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Recently, hemophiliac patients receiving factor VIII concentrate therapy have developed the acquired immunodeficiency syndrome. Because abnormalities of cell-mediated immunity are found in this syndrome, we evaluated the peripheral blood immunologic status of 24 patients with classic hemophilia and 5 patients with factor IX deficiency. Both groups had decreased percentages and numbers of helper-inducer lymphocytes (OKT4+) and increased percentages of suppressor-cytotoxic T-lymphocytes (OKT8+) which resulted in depressed OKT4/T8 ratios. Abnormalities of the T-lymphocyte subpopulation were most severe in 7 patients with factor VIII deficiency with lymphadenopathy who also had increased Ia+ cells and profoundly suppressed lymphocyte mitogenic responses. No correlation was found between OKT4/OKT8 ratios or lymphocyte responses to mitogen and the amount of factor VIII concentrate used per year. Evaluation of five wives of factor-VIII-deficient patients who had abnormal OKT4/OKT8 ratios showed decreased percentages of OKT4 cells, but normal lymphocyte mitogenic responses. Serum levels of IgG were elevated in factor-VIII-deficient patients but not their wives or factor-IX-deficient patients. We conclude that T-lymphocyte subpopulation abnormalities and lymphocyte mitogenic responses are depressed in asymptomatic hemophiliac patients receiving either factor VIII or factor IX concentrates. These abnormalities are most severe in otherwise asymptomatic hemophiliac patients who have developed lymphadenopathy.

Thirty-seven heterosexual hemophiliac patients underwent prospective evaluation with clinical examinations, serologic studies for antibody to human immunodeficiency virus (HIV), and tests of immune function for an average of 37 months. At the time of entry into the study in 1982 to 1983, 18 subjects (49 percent) were already seropositive for HIV and 11 (30 percent) had persistent generalized lymphadenopathy. Seventy percent of the total population were clinically asymptomatic. In nine subjects, seroconversion occurred during the study such that 81 percent of the population was seropositive at the conclusion. During the same period, lymphadenopathy developed in six subjects, there was progression to AIDS-related complex (ARC) in four, and acquired immunodeficiency syndrome (AIDS) developed in one patient. Thus, at the end of the study, 54 percent were clinically asymptomatic, 32 percent had persistent lymphadenopathy, and 11 percent had ARC. Subjects who remained seronegative had received less factor concentrate than seropositive subjects, remained asymptomatic, and had normal results on tests of immune function. In those who had experienced seroconversion, there were decreased absolute numbers of CD4+ lymphocytes prior to seroconversion, and abnormalities of lymphocyte function developed after seroconversion. The development of persistent generalized lymphadenopathy was associated temporally with seroconversion. The presence of persistent generalized lymphadenopathy did not appear to be associated with an increased risk for AIDS in seropositive persons, since the condition of most hemophiliac patients with persistent generalized lymphadenopathy at the time of initial evaluation remained clinically and immunologically stable. In contrast to patients with persistent generalized lymphadenopathy, asymptomatic seropositive subjects had progressive abnormalities of lymphocyte function over time that were independent of the numbers of CD4+ cells in the peripheral blood.

Combined tumor syndromes, specifically reticuloendothelial malignancies and Kaposi's sarcoma, have long been recognized. With the recognition of the acquired immunodeficiency syndrome (AIDS), several patients with concurrent non-Hodgkin's lymphoma and Kaposi's sarcoma have been reported at high risk for developing AIDS. The present Centers for Disease Control definition of AIDS excludes these patients on the assumption that one tumor is affecting the cellular immunity, allowing for the development of the second malignancy. In evaluating such a patient who had serologic evidence of human T-cell lymphotropic virus type III infection, the probable cause of AIDS, we have reviewed reports of patients with similar concurrent malignancies before and since the onset of the AIDS epidemic. We conclude that patients in high-risk groups for AIDS who develop similar combined tumor syndromes should be classified as having AIDS.

To explore the mechanisms of asbestos-related perturbations of the immune system, we evaluated the in vitro cell-mediated immunity of five asymptomatic asbestos workers with hypergammaglobulinemia and decreased T-cell numbers. These results were compared with those in 10 matched controls. Analysis of T-lymphocyte populations revealed decreased absolute numbers of OKT4+ (helper/inducer) T cells in the peripheral blood and phytohemagglutinin (PHA)-stimulated mononuclear cell cultures of the workers. When chrysotile asbestos was added to PHA cultures, expansion of OKT4+ cell populations was disproportionately inhibited in workers' cultures. Furthermore, control proliferative responses to PHA became indistinguishable from initial worker responses. These effects were incompletely explained by the cytotoxic effects of asbestos on cultured lymphocytes. We conclude that both in vivo and in vitro exposure of mononuclear cell populations to asbestos may lead to a diminution of helper-inducer T-cell numbers. In asbestos-exposed individuals, this latter lymphocyte subpopulation appears to be especially sensitive to in vitro asbestos exposure. Although the clinical implications of these findings are unclear, we hypothesize that many of the immunologic abnormalities that occur in asbestos workers could be explained by direct asbestos effects on the OKT4+ immunoregulatory population.

In this study we sought to characterize the tissue leukocytes in murine lung which (when derived from peripheral lymphoid organs) have been associated with host defense against tumors and certain microbial agents. Numerical and functional properties of lung lymphoid populations obtained by collagenase digestion were evaluated in inbred mice. Flow cytometric analysis of monoclonal and polyclonal antibody labelled preparations revealed that lung cells so derived were 47% T-lymphocytes (helper-suppressor ratio 4.25), 23% B-cells (surface immunoglobulin+) and 26% asialo GM1 (natural killer) cells. Lung T-cells responded well to mitogen stimulation after partial depletion of adherent macrophages, but the magnitude of this response was less than that of autologous spleen cells. Natural killer cell (NK) activity against chromium labelled tumor target cells was also manifested by lung cells and was similar to that of peripheral spleen cells. This lung NK activity could be boosted in vitro by incubation with interferon and in vivo by treatment with poly I:C. Together, these data indicate that normal murine lung contains a large number of functional T-cell and NK cell mononuclear populations. The characterization of the cell populations presented here should facilitate future studies of their role(s) in host defense against infection and neoplasia.

We evaluated the ability of mononuclear cell populations from 56 hemophiliac subjects, 69 homosexuals, and 32 control subjects to proliferate spontaneously in vitro. Levels of spontaneous proliferation (SP) were not significantly different among homosexuals or hemophiliac subjects when they were grouped as asymptomatic human immunodeficiency virus (HIV) seronegative, asymptomatic seropositive, persistent generalized lymphadenopathy, acquired immunodeficiency syndrome-related complex, or acquired immunodeficiency syndrome groups. There was, however, a stepwise increase in levels of SP corresponding with progression of disease in both patient groups. No correlations were noted between SP and CD8+ cell populations or mitogenic responses in study subjects, but SP correlated inversely to percentages and numbers of CD4+ lymphocytes. Depletion of CD4+ cells from mononuclear cell populations of HIV-infected subjects decreased SP. Thus, in HIV-1-infected subjects, SP increases as HIV-1-related disease progresses and appears to be CD4 dependent.

With the increasing number of drugs, the list of agents which are capable of inducing pulmonary reactions continues to lengthen. This article is a compendium of presently available information on drug induced pulmonary reactions which we have found clinically useful. We have divided the drugs in groups on the basis of two features, pharmacologic actions and type of pulmonary reactions. A total of 109 drugs are cited. Categories of pharmacologic actions include cytotoxic drugs, analgesic and antirheumatic drugs, antimicrobial agents, vasoactive drugs, tranquilizers, anticonvulsants, antidepressants, antiarrhythmics, oral antidiabetics and a group of miscellaneous drugs. Type of pulmonary reactions include pulmonary eosinophilia, bronchoconstriction, acute interstitial pulmonary disease, mediastinic involvement, pleural effusion, pulmonary hypertension, pulmonary calcifications, pulmonary infections and drugs reported to cause drug-induced Systemic Lupus Erythematosus.

Hemophiliac patients receiving factor VIII replacement therapy and homosexual subjects are at risk for the acquired immune deficiency syndrome. Immunologic abnormalities, especially depletion of helper T cell populations, have been noted in members of these groups and may parallel their clinical state. We have evaluated the peripheral blood immunologic status of a group of hemophiliac and homosexual subjects with and without persistent generalized lymphadenopathy (PGL). Although individuals with PGL had more abnormal T-lymphocyte parameters, including lower helper/suppressor ratios, than group members without lymphadenopathy, there were no significant differences noted within each respective risk group. However, differences between hemophiliac and homosexual patient groups were noted. T-lymphocyte subpopulations of hemophiliac patients with lymphadenopathy were significantly more abnormal than the corresponding homosexual groups. All groups had decreased lymphocyte proliferative responses to mitogen. Homosexual subjects with lymphadenopathy exhibited the most profoundly depressed lymphocyte mitogenic responses. We conclude that, although abnormalities of T-lymphocyte subpopulation and lymphocyte mitogenic responses exist within each risk group, homosexual subjects (both asymptomatic and with PGL) had lower mitogenic responses than would be expected for their T-lymphocyte helper/suppressor ratios as compared to either control subjects or hemophiliac patients. These findings suggest that additional factors are operative in the mononuclear cell populations of homosexual subjects that depress lymphocyte function. An analysis of these factors may help explain the higher incidence of AIDS in homosexual subjects as compared to hemophiliac patients.

We investigated the ability of smoker and nonsmoker pulmonary alveolar macrophages (AM) to facilitate lymphocyte proliferative responses in a novel system allowing separation of lymphocyte and AM effects. Bronchoalveolar lavage cells (BLC) were obtained from 7 nonsmokers and 5 older smokers and cultured with purified peripheral blood lymphocytes (PL) and the mitogen phytohemagglutinin. Increasing amounts of BLC were added such that BLC/PL ratios were 1:100, 1:10, 1:2, 1:1 of either autologous or homologous PL. Lymphocyte proliferation was dose-related, increasing with 1:100 and 1:10 BLC/PL ratios, and decreasing to or below initial responses with 1:2 or 1:1 ratios. Depletion of T-lymphocytes from BLC demonstrated that these effects were mediated by AM. Phytohemagglutinin (PHA) dose-response curves of nonsmokers obtained using autologous or homologous PL were not different. When BLC from smokers were cultured with autologous PL, lymphocyte proliferative responses were less than those of similar cultures from nonsmokers. However, when similar smoker BLC were cultured with homologous PL from nonsmokers, proliferative responses were not different from those of nonsmokers. Peak proliferative responses of peripheral blood mononuclear cells were not different from maximal proliferative responses of PL-BLC cultures at any PHA dose. These data show that human AM provide dose-related help and suppression of mitogen-induced lymphocyte proliferation similar to that reported with peripheral blood macrophages. Smoker AM facilitated mitogen-driven proliferation of homologous PL in a normal fashion, demonstrating the utility of this culture system in distinguishing lymphocyte effects present in autologous cultures.

Fifteen diabetics with recurrent painful local reactions to insulin were studied. Reactions occurring after intradermal insulin injection were observed in nine patients over 48 hr and biopsies were taken at intervals for microscopic study using the 1 mu Giemsa technique. Insulin-specific IgE and IgG levels were measured on all patients. Five patients had biphasic reactions in which wheal and flare (WFR) were followed by an indurated lesion 4 to 6 hr later. These reactions lasted up to 24 hr and were histopathologically identical to similar "late-phase reactions" seen with ragweed. They were transferable with Prausnitz-Küstner (P-K) testing. Three patients had reactions that developed 8 to 12 hr after injection, peaked around 24 hr, and were not preceded by WFR. These reactions were morphologically delayed hypersensitivity reactions and were not transferred by P-K testing. One patient had a reaction that developed in 4 to 6 hr after injection and peaked by 12 hr. Histologically, this reaction was "Arthus" in type and was not transferred by P-K testing. Specific insulin antibody determinations were not helpful in distinguishing patients with different types of reactivity. These data show that recurrent local reactions to insulin may be of three distinct types: "late-phase reactions" (which are IgE dependent), "Arthus" local vasculitic reactions, or tuberculin-type delayed hypersensitivity reactions. These findings may influence the approach to management of these reactions.

Biologic response modifiers (BRM) such as interleukin-2 (Il-2) and gamma-interferon (gamma IFN) can augment preexisting or initiate new cytotoxic capacity of human lymphocytes against tumor cells. Although in vivo therapy with BRM or adoptive immunotherapy with BRM-treated cells seems logical in the treatment of bronchogenic carcinoma, recent studies have shown that lymphocytes from the lung and tumor tissues of patients with bronchogenic carcinoma have defective cytotoxic function. We sought to determine if defects in lung cytotoxic cell function are primary or secondary to local tumor effects, and if peripheral blood lymphocyte populations from patients can serve as a source for BRM-stimulated cytotoxic cells. We evaluated the natural killer (NK) cell and lymphokine (Il-2) activated killer cell activity (LAK) activity of mononuclear cell populations from 11 patients with newly diagnosed bronchogenic carcinoma and three control groups. Cultured human squamous cell and adenocarcinoma cell lines proved useful in evaluating LAK activity in these studies. Levels of NK and LAK activity in patients compared favorably with both those of non-smokers in two different age ranges and with smokers. Peripheral blood cytotoxic cell function remains intact and responsive to augmentation by BRM in patients with recently diagnosed bronchogenic carcinoma. Reported defects in patient lung cell cytotoxic function appear to be local tumor-related defects not present in peripheral blood lymphocytes.

Purpose: Although clusters of individuals infected with the human T-cell lymphotrophic virus type I (HTLV-I) have been identified in the United States, no systematic evaluation of the immunologic status of these persons has been reported. We therefore studied a group of 11 HTLV-I-infected former intravenous drug abusers who were long-term participants in a methadone maintenance program in New Orleans, Louisiana, to determine the effects of HTLV-I and chronic opiate use on immunity., Patients and Methods: Mitogenic responses and results of serologic studies, cell phenotype analysis, and cytotoxicity assays were compared to those in two other HTLV-I seronegative groups: a similar group of 17 methadone users and 15 healthy age-, sex-, and race-matched control subjects. All study participants were seronegative for human immunodeficiency virus type 1., Results: Percentages and numbers of total T lymphocytes (CD2+,CD3+), T-suppressor/cytotoxic lymphocytes (CD8+), cytotoxic lymphocytes (Leu7+, Leu11+, NKH-1+) and B lymphocytes (B4+) were similar among the study groups. Although percentages and numbers of total T-helper lymphocytes (CD4+) were also similar among the groups, HTLV-I-infected subjects had higher percentages and proportions of helper/inducer cells (CD4:4B4+) than did HTLV-I seronegative methadone users. Both methadone using groups had decreased percentages and numbers of suppressor/inducer T lymphocytes (CD4:2H4+). Major histocompatibility complex unrestricted T-cell cytotoxicity (lectin-dependent cellular cytotoxicity), natural killer cell function, and mitogenic responses to the T-cell mitogen phytohemagglutin were similar among the three study groups. Pokeweed mitogen responses were severely depressed in the HTLV-I-infected population., Conclusions: We conclude that HTLV-I infection is associated with abnormalities in T-cell-dependent B-cell proliferative responses. Furthermore, both long-term methadone use and HTLV-I infection are associated with abnormalities in the distribution of CD4+ cell subpopulations. The increase in the helper/inducer and T-cell cell populations and decrease in the pokeweed mitogenic response noted in HTLV-I-infected subjects appear to be markers for infection with this retrovirus.

The authors studied the natural history of human immunodeficiency virus (HIV) exposure in 187 hemophiliacs followed for an average of 45 months. Overall, 55 percent developed antibody specific for HIV and 21 percent developed persistent generalized lymphadenopathy. Most patients seroconverted sometime between early 1982 and the end of 1984. Four patients developed acquired immune deficiency syndrome (AIDS) and four seropositive patients developed idiopathic thrombocytopenia (ITP). One of the four patients who developed AIDS and three of the four with ITP had preexisting lymphadenopathy. None of the 10 patients with lymphadenopathy or the 20 asymptomatic patients was seropositive for human T-lymphotropic virus, type I. Although seropositivity and lymphadenopathy have been found in many of the authors' patients, few have developed clinical disease that can be related to HIV infection.

A survey of suburban residents of New Orleans, La., revealed that 58% of the individuals who responded had been stung by imported fire ants (IFA) within the previous year. More than half of the patients stung had dermal reactions that were distinct from the previously reported reactions to IFA in that immediate wheal-and-flare reactions evolved into pruritic, edematous lesions that persisted about the developing pustule for 24 hr or more. Twenty-one volunteers were stung with live IFA, and the course of the reactions was observed. Nine developed persistent reactions after stings. These reactions could be reproduced by the intradermal injection of IFA--whole body extract in only four of these nine subjects. Biopsy specimens of sting reactions at 6 hr demonstrated the reactions to be "late phase reactions" characterized by dense fibrin deposits like those previously noted in dermal reactions to ragweed and insulin. Eosinophils were present in the sting-associated pustules only in individuals who developed late-phase reactions. These data demonstrate that late-phase reactions occur commonly to IFA stings and that this form of insect hypersensitivity may not always be diagnosed by skin testing with whole body extract.

Diagnosis of Rocky Mountain spotted fever was made as early as the fourth day of febrile illness in rhesus monkeys (Macaca mulatta), with a monocyte culture technique that is easily amenable to use in humans. Rickettsia rickettsii were identified by direct immunofluorescent and Gimenez staining of cultures of circulating monocytes from four experimentally infected monkeys, even in the presence of a mild or inapparent disease in three. Levels of rickettsemia were estimated by the plaque-assay technique, and specific antibody titers were determined by complement fixation.

RAST determinations using imported fire ant (IFA) whole-body extract (IFAWBE) and venom (IFAV) were performed with the sera of 29 sting-sensitive patients. Only 48% (14/29) of sera were positive (percent binding greater than or equal to 6%) in RAST to IFAWBE compared with 79% (23/29) positive to IFAV, and there was significantly greater binding to IFAV than to IFAWBE (p less than or equal to 0.0002). Thus, RAST with IFAV identified 31% more sting-sensitive individuals than RAST with IFAWBE, a finding similar to that noted in studies using IFAV and IFAWBE for skin testing. We conclude that IFAV is the more appropriate allergen for use in in vitro tests to detect IFA-specific IgE antibody in allergic patients.

Silicosis and asbestosis are two forms of fibrotic lung disease resulting from the inhalation of inert materials indigestible by pulmonary alveolar macrophages. Results of studies of the host response to these particulates have not always been consistent. It is clear, however, that after phagocytosis, both cause alveolar macrophage damage, with resultant release of macrophage products, including fibrogenic factors and chemotactic factors for neutrophils. The latter cells also release lysosomal enzymes and free radicals when exposed to silica and asbestos. The net effect of these observations suggests that the combination of tissue damage and fibroblast stimulation results in the pulmonary fibrosis characterizing these diseases. Patients with silicosis and asbestosis have normal or decreased cell-mediated and increased humoral immunity with a high incidence of circulating immune complexes and autoantibodies. Whether these abnormalities are related to the pathogenesis of pulmonary fibrosis or are epiphenomena remains to be determined.

Adverse reaction to drugs is a common problem in the pediatric population. This article discusses the different types of adverse drug reactions and their mechanisms. Also included are representative clinical syndromes of drug hypersensitivity reactions, as well as certain organ systems syndromes. Finally, diagnosis and management of allergic reactions to particular drugs such as penicillin, iodinated contrast dye, insulin, and others are discussed.