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Biomedical subjects

D Mildvan

Publications and source records attributed to D Mildvan.

At least 55 records · Page 3Linked to original sources

Entamoeba histolytica antigen-specific induction of human immunodeficiency virus replication.

Replication of human immunodeficiency virus (HIV) may be initiated in infected lymphocytes by antigenic or mitogenic stimulation. A soluble protein derived from an invasive strain of Entamoeba histolytica (amoebic antigen [AA]) was used to study the lymphoblastic responses of T lymphocytes derived from 8 HIV-seronegative homosexual men (controls) and 15 HIV-seropositive homosexual men (patients). The soluble protein was also used in long-term cultures as a stimulus for HIV replication. No control or patient produced detectable lymphoblastic responses to AA in a 6-day tritiated-thymidine incorporation assay. Of 15 patients, 5 (33%) produced HIV p24 (ranging from 31 pg/ml to 151 ng/ml) in response to AA in 30-day cell cultures. HIV p24 was expressed in three of seven patients in response to AA but not to the T-lymphocyte mitogen phytohemagglutinin. Implications for managing HIV-infected patients are discussed.

AIDS-Related Complex↗

Bone invasion in secondary syphilis: case reports.

The affinity of treponemes for bone tissue is well known, but the incidence of bone infection in the early stages of syphilis is uncertain. Although case reports of early bone invasion are few, reviews of large numbers of patients with early syphilis indicate that the incidence is probably greater than at present believed. Two case reports are presented.

Adult↗

Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group.

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5, 1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 mumol/L or higher (greater than or equal to 2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemo-pneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS.

AIDS-Related Complex↗

The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by Pneumocystis carinii pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P less than 0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P less than 0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P less than 0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P less than 0.001). These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex, at least over the 8 to 24 weeks of observation in this study.

AIDS-Related Complex↗

The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.

AIDS-Related Complex↗

Ganciclovir for the treatment and suppression of serious infections caused by cytomegalovirus.

Ganciclovir is a congener of acyclovir with in vitro activity against cytomegalovirus. Ninety-seven patients with the acquired immune deficiency syndrome (AIDS) and a serious cytomegalovirus infection received ganciclovir, 3.0 to 15 mg/kg per day. Viremia cleared during drug therapy in 88 percent of patients. Viral shedding from urine and throat ceased or became inapparent during treatment in 78 percent and 68 percent of patients, respectively. Among patients with cytomegalovirus retinitis, 87 percent of evaluable patients had improvement in (30 of 60) or stabilization (22 of 60) of their disease. However, when the drug was discontinued, progression or recurrence of disease always occurred. Long-term suppressive therapy with ganciclovir, 5.0 mg/kg five to seven times weekly, prevented the recurrence of cytomegalovirus disease (p less than 0.001). The drug was eliminated by renal excretion, and in patients without renal impairment (creatinine clearance rates of more than 60 ml/minute/1.73 m2), ganciclovir has a mean half-life of 4.2 hours. Significant neutropenia and leukopenia occurred in 55 percent and 32 percent of patients, respectively.

Acquired Immunodeficiency Syndrome↗

Combined short- and long-term therapy for the treatment of cytomegalovirus retinitis using ganciclovir (BW B759U).

A total of 66 eyes in 41 patients were treated for cytomegalovirus (CMV) retinitis with a new acyclic nucleoside, ganciclovir (BW B759U). At the completion of the short-term therapy period of 21 days, 87.7% of eyes had stabilized or improved. Seventy-two percent of eyes stabilized or improved during long-term home maintenance therapy. Leukopenia and increased liver function abnormalities were the most common adverse drug reactions seen in this series. Ganciclovir dramatically improved the quality of life in these patients, but clinical evidence suggests that it is a virostatic medication requiring indefinite long-term maintenance therapy.

Acquired Immunodeficiency Syndrome↗

Nonrandom development of immunologic abnormalities after infection with human immunodeficiency virus: implications for immunologic classification of the disease.

Blood specimens from 165 intravenous drug users who were seropositive for the human immunodeficiency virus (HIV), from 158 seropositive homosexual men with lymphadenopathy, and from 77 patients with acquired immunodeficiency syndrome (AIDS) were assessed immunologically. Immunologic parameters were analyzed by the Guttman scalogram technique to determine if immunologic abnormalities occurred in a nonrandom pattern. The following four patterns emerged: (i) seropositivity for HIV with no immunologic abnormalities; (ii) seropositivity for HIV with a depressed T4/T8 cell ratio; (iii) seropositivity with a depressed T4/T8 cell ratio and T4-cell depletion; and (iv) seropositivity with a depressed T4/T8 cell ratio, T4-cell depletion, and lymphopenia. Ninety-two to 100% of subjects in each of the three groups of patients were found "to scale" because the abnormalities occurred in the cumulative, ordered fashion described. This nonrandom occurrence of abnormalities indicates an ordered progression of immunologic abnormalities in individuals infected with HIV, a finding useful in the staging of both symptomatic and asymptomatic HIV-seropositive subjects.

AIDS-Related Complex↗

Tuberculosis and the acquired immunodeficiency syndrome at a New York City hospital: 1978-1985.

Recent reports have described an increase in cases of tuberculosis in several urban centers. To investigate the possible relationship between tuberculosis and the acquired immunodeficiency syndrome (AIDS), we reviewed case records at a New York City hospital between 1978 and 1985. During this period, tuberculosis occurred in 15.1 percent of AIDS patients with a history of parenteral drug use and 4.4 percent of all other patients with AIDS. The yearly rate of tuberculosis more than doubled during the study period; this increase was entirely attributable to cases among patients with AIDS or AIDS-related complex and parenteral drug users, a group at high risk for the development of AIDS. Patients with AIDS and tuberculosis were younger and more frequently men than other patients with tuberculosis, and were more likely to have extrapulmonic disease. In the majority of patients, tuberculosis occurred prior to confirmation of CDC-defined AIDS. Forty-four percent of patients with AIDS-related complex at the time of diagnosis of tuberculosis subsequently developed AIDS. Mycobacterium tuberculosis appears to be yet another opportunistic agent to which patients with AIDS retroviral-induced immunodeficiency are susceptible.

AIDS-Related Complex↗

Development of AIDS, HIV seroconversion, and potential co-factors for T4 cell loss in a cohort of intravenous drug users.

A cohort of 334 intravenous (IV) drug users from New York City drug treatment programs were followed over a mean 9-month period. Among the 165 who were seropositive at enlistment, four developed clinical AIDS, for an annual rate of 3%. Elevated IgA was a significant predictor of developing AIDS. Among 72 subjects who were initially seronegative and who were re-interviewed, four were seropositive at follow-up, for a seroconversion rate of 7% per year among seronegatives. Among seropositive subjects who did not develop AIDS or fatal AIDS related complex (ARC), continued drug injection was associated with rate of T4 cell loss, and there was a non-significant trend for males to lose T4 cells more rapidly than females. While it was not possible to distinguish the mechanism underlying the relationship between continued drug injection and T4 cell loss, seropositive IV drug users should be warned that continued injection may lead to increased HIV-related immunosuppression as well as, if injection equipment is shared, risking viral transmission to others.

Acquired Immunodeficiency Syndrome↗

Risk factors for infection with human immunodeficiency virus among intravenous drug abusers in New York City.

We report here the results of a survey of 308 intravenous drug abusers recruited from hospital-based methadone maintenance or drug detoxification programmes located in Manhattan, New York City. Complete interviews and serological analyses for antibodies to human immunodeficiency virus (HIV) using both enzyme-linked immunosorbent and Western blot assays were obtained from 290 (94%) of the subjects. HIV antibodies were found by both assays in 147 (50.7%) of the tested subjects; conflicting results were found in three (1%) of the subjects; and negative results on both tests were found in 140 (48.3%) of the subjects. Logistic regression analysis identified significant relative risks for HIV infection associated with the frequency of drug injection and the proportion of injections in 'shooting galleries'. Additional risk among men was associated with a history of homosexual relations. Traditional efforts taken by subjects to clean syringes between uses, such as washing with water or alcohol, showed no evidence of being protective. Programmes aimed at prevention of HIV infection should focus on reducing use of shooting galleries and sharing of needles and syringes as well as reducing intravenous drug abuse generally.

Adult↗

Herpes zoster ophthalmicus in patients at risk for the acquired immune deficiency syndrome (AIDS).

In a prospective investigation of 54 consecutive cases of herpes zoster ophthalmicus, conducted over a two-year period, immunologic evaluations included enumeration of T lymphocyte subsets and serum immunoglobulin levels. Herpes zoster ophthalmicus occurred with frequent ocular complications in a subgroup of adults distinguishable by their young age, the presence of AIDS-risk factors, alterations in T-cell subpopulations, and polyclonal increases of serum gammaglobulin. Over the study duration, 21% (three of 14) of the AIDS-risk subgroup patients have developed AIDS with a 14% (two of 14) mortality. Herpes zoster ophthalmicus in AIDS-risk group members appeared to be an early clinical marker for the immune deficiency induced by AIDS retroviral infection.

Acquired Immunodeficiency Syndrome↗