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Biomedical subjects

D I Abrams

Publications and source records attributed to D I Abrams.

At least 37 records · Page 2Linked to original sources

Current therapeutic options for Kaposi's sarcoma.

Treatment options for patients with acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) have changed very little over the past decade. Research has been hampered by the absence of an accepted staging system for KS and the lack of a uniform definition of response. New advances in understanding the pathogenesis of KS, particularly the role of angiogenesis and growth factors, may help in the future development of additional therapies. At present, available options include radiation therapy, chemotherapy, and biologic response modifiers. Improved delivery systems for existing chemotherapeutic agents may help to target more effective doses to KS lesions and to prevent certain dose-limiting side effects. Our goal should be to recommit ourselves to finding ways to improve the survival of patients with AIDS-related KS, not j ust to deliver cosmetic or palliative treatments.

Antineoplastic Agents↗

Continuous low-dose interferon-alpha therapy for HIV-related immune thrombocytopenic purpura.

Our objective was to examine the efficacy and toxicity of continuous, low-dose interferon-alpha therapy for human immunodeficiency virus-related immune thrombocytopenic purpura (HIV-ITP) in a Phase II clinical trial overseen by a community-based consortium of physicians conducting clinical trials in HIV-related diseases. Sixteen patients with HIV-ITP defined by prospective clinical criteria were enrolled; the majority had failed other therapies for HIV-ITP. Baseline and serial measurements were made of platelet counts, complete blood counts, serum chemistries, platelet-associated immunoglobulin, and CD4+ T-lymphocyte counts; subjective symptoms and bleeding were recorded. Three million units of interferon-alpha 2b were self-administered by subcutaneous injection every Monday, Wednesday, and Friday for 16 weeks. Thirteen participants were evaluable for response. One obtained a complete response, eight had partial responses, and four had no response to interferon-alpha therapy. The mean absolute platelet count of the group rose from 15.5 x 10(9)/L at baseline to 47.3 x 10(9)/L at 2 weeks and remained in this range for the duration of the study. CD4+ T-lymphocyte counts and serum chemistries did not change significantly during therapy. Ability to detect platelet-associated immunoglobulin did not change in a predictable manner in relation to platelet count response. Hematologic toxicity was limited to one episode of granulocytopenia, which resolved after a lowering of zidovudine dosage. Subjective toxicities were mild and tolerable, and minor bleeding problems improved in all participants so affected. Low-dose, continuous therapy with interferon-alpha resulted in meaningful increases in the platelet counts of the majority of study participants with HIV-ITP. Interferon-alpha was safe and tolerable for most participants with HIV-ITP at the dosage and schedule employed in this study. Interferon-alpha for clinically significant thrombocytopenia and who have failed to respond to zidovudine.

Adult↗

A comparative trial of didanosine or zalcitabine after treatment with zidovudine in patients with human immunodeficiency virus infection. The Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: Both didanosine and zalcitabine are commonly used to treat patients with human immunodeficiency virus (HIV) infection who cannot tolerate zidovudine treatment or who have had disease progression despite it. The relative efficacy and safety of these second-line therapies are not well defined. METHODS: In this multicenter, open-label trial we randomly assigned 467 patients who previously received zidovudine and had 300 or fewer CD4 cells per cubic millimeter or a diagnosis of the acquired immunodeficiency syndrome (AIDS) to treatment with either didanosine (500 mg per day) or zalcitabine (2.25 mg per day). RESULTS: After a median follow-up of 16 months, disease progression or death occurred in 157 of 230 patients assigned to didanosine and 152 of 237 patients assigned to zalcitabine, for a relative risk of 0.93 for the zalcitabine group as compared with the didanosine group (P = 0.56), which decreased to 0.84 (P = 0.15) after adjustment for the CD4 count, Karnofsky score, and presence of AIDS at base line. There were 100 deaths in the didanosine group and 88 in the zalcitabine group, for a relative risk of 0.78 (P = 0.09) and an adjusted relative risk of 0.63 (P = 0.003). A majority of patients in each group (66 percent) had at least one adverse event during treatment (153 patients taking didanosine and 157 taking zalcitabine). Peripheral neuropathy and stomatitis occurred more often with zalcitabine and diarrhea and abdominal pain more frequently with didanosine. CONCLUSIONS: For patients with HIV infection who have not responded to treatment with zidovudine, zalcitabine is at least as efficacious as didanosine in delaying disease progression and death.

Acquired Immunodeficiency Syndrome↗

Treatment options in zidovudine intolerance or failure.

AIM: To compare the efficacy and safety of didanosine and zalcitabine in patients who could not tolerate zidovudine or who had failed to respond adequately. PATIENTS AND METHODS: A multicentre, randomly allocated, open-label clinical trial was set up with 230 patients treated with didanosine and 237 treated with zalcitabine. All had previously been treated unsuccessfully with zidovudine. The patients were followed for at least 1 year, with an average of 16 months. RESULTS: Disease progression or death occurred in 157 patients taking didanosine and 152 taking zalcitabine. There appeared to be a slight trend in favour of survival in the latter group. CONCLUSIONS: There is an urgent need for more effective and better tolerated antiretroviral agents in the treatment of HIV infection. Zalcitabine is at least as effective as didanosine and may provide a survival advantage in patients treated unsuccessfully with zidovudine.

Acquired Immunodeficiency Syndrome↗

Tolerability of combined ganciclovir and didanosine for the treatment of cytomegalovirus disease associated with AIDS.

Ganciclovir is one of only two drugs licensed by the U.S. Food and Drug Administration for the treatment of opportunistic cytomegalovirus (CMV) disease. The combination of ganciclovir and zidovudine has been reported to be poorly tolerated because of dose-limiting hematologic toxicity; thus we retrospectively examined the tolerability of combination therapy with ganciclovir and didanosine in 32 patients with AIDS. These patients were receiving ganciclovir for CMV disease in addition to didanosine in the Videx U.S. Expanded Access Program. During the period of combined therapy, dose-limiting hematologic toxicity (absolute neutrophil count, < 500 cells/microL) developed in only 9.4% of patients and severe anemia (hemoglobin level, < 8.0 g/dL) in only 12.5%. Rates of dose-limiting intolerance to didanosine were similar to those previously reported in the Expanded Access Program. Overall, 15 of 32 patients in the current study tolerated therapeutic doses of didanosine in combination with ganciclovir; in contrast, only 5 of 29 patients tolerated zidovudine (600 mg/d) in combination with ganciclovir in the largest trial of therapy with this combination whose results have been published to date (P = .02, Fisher's exact test). Since recent data suggest that the administration of some form of antiretroviral therapy prolongs survival in patients with CMV retinitis, coadministration of didanosine with ganciclovir should be considered for such patients who do not tolerate other regimens with activity against both retroviruses and CMV.

AIDS-Related Opportunistic Infections↗

Clofazimine as prophylaxis for disseminated Mycobacterium avium complex infection in AIDS.

A randomized, prospective, open-label, treatment versus no treatment community-based clinical trial was conducted to evaluate the safety and efficacy of clofazimine as prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with human immunodeficiency virus (HIV) disease. Subjects were 110 patients with a first episode of Pneumocystis carinii pneumonia 2-4 months before enrollment or CD4 lymphocyte counts < or = 100/mm3; they were randomized to receive 50 mg of clofazimine daily or no treatment. Seven patients randomized to clofazimine developed disseminated MAC infection, compared with 6 patients receiving no treatment. Seventeen patients died: 9 in the treatment group and 8 receiving no treatment. Clofazimine at a dose of 50 mg/day is well tolerated by patients with HIV disease. Reduction in CD4 lymphocyte count to < 50/mm3 is a significant predictor of the development of disseminated MAC infection.

Acquired Immunodeficiency Syndrome↗

Burnout among HIV/AIDS health care providers. Helping the people on the frontlines.

Human immunodeficiency virus disease has presented the medical professional with many challenges over the past 10 years. In the decade ahead, one aspect of working in the field that is certainly becoming an increasingly formidable issue will be dealing with AIDS-related burnout among health care professionals. The risks of AIDS-related burnout are multiple. If providers cannot find effective strategies for coping, it is possible that some of the most sensitive and compassionate workers in the field may leave to seek less stressful career opportunities. Those who focus on the negative impact that HIV disease has had on society will react with increased finger pointing to the risk of burning out as another negative consequence of working with HIV infection. Individual burnout will ultimately impact on the organization requiring interventions at that level as well. Setting up mechanisms for both individuals and organizational systems to combat AIDS-related burnout will, in the short run, add to increased costs of care in a disease already noted for its high treatment expense. However, intervening to prevent AIDS-related burnout will ultimately be cost effective by minimizing its negative effects on individuals and institutions. Learning how to cope with AIDS-related burnout may benefit the medical professional caring for patients with HIV disease as well as the profession as a whole. Facilitation of communication among individuals will certainly be fostered. Already we have seen a reorganization of delivery of health care that encourages the emphasis on integration of the patient into a true partnership with their provider. Becoming aware of the problem of AIDS-related burnout and attempting to prevent it can only serve to foster greater humanism in service professionals. A report of the National Academy of Science Committee for the oversight of AIDS activities recommended in 1988 that "research funding be made available to examine the feasibility and effectiveness of programs to alleviate stress in health care workers who care for AIDS patients." Such funding is long overdue and should be made available immediately. As we enter the second decade of facing the complex challenges of the HIV epidemic, the stress could potentially become overwhelming. Dysfunctional health care providers need not become part of the problem. Now is the time to find solutions.

Acquired Immunodeficiency Syndrome↗

Continuous, low-dose therapy with interferon-alpha for human immunodeficiency virus (HIV)-related immune thrombocytopenic purpura.

A patient with HIV-related immune thrombocytopenic purpura (HIV-ITP) had a rapid rise in platelet count when treated with interferon-alpha 2b, 3 million units three times weekly. There were no significant toxicities with therapy. His platelet count fell to pretreatment levels when therapy was discontinued, then increased again when therapy was reinstituted at 1.5 million units three times weekly. Interferon-alpha 2b, administered continuously at low doses, is well tolerated, effective, and possibly less immunosuppressive than other treatments for HIV-ITP.

Adult↗

Clinical and virologic effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma: results of a randomized trial.

Thirty patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL) receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomized to receive either subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) or no additional therapy. Recombinant rGM-CSF (at a dose of 10-20 micrograms/kg/d) was given on days 1 to 10 (early rGM-CSF) to the first five patients, but was changed to days 4 to 13 (delayed rGM-CSF) of each chemotherapy cycle in subsequent patients. Compared with the control group (N = 10), the delayed rGM-CSF group (N = 11) had higher mean nadirs of the absolute neutrophil count (0.36 v 0.89 x 10(9)/L; P = .009), shorter mean durations of neutropenia (4.9 v 1.3 days; P = .02), fewer chemotherapy cycles complicated by neutropenia and fever (67% v 27%; P = .001), fewer days hospitalized for fever and neutropenia (4.9 v 1.8; P = .004), fewer reductions in chemotherapy dosages, and less frequent delays in chemotherapy administration. No significant differences were observed between patients in the control group and those in the early rGM-CSF group (N = 5). Median levels of serum HIV-1 p24 antigen decreased to 18% and 17% of baseline values in control (N = 4) and rGM-CSF groups (N = 6), respectively, 1 week following administration of the first cycle of chemotherapy. In the third week after chemotherapy, median antigen levels remained below baseline in the control group, but rose to 243% of baseline values in the rGM-CSF group (P = .01), suggesting stimulation of HIV replication. The effect of this change in HIV activity on clinical outcome of treated patients could not be determined, and therefore the clinical significance of this finding remains unclear. Complete response rates of 67%, 70%, and 60% were observed in the control, delayed rGM-CSF, and early rGM-CSF groups, respectively, with corresponding survival times of 9.0, 11.4, and 8.0 months.

Adult↗

Acquired immunodeficiency syndrome and related malignancies: a topical overview.

As we enter the second decade of confronting human immunodeficiency virus (HIV)-induced disease, progress in the prophylaxis and treatment of acquired immunodeficiency syndrome (AIDS)-related opportunistic infections is encouraging. While the infectious manifestations of HIV become more manageable, AIDS-related malignancies remain problematic. In the era of infection prophylaxis and antiretroviral therapy, the incidence of Kaposi's sarcoma (KS) and aggressive non-Hodgkin's lymphoma (NHL) appears to be increasing. Mounting evidence suggests that KS may result from infection with an as yet unidentified sexually transmitted agent. The increase in NHL cases may result from patients surviving longer with severe immune compromise with a possible contribution of antiretroviral therapy itself. Despite effective cosmetic treatments, survival in recently diagnosed KS patients is actually shorter than patients diagnosed with KS earlier in the epidemic. The addition of growth factors to the chemotherapeutic regimen of patients with AIDS-related NHL has not yet been translated into a survival advantage. In vitro antiviral activity and clinical evidence of possible synergy with other antiretrovirals suggests that continued investigation of alpha-interferon in treatment of AIDS-related malignancies is a priority for the second decade of challenging AIDS.

Acquired Immunodeficiency Syndrome↗

Risk factors for rapid progression from hairy leukoplakia to AIDS: a nested case-control study.

To determine risk factors for early progression from oral hairy leukoplakia to AIDS, this case-control study compared 27 patients who had not progressed to AIDS within 1,000 days of diagnosis of hairy leukoplakia with 28 patients who progressed rapidly. The risk factors that proved most predictive fell into two categories: (a) those reflecting sexual practices that correlated with how early in the epidemic patients were likely to have been infected, and (b) those reflecting immune competence. Hepatitis B was associated with a fourfold risk for early progression and syphilis with a nearly threefold risk. Skin test anergy for Candida species was strikingly predictive: all of 17 tested in the early progression group were anergic, compared with only two of 12 tested in the late progression group. Although skin testing has been largely supplanted by assessment of T-cell subsets, Candida species skin testing may be of particular prognostic value in otherwise apparently healthy HIV-infected persons.

Acquired Immunodeficiency Syndrome↗

The usefulness of diagnostic bone marrow examination in patients with human immunodeficiency virus (HIV) infection.

To determine the utility of bone marrow examination for the diagnosis of opportunistic infections and lymphoma in patients with known or suspected human immunodeficiency virus (HIV) infection, we retrospectively reviewed the medical and laboratory records of all patients undergoing diagnostic bone marrow examinations at San Francisco General Hospital between January 1, 1988 and December 31, 1989. All marrow examinations of patients with known or suspected HIV infection in which specimens were examined histopathologically and/or microbiologically for opportunistic pathogens or lymphoma were analyzed. Bone marrow examination resulted in the diagnosis of mycobacterial infection in 16% of the patients studied. Blood culture was 77% sensitive and bone marrow culture was 86% sensitive for detecting disseminated mycobacterial infection. This difference was not statistically significant (p greater than 0.05). Disseminated fungal infections occurred in less than 5% of the patients studied, and most were rapidly and accurately detected by examination of stained bone marrow samples. No case of lymphoma was diagnosed by bone marrow examination. Bone marrow examination may be useful for diagnosing opportunistic infections in patients with HIV infection. Mycobacterial blood cultures have a sensitivity comparable to bone marrow cultures in detecting disseminated mycobacterial infections, are less invasive, and may be less costly. Marrow examination is not useful for diagnosing lymphoma but can determine the extent of lymphoma that has been diagnosed by other means.

Bone Marrow Examination↗

Clinical manifestations of HIV infection, including persistent generalized lymphadenopathy and AIDS-related complex.

The ability to recognize disease related to the human immunodeficiency virus (HIV) and subsequent acquired immunodeficiency syndrome (AIDS) has improved in recent years with refinement of laboratory techniques. Because of this progress, several clinical conditions can now be identified as "pre-AIDS" syndromes. These include the persistent generalized lymphadenopathy syndrome, immune thrombocytopenic purpura, the wasting syndrome, and certain predominantly neurologic presentations. All are characterized by the presence of infection with HIV, symptomatic disease, and, over time, an increasing tendency to progress to "full-blown" AIDS.

AIDS-Related Complex↗

Effects of the use of AZT on the medical care costs of persons with AIDS in the first 12 months.

It is important in planning to meet resource needs and financing of care of people with acquired immune deficiency syndrome (AIDS) to determine the effect of the use of azidothymidine (AZT) on overall medical care costs. This study compares the medical care costs of people with AIDS (PWAs) who received AZT with those of PWAs not receiving it. Seven of the nine PWAs who were on the AZT arm of the phase II drug trial of AZT at San Francisco General Hospital (SFGH) in 1986 and a matched sample of PWAs at SFGH who were eligible for the trial but did not participate in it were included in the study and followed for 12 months. It was found that costs in the first 12 months and especially in the first 6 months were lower for persons using AZT, primarily because of significantly lower use of hospital services. However, costs began to rise in the second 6 months for those using AZT. The authors therefore doubt that the lifetime costs of PWAs are lowered by the use of AZT and conclude that they are likely to be the same as those of PWAs not using the drug. If this is indeed the case, the use of the drug is likely to be relatively cost-effective.

Acquired Immunodeficiency Syndrome↗