 用HIF-1α荧光蛋白报告质粒转染NCI-H441细胞连续测定肿瘤乏氧水平,并观察贝伐单抗与放射线(122Scγ射线)早晚联合后HIF-1α水平变化、血管数量和渗透性、肿瘤反应、乏氧分子标记、凋亡率和肿瘤生长延迟的异同.结果 单纯贝伐单抗作用后24 h肿瘤HIF-1α表达水平较对照组轻度下降(3.1×106:6.1×106;t=-1.73,P>0.05),功能血管密度升高(16.6:12.1;t=-1.40,P>0.05)和血管渗透指标明显改善(2.9%:11.5%;t=6.80,P<0.01);随后HIF-1α表达水平迅速升高(7.4×106:20.4×106;t=2.36,P<0.05)并维持至疗后8～10 d(第3天时高于对照组3～4倍)且总血管密度明显下降(37.4:15.9;t=5.36,P<0.01).贝伐单抗治疗72 h后联合放射线作用组比24 h后联合作用组肿瘤血管记数高(联合作用后第3天,9.33:3.17;t=-2.43,P<0.05)、凋亡记数低(联合作用后第3天,23.33:43.83;t=2.54,P<0.05),生长延迟时间也明显缩短(10.5:23.0;t=2.67,P<0.05).结论 贝伐单抗联合放射线作用后72 h贝伐单抗诱导的乏氧对血管和肿瘤细胞具有明显的放射抵抗作用,提示血管靶向药物联合放射作用可能存在时间增益窗口.     

Ventricular Late Potential in Patients with Apparently Normal Electrocardiogram; Predictor of Brugada Syndrome

Backgrounds: Brugada syndrome can be overlooked due to its dynamic change in its electrocardiogram (ECG) manifestation. We hypothesized that positive ventricular late potential (VLP) in patients with nonspecific ECG would predict the inducible coved ST elevation (type‐1 Brugada ECG) and the patients at high risk. Methods: Thirty‐four patients of nonspecific ECG without structural heart disease were eligible for this study. All patients were referred for evaluation of syncopal episodes and/or cardiac arrest and/or frequent episodes of ventricular premature contractions. We assessed the correlation between baseline VLP and the alteration to a drug‐induced type‐1 Brugada ECG, and also evaluated the diagnostic accuracy of positive VLP in normal ECG subjects for the appearance of a drug‐induced type‐1 Brugada ECG. Results: Twenty‐one patients presented positive VLP and 13 patients showed negative VLP. Parameters of VLP (fQRSd, RMS₄₀, LAS₄₀) presented significant correlation with the alteration to a type‐1 ECG by pilsicainide. VLP demonstrated high sensitivity and negative predictive value for the prediction of type‐1 Brugada ECG. Furthermore, in their follow‐up, at least two cases of ventricular fibrillation were recognized in 21 of positive VLP patients with apparently normal ECGs. Conclusions: VLP in apparently normal ECG can predict the alteration to a drug‐induced type‐1 Brugada ECG and unmask the patients at risk. (PACE 2010; 33:266–273)     

Acute Effects of Different Atrial Pacing Sites in Patients with Atrial Fibrillation: Comparison of Single Site and Biatrial Pacing

It has been reported that a trial single site or biatrial pacing can suppress the occurrence of AF. However, its mechanism remains unclear. The study population included 32 patients with AF (n = 20: AF group), or without paroxysmal AF (n = 12: control group). The mechanism and efficacy of atrial pacing were investigated by electrophysiological studies to determine which was more effective for suppressing AF induction; single site pacing of the right atrial appendage (RAA) or distal coronary sinus (CS-d), or biatrial (simultaneous BAA and CS-d) pacing. In the AF group, AF inducibility was significantly higher with BAA extrastimulus during RAA (12/20; P < 0.0001) or biatrial paced drive (7/20; P < 0.01) than during CS-d paced drive (0/20). In the control group, AF was not induced at any site paced. In the AF group, the conduction delay and other parameters of atrial vulnerability significantly improved during CS-d paced drive. The atrial recovery time (ART) at RAA and CS-d was measured during each basic pacing mode. ART was defined as the sum of the activation time and refractory period, and the difference between ARTs at RAA and CS-d was calculated as the ART difference (ARTD). The ARTD was significantly longer during BAA pacing in the AF group than in control group (155.0 +/- 32.8 vs 128.8 +/- 32.9 ms, P < 0.05). In the AFgroup, ARTDs during biatrial (52.0 +/- 24.2 ms) and CS-d pacing (51.7 +/- 26.0 ms) were significantly shorter than ARTD during RAA pacing. The CS-d paced drive was more effective for suppressing AF induction than biatrial or RAA paced drive by alleviating conduction delay. CS-d and biatrial pacing significantly reduced ARTD compared with RAA pacing.     

Renal functional measurements in young rats with chronic inhibition of nitric oxide synthase

The purpose of the present study was to examine renal functional changes caused by chronic blockade of nitric oxide (NO) synthesis in young rats. Two types of NO synthase inhibitor were used: N^G-nitro-L-arginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the inducible isoform. Oral administration of L-NAME (20–80 mg/dL of drinking water), not AG (400 mg/dL), for 4 weeks induced systemic hypertension in the treated rats. Both inhibitors caused a significant reduction in urinary excretion of NO₂^?/NO₃^?. Rats treated with L-NAME developed proteinuria and tubular enzymuria (high excretion of N-acetyl-β-D-glucosaminidase) in a dose-dependent fashion, with normal serum levels of creatinine, albumin and cholesterol. Chronic AG administration did not alter the urinary levels of protein and N-acetyl-β-D-glucosaminidase or serum laboratory values. Overall, these observations highlight the importance of the continuous generation of NO by the constitutive isoform in the control of vascular tone and the maintenance of renal glomerular and tubular function. Oral administration of L-NAME may serve as a model of chronic NO-deficient hypertension with renal injury in young rats.     

Epidural air associated with spontaneous pneumomediastinum in children: Uncommon complication?

BACKGROUND: The purpose of the present study was to evaluate the incidence of epidural air associated with spontaneous pneumomediastinum in children. METHODS: The subjects consisted of 25 boys and 17 girls with an age range of 3-14 years (mean age: 8.5 years) who underwent chest computed tomography (CT) for evaluation of spontaneous pneumomediastinum. The CT scans and medical records were reviewed retrospectively. RESULTS: Of the 42 patients, four (9.5%) had intraspinal air on CT. The air was interpreted as epidural in every patient. The small number of patients with epidural air meant that there was no significant difference in age, gender, or clinical manifestations between groups with and without epidural air. Subcutaneous emphysema was identified in all four patients with epidural air versus 18 out of 38 patients (47%) without epidural air. The patients with epidural air did not have any neurologic symptoms. Irrespective of the presence or absence of epidural air, every patient had a favorable outcome without any serious complications. CONCLUSION: In patients with spontaneous pneumomediastinum, epidural air may be more common than was previously realized. It is suggested that an air leak may spread from the mediastinum into the epidural space via the cervical fascial planes and neural foramina.     

Interventional Catheterization in Kawasaki Disease

The experiences of catheter interventional treatment in Kawasaki disease are quite limited. In this article, we report our experiences of catheter intervention. We performed the percutaneous transluminal coronary revascularization (PTCR) in 18 cases, the percutaneous transluminal coronary angioplasty (PTCA) in 12, the stent implantation in 7, and the percutaneous transluminal coronary rotational ablation (PTCRA) in 7, which resulted in success in 55.5%, 75%, 100%, and 100%, respectively. In this article, we discuss the indications and methods for coronary artery lesions of long-term Kawasaki disease. PTCR is useful for treatment of acute myocardial infarction and for prevention of massive thrombus formation, particularly within 2 years from the onset of Kawasaki disease. PTCA is effective in many instances, particularly in patients without severe calcification of the coronary artery. However, neoaneurysm had developed in a certain number of the patients. Stent implantation is more preferable than PTCA, because it may potentially prevent neoaneurysmal formation and restenosis. Rotational ablation is effective for the stiff stenotic lesions with severe calcification, particularly for ring calcification, which frequently develops in the long-term Kawasaki disease patients. The intravascular ultrasound is very useful in evaluating the tissue characterization of the coronary artery and to select the treatment strategy, and to evaluate the catheter interventional treatment.     

Imaging characteristics of papillary renal cell carcinoma by computed tomography scan and magnetic resonance imaging

AIM: To analyse the differences in the patterns between clear and papillary renal cell carcinomas using magnetic resonance imaging (MRI) and dual-phase helical computed tomography (CT). METHODS: We examined seven patients with papillary renal cell carcinoma, and six with clear cell carcinoma. The highest attenuation value of tumors in the corticomedullary phase (CMP) and the excretory phase (EP) was measured using the observer-defined region of interest (ROI). MRI consisted of T1-weighted and T2-weighted spin-echo imaging. RESULTS: All five tumors except for one with papillary renal cell carcinoma showed homogenous hypointensity, but all six tumors with clear cell carcinoma showed heterogeneous hyperintensity on their T2-weighted images. In the CMP, the mean CT numbers of the papillary renal cell carcinomas were significantly lower than those of the clear cell carcinomas. The mean enhancement of the papillary renal cell carcinomas in the CMP and the EP was significantly lower than that of the clear renal cell carcinomas. The mean CT numbers of the clear cell carcinomas in the CMP were markedly increased from those on the unenhanced CT; those in the EP were decreased gradually. But the mean CT numbers of the papillary renal cell carcinomas in the EP were still slightly more increased than those in the CMP. The enhancement patterns of the papillary renal cell carcinomas in the CMP and the EP were homogenous, but those of the clear cell carcinomas were heterogeneous. CONCLUSIONS: We can speculate the differential diagnosis from clear to papillary renal cell carcinoma using MRI and dual-phase helical CT.     

Concurrent diagnosis of urothelial carcinoma and squamous cell carcinoma of the bladder in a patient with a vesicorectal fistula from invasive rectal cancer

A 47-year-old man underwent a low anterior resection of the rectosigmoid colon with en bloc cystoprostatectomy for vesicorectal fistula due to a locally advanced rectal cancer. Histopathological examination of the bladder revealed two additional primary malignancies: urothelial carcinoma and squamous cell carcinoma. To our knowledge, this is the first reported case of two histologically distinct urothelial malignancies that were diagnosed during a work up of vesicorectal fistula due to adenocarcinoma of the rectum.