A search for hepatitis C virus polymerase chain reaction-positive but seronegative subjects among blood donors with elevated alanine aminotransferase

BACKGROUND: Previous studies reported the existence of hepatitis C virus (HCV) polymerase chain reaction (PCR)-positive but seronegative sera. This is not surprising in the case of window-phase specimens, because PCR can detect HCV RNA many weeks before the appearance of antibody. To determine whether such sera can also be found in chronically infected subjects, a high-risk population of blood donors with elevated alanine aminotransferase was studied. STUDY DESIGN AND METHODS: Freshly frozen plasma from 301 donors with alanine aminotransferase > 100 IU per L was tested with PCR assays that were rigidly controlled for specificity and contamination, and with current and newer versions of assays for anti-HCV. Sera were classified as seropositive if positive in two screening assays and one supplemental assay or if positive in two screening assays and PCR. RESULTS: New versions of screening assays detected 100 percent of seropositive samples. A second-generation immunoblot assay detected 98 percent of seropositive sera, a second-generation recombinant immunoblot assay detected 96 percent, and an enzyme immunoassay for antibody to the envelope protein of HCV detected 98 percent. Fifty-one of 54 seropositive sera were PCR positive. None of the 247 seronegative samples was reproducibly positive on PCR. CONCLUSION: No PCR-positive but seronegative donors were found in this high-risk donor population. The possible benefit of PCR screening of blood donors can be determined only by large-scale comparative testing of donor populations and may be limited to the detection of window-phase infections.     

Characteristics of a donor population in western Venezuela

To determine the characteristics of blood donors in western Venezuela, we collected data from 1983 to 1985 on 31,320 volunteer donors at the Blood Bank of the State of Zulia in Maracaibo. Fifty-nine percent of the donors were blood group O, 30 percent were group A, 9 percent were group B, and 2 percent were group AB. Most of the donors (93%) were Rh positive. One percent of donors had positive reactions to hepatitis B surface antigen, 3.15 percent for syphilis, 1.43 percent for antibodies to Trypanosoma cruzi, and 0.32 percent to human immunodeficiency virus antibodies. About one-half of the donors were between 18 and 30 years old, and only 10 percent were women. To determine if iron deficiency anemia was a cause for the small size of the female donor pool, we measured serum ferritin in 50 first-time female donors. Ten of these (20%) had serum ferritin values below normal, and the distribution of serum ferritin levels of all 50 was very similar to that reported for frequent donors in Europe and the United States, with a clustering of ferritin values between 10 and 70 ng per ml. The data indicate that blood donors in western Venezuela are markedly different from those in the United States and that iron supplementation may be indicated for female Venezuelan donors.     

鸡胚胎素对小鼠红细胞数量及免疫器官质量的影响

目的:建立血虚和免疫抑制动物模型,观察鸡胚胎低温提取物对其红细胞造血以及免疫器官质量的影响。方法:实验于2001-04/2002-09在新乡医学院药物研究室完成。①实验材料:健康昆明种小鼠50只,雌雄各半。鸡胚胎素[中国发明专利公开(公告)号:CN1748713],符合研究者申报专利时提出的质量检验标准。②鸡胚胎素对血虚模型小鼠红细胞数值及血红蛋白含量的影响:取20只小鼠,随机排列表法分为鸡胚胎素组、模型对照组,10只/组,建立失血性血虚动物模型。失血后24h当红细胞数<3.2×1012L-1、血红蛋白含量<84g/L,且小鼠外观出现皮色苍白、食欲不振等现象时,代表造模成功。次日,鸡胚胎素组给予鸡胚胎素5g/(kg·d)灌胃,模型对照组给予生理盐水20mL/(kg·d)灌胃,连续14d。分别于失血前、失血后24h、末次给鸡胚胎素后2h尾部采血测定两组红细胞数量及血红蛋白含量的变化。③鸡胚胎素对免疫抑制模型小鼠免疫器官质量的影响:取30只小鼠,随机排列表法分为鸡胚胎素组、模型对照组、正常对照组,10只/组。鸡胚胎素组给予鸡胚胎素5g/(kg·d)灌胃,模型对照组和正常对照组均灌服等量生理盐水,连续14d。在第11天上午鸡胚胎素灌胃2h后,鸡胚胎素组、模型对照组腹腔注射环磷酰胺60mg/(kg·d),连续4d,复制免疫抑制动物模型。末次给予环磷酰胺2h后颈椎脱位法处死小鼠,计算胸腺、脾脏质量指数。结果:50只小鼠均进入结果分析。①失血前及失血后24h鸡胚胎素组与模型对照组的红细胞数值、血红蛋白含量基本相似(P>0.05)。末次给鸡胚胎素后2h与模型对照组比较,鸡胚胎素组红细胞数值、血红蛋白含量均明显升高(t=3.39,P<0.01;t=2.52,P<0.05)。②末次给环磷酰胺2h后与模型对照组比较,鸡胚胎素组、正常对照组的胸腺质量指数和脾脏质量指数均明显升高(t=6.62,P<0.01;t=2.47,P<0.05)。结论:鸡胚胎素灌胃对血虚小鼠具有较好的促红细胞造血功能,同时对环磷酰胺造成的免疫器官质量下降具有明显的增重作用。     

Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non- B, non-C outcomes

BACKGROUND: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B, non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti- HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. STUDY DESIGN AND METHODS: Data on blood donors and recipients enrolled in the Transfusion- Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. RESULTS: For HCV cases, donor ALT alone (at > or = 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at > or = 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected]. CONCLUSION: The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.     

Transmission of human T-lymphotropic virus type I by blood components from a donor lacking anti-p24: a case report. The Transfusion Safety Study Group

The present criteria for confirmation of human T-lymphotrophic virus types I and II (HTLV-I/II) infection in blood donors are based on seroreactivity to p24 (gag) and gp46 and/or gp61 (env) on Western blot (WB) and radioimmunoprecipitation assays (WB/RIPA). Any single band and other combinations are classified as indeterminate. This case report documents infection in a donor with a repeatedly indeterminate pattern. The blood donor was anti-HTLV-I/II positive on enzyme-linked immunoassay, and two sera taken 5 years apart were WB/RIPA-indeterminate (p19 and gp68 only). His donations in the interval were associated with transmission of HTLV-I to four of the six recipients available for study. Other recipients of blood from donors whose WB/RIPA results were indeterminate by present criteria should be examined to determine if additional patterns are at least occasionally associated with transmission. The likelihood that such donors are infected is important to those who are counseling them and making decisions concerning recipients of their bloody.     

Inhibition, flexibility, working memory and planning in autism spectrum disorders with and without comorbid ADHD-symptoms

Background

Recent studies have not paid a great deal of attention to comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms in autistic children even though it is well known that almost half of children with autism spectrum disorder (ASD) suffer from hyperactivity, inattention and impulsivity. The goal of this study was to evaluate and compare executive functioning (EF) profiles in children with ADHD and in children with ASD with and without comorbid ADHD.

Methods

Children aged 6 to 18 years old with ADHD (n = 20) or ASD (High-Functioning autism or Asperger syndrome) with (n = 20) and without (n = 20) comorbid ADHD and a typically developing group (n = 20) were compared on a battery of EF tasks comprising inhibition, flexibility, working memory and planning tasks. A MANOVA, effect sizes as well as correlations between ADHD-symptomatology and EF performance were calculated. Age- and IQ-corrected z scores were used.

Results

There was a significant effect for the factor group (F = 1.55; dF = 42; p = .02). Post-hoc analysis revealed significant differences between the ADHD and the TD group on the inhibition task for false alarms (p = .01) and between the ADHD group, the ASD+ group (p = .03), the ASD- group (p = .02) and the TD group (p = .01) for omissions. Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities. The ASD+ group showed compared to the ASD- group more problems in inhibitory performance but not in the working memory task.

Conclusion

Our findings replicate previous results reporting impairment of ADHD children in inhibition and working memory tasks and of ASD children in planning and flexibility abilities. The ASD + group showed similarities to the ADHD group with regard to inhibitory but not to working memory deficits. Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for differential diagnosis between ADHD and ASD. It might be useful for evaluating strengths and weaknesses in individual children.     

Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.     

Binding of heme by glutathione S-transferase: a possible role of the erythrocyte enzyme

Human erythrocyte glutathione S-transferase activity is inhibited, probably competitively, by hemin with a Ki of 10(-7) M. It is postulated that glutathione S-transferase functions physiologically as a hemin-binding and/or transport protein in developing erythroid cells.     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.