Glutathione S-transferase levels in autoimmune chronic active hepatitis: a more sensitive index of hepatocellular damage than aspartate transaminase

Glutathione S-transferase (GST; EC 2.5.1.18), a sensitive marker of hepatocellular damage, was measured in patients on therapy for histologically proven, autoimmune chronic active hepatitis at various stages of the disease. GST levels were elevated in 65% of serum samples despite immuno-suppressive treatment compared with aspartate transaminase (AST) which was increased in only 23% of samples. In 55% of samples with normal AST concentrations, GST was elevated. No samples demonstrated abnormal transaminase with normal GST levels. It is concluded that continuing hepatocellular damage occurs in patients with autoimmune chronic active hepatitis on immuno-suppressive treatment.     

甘草酸二铵脂质复合物肠溶胶囊口服治疗慢性乙型肝炎的临床观察

目的观察甘草酸二铵脂质复合物肠溶胶囊（商品名：天晴甘平），治疗慢性乙型肝炎的疗效。方法治疗组40例，服用甘草酸二铵脂质复合物肠溶胶囊（江苏正大天晴药业生产），3次／d，每次150mg；对照组40例，服用甘利欣胶囊（江苏正大天晴药业生产），3次／d，每次150mg。两组均服用8周。结果治疗8周后，治疗组ALT：复常38例，好转2例，AST：复常36例，好转4例。对照组ALT复常8例，好转30例，另有2例ALT反复升高。AsT复常8例，好转30例，另有2例ALT反复升高。治疗组ALT复常率明显高于对照组（P〈0．05），治疗组AST复常率明显高于对照组（P〈0．05）。结论甘草酸二铵脂质复合物因其降酶疗效高，不良反应小，使用方便等特点，为肝病患者提供了有效、方便的口服治疗药物。     

Prevalence of gestational diabetes and macrosomic newborns in a Mexican population

Prevalence of gestational diabetes was investigated in 693 pregnant patients between the 24th and 28th wk of gestation. A glucose screening test (GST) was performed with a 50-g glucose load, followed by a blood sample 1 h later. Patients with glucose levels greater than 140 mg/dl 1 h after the GST were scheduled for a full oral glucose tolerance test (OGTT). One hundred seven patients had an abnormal GST, and 30 patients (4.3%) were diagnosed as having gestational diabetes mellitus (GDM). The percentage of GDM increased significantly when glucose levels were greater than 180 mg/dl to a maximum of 84.61% when glucose levels were greater than 200 mg/dl. Also, patient age was directly related to GDM, which increased in incidence to 20% when patients greater than 26 yr had an abnormal GST. After delivery, newborn weights were compared between those born to mothers with GDM (n = 30) and those born to mothers with an abnormal GST (n = 77). Patients with an abnormal GST and normal OGTT had 12 (15.58%) macrosomic and 2 premature newborns. However, patients with GDM had 5 (16.66%) macrosomic and no premature newborns. Patients with a normal GST had 7.33% of the macrosomic newborns. There was no perinatal mortality in newborns of GDM mothers; only 1 of the 5 macrosomic newborns presented transient hypoglycemia. Evaluation of 26 GDM patients was possible after delivery, disclosing 3 (11.53%) with non-insulin-dependent diabetes mellitus and 5 (19.23%) with impaired glucose tolerance. These results showed 4.3% undetected GDM in our population and no differences in the proportion of macrosomic newborns between those born to mothers with GDM and those born to mothers with an abnormal GST.     

A descriptive analysis of aspartate and alanine aminotransferase rise and fall following acetaminophen overdose

Context: Risk prediction following acetaminophen (paracetamol, APAP) overdose is based on serum APAP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. One recently proposed risk stratification tool, the APAPxAT multiplication product, uses either AST or ALT, whichever is higher, yet their interrelation is not well known following APAP-induced hepatic injury. Objective: To describe the kinetics of AST and ALT release into and disappearance from the circulation following APAP overdose. Materials and Methods: An observational case series of adult patients with peak AST or ALT > 100 IU/L attributable to APAP toxicity. Cases were identified by electronic search of hospital laboratory database and by discharge diagnosis corroborated by structured explicit medical record review. Results: Of 68 cases identified (mean age (SD): 39 (18) years, 63% female, and 21% ethanol co-ingested), 28 (41%) developed hepatotoxicity (peak AST or ALT > 1000 IU/L), 28 (41%) coagulopathy (international normalized ratio or INR > 2), and 21 (31%) both. Three patients (4%) were transferred for liver transplantation and ultimately six (8.8%) died. Serum AST and ALT activity rose in a closely aligned 1:1 AST:ALT ratio, but fell at distinctly different rates: AST activity fell with a half-life (interquartile range [IQR]) of 15.1 (12.2, 19.4) hours, and ALT 39.6 (32.9, 47.6) hours. Using an aminotransferase falling to below 50% of peak as the basis for discontinuing acetylcysteine would have resulted in antidotal treatment being stopped 24 (IQR: 9.6, 40) hours earlier (and in no cases later) using AST rather than ALT. Only six patients had an AST:ALT ratio greater than 2:1 at the time of acetylcysteine administration; of these six, four died and one survivor developed coagulopathy. Discussion: AST and ALT release into the circulation appears tightly linked and numerically similar, except in the sickest patients. Once the aminotransferases peak, AST returns to baseline more quickly. Conclusion: Either AST or ALT can be used for early risk stratification tools when only one is known. Any criterion for N-AC discontinuation should be based on the decline of AST rather than ALT, with a potential benefit measured in days.     

多项指标联合检测对乙型肝炎后肝硬化诊断治疗中的观察分析

目的探讨肝纤维化四项与天门冬氨酸氨基转移酶(AST)/丙氨酸氨基转移酶(ALT)比值、乙型肝炎病毒(HBV)DNA指标联合检测对乙型肝炎(简称乙肝)后肝硬化诊断治疗的临床应用价值。方法选择2009年5月至2011年5月在该院消化内科收治的130例乙肝后肝硬化患者,同时选择80例单纯慢性乙肝为对照组,检测其血清透明质酸(HA)、Ⅲ型前胶原蛋白(PⅢNP)、Ⅳ型胶原蛋白(Ⅳ-Col)、层黏连蛋白(LN)、AST/ALT比值及乙肝DNA(HBV-DNA)指标水平。结果 (1)乙肝后肝硬化血清中HA、Ⅳ-Col、PⅢNP、LN明显高于单纯慢性乙肝组(P<0.01)。(2)肝纤维化四项指标在乙肝后肝硬化血清中HBV DNA>106copy/mL组中除LN外,其他指标水平明显高于乙肝后肝硬化血清中HBV DNA在103～105copy/mL组和HBV DNA<103copy/mL组的水平,差异有统计学意义(P<0.01);在HBV DNA 103～105copy/mL和HBV DNA<103copy/mL两组间肝纤维化四项指标升高水平差异无统计学意义(P>0.05)。(3)肝纤维化四项指标水平在AST/ALT>2、12时为(785.2±216.4)μg/L,各组间差异有统计学意义(P<0.05);Ⅳ-Col升高水平在AST/ALT>2[(598.2±158.6)μg/L]和AST/ALT<1[(438.7±146.1)μg/L]组间差异统计学意义(P<0.05);PⅢNP和LN升高的水平在各组间差异无统计学意义(P>0.05)。结论联合检测肝纤维化四项与AST/ALT比值、HBV DNA有利于临床对乙肝后肝硬化患者病程的监测,同时为临床对乙肝后肝硬化患者的抗病毒和抗纤维化治疗及疗效的判定提供实验室依据。     

Glutathione S-transferase in human bile

Glutathione S-transferase (GST) isoenzymes have been measured by specific radioimmunoassay in human bile samples. GST Mu was found in 50% of samples while GST Pi, GST B1 and GST B2 were present in all samples; GST Pi constituted the major isoenzyme identified. The findings of the radioimmunoassay were confirmed by a one-step purification of GST from bile, using affinity chromatography, followed by their identification using sodium dodecyl sulphate-polyacrylamide gel (SDS-PAGE). Inhibition studies showed that, at the concentrations of bile salts found in bile, GST Pi would have little or no enzymic activity. It is proposed that GST Pi acts as a carrier protein of toxic, non-substrate, ligands to remove as yet unidentified substances from biliary epithelial cells and prevent their reabsorption.     

IL-33和ST2在慢加急性乙型肝炎肝衰竭和慢性乙型肝炎患者中水平差异及应用研究

目的探讨白细胞介素-33(IL-33)和ST-2蛋白(ST2)在慢加急性乙型肝炎肝衰竭(ACHBLF)和慢性乙型肝炎患者中水平差异及应用价值。方法选取该院42例ACHBLF患者作为研究组A组,45例慢性乙型肝炎患者作为研究B组,另选取45例同期于该院行健康体检的健康志愿者作为健康对照组。采用酶联免疫吸附试验对血清IL-33和ST2水平进行检测,并对比检测结果。分别采用赖氏法、酶联免疫吸附试验、溴甲酚绿法对3组研究对象丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、清蛋白(ALB)水平进行检测,并分析在研究A组和研究B组中血清IL-33和ST2分别与ALT、AST和ALB的临床关系。结果研究A组血清IL-33和ST2、ALT和AST水平较研究B组和健康对照组显著升高,差异均有统计学意义(P0.05),且研究B组IL-33和ST2、ALT和AST水平也较健康对照组显著升高,差异有统计学意义(P0.05);研究A组血清ALB水平较研究B组和健康对照组显著降低,差异有统计学意义(P0.05),且研究B组ALB水平显著低于健康对照组,差异有统计学意义(P0.05);研究A组血清IL-33和ST2与ALT、AST水平呈显著正相关,与血清ALB呈显著负相关;研究B组血清IL-33和ST2与ALT、AST水平呈显著正相关,与血清ALB无明显相关性。结论 ACHBLF患者血清IL-33和ST2水平较慢性乙型肝炎患者显著升高,推测可能与加重炎性反应和肝损伤有关。     

Combined glutathione-S-transferase M1 and T1 genetic polymorphism and tacrine hepatotoxicity

BACKGROUND: Glutathione conjugation of tacrine reactive metabolites depends in part on the activity of glutathione-S-transferases (GST), of which two isozymes (GST M1 and GST T1) are polymorphically expressed. OBJECTIVE AND METHODS: To determine whether GST M1, GST T1, and the combined GST M1 and GST T1 null genotypes predict individual susceptibility to tacrine hepatotoxicity, 141 patients with mild to moderate Alzheimer's disease treated with tacrine were genotyped. RESULTS: During the treatment period, 52 patients had elevated alanine aminotransferase (ALT) levels at least three times the upper limit of normal, whereas 89 patients had normal ALT values (< or = upper limit of normal). Both groups were comparable in demographic and clinical characteristics. Twenty-eight patients were found to be GST T1-negative (20%; with a 95% confidence interval [95% CI] from 13% to 27%), and 68 patients (48%; 95% CI from 40% to 57%) were GST M1-negative. The combined GST M1-T1 null genotype was observed in 18 patients (13%; 95% CI from 7% to 18%) of whom 13 had an elevated plasma ALT at least three times the upper limit of normal during the study period. Although the cumulative percentage of elevated plasma ALT tended to be higher in the GST M1 null genotype, neither GST M1 nor GST T1 alone could predict individual susceptibility to tacrine hepatotoxicity. Multivariate Cox hazards model showed that the association of the GST M1-T1 null genotype was an independent risk factor of hepatotoxicity. CONCLUSIONS: The presence of combined alleles M1 and T1 deficiencies in glutathione-S-transferase genes increases the susceptibility to tacrine hepatotoxicity.     

慢性乙型肝炎患者病毒基因组与乙型肝炎病毒e抗原、肝功能关系分析

目的探讨乙型肝炎病毒基因组(HBV-DNA)、乙型肝炎病毒e抗原(HBeAg)、肝功能的相关关系,为临床治疗提供参考。方法回顾分析401例患者的HBV-DNA、HBeAg、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平,对HBVDNA与HBeAg进行相关性分析。根据患者的HBV-DNA、HBeAg水平进行分组,比较各组的ALT、AST水平差异。结果 (1)HBV-DNA与HBeAg的阳性率存在相关性,相关系数r=0.671(P0.01);(2)HBV-DNA载量达105 copies/mL时,血清ALT、AST较HBV-DNA阴性组及低载量组显著升高,差异有统计学意义(P0.05);(3)在HBV-DNA载量相当时,HBeAg阳性组与阴性组ALT、AST活性差异无统计学意义(P0.05)。结论 (1)HBeAg与HBV-DNA具有相关性;(2)HBV-DNA载量较高的患者容易出现肝功能异常;(3)HBeAg的存在情况与肝功能无显著相关性。     

妊娠期肝功能损害孕妇生化指标与血小板4项参数的关系

目的　探讨妊娠期肝功能损害孕妇生化指标与血小板 4项参数的关系。方法　分析对比门诊随访正常孕妇 (2 8例 )、单纯ALT升高组患者 (3 0例 )及黄疸伴ALT升高组患者 (2 7例 )的血生化和血小板 4项参数。结果　单纯ALT升高组ALT、AST、DB、TBA、GGT均高于正常孕妇组 (P <0 .0 1)、TB、MPV均高于正常孕妇组 (P <0 .0 5 )、PCT、PLT低于正常孕妇组 (P <0 .0 5 ) ,而两组间ALP、PDW无显著性差异 (P >0 .0 5 ) ;黄疸伴ALT升高组ALT、AST、TB、DB、TBA、ALP均高于单纯ALT升高组 (P <0 .0 1)、MPV高于单纯ALT升高组 (P <0 .0 5 )、PCT、PLT低于单纯ALT升高组 (P <0 .0 5 ) ,而两组间GGT、PDW无显著性差异 (P >0 .0 5 )。所有 5 7例肝损害孕妇生化指标和PLT4项参数进行相关分析 ,其中MPV与ALT、AST、GGT均存在正相关 (P <0 .0 5 ) ;PLT与TB、DB存在负相关 (P <0 .0 1) ;PCT与TB、DB存在负相关 (P <0 .0 5 ) ;其余生化指标和PLT4项参数不存在相关性 (P >0 .0 5 )。结论　GGT、ALP可能不是判断妊娠期肝功能损害的敏感指标 ;黄疸引起妊娠肝损害孕妇PLT计数减少     

白血病细胞内谷胱甘肽硫转移酶的表达与化疗耐药的关系

为了探讨白血病细胞内谷胱甘肽硫转移酶 (GST)的表达与化疗耐药的关系 ,本研究采用 1 氯 2 ,4 二甲基为底物的比色分析法和原位杂交法对 5 6例白血病患者白血病细胞内GST的表达进行检测 ,并结合临床化疗药物敏感度和治疗效果进行临床分析。结果显示 :①同类型白血病患者的白血病细胞内GST表达 ,无显著性差异 ;②初治和复发白血病患者白血病细胞内GST活性分别为 (4.5± 1.0 )U和 (7.9± 1.5 )U ,GSTmRNA表达率分别为33.3%和 6 6 .3% ;③ 5 6例白血病患者在临床完全缓解 (CR ,19例 )、部分缓解 (PR ,2 0例 )和未缓解 (NR ,17例 )组的GST活性分别为 (1.7± 0 .7)U ,(5 .9± 2 .0 )U和 (9.3± 1.7)U ,GSTmRNA表达率分别为 13.3% ,2 9.7%和76 .6 %。结论提示 :白血病细胞内GST异常表达与白血病化疗耐药明显相关 ,高表达GST的患者易复发 ,检测白血病细胞内GST活性可作为白血病治疗评价和预后判断的有用指标     

阿德福韦酯联合胸腺五肽治疗乙型肝炎病毒e抗原阳性慢性乙型肝炎的近期疗效观察

目的观察阿德福韦酯联合胸腺五肽治疗乙型肝炎病毒e抗原(HBeAg)阳性慢性乙型肝炎2年的疗效。方法 2007年1月-2009年1月间178例慢性乙型肝炎患者随机分为试验组91例和对照组87例。试验组给予胸腺五肽1 mg,隔日皮下注射,疗程52周;同时阿德福韦酯10 mg/d口服104周。对照组给予阿德福韦酯10 mg/d,口服104周。治疗26、52、104周及停药52周时,分别检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、乙型肝炎病毒(HBV)DNA含量及HBV血清标志物。结果治疗52周后,试验组在ALT复常率、AST复常率、HBV DNA转阴率、HBeAg转阴率与HBeAg/HBeAb血清转换率方面都比对照组高。停药52周时,试验组与对照组的ALT复常率、AST复常率、HBV DNA转阴率、HBeAg转阴率、HBeAg/HBeAb血清转换率分别为74.73%与51.72%、75.82%与54.02%、25.27%与8.05%、26.37%与10.34%、18.68%与8.05%(χ2=10.652、9.313、9.421、7.574、4.313,P<0.05)。结论阿德福韦酯联合胸腺五肽治疗HBeAg阳性慢性乙型肝炎比单独使用阿德福韦酯抗病毒治疗效果更好,有助于提高HBeAg/HBeAb血清转换率,减少停药后病毒学突破,并且使用安全。     

Plasma glutathione S-transferase and F protein are more sensitive than alanine aminotransferase as markers of paracetamol (acetaminophen)-induced liver damage

Concentrations of glutathione S-transferase (GST; glutathione transferase; EC 2.5.1.18) B1 subunits, F protein, and the activity of alanine aminotransferase (ALT; EC 2.6.1.2) were measured in sequential plasma samples taken from nine patients with self-administered paracetamol (acetaminophen) poisoning. GST exceeded the reference interval in all patients at the time of admission, and F protein was increased in seven. In contrast, abnormal activities of ALT in plasma were found in only one of the nine on admission, a patient admitted 12 h after poisoning. Subsequent to admission nine, eight, and five patients, respectively, had abnormal concentrations of GST, F protein, and ALT. When expressed as multiples of the upper reference limit, the highest values for GST measured in each patient always far exceeded the greatest abnormalities in ALT; this was true for F protein in only five patients. Patients in whom the concentration of GST exceeded 10 micrograms/L on admission subsequently went on to develop moderate or severe liver damage, despite treatment with N-acetylcysteine. F protein and ALT measurements on admission were not as efficient as GST at predicting the clinical outcome of the patients. We conclude that GST and F protein offer clear advantages over ALT for detecting minor degrees of acute liver dysfunction, particularly when only centrilobular damage may be involved.     

Serodiagnostic applicability of recombinant antigens of Clonorchis sinensis expressed by wheat germ cell-free protein synthesis system

We evaluated the diagnostic applicability of recombinant proteins from Clonorchis sinensis, the human liver fluke. Four recombinant proteins, 7-kDa protein (Cs7P), 28-kDa cysteine protease (Cs28CP), and 26- and 28-kDa glutathione s-transferases (Cs26GST and Cs28GST), were expressed by wheat germ cell-free protein synthesis system. In ELISA, crude antigen showed the highest sensitivity (92.7%). However, sensitivities of r7P (47.3%), r28CP (30.9%), r26GST (21.8%), and r28GST (14.5%) were dramatically lower. The overall specificities of the crude antigen, r7P, r28CP, r26GST, and r28GST, were 100%, 94.5%, 96.7%, 94.5%, and 98.9%, respectively. Taken together, r7P and r28CP showed moderate sensitivities and high specificities, whereas r26GST and r28GST revealed low sensitivities and high specificities. We demonstrated that recombinant antigens, when used as a single antigen for ELISA, are not sensitive enough to diagnose clonorchiasis. Cocktail or chimeric antigens may be useful to increase the sensitivity of each antigen and may improve the serodiagnosis of clonorchiasis.     

Gustatory sensitivity threshold to table salt and efficacy of the treatment of newly diagnosed patients with antihypertensive therapy

Gustatory sensitivity threshold to table salt (GST) and extracellular fluid volume (EFV) were determined in 128 patients with arterial hypertension (mean age 54.1+-0.5 yr; 79 men) before and 3 month after antihypertensive therapy. Those with the initially high GST (sensing salt in its 0.32% solution) had AP 161+-2/97+-1 mm Hg, myocardial mass 235.1+-13.2 g and left ventricular diastolic size 4.91+-0.07 compared with 151 +- 1/93+-1, 203.5+-7.8 and 4.71+-0.05 respectively in patients with low GST. The treatment resulted in a decrease of AP and EFV by 14-19 and 12% respectively in all the patients. In those with high GST it decreased after intake of indapamide by 49% vs 24 % in the absence of therapy. In patients with initially low GST it decreased (by 37%) only after intake of diuretics. It is concluded that changes of GST reflect activation of mechanisms leading to a stable drop of AP.     

慢性乙肝患者血清 Tim-3，HBsAg，TGF-β1水平表达与病情程度相关性研究

目的　探讨慢性乙肝患者血清T 淋巴细胞免疫球蛋白黏蛋白分子3（T lymphocyte immunoglobulin mucin molecule 3,Tim-3）、乙肝表面抗原（hepatitis B surface antigen,HBsAg）和转化生长因子β1（transforming growth factor beta 1,TGF-β1）表达与病情程度关联性。方法　选取宝鸡市口腔医院2017 年10 月~2019 年6 月诊断为慢性乙肝患者103 例为研究组,选择同期健康体检者103 例为对照组,两组患者均检测肝功能[ 肝胆酸（cholyglycine,CG）、谷氨酸 氨基转移酶（alanine aminotransferase,ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase,AST）、直接胆红素 （direct bilirubin,DBIL）、总胆红素（total bilirubin,TBIL）]、TGF-β1,HBsAg 和Tim-3 表达情况,并分析慢性乙肝 发病影响因素、各指标水平与肝功能指标水平关联性、诊断效能。结果　①研究组TBIL,DBIL,CG,AST 和ALT 血 清水平高于对照组,差异均有统计学意义（t =24.412~53.782,均P ＜ 0.05）。②研究组Tim-3,TGF-β1 及HBsAg 水平 高于对照组,差异均有统计学意义（t =29.878~37.574,均P ＜ 0.05）。③ HBsAg（OR=2.234）、Tim-3（OR=2.634） 及TGF-β1（OR=2.768）均为影响慢性乙肝发病的独立危险因素（χ2=5.862~11.140,均P ＜ 0.05）。④ TGF-β1,Tim-3 及HBsAg 与肝功能指标CG,ALT,AST,DBIL,TBIL 存在显著正相关关系（均P ＜ 0.05）。⑤联合诊断敏感度 （95.15%）、特异度（92.23%）和准确度（93.69%）高于TGF-β1（79.61%,76.70% 和78.16%）、Tim-3（77.67%, 80.58% 和79.13%）及HBsAg（82.52%,83.50% 和83.01%）单独诊断,差异有统计学意义（χ2=9.662~22.685,均P ＜ 0.05）。 结论　慢性乙肝患者Tim-3,HBsAg 和TGF-β1 水平与肝功能存在正相关关系,通过联合检测可提升慢性乙肝诊断敏感 度及准确度、特异度。     

高密度脂蛋白胆固醇试剂对天门冬氨酸氨基转移酶测定结果的影响

目的探讨某国产试剂(B公司)高密度脂蛋白胆固醇(HDL-C)试剂对天门冬氨酸氨基转移酶(A ST)测定结果的影响。方法按照EP 9-A 2文件,实现B公司A ST测定结果与可溯源罗氏公司(A公司)A ST测定结果的可比性。分别单独用A公司、B公司的A ST试剂测定筛选出的40份不同浓度的A ST新鲜血清标本。用上述40份新鲜标本,先用A公司的HDL-C试剂,先进行HDL-C测定,等加完试剂2后,启动紧急停机程序,过反应时间,再用A公司的A ST试剂测定A ST,以保证两个项目前后在同一个比色杯反应。再按同样方法用A公司的HDL-C试剂与B公司的A ST试剂,B公司的HDL-C试剂与B公司的A ST试剂、A公司的A ST试剂测定A ST。结果A公司与B公司的A ST试剂测定结果具有可比性。A公司的HDL-C试剂对A公司和B公司的A ST试剂测定A ST结果与单独用A公司A ST试剂测定A ST结果均具有可比性。B公司的HDL-C试剂对A公司试剂、B公司A ST试剂测定A ST结果与单独用A公司A ST试剂测定A ST的结果之间完全没有可比性。结论由于比色杯的交叉污染,B公司的HDL-C试剂对A公司、B公司A ST试剂测定A ST结果均有严重干扰。     

Effects of therapeutic coronary reperfusion on aspartate aminotransferase isoenzymes in sera of patients with acute myocardial infarction

We examined the kinetics of the catalytic activities of aspartate aminotransferase (AST, EC 2.6.1.1) isoenzymes in serum of 28 patients with myocardial infarction who were to receive either intracoronary urokinase--reperfusion angiographically proved--or conventional therapy (control group). Cytosolic (soluble) AST (s-AST) activity in serum increased rapidly immediately after recanalization, reaching a maximum 12 h after the onset of infarction. In the control group, this peak was reached 28 h after the onset (P less than 0.001). Peak s-AST activity was similar in the two groups. Peak activity and peak time for mitochondrial AST (m-AST) were the same for the two groups of patients; intervention that affects myocardial perfusion caused only a slight additional increase in m-AST activity in the early post-infarct period. There may be advantages to measuring m-AST, which is briefly influenced by reperfusion, instead of the usual cytosolic enzymes for assessment of myocardial damage in patients with myocardial infarction treated with thrombolytic therapy.     

Phase I trial of bortezomib during maintenance phase after high dose melphalan and autologous stem cell transplantation in patients with multiple myeloma

We enrolled 15 patients in this phase I dose de-escalation trial. Twelve patients are evaluable. The primary objective was to determine the safest and best tolerated maintenance dosing (MD) of bortezomib (B). The secondary endpoints were to evaluate complete response (CR), overall response (OR) and response duration. All patients receiving autologous stem cell transplant (ASCT) were eligible and registered between D+30 to D+120 after ASCT. A maximum number of 8 cycles of B was planned. Two evaluable patients in level (L) 1 received therapeutic dose of B 1.3 mg/m(2) intravenously on days (D) 1, 4, 8, and 11 in a 21 day cycle. Both these patients experienced dose limiting toxicities (DLTs). Four evaluable patients were then enrolled in dose L2 utilizing B 1.3 mg/m(2) on D 1, 4, 8, and 11 in a 28 day cycle. Two patients in L2 developed DLTs. Six evaluable patients were thereafter enrolled in L3 utilizing B 1 mg/m(2) on D 1, 8, and 15 in a 28 day cycle. Median 8 cycles of B were administered (2-8). No DLTs were observed in L3. The median duration of follow up for the entire cohort is 33 months (12-62). The median duration of response in L3 is 29.1 months (12-33). We conclude that B 1 mg/m(2) administered intravenously and may be subcutaneously on D 1, 8, and 15 in a 28 day cycle is the best tolerated MD and can be safely given beginning around D+100 post-ASCT.     

Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report.

The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted.