肝移植患者术后白蛋白的应用

目的:低白蛋白血症是肝移植患者的常见并发症,也是患者预后的重要影响因素。肝移植术后选择合理的白蛋白应用方案将有益于提高肝移植患者术后近远期疗效。方法:选择2000-10/2005-06于北京大学第三医院行肝移植并且随访时间大于6个月的患者80例,对治疗方案均知情同意。医院自2003年8月开始改变了肝移植术后白蛋白的输入方案:①方案改变之前患者即白蛋白输入方案未改变组(n=50),术后早期常规输入白蛋白剂量大于60g/d。②方案改变之后患者即白蛋白输入方案改变组(n=30),适当减少术后早期白蛋白输入的常规剂量至0￣20g/d。统计分析两组患者的一般情况、术后白蛋白使用情况、预后情况及住院费用。另外,对于两组中术后存在低白蛋白相关严重并发症的患者进行进一步的比较分析。结果:80例患者全部进入结果分析。①两组患者术前及术中一般情况差异无显著性意义(P>0.05)。②白蛋白输入方案改变组术后早期白蛋白的使用量及其费用/总住院费用比例显著低于白蛋白输入方案未改变组(P<0.01)。但两组患者术后第3天肝功能情况、白蛋白水平、早期并发症发生率、早期死亡率、半年生存率及呼吸机时间等情况差异均无显著性意义(P>0.05)。③两组中术后出现低白蛋白相关严重并发症患者术后第3天肝功能情况、白蛋白水平、早期死亡率、半年生存率及呼吸机应用时间等情况差异均无显著性意义(P>0.05)。结论:肝移植术后过多输入白蛋白不能改善患者预后;适当减少术后白蛋白的常规输入剂量,同时根据血白蛋白水平及并发症情况随时调整白蛋白的输入量能够减少白蛋白的用量,对患者预后因素亦无明显影响。     

Four cases of disseminated Mycobacterium bovis infection following intravesical BCG instillation for treatment of bladder carcinoma

Intravesical BCG (bacillus Calmette-Guérin) instillation is a first-line treatment for superficial transitional cell carcinoma of the bladder. A rare but severe complication of BCG immunotherapy is the development of disseminated BCG disease, which can result in miliary pneumonitis, granulomatous hepatitis, soft tissue infections, bone marrow involvement, and sepsis. Symptoms can present as early as a few hours or as late as several months following the BCG therapy. The key finding in disseminated BCG disease is the formation of caseating granulomas in distant organs; detection of BCG organisms from tissue samples can be difficult. Recommended treatment for disseminated BCG disease includes a combination of antituberculous medications (with the exception of pyrazinamide, to which BCG is typically resistant) and a tapering course of steroids. We present the cases of four patients who developed granulomatous infection consistent with disseminated disease after intravesical BCG treatment and provide a summary of current clinical management recommendations.     

Effects of ezetimibe/simvastatin on lipoprotein subfractions in patients with primary hypercholesterolemia: an exploratory analysis of archived samples using two commercially available techniques

BACKGROUND: Cholesterol-rich lipoproteins, including low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol (IDL-C), and very-low-density lipoprotein cholesterol (VLDL-C), are known to promote atherosclerosis. Ezetimibe/simvastatin (E/S) is an efficacious lipid-lowering treatment that inhibits both the intestinal absorption and biosynthesis of cholesterol. OBJECTIVE: The aim of the current analysis was to compare the effects of ezetimibe and simvastatin monotherapy and E/S treatment on lipoprotein subfractions and LDL particle size in patients with primary hypercholesterolemia. METHODS: This was an exploratory (hypothesis generating) analysis of archived plasma samples drawn from patients in a multicenter, randomized, double-blind, placebo-controlled, parallel-arm study. After a washout and diet/placebo run-in, patients with hypercholesterolemia (LDL-C, > or =145- < or =250 mg/dL; triglycerides, < or =350 mg/dL) were randomized equally to 1 of 10 daily treatments for 12 weeks: E/S (10/10, 10/20, 10/40, or 10/80 mg), simvastatin monotherapy (10, 20, 40, or 80 mg), ezetimibe monotherapy (10 mg), or placebo. A subset of patients had lipid subfraction measurements taken at baseline (week 0) and postrandomization (week 12). Plasma samples were used to quantify cholesterol associated with VLDL subfractions (VLDLI+2 and VLDL3), IDL, and 4 LDL subfractions (LDL1-4) via the Vertical Auto Profile II method. LDL-C particle size was determined using segmented gradient gel electrophoresis. The primary end point was median percent change in subfraction cholesterol for E/S versus ezetimibe or simvastatin monotherapy, pooled across doses. RESULTS: Of the 1528 patients randomized in the original study, 1397 (91%) had lipid subfraction measurements taken. E/S was associated with significant reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe, simvastatin, and placebo. E/S resulted in near-additive reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe and simvastatin monotherapy. Of the subfractions examined, with regard to E/S, the greatest reductions were observed in IDL-C and LDL-C1, LDL-C2, and LDL-C3. When compared with placebo, ezetimibe, simvastatin, and E/S did not shift the distribution of LDL particles toward a larger, more buoyant LDL subclass pattern. CONCLUSION: E/S was more effective than ezetimibe and simvastatin monotherapy in reducing atherogenic lipoprotein subfractions in these patients with primary hypercholesterolemia.     

Familial amyloidotic patients' experience of the disease and of liver transplantation

Liver transplantation is a new treatment for familial amyloidotic polyneuropathy (FAP). No qualitative study examining these patients' experiences of the disease and the treatment has been published. The purpose of this study was to explore and describe the experience of the disease and the liver transplantation from the FAP patient's perspective. In-depth interviews with 11 liver transplant FAP patients were performed. The process of the FAP disease and a liver transplantation was found to involve the following categories: going downhill, defence and denial, a chance of surviving, the decision — no choice, waiting powerless and uncertain, the first few steps after surgery, freed from the death sentence, still disabled, mastering up strength to recover, and the need for support and help.     

Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation

In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation specifically to hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 +/- 0.2 hours, presumably reflecting rapid antigen- specific binding. The mean radiation absorbed doses (cGy/mCi131I administered) were as follows: marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1 +/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer retention of radionuclide in marrow. Twenty patients were treated with a dose of 131I estimated to deliver 3.5 Gy (level 1) to 7 Gy (level 3) to liver, with marrow doses of 4 to 30 Gy and spleen doses of 7 to 60 Gy, followed by 120 mg/kg cyclophosphamide (CY) and 12 Gy total body irradiation (TBI). Nine of 13 patients with AML or refractory anemia with excess blasts (RAEB) and two of seven with acute lymphocytic leukemia (ALL) are alive disease-free at 8 to 41 months (median, 17 months) after BMT. Toxicity has not been measurably greater than that of CY/TBI alone, and the maximum tolerated dose has not been reached. This study demonstrates that with the use of 131I-BC8 substantially greater doses of radiation can be delivered to hematopoietic tissues as compared with liver, lung, or kidney, which may improve the efficacy of marrow transplantation.     

Role of upstream DNase I hypersensitive sites in the regulation of human alpha globin gene expression

Erythroid-specific DNase 1 hypersensitive sites have been identified at the promoters of the human alpha-like genes and within the region from 4 to 40 kb upstream of the gene cluster. One of these sites, HS-40, has been shown previously to be the major regulator of tissue-specific alpha-globin gene expression. We have now examined the function of other hypersensitive sites by studying the expression in mouse erythroleukemia (MEL) cells of various fragments containing these sites attached to HS-40 and an alpha-globin gene. High level expression of the alpha gene was observed in all cases. When clones of MEL cells bearing a single copy of the alpha-globin gene fragments were examined, expression levels were similar to those of the endogenous mouse alpha genes and similar to MEL cells bearing beta gene constructs under the control of the beta-globin locus control region. However, there was no evidence that the additional hypersensitive sites increased the level of expression or conferred copy number dependence on the expression of a linked alpha gene in MEL cells.     

A systematic review of risk of HIV transmission through biting or spitting: implications for policy

Objectives

The perceived threat of HIV transmission through spitting and biting is evidenced by the increasing use of “spit hoods” by Police Forces in the UK. In addition, a draft parliamentary bill has called for increased penalties for assaults on emergency workers, citing the risk of communicable disease transmission as one justification. We aimed to review literature relating to the risk of HIV transmission through biting or spitting.

Methods

A systematic literature search was conducted using Medline, Embase and Northern Lights databases and conference websites using search terms relating to HIV, AIDS, bite, spit and saliva. Inclusion and exclusion criteria were applied to identified citations. We classified plausibility of HIV transmission as low, medium, high or confirmed based on pre‐specified criteria.

Results

A total of 742 abstracts were reviewed, yielding 32 articles for full‐text review and 13 case reports/series after inclusion and exclusion criteria had been applied. There were no reported cases of HIV transmission related to spitting and nine cases identified following a bite, in which the majority occurred between family (six of nine), in fights involving serious wounds (three of nine), or to untrained first‐aiders placing fingers in the mouth of someone having a seizure (two of nine). Only four cases were classified as highly plausible or confirmed transmission. None related to emergency workers and none were in the UK.

Conclusions

There is no risk of transmitting HIV through spitting, and the risk through biting is negligible. Post‐exposure prophylaxis is not indicated after a bite in all but exceptional circumstances. Policies to protect emergency workers should be developed with this evidence in mind.     

Incidence, etiology, and impact of diarrhea among long-term travelers (US military and similar populations): a systematic review

To determine regional estimates of pathogen-specific prevalence and incidence, as well as, describe morbidity associated with diarrhea among deployed US military and similar populations, a systematic review was conducted for publications between January 1990 to June 2005. Point estimates and confidence intervals of pathogen prevalence and travelers' diarrhea incidence were combined in a random effects model and assessed for heterogeneity. In total, 262 studies were identified for potential inclusion, of which 52 fulfilled inclusion criteria. Overall, 38% were from the Middle East, 29% from Southeast Asia, 27% from Latin America/Caribbean, and 6% from sub-Saharan Africa. Median duration of travel was 1.5 months (interquartile range, 1-3 months). Enterotoxigenic Escherichia coli (ETEC), Campylobacter, and Shigella were identified as causing 38-45% of diarrhea, with regional and population differences. Incidence based on self-report was higher than studies using passive surveillance or clinic-based methods (29 versus 7 versus 6 episodes per 100 person-months, respectively) without regional differences.