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Biomedical subjects

J W Gold

Publications and source records attributed to J W Gold.

At least 19 recordsLinked to original sources

Convergent validity of three posttraumatic symptoms inventories among adult sexual abuse survivors.

We examined the convergent validity of three posttraumatic symptoms inventories, the civilian version of the Mississippi Scale for Combat-Related PTSD (CM-PTSD), the Trauma Symptom Checklist-40 (TSC-40), and the Response to Childhood Incest Questionnaire (RCIQ), in a sample of 52 adult sexual abuse survivors. The significant and moderate to strong correlations (r = .6 or higher) among these inventories supported their convergent validity. Comparison with other studies also suggests that these instruments can adequately discriminate clinical from nonclinical populations.

Adult↗

The diagnosis and management of HIV infection.

In the past 15 years HIV infection and AIDS have become pandemic in the world. Infectious and neoplastic complications have evolved in response to medical advances and to the appearance of HIV infection in different populations. Because AIDS patients live longer with severe immunosuppression and new treatments have controlled opportunistic infections, the spectrum of complications of AIDS has changed. New and more effective antiretroviral drugs are being developed, and physicians are learning how to use them more effectively. Currently, medical management of HIV-infected patients focuses on the appropriate use of antiretrovirals and the prevention, early diagnosis, and treatment of complicating illnesses. A coordinated continuum of care and patient education and involvement are also key elements of effective management of HIV infection.

Antiviral Agents↗

HIV-1 infection. Diagnosis and management.

This article discusses the epidemiology, diagnostic methods, prevention of complications, and medical management of HIV-1 infection. Many different therapeutic strategies for HIV-1 infection are being evaluated, but until the immune suppression is eradicated, presumably through more effective antiviral therapy, complications of AIDS and HIV-1 infection will continue to be encountered.

AIDS Serodiagnosis↗

Three-drug synergistic inhibition of HIV-1 replication in vitro by 3'-fluoro-3'-deoxythymidine, recombinant soluble CD4, and recombinant interferon-alpha.

3'-Fluoro-3'deoxythymidine (FLT), recombinant soluble CD4 (CD4), and recombinant interferon-alpha (IFN alpha) were evaluated in two- and three-drug regimens against HIV-1 replication in vitro. Peripheral blood mononuclear cells were studied using p24 antigen production as the virologic endpoints. FLT showed 2.5-fold higher efficacy and a similar selectivity index to zidovudine. Drug interactions were evaluated by the median effect principle and the isobologram technique. FLT, CD4, and interferon alpha at noncytotoxic concentrations inhibited HIV-1 synergistically in two- and three-drug combinations with a combination index smaller than one and dose reduction index greater than one. The three-drug regimen provided greater virus suppression than the two-drug regimen. These results suggest that FLT is an alternative agent to AZT for the treatment of HIV infection either as a single agent or in combination with CD4 and/or interferon-alpha.

Antiviral Agents↗

Standardization of sensitive human immunodeficiency virus coculture procedures and establishment of a multicenter quality assurance program for the AIDS Clinical Trials Group. The NIH/NIAID/DAIDS/ACTG Virology Laboratories.

An independent quality assurance program has been established by the Division of AIDS, National Institute of Allergy and Infectious Diseases, for monitoring virologic assays performed by nearly 40 laboratories participating in multicenter clinical trials in the United States. Since virologic endpoints are important in evaluating the timing and efficacy of therapeutic interventions, it is imperative that virologic measurements be accurate and uniform. When the quality assurance program was initially created, fewer than 40% of the laboratories could consistently recover human immunodeficiency virus (HIV) from peripheral blood mononuclear cells (PBMCs) of HIV-infected patients. By comparing coculture procedures in the more competent laboratories with those in laboratories who were struggling to isolate virus, optimal conditions were established and nonessential reagents and practices were eliminated. Changes were rapidly introduced into a laboratory when experience dictated that such modifications would result in a favorable outcome. Isolation of HIV was enhanced by optimizing the numbers and ratios of patient and donor cells used in cultures, by standardizing PBMC separation procedures, by using fresh rather than frozen donor PBMCs, by processing whole blood within 24 h, and by using natural delectinated interleukin 2 instead of recombinant interleukin 2 products in existence at that time. Delays of more than 8 h in the addition of phytohemagglutinin-stimulated donor cells to freshly separated patient PBMCs reduced recovery. Phytohemagglutinin in cocultures and the addition of Polybrene and anti-human alpha interferon to media were not important in HIV isolation. The introduction of a consensus protocol based on this information brought most laboratories quickly into compliance. In addition, monthly monitoring has successfully maintained proficiency among the laboratories, a process that is critical for the scientific integrity of collaborative multicenter trials. Problems which might not be appreciated for months are now being resolved early, before data can be compromised unknowingly. This consensus protocol is recommended for any laboratory attempting to isolate HIV for the purpose of standardizing recovery and for accessing virologic endpoints in clinical trials.

Culture Media↗

Interferon-alpha, zidovudine, and granulocyte-macrophage colony-stimulating factor: a phase I AIDS Clinical Trials Group study in patients with Kaposi's sarcoma associated with AIDS.

PURPOSE: To increase the hematologic tolerance of interferon-alpha (IFN alpha) and zidovudine combination therapy by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF), and to evaluate the safety, tolerance, and potential efficacy of the combination in patients with Kaposi's sarcoma and AIDS. PATIENTS AND METHODS: Seventeen patients with Kaposi's sarcoma associated with AIDS received zidovudine 200 mg orally every 4 hours and GM-CSF 5 micrograms/kg/d subcutaneously. Successive cohorts received IFN-alpha 2b at a daily subcutaneous dose of 5, 10, or 20 million units. The dose of GM-CSF was titrated to maintain the neutrophil count between 1 and 5 x 10(9) cells/L. Doses of all three drugs were reduced, as required, for nonhematologic toxicities. RESULTS: GM-CSF induced leukocytosis in all patients. On average, a dose of 1.25 micrograms/kg/d was sufficient to maintain the neutrophil count within the desired range. The combination of 20 million units of IFN-alpha with zidovudine and GM-CSF induced dose-limiting toxicity in four of six patients. The major side effects were constitutional symptoms, which included malaise, anorexia, fatigue, fever, and were dose-limiting in three patients. Severe anemia and/or thrombocytopenia developed in three patients. Seven patients (41%; 95% confidence interval [CI], 18% to 64%) showed objective tumor regression that persisted for a median of 51 weeks. A rapid decrease in free-serum p24 antigen levels was observed in seven patients who had measurable levels at baseline; the mean time required to isolate human immunodeficiency virus (HIV-1) from peripheral-blood cells was increased by 7 days. The number and percentage of CD4-positive lymphocytes showed no significant change. CONCLUSIONS: GM-CSF prevents neutropenia induced by the IFN-alpha and zidovudine combination and induced no adverse effects on immune function or HIV activity. However, nonhematologic toxicity precluded a major increase in the maximum-tolerated doses of IFN-alpha and zidovudine.

Acquired Immunodeficiency Syndrome↗

Pneumothorax in AIDS.

OBJECTIVE: To determine risk factors for the development of pneumothorax in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective cohort study. SETTING: Tertiary care center. PATIENTS: Of 1030 patients with AIDS who were followed at Memorial Sloan-Kettering Cancer Center between 1 January 1980 and 30 September 1989, 20 (2%) developed pneumothorax that was unrelated to trauma or a pulmonary procedure. RESULTS: Of 20 patients with AIDS who presented with pneumothorax, 19 had compelling evidence of concurrent Pneumocystis carinii pneumonia. Using bivariate analysis, patients receiving aerosol pentamidine prophylaxis (relative risk, 17.6) and those with a history of P. carinii pneumonia (relative risk, 14.5) were more likely to develop pneumothorax. By Mantel-Haenszel stratified analysis, aerosol pentamidine use was a statistically significant risk factor independent of a history of P. carinii pneumonia. The pneumothorax-related mortality rate was 10% and there was considerable morbidity. CONCLUSIONS: Patients with AIDS at the highest risk for developing pneumothorax are those with a history of P. carinii pneumonia who are receiving aerosol pentamidine prophylaxis but who nevertheless develop P. carinii pneumonia. The benefits of aerosol pentamidine prophylaxis in these patients far outweigh this risk. Pneumocystis carinii pneumonia should be considered as the most likely diagnosis in any patient with AIDS who develops a pneumothorax.

Acquired Immunodeficiency Syndrome↗

Differences in human immunodeficiency virus type 1 (HIV-1) anti-p24 reactivities in serum of HIV-1-infected and uninfected subjects: analysis of indeterminate western blot reactions.

Anti-p24 reactions in sera from 42 human immunodeficiency virus type 1 (HIV-1)-infected and 36 uninfected people with indeterminate Western blot antibody tests for HIV-1 were studied. Anti-p24 reactivity in HIV-1-infected people was completely blocked by HIV-1 recombinant p24 antigen, whereas the reaction in uninfected individuals with indeterminate patterns was inhibited partly or not at all. In contrast to infected individuals, anti-p24 reactivity from uninfected individuals could not be detected by an inhibition ELISA for HIV-1 p24 antibody. These results suggest a practical way to distinguish anti-p24 reactivity in sera from patients with HIV-1 infection from that seen in uninfected patients with indeterminate Western blot reactions.

Adult↗

Synergistic inhibition of human immunodeficiency virus type 1 replication in vitro by two-drug and three-drug combinations of 3'-azido-3'-deoxythymidine, phosphonoformate, and 2',3'-dideoxythymidine.

The effects of 3'-azido-3'-deoxythymidine (AZT), phosphonoformate (PFA), and 2',3'-dideoxythymidine (ddT) and their combination on human immunodeficiency type 1 (HIV-1) replication were studied by measuring the HIV-1 p24 antigen expression and reverse transcriptase (RT) release in HIV-1-infected MT4 cells in vitro. RT activity was also measured in a cell-free system by using poly(rA)-oligo(dT) as the primer-template, and cell growth inhibition was measured in noninfected MT4 cells. The interactions of these two- and three-drug combinations were evaluated by the combination index (CI) method and isobologram techniques. The 50% effective concentrations (EC50s) of AZT, PFA, and ddT were 0.014 to 0.005, 9.4 to 8.8, and 8.4 to 2.5 microM, respectively, for p24 enzyme-linked immunosorbent assays (ELISAs) and 0.005 to 0.0034, 1.43 to 1.37, and 2.87 to 2.83 microM, respectively, for RT activity in vitro; for RT activity in the cell-free system, the EC50s were 0.00019 to 0.00024, 0.012 to 0.02, and 0.00074 to 0.0005 microM, for AZT-5'-triphosphate, PFA, and ddT-5'-triphosphate, respectively. AZT in combination with PFA (1:200) or ddT (1:5) as well as the combination of these three drugs (1:200:5) synergistically inhibited HIV-1 replication and RT activity in the cell-free system over a wide range of drug concentrations, with the CIs ranging from 0.5 to 0.09, in which CIs of less than 1, 1, and greater than 1 indicate synergism, additive effect, and antagonism, respectively. Three- and two-drug combinations of AZT, PFA, and ddT showed similar degrees of synergism against HIV-1 replication in p24 assays and RT release assays, whereas the combination of AZT and ddT was found to be the most selective in terms of its anti-HIV-1 effect versus cytotoxicity. Dose reduction indices calculated from both HIV-1 replication inhibition, as measured by p24 ELISA and by RT activity in the cell-free system, indicated that two- and three-drug combinations at high effect levels and the selected combination ratios allow 2- to 240-fold dose reduction over the single drug alone in terms of their anti-HIV-1 effects. The three-drug combination showed the highest dose reduction index. These finding suggest that increased efficacy and reduced toxicity may be achieved in AIDS therapy by using AZT, PFA, and ddT in two- or three-drug combinations.

Antiviral Agents↗

Small non-cleaved-cell lymphoma (undifferentiated lymphoma, Burkitt's type) in American adults: results with treatment designed for acute lymphoblastic leukemia.

PURPOSE: Small non-cleaved-cell lymphoma (SNCL) "Burkitt's type," a rapidly growing lymphoma, has been rare among adults in the United States, but has greatly increased in incidence with the acquired immunodeficiency syndrome epidemic. This report details the results of treatment of adult SNCL with a series of protocols originally designed for the treatment of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Between July 1973 and May 1987, 29 adults with newly diagnosed SNCL were treated at Memorial Hospital with intensive chemotherapy originally designed for ALL: the cyclophosphamide L-2, L-10, L-17, and L-20 protocols. Nine patients had positive serologies for human immunodeficiency virus (HIV) infection. One patient with all measurable disease resected was not evaluable for response. RESULTS: Sixteen of 28 evaluable patients (57%) achieved a complete remission with treatment. With follow-up as long as 153 months (median, 47 months), 50% of all patients and 59% of patients with negative or unknown HIV serologies have survived and are probably cured. Patients with an initial serum lactic acid dehydrogenase (LDH) level of greater than 500 U/L had a significantly shortened survival as compared with those with a lower serum LDH. Other pretreatment patient characteristics associated with a shortened survival of borderline statistical significance were high National Cancer Institute stage (C, D) and bone marrow involvement. These results are similar to those for ALL and lymphoblastic lymphoma and are comparable to those for American SNCL in the literature. CONCLUSIONS: Approximately one half of adults with SNCL are curable with intensive chemotherapy. More intensive chemotherapy with hematopoietic growth factor and/or autologous bone marrow or peripheral stem cell support may increase curability.

Adolescent↗

Interferon-alpha with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS)

OBJECTIVE: To evaluate safety, tolerance, and potential efficacy of interferon-alpha and zidovudine combination therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). DESIGN: Open, phase-I study with randomization between two preparations of interferon-alpha. SETTING: Outpatient clinic of a cancer research center. PATIENTS: Forty-three patients with Kaposi sarcoma associated with AIDS. INTERVENTIONS: Patients were treated with interferon-alpha, 4.5, 9, or 18 million U/d, and zidovudine, 100 or 200 mg orally every 4 hours. MEASUREMENTS AND MAIN RESULTS: Neutropenia was the major dose-limiting toxicity. Fatigue, liver enzyme elevation, anemia, and thrombocytopenia were dose-limiting in some patients. Maximum tolerated dosages for interferon-alpha 2a with zidovudine, respectively, were 4.5 million U/d with 200 mg every 4 hours or 18 million U/d with 100 mg every 4 hours. An interferon-alpha n1 [corrected] dosage of 9 million U/d with zidovudine dosages of either 100 or 200 mg every 4 hours induced dose-limiting toxicity in most patients. Of 37 evaluable patients, 17 (46%; 95% CI, 30% to 62%) showed complete or partial tumor regression. Antitumor effects occurred more frequently in patients with baseline CD4 counts above 200 x 10(6) cells/L (65%) than in patients with lower baseline counts (30%, P = 0.05). Effects on CD4 cells were related to both initial CD4 count and interferon dose. Increased skin test reactivity and decreased serum human immunodeficiency virus (HIV) p24 antigen and virus recovery from blood cells were seen. CONCLUSIONS: Combined therapy with interferon-alpha and zidovudine can be safely administered to patients with AIDS and Kaposi sarcoma. The observed effects on tumor growth, HIV replication, and immune function support further studies of the combination in patients at various stages of HIV infection.

Acquired Immunodeficiency Syndrome↗

An ELISA-inhibition assay for antibody to human immunodeficiency virus core antigen (p24).

An ELISA-inhibition assay based on commercially available HIV-1 p24 antigen tests was developed for detecting p24 antibodies. The test is specific and simple. p24 antibody was detectable in all p24 antigen negative Western blot positive sera, but was detectable infrequently in antigen positive sera. Sera from patients with indeterminate HIV-1 reactions (individuals without evidence of HIV-1 infection who nevertheless had p24 antibody) were p24 antigen negative and p24 antibody negative in the ELISA-inhibition reaction.

Acquired Immunodeficiency Syndrome↗

Serologic responses to Pneumocystis carinii antigens in health and disease.

Serum antibodies to human Pneumocystis carinii antigens were measured in greater than 400 specimens from different population groups by the immunoblotting technique. Serologic responses varied during the first 2 years of life, but in children greater than or equal to 2 1/2 years and in adults antibodies to a 40-kDa band were found in greater than 85% of the specimens; antigens to bands of 66, 92, and 116 kDa were also detected frequently. The prevalence of serum antibodies in immunosuppressed patients varied at different institutions and was usually lower than that of healthy controls. Seven (41%) of 17 patients with single episodes of pneumocystosis and 13 (93%) of 14 patients with recurrent episodes followed sequentially developed active serum IgM and/or IgG antibody responses to the 40-kDa antigen. Serologic responses to P. carinii were also detected, though less frequently, by immunofluorescence. These data suggest that the 40-kDa antigen is a major marker of P. carinii infection and that immunoblotting is useful in measuring serum antibody responses to the organism in both normal and immunocompromised hosts.

Acquired Immunodeficiency Syndrome↗

Psychological responses to serological testing for HIV.

To determine the emotional impact of serological testing for HIV, 218 physically asymptomatic adults were evaluated in a confidential clinical setting 2 weeks before HIV test notification, immediately before and after notification, and 2 and 10 weeks later. All received extensive pre- and post-test counseling. The 179 seronegatives reported one or more HIV risk behaviors: homosexual intercourse (n = 111), heterosexual intercourse with possibly infected partners (n = 62), intravenous drug use (n = 20). Immediately after notification, seronegatives had significant decreases in visual analogue scale (VAS) measures of anxiety, depression, fear of getting AIDS, and fear of having infected others. Reductions were sustained at both follow-up assessments and were complemented by significant reductions on standardized self-reported measures of anxiety (Spielberger State Anxiety Inventory, SAI), depression (Beck Depression Inventory, BDI), and psychiatric symptoms (Brief Symptom Inventory, BSI) as well as by clinical ratings of depression (Hamilton Depression Rating Scale, HDRS). Of 39 seropositives, 35 had homosexual risk behaviors, seven had been intravenous drug users (IVDUs; four of whom were homosexual men), and one was a female partner of an IVDU. Immediately after notification, VAS measures of their anxiety were not significantly increased, and at 10 weeks after notification, their VAS measures of distress and mean scores on BDI, SAI and BSI were significantly lower than at entry. Their HDRS ratings were not significantly increased.

AIDS Serodiagnosis↗

Toxoplasma gondii serology in HIV-infected patients: the development of central nervous system toxoplasmosis in AIDS.

Central nervous system (CNS) toxoplasmosis is an important infectious complication of AIDS which requires prolonged treatment. Most cases occur in patients with serologic evidence of prior exposure and therefore appear to result from reactivation of a previously acquired infection. Antibody to Toxoplasma gondii was found in 130 out of 411 patients with AIDS (32%). Of these, CNS toxoplasmosis developed in 31 (24%). By survival analysis, the estimated probability of ever developing CNS infection in antibody-positive individuals was 28%, occurring in 26% of patients within 2 years of the onset of AIDS. All patients with HIV infection should be tested for antibody to T. gondii and monitored for any neurologic change. Methods of prophylaxis for CNS toxoplasmosis in these high-risk patients need to be developed.

Acquired Immunodeficiency Syndrome↗