HLA-A,B,C and DR antigen frequencies in acquired immunodeficiency syndrome (AIDS) patients with opportunistic infections.

During the past three years, an epidemic of acquired immunodeficiency syndromes (AIDS) involving the presence of specific forms of cancer (notably Kaposi's sarcoma) and infection (e.g., pneumocystis carinii) ordinarily seen only in severely immunosuppressed hosts has occurred among active homosexuals, Haitian immigrants, drug users, and hemophiliacs in large cities in the United States and elsewhere. An as yet unidentified viral agent is presumably the cause of the initial immunodeficiency and host genetic factors may influence the subsequent development of different clinical symptoms in different patients. We have previously reported that the HLA antigens DR5 and DR2 are associated with susceptibility to Kaposi's sarcoma (KS) in different Caucasian subpopulations. We now have also noted that AIDS patients with opportunistic infections have a normal frequency of DR2 and DR5 and a significantly increased frequency of DR3 and that the ultimate clinical expression of AIDS in patients with unexplained lymphadenopathy may depend upon genetic factors associated with these particular DR types.

Acquired immune deficiency syndrome. A surgical perspective.

Eighty-nine lymph node biopsies were performed on 82 patients with lymphadenopathy, immunosuppression, and possible acquired immune deficiency syndrome. The 21 patients with diagnoses of lymphoma or Kaposi's sarcoma were older, had more sexual contacts, and were sexually active for more years than patients with benign diagnoses. Cytomegalovirus and Epstein-Barr viral titers were elevated in both groups but were not significantly different in the benign and malignant groups. Skin flora were cultured from lymph node tissue in 24.7% of the patients. Two patients (2.5%) had wound infections with the same bacterium present in the lymph node culture, while 66 patients initially had two different benign pathologic patterns. Fifty-six patients had explosive follicular hyperplasia, and ten had follicular involution. Four of the patients with follicular involution and one with follicular hyperplasia subsequently had malignant tumors.

Hodgkin's disease and AIDS. Twenty-three new cases and a review of the literature.

Despite numerous reports suggesting an association of Hodgkin's disease (HD) with the acquired immunodeficiency syndrome (AIDS), HD in an individual seropositive for the human immunodeficiency virus (HIV) still is not considered a criterion for the diagnosis of AIDS. The authors report 23 new cases of HD in individuals at risk for AIDS and review the literature. As a group, individuals at risk for AIDS who develop HD have a more aggressive form of the illness (82% with stage III or IV), have or develop AIDS-related opportunistic infections (54%), second neoplasms (10%), and /or profound cytopenias (32%), and 85 to 90% are HIV positive when tested. More than two thirds die within 1 year of the diagnosis of HD. The authors conclude that HIV infection alters the clinical course of HD, that advanced or high-grade HD in HIV-infected individuals should be considered indicative of AIDS, and all patients with HD should be tested for HIV.

Diagnostic pathology in the acquired immunodeficiency syndrome. Surgical pathology and cytology experience with 67 patients.

We report the pathologic findings in specimens submitted for histologic and cytologic evaluation from 67 patients with the acquired immunodeficiency syndrome. A wide variety of opportunistic pathogens were identified in 41 patients. Mycobacterium avium-intracellulare evoked only a mild host response: granulomas, if present, were poorly formed. Biopsy specimens showing cytomegalovirus gastroenteritis required sections at multiple levels to demonstrate inclusions. Combined histologic and cytologic evaluation can increase the diagnostic yield in pulmonary and esophageal infections. Kaposi's sarcoma was found in biopsy specimens from 29 patients. Early lesions were often extremely subtle, yet distinct from, benign vascular proliferations in involuted lymph nodes. Malignant lymphoma was diagnosed in ten homosexual men who were suspected of having the acquired immunodeficiency syndrome. The lymphomas were characterized by B-cell origin, a diffuse pattern, frequent extranodal presentations, and an aggressive clinical course with prominent central nervous system involvement.

Malignant lymphomas and the acquired immunodeficiency syndrome. Evaluation of 30 cases using a working formulation.

Malignant lymphomas occurring in 29 homosexual men and one thalassemic woman with the acquired immunodeficiency syndrome or the acquired immunodeficiency syndrome-related complex are reported using a working formulation for non-Hodgkin's lymphomas (NHLs). The patients' ages ranged from 25 to 59 years, with an average age of 42 years. Ninety percent of the cases were extranodal; 67% were exclusively extranodal. One case of Hodgkin's disease was encountered. All NHLs were of the diffuse types in both the intermediate- and high-grade categories, with the largest single group (49%) being of the diffuse, large, follicular-center-cell types. The NHLs in this series were classifiable as B-cell neoplasms and were aggressive as evidenced by markedly reduced median survivals. The morphological diagnosis as defined in the working formulation, especially for the intermediate-grade lesions, offered little significant prognostic information.

Kaposi's sarcoma of the penis in patients with acquired immunodeficiency syndrome.

With the growing number of patients with the acquired immunodeficiency syndrome there has been a marked increase in the incidence of Kaposi's sarcoma. Kaposi's sarcoma of the penis was the initial presenting manifestation of acquired immunodeficiency syndrome in 4 patients. Overall, less than 3% of all acquired immunodeficiency syndrome patients with Kaposi's sarcoma have the initial lesion on the penis. However, eventually almost 20% of those with Kaposi's sarcoma will have lesions on the genitalia. Therefore, urologists must have an understanding of the entity and its management. A conservative approach to treatment of these lesions is recommended.

Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients.

Fifty patients with acquired immune deficiency syndrome had complications affecting the central or peripheral nervous systems or both. The patients were either male homosexuals, intravenous drug abusers, or recently arrived Haitian refugees. They ranged in age from 25 to 56. Central nervous system complications were of four kinds: (1) Infections included Toxoplasma gondii abscesses in 5 patients, progressive multifocal leukoencephalopathy in 2, cryptococcal meningitis in 2, Candida albicans in 1, and possible Mycobacterium avium intracellulare in 3. Eighteen patients suffered a subacute encephalitis possibly attributable to cytomegalovirus infection. (2) Tumors consisted of primary lymphoma of the brain in 3 patients and meningeal invasion by systemic lymphoma in 4. (3) Vascular complications included nonbacterial thrombotic endocarditis in 2 patients and cerebral hemorrhages in the setting of thrombocytopenia in 3. (4) Undiagnosed central nervous system problems were evidenced as focal brain lesions in 3 patients and self-limiting aseptic meningitis in 4. Peripheral neuropathy occurred in 8 patients.

Weekly oral etoposide in patients with Kaposi's sarcoma associated with human immunodeficiency virus infection: a phase I multicenter trial of the AIDS Clinical Trials Group.

We conducted a Phase I trial to evaluate the safety, maximally tolerated dose (MTD), antitumor activity, and pharmacology of once-weekly oral etoposide in patients with Kaposi's sarcoma (KS) and AIDS. From September 1990 to October 1991, 27 eligible patients with biopsy-confirmed KS were treated at six etoposide dose levels, ranging from 150 to 400 mg weekly. Patients were treated until their tumor progressed or until unacceptable toxicity developed. On the first day of therapy, etoposide plasma concentrations were measured by high-performance liquid chromatography. The MTD was defined as the etoposide dose that induced reversible grade 3 toxicity in three of six patients during the first 4 weeks. Although dose-limiting toxicity was uncommon during the first 4 weeks of treatment (three of 27 patients), and the MTD was not reached, with longer treatment > 50% of patients developed dose-limiting toxicities, most commonly neutropenia. Responses were observed at all dosage levels (except 350 mg weekly), with partial tumor regression documented in nine (36%) of 25 evaluable patients. There was marked variability in etoposide area under the plasma concentration versus time curve, elimination half-time (t1/2), and urinary excretion. These pharmacokinetic features were not, however, associated with the presence of gastrointestinal symptoms, the severity of side effects, or tumor response. We conclude that weekly oral etoposide can be safely administered to patients with AIDS and KS. The observed antitumor effects over a wide range of doses support further studies with very low and minimally toxic etoposide doses, alone or in combination with other agents.

Chromosome abnormalities in AIDS-associated lymphadenopathy.

Cytogenetic studies were performed on direct and 24-hour culture preparations of eight lymph node biopsies from seven patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC)-associated lymphadenopathy in whom histological evidence of lymphoma was not detected. Three of these seven had chromosomal abnormalities, including chromosome instability in one and clonal chromosomal abnormalities in two; one of the latter was a t(8;14)(q24;q32). The remaining five showed normal karyotypes. Epstein-Barr virus (EBV) titers were elevated in all three patients that exhibited chromosome abnormalities, two of whom later developed malignant lymphoma. A control group of five patients with reactive lymphadenopathy not associated with AIDS failed to reveal chromosomal aberrations, but elevated EBV titers were present in two. These data are consistent with current views on the role of EBV and chromosome change in the development of lymphoma in immunodeficient states and suggest that karyotypically abnormal AIDS-related lymphadenopathy represents a prelymphomatous proliferation.

Generalized lymphadenopathy in homosexual men.

The cases of 90 homosexual or bisexual men with generalized lymphadenopathy were studied by epidemiologic, clinical, pathologic, immunologic, and genetic methods. The patients ranged in age from 20 to 52 years and had histories of multiple sexually transmitted diseases and both recreational and prescription drug use. Histologically, their lymph nodes showed three patterns: explosive follicular hyperplasia; follicular involution with expansion of the paracortical area; and a mixed pattern of follicular hyperplasia and follicular involution in the same lymph node. The frequency of HLA-DR5 was significantly increased in these patients (p less than 0.005) compared with that in controls. All patients had impaired cell-mediated immunity. Opportunistic infections, lymphomas, or Kaposi's sarcoma subsequently developed in 15 patients who had had severe immune dysfunction for the previous 3 to 13 months. We suggest that generalized lymphadenopathy is part of the spectrum of a disorder manifested by acquired immunodeficiency, opportunistic infections, Kaposi's sarcoma, and malignant lymphomas.

Pheasant virus: new class of ribodeoxyvirus.

Cocultivation of cells derived from embryos of golden pheasants or Amherst pheasants with chicken embryo cells infected with Bryan strain of Rous sarcoma virus resulted in the detection of viruses which appear to be endogenous in these pheasant cells. The pheasant viruses (PV) were similar to avian leukosis-sarcoma viruses (ALSV) in their gross morphology, in the size of their RNA, in the presence of a virion-associated RNA-dependent DNA polymerase (DNA nucleotidyltransferase; deoxynucleoside triphosphate: DNA deoxynucleotidyltransferase; EC 2.7.7.7), and in their growth characteristics. PV also serves as a helper for the glycoprotein-defective Rous sarcoma virus. However, PV was shown to be different from both ALSV and reticuloendotheliosis virus in the following properties: (i) PV does not have ALSV group specific antigens; (ii) the protein composition of PV is different from those of the other two groups of viruses; (iii) PV fails to complement the defective polymerase of alpha type Rous sarcoma virus; and (iv) PV RNA shows no detectable homology with nucleic acids of the other two groups of viruses. Thus, PV appears to be a new class of RNA viruses which contain RNA-dependent DNA polymerase.

Non-Hodgkin's lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome.

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.