Bijan Safai

Preliminary Observations on the Effect of Recombinant Leukocyte a Interferon in Homosexual Men with Kaposi's Sarcoma

Preliminary clinical trials have shown that both natural and recombinant-DNA-produced human interferons are occasionally capable of inhibiting the growth of some tumors.1 2 3 4 Although the tumors ...

National Case-Control Study of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia in Homosexual Men: Part 1, Epidemiologic Results

To identify risk factors for the occurrence of Kaposis sarcoma and Pneumocystis carinii pneumonia in homosexual men, we conducted a case-control study in New York City, San Francisco, Los Angeles, and Atlanta. Fifty patients (cases) (39 with Kaposis sarcoma, 8 with pneumocystis pneumonia, and 3 with both) and 120 matched homosexual male controls (from sexually transmitted disease clinics and private medical practices) participated in the study. The variable most strongly associated with illness was a larger number of male sex partners per year (median, 61 for patients; 27 and 25 for clinic and private practice controls, respectively). Compared with controls, cases were also more likely to have been exposed to feces during sex, have had syphilis and non-B hepatitis, have been treated for enteric parasites, and have used various illicit substances. Certain aspects of a lifestyle shared by a subgroup of the male homosexual population are associated with an increased risk of Kaposis sarcoma and pneumocystis pneumonia.

The Natural History of Kaposi's Sarcoma in the Acquired Immunodeficiency Syndrome

Kaposis sarcoma is a multifocal systemic neoplasm histologically characterized by proliferating fibroblastic and microvascular elements. Initial signs include macules, papules, or nodules on the skin or mucosal surface. Lesions are frequently found on the trunk, arms, and head and neck. In general, sites of involvement and tumor load do not correlate with prognosis. A general decrease in the functional capacities of T and B cells is found in most patients. Kaposis sarcoma is reported as the initial manifestation of the acquired immunodeficiency syndrome (AIDS) in approximately 30% of cases. Most cases are in men, although it has been reported in all risk groups. Kaposis sarcoma in AIDS is more frequent among whites and homosexuals than blacks and intravenous drug abusers. Overall mortality is approximately 41%, with over 60% of patients alive at 1 year and 50% at 22 months. Overall survival is 18 months; however, some patients who have had the disease for 3 to 4 years are still doing well.

SEROEPIDEMIOLOGICAL STUDIES OF HUMAN T-LYMPHOTROPIC RETROVIRUS TYPE III IN ACQUIRED IMMUNODEFICIENCY SYNDROME

In a double-blind study, sera of 34 patients with acquired immunodeficiency syndrome (AIDS), 19 patients with lymphadenopathy syndrome, and 14 homosexual men with an increased risk of AIDS were screened for antibodies to proteins of the novel human T-lymphotropic retrovirus (leukaemia virus), HTLV-III, recently isolated from cultured T cells of AIDS patients. On a combination of a convenient and rapid enzyme-linked immunosorbent assay and a more sensitive electroblot (Western) assay, 100% of the AIDS sera were scored positive. Similarly, 84% of the lymphadenopathy patients were found to have serum antibodies to HTLV-III. A lower, but significant, proportion (21%) of healthy homosexual men with an increased risk of AIDS were also positive. No heterosexual controls, including those with heterophile antibodies during the course of infectious mononucleosis and patients with T-cell or B-cell lymphoma, had antibodies to HTLV-III. The results strongly indicate that the antibodies to HTLV-III are diagnostic of AIDS or indicate significant risk of the disease, and suggest that HTLV-III is the primary cause of human AIDS.

Association of Kaposi's sarcoma with second primary malignancies possible etiopathogenic implications

The association of Kaposis sarcoma (KS) with second primary cancers, especially of the lymphoreticular system, has been frequently noted. To confirm these reports in a systematic way, data on a series of 92 patients with KS treated at Memorial Sloan‐Kettering Cancer Center (MSKCC) 1949–1975 were subjected to extensive statistical analysis. Use was made also of 4517 double primaries including all sites, diagnosed at MSKCC 1949–1974, and 1959 simultaneous double primaries from the Third National Cancer Survey. Some key results: (1) 37% of KS patients had toher primary malignancies; (2) there was a 20‐fold increase in the incidence of lymphoreticular malignancies after diagnosis of KS; (3) in the MSKCC series of double primaries, lymphoreticular malignancies were involved in 8% of cases; for KS alone the corresponding figure was 58%. Our findings provide evidence in support of possible etiopathogenic mechanisms that may be involved in the natural course of KS.

Defective T-cell response to PHA and mitogenic monoclonal antibodies in male homosexuals with acquired immunodeficiency syndrome and its in vitro correction by interleukin 2.

We studied the ability of phytohemagglutinin (PHA) and two anti-T-cell monoclonal antibodies OKT3 and Pan T2, to induce proliferation and interleukin 2 (IL2) production in peripheral blood lymphocytes (PBL) from 21 homosexual patients: 12 with Kaposis sarcoma (KS), 4 with reactive lymphadenopathy, and 5 with opportunistic infections. All patients with KS and opportunistic infections had significantly lower mitogen-stimulated DNA synthesis, as compared to the controls, irrespective of the mitogen used (P<0.01). The patients with lymphadenopathy exhibited significantly lower responses only in the OKT3 assay as compared to normals (P=0.009). The production of endogenous IL2 was significantly lower in PBL cultures from patients with KS and with opportunistic infections, irrespective of the mitogen used, as compared to healthy male controls, and also significantly lower in the Pan T2-stimulated cultures from patients with lymphadenopathy. The addition of highly purified IL2 was able to restore partially lymphocyte proliferationin vitro in the presence of these mitogens in all patients. Our studies demonstrate (1) that male homosexuals even without clinical manifestations of immunodeficiency frequently exhibit a proliferative T-cell defect when anti-T-cell monoclonal antibodies rather than PHA are used as mitogens, (2) that this proliferative defect is associated with defective IL2 production, and (3) that this defect is at least in part correctablein vitro by highly purified IL2.

Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin

In 15 months we encountered eight patients with intracranial tumors who developed erythema multiforme (EM) or erythema multiforme bullosa (Stevens-Johnson syndrome). All occurred shortly after use of phenytoin (DPH) and brain radiation therapy (WBRT). The clinical picture differed from the classic form of EM in that the erythema began on the scalp and spread to the extremities, progressing in three cases to extensive bullous formation. There were no cases of EM among patients who received either DPH or radiotherapy alone. The combination of DPH, WBRT, and tapering of steroids seems to predispose to EM. The pathogenesis of the disorder is probably immunologic. In the absence of seizures, anticonvulsants should not be given routinely to patients with brain tumors. When anticonvulsants are necessary in patients scheduled for WBRT, DPH may not be the drug of choice.

Kaposi's sarcoma: Retrospective study of 90 cases with particular emphasis on the familial occurrence, ethnic background and prevalence of other diseases

Identification of familial cases of Kaposis sarcoma may help elucidate the role of genetic factors in this disease. To assess the prevalence of familial occurrences, the ethnic distribution of Kaposis sarcoma and the prevalence of other diseases in our patient population, we have reviewed all cases of Kaposis sarcoma seen at Memorial Sloan-Kettering Cancer Center between 1954 and 1975. Each patient was categorized on the basis of sex, age of onset of Kaposis sarcoma, ethnic background, nativity, family history of Kaposis sarcoma and prevalence of other diseases. Only one documented occurrence of familial Kaposis sarcoma was found out of 90 cases reviewed. The frequency of familial Kaposis sarcoma in our patient population supports the findings of other investigators. An ethnic predominance of Kaposis sarcoma was substantiated, with most patients being immigrants from high-incidence areas (54 of 77) and predominantly of Jewish and italian heritage (52 Jewish and 17 Italian of 87).

Importance of complete cutaneous examination for the detection of malignant melanoma.

With the rate of melanoma increasing 1,000% in the past 50 years, the early detection of the disease is becoming more important. Data from 2,239 persons seen at the Manhattan Melanoma/Skin Cancer Detection Screening Program were analyzed to determine if a complete cutaneous examination would significantly increase the chance of detecting melanoma. Thirteen of the fourteen melanomas detected were on anatomic sites normally covered by clothing. Patients having complete skin examinations were 6.4 times more likely to have a melanoma detected than those having partial examinations (p = 0.025). These findings reinforce the importance of complete skin examination for the early detection of malignant melanoma.

Outbreak of Kaposi's sarcoma with cytomegalovirus infection in young homosexual men

Kaposis sarcoma, a multicentric malignant neoplasm, occurs in certain geographic areas in the world. It is most common in Equatorial Africa and Eastern Europe. The annual incidence of Kaposis sarcoma in the United States is between 0.021 and 0.061 per 100,000 persons. The appearance of an outbreak of Kaposis sarcoma in young homosexual men in New York and California is a new and unique phenomenon. Certain differences are already recognized between the disease in these young men and the ordinary Kaposis sarcoma. Herein we report our observations of the first 10 cases of Kaposis sarcoma in young homosexual men. In these patients, the disease follows an aggressive clinical course characterized by widespread skin lesions with early involvement of the lymph nodes. In some of these patients, the result was death in a short period of time after initial diagnosis. In addition, cytomegalovirus infections were seen in these patients, which suggests at least a possible association between this viral and the disease.