The clinical and pathological characteristics of Chinese patients with pauci-immune crescent golmerulonephritis

Objective　To investigate the clinical and pathological characteristics of pauci-immune crescent glomerulo～nephritis (PICGN) in Chinese patients. Methods　During 13 years (1985-1998), 6400 patients underwent non-transplanting renal biopsy. Twenty-four patients were diagnosed as PICGN. All clinical and laboratory data of these patients were collected from the patients’ records and used for detailed analysis. The diagnosis is based on clinico-pathologic findings. Results　Of the 24 patients, 16 were females and 8 were males, with median age of 33 years (ranged 10-76 years). Microscopic polyarteritis (MPA) (33.3%) and systemic vasculitis (8.3%) were the secondary diseases. The incidence of PICGN was 0.38% in renal biopsies and 22.9% in crescentic glomerulonephritis. Clinically, most patients (75.0%) showed rapidly progressive nephritis with enlarged kidneys. At onset, gross hematuria was noted in 58.3% of patients, hypertension in 45.8%, nephrotic syndrome in 41.7%, and oliguria in 25.0%. However, systemic symptoms were rare except for anemia. Pathologically, necrosis of glomerular capillaries (62.5%), infiltration of monocytes and neutrophil cells in glomeruli (66.7%), and vasculitis in the interstitium (53.3%) were observed. In addition, glomerulosclerosis was noted in 45.8%, severe tubular atrophy in 83.3% and interstitial fibrosis in 75.0%. Anti-neutrophil cytoplasmic antibodies (ANCAs) were positive in 52.2%. All patients except two received intensively immunosuppressive therapy. Sixteen patients were available for long-term follow up (median 29.8 months, range 8-92 months). Twelve of them had life-sustaining renal function, four had normal serum creatinine (<124?μmol/L) and only 4 patients were dialysis-dependent. Conclusion　PICGN is not rare in China. Early diagnosis and administration of immunosuppressive therapy, particularly in patients with rapidly progressive glomerulonephritis (RPGN), are important for good prognosis.     

Second‐look endoscopy with thermal coagulation or injections for peptic ulcer bleeding: A meta‐analysis

Background and Aims: In the management of peptic ulcer bleeding, the benefits of second‐look endoscopic treatment with thermal coagulation or injections in controlling recurrent bleeding is unsure. This study set out to compare efficacy of routine second‐look endoscopy with treatment using either thermal coagulation or injections versus single endoscopy by pooling data from published work. Methods: Full publications in the English‐language published work as well as abstracts in major international conferences were searched over the past 10 years, and six trials fulfilling the search criteria were found. Outcome measurements included: (i) recurrent bleeding; (ii) requirement of surgical intervention; and (iii) mortality. We examined heterogeneity of trials and pooled the effects by meta‐analysis. The quality of studies was graded according to the prospective randomization, methods of patient allocation, the list of exclusion criteria, outcome definitions and the predefined salvage procedures for uncontrolled bleeding. Results: Among 998 patients recruited in these five randomized trials, 119 received routine second‐look endoscopy with thermal coagulation, and 374 received second‐look with endoscopic injection and 505 had single endoscopic therapy. Less recurrent bleeding was reported after thermal coagulation (4.2%) than single endoscopy (15.7%) (relative risk [RR] = 0.29; 95% confidence interval [CI] = 0.11–0.73), but no reduction was reported for the requirement of surgical intervention and all‐cause mortality. Injection therapy did not reduce re‐bleeding (17.6%) when compared to single endoscopy (20.8%; RR = 0.85; 95% CI = 0.63–1.14), requirement for surgery and mortality. Conclusion: Routine second‐look endoscopy with thermal coagulation, but not injection therapy, reduced recurrent peptic ulcer bleeding. There is no proven benefit in reducing surgical intervention and overall mortality.     

Functional role of beta-adrenergic receptors in the mitogenic action of nicotine on gastric cancer cells.

We previously reported that nicotine promoted gastric cancer cell growth via upregulation of cyclooxygenase 2 (COX-2). In the present study, we further investigated whether beta-adrenoceptors, protein kinase C (PKC), and extracellular signal-regulated kinase-1/2 (ERK1/2) were involved in the modulation of COX-2 expression and cell proliferation by nicotine in AGS, a human gastric adenocarcinoma cell line. Results showed that nicotine dose dependently increased the phosphorylation of EKR1/2 and the expression of AP-1 subunits c-fos and c-jun. In this connection, the ERK1/2 inhibitor U0126 abrogated the upregulation of AP-1 and COX-2 as well as cell proliferation induced by nicotine. Moreover, nicotine induced the translocation of PKC-betaI from cytosol to membrane and increased the total levels of PKC expression. Inhibition of PKC by staurosporine attenuated nicotine-induced ERK1/2 phosphorylation and COX-2 expression. Furthermore, atenolol and ICI 118,551, a beta1- and beta2-adrenoceptor antagonist, respectively, reversed the stimulatory action of nicotine on the expression of PKC, ERK1/2 phosphorylation, and COX-2 together with cell proliferation. Collectively, these results suggest that nicotine stimulates gastric cancer cell growth through the activation of beta-adrenoceptors and the downstream PKC-betaI/ERK1/2/COX-2 pathway.     

Pro-oxidative effects of Chinese herbal medicine on G6PD-deficient erythrocytes in vitro.

Glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects are susceptible to chemical-induced oxidative haemolysis. Little is known concerning the haemolytic properties of Chinese herbal medicine on G6PD-deficient subjects. Our objective was to investigate the pro-oxidative effect of 18 commonly used Chinese herbal medicine (CHM) on human G6PD-deficient red blood cells. G6PD-deficient (n=10) and normal (n=10) whole blood samples were incubated with water extracts of CHM. The resulting levels of reduced glutathione (GSH) and methaemoglobin (MetHb) were determined by biochemical assays. Rhizoma Coptidis significantly reduced GSH level by 48.9+/-5.4% (at 1 mg/mL) in the G6PD-deficient erythrocytes (P<0.001) compared with the respective control group without challenge. Similar dose-dependent responses were observed at higher concentrations of Cortex Moutan, Radix Rehmanniae, Radix Bupleuri, Rhizoma Polygoni Cuspidati and Flos Chimonanthi (P<0.01, 5-10 mg/mL). In addition, the levels of MetHb were elevated significantly when challenged with Rhizoma Coptidis (2.8 fold at 5 mg/mL) and Cortex Moutan (3.4 fold at 10 mg/mL). This is the first report on the pro-oxidative action of CHM on G6PD-deficient blood samples in vitro as demonstrated by the decrease of GSH and increase of MetHb. G6PD-deficient subjects should restrain from excessive consumption of these pro-oxidative herbs.     

Modulation of breast cancer resistance protein (BCRP/ABCG2) by non-basic chalcone analogues

Chalcones are biosynthetic precursors of flavonoids found to possess cytotoxic and chemopreventive activities. In this study, 17 non-basic chalcone analogues were synthesized and evaluated for their ability to modulate the function of either the human wild-type (482R) or mutant (482T) breast cancer resistance protein (BCRP/ABCG2) stably expressed in breast cancer MDA-MB-231 cells. At 5muM, chalcones with 2,4-dimethoxy groups or 2,4-dihydroxyl groups on ring A were found to increase mitoxantrone accumulation to a greater extent than an established BCRP inhibitor, fumitremorgin C. At the same time, these chalcones had negligible effect on calcein accumulation in P-glycoprotein overexpressing MDCKII cells, indicating their potential as selective BCRP inhibitors. Functionally, these compounds were able to increase the sensitivity of BCRP-overexpressing cancer cells to mitoxantrone by 2-5-fold. The effect of chalcone compounds on both wild-type and mutant BCRP ATPase activity was also examined and variable effects were observed. A stimulatory effect was mostly observed with chalcones with 2,4-dimethoxy substitution on ring A which were earmarked as good BCRP inhibitors in the MX accumulation and cytotoxicity assays. These findings underscore the potential of methoxylated and hydroxylated chalcones as selective and potent inhibitors of BCRP whose mode of action may not involve the inhibition of ATPase activity.     

Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia

The effect of traumatic lumbar puncture at the time of initial diagnostic workup on treatment outcome in children with newly diagnosed acute lymphoblastic leukemia (ALL) was investigated. The findings of the first 2 lumbar punctures performed on 546 patients with newly diagnosed ALL treated on 2 consecutive front-line studies (1984-1991) at St Jude Children's Research Hospital were retrospectively reviewed. Lumbar punctures were performed at the time of diagnosis and again for the instillation of first intrathecal chemotherapy. The event-free survival (EFS) experience for patients with 1 cerebrospinal fluid (CSF) sample contaminated with blast cells was worse than that for patients with no contaminated CSF samples (P =.026); that of patients with 2 consecutive contaminated CSF samples was particularly poor (5-year EFS = 46 +/- 9%). In a Cox multiple regression analysis, the strongest prognostic indicator was 2 consecutive contaminated CSF samples, with a hazard ratio of 2.39 (95% confidence interval, 1. 36-4.20). These data indicate that contamination of CSF with circulating leukemic blast cells during diagnostic lumbar puncture can adversely affect the treatment outcome of children with ALL and is an indication to intensify intrathecal therapy.     

穴位注射治疗尖锐湿疣及对免疫功能的影响

目的：探讨穴位注射治疗CA的临床疗效及对CA患者免疫功能的影响。方法：149例患者随机分为治疗组（A组）、药物对照组（B组）和空白对照组（C组）。运用激光治疗消除疣体后，A组用卡介菌多糖核酸穴位注射，B组用卡介菌多糖核酸肌肉注射，C组仅行激光消除疣体治疗。分别于治疗前及6个月以后检测患者细胞免疫功能。另设健康人对照组40例，检测项目同上。结果：治疗前与健康人相比，CA患者CD4^＋百分率降低，CD8^＋百分率升高，CD4^＋／CD8^＋比值降低，NK细胞活性降低（P〈0．05或P〈0．01）。运用穴位注射卡介菌多糖核酸治疗后，治疗组CD4^＋百分率升高，CD8^＋百分率降低，CD4^＋／CD8^＋比值升高，NK细胞活性升高（P〈0．05或P〈0．01）。结论：穴位注射卡介菌多糖核酸疗法对CA的T淋巴细胞亚群、自然杀伤（NK）细胞有良性调节作用；可明显降低尖锐湿疣复发率，提高细胞免疫调节作用，是防止尖锐湿疣复发的机制之一。