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Biomedical subjects

D Mildvan

Publications and source records attributed to D Mildvan.

At least 37 records · Page 2Linked to original sources
PubMed1995

Predictors and outcome of multidrug-resistant tuberculosis.

We identify early predictors of multidrug-resistant tuberculosis and describe improved clinical outcomes, including survival, for patients with human immunodeficiency virus (HIV)-related multidrug-resistant tuberculosis (MDR-TB) when they are prospectively identified and receive treatment under direct observation. Analysis by means of a Cox proportional hazards model revealed that failure to defervesce while receiving a standard four-drug antituberculous regimen was independently associated with multidrug resistance (P = .004). When patients with HIV-related MDR-TB were prospectively identified and treated with at least two agents that were active in vitro, 100% bacteriologic conversion and improved survival (> or = 4 months for 88% of patients and > or = 1 year for 59% of patients) were observed. For patients with HIV-related tuberculosis, poorer survival was associated with a CD4+ lymphocyte count of < 25 mm3 (P = .03); multidrug resistance was not a predictor of poor outcome (P = .82). These data suggest that patients with prolonged fever who are receiving antituberculous therapy may be an appropriate subgroup to target for broader empirical therapy. The findings also demonstrate that improved outcomes can be achieved with HIV-related MDR-TB when patients are prospectively identified and treated with agents that are active in vitro.

AIDS-Related Opportunistic Infections↗
PubMed1994

Continuity and change within an HIV epidemic. Injecting drug users in New York City, 1984 through 1992.

OBJECTIVES: To examine trends in acquired immunodeficiency syndrome (AIDS) risk behavior and human immunodeficiency virus (HIV) seroprevalence among injecting drug users (IDUs) in New York City from 1984 through 1992. DESIGN AND SETTING: Comparisons were made between two surveys of IDUs at the same hospital-based New York City drug abuse detoxification program: 141 IDUs in 1984 and 974 IDUs in 1990 through 1992. National Death Registry, New York City Health Department, and drug treatment program records were also used. PARTICIPANTS: Persons attending detoxification program randomly selected for participation. Eligibility was based on injection within previous 2 months; 99% acceptance rates were obtained. Participants in the 1984 and 1990 through 1992 surveys were 66% and 79% men, 21% and 19% white, 33% and 34% African American, and 45% and 46% Latin American, respectively. INTERVENTIONS: Community-based AIDS prevention programs, including underground syringe exchanges. MAIN OUTCOME MEASURES: Acquired immunodeficiency syndrome risk behaviors; HIV serostatus; CD4+ cell counts; death rates among 1984 subjects; and injection and intranasal routes of drug administration. RESULTS: The HIV seroprevalence remained stable at slightly more than 50%. Mean CD4+ cell counts declined from 0.716 x 10(9)/L (716/microL) to 0.575 x 10(9)/L (P < .009). Annual death rate among 1984 subjects was 3%, with a significantly higher rate among HIV-seropositive subjects (relative risk, 2.57; 95% exact binomial confidence interval, 1.12 to 6.61). Large-scale declines were observed in AIDS risk behaviors, eg, use of potentially contaminated syringes declined from 51% to 7% of injections (P < .001). Recent additional risk reduction was associated with use of the underground syringe exchanges. Intranasal heroin use was the primary route of drug administration for 46% of heroin admissions to New York City drug treatment programs. CONCLUSIONS: The HIV seroprevalence has remained stable among this population of New York City IDUs for almost a decade. Continuation of current trends should lead to further reduction in HIV transmission, although reversal of the trend to intranasal use could lead to substantially increased transmission.

Adult↗
PubMed1993

CD4 lymphocytopenia among injecting drug users in New York City.

Recent cases of "AIDS-like" CD4 lymphocytopenia in the absence of HIV infection have generated considerable scientific and public interest. We studied CD4 cell counts and percentages from 1984 to 1992 among 1,246 HIV-seronegative injecting drug users in New York City, a population at very high risk for exposure to bloodborne pathogens. Severe CD4 lymphocytopenia was rare, and there was no evidence of an increase over time. Of 229 subjects with longitudinal data, only four met the surveillance definition for "idiopathic CD4 lymphocytopenia" (ICL). CD4 cell counts of < 500 cells/microliters were, however, associated with subsequent HIV seroconversion (12.7/100 person-years at risk, relative risk (RR) = 4.53, 95% exact binomial confidence interval (CI) 1.7-10.7, p = 0.002).

Adult↗
PubMed1992

Endogenous interferon and triglyceride concentrations to assess response to zidovudine in AIDS and advanced AIDS-related complex.

To improve evaluation of new antiretroviral drugs in the acquired immunodeficiency syndrome (AIDS), sensitive biological markers that accurately predict response to treatment are needed. Two possible markers are endogenous interferon (E-IFN), which is a cytokine involved in the pathophysiology of AIDS, and serum triglycerides (TG), which are raised in patients with AIDS, possibly reflecting enhanced cytokine activity. E-IFN, TG, body-mass index, CD4 count, and HIV p24 were measured in 19 patients (15 with AIDS, 4 with AIDS-related complex), who were part of the phase II licensing trial of zidovudine (ZDV). 10 received ZDV and 9 received placebo. Rapid, significant, and sustained declines from initial values in E-IFN and TG concentrations were observed in ZDV patients but not in placebo patients. Baseline values of E-IFN and TG concentrations after 4 months on ZDV treatment were both important contributors to long-term survival. The findings suggest that these indicators of abnormal cytokine expression may be useful measures of not only disease severity but also efficacy of antiretroviral therapy in AIDS.

AIDS-Related Complex↗
PubMed1992

The spectrum of HIV-1-related disease among outpatients in New York City.

OBJECTIVES: To define the spectrum of HIV-1-related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations. DESIGN AND METHODS: The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively. RESULTS: Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts less than 200 x 10(6)/l than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts less than 500 x 10(6)/l, of whom 41 had CD4 counts less than 200 x 10(6)/l; thus, in addition to an estimated 16,425 individuals living with AIDS in NYC, we estimate that there are at least 14,454 HIV-infected individuals without AIDS with CD4 counts less than 500 x 10(6)/l, of whom 6734 have CD4 counts less than 200 x 10(6)/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study. CONCLUSIONS: These data indicate that there are more than 30,000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations.

Adult↗
PubMed1992

Comparative in vitro activities of teicoplanin, daptomycin, ramoplanin, vancomycin, and PD127,391 against blood isolates of gram-positive cocci.

The in vitro activities of teicoplanin, daptomycin, ramoplanin, and PD127,391, a new quinolone, were compared with that of vancomycin. Teicoplanin showed the lowest MICs against Enterococcus faecalis. Ramoplanin was slightly more active than the other peptide antibiotics against oxacillin-resistant Staphylococcus aureus. The MICs of the four peptide antibiotics were similar for the oxacillin-susceptible S. aureus. Daptomycin had good activity against staphylococci but was the least active agent against E. faecalis. The MICs of vancomycin against all isolates were in general higher than those of the new antibiotics, with the exceptions of the MICs of daptomycin against E. faecalis and teicoplanin against oxacillin-resistant Staphylococcus epidermidis. PD127,391 was the most active agent against all staphylococcal isolates.

Anti-Bacterial Agents↗
PubMed1991

Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine.

OBJECTIVE: To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of beta 2 microglobulin, neopterin, or HIV p24 antigen or antibody are correlated with survival in patients with AIDS or AIDS related complex. DESIGN: Retrospective study of changes in laboratory markers and survival. SETTING: Multicentre trial at university hospital clinics. SUBJECTS: 90 Patients with AIDS or AIDS related complex. INTERVENTION: Patients started zidovudine 200 mg orally every four hours. Fifty six of the patients died a median 17 months after starting zidovudine; the remaining 34 patients were followed up for a median 25.5 months. MAIN OUTCOME MEASURES: Changes in CD4+ lymphocyte count and serum concentrations of p24 antigen and antibody, beta 2 microglobulin, and neopterin; survival of the patient. RESULTS: The pretreatment characteristics that independently predicted poor survival were determined using a multivariate proportional hazards model: a diagnosis of AIDS (v AIDS related complex), age over 45 years, and the logarithm of serum neopterin concentration. When these baseline characteristics were controlled for the logarithm of CD4+ lymphocyte count at weeks 8-12 of treatment (p = 0.007) and an increase in serum beta 2 microglobulin concentration at weeks 8-12 (p = 0.05) also independently correlated with survival. In the 38 patients with a better pretreatment prognosis, 24 month survival estimated by the product-limit method was 88% for those with a good response on both surrogate markers during early treatment compared with only 50% for those with a poor response on either marker. In the 38 with a worse pretreatment prognosis, 24 month survival was estimated to be 49% for those with a good response on both surrogate markers compared with only 18% for those with a poor response on either. CONCLUSION: These data suggest that CD4+ lymphocyte count at 8-12 weeks and, perhaps, change in serum beta 2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.

AIDS-Related Complex↗
PubMed1991

Thoracic surgery in the AIDS patient.

AIDS is a syndrome caused by HIV. The virus is spread by homosexual or heterosexual transmission and by infected blood or certain body fluids. Respiratory infections are the commonest cause of death, and diagnosis may be difficult. The fiberoptic bronchoscope (FOB) plays an essential role in diagnosing respiratory infections in AIDS and is important in minimizing the need for open lung biopsies. Various problems require thoracic surgical consultation and treatment. We do not consider it ethical to deny these patients help. There can be no "double standard" in the care of patients in the hospital or in the operating room since any of our patients may have HIV without our knowledge.

Acquired Immunodeficiency Syndrome↗
PubMed1991

An open-label, dose-ranging trial of AL 721 in patients with persistent generalized lymphadenopathy and AIDS-related complex.

AL 721, a lipid mixture with reported in vitro activity against human immunodeficiency virus (HIV) via cell membrane or virion cholesterol depletion, was evaluated in a multicenter, open-label, dose-ranging trial. Forty men with persistent generalized lymphadenopathy or AIDS-related complex were treated with doses of 20, 30, 40, or 50 g orally twice daily for 8 weeks, and monitored for toxicity, disease progression, and with immunologic, virologic, and serum lipid profiles. The compound was found to be well tolerated over the broad range of doses examined; adverse reactions were confined to the gastrointestinal tract, of mild to moderate severity, and self-limited in duration. Modest weight gains observed on treatment were reversed within 4 weeks following cessation of therapy. While disease progression was not observed in this short-term study, we could find no indication of an immunorestorative or antiviral effect of AL 721, as determined by T-lymphocyte subset quantitation or HIV culture. All three patients who were HIV p24 antigenemic at entry retained positive antigen levels throughout treatment. As a consequence of therapy, however, significant increases in serum lipids were observed, including elevations in both triglyceride and total cholesterol levels. In conclusion, our experience on the largest group of HIV-infected patients treated with the highest doses of AL 721 provides no support for the use of this compound as an antiretroviral agent.

AIDS-Related Complex↗
PubMed1990

Prognostic significance of quantitative levels of HIV p24 binding capacity in HIV infection.

Human immunodeficiency virus, type 1 (HIV-1), produces a chronic infection with a long latency before clinical disease. We followed 214 untreated subjects for 12-42 months to study the natural history of HIV infection: 110 were classified as asymptomatic, 11 as AIDS-related complex (ARC), 15 as AIDS with Kaposi's sarcoma (KS), 31 as AIDS with opportunistic infections (AIDS/OI), and 47 were HIV-seronegative controls. The quantitative capacity of serum to complex HIV p24 antigen, termed the p24 binding capacity (p24 BC), and quantitative levels of HIV p24 antigen in serum were determined at regular intervals. For people in all diagnostic groups, a p24 BC below 31 ng/ml was more closely associated with progression to AIDS/OI than was p24 antigen positivity; 94% of AIDS/OI, 86% of ARC, 56% of AIDS/KS, and 19% of asymptomatic subjects had p24 BC less than 31 ng/ml during the study period, while 67% of AIDS/OI, 27% of ARC, 61% of AIDS/KS, and 20% of asymptomatic subjects were p24 antigenemic. Prospective analysis of 47 asymptomatic seropositive men followed for 3 years, who showed actuarial progression rates to ARC at 4%, 13%, and 23% and to AIDS at 5%, 8%, and 8% at 1, 2, and 3 years, indicated that entry levels of p24 BC below 31 ng/ml were as strongly associated with progression to ARC/AIDS as was p24 antigenemia (p = 0.0003 vs. p = 0.008). The p24 binding capacity assay is a new and convenient methodology to measure immunocomplexing antibody to HIV p24 and is a powerful indicator of progressive HIV disease.

AIDS-Related Complex↗
PubMed1990

Patterns of HIV-1 and HTLV-I/II in intravenous drug abusers from the middle atlantic and central regions of the USA.

Seroprevalence of human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus types I and II (HTLV-I/II) was determined among 1160 intravenous (iv) drug abusers from five drug treatment or medical centers (Manhattan, Brooklyn, New Jersey, Detroit, and New Orleans). HIV-1 infection ranged from 5% in New Orleans to 48% in New York City. Hispanics and blacks had a significantly higher rate of HIV-1 infection than whites (P less than .01), but within each group rates were similar between males and females and by age stratum. HTLV-I/II seroprevalence increased with age from 3% in the 20-29 year age group to 37% in the group greater than 50 years. New Orleans and Manhattan (24%) had the highest rate, and blacks (19%) had a higher rate than either Hispanics (6.3%) or whites (7.3%). No association between HIV-1 and HTLV-I/II infection was observed except in Manhattan. When compared with iv drug abusers infected only with HIV-1, dually infected subjects had more clinical symptoms related to immune deficiency but a lower prevalence of HIV antigenemia. These data document the frequent occurrence of retroviral infections in iv drug abusers. The contrast between the two classes of virus suggests that HIV-1 is more efficiently transmitted, while the age-dependent rise in HTLV-I/II seroprevalence suggests cumulative exposure of a less-transmissible agent.

Adult↗
PubMed1990

[Aspergillus osteomyelitis of the sternum. Description of a case and review of the literature].

Fungal infections by Aspergillus are rare in hosts with and uncompromised immunological status, but are not uncommon in immunologically compromised patients. Bone involvement is exceedingly rare, except for infections of the sinuses and periorbital area, and is usually due to the direct extension of the infection from a neighboring organ or to hematogenous dissemination in critically ill patients. The authors report a case of sternal osteomyelitis by Aspergillus flavus in a diabetic, immunologically competent patient, and review the literature on that condition.

Aspergillosis↗
PubMed1989

Prolonged zidovudine therapy in patients with AIDS and advanced AIDS-related complex. AZT Collaborative Working Group.

We examined the long-term safety and efficacy of zidovudine therapy in 229 subjects with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex who previously participated in a placebo-controlled study of zidovudine. One hundred two placebo recipients (delayed treatment group) and 127 zidovudine recipients (original treatment group) were followed up while receiving zidovudine therapy for a mean of 21 months. Survival rates for the original treatment group were 84.5% and 57.6% at 12 and 21 months, respectively; for the delayed treatment group, 78.8% and 64.6% at 12 and 21 months, respectively, and 78.8% and 47.5% at 12 and 21 months, respectively, for 77 subjects with AIDS and 93.0% and 71.8%, respectively, for 50 subjects with AIDS-related complex in the original treatment group. Adverse reactions decreased over time and newly observed toxic reactions were unusual. The clinical course of these subjects suggests continued survival benefits with long-term zidovudine therapy.

AIDS-Related Complex↗
PubMed1989

HIV-1 infection among intravenous drug users in Manhattan, New York City, from 1977 through 1987.

Intravenous drug users are the second largest group to develop the acquired immunodeficiency syndrome, and they are the primary source for heterosexual and perinatal transmission in the United States and Europe. Understanding long-term trends in the spread of human immunodeficiency virus among intravenous drug users is critical to controlling the acquired immunodeficiency syndrome epidemic. Acquired immunodeficiency syndrome surveillance data and seroprevalence studies of drug treatment program entrants are used to trace seroprevalence trends among intravenous drug users in the borough of Manhattan. The virus entered this drug-using group during the mid-1970s and spread rapidly in 1979 through 1983. From 1984 through 1987, the seroprevalence rate stabilized between 55% and 60%--well below hepatitis B seroprevalence rates. This relatively constant rate is attributed to new infections, new seronegative persons beginning drug injection, seropositive persons leaving drug injection, and increasing conscious risk reduction.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Prevalence of human T-cell leukemia/lymphoma virus (HTLV) type II infection among high-risk individuals: type-specific identification of HTLVs by polymerase chain reaction.

The extent of human T-cell leukemia/lymphoma virus type II (HTLV-II) infection and its rate of spread have been difficult to determine owing to the serological cross-reactivity between HTLV-I and HTLV-II. The present study overcame this problem by directly detecting type-specific proviral sequences by means of the polymerase chain reaction (PCR) and liquid hybridization. Screening was performed on a cohort of primarily white intravenous drug abusers (IVDAs), and individuals of other behaviorally defined risk groups from the New York City area. Eleven percent (19 of 169) of the individuals in these high-risk groups were determined by PCR to have HTLV-II proviral infections. One of these patients displayed an exfoliative erythrodermatitis. Thirteen of the 19 subjects were positive in an HTLV-II enzyme-linked immunosorbent assay (ELISA). The remaining six individuals, although negative in the HTLV-II ELISA, were confirmed as HTLV-II positive by analyzing their DNA with a second HTLV-II-specific primer detector system. Four additional individuals were reactive in the HTLV-II ELISA but were PCR-negative for HTLV-II. PCR analysis for HTLV-I revealed that all four were positive for that virus. Thirty-seven percent (seven of 19) of the HTLV-II PCR-positive subjects were also PCR-positive for HTLV-I, and 84% (16 of 19) of the HTLV-II positive individuals were infected with human immunodeficiency virus (HIV-1). Six individuals were triply infected with HTLV-I, HTLV-II, and HIV-1.

Enzyme-Linked Immunosorbent Assay↗
PubMed1988

A larger spectrum of severe HIV-1--related disease in intravenous drug users in New York City.

Increasing mortality in intravenous (IV) drug users not reported to surveillance as acquired immunodeficiency syndrome (AIDS) has occurred in New York City coincident with the AIDS epidemic. From 1981 to 1986, narcotics-related deaths increased on average 32% per year from 492 in 1981 to 1996 in 1986. This increase included deaths from AIDS increasing from 0 to 905 and deaths from other causes, many of which were infectious diseases, increasing from 492 to 1091. Investigations of these deaths suggest a causal association with human immunodeficiency virus (HIV) infection. These deaths may represent a spectrum of HIV-related disease that has not been identified through AIDS surveillance and has resulted in a large underestimation of the impact of AIDS on IV drug users and blacks and Hispanics.

Acquired Immunodeficiency Syndrome↗