Transplanting blood group A, B, or O (ABO)-incompatible (ABO-I) liver grafts has resulted in lower patient and graft survival with an increased incidence of vascular and biliary complications and rejection. We report that, without modification of our standard immunosuppression protocol, crossing blood groups is an acceptable option for children requiring liver transplantation. In our study, ABO-I liver grafts -- regardless of recipient age -- have comparable long-term survival (mean follow-up of 3.25 yr) with ABO-compatible grafts without any difference in rejection, vascular or biliary complications. From January 1, 1999 to October 1, 2005, we studied 138 liver transplants in 121 children: 16 (13.2%) received an ABO incompatible liver allograft. One-year actuarial patient survival for ABO-matched grafts vs. ABO-I grafts was 93.0% and 100%, respectively, whereas graft survival was 83.4% and 92.3%. Additionally, 6 of 16 (37.5%) ABO-I transplanted children had 8 rejection episodes, whereas 47 patients (44.8%) had 121 rejection episodes in the ABO-compatible group. There were no vascular complications and 2 biliary strictures in the ABO-I group. Plasmapheresis was not used for pretransplantation desensitization and was only required in 1 posttransplantation recipient. No child was splenectomized. Six of the 16 children were older than 13 yr of age, suggesting the possibility of successfully expanding this technique to an older population. In conclusion, our outcomes may support the concept of using ABO-I grafts in a more elective setting associated with split and living donor liver transplants.
Background The enzymatic method of caeruloplasmin measurement is based on copper-dependent oxidase activity. The advantage of the oxidase determination is that it has a much lower detection limit compared with immunoassay-based methods. It has found its application in both the diagnosis of Wilson’s disease and also in the monitoring of patients’ response to treatment. Methods The method previously described in literature was adapted for use on a 96-well plate. Caeruloplasmin oxidase activity results were derived from the equation: caeruloplasmin oxidase activity = (A 15 −A 5 ) × 185 U/L. Results Repeatability (intra-batch) imprecision ranged from 6 to 15% and intermediate (inter-batch) imprecision varied from 7 to 16% for caeruloplasmin oxidative activities of 14, 29, 45 and 99 U/L. Between 3 and 92 U/L, the assay appeared linear with a regression coefficient R 2 = 0.9958. The lower limit of quantification was 4 U/L. Samples were stable over a five-week period at 4℃ and for at least four freeze–thaw cycles. There was a statistically significant difference between the areas under ROC curve for copper-to-caeruloplasmin ratios between caeruloplasmin oxidative activity and immunoassay-based methods ( P < 0.0171). The reference interval for caeruloplasmin activity was determined to be 12–166 U/L. Conclusions Using the oxidative assay provides a cost-effective means of estimating caeruloplasmin concentrations. The method is easily adaptable to a 96-well plate format that facilitates high throughput of samples in a busy laboratory. The enzymatic method is more sensitive and specific for differentiating between Wilson’s and non-Wilson’s when compared with immunoassay-based methods.
Methods of monitoring disease activity and detecting cardiac involvement in myositis are inadequate, contributing to poor outcomes. We investigated the potential for a panel of serum muscle damage markers to address these issues.
Methods
Disease activity and cardiac involvement in adult myositis patients was assessed and serum total creatine kinase (CK), cardiac troponin-T (cTnT), cardiac troponin-I (cTnI) and CK-MB were measured. Convergent construct validity assessment using Spearman’s ranked correlation and logistic regression were used.
Results
Of 46 patients, most had dermatomyositis (39%). The mean age was 52 years. 72% were female. Strongest correlations were observed between cTnT and manual muscle testing scores (rho −0.53, p<0.001), and between CK-MB and the Health Assessment Questionnaire (HAQ) (rho 0.44, p=0.002). Combining an abnormal CK and CK-MB identified a group with a significantly higher HAQ (OR 2.06, 95% CI 1.07–3.97, p=0.031), whereas this was not found in those with an abnormal CK alone. Serum muscle damage marker levels were not significantly different in those with cardiac involvement (n=8) although an abnormal cTnI had 95% specificity for cardiac involvement.
Conclusion
When assessing disease activity in myositis, serum cTnT and CK-MB appear useful in addition to total CK, whereas cTnI may assist identification of cardiac involvement.
Background: This study aimed to describe the baseline renal, histopathological and hematological characteristics and any clinical or biochemical associations of patients with a first coded diagnosis of multiple myeloma (MM). The incidence of renal replacement therapy (RRT) and association with mortality were also investigated. Methods: A retrospective case review was performed to identify 287 MM patients from two European centers. Statistical analyses were performed using SPSS version 2.0 and SAS version 9.2. Results: MM patients referred to renal centers were more likely to be elderly and male. The most common form of renal impairment was acute kidney injury (AKI). The most common paraprotein-associated lesions were myeloma cast nephropathy (MCN, 51%), light chain deposition disease (17%) and AL-amyloidosis (9.4%). MM with AKI was found to be a more aggressive disease, being associated with worse hematological features and increased risk of short-term death. Of the AKI patients requiring RRT, 80% required it at presentation. There was no increased risk of death in the RRT requiring vs. non-RRT requiring cohort. Monoclonal gammopathy of undetermined significance (MGUS) may predispose to renal damage and may increase likelihood of AKI in context of MM. Conclusion: MM-related renal failure is a medical emergency with the need for rapid diagnosis and prompt supportive care, RRT and MM-directed therapy. J Hematol. 2016;5(1):8-16 doi: http://dx.doi.org/10.14740/jh229w
Cardiometabolic disease is more common in patients with schizophrenia than the general population.The purpose of the study was to assess lifestyle factors, including diet and exercise, in patients with schizophrenia and estimate the prevalence of metabolic syndrome.This is a cross-sectional study of a representative group of outpatients with schizophrenia in Salford, UK. An interview supplemented by questionnaires was used to assess diet, physical activity, and cigarette and alcohol use. Likert scales assessed subjects' views of diet and activity. A physical examination and relevant blood tests were conducted.Thirty-seven people were included in the study. 92% of men had central adiposity, as did 91.7% of women (International Diabetes Federation Definition). The mean age was 46.2 years and mean illness duration was 11.6 years. 67.6% fulfilled criteria for the metabolic syndrome. The mean number of fruit and vegetable portions per day was 2.8 ± 1.8. Over a third did not eat any fruit in a typical week. 42% reported doing no vigorous activity in a typical week. 64.9% smoked and in many cigarette use was heavy. The Likert scale showed that a high proportion of patients had insight into their unhealthy lifestyles.Within this sample, there was a high prevalence of poor diet, smoking and inadequate exercise. Many did not follow national recommendations for dietary intake of fruit and vegetables and daily exercise. These factors probably contribute to the high prevalence of metabolic syndrome. Many had insight into their unhealthy lifestyles. Thus, there is potential for interventions to improve lifestyle factors and reduce the risk of cardiometabolic disease.
T cells recognize microbial glycolipids presented by CD1 proteins, but there is no information regarding the generation of natural glycolipid antigens within infected tissues. Therefore, we determined the molecular basis of CD1b-restricted T cell recognition of mycobacterial glycosylated mycolates, including those produced during tissue infection in vivo. Transfection of the T cell receptor (TCR) α and β chains from a glucose monomycolate (GMM)-specific T cell line reconstituted GMM recognition in TCR-deficient T lymphoblastoma cells. This TCR-mediated response was highly specific for natural mycobacterial glucose-6-O-(2R, 3R) monomycolate, including the precise structure of the glucose moiety, the stereochemistry of the mycolate lipid, and the linkage between the carbohydrate and the lipid. Mycobacterial production of antigenic GMM absolutely required a nonmycobacterial source of glucose that could be supplied by adding glucose to media at concentrations found in mammalian tissues or by infecting tissue in vivo. These results indicate that mycobacteria synthesized antigenic GMM by coupling mycobacterial mycolates to host-derived glucose. Specific T cell recognition of an epitope formed by interaction of host and pathogen biosynthetic pathways provides a mechanism for immune response to those pathogenic mycobacteria that have productively infected tissues, as distinguished from ubiquitous, but innocuous, environmental mycobacteria.
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