Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide

A prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty-nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY-TBI), and 73 patients received 16 mg/kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TBI and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event-free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence of venocclusive disease of the liver. The 4-year probabilities of survival and event- free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TBI group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY- TBI group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TBI group than in the BU-CY group. In conclusion, the BU-CY regimen was better tolerated than, and associated with survival and relapse probabilities that compare favorably with, the CY-TBI regimen.     

Fanconi's anemia treated by allogeneic marrow transplantation

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.     

Effect of hepatic dysfunction on oral cyclosporin pharmacokinetics in marrow transplant patients

The effect of hepatic dysfunction, defined as abnormal serum bilirubin level, on oral cyclosporin (CSP) pharmacokinetics was examined in 28 marrow transplant patients who received CSP for prophylaxis of graft-v- host disease. Serum CSP concentrations were measured by radioimmunoassay. Forty-one concentration-time courses were studied, divided among patients with no (less than 1.2 mg/dL), mild (1.2 to 2.0 mg/dL), and moderate (2.0 to 5.0 mg/dL) hepatic dysfunction. CSP elimination, as determined by elimination rate constant and clearance, was delayed in patients with moderate hepatic dysfunction compared to those with no hepatic dysfunction (P less than .05). The volume of distribution, lag time for absorption, maximum serum concentration, and time at which the maximum concentration was achieved was not affected by hepatic function. These data indicate that patients with moderate hepatic dysfunction have delayed CSP or CSP metabolite elimination and may be at higher risk for developing CSP-related toxicity.     

Isothermal microcalorimetry: an analytical technique for assessing the dynamic chemical stability of UHMWPE

In this work, isothermal microcalorimetry (IMC) was utilized to measure the exothermic heat flow from specimens of ultra-high-molecular-weight polyethylene (UHMWPE), that had been sterilized by various standard methods, under simulated shelf storage (air at 25 degrees C, 30% r.h.) and simulated implantation (phosphate buffered saline, PBS, at 37 degrees C) conditions. Gamma-radiation sterilized UHMWPE yielded initial heat flow rates approximately 7-10 times higher in simulated shelf storage and 2-3 times higher in simulated implantation (even after 1 month in PBS) than specimens which were unsterilized or sterilized using either ethylene oxide gas (ETO) or gas plasma (GP). These results show that gamma sterilization of UHMWPE produces many more unstable bonds in the polymer than is the case when ETO or GP is used, and that the net exothermic physico-chemical change proceeds steadily in a diffusion-limited manner in air or saline. In addition, gamma sterilization in nitrogen rather than in air did not prevent the creation of unstable bonds, but did defer physico-chemical change until the UHMWPE was exposed to oxygen. These results demonstrate the usefulness of IMC as a viable method for studying the stability of polymeric implant materials.     

垂全催乳素瘤的诊断和治疗指南

3.男性:高催乳素血症通常导致阳痿、不孕和性功能低下.男性患者通常为大腺瘤,有神经系统症状.其原因可能是对症状认识的延误或者肿瘤生物学行为的差异.     

Breaking the habit: a retrospective analysis of desistance factors among formerly problematic heroin users

Introduction and Aims . The aim of this study was to examine heroin careers among former users to assess desistance factors and explanations for sustained abstinence. Design and Methods . The study surveyed 107 former problematic heroin users who have achieved long‐term abstinence about their experiences of achieving and sustaining abstinence. The cohort was recruited opportunistically from three sources, drawing heavily on former users working in the addictions field. Results . On average, the group had heroin careers lasting for just under 10 years, punctuated by an average of 2.6 treatment episodes and 3.1 periods of abstinence, and had been heroin abstinent for an average of 10 years at the time of completing the survey. The most commonly expressed reason for finally achieving abstinence was ‘tired of the lifestyle followed by reasons relating to psychological health. In contrast, when asked to explain how abstinence was sustained, clients quoted both social network factors (moving away from drug‐using friends and support from non‐using friends) and practical factors (accommodation and employment) as well as religious or spiritual factors. Treatment was not mentioned widely either in achieving or sustaining abstinence, in contrast to 12‐Step, which was endorsed widely. Discussion and Conclusions . The study supports a careers perspective for examining heroin careers and indicates that, while achieving abstinence is possible for chronic opiate users, the path to sustained abstinence is complex and often reliant upon external support systems.