Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women's Interagency HIV Study

BACKGROUND: Anemia is common in HIV-infected individuals and may be associated with decreased survival. OBJECTIVE: To ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women. METHODS: A prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women's Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period. RESULTS: Among HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/microL (OR = 0.56; P < 0.001); HIV-1 RNA level > or =50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/microL (HR = 5.83; P < 0.001), HIV-1 RNA level > or = 50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001). CONCLUSIONS: Anemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia.     

Study of nuclear diameters in non-Hodgkin's lymphomas

The mean maximum nuclear diameter (D_max) in 21 cases of non-Hodgkin's lymphoma (NHL) has been determined, using the Reichert-Jung (Kontron) MOP-AMO₃ user-controlled image analyser. Nuclear diameters of high-grade malignancy NHL were found to be considerably greater than those of low-grade malignancy lymphomas, although there was some overlap of their ranges. These findings confirm objectively subjective estimates of nuclear size in NHL. The relative usefulness of the user-controlled (interactive) image analyser for the measurement of nuclei in tissue sections is compared with that of a fully automatic machine.     

Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system

Targeted recombination was carried out to select mouse hepatitis viruses (MHVs) in a defined genetic background, containing an MHV-JHM spike gene encoding either three heptad repeat 1 (HR1) substitutions (Q1067H, Q1094H, and L1114R) or L1114R alone. The recombinant virus, which expresses spike with the three substitutions, was nonfusogenic at neutral pH. Its replication was significantly inhibited by lysosomotropic agents, and it was highly neuroattenuated in vivo. In contrast, the recombinant expressing spike with L1114R alone mediated cell-to-cell fusion at neutral pH and replicated efficiently despite the presence of lysosomotropic agents; however, it still caused only subclinical morbidity and no mortality in animals. Thus, both recombinant viruses were highly attenuated and expressed viral antigen which was restricted to the olfactory bulbs and was markedly absent from other regions of the brains at 5 days postinfection. These data demonstrate that amino acid substitutions, in particular L1114R, within HR1 of the JHM spike reduced the ability of MHV to spread in the central nervous system. Furthermore, the requirements for low pH for fusion and viral entry are not prerequisites for the highly attenuated phenotype.     

Development of human visual cortex: a balance between excitatory and inhibitory plasticity mechanisms

Formation of neural circuitry in the developing visual cortex is shaped by experience during the critical period. A number of mechanisms, including N-methyl-D-aspartate (NMDA) receptor activation and gamma-aminobutyric acid (GABA)-mediated inhibition, are crucial in determining onset and closure of the critical period for visual plasticity. Animal models have shown that a threshold level of tonic inhibition must be reached for critical period plasticity to occur and that NMDA receptors contribute to Hebbian synaptic plasticity in the developing visual cortex. There are a number of developmental changes in these glutamatergic and GABAergic mechanisms that have been linked to plasticity; however, those changes have been shown only in animal models, and their development in the human visual cortex is not known. We have addressed this question by studying the expression of the major glutamatergic receptors, GABA(A) receptors, and glutamic acid decarboxylase (GAD) isoforms during the first 6 years of postnatal development of human visual cortex. There are significant changes in the expression of these proteins during postnatal development of human visual cortex. The time course of the changes is quite prolonged and suggests that it may set the pace for the prolonged critical period in human visual development. The changes also affect the nature of spatial and temporal integration in visual cortical neurons and thereby contribute to the maturation of visual functions.     

High incidence of the Cys 282 Tyr mutation in the HFE gene in the Irish population -implications for haemochromatosis

Abstract: A simple PCR-SSOP approach based on a single PCR product has been developed to screen the HFE gene for the haemochromatosis-associated mutations Cys 282 Tyr and His 63 Asp. Using this approach the prevalence of these mutations in a cohort (30) of haemochromatosis patients and normal controls (404) was determined. Ninety percent of the haemochromatosis patients were homozygous for the Cys 282 Tyr mutation. In the normal population we found an increased incidence of the Cys 282 Tyr mutation (17.3%; 95% confidence limits 0.136–0.209) which was also reflected in the higher frequency of Cys 282 Tyr homozygotes (1.24%; 95% confidence limits 0.0015–0.0232). Linkage disequilbrium analysis confirmed the association between A*03 and Cys 282 Tyr. However, strong linkage disequilibrium occurred with the HLA-A*03-associated allele HLA-B*14 but not the HLA-A*03-associated allele HLA-B*07. The His 63 Asp was found to be in linkage disquilibrium with HLA-A*29.     

Detecting Candida albicans in human milk

Procedures for diagnosis of mammary candidosis, including laboratory confirmation, are not well defined. Lactoferrin present in human milk can inhibit growth of Candida albicans, thereby limiting the ability to detect yeast infections. The inhibitory effect of various lactoferrin concentrations on the growth of C. albicans in whole human milk was studied. The addition of iron to the milk led to a two- to threefold increase in cell counts when milk contained 3.0 mg of lactoferrin/ml and markedly reduced the likelihood of false-negative culture results. This method may provide the necessary objective support needed for diagnosis of mammary candidosis.     

Effects of topical administration of levocabastine on psychomotor and cognitive function.

The possible central nervous system effects of topical administration of levocabastine, a new H1-antagonist, were investigated in a double-blind, placebo-controlled, crossover study using a battery of objective and subjective tests. These were carried out in 12 volunteers up to five hours postapplication. Neither the recommended (0.5 mg/mL) nor the four times higher (2.0 mg/mL) concentration level was found to be distinguishable from placebo, while the verum (triprolidine 10 mg) was significantly worse, on both objective and subjective measures.     

Histopathologic analysis of atypical lesions in image-guided core breast biopsies.

Appropriate follow-up of patients with needle core breast biopsies (NCBB) showing atypical hyperplasia remains unclear because previous studies show that subsequent open biopsies in variable proportions of these patients reveal ductal carcinoma in situ (DCIS) or even invasive carcinoma, indicating significant sampling artifact. NCBB with diagnoses of atypia were morphologically classified into groups as follows: I, ALH (n = 24); II, ADH with minimal cytologic atypism (n = 90); III, atypia, other (9 columnar, 2 apocrine, 11 atypical papillary); IV, severe ADH/borderline DCIS (n = 31). Mammographic and histologic features, including the number of foci of atypia in the NCBB and the calcification span, were then correlated with presence of DCIS or invasive tumor in subsequent open excisions. Open excisional biopsies showed more severe lesions in 12% of Group I-III cases (8% in Group I, 9% in Group II, and 27% in Group III), of which 15 were DCIS and one was an invasive tubular carcinoma (0.3 cm). Of the DCIS, 60% (n = 9) were < or =5 mm, and 13 of 15 (87%) were low grade. The NCBB cavity was immediately adjacent to the more severe lesions in 88% (n = 14) of cases, in keeping with sampling error. The subset showing severe ADH with borderline nuclear features in contrast was associated with a high likelihood (63%) of DCIS in follow-up excisions. NCBB with atypical papillary features also showed a high frequency of DCIS (4/11, 36%) in subsequent open excisions. Other factors associated with more severe lesions on open biopsy included the number of atypical foci in the NCBB (>4, P <.05) and the mammographic calcification span (>2.0 cm, P <.0001). Atypical lesions diagnosed in NCBB samples are radiographically and morphologically heterogeneous, accounting for the variable frequency of DCIS or invasive neoplasm identified in subsequent open excisions, which are usually focal, low grade, and a consequence of sampling artifact (i.e., adjacent to the NCBB cavity). DCIS is more likely if microcalcifications are mammographically extensive or if atypia is multifocal or is associated with borderline cytologic features.