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Biomedical subjects

G N Beall

Publications and source records attributed to G N Beall.

At least 19 recordsLinked to original sources

The value of patient-reported adherence to antiretroviral therapy in predicting virologic and immunologic response. California Collaborative Treatment Group.

OBJECTIVE: To correlate self-reported antiretroviral adherence with virologic suppression. DESIGN: Prospective observational study of adherence to therapy nested in a randomized comparative trial of frequent versus infrequent monitoring of plasma HIV RNA. SETTING: Five university-affiliated HIV clinics. PATIENTS: A group of 173 HIV-infected patients with a mean baseline CD4 count of 142 x 10(6) cells/l (range 3-515) of whom 164 and 119 completed adherence questionnaires at 2 and 6 months, respectively. INTERVENTION: Individualized, unrestricted antiretroviral therapy. MEASUREMENTS: Patients were classified into four groups by adherence to therapy in the previous 4 weeks (< 80%, 80-95%, 95-99%, 100%). Plasma HIV RNA levels and CD4 lymphocyte counts were measured bimonthly. RESULTS: Recreational drug or alcohol use was associated with decreased adherence, whereas frequency of HIV RNA monitoring, demographic variables, (age, gender, education, and risk group) and stage of disease had no effect. Greater HIV suppression at 6 months was seen across four categories of increasing adherence (P = 0.009 for linear trend). Patients reporting < 80% adherence at 6 months had a 0.2 log10 copies/ml increase in HIV RNA and a loss of 19 x 10(6) CD4 cells/l compared with a 1.1 log10 copies/ml decrease in HIV RNA and an increase of 72 x 10(6) CD4 cells/l in those reporting 100% adherence (P = 0.02). CONCLUSION: Self-reported poor adherence (< 80%) and drug or alcohol use predicted non-response of HIV RNA at 6 months of antiretroviral therapy.

Adult↗

Food allergy in human immunodeficiency virus (HIV) infection.

BACKGROUND: Gastrointestinal complaints and pruritic skin conditions are common in patients infected with human immunodeficiency virus (HIV). Because atopic disorders such as drug allergy, asthma, and allergic rhinitis are apparently increased, we hypothesized that food allergy may also be more common in patients with HIV. OBJECTIVE: The purpose of this study was to estimate the prevalence of food allergy in patients infected with HIV. METHODS: Consecutive patients visiting our outpatient adult HIV clinic were screened for possible food allergy by use of a questionnaire. One hundred seventy-six patients responded. Sixty-two of these patients reported symptoms compatible with a possible food allergy. Followup of the 62 subjects was possible in 40. Thirty-one patients were skin tested for foods thought to produce reactions. RESULTS: Three patients (1.7%) described previous anaphylactic responses to specific foods and were therefore not skin tested or challenged orally. Six patients (3.4%) described very strong histories of food allergy but either refused or were too ill for testing. Twenty-nine of the 31 patients had negative skin tests. One of the two patients with a positive skin test to a suspected food also had a positive double-blind, placebo-controlled food challenge (DBPCFC). There was no correlation between CD4 cell count and likelihood of food allergy. Based on a strong history alone, the maximal estimated prevalence of food allergy in this group was 5.7% (10 of 176). By using the more strict criterion of positive DBPCFC, the prevalence of food allergy in this patient population was 0.57% (1 of 176). CONCLUSION: These results suggest that food allergy is an uncommon disease in patients with HIV infection with an estimated prevalence similar to that found in the general adult population. Our data do not suggest an obvious direct correlation between HIV infection and food allergy.

Adult↗

Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials.

OBJECTIVE: To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy. DESIGN: Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials. SETTING: Multiple centers in the United States. PATIENTS: Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety. INTERVENTION: Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks. MEASUREMENTS: Changes in mean hematocrit, transfusion requirement, and quality of life. RESULTS: Sixty-nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections. CONCLUSION: Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.

Acquired Immunodeficiency Syndrome↗

A comparison of the effectiveness of three regimens in the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and the leading cause of death in patients with the acquired immunodeficiency syndrome. The prevention of the occurrence and recurrence of PCP is a cornerstone in the treatment of patients infected with the human immunodeficiency virus. There are few studies comparing PCP prophylactic regimens. METHODS: The efficacy of three regimens for prophylaxis against PCP was assessed in a retrospective chart review of 211 human immunodeficiency virus-infected patients at risk for the disease. Over the course of the 2-year study period, 133 patients were prescribed trimethoprim-sulfamethoxazole (one double-strength tablet twice a day, thrice weekly) for a mean of 7.4 months (range, 1 to 25 months). Seventy-seven patients received dapsone (50 mg daily) for a mean of 5.7 months (range, 1 to 23 months), and 125 patients received aerosolized pentamidine (300 mg via nebulizer once monthly) for a mean of 9.3 months (range, 1 to 21 months). The majority of patients (62%) received primary prophylaxis; 38% had one or more previous episodes of PCP; and 73% were receiving concomitant antiretroviral therapy. RESULTS: Pneumocystis carinii pneumonia did not develop in any patient receiving trimethoprim-sulfamethoxazole in 981 patient-months. Five patients receiving dapsone for 437 patient-months and 17 patients receiving aerosolized pentamidine for 1166 patient-months developed PCP. Fifty-six percent of the trimethoprim-sulfamethoxazole group and 55% of the dapsone group changed drug due to adverse reactions, while only 2% in the aerosolized pentamidine group required drug change. CONCLUSION: Despite its adverse reaction profile, trimethoprim-sulfamethoxazole is the most effective agent to prevent the occurrence and recurrence of PCP.

Acquired Immunodeficiency Syndrome↗

Infection with HIV is associated with elevated IL-6 levels and production.

Polyclonal B cell activation is commonly observed in AIDS and in infection with HIV. Because IL-6 (B cell stimulatory factor 2) plays an essential role in the differentiation of activated B cells to Ig-secreting cells, and because IL-6 production is induced by exposure of human PBMC to HIV, we measured the level of circulating plasma IL-6, spontaneously-produced IL-6, and IL-6 mRNA in HIV-infected donors and in healthy control donors. Elevated levels of plasma IL-6 and IL-6 mRNA were detected in HIV-infected donors. PBMC isolated from the peripheral circulation of HIV-infected donors, and cultured without added exogenous activators of IL-6 production, produced markedly elevated amounts of IL-6 when compared with cells isolated from healthy donors. Interestingly, levels of an acute-phase protein, which is known to be induced by IL-6, was also increased in HIV-infected donors. These results demonstrate that elevated levels of IL-6 are associated with HIV-infection, and suggest that IL-6 over-production may contribute to the polyclonal B cell activation seen in AIDS and HIV infection.

C-Reactive Protein↗

Outcomes of treatment with AZT of patients with AIDS and symptomatic HIV infection.

Although many experimental treatments are being evaluated for the treatment of acquired immunodeficiency syndrome (AIDS) and symptomatic HIV infection (ARC), only zidovudine (AZT) has been shown to prolong the lives of such patients. This article reviews the authors' experience with 101 patients with AIDS (73) or ARC (28) treated with AZT at a public hospital clinic in Los Angeles County. The patients were seen at least monthly for five to 87 weeks (means = 27.6) by nurse practitioners and physicians. Initiation of AZT therapy required a CDC-defined diagnosis of AIDS or an absolute CD4 lymphocyte cell count of 200/mm3 or less. The demographic distribution of the patient population was as follows: Caucasian, 59; Hispanic, 22; and black, 20. The mean age of the population was 37.4 years, and the predominant risk factor was homosexual contact (76 percent). Forty-one patients required modification of their AZT doses secondary to anemia, neutropenia, a combination of anemia and neutropenia, or for personal reasons. Thirty-four of the 41 patients (83 percent) never returned to full dose after reductions. The majority of these patients (81 percent) had AIDS and/or CD4 lymphocyte counts less than 150/mm3. Hematologic toxicity was common; 27 percent required blood transfusions. Of the 101 patients followed from five to 87 weeks, 87 percent were surviving after a mean of 45 weeks of AZT therapy. The article underscores the effectiveness of AZT in prolonging the lives of AIDS and ARC patients.

AIDS-Related Complex↗

Detection of cells producing anti-idiotypic antibody to thyroid stimulating hormone-reactive antibodies.

BALB/c mice were immunized either with bovine (b) or human (h) thyroid stimulating hormone (TSH) or with one of several mouse monoclonal anti-hTSH antibodies. The binding of biotinylated mouse monoclonal anti-hTSH to sections of spleen, kidney, liver and lung was assessed with fluorescein isothiocyanate labelled avidin. Clusters of cells in the spleens of mice immunized with bTSH bound the labelled monoclonal anti-TSH. We suggest that these cells synthesized auto-anti-idiotypic antibodies to anti-TSH.

Animals↗

Immediate hypersensitivity reactions to beta-lactam antibiotics.

Allergic reactions to the beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams) are a major factor limiting their use. Immediate hypersensitivity reactions to penicillins depend on the presence of preformed allergic (IgE) antibodies to several penicillin determinants. These materials can be used in in-vivo skin testing to exclude those patients at risk for immediate or accelerated allergic reactions. The cephalosporins have not had their relevant determinants defined as related to allergic reactions. The results of in-vivo challenges of patients with IgE to penicillin suggest the incidence of reactivity of cephalosporins in patients allergic to penicillin is less than generally appreciated. The monocyclic beta-lactam antibiotic, aztreonam (a monobactam), failed to show cross-reactivity with penicillin antibodies, because immune reactivity toward the monobactam was directed against side chain rather than nuclear determinants. On the other hand, the new bicyclic carbapenem beta-lactam drugs, represented by imipenem, showed extensive in-vivo cross-reactivity with penicillins.

Anti-Bacterial Agents↗

Failure to demonstrate anti-lymphocytic antibody in serum of patients with AIDS.

Several studies have produced evidence for anti-lymphocytic antibodies (ALA) in AIDS. We attempted to demonstrate ALA by immunofluorescent flow cytometry. Normal human peripheral blood lymphocytes (PBL) and the T-cell line, CEM, were incubated with sera from patients with AIDS, patients with chronic HIV infection and HIV-seronegative blood donors. ALA were not detected in the AIDS sera with fluorescein isothiocyanate (FITC)-labelled rabbit anti-mu, anti-alpha or the F(ab)2 fragment of anti-human gamma. A small number of CEM cells (2%) fluoresced with either AIDS or normal serum. A larger proportion of PBL were immunofluorescent after serum treatment but there was no difference between normal and AIDS serum. We were able to detect ALA in the serum of patients with systemic lupus erythematosus with both CEM and PBL. In contrast, incubation of either CEM or PBL with some AIDS sera, and to a lesser degree normal sera, enhanced the binding of intact FITC-rabbit anti-gamma. Anti-gamma was not bound by CEM cells unexposed to human serum. The binding was blocked by rabbit immunoglobulin, demonstrable with CEM fixed in 1% formalin, and unrelated to the density of CD4 on CEM cells.

Acquired Immunodeficiency Syndrome↗

Studies on auto-anti-idiotypic thyroid-stimulating antibodies.

We immunized rabbits with human (h) or bovine (b) thyroid-stimulating hormone (TSH), hTSH beta chains or human serum albumin. Serum from the rabbits was then assayed for thyroid-stimulating activity, using the thyroid-cell bioassay. Anti-idiotypic antibodies (anti-ID) to monoclonal anti-TSH were detected in these rabbit antisera after removal of rheumatoid factor by absorption with IgG. Anti-ID activity was detected in the serum of the rabbits immunized with bovine TSH. Thyroid-stimulating antibody (TSI) activity, too, was most prominent in the sera obtained from bTSH-immunized rabbits. Anti-ID activity seemed to arise sooner than did TSI, but both tended to peak 3 months after an initial series of immunizations. Since thyroid-stimulating immunoglobulins can develop following TSH immunization of rabbits, it is possible that a similar immunopathogenesis may be responsible for some instances of Graves' hyperthyroidism.

Animals↗

Immunologic and clinical correlates of bronchial challenge responses to Bermuda grass pollen extracts.

We have studied 26 patients with asthma who had positive skin tests for Bermuda grass pollen antigen (BGP) with history, immunologic assays, and bronchial challenge with BGP. In these patients IgE anti-BGP RAST titers were higher in those with positive, 6.8 +/- 4.4% (mean +/- SEM) compared to those with negative bronchial challenges, 2.7 +/- 0.4% (p less than 0.02). Historical data did not predict bronchial challenge response. IgG4 anti-BGP RAST was not different in patients with positive and negative challenges but was markedly increased, 15.3 +/- 11.9%, in patients who had previously had BGP immunotherapy when compared to untreated patients, 3.6 +/- 5.1% (p less than 0.01). IgE anti-Bermuda grass appears to be the major contributor to susceptibility to BGP bronchial challenge. IgG4 anti-Bermuda grass is apparently unrelated to the sensitivity to challenge but appears to be a significant component of the immunologic response to immunotherapy.

Antibodies, Anti-Idiotypic↗

Rabbits immunized with thyroid-stimulating hormone produce autoantiidiotypic thyroid-stimulating antibodies.

We immunized rabbits with thyroid-stimulating hormone (TSH) to investigate the hypothesis that such immunization could result in production of thyroid-stimulating autoantiidiotypic antibodies to anti-TSH. Thyroid-stimulating immunoglobulin (TSI) appeared in the serum of several rabbits after immunization. At 160 d, TSI equivalent to 6-18 microU TSH/1.5 mg IgG was present in two of six human (h)TSH-, two of six hTSH beta chain-, and two of the four surviving bovine (b)TSH-immunized animals. Control (human serum albumin-immunized rabbits) serum TSI was 4.3 +/- 0.4 (mean +/- SD) at this time. Antiidiotypic antibodies that could bind to monoclonal anti-hTSH were found in the sera of the bTSH-immunized rabbits. The peak TSI activity occurred 3 mo after a TSH booster immunization and declined gradually during subsequent weeks. Evidence that antiidiotypic antibodies to anti-TSH can cause thyroid stimulation strengthens the notion that such antibodies may be the cause of Graves' hyperthyroidism.

Animals↗