Immunohistochemical analysis of intestinal biopsies in individuals with celiac disease.

Background and Aims: The immunohistochemical application of CD3 (T lymphocytes) and CD20 (B lymphocytes) markers in duodenal biopsy can facilitate the detection of the number and distribution of intraepithelial lymphocytes along the villi, which is regarded as a key factor for accurate diagnosis of celiac disease. This study aims at finding a relationship between CD3 and CD20 immunohistochemical and histopathological alterations of celiac disease, and at investigating whether the application of those immunohistochemical stainings would improve the detection of lymphocytosis within the epithelium and add advantages to celiac disease diagnosis. Methods: Biopsies were obtained from 100 individuals and stained with hematoxylin and eosin (H&E). They were then evaluated according to the Marsh classification. After that, staining for CD3 and CD20 was individually done and assessed. Results: The overall mean intraepithelial lymphocyte count per 100 enterocytes for H&E was 23.1 (95% confidence interval [CI] = 19.52-26.68), and for immunohistochemistry by CD3 and CD20 was 27.84 (95% CI = 24.31-31.38). The difference was highly significant, P = 0.001. The expression of CD3 immunohistochemically was as follows: Less-than-half staining pattern was reported in 16% cases, and half staining pattern was seen in 26%, while most cases 58% had more than half staining pattern. This discovery was consistent with the histological classification of March III among most cases. The expression of CD20 immunohistochemically was as follows: mild crypt involvement was observed in 16% of cases, while moderate crypt involvement and intense crypt involvement were seen in 43% and 41% of cases, respectively.

Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype.

OBJECTIVE: Activating mutations of the fms-like tyrosine kinase 3 gene (FLT3) by internal tandem duplications (ITDs) in the juxtamembrane domain (JMD) have been reported in ~30% of adult acute myeloid leukemia (AML) patients with cytogenetically normal karyotype (CN). However, FLT3/ITD mutations are frequently accompanied with leukocytosis, high percentage of blasts in bone marrow (BM), and increased the risk of treatment failure in AML patients. FLT3-ITD mutated AML patients mainly with normal karyotype have higher relapse probability and shorter duration of complete remission (CR) after chemotherapy, so FLT3-ITD mutation is considered as an independent poor prognostic factor in AML. METHODS: FLT3-ITD and FLT3-KTD were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism- PCR (RFLP-PCR) in 44 adults AML patients with cytogenetically normal karyotype (AML-CN) at diagnosis to characterize FLT3 status. The results were correlated with the prognostic factors. RESULTS: In this study, FLT3-ITD mutations were identified in 7 (15.9%) of the 44 AML-CN patients. Among the 7 patients with FLT3/ITD mutations, 6 patients revealed a typical ITDs mutation (fragment size was 329 bp) and one patient showed untypical ITD mutation (fragment size was ~400 bp). Whereas 37 patients (61.7%) were FLT3-ITD. None of all AML-CN patients examined showed FLT3-KTD mutations. CONCLUSIONS: Our results support that FLT3-ITD are independent adverse prognostic factors for elderly AML-CN patients and are associated with low overall survival (OS), low rate of CR, high relapse rate (RR), and high percentage of BM blast at diagnosis. We concluded, FLT3 mutation analysis should be performed as a routine test in AML-CN patients.

Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment.

D-Ala1-peptide T-amide (DAPTA) has shown neuroprotection in vitro against gp120-induced loss of dendritic arborization and is promulgated as a CCR5 antagonist. A multisite, randomized, double-blind clinical trial of DAPTA versus placebo prior to combination antiretroviral therapy conducted with human immunodeficiency virus (HIV)-1 seropositive participants having cognitive impairment showed no overall cognitive effect, though subgroups with greater impairment and CD4 cell counts of 201 to 500 cells/mm3 at baseline showed significant improvement. The objective of this study was to examine whether intranasal administration of DAPTA at a dose of 2 mg three times per day (tid) was associated with a reduction of cerebrospinal fluid (CSF) and peripheral (plasma and serum) viral load among a subgroup of participants completing 6 months of treatment. Baseline and 6-month CSF (n = 92) and peripheral (plasma n = 33; serum n = 24) viral load were measured by the Roche Ultrasensitive assay, version 1.5, with reflexive use of the AMPLICOR assay and preservation of the blind. A DAPTA treatment indicator variable was tested using generalized linear models on change in viral load. Peripheral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group. No group differences in CSF viral load were found. This retrospective study on a limited subgroup of the original trial sample indicated that DAPTA treatment may reduce peripheral viral load without concomitant CSF effects. Future studies should be undertaken to confirm the existence of this result and the CSF-periphery dissociation observed with respect to HIV-1-associated cognitive-motor impairment.

Older age and plasma viral load in HIV-1 infection.

BACKGROUND: The purpose of the study was to examine the relationship between age and plasma viral load in HIV-1-infected individuals. DESIGN: The experimental method was to recruit older (> 50 years of age) and younger (18-39 years of age) HIV-1-infected individuals. The plasma viral load was measured using the Roche Molecular Systems UltraSensitive Roche HIV-1 Monitor test reflexively with the standard Amplicor HIV Monitor test to quantify viral load in the range of 50-750,000 copies of HIV-1 RNA/ml plasma. SUBJECTS: A total of 135 HIV-1-seropositive individuals (at Centers for Disease Control and Prevention early symptomatic stage B or late symptomatic stage/AIDS C) were enrolled as part of a larger cohort also consisting of HIV-1-seronegative individuals. RESULTS: A generalized linear models statistical analysis was conducted in order to evaluate age category as a predictor of plasma viral load. The result was a significant effect of age category, with older age associated with a lower plasma viral load. The association held controlling for antiretroviral therapy usage, disease stage, antiretroviral medication adherence, HIV-1 serostatus duration, alcohol and substance use, recent sexually transmitted disease, and sociodemographics (except income). CONCLUSION: Older age was associated with lower levels of HIV-1 replication in this sample, independent of antiretroviral therapy usage, regimen adherence, and disease stage. It is suggested that the effect may be caused by changes in viral evolution or immunological monitoring specific to older individuals with HIV-1 infection.

Regional quantitative comparison of multispliced to unspliced ratios of HIV-1 RNA copy number in infected human brain.

Infection of the brain by HIV-1 often results in cognitive- motor disorders, the most severe form being HIV-1 associated dimentia (HAD). However, the etiology and pathogenesis of neuroAIDS at the molecular level is still not fully understood and controversial issues remain, including the significance of abortive infection and localized viral load. This paper proposes that quantitative comparison of HIV-1 proviral and RNAloads across the brain will clarify some of these issues. It was hypothesized that there are differences in ratios of multispliced and unspliced HIV RNA in different regions of brain by analogy with prior findings of brain regional differences in virus and strains of HIV-1. A competitive RT-PCR method was used to compare ratios of multispliced to unspliced HIV-1 RNA's across brain regions of one case with HAD. Statistical analysis results showed that data obtained by repeated assays for each RNA preparation were not significantly different. Significant differences were detected between specimens obtained from different regions of the brain. The ratio of MS/US RNA in the frontal lobe was significantly greater than in the basal ganglia, medial temporal lobe, and another site in the temporal lobe. It must be noted that our approach has been the analysis of macroscopic brain regions separated by several centimeters; future studies will analyze microscopic analysis of these brain regions. The current study was preformed to produce results on gross differences in neuroanatomical locations at cm distances. Future studies will be performed to compare different regions with microscopic anatomic specificity.

Cognitive functioning in younger and older HIV-1-infected adults.

In young adults, a major neurologic complication of HIV-1 infection is cognitive motor impairment. Epidemiologic findings suggest that increasing age is a significant risk factor for HIV-1-associated dementia as the AIDS-defining illness. Findings from the few studies that have directly measured cognition in younger and older HIV-1-infected adults, however, have been mixed, in part, because of small sample sizes and other methodologic differences between studies. The authors present preliminary findings on cognitive functioning in symptomatic HIV-1-infected younger (aged 20-39 years) and older (aged 50 years or older) adults. Independent of age, HIV-1 infection was accompanied by learning and memory retrieval deficits, which were significantly associated with high plasma viral loads in the young adults. Relative to the younger and older HIV-1-negative (HIV-1-) groups, only the younger HIV-1-positive (HIV-1+) group had significantly longer reaction times (RTs). Within the older HIV-1+ group, however, longer simple and choice RTs were significantly correlated with higher viral loads and lower CD4 cell counts. Although HIV-1 infection affects cognition independent of age, longitudinal studies involving large numbers of older individuals are needed to determine whether there are age differences in the prevalence, nature, and severity of HIV-1-associated cognitive dysfunction.

"Putting a face" on HIV infection/AIDS in older adults: a psychosocial context.

Older HIV-1-seropositive individuals largely have not been investigated with respect to their psychosocial characteristics. In this article, the authors review research reported to date regarding the psychosocial context of this growing subgroup of HIV-1-infected individuals. Specifically, the authors consider the characteristics of mood state, life stressor burden, social support network, and coping strategies that individuals older than 50 years are more likely to adopt in adjusting to HIV-1 infection. The authors also separately consider issues of caregiving burden. Data supporting a theoretically based stressor-support-coping model are presented and related to targeting psychotherapeutic interventions for this age group.

Effects of physiologic human brain motion on proton spectroscopy: quantitative analysis and correction with cardiac gating.

SUMMARY: Proton MR spectroscopy is a powerful noninvasive method that enables measurement of certain brain metabolites in healthy subjects and patients with diseases. A major difficulty with clinical and research applications of in vivo proton MR spectroscopy is the variability of metabolite concentrations, especially in regions with substantial physiologic motion. In our preliminary evaluation, we tested the hypothesis that physiologic brain motion leads to lower mean metabolite concentrations and higher SDs for the measured metabolite concentrations.