Long-term treatment with doxazosin in men with benign prostatic hyperplasia: 10-year follow-up

INTRODUCTION AND OBJECTIVES: Benign prostatic hyperplasia (BPH) is a progressive condition that is characterized by an increased risk of acute urinary retention and BPH-related surgery. This study evaluates the safety and efficacy of doxazosin over 10 years in men with BPH. MATERIAL AND METHODS: The trial enrolled men (aged 49-83 years--mean 64.0) with symptomatic BPH (clinical stage II according to Alken) and no evidence of prostate cancer. The trial involved a 1.5 year controlled efficacy study with doxazosin (4 mg/day) 64 ambulatory patients with BPH, followed by a 5-year extension. During the study after 1 year 11 pts discontinued it (expense given as reason) and 6 pts underwent surgery. Then 47 pts (100%) receiving doxazosin continued therapy. After 5 years 32 pts (60%) aged 54-92 years--mean 69.4 years continued to be followed for further 5 years, giving a total follow-up of 10 years (next 8 pts underwent surgery; total 14 (26%) pts; and 14 (26%) pts died. RESULTS: Twenty (38%) of the 47 pts (100%) enrolled into doxazosin were judged as being successfully treated during the 10-year follow-up. In further 5 years only 2 pts underwent surgery and 7 pts (13%) died for reasons unrelated to doxazosin treatment. Three pts after 6 years therapy left study. Excluding 14 pts who died plus 14 pts who left the trial it means that after 10 years 20 pts remained successfully treated and 16 pts who had to be surgically treated. Assuming that all group make 36 pts (100%) than long term follow-up showed effective results in doxazosin treated 20 pts (56%) and thus can obviate surgery. Adverse events associated with doxazosin therapy were insignificant. 10 years therapy proved effective in increasing urina flow rates and decreasing residual urine volume--respectively 14.6 ml/s and 57.0 ml (mean value). CONCLUSIONS: 1. Long-term 10 years doxazosin (4 mg/daily) therapy has demonstrated that appropriately selected BPH patients are likely to have an excellent response. 2. The a/m trial indicates that surgery can be obviated in up to half of BPH treated patients. 3. The results of the trial demonstrate that doxazosin is safe, efficacious and well-tolerated.     

Functional identification and monitoring of individual α and β cells in cultured mouse islets of Langerhans

Abstract The aim of the present study was to evaluate, by use of fluorescence microscopy and immunofluorescence stainings, the use of a fluorescent membrane potential sensitive probe as a means to identify and monitor changes in membrane potential of individual cell types in whole islets of Langerhans over time. Our work supports the use of the fluorescent probe bis-(1,3 dibutylbarbituric acid) trimethine oxonol (diBAC₄(3)), in identification of single and cells in the periphery of mouse pancreatic islets cultured on extracellular matrix. At a low extracellular glucose concentration (3 mM), heterogeneous staining of the islets was observed. Approximately 97% of the peripheral cells that stained brightly with diBAC₄(3) were glucagon positive. Additional diBAC₄(3) studies, demonstrated that an increase in glucose concentration from 3 to 10 mM is paralleled by repolarization of cells and depolarization of cells. This suggests that reciprocity of glucagon and insulin release upon glucose stimulation is coupled to divergent changes in membrane potential of these cell types and supports the use of diBAC₄(3) as a means to detect changes in secretion in both cell types.     

脉冲磁场对肝癌细胞株HepG2细胞增殖和分化的影响

目的　研究低频脉冲磁场对肝癌细胞株HepG2细胞增殖和分化的影响。方法　 2种频率不同场强相同的低频脉冲磁场处理HepG2细胞 ,以 2 对磺酸基苯基 3 ( 4 ,5 二甲基噻唑 ) 5 ( 3 羧甲氧基苯基 ) 二氢四唑嗡盐 (MTS)方法检测细胞的增殖情况 ,酶联免疫法测定HepG2细胞甲胎蛋白的分泌量。结果　 80Hz、1.5 5mT磁场分别处理HepG2细胞 1、4、8、12和 2 4h ,对HepG2细胞的增殖均无明显影响 ,差异无显著性 (P >0 .0 5 )。 16Hz脉冲磁场分别处理HepG2细胞 1、4、8和 2 4h ,对HepG2细胞的增殖和甲胎蛋白 (AFP)的分泌量均无明显影响 ,差异无显著性 (P >0 .0 5 )。结论　本研究没有观察到 16、80Hz脉冲磁场对肝癌细胞株HepG2的增殖和特征蛋白 (AFP)分泌存在“窗口”效应     

血清甘氨酰脯氨酸二肽氨基肽酶和甲胎蛋白对原发性肝癌的诊断价值

目的:探讨了原发性肝癌患者血清甘氨酰脯氨酸二肽氨基肽酶(GPDA)和甲胎蛋白(AFP)的水平变化及意义。方法:分别应用生化法和放免法对33例原发性肝癌患者进行了GPDA和AFP水平测定,并与35名正常健康人比较。结果:原发性肝癌患者血清GPDA和AFP水平均非常显著地高于正常人组(P<0.01),且GPDA与AFP水平呈明显正相关(r=0.6815,P<0.01)。结论:检测原发性肝癌患者血清GPDA和AFP水平的变化对诊断、治疗和预后观察均具有十分重要的临床意义。     

AFP阳性胰腺癌和壶腹乳头部癌的临床病理研究

目的:研究AFP阳性胰腺癌(4例)和壶腹乳头部(1例)癌的临床病理特征.方法:收集并分析5例此癌患者的临床资料,对其病理标本应用光镜、免疫组织化学进行研究.结果;此类癌多见于中老年人,血清AFP明显增高;5例均发生肝转移,于1年内死亡,平均生存期5个月;病理组织形态:均为浸润性癌,脉管内常见癌栓;2例为分化差腺癌,2例为肝样腺癌(1例为壶腹乳头部,1例为胰腺),后者癌组织由两种不同而又密切相关的腺癌区和肝样分化区组成,肝样区癌细胞具有与肝细胞癌相类似的形态特征,其癌细胞AFP染色呈阳性表达.结论:此类癌由于AFP具有免疫抑制作用,癌细胞侵袭性强易发生肝转移,病人预后不良,属高度恶性肿瘤.     

A study of the pharmacokinetic interaction between lamivudine and alpha interferon

Objective: This study was designed to investigate any possible pharmacokinetic interaction between lamivudine and alpha interferon as potential candidates for combination therapy for the treatment of hepatitis B virus (HBV). Methods: Nineteen healthy male, Caucasian volunteers, aged 20–41 years and weighing 60.5–83.5 kg completed this open, non-randomised study. They each received a single, abdominal, deep s.c. injection of 10 mIU alpha interferon on day 1, followed by a wash-out period of at least 1 week. Subjects then began a 7-day course of lamivudine (100 mg) followed by a further 10-mIU alpha-interferon injection directly after oral lamivudine dosing. Blood and urine samples were taken pre- and post-dose for alpha-interferon and/or lamivudine assay. Results: Lamivudine was safe and well tolerated in all subjects. No adverse events were reported in subjects on lamivudine, whereas 106 adverse events considered attributable to alpha interferon were recorded. Statistical analysis of pharmacokinetic parameters indicated no significant effect of lamivudine on alpha-interferon pharmacokinetics. There was a small statistically significant reduction (∼10%) in the area under the lamivudine concentration–time curve on co-administration with alpha interferon and a concomitant increase in clearance, which is not considered clinically relevant. Conclusions: Alpha interferon and lamivudine can be co-administered with no requirement for dose modification, as there was no clinically significant difference in the pharmacokinetics of either drug. Received: 22 November 1999 / Accepted in revised form: 22 March 2000     

Role of Lu/BCAM in abnormal adhesion of sickle red blood cells to vascular endothelium

Lutheran (Lu) blood group and Basal Cell Adhesion Molecule (BCAM) antigens are both carried by two glycoprotein (gp) isoforms of the immunoglobulin superfamily representing receptors for laminin alpha5 chain. They are expressed in red blood cells, in endothelial cells of vascular capillaries and in epithelial cells of several tissues. Lu/BCAM gps are overexpressed in sickle red blood cells (SS RBCs). Stimulation of SS RBCs by epinephrine activates the PKA depending signaling pathway and induces reinforced Lu/BCAM-mediated adhesion to laminin10/11. We have analyzed the phosphorylation state of Lu/BCAM long isoform cytoplasmic tail and showed that it is phosphorylated by CKII, GSK3b and PKA. Phosphorylation of this isoform in transfected K562 cells is stimulated by effectors of the PKA pathway and induces cell adhesion to laminin10/11. Lu/BCAM gps are highly expressed in endothelial cells and exhibit potential integrin binding motifs. We showed that they interact with integrin alpha4beta1, the unique integrin expressed on the surface of young reticulocytes. Adhesion assays under flow conditions showed that SS RBCs adhere to primary human endothelial cells (HUVEC) after selective activation of intergin alpha4beta1 and that this adhesion is mediated by endothelial Lu/BCAM gps. Our studies show that Lu/BCAM gps expressed either on erythroid or on endothelial cells are involved in SS RBC-endothelium interactions and could play a role in the abnormal adhesion of SS RBCs to vascular endothelium contributing to the vaso-occlusive crises reported for sickle cell disease patients.     

A primary standard for the measurement of alpha and beta particle surface emission rate at the National Metrology Institute of South Africa

An absolute alpha and beta particle measurement system for the calibration of extended area sources has been established at the National Metrology Institute of South Africa (NMISA). Various characteristics of the measurement system were studied. Dead time and optimal values for high-voltage and low-energy discrimination were determined. The surface emission rates from four extended area sources (Am-241, Sr-90/Y-90, Cl-36 and C-14) that were previously certified by National Physical Laboratory (NPL) were measured. The results obtained with the NMISA measurement system and those from the NPL were in excellent agreement with E_n values of below 0.25 being observed for all four sources.