Systemic features and early prognostic factors in Hispanic and non-Hispanic children from the United States of America and Mexico with systemic juvenile idiopathic arthritis.

OBJECTIVE: To investigate if the persistence of systemic features is longer in Hispanic children with systemic juvenile idiopathic arthritis (S-JIA) than in non-Hispanic children with S-JIA and to determine early predictors of systemic and articular disease. METHODS: We performed a multi-center retrospective chart review of patients followed in six pediatric rheumatology centers with onset of S-JIA from 1974 to 2004. Patients were included in the study if they had been followed for > or = 1 year after disease onset. Information collected included demographic, clinical, laboratory and treatment data. Systemic features included fever, rash, lymphadenopathy, hepatosplenomegaly, pericarditis, and pleuritis. RESULTS: Of the 159 S-JIA patients screened, 120 (75%) met our inclusion criteria. There were 65 boys and 55 girls. The mean follow-up period for Hispanic patients was 5.7 years (SD 4.0) and for non-Hispanic patients was 8.6 years (SD 7.2). There was no significant difference in the presence of systemic features between Hispanic and non-Hispanic patients at 0.5, 1, 2, 4, 6, 8, and 10 years of follow-up. Polyarthritis at the 6-month visit was predictive of systemic features (OR 9.7, 95% CI 1.16-81.35, p = 0.036) and polyarthritis (OR 5.6, 95% CI 1.42-21.8, p = 0.014) at last follow-up. CONCLUSION: In children with S-JIA, Hispanics did not demonstrate longer persistence of systemic features than non-Hispanics. Polyarthritis at 6 months strongly predicted the development of persistent systemic features and chronic polyarticular disease.

Comparison of in vivo efficacy and mechanism of action of antimurine monoclonal antibodies directed against TCR alpha beta (H57-597) and CD3 (145-2C11).

Monoclonal antibodies (mAbs) directed against the T cell receptor (TCR)-associated CD3 chains and against the TCR-alpha beta heterodimer can inhibit allograft rejection in humans and in experimental animals. Since the effects of stimulation through these cell surface structures may differ, it has been suggested that there could be advantages to targeting one structure versus the other. In order to directly compare two such mAbs for in vivo immunosuppressive properties and mechanisms of action, C57BL/10 mice were treated with mAbs H57-597 (H57, anti-alpha beta) or 145-2C11 (2C11, anti-CD3), either as intact mAb or as F(ab')2 fragments. F(ab')2 fragments of both mAbs had similar effects. Both prolonged skin allograft survival, preferentially depleted CD4+ T cells, downregulated IL-2 secretion, and failed to inhibit CTL. In contrast, the effects of the intact form of the two mAbs differed significantly. Intact H57 was far more effective than 2C11 in prolonging skin allograft survival and in inhibiting cytokine secretion and CTL function. This increased immunosuppressive effect was associated with a significantly more complete and prolonged depletion of both CD4+ and CD8+ T cells and down-modulation of TCR expression on remaining T cells. A markedly greater half-life was observed for H57, associated with reduced immunogenicity. These data suggest that the increased immunosuppressive properties of H57 are due to its reduced immunogenicity, rather than to differences in signal transduction, and support the argument that reducing the immunogenicity of mAbs in the clinical setting by "humanization" may result in improved efficacy.

A mobile HIV education, counseling, and testing unit: a pilot initiative.

In May and June, 1989, the Hartford (CT) Health Department piloted a mobile educational unit, the "HIVan," which also included an HIV counseling and testing component. The intent of this initiative was to reach African-American and Latino communities, and intravenous drug users (IVDUs) and sex workers, all communities at demonstrated risk for HIV infection in Hartford. Results indicate a high degree of success in reaching the targeted communities with the HIVan with HIV counseling and testing: 95.2% of the HIVan clients were African-American or Latino, 59.2% were IVDUs. Of 79 persons tested on the HIVan seroprevalence was 26.5%, almost five times that of the primary clinic site. Return for posttest counseling and results is currently low (20.2%), but will be monitored over time, as the rate of return for results increases over time. A recommendation is made to find and implement similar mobile initiatives in communities where at-risk persons are reluctant to enter a clinical setting.

HIV seroprevalence, risk behaviors, and cognitive factors among Asian and Pacific Islander American men who have sex with men: a summary and critique of empirical studies and methodological issues.

The goals of this article are to (a) summarize and discuss published empirical studies addressing HIV seroprevalence rates and HIV-related behaviors and cognitive factors among Asian and Pacific Islander American (API) men who have sex with men (MSM) in the United States, (b) examine existing population-based research methodologies for studying HIV and AIDS prevention, (c) describe a conceptual framework to facilitate the identification of ecologically sound or culturally appropriate and competent methodologies for studying HIV prevention among API MSM, and (d) discuss methodological issues and recommend alternative methodologies to better understand this population in HIV prevention. A total of eight published empirical studies reported the HIV seroprevalence rates, HIV-risk behaviors, and attitudes toward HIV and AIDS among API MSM. Specifically, seven studies reported HIV seroprevalence rates that were based on either self-disclosure of HIV status or HIV test results among the study participants. Four studies also reported findings about the relationships between HIV-related behaviors and cognitive factors. There are five population-based databases on HIV and AIDS epidemiology and surveillance which have been managed by the Centers for Disease Control and Prevention. Findings from the seven studies indicate that API MSM are as likely to engage in HIV-risk behaviors as other groups. The present analysis reveals that conventional surveillance or epidemiological techniques (e.g., random digit telephone dialing), based on a singular model of populations, are not appropriate to address culturally, linguistically and racially/ethnically diverse groups of API MSM. To address the diversity of this group, ecologically sound or culturally appropriate and competent research methodologies are needed. Thus, a conceptual framework for such methodologies with examples was reviewed. Two alternative methodologies, network analysis and venue-based sampling, were briefly discussed.

PIP: This article presents a summary of HIV seroprevalence rate and HIV-related behavior empirical studies. Results of population-based HIV and AIDS prevention programs are analyzed. Furthermore, this paper describes a conceptual framework for HIV prevention and discusses methodological issues and alternative HIV prevention programs among Asian and Pacific Islander (API) American men who have sex with men (MSM). This study analyzed 8 published studies on HIV seroprevalence rates, HIV risk behaviors, and HIV/AIDS attitudes among API MSM, particularly 7 studies on HIV seroprevalence rates which were based on HIV status self-disclosure and HIV test results. Of the 8 studies, 4 were able to focus on API MSM. The Center for Disease Control, which controls the surveillance of population-based HIV/AIDS epidemiology, utilizes 5 databases. These studies indicate that API MSM were likely to practice unsafe behaviors compared with other risk groups. The use of conventional surveillance or epidemiological techniques based on a singular model of populations is inadequate in response to the culturally, linguistically, and racially/ethnically diverse groups of API MSM. It was suggested that the use of ecologically sound or culturally appropriate and competent research methodologies is necessary to address the diversity of this group. Finally, a discussion on the use of two alternative methodologies, particularly network analysis and venue-based sampling within a conceptual framework, is presented.

Clinical outcomes and patient perceptions of acupuncture and/or massage therapies in HIV-infected individuals.

This paper uses an innovative methodology to evaluate clinical outcomes and patient perceptions of acupuncture and massage therapies in an HIV medical outpatient setting. Using a quasi-experimental retrospective case control design, treatment subjects were matched by intake date and CD4 count with non-treatment subjects. All subjects had equal opportunity to access HAART therapies and other standard treatments for HIV. There were three treatment groups: acupuncture-only (n = 8), massage-only (n = 34) and acupuncture-and-massage (n = 21). Pre-treatment and post-treatment measures were compared within groups, and treatment and non-treatment group clinical outcomes were compared with each other. Using nonparametric statistical analysis, it was found that the means of the treatment groups' differences in pre- and post-CD4 counts showed improvement when compared with the non-treatment control group's pre- and post-CD4 counts. Treatment subjects were then interviewed and asked to rate their experiences of the therapies; the subjective experience was very positive. The reasons for these findings may be complex, including the possibility that some people may choose to manage their disease more aggressively, and may select a range of treatments. While no large claims are made for this study, these findings may be of interest both to clinicians and funders of acupuncture and/or massage therapies.

Reduction of mortality and lymphadenopathy in MRL-lpr/lpr mice treated with nonmitogenic anti-CD3 monoclonal antibody.

OBJECTIVE: To evaluate the therapeutic efficacy of nonmitogenic anti-CD3 monoclonal antibody (MAb) in a preexisting autoaggressive response, using the MRL-lpr/lpr (MRL/l) murine model of autoimmune disease. METHODS: Female MRL/l mice, 8-10 weeks of age, were treated with nonmitogenic anti-CD3 MAb or phosphate buffered saline and effects on mortality, lymphadenopathy, T cell phenotypes, anti-DNA titers, and total IgG titers were measured. RESULTS: Nonmitogenic anti-CD3 MAb treatment resulted in a dramatic reduction in lymphadenopathy and mortality, as well as an early reduction in alpha/beta+, CD4-, CD8-, Thy+, B220+ (double-negative) lymph node cells. No significant effects on anti-DNA or IgG titers were observed. No morbidity was observed following administration of nonmitogenic anti-CD3 MAb. CONCLUSION: A short course of treatment with nonmitogenic anti-CD3 MAb can suppress preexisting autoimmune responses without inducing the cytokine-mediated toxicity characteristic of mitogenic forms of anti-CD3 MAb. The use of nonmitogenic anti-CD3 MAb may be efficacious in the clinical setting for the treatment of T cell-mediated autoimmune disorders.

The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers.

Mutations in the extracellular domain of the 55-kD tumor-necrosis factor (TNF) receptor (TNFRSF1A), a key regulator of inflammation, define a periodic-fever syndrome, TRAPS (TNF receptor-associated periodic syndrome [MIM 142680]), which is characterized by attacks of fever, sterile peritonitis, arthralgia, myalgia, skin rash, and/or conjunctivitis; some patients also develop systemic amyloidosis. Elsewhere we have described six disease-associated TNFRSF1A mutations, five of which disrupt extracellular cysteines involved in disulfide bonds; four other mutations have subsequently been reported. Among 150 additional patients with unexplained periodic fevers, we have identified four novel TNFRSF1A mutations (H22Y, C33G, S86P, and c.193-14 G-->A), one mutation (C30S) described by another group, and two substitutions (P46L and R92Q) present in approximately 1% of control chromosomes. The increased frequency of P46L and R92Q among patients with periodic fever, as well as functional studies of TNFRSF1A, argue that these are low-penetrance mutations rather than benign polymorphisms. The c.193-14 G-->A mutation creates a splice-acceptor site upstream of exon 3, resulting in a transcript encoding four additional extracellular amino acids. T50M and c.193-14 G-->A occur at CpG hotspots, and haplotype analysis is consistent with recurrent mutations at these sites. In contrast, although R92Q also arises at a CpG motif, we identified a common founder chromosome in unrelated individuals with this substitution. Genotype-phenotype studies identified, as carriers of cysteine mutations, 13 of 14 patients with TRAPS and amyloidosis and indicated a lower penetrance of TRAPS symptoms in individuals with noncysteine mutations. In two families with dominantly inherited disease and in 90 sporadic cases that presented with a compatible clinical history, we have not identified any TNFRSF1A mutation, despite comprehensive genomic sequencing of all of the exons, therefore suggesting further genetic heterogeneity of the periodic-fever syndromes.