Establishment of a system to standardize acceptability criteria for alanine aminotransferase activity in donated blood

A multilaboratory study was conducted to develop a system for standardizing alanine aminotransferase (ALT) acceptability criteria ("cutoffs") for donated blood. Without standardized cutoffs, each laboratory must develop its own cutoff, and this may not make optimal use of ALT testing to reduce transmission of non-A, non-B hepatitis (NANB). Defining an ALT acceptability criterion in absolute terms is necessary because relative cutoffs based on local donor populations may be affected by the prevalence of NANB in each community. This study involved 16 laboratories using 23 different analytic systems. The ALT results of the analysis of a plasma reference sample could be used to translate mathematically a single, absolute cutoff to units applicable to each analytic system. The distribution of ALT results in 1.4 million donations from across the country was established; basing the cutoff on this sample avoids the problems inherent in using a local donor base to establish a cutoff. We propose the implementation of a system to standardize ALT acceptability criteria to an activity level defined by analysis of a nationwide donor sample.     

Predictors of growth and body composition in HIV‐infected children beginning or changing antiretroviral therapy

Objectives

The aim of the study was to describe growth and body composition changes in HIV‐positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters.

Methods

Ninety‐seven prepubertal HIV‐positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999–2002 (NHANES) to generate z‐scores and with results for HIV‐exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters.

Results

All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height²) z‐scores increased over time (P=0.004, 0.037 and 0.027, respectively) and the waist:height ratio z‐score decreased (P=0.045), but body mass index and per cent body fat z‐scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid‐thigh circumference and FFM z‐scores related to CD4 percentage (P=0.029, P=0.008 and 0.020, respectively) and change in FFM and FFM index z‐scores to CD4 percentage increase (P=0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid‐thigh muscle circumference were also associated with CD4 percentage. Case–control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time.

Conclusions

In these HIV‐positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

Physiological determinants of residual cerebral arterial pulsatility on best medical treatment after TIA or minor stroke

Cerebral arterial pulsatility is strongly associated with cerebral small vessel disease and lacunar stroke yet its dependence on central versus local haemodynamic processes is unclear. In a population-based study of patients on best medical managment, 4–6 weeks after a TIA or non-disabling stroke, arterial stiffness and aortic systolic, diastolic and pulse pressures were measured (Sphygmocor). Middle cerebral artery peak and trough flow velocities and Gosling’s pulsatility index were measured by transcranial ultrasound. In 981 participants, aortic and cerebral pulsatility rose strongly with age in both sexes, but aortic diastolic pressure fell more with age in men whilst cerebral trough velocity fell more in women. There was no significant association between aortic systolic or diastolic blood pressure with cerebral peak or trough flow velocity but aortic pulse pressure explained 37% of the variance in cerebral arterial pulsatility, before adjustment, whilst 49% of the variance was explained by aortic pulse pressure, arterial stiffness, age, gender and cardiovascular risk factors. Furthermore, arterial stiffness partially mediated the relationship between aortic and cerebral pulsatility. Overall, absolute aortic pressures and cerebral blood flow velocity were poorly correlated but aortic and cerebral pulsatility were strongly related, suggesting a key role for transmission of aortic pulsatility to the brain.     

An australian audit of vaccination status in children and adolescents with inflammatory bowel disease

Background

Pre-existing polyps, especially large polyps, are known to be the major source for colorectal cancer, but there is limited available information about factors that are associated with polyp size and polyp growth. We aim to determine factors associated with polyp size in different age groups.

Methods

Colonoscopy data were prospectively collected from 67 adult gastrointestinal practice sites in the United States between 2002 and 2007 using a computer-generated endoscopic report form. Data were transmitted to and stored in a central data repository, where all asymptomatic white (n = 78352) and black (n = 4289) patients who had a polyp finding on screening colonoscopy were identified. Univariate and multivariate analysis of age, gender, performance site, race, polyp location, number of polyps, and family history as risk factors associated with the size of the largest polyp detected at colonoscopy.

Results

In both genders, size of the largest polyp increased progressively with age in all age groups (P < .0001). In subjects ≥ 80 years the relative risk was 1.55 (95% CI, 1.35-1.79) compared to subjects in the youngest age group. With the exception of family history, all study variables were significantly associated with polyp size (P < .0001), with multiple polyps (≥ 2 versus 1) having the strongest risk: 3.41 (95% CI, 3.29-3.54).

Conclusions

In both genders there is a significant increase in polyp size detected during screening colonoscopy with increasing age. Important additional risk factors associated with increasing polyp size are gender, race, polyp location, and number of polyps, with polyp multiplicity being the strongest risk factor. Previous family history of bowel cancer was not a risk factor.     

Polyethylene glycol versus low-ionic-strength solution in pretransfusion testing: a blinded comparison study

BACKGROUND: Polyethylene glycol (PEG) has been shown to potentiate antigen-antibody reactions. STUDY DESIGN AND METHODS: To investigate the utility of PEG in pretransfusion testing, a blinded comparison study of PEG and a low-ionic-strength additive solution (LISS) was conducted. A total of 500 patient samples were tested in parallel with reagent antibody-detection cells using blind-coded PEG and LISS potentiators. RESULTS: In 34 (34%) of 100 samples with known antibodies in the Rh, Kell, Duffy, Kidd, and MNS systems, PEG antiglobulin reactions were stronger (total score, 382) than LISS antiglobulin reactions (total score, 216), and in 66 cases (66%), they were equal to those of LISS. Of 400 samples without detectable antibodies, 384 were negative with PEG and LISS, and 16 were positive in PEG tests and negative in LISS. Seven of the 16 were clinically important antibodies (D, 1; E, 3; Fya, 1; Jka; 1; Jkb, 1), and four were clinically benign antibodies (Le(a), 2; McCc, 1; Sda, 1). Five of the 16 demonstrated inconclusive PEG reactions, for a false-positive rate of 5 in 400 (1.3%). Of the 500 samples, none was negative in PEG tests and positive in LISS (0% false-negative rate). CONCLUSION: Although PEG demonstrates a relatively high false-positive rate, PEG is more sensitive than LISS in detecting clinically significant antibodies.     

三叶因子与胃黏膜保护的研究进展

三叶因子家族是一群主要由胃肠道黏液细胞分泌的小分子多肽.其共同特征为均含一特殊的P结构域及三叶状结构.这种稳定的结构使三叶因子家族具有明显的抗蛋白酶水解、酸消化及耐热特性,因而能在消化道复杂的环境中保持生物活性.目前在哺乳动物体内发现的有pS2/TFF1、SP/TFF2和ITF/TFF3三种,它们具有黏膜保护与修复、肿瘤抑制、信号传导、调节细胞凋亡等功能.本文阐述了三叶因子家族发现的历史,并初步探讨了其作用.同时也对三叶因子受体这一热点的研究现状进行总结.