Use of multiple T cell-directed intact ricin immunotoxins for autologous bone marrow transplantation

The monoclonal antibodies (MoAb) T101, G3.7, 35.1, and TA-1 were conjugated to intact ricin using a thioether linkage. These MoAb detect, respectively, the CD5[gp67], CD7[p41], CD2[p50], and [gp95, 170] determinants that are found in the vast majority of cases of T cell acute lymphocytic leukemia (T-ALL). The resulting immunotoxins (ITs) and an equimolar mixture of these ITs were evaluated as potential purgative reagents for autologous transplantation in T-ALL. Leukemic cell lines were used to compare the kinetics of protein synthesis inactivation mediated by each IT. The cells were treated with IT in the presence of lactose in order to block the native binding of ricin. The observed rates of protein synthesis inactivation correlated with target antigen expression detected by fluorescence-activated cell sorter analysis. Of the four ITs, T101-ricin (T101-R) exhibited the fastest rate of inactivation, followed in order by G3.7-ricin, TA-1-ricin, and 35.1-ricin. At concentrations greater than 300 ng/mL, a cocktail containing an equimolar amount of all four ITs (referred to as the four- IT cocktail) exhibited kinetics that were as fast or faster than those of T101-R. The long-term cytotoxic effects of individual ITs and the four-IT cocktail were evaluated using a sensitive clonogenic assay. Each IT was specifically cytotoxic and inhibited 1 to 4 logs of clonogenic leukemic cells at doses (300 to 600 ng/mL) that can be used clinically. The four-IT cocktail was highly cytotoxic; a concentration of 300 ng/mL inhibited greater than 4 logs of leukemic cells while sparing the majority of committed (CFU-GM, CFU-E) and pluripotent (CFU- GEMM) hematopoietic stem cells. The determination of both short-term kinetics of protein synthesis inactivation and longer-term inhibition of clonogenic growth allowed new insight into cell killing by IT. Our results suggest that ITs continue to act on clonogenic target cells for a period of three to five days. Interestingly, the four-IT cocktail was not as potent against clonogenic leukemic cells as T101-R alone, although it exhibited kinetics of protein synthesis inhibition that were as fast as those of T101-R alone. This finding suggests that internalized ITs may differ in the length of time they remain active within the cell. Our results also demonstrate the importance of using several different assays to evaluate IT reagents.     

Chylopericardium: a rare complication of a Waterston shunt.

A case of chylopericardium occurring after a Waterston shunt was successfully managed by pericardial drainage of chyle and substitution of dietary fats with medium chain triglycerides.     

中心静脉压联合全心舒张末容积指数指导感染性休克患者容量治疗的效果

目的 评价中心静脉压(CVP)联合全心舒张末容积指数(GEDVI)指导感染性休克患者容量治疗的效果.方法 感染性休克患者23例,性别不煨,年龄18～64岁,休克时间＜6h,急性生理和慢性健康状况评分13～31分,采用随机数字表法,将其随机分为2组:CVP指导容量治疗组(Ⅰ组,n=12)和CVP联合GEDVI指导容量治疗组(Ⅱ组,n=11).2组均静脉输注生理盐水和6％羟乙基淀粉200/0.5,晶体液和胶体液的比例为1∶(0.5 ～ 1.0),输注速率800～ 1600 ml/h,容量治疗过程中Ⅰ组维持CVP8～ 12mmHg;Ⅱ组维持CVP＞8 mm Hg和GEDVI 600 ～ 750 ml/m2.分别于容量治疗前及容量治疗开始后6h时采集动脉及中心静脉的血样,测定血乳酸浓度和中心静脉血氧饱和度(ScvO2),计算乳酸和ScvO2的变化率.结果 与Ⅰ组比较,Ⅱ组乳酸变化率升高(P＜0.05),ScvO2变化率差异无统计学意义(P＞0.05).结论 与CVP指导容量治疗比较,CVP联合GEDVI指导感染性休克患者容量治疗时可增加组织灌注,其效果较好.     

Squamous cell carcinoma and transitional cell carcinoma arising in bladder augmentations

Tumours arising in bowel-augmented bladders are rare. Usually these tumours are adenocarcinomas that occur along the anastomotic line. We present two unusual tumours, squamous cell carcinoma and transitional cell carcinoma, that occurred in bladder augmentations. We also emphasize the need for regular cystoscopic surveillance.     

Epidemiology of surgically treated gastric cancer in the United States, 1988-2000

The incidence of gastric cancer and the need for subsequent surgery has been decreasing in the United States. However, very few population-based studies on the magnitude of these changes are available. The objective of the present study was to characterize temporal trends in the use of gastric resection in the treatment of gastric cancer. Patients with a primary diagnosis code for gastric cancer (N = 105,887) and a procedure code for gastric resection (N = 23,690) in the Nationwide Inpatient Sample for 1988–2000 were included. The Nationwide Inpatient Sample represents a 20% stratified random sample representative of all United States hospitals. Outcome variables included the overall incidence, in-hospital mortality rate, and length of stay. Rates of surgery are shown as the number of cases per 100,000 hospital discharges. Hospital volume was defined as follows: low volume (1 to 4 cases per year), medium volume (5 to 8 cases per year), and high volume (9 or more cases per year). Rates of gastric resection have shown a 20% decline from 30 cases per 100,000 (1988-1989) to 24 cases per 100,000 (1999-2000) (P = 0.001). In-hospital mortality has not changed over the 13-year period and remains at 7.4%. There was significant variation in mortality across hospitals, with very low-volume centers having an 8.9% mortality rate, whereas very high-volume centers had a 6.4% mortality rate (P < 0.001). The market share of gastric resections performed at high-volume centers increased a small amount from 43% (1988–1989) to 48% (1999-2000) (P = 0.023). Over the 13-year period, length of stay decreased from 15 days (interquartile range [IQR] 11–23) in 1988 to 11 days (interquartile range [IQR] 8–16) in 2000 (P < 0.001). Rates of gastric resection for cancer have shown a modest decline over the past 13 years in the United States. Although the length of stay for these patients has decreased, no significant changes to in-hospital mortality have occurred. Given the declining rates of gastric cancer surgery, and the superior outcomes at high-volume centers, regionalization of care may improve mortality rates for this high-risk surgical procedure. Presented at the Forty-Fourth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Florida, May 18-22, 2003 (poster presentation).     

咪达唑仑复合氯胺酮应用于小儿基础麻醉的临床探讨

 目的 探讨应用咪达唑仑复合氯胺酮不同给药方法在小儿基础麻醉中的优化方案.方法 200例1～6岁,ASAⅠ～Ⅱ级患儿随机分成以下五组:A组为口服咪达唑仑0.7 mg/kg;B组为口服氯胺酮8 mg/kg;C组为肌注氯胺酮5mg/kg;D组为口服咪达唑仑0.5 mg/kg和氯胺酮4 mg/kg;E组为先口服咪达唑仑0.5 mg/kg,再肌注氯胺酮4 mg/kg.观察各组诱导结果及呼吸循环变化、不良反应.结果 ①A组与B组比较,A组起效更快(P<0.01),合作更好,不良反应较少;②A组、B组均比C组更合作,但不如C组起效更快;③D组和E组相比,患儿更合作,不良反应更少,但起效更慢,两组诱导效果无显著差异(P>0.05).结论 咪达唑仑复合氯胺酮优于单独给药,对循环呼吸影响小;口服给药可行性更佳.     

Off pump coronary artery bypass (OPCAB) in critical left mainstem stenosis—Our experience

Background Beating heart surgery has now become the commonest technique of doing Coronary Artery Bypass Graft Surgery (CABG) in our country. It is being used even in such high risk situations like diffuse coronary disease and Critical Left Main stem Stenosis (LMCS) with good results. The aim of this study is to retrospectively review our results in Off-Pump Coronary Artery Bypass Surgery (OPCAB) in patients with critical left main stem stenosis. Methods This study is a retrospective analysis of the data of patients who underwent primary coronary artery bypass surgery. During the period from April 2003 to September 2005 a total of 64 patients underwent OPCAB procedure for critical LMCS. During the same period 10 patients underwent CABG on Cardio Pulmonary Bypass (CPB). The age range was 36–77yrs. The sex distribution was M: F 53∶10. Ten patients were done as emergency. 2 of them were on Intra Aortic Balloon Pump (IABP) support preoperatively. 10 patients were high risk with a Euro score of ≥5. Results Left Internal Mammary Artery (LIMA) was used in 78% of cases. Average grafts per patient was 2.96. The median ventilation time was 5.91 hrs. New IABP insertion in postoperative period was required in 1 patient. One patient was reexplored for bleeding. There was one perioperative myocardial infarction. 57% of patients did not need any blood transfusion. There was no conversion to CPB. There was no operative mortality. Inotropes were used in ten cases. Conclusions OPCAB is a safe method of revascularization in patients with critical LMCS. Preoperative IABP is useful in patients with cardiogenic shock. However, there is a place for CPB in patients needing additional procedures like Mitral Valve repair (MV repair) or Dor's procedure or when the vessels are very diffusely diseased. Those patients who are unstable despite IABP support may be managed by Beating heart On Pump (BHOP) technique.     

健脾补肾方增加β-catenin、Runx2表达而促进骨质疏松性骨折愈合的疗效观察

目的研究健脾补肾方促进骨质疏松性骨折愈合的疗效机制,探讨"脾肾相关"、"先后天之本"中医理论在骨质疏松性骨折防治中的运用。方法建立去卵巢骨质疏松性骨折小鼠模型,随机分为7、14、28d 3个时间点,每个时间点分生理盐水、健脾补肾方2组。于骨折术后第2天给予相应药物灌胃治疗,分别于治疗3个时间点后处死小鼠,取材,进行影像学观察和病理组织学染色。结果 X-ray、Micro-CT结果显示,健脾补肾组7、14、28d均可促进骨痂形成及骨折愈合;Micro-CT定量分析显示,健脾补肾组7、14d骨痂BV/TV、Conn.D、mean/density of TV、mean/density of BV均明显高于生理盐水组(P0.05);有限元分析结果提示,健脾补肾组28d骨折部位刚度、弹性模量结果均高于生理盐水组(P0.05);HE染色、ABH/OG染色结果显示,健脾补肾方可以促进骨折部位早、中期膜内成骨和软骨内成骨,加速骨折愈合;免疫组化染色结果显示,健脾补肾方能增加骨痂部位β-catenin、Runx2的表达,促进骨折愈合。结论健脾补肾方可以促进骨质疏松性骨折的愈合,其机制可能与增加β-catenin、Runx2的表达相关。