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Biomedical subjects

P A Volberding

Publications and source records attributed to P A Volberding.

At least 73 records · Page 4Linked to original sources
PubMed1989

Intralesional recombinant tumor necrosis factor-alpha for AIDS-associated Kaposi's sarcoma: a randomized, double-blind trial.

The effect of recombinant tumor necrosis factor-alpha (rTNF), injected directly into the tumor, was evaluated in a Phase I/II study of 27 patients with AIDS-associated Kaposi's sarcoma (KS). The maximally tolerated intralesional dose was less than 100 micrograms/m2 and the recommended intralesional dose was 25 micrograms/m2. In a double-blind, randomized, placebo-controlled study, rTNF reduced the cross-sectional area of 15 of 16 (94%) of the injected KS lesions and caused complete disappearance of 3 of 16 (19%) lesions. Only injected lesions showed a response. Rigors and fever were common dose-dependent side effects and were attenuated by meperidine. There were no changes in human immunodeficiency virus (HIV) activity as determined by serum p24 antigen levels. While biologically active, the systemic toxicity of rTNF as well as the lack of distant antitumor effects in noninjected lesions limits its clinical usefulness under the conditions employed in this trial.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Providing clinical pharmacy services in an AIDS--oncology ambulatory-care clinic.

The activities of a pharmacist in an ambulatory-care AIDS-oncology clinic are described. In December 1984, the chief of the AIDS Activities Division of San Francisco General Hospital's Department of Medicine hired a clinical pharmacist to develop the pharmacokinetics sections of investigational drug protocols, provide drug therapy consultations, and supervise the reorganization of the drug storage and inventory system. Since joining the clinic staff, the pharmacist has become active in a variety of clinical, research, and educational activities. The pharmacist conducts weekly medication refill clinics and developed drug information sheets for clinic patients and health-care professionals. The pharmacist also supervises timely collection of blood samples for serum drug concentration determinations and helps to prepare the investigational drugs for dispensing. The pharmacist developed policies and procedures for the safe handling of antineoplastic agents and standardized the accountability procedures for investigational drugs. The pharmacist also serves as a liaison between the clinic and the hospital's department of pharmacy and as a preceptor of pharmacy students and residents. A clinical pharmacist can make an important contribution to the research and patient-care activities in an AIDS-oncology clinic.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Caring for the patient with AIDS. An integrated approach.

Caring for patients with AIDS poses new and serious challenges for the medical care system, particularly the hospital. Stresses associated with the care of AIDS patients are generated by the medical complexities of the disease, by the stigma attached to the disease and the patients affected, and by the often overwhelming psychosocial support requirements. These stresses and concerns about the cost of AIDS care have contributed to apprehension about AIDS involvement on the part of many in the health care system. This paper addresses these concerns from the perspective of San Francisco General Hospital, which has developed what many consider to be a model of care in which comprehensive medical management is combined with cost effectiveness in a setting where much of the care is conducted in an outpatient and community-based setting.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Kaposi's sarcoma involving the lung in patients with the acquired immunodeficiency syndrome.

To determine the distinguishing features of pulmonary Kaposi's sarcoma (KS) in patients with the acquired immunodeficiency syndrome (AIDS), we compared three groups of patients, 16 with endobronchial KS, 15 with endobronchial KS and an opportunistic lung infection, and 40 with Pneumocystis carinii pneumonia (PCP) without concomitant pulmonary KS. The majority of pulmonary KS patients had extensive cutaneous disease at the time of pulmonary diagnosis, and the diagnosis of pulmonary KS was easily established by the characteristic appearance of the endobronchial lesions. Dyspnea, fever, and cough were common presenting symptoms, but occurred more commonly in association with accompanying opportunistic infection. Diffuse interstitial infiltrates were observed in most patients in both groups, but the findings of nodular parenchymal densities or pleural effusion were more commonly observed in patients with pulmonary KS than in those with PCP alone. Pulmonary uptake of gallium-67 citrate or a diffusing capacity less than 80% were unusual in patients with pulmonary KS alone, but common in those with accompanying opportunistic infection or with PCP alone. Median survival in patients with pulmonary KS was only 2 months, and most patients had complicating opportunistic infections at the time of death. Pulmonary KS is generally a late and often preterminal manifestation of AIDS. Chest radiographs, gallium lung scans, and pulmonary function testing may provide diagnostic information that is helpful in distinguishing pulmonary KS from opportunistic lung infections.

Acquired Immunodeficiency Syndrome↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Lack of response to suramin in patients with AIDS and AIDS-related complex.

Forty-one homosexual men with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex were treated with 0.5, 1.0, or 1.5 g of suramin weekly for up to six months. In no patient was evidence of symptomatic improvement or regression of Kaposi's sarcoma shown. Opportunistic infections developed in 16 patients during therapy. Only six patients (15 percent) became human immunodeficiency virus (HIV) culture-negative during treatment, despite documentation of adequate serum suramin levels. All but one of these six have had disease progression. Decreases in the numbers of total T4 cells with time were observed in both AIDS and AIDS-related complex subgroups. Toxicity was significant and consisted of fatigue, fever, and hepatic and renal dysfunction, all of which were observed most frequently with the 1.0 or 1.5 g dosages. Fatal hepatic failure developed in two patients, and adrenal insufficiency was documented in eight patients. Suramin is a toxic agent that shows no virologic, immunologic, or clinical benefit in patients with HIV-related disease.

AIDS-Related Complex↗
PubMed1987

Treatment of patients with acquired immunodeficiency syndrome and associated manifestations.

Treatment of AIDS is multidisciplinary and often involves input from a number of medical subspecialties. Treatment of opportunistic infections and malignancies in AIDS is largely palliative in that these treatments do not reverse the underlying immunodeficiency. Investigational approaches to the treatment of this syndrome with immunomodulators and antiviral agents are currently being investigated with the hope that these agents, either alone or in combination, will be active against this devastating disease.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Treatment of Kaposi's sarcoma with interferon alfa-2b (Intron A).

The activity of the alpha interferons against AIDS-related Kaposi's sarcoma (KS) has been demonstrated in numerous clinical trials. Unfortunately, most reports have involved small patient cohorts and a variety of dosages and schedules of administration. We report here a series of Phase II trials with interferon alfa-2b (Intron A, Schering Corp., Kenilworth, NJ) involving 114 patients using three dose regimens. Patients received 50 X 10(6) IU/m2 intravenously (high dose), 30 X 10(6) IU/m2 subcutaneously (intermediate dose), or 1 X 10(6) IU/m2 subcutaneously (low dose). Clinical responses were seen in all regimens and, overall, 35% of the patients obtained complete or partial remissions. The response rates in the low-, intermediate-, and high-dose groups were 33%, 28%, and 45%, respectively. In addition, high-dose therapy was associated with more rapid time to response. Patients with low-stage (I or II) disease and those who lack B symptoms were more likely to respond to therapy; i.e., response rates for patients without B symptoms were 38%, 44%, and 60% in the low-, intermediate-, and high-dose groups, respectively. Seventy (61%) patients had died at the time of data collection, with a median survival of 15 months. Disease stage and the presence of B symptoms significantly affected mortality. Responders enjoyed significantly longer survival (P less than 0.10) than did nonresponders both overall and when adjusted for disease stage. Interferon alfa-2b was generally well tolerated, although almost all patients experienced flu-like symptoms. No life-threatening toxicities occurred and only six (6%) patients discontinued treatment due to adverse reactions. No significant improvement in immunologic parameters was detected during this study. These studies suggest that, in this disease setting, interferon alfa-2b may be acting through direct antiproliferative effects rather than as an immunomodulator, and higher doses appear to be more effective than very low doses.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The role of chemotherapy for epidemic Kaposi's sarcoma.

Studies of classic, and especially African, Kaposi's sarcoma in the 1970s showed that both forms of the disease respond to cytotoxic chemotherapy. The agents that had proven effective against these forms of neoplasm were among the first to be tried for managing epidemic Kaposi's sarcoma (EKS). Thus far, single-agent regimens using either vinblastine, vincristine, or etoposide have apparently shown the greatest efficacy in AIDS-associated Kaposi's sarcoma, with overall response rates of up to nearly 90% in some trials. Various combination regimens have been studied with a view to reducing side effects, particularly immune suppression, while maintaining overall efficacy. Thus far, only an alternating regimen of vinblastine and vincristine shows promise. Despite intrinsic shortcomings, chemotherapy, using cytotoxics alone or in combination with biologic response modifiers and other modalities, will play a role in managing EKS, even as the search for the optimal regimen continues.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Alpha interferon therapy of AIDS-associated Kaposi's sarcoma.

Alpha interferon has been the most widely studied biologic response modifier for the treatment of Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS). At San Francisco General Hospital's AIDS Clinic, three sequential trials of recombinant interferon alfa-2b (Intron A) were conducted between August 1982 and April 1984. In the first study, ten patients with early KS were randomized to receive either low-dose (1 MU/m2) subcutaneous (SC) or high-dose (50 MU/m2) intravenous (IV) treatment 5 days per week, every other week, for eight weeks. A perceived advantage of the latter regimen led to a subsequent trial in which 20 subjects received high-dose IV therapy. A 32% objective response rate was achieved, despite the fact that these patients had less favorable disease status and more constitutional symptoms than those in the first trial and had also experienced previous opportunistic infections (Ols). A final 8-week investigation evaluated the use of 30 MU/m2 three times per week in 30 subjects. Drug-related toxicity seemed more pronounced with this regimen, but overall objective responses were identical to those seen in the high-dose IV study. None of the trials produced evidence of immune reconstitution on laboratory evaluation. The patients were not protected from developing AIDS-related OI either during or following interferon therapy, although OI was diagnosed less frequently in responders, who also displayed a distinct survival advantage over those with progressive disease. These trends remained evident when the data from the three studies were pooled with those from three parallel trials conducted at the University of California, Los Angeles (UCLA). Studies evaluating the combined use of alpha interferon and chemotherapeutic agents known to be active against AIDS-related KS (such as VP-16 and vinblastine) have thus far failed to demonstrate a synergistic antitumor effect, while toxicity has increased. In light of in vitro evidence that alpha interferon suppresses the AIDS retrovirus and has clinical efficacy in KS comparable to that of cytotoxic agents, additional investigations, focusing on maximizing therapeutic potential, are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Kaposi's sarcoma and the acquired immunodeficiency syndrome.

This review has briefly summarized the place of KS in the AIDS epidemic, offering a framework for more critical evaluation of difficult therapeutic decisions. It should be expected (and it is hoped) that with the current rapid pace of AIDS research, many of these issues will be resolved shortly, and that therapy will become more rational. Until then, however, conventional approaches will be used. Given the hazards of these, it is incumbent upon the physician to remain up to date on developments in this rapidly evolving field.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Routine care and psychosocial support of the patient with the acquired immunodeficiency syndrome.

Due to the magnitude of the AIDS epidemic in San Francisco, centralization of services has been essential for providing maximal patient care and support, and allowing for efficient performance of clinical investigation. While other locales with fewer numbers of documented cases may not have the need for such extensive organization, lessons can be adopted from the San Francisco experience. It is never an easy task to provide routine medical care and psychosocial support for a young patient with an ultimately fatal illness. Close cooperation of the medical establishment and the community at large, with governmental assistance and support, facilitates this difficult undertaking.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Serological characterization of HTLV-III infection in AIDS and related disorders.

Current efforts to test blood donors and other persons for exposure to the human T cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome (AIDS), are based on the measurement of serum antibodies to viral antigens. We studied presence of serum antibodies to HTLV-III-related antigens from 767 individuals with AIDS or AIDS-related complex (ARC) or asymptomatic persons at risk for AIDS by using ELISA and immunoblot techniques. Of the 280 specimens from AIDS and ARC subjects that were tested, 99% were ELISA reactive and 96% were immunoblot reactive. Greater than 96% of the seropositive subjects manifested antibodies to the p24 core antigen, whereas only 88% had antibodies to the gp41 envelope-related glycoprotein. Contrary to previous reports, a short incubation time in the immunoblot assay failed to detect low-titer or low-affinity antibodies that were detected by overnight incubation. There was no apparent difference in pattern of antibodies to HTLV-III-related antigens in symptomatic vs. asymptomatic seropositive individuals.

Acquired Immunodeficiency Syndrome↗