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Peripheral blood and bone marrow findings are presented for six homosexual males with Kaposi's sarcoma. Cytopenia in one or more cell lines was common in this group of patients, including two individuals with pancytopenia. Bone marrow findings in all patients, while not specific, were similar in that adequate numbers of normal appearing erythroid, myeloid, and megakaryocytic elements were present. Mild plasmacytosis as well as reticulin fiber increase were common findings. No patient, at time of study, demonstrated marrow involvement with Kaposi's sarcoma. We conclude that depression of peripheral blood counts in these patients was not due to marrow underproduction, and discuss possible mechanisms for increased blood cell destruction.

Human immunodeficiency virus (HIV) infection produces a spectrum of clinical syndromes, progressing in severity from asymptomatic infection through the life-threatening diseases of the acquired immunodeficiency syndrome (AIDS). Current knowledge about the epidemiology, virology, and clinical manifestations of HIV infection and AIDS are reviewed.

We report five patients who illustrate the usefulness of fine-needle aspiration cytology (FNAC) in the differential diagnosis of lymphadenopathy in homosexual males. This differential includes hyperplasia, disseminated Kaposi's sarcoma, mycobacterial infections, and non-Hodgkin's lymphoma.

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.

The characteristics of acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma in 84 patients diagnosed and treated at San Francisco General Hospital are presented herein. While the majority were high-grade B-cell lymphomas, one cutaneous T-cell and one peripheral T-cell lymphoma were observed. In addition, three other tumors were suspicious for T-cell lymphoma. Sixty-seven percent of patients had stage IV disease, often at unusual sites. Epstein-Barr virus DNA sequences were identified in only five of 15 tumors by dot-blot analysis. Patients were treated with a variety of standard chemotherapeutic regimens, with radiation therapy alone, or with a novel chemotherapy protocol (COMET-A). No significant differences in complete response rates were observed. The most important predictor of survival was the total number of CD4-positive lymphocytes. Other predictors of survival included history of a diagnosis of acquired immunodeficiency syndrome, Karnofsky performance score, and the presence of extranodal disease. Survival was shorter among patients who received higher doses of cyclophosphamide (greater than 1 g/m2), including those treated with the COMET-A regimen. Implications for therapeutic decision making are discussed.

We describe the histologic and clinical features of non-Hodgkin's lymphoma diagnosed between January 1980 and December 1983 in 90 homosexual men from San Francisco, Los Angeles, Houston, and New York. The median age was 37 years, with an age distribution identical to that for cases of AIDS reported to the Centers for Disease Control. Sixty-two per cent of the patients had high-grade (aggressive) subtypes of lymphoma, 29 per cent had subtypes of intermediate grade, and 7 per cent had low-grade subtypes. Histologic subtypes and malignant cell phenotypes were consistent with a B-cell origin. All but two men had extranodal lymphoma: central-nervous-system, bone-marrow, bowel, and mucocutaneous sites were most commonly involved. Thirty-five of 66 evaluable men (53 per cent) had complete responses to combination chemotherapy or radiotherapy or both, and thus far, 19 (54 per cent) of them have had a relapse. Mortality and morbidity were closely related to prodromal manifestations; death or illness have occurred in 19 (91 per cent) of the 21 men who presented with AIDS, in 26 (79 per cent) of the 33 who presented with generalized lymphadenopathy, and in 5 (42 per cent) of the 12 who had no prodromal manifestations. Mortality rates analyzed according to histologic grade were higher than currently reported rates in other patient populations. Kaposi's sarcoma or severe opportunistic infections characteristic of AIDS developed in 14 of 33 men (42 per cent) who presented with generalized lymphadenopathy and in 3 of 12 (33 per cent) without prodromal manifestations. We conclude that non-Hodgkin's lymphoma in members of an AIDS risk group is a serious manifestation of AIDS and the AIDS-related complex.

Seventy homosexual men with unexplained persistent diffuse lymphadenopathy enrolled in a prospective natural history study from November 1981 to November 1982. These men had demographic, clinical, and laboratory findings similar to those of homosexual patients with the acquired immunodeficiency syndrome. Pathologic examination of lymph node biopsies from 35 patients showed florid follicular hyperplasia. Despite benign reactive pathologic findings, most patients had constitutional symptoms and recurrent non-life-threatening infections. All had evidence of immune dysfunction with B-lymphocyte activation and inversion of the T-lymphocyte helper: suppressor ratio. To date, none of our patients has developed the more malignant manifestations of the acquired immunodeficiency syndrome. The lymphadenopathy syndrome may be an alternative phenotypic response to the "acquired immunodeficiency syndrome agent."

Recent evidence indicates that individuals with acquired immunodeficiency syndrome (AIDS) or those at high risk for AIDS have an increased occurrence of lymphoma. AIDS-related lymphomas (ARLs) often present with an advanced stage of disease and highly malignant histologic subtypes. This study reviewed the abdominal computed tomographic (CT) findings in 29 patients with ARL, including ten with Hodgkin disease (HD) and 19 with non-Hodgkin lymphoma (NHL). Focal splenic and hepatic involvement was more common in both AIDS-related HD (10%) and NHL (26%) than reported in the non-AIDS population. In addition, mesenteric lymphadenopathy was demonstrated in 20% of patients with AIDS-related HD, compared with less than 5% in non-AIDS patients. In this series, patients with NHL had pelvic nodal masses in 37%, bowel involvement in 26%, and renal lesions in 11%. The authors conclude that ARLs are highly aggressive neoplasms that often present with atypical features compared with lymphomas in other patients. Potential problems in the CT interpretation of ARL for homosexual men are discussed.

Acquired immunodeficiency syndrome (AIDS) is a lethal infectious disease that has reached epidemic proportions in urban centers of the United States. Intraabdominal opportunistic infections and malignancies are common features of this syndrome. A prodromal phase or possibly milder form of infection is known as the AIDS-related complex. Abdominal computed tomography (CT) in patients with AIDS-related complex often demonstrates a triad of mild retroperitoneal and mesenteric adenopathy, splenomegaly, and perirectal inflammation. Lymph node enlargement greater than 1.5 cm is unusual in the AIDS-related complex and should prompt CT-guided biopsy. Abdominal adenopathy (greater than 1.5 cm) in AIDS, in our experience, is most commonly related to non-Hodgkin lymphoma, Kaposi sarcoma, or infection with Mycobacterium avium-intracellulare. In most instances, CT-guided biopsy with appropriate staining technique can readily distinguish these entities. However, the subtyping of non-Hodgkin lymphoma by fine-needle aspiration biopsy alone remains controversial. Unusual features of abdominal malignancies are common in AIDS. These include a purely lymphadenopathic form of AIDS-related Kaposi sarcoma and a predilection for extranodal sites of lymphoma in AIDS. In general, patients with AIDS-related lymphoma present with advanced stages of disease with highly malignant histologic subtypes. Abdominal CT may be useful clinically for diagnosing intraabdominal complications of AIDS.

We prospectively studied 40 hospitalized patients who had well-established diagnoses of acquired immunodeficiency syndrome. Patients with confounding risk factors for neuropathy were excluded; none of the study patients had known vitamin deficiency, alcoholism, or any metabolic, drug, or toxic factor. Clinical and electrophysiologic evidence of a distal symmetric polyneuropathy was found in 35% (13/37) of the patients. Symptoms and signs of neuropathy were usually mild, and painful dysesthesias were uncommon. Amplitude reduction of sural nerve action potentials distinguished all patients with from those without clinical neuropathy. Results of other electrophysiologic studies of sural, peroneal, and median nerves were typically normal. These results provide evidence of distal axonal degeneration. Neuropathy occurred only in patients with systemic illness longer than five months' duration. When compared with patients without neuropathy, these patients had more severe weight loss and a higher incidence of clinical dementia. Follow-up evaluation showed no evidence of clinical progression over a six-month period. The pathogenesis of this common distal axonal polyneuropathy is unknown and warrants further investigation.

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.

A clinical trial was conducted to determine the tolerance and toxicity of recombinant tumor necrosis factor (rTNF) and recombinant interferon gamma (rIFN-gamma) when administered concurrently by continuous intravenous infusion to 11 patients with the AIDS-related complex (ARC). In addition, HIV culture, p24 antigen levels, and CD4 positive lymphocytes were monitored to obtain preliminary evidence of antiviral and immunologic effects. Two 5-day treatment cycles were separated by a 9-day washout period. Two patients were entered at each dosage level and each patient received the two 5-day treatment cycles at two sequential dose levels ranging from 1 to 25 micrograms/m2. Two patients did not complete their second treatment cycle--one due to the development of a rash, the second due to central venous catheter discomfort. The occurrence of phlebitis with peripheral vein administration of these agents necessitated administration via central venous catheter. With the exception of a single patient who developed severe headache at the 25 micrograms/m2 dose, severe clinical toxicities were not observed. Fever, chills, headache, and myalgias were the most significant clinical toxicities observed and all were dose dependent. The percentage fall in total granulocytes was dose dependent and ranged from 17% at the 1 microgram/mm2 dose to 48% at both the 15 and 25 micrograms/mm2 dose levels. The mean nadir granulocyte count was 1694/mm3. No significant renal or hepatic toxicity was observed. Of 22 treatment cycles the CD4 cell number was increased in 11, unchanged in 7, and decreased in 4. The mean CD4 cell number did not change significantly (176 +/- 143/mm3 pretherapy versus 279 +/- 305/mm3 posttherapy).(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormally elevated serum beta 2-microglobulin has been associated with progression of human immunodeficiency virus (HIV) disease and could reflect in vivo HIV activity. We prospectively studied the effect of azidothymidine therapy on serum beta 2-microglobulin concentration in 41 patients with AIDS or AIDS-related complex. Median beta 2-microglobulin concentration decreased from 4.02 mg/L before therapy to 3.73 mg/L at week 24 of therapy (P = .016). Individual changes in beta 2-microglobulin during azidothymidine therapy correlated with changes in serum HIV p24 antigen (Spearman, r = .42, P = .007). Also, in a randomized placebo-controlled study, median beta 2-microglobulin concentration decreased after 16 w of therapy in 5 azidothymidine-treated patients compared with levels in 7 placebo-treated controls (P = .05). Serum beta 2-microglobulin appears to be a sensitive marker for in vivo antiretroviral drug activity and may be a better marker than serum p24 antigen for early intervention trials involving antiretroviral agents.

Abdominal computed tomography (CT) was performed in 31 patients with Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS), three patients with classic KS, and 12 patients with the newly described lymphadenopathy syndrome (LNS). The frequency, distribution, and appearance of lymphadenopathy and splenomegaly were similar in the AIDS-related KS and LNS groups. Rectal and perirectal disease was identified in 86% of the homosexual men studied; rectal KS could not be distinguished from proctitis on CT criteria alone. No CT abnormalities were seen in patients with classic KS. The CT demonstration of retroperitoneal, mesenteric, or pelvic adenopathy or of rectal or perirectal disease in patients with AIDS-related KS is not necessarily indicative of widespread involvement with the disease.

10 homosexual men with Kaposi's sarcoma (KS) were studied for evidence of cytomegalovirus (CMV) infection. IgG and IgM antibodies to CMV were detected in 9 out of 9 and in 7 out of 9 of these patients, respectively. CMV was recovered from body secretions or peripheral blood of 7 patients. Viral cultures of KS tumour biopsy specimens were negative in 8 out of 8 patients, but CMV RNA was detected by in-situ hybridisation in 2 out of 3 and CMV antigen(s) by immunofluorescence in 6 out of 9. Normal tissue specimens from 3 KS patients were negative for CMV antigen. These observations suggest an association of CMV with KS.

The possibility that cyclooxygenase products of arachidonic acid might contribute to the defective T lymphocyte function of homosexual men with the reactive lymph node syndrome was examined in vitro. T lymphocyte proliferation, assessed by the uptake of [3H]thymidine after the addition of phytohemagglutin, was 72,870 +/- 66,816 counts per minute (mean +/- SD) for eight patients and 119,589 +/- 64,913 counts per minute for 30 controls (P less than 0.05, Student's t test). Treatment with the cyclooxygenase inhibitor indomethacin increased the phytohemagglutin-induced proliferation of the T lymphocytes from five of eight patients, but none of 12 healthy homosexual and heterosexual control subjects. The production of prostaglandin E2 by T lymphocytes from six patients was 16.1 +/- 10.5 pg/5 X 10(6) cells/hr, as contrasted with that of 4.9 +/- 1.3 and 4.3 +/- 2.1 pg/5 X 10(6) cells for four healthy homosexual and six healthy heterosexual control subjects, respectively (P less than 0.01, Student's t test). The production of prostaglandin E2 by the patients' monocytes was normal. Abnormalities of the cyclooxygenase pathway of T lymphocytes of patients with the reactive lymph node syndrome may reflect an immunoregulatory defect, which predisposes to infections and may evolve into the more severe abnormalities of the acquired immune deficiency syndrome.

With the passage of time and the refinement of laboratory techniques, the ability to recognize disease related to human immunodeficiency virus infection has improved. Currently, a number of clinical conditions can be identified as "pre-AIDS" syndromes. These include the syndrome of persistent generalized lymphadenopathy, immune thrombocytopenic purpura, the wasting syndrome, and certain predominantly neurologic presentations. All are characterized by the presence of human immunodeficiency virus infection, symptomatic illness, and a tendency to progress to a diagnosis of full-blown AIDS that appears to be ever increasing with the passage of time.

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 (OIs). 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.

The presence of mediastinal and/or hilar adenopathy was assessed from the chest radiographs of two groups of homosexual men: 30 with diffuse, persistent lymphadenopathy syndrome and 45 with acquired immunodeficiency syndrome (AIDS). Intrathoracic adenopathy was not seen on the chest radiographs of the 30 men having diffuse, persistent lymphadenopathy and is therefore not a manifestation of that syndrome. Nine of the 45 men with AIDS demonstrated intrathoracic adenopathy. In each instance, adenopathy was indicative of serious intrathoracic disease. Seven of the nine had minimal or no respiratory symptoms. In four of the nine, the intrathoracic adenopathy detected from the chest radiographs was the first indication of AIDS. In six of the nine patients, one or more opportunistic infections were diagnosed from material obtained at bronchoscopy. Two patients had Hodgkin disease, diagnosed by lymph-node biopsy. The ninth patient, who died, had an immunoblastic sarcoma. Mediastinal and/or hilar adenopathy in patients with AIDS, or in patients at high risk for AIDS, necessitates immediate investigation, including bronchoscopy or lymph-node biopsy.

We conducted a study to identify the viruses in tissue specimens of oral "hairy" leukoplakia, a lesion that is found in immunosuppressed male homosexuals and that is associated with the subsequent development of the acquired immunodeficiency syndrome. When stained for papillomavirus core antigen, 49 of 67 biopsy specimens (73 per cent) yielded positive results in epithelial-cell nuclei. Electron microscopy showed papillomavirus-like particles in all of 25 specimens, and the herpes-type virus described in a previous report was seen in 23 of the 25 specimens. Three specimens had both types of particle in the same individual epithelial cells. Immunofluorescence for herpes simplex virus, varicella-zoster virus, and cytomegalovirus gave negative results in all cases, but 19 of 20 specimens showed intense nuclear staining in epithelial cells for the viral capsid antigen of Epstein-Barr virus (EBV). DNA hybridization using EBV probes in Southern blots demonstrated EBV DNA in all of 13 specimens and found 200 or more viral DNA molecules per cellular genome in 11 of the 13. The whole EBV genome was also demonstrated in the specimens and found to be in linear virion form. We conclude that EBV replicates within the epithelial cells in hairy leukoplakia.

A syndrome of isolated immune thrombocytopenic purpura (ITP) has recently been described in homosexual men. We have identified an antiplatelet antibody in the serum of 29 of 30 homosexual men with isolated ITP. The antibody binds to a platelet membrane antigen of 25,000 daltons, and binding is effected by the F(ab)2 portion of the immunoglobulin. Similar antibody activity was not detected in serum from 30 nonhomosexual patients with either ITP or nonimmune thrombocytopenia. The 25,000-dalton antigen was not found on other hematopoietic cells, and it was distinct from the core protein of the AIDS-associated retrovirus. In contrast, serum antibody reacted with a 25,000-dalton antigen associated with cultured herpes simplex virus Types I and II. In these experiments the antigen appeared to be derived from green-monkey kidney cells in which the herpes simplex viruses were grown. Identical antigenic activity was also demonstrated in uninfected human skin fibroblasts. We conclude that ITP in homosexual men is accompanied by a serum antibody directed against a platelet antigen of 25,000 daltons. The nature of the antigen and the relation of the serum antibody to ITP require further study.

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.

Prolongation of partial thromboplastin time was noted in patients with acquired immunodeficiency syndrome (AIDS) who were admitted to the hospital for diagnosis of opportunistic infection. As biopsy procedures were often indicated, detailed investigation of the abnormal coagulation study was performed in four patients. Results confirmed the presence of a lupus anticoagulant. Partial thromboplastin times of 34 consecutive subsequent patients hospitalized with the diagnosis of AIDS-associated opportunistic infection were recorded; prolongation was noted in 24 of these. None of these 38 patients exhibited clinical evidence of bleeding. One patient had a confirmed thrombotic episode. Prolonged partial thromboplastin time is a common finding in hospitalized patients with AIDS and opportunistic infection. If no clinical history of unusual bleeding is noted, the lupus anticoagulant should be suspected. Many patients with AIDS require invasive procedures for disease management; the lupus anticoagulant, an in vitro phenomenon, should not prevent these studies.

In 35 homosexual men with isolated thrombocytopenia at initial presentation, who were evaluated and treated between 1982 and 1984, hematologic studies showed immune destruction. In contrast to findings in other autoimmune conditions, T-lymphocyte subsets in these patients were reversed, with a mean helper to suppressor ratio of 0.4 and with an absolute depletion of helper cells to 390/mm3. An enzyme-linked immunosorbent assay detected antibodies to human T-lymphotropic virus type III in 21 of 25 patients tested; Western blot analysis confirmed seropositivity in the other 4 patients, who had borderline findings. Although 19 of 24 patients treated with steroids responded, only 2 achieved sustained normal platelet counts. Ten of fifteen patients who had splenectomy achieved remissions. Three patients treated with steroids or splenectomy developed diagnoses compatible with the acquired immunodeficiency syndrome 16 to 34 months after their initial presentation with thrombocytopenia. These findings indicate that immune thrombocytopenia is part of the clinical spectrum of the acquired immunodeficiency syndrome.