多种血管新生指标在肝细胞肝癌中的表达及敏感性比较

目的　探讨血管新生指标CD34、CD31、vWF、Ⅳ型胶原纤维及层粘连蛋白在肝细胞肝癌(HCC)中的表达及意义 ,同时比较上述几种血管新生因子与增殖细胞核抗原 (PCNA)、病理指标及预后的相关性 ,以便筛选出有效的临床预后指标。方法　采用免疫组化方法 ,对 5 3例肝细胞肝癌的标本进行CD31、CD34、vWF、Ⅳ型胶原纤维及层粘连蛋白的染色、计数 ,并用检测数据与患者的临床资料进行统计分析。结果　统计染色的血管面积后发现 ,CD34与多种临床病理指标无相关性 ;CD31与肝内门静脉浸润相关 ;vWF与肿瘤的TNM分期及肝内门静脉浸润呈正相关 ;CollⅣ与肝内门静脉浸润呈正相关、与术后生存期呈负相关 ;Lam与肝硬化及术中出血量呈负相关、与术后生存期呈正相关。PCNA与肿瘤TNM分期有关。结论　在HCC中 ,CollⅣ、vWF、及CD31为肝细胞肝癌的有效血管新生及预后指标 ;Lam则与肝硬化及术中出血相关 ;PCNA指数肿瘤分期有关 ;CD34不能用作血管新生或预后指标     

Altered motility and bacterial flora after functional end-to-end anastomosis

The functional end-to-end technique with a gastrointestinal stapler is commonly used for small-bowel anastomosis, but the effects of this anatomically side-to-side anastomosis on motility are unknown. Fasting small-bowel myoelectric activity and culture results were compared in six animals undergoing handsewn end-to-end and functional end-to-end anastomoses. Serosal electrodes were placed at 10 cm intervals, and the small bowel was divided 25 and 55 cm from the ligament of Treitz. The functional end-to-end and end-to-end techniques were performed in each animal in random order. Fasting myoelectric recordings were obtained at weekly intervals for up to 20 weeks after operation. New electrodes were placed, and additional recordings were obtained from 29 to 39 weeks, 51 to 63 weeks, and 108 to 112 weeks after operation. The recordings were visually inspected for passage of phase 3 of the migrating myoelectric complex (MMC). By 12 to 20 weeks after operation, 91% of MMCs crossed the end-to-end anastomoses versus 22% across the functional end-to-end anastomosis (p less than 0.001). Even 2 years after surgery only 56% of MMCs crossed the functional end-to-end anastomosis. Quantitative bacterial cultures suggested a trend toward bacterial overgrowth in the functional end-to-end anastomosis. These results demonstrate that the functional end-to-end anastomosis alters small-bowel motility to a greater degree than an end-to-end anastomosis and may predispose to bacterial overgrowth.     

Molecular oncogene markers and their significance in cutaneous malignant melanoma

Background: Oncogenes and other molecular tumor markers that predict tumor aggressiveness may allow individualization and optimization of surgical therapy of intermediate-thickness malignant melanoma. We examined the expression of selected markers, including the HLA-DR antigen, the heat shock protein-70 (HSP-70), and the c-myc oncogene in primary melanoma and regional nodes and related these findings to metastatic potential and survival. Methods: Forty patients with primary melanoma (1.5–4.0 mm) were studied, all of whom had prophylactic lymph node dissection and were followed for 18 months to 7 years. The primary tissue and nodes were examined using immunohistochemical techniques for the presence of HLA-DR antigen and HSP-70 protein and the expression of the c-myc oncogene. Results: Of 40 patients, there were 23 with lesions 1 to 2.9 mm thick and 17 with lesions 3 to 4 mm thick. Nodal metastases were present in 25 of the 40 patients who had elective node dissection. HLA-DR antibody stained the primary tumor in 10 patients (25%), but there was no correlation with survival in this group. HLA-DR antibody stained the stroma and cellular infiltrates surrounding the primary tumor in 28 of 40 patients; in this group there was a correlation of HLA-DR staining of the peritumoral stroma with improved survival overall. HLA-DR staining of the peritumoral stroma also influenced survival when patients were stratified by tumor thickness groups 1 to 2.9 mm and 3 to 4 mm and presence of nodal metastases. HSP-70 was demonstrated in the primary tumor in 25% of patients, who were also shown to have significantly improved survival when compared with those whose primary tumor did not stain with HSP-70. C-myc was expressed in the primary tumor in 25%, but showed no correlation with survival. None of these proteins correlated with or predicted the presence of nodal metastases. Conclusion: We conclude that the use of specific molecular-oncogene markers in intermediate-thickness primary melanoma may identify patients at high risk for conventional treatment failure and reduced survival who may profit from more aggressive surgery, adjuvant therapy, or both.Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Anaphylactoid reactions associated with reuse of hollow-fiber hemodialyzers and ACE inhibitors.

From July 18 through November 27, 1989, 12 anaphylactoid reactions (ARs) occurred in 10 patients at a hemodialysis center in Virginia. One patient required hospitalization; no patients died. ARs occurred within minutes of initiating dialysis and were characterized by peripheral numbness and tingling, laryngeal edema or angioedema, facial or generalized sensation of warmth, and/or nausea or vomiting. All 12 ARs occurred with dialyzers that had been reprocessed with an automated reprocessing system. A cohort study, including all patients undergoing dialysis sessions on the six days when an AR occurred, showed that the patients who experienced ARs were significantly more likely than patients who did not to be treated with angiotensin-converting enzyme (ACE) inhibitors (7/10 vs. 3/33; relative risk = 7.9; 95% confidence interval = 2.5 to 25.2) and to have been exposed to reused dialyzers rather than to new dialyzers (12/70 sessions vs. 0/31; P = 0.016). In those sessions using a reused dialyzer, the mean number of dialyzer uses in case-sessions was significantly higher than for noncase-sessions (10.3 vs. 6.2; P = 0.016). After reuse of dialyzers was discontinued at the center, no further ARs occurred, despite the continued administration of ACE inhibitors. This is the first report of an outbreak of ARs associated exclusively with reused dialyzers. We hypothesize that interactions between a dialyzer that has been repeatedly reprocessed and reused, blood, and additional factors, such as ACE inhibitors, increased the risk of developing ARs.     

Development of a functional scoring system for rheumatoid arthritis patients with cervical myelopathy.

OBJECTIVE: To be able to measure disability objectively in rheumatoid arthritis complicated by cervical myelopathy. METHODS: The responses to the Stanford health assessment questionnaire disability index were recorded from 250 consecutive patients (group 1) referred to our unit for spinal surgery. Using principal components analysis the questionnaire was reduced from 20 questions to 10 questions. In the second part of the study, the results of the questionnaire for those patients undergoing surgery from the original group of 250 patients were analysed with respect to outcome. RESULTS: The reduction in the number of questions results in no significant loss of information, reliability (internal consistency Cronbach's alpha = 0.968) or sensitivity. The new scale, the myelopathy disability index, measures only one dimension (Eigen value 6.97) and may be more finely tuned to the measurement of disability in these myelopathic patients. When administered to the 194 patients undergoing cervical spine (group 2) surgery the myelopathy disability index was an accurate predictor of neurological and functional outcome, as well as survival following surgery (P < 0.0001). CONCLUSIONS: The myelopathy disability index provides a much needed objective and reliable means of assessing disability in patients with rheumatoid involvement of the cervical spine and also in predicting outcome following surgical intervention. It also provides information for both the patient and surgeon alike, on what to realistically expect from surgery. Its adoption should facilitate comparisons between different forms of surgical intervention.     

Outbreak of gram-negative bacteremia and pyrogenic reactions in a hemodialysis center

During the period from April 4, 1988, to April 20, 1988, nine pyrogenic reactions and five gram-negative bacteremias occurred in 11 patients undergoing dialysis. All pyrogenic reactions and gram-negative bacteremias occurred among patients in whom a reprocessed dialyzer was used. The rate of pyrogenic reactions or bacteremias per 100 sessions using a reprocessed dialyzer was higher than in sessions during which a new dialyzer was used (4.5 vs. 0; p = 0.03). Dialyzers were manually reprocessed with 2.5% Renalin germicide. The Renalin concentrations varied widely in 12 dialyzers stored after manual reprocessing during the epidemic period (0.9-4.2%); the median endotoxin concentrations varied from 0 to 246 ng/ml and were higher in dialyzers with Renalin concentrations less than or equal to 1.0% than in dialyzers with higher concentrations (p = 0.01). Experiments using a dilution technique described by a technician resulted in Renalin concentrations ranging from 1.4% at the surface to 3.5% at the bottom of the preparation container. These findings suggest that failure to adequately admix Renalin during dilution may be associated with low levels of disinfectant, high levels of bacteria and endotoxins in dialyzers, and outbreaks of pyrogenic reactions and gram-negative bacteremias in dialysis patients.     

Integrin stimulation regulates polymorphonuclear leukocytes inflammatory cytokine expression.

OBJECTIVE: The purpose of these studies is to investigate the role of integrin binding on the regulation of polymorphonuclear leukocyte (PMN) cytokine receptor expression. SUMMARY BACKGROUND DATA: Current knowledge in this area revolves around the ability of beta 2 integrins to mediate PMN adherence and chemotaxis. The role of alpha 1-6/beta 1 integrins in regulating cytokine receptor expression has not been probed. METHODS: Purified human PMN were adhered on plastic, fibronectin, or laminin-coated surfaces followed by the addition of iodine 125 (125I) monoclonal antibodies (mAbs) directed against tumor necrosis factor-alpha R (TNF-alpha R) p60, p80, or interleukin-1 beta R (IL-1 beta R) types I, II. Receptor expression was calculated based on the counts per minute (cpm) bound. The role of individual beta 1 integrins was assessed using mAbs directed against the alpha 1-6 subunit of the beta 1 complex, and integrin cross-linkage was achieved using secondary goat antimouse F(ab')2 antibodies. Polymorphonuclear leukocytes were pretreated with herbimycin A to determine the role of protein tyrosine kinase in mediating the effect of the beta 1 integrins. RESULTS: Adherence of PMN to Ln decreased IL-1 beta types I, II receptor expression, whereas adherence to Fn increased TNF-alpha R p60 and p80 expression. Anti-VLA-5 (CD49e) but not anti-VLA-1 through VLA-4 and VLA-6, blocked the effect of Fn on TNF-alpha receptors, whereas anti-VLA-6 but not anti-VLA-1 through VLA-5 blocked the effect of Ln on IL-1 beta receptors. Modulation of IL-1 beta and TNF-alpha receptors by VLA-5 and VLA-6 required protein tyrosine kinase activation as herbimycin A (10 micrograms/mL) blocked the affect of Fn and Ln. Changes in PMN cytokine receptor expression led to parallel changes in functional activity as assessed by the binding of 125I IL-1 beta and TNF-alpha. CONCLUSIONS: Integrin stimulation regulates the cell surface expression of PMN cytokine receptors. Ligation of CD49e upregulates TNF-alpha receptor expression, whereas binding of CD49f downregulates IL-1 beta receptor expression. Both processes are protein tyrosine kinase dependent. Changes in PMN cytokine receptor expression led to corresponding changes in functional activity. These results provide the first demonstration that chemotaxis of PMN into the interstitium provides a mechanism for ongoing participation in the local inflammatory response and is regulated by matrix protein integrin receptors.