Epstein-Barr virus lymphoproliferation after bone marrow transplantation

We review 15 cases of secondary B-cell lymphoproliferative disorders that occurred among 2,475 patients who received allogeneic bone marrow transplants (BMTs) at the Fred Hutchinson Cancer Research Center (Seattle) between 1969 and 1987. The histopathologic findings in 14 of the 15 patients spanned a wide spectrum of lymphoproliferative lesions. One patient had features characteristic of angioimmunoblastic lymphadenopathy. Epstein-Barr virus (EBV) genomic sequences were identified by Southern blot analysis in each of the 13 patients evaluated. Ten of the 12 lesions evaluated originated in donor cells. In two patients, who had mixed chimerism after transplantation, the lesions originated in host cells. The combined evidence from immunoglobulin light chain staining and the analysis of immunoglobulin heavy chain gene rearrangement indicated that the lesions in most patients represented polyclonal proliferations that gave rise to clonal subpopulations. The results indicate an overall actuarial incidence of 0.6% for this complication in BMT recipients. Anti-CD3 monoclonal antibody (MoAb) treatment of acute graft-v-host disease (GVHD) and T cell depletion of the donor marrow were statistically significant risk factors, and GVHD appeared to play a contributing role, particularly in the setting of human leukocyte antigen (HLA) disparity. Two patients had no identifiable risk factors. Prophylaxis or treatment with acyclovir had no detectable effect in the patients; all but two died with uncontrolled lymphoproliferation.     

Patients’ experiences of dialysis services: are national health strategy targets being met?

Background The National Health Strategy envisages a health system incorporating patient views; and providing accessible, consultant-led dialysis services with patient choice of dialysis modality, in all regions. Aims To describe patients’ experiences of renal services against National Health Strategy objectives. Methods Telephone interviews with 192 dialysis patients from three hospitals in the Eastern region. Results One-quarter of participants (16% of haemodialysis [HD] and 46% of peritoneal dialysis patients) lived outside the Eastern region, and travelled there because dialysis was not available locally. Two-thirds (65%) had a choice of dialysis modality. High satisfaction with interpersonal care was observed (83–98% satisfaction). Dissatisfaction with physical environment included parking (39–56%), waiting areas (62–69%), HD unit space (74%). Regarding support services, dietary services were satisfactory (92–95%), with lower satisfaction ratings for social and financial support services (62%). Conclusions Structural and management issues must be addressed to advance a quality agenda for renal care in Ireland.     

Risk factors for the presence of high-level shedders of Escherichia coli O157 on Scottish farms

Escherichia coli O157 infections are the cause of sporadic or epidemic cases of often bloody diarrhea that can progress to hemolytic uremic syndrome (HUS), a systematic microvascular syndrome with predominantly renal and neurological complications. HUS is responsible for most deaths associated with E. coli O157 infection. From March 2002 to February 2004, approximately 13,000 fecal pat samples from 481 farms with finishing/store cattle throughout Scotland were examined for the presence of E. coli O157. A total of 441 fecal pats from 91 farms tested positive for E. coli O157. From the positive samples, a point estimate for high-level shedders was identified using mixture distribution analysis on counts of E. coli O157. Models were developed based on the confidence interval surrounding this point estimate (high-level shedder, greater than 10(3) or greater than 10(4) CFU g(-1) feces). The mean prevalence on high-level-shedding farms was higher than that on low-level-shedding farms. The presence of a high-level shedder on a farm was found to be associated with a high proportion of low-level shedding, consistent with the possibility of a higher level of transmission. Analysis of risk factors associated with the presence of a high-level shedder on a farm suggested the importance of the pathogen and individual host rather than the farm environment. The proportion of high-level shedders of phage 21/28 was higher than expected by chance. Management-related risk factors that were identified included the type of cattle (female breeding cattle) and cattle stress (movement and weaning), as opposed to environmental factors, such as water supply and feed.     

治疗性单克隆抗体药动学相互作用的风险评估策略

生物制剂可用于治疗各种疾病,包括肿瘤、风湿、胃肠道疾病、皮肤科疾病、呼吸道疾病、激素缺乏症和感染。尽管近来批准了很多生物制品,但有关其药物间相互作用临床研究还不多。单克隆抗体是最主要的一类治疗性生物制品,本文介绍评价其药物间相互作用的风险评估策略,指出了评估中的关键因素,并建议将相互作用风险评估作为治疗性生物制品综合药物开发的一部分。     

Semen parameters and testicular pathology in men with testicular cancer and contralateral carcinoma in situ or bilateral testicular malignancies

We evaluated 14 patients with bilateral testicular tumour, one-sided tumour and contralateral carcinoma in situ (CIS) of the testis or testis tumour in single testis with respect to their fertility. We analysed semen parameters, serum hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone], testicular sonography, testicular volumes and testicular histology prior to further anti-cancer treatment. Ten out of 14 patients showed normal or reduced sperm concentrations, while 4/14 patients were azoospermic. Serum FSH levels showed a significant negative correlation with sperm concentrations in patients with testicular malignancies (r = -0.64, P = 0.025). Testicular volumes revealed a significant positive correlation with semen parameters in patients with testes that were affected by CIS (r = 0.733, P = 0.038). We conclude that even bilateral testicular cancer and/or CIS do not preclude fertility and, therefore, patients should be offered andrological investigation and therapy, including possibly surveillance strategy or the chance for cryopreservation of the semen prior to further treatment in order to preserve their chances for paternity.      

The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05). Furthermore, the frequencies of the APOA5 c.56 G>C polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, P<0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G>C/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2.