Vascular Endothelial Growth Factor Expression and Cyclosporine Toxicity in Renal Allograft Rejection

The aim of this study was to evaluate the influence of vascular endothelial growth factor (VEGF) on renal function and on development of interstitial fibrosis (IF) in renal allografts. Tubular and interstitial expressions of VEGF and TNF-α, and density of macrophages in the interstitium were examined in 92 patients with nonrejected kidneys, acute rejection (AR), chronic allograft nephropathy (CAN), borderline changes (BC) and acute cyclosporin A (CsA) toxicity. Follow-up biopsy specimens from patients with AR and BC were evaluated for development of IF. A significant difference in tubular and interstitial VEGF expressions was found between patients with AR, BC, CAN and CsA toxicity (p < 0.001). Macrophage infiltration was positively correlated with VEGF and TNF-α expressions (p < 0.001). VEGF expression increased with increasing expression of TNF-α (p < 0.001). Renal function in first 6 months after initial biopsy was better in patients with marked tubular VEGF expression (p < 0.01); however, in follow-up, development of IF and graft loss was found earlier in these patients (p < 0.01 and p < 0.05, respectively). Increased renal VEGF expression has protective properties immediately following renal allograft but allows for increased risk of early IF, and therefore poor graft outcome in the long term.     

Radiofrequency-ablation of unresectable primary and secondary liver tumors: results in 88 patients

Background and aims Radiofrequency-ablation (RFA) is increasingly used for destruction of unresectable primary and secondary liver tumors. We report our experience in the use of RFA for the management of unresectable hepatic malignancies. Patients and methods Between February 2000 and December 2004 we have undertaken 120 RFA procedures to ablate 426 unresectable primary or metastatic liver tumors in 88 patients. RFA was performed via laparotomy (n=68), laparoscopy (n=9) or a percutaneous approach (n=43). Primary liver cancer was treated in seven patients (8%) and metastatic liver tumors were treated in 81 patients (92%). All patients were followed to assess complications, treatment response and recurrence of malignant disease. Results Procedure-related complication rate was low (3.4%). During a mean follow-up of 21.2 months, 15 patients had local tumor progression (17%), 21 patients (23,9%) had new malignant disease and 27 patients (30.7%) died from intervention-unrelated complications of their malignant disease. Additional liver lesions were identified in 27 (35%) of 77 cases by intraoperative ultrasound. Thirty-six patients received simultaneous resection and RFA. Conclusion RFA is a safe, well-tolerated and effective treatment for patients with unresectable primary and secondary liver malignancies.     

Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre-cancerous condition of the oral mucosa affecting predominantly south Asians. It is histopathologically characterized by epithelial atrophy and fibrosis of the subepithelial connective tissue. Fibrosis extends all the way into the muscle layer, leading to difficulty in mouth opening. However, the dynamics of extracellular matrix (ECM) remodeling with OSF progression is largely unknown. METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were examined for expression/deposition modes of eight ECM molecules by histochemistry, immunohistochemistry, and in situ hybridization. RESULTS: In the early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were characteristically enhanced in the lamina propria and the submucosal layer. In the intermediate stage, the ECM molecules mentioned above and elastin were extensively and irregularly deposited around muscle fibers. In the advanced stage, such ECM depositions decreased and were entirely replaced with collagen type I only. Their gene expression levels varied with progression of fibrosis, but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic areas. CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are similar to each phase of usual granulation tissue formation. Restricted mouth opening may be a result of loss of variety of ECM molecules including elastin into the homogeneity of collagen type I replacing muscle fibers.     

Significance of the hepatic mitochondrial redox state in the development of posttraumatic jaundice

The effect of the hepatic energy status on the development of posttraumatic jaundice (PTJ) was studied to clarify the mechanism of PTJ. Fifty-four patients with severe torso injury who were expected to develop PTJ on admission with an average Injury Severity Score of 27 were selected for this study. They were retrospectively divided into three groups according to their maximum bilirubin concentration by day 10: group H, 12 patients with marked elevation of serum bilirubin (>8 g/dl); group L, 23 with mild bilirubinemia (2–8 g/dl); and group N, 19 with no bilirubinemia (<2 g/dl). Group H patients, in whom trauma-related shock was severe and prolonged, developed severe hyperbilirubinemia, and their arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state and is closely correlated to its energy production, was significantly lower throughout the first week. In contrast, the AKBR increased to an above normal level, indicating enhanced energy production in groups N and L. The serum direct/total bilirubin was also higher in group H. The abnormal hepatic energy metabolism is considered to have reduced the excretion of conjugated bilirubin from the hepatocytes into the bile canaliculi, which is a process that has to proceed against the bilirubin concentration gradient. The subsequent diffusion of the accumulated water-soluble conjugated bilirubin in hepatocytes into the blood is thus considered to be one of the causes of PTJ.     

继发性肝癌的联合治疗

采用手术切除联合术后B超引导肝内门静脉区域化疗（简称PHPC）治疗胃肠道癌异时肝转移24例。随访4～54个月，结果：术后经3个疗程的PHPC，8例已存活肥18～48个月；13例分别经过2～11次的PHPC，已存活5～39p个月；另3例死亡。作者认为，对继发性肝癌采用手术切除配合术后B超引导的PHPC是一种延长患者生存期的有效联合治疗方案。     

Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

Liver transplantation for fulminant hepatic failure: importance of renal failure

Abstract One hundred eighty-one consecutive patients with fulminant hepatic failure (FHF) presenting in a 2-year period were reviewed. In this cohort we examined the impact of pretransplant renal failure on mortality and morbidity following orthotopic liver transplantation (OLTx). Twenty-seven patients (18 female, 9 male) with a median age of 43.5 years (range 19–65 years) underwent OLTx. FHF was due to idiosyncratic drug reaction ( n = 4), paracetamol overdose ( n = 3), seronegative hepatitis ( n = 17), hepatitis B ( n = 1), veno-occlusive disease ( n = 1), and Wilson's disease ( n = 1). Renal failure was present in 14 patients, 7 of whom died (whereas there was 100 % survival in patients without renal failure). Pretransplant renal failure was associated with prolonged mechanical ventilation (13 days vs 6 days, P = 0.05), prolonged intensive care stay (17 days vs 8 days, P - 0.01) and prolonged hospital stay (27 vs 21 days, P = NS). Pretransplant renal failure did not predict renal dysfunction at 1 year after OLTx. We conclude that the survival of patients transplanted for FHF is inferior to that of patients transplanted for chronic liver disease (67 % vs 88 % 1-year survival in Birmingham). For patients with FHF undergoing transplantation, pretransplant renal failure strongly predicts poor outcome with significantly greater consumption of resources.     

胎盘型谷胱甘肽S转移酶mRNA在大鼠肝癌癌前病变组织中的原位表达

应用原位杂交技术，观察了二乙基亚硝胺（ＤＥＮ）诱发大鼠肝癌前病变组织中胎盘型谷胱甘肽Ｓ转移酶（ＧＳＴ－Ｐ）ｍＲＮＡ的表达。结果显示，ＧＳＴ－ＰｍＲＮＡ主要在癌前病变肝组织中的变异灶及灶外卵圆形细胞内表达，且在变异灶间或和同一灶内阳性细胞间表达程度不尽一致，而正常肝、再生肝组织中未见其表达。提示在分子水平上变异灶细胞及卵圆型细胞可能成为实验性肝癌的癌前期细胞     

生长激素、肝细胞生长因子和烟酰胺对人胎胰岛细胞的增殖作用

目的研究生长激素(GH)，肝细胞生长因子(HGF)和烟酰胺(NIC)对体外培养的人胎胰岛细胞的增殖作用及其交互作用。方法采用La(2^7)正交设计法在体外培养的人胎胰岛细胞的各组中分别加入不同浓度及组合的GH，HGF和NIC，培养48h后，收集各孔细胞，DTZ染色，计数。结果GH，HGF和NIC均起主要作用，HGF和NIC的交互作用不可忽视，最佳的生长因子组合及适配浓度为GH(100ng／ml)HGF(25ng／ml)NIC(100mmol／L)。结论GH，HGF和NIC均能促进体外培养的胰岛细胞的增殖，且组合GH(100ng／ml)HGF(25ng／ml)NIC(100mmol／L)的作用最大。