Kaposi's sarcoma with a non-Hodgkin's lymphoma. Its association in a male homosexual with human T-cell lymphotropic virus type III infection.

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.

Studies in homosexual patients with and without lymphadenopathy. Relationships to the acquired immune deficiency syndrome.

We studied the immunologic function of 19 sexually active homosexual men, ten of whom had persistent lymphadenopathy. Analysis of mononuclear cell populations distinguished homosexuals from heterosexual controls since, as a group, homosexuals had increased percentages of natural killer cells (Leu 7+), decreased helper-inducer T lymphocytes (OKT-4+), increased suppressor/cytotoxic (OKT-8+) T lymphocytes, low OKT-4:OKT-8 ratios, and depressed mitogenic responses. Homosexuals without lymphadenopathy were distinguishable from controls by increased percentages of Ia+ cells, decreased OKT-4+ cells, and decreased OKT-4:OKT-8 ratios. Four had positive findings simultaneously for hepatitis B surface antigen (HBsAg) and surface antibody, and five had positive findings for HBsAg alone. Homosexuals with lymphadenopathy were distinguishable from controls by increased percentages of Leu 7+ cells, increased total lymphocyte numbers per cubic millimeter, decreased percentages of both OKT-4+ and OKT-8+ cells, abnormal OKT-4:OKT-8 ratios, and depressed mitogenic responses. Only histories of larger numbers of sexually acquired diseases, higher numbers of OKT-8+ cells per cubic millimeter, and lower mitogenic responses in homosexuals with lymphadenopathy distinguished this group from homosexuals without lymphadenopathy. Furthermore, none of the nine patients tested in this group was HBsAg positive. We conclude that homosexuals without lymphadenopathy are distinguishable from those with lymphadenopathy by both immunologic and serologic abnormalities.

Evaluation of patients with local reactions to insulin with skin tests and in vitro techniques.

To better understand the part played by IgE and IgG antibody in the production of dermal reactions to insulin and the usefulness of skin tests in the evaluation of these reactions, we studied 21 diabetic patients referred for evaluation of large local insulin reactions, 46 diabetic patients without local insulin reactions, and 22 healthy nondiabetic controls. Study subjects were skin tested with 15 different insulins, and the results were evaluated over 48 h. All control subjects and 41 of 46 diabetic patients without local reactions were skin-test negative to insulin. The 11% of diabetic patients who reacted had positive wheal-and-flare reactions at 20 min to animal-species insulin but negative skin tests to human insulin. Study revealed two subgroups of patients with histories of local reactions. Ten (48%) of these patients had negative skin tests to insulin. Five of this subgroup remained skin-test negative to quantities of less than or equal to 8 U insulin/skin test. Eleven (52%) of the patients formed a subgroup with positive insulin skin tests; most of these patients were skin-test positive to human insulin and to beef, pork, or both insulins as well. Although the group mean insulin-specific IgE values of this latter subgroup were significantly higher than those of any other study group, overlap of these individual IgE values did not allow separation of specific individuals with positive skin tests from those of patients on insulin without dermal reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Human immunodeficiency virus infection in hemophiliac patients. A three-year prospective evaluation.

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.

Immunologic assessment of a cluster of asymptomatic HTLV-I-infected individuals in New Orleans.

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.

Lidocaine effects on immunocompetent cells. Implications for studies of cells obtained by bronchoalveolar lavage.

Immunologic data obtained from bronchoalveolar lavage (BAL) is useful for both clinical and investigative purposes. Although lidocaine, used for local anesthesia, is present in BAL in up to 12 mmol concentration, its effects on immunologic tests are unclear. The results of our study show that lidocaine has profound effects on the results of functional studies of immuno-competent cells. Care should be taken to quantify, standardize, and limit the exposure of alveolar cells to lidocaine during bronchoscopy if such studies are to be performed. However, exposure of cells for 25 minutes or less to lidocaine solutions up to 12mmol in concentration does not affect a variety of immunologic tests of interest. At the same time, carefully controlled use of lidocaine in lavage solutions significantly increases the number of cells obtained for study.

Cytotoxic cell function in bronchogenic carcinoma.

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.

Diminished natural killer-cell activity of interstitial pulmonary cell populations from patients with carcinoma of the lung.

Natural killer-cell activity of fresh interstitial pulmonary cell populations from patients with squamous cell and adenocarcinoma of the lung and carcinoma metastatic to the lung was assessed and compared to that of apparently normal lung. No increase in the percentage of lymphoid cell populations was noted in the interstitium of lung contiguous with tumor, and the cytotoxic capacity of the cells present was depressed as compared to that of normal lung. Natural killer-cell function appears to be down regulated in lung cancer and may be amenable to therapies which activate such cytotoxicity in vivo.

Natural killer cell activity in asbestos workers. Interactive effects of smoking and asbestos exposure.

Both the numbers and function of natural killer (NK) cells in 60 were evaluated in asbestos cement workers grouped by smoking history and chest roentgenogram findings (ILO profusion scores less than 1/0 or greater than or equal to 1/0, or isolated pleural plaques). Worker and control subjects who smoked had smoking histories of less than 27 pack-years, a level of smoking lower than that previously determined to adversely affect NK function. Asbestos workers who did not smoke had percentages and total numbers of NK cells and NK function not different from that of nonsmoker control subjects. Workers who smoked and had evidence of asbestosis (ILO profusion category greater than or equal to 1/0) had significantly lower total numbers of NK cells and mononuclear cell NK activity than did smoker control subjects or smokers with pleural plaques only (p less than or equal to 0.05). Numbers of NK cells and NK cell function were not decreased in either of the asbestos-exposed smoking groups without asbestosis when compared to nonsmoker controls. We conclude that smoking and asbestos exposure interact to decrease mononuclear cell NK function in workers with levels of asbestos exposure sufficient to induce asbestosis. This finding may explain in part the previously reported synergistic effect of smoking and asbestos exposure on the risk of lung cancer. Furthermore, the data presented here clarify previous conflicting reports on NK function where asbestos exposed groups have not been stratified for analysis of data.

Pulmonary immunologic features of alveolar septal amyloidosis associated with multiple myeloma.

A 74-year-old man presented with interstitial pulmonary disease which was proven to be alveolar septal amyloidosis by transbronchial biopsy. Multiple myeloma was diagnosed on the basis of monoclonal IgG-lambda protein in serum, monoclonal lambda light chains in urine, a bone marrow plasmacytosis of 22 percent, and serum IgA and IgM levels less than 100 mg/dl and 50 mg/dl, respectively. Appropriate investigations failed to show additional sites of deposition of amyloid. Analysis of fluid from bronchoalveolar lavage showed an increase in total cells recovered, a lymphocytosis with a ratio of T helper over T suppressor cells greater than that in peripheral blood, the presence of an IgG-lambda paraprotein, and an IgG/albumin ratio greater than that in serum. While plasma cells could not be identified in the recovered cell population, cultured cells from bronchoalveolar lavage fluid showed increased production of IgG. These findings provide evidence of an ongoing pulmonary immune response resulting in excess IgG-lambda protein in the pulmonary compartment, a factor which may contribute to the development of amyloidosis.

A new classification and diagnostic criteria for invasive fungal sinusitis.

OBJECTIVE: To develop criteria for the diagnosis of invasive fungal sinusitis. DESIGN: Review of the literature on invasive fungal sinusitis in the context of a population of 30 patients with fungal sinusitis and 24 patients with chronic bacterial sinusitis. SETTING: Tertiary care medical center. RESULTS: Our review revealed no consensus in the literature on the classification of the syndromes of invasive fungal sinusitis and no criteria for their diagnosis. Moreover, the existing syndromes of invasive fungal sinusitis lacked specificity and one of the more commonly cited syndromes, primary aspergillosis of the paranasal sinuses, is a granulomatous disease that occurs rarely outside Africa. Two of our 30 patients with fungal sinusitis had a previously unrecognized form of invasive disease. Both were middle-aged adults with well-controlled type 2 diabetes mellitus, apical orbital syndrome, and a similar course: proptosis resulting from fungal expansion out of an ethmoid sinus, a protracted illness of 6 months or longer, visual changes, late neurological symptoms reflecting cavernous sinus invasion, and death. The syndrome in these 2 patients is distinct from the syndrome of fulminant invasive fungal sinusitis, (eg, mucormycosis) with nasal eschar, intracerebral fungal dissemination by vascular invasion, and death in days, and the granulomatous form. CONCLUSIONS: We conclude that there are 3 forms of invasive fungal sinusitis and propose that they be termed (1) granulomatous, (2) acute fulminant, and (3) chronic invasive. The latter category reflects the syndrome seen in our 2 patients. Furthermore, the following 2 diagnostic criteria for invasive fungal sinusitis are proposed: (1) sinusitis confirmed by radiological imaging and (2) histopathological evidence of hyphal forms within sinus mucosa, submucosa, blood vessels, or bone. The specificity of hyphae within sinus mucosa for tissue invasion was supported by the absence of stainable hyphae in the mucosa of patients with chronic bacterial sinusitis or in the mucosa of our described patients with allergic fungal sinusitis and mycetoma.

Fungal sinusitis.

Until several years ago, no criteria for diagnosis or consensus on the classification of fungal sinusitis existed. Many reports were grouped under the heading of "aspergillus sinusitis," regardless of invasiveness; thus, published information on the diagnosis, natural history, and treatment of fungal sinusitis was of limited value. Diagnostic criteria and clinical descriptions for allergic fungal sinusitis, sinus mycetoma, and invasive fungal sinusitis have now been published. These criteria, a new classification system, and the clinical approach to patients with fungal sinusitis are reviewed in this article. Although fungal sinusitis is not a rare disease, much remains to be learned about its optimal clinical management.

Chronic fatigue syndrome: a conundrum.

Chronic fatigue syndrome (CFS) is a multi-faceted disorder for which no etiology has been determined. This paper discusses the implications of the new clinical case definition of CFS on previous and future studies of this illness. The authors' own management approach is also discussed.

Immunomodulation by bronchial lavage cells in normal individuals and patients with bronchogenic carcinoma.

The ability of bronchoalveolar lavage cells to facilitate lymphoproliferation to mitogen in a system which allows assessment of pulmonary alveolar macrophage accessory cell function was investigated. Bronchoalveolar lavage cells were obtained from healthy non-smokers and smokers and from patients undergoing diagnostic bronchoscopy. Lavaged cells were cultured with monocyte-depleted homologous blood lymphocytes obtained from healthy, young volunteers and stimulated with suboptimal (2 micrograms/ml) or optimal (20 micrograms/ml) concentrations of phytohemagglutinin. Mitogen responses of lymphocytes in all groups were related to the number of lavage cells added, increasing with 1:100 and 1:10 bronchoalveolar lavage cell to lymphocyte ratios and decreasing with 1:2 and 1:1 ratios. Lymphoproliferative responses observed in smoker and nonsmoker cultures were not different. In contrast, maximal proliferative responses of cell cultures from patients with epidermoid and small cell carcinoma were decreased compared with cultures from patients with adenocarcinoma or controls. These data show that pulmonary bronchial lavage cells from smokers and nonsmokers provide similar dose related augmentation and suppression of lymphocyte mitogenic responses. Furthermore, accessory cell function of lavage cell populations is normal in patients with adenocarcinoma, but depressed in patients with epidermoid or small cell carcinoma.

Reliability of cell counts and protein determinations in serial bronchoalveolar lavage procedures performed on healthy volunteers.

We measured the variability in volume, total cells, cell types, and proteins in the bronchoalveolar lavage fluid recovered from 10 volunteers (five smokers, five non-smokers) lavaged repeatedly over a three-year period. Thirty lavages were performed using a rigorously standardized approach. Differential counts on the cytospin preparations were performed by three independent readers and interobserver variability in the interpretation of these counts measured. Variability in interpreting the cellular counts was less in smokers than non-smokers and decreased as the number of cells of any particular type increased. Only one reader interpreting the mean percentage of cells recovered of one cell type (neutrophils) in only one smoking group, the nonsmokers, was significantly different from the other two. There was also considerable variability in bronchoalveolar lavage fluid total protein, albumin, IgG, and IgA. Expressing albumin and IgG as a percentage of total protein recovered and expressing IgA and albumin as a ratio in nonsmokers lessened the variability of these parameters. Mean and standard deviations of the cellular and protein concentrations showed that large differences in these parameters would be necessary in order to attribute these changes to changes in the underlying pulmonary status. Excessive variability in nearly all parameters in this group without recognized lung disease challenges the usefulness of this test in the clinical assessment of patients serially followed because of underlying lung disease.

Drug allergy.

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.

Insulin allergy and insulin resistance: two immunologic reactions.

Insulin allergy and insulin resistance can cause life-threatening problems for diabetic patients. Fortunately, allergic manifestations are usually localized, but increasingly severe local reactions can precede a systemic reaction. How use of newer and purer insulin preparations than those previously available will affect the incidence of immunologic reactions is yet to be determined.

The spectrum of systemic vasculitis: a classification to aid diagnosis.

Determining the cause of systemic vasculitis can be facilitated by a clinicopathologic classification of the syndrome. The considerations in differential diagnosis include periarteritis nodosa, leukocytoclastic angiitis (hypersensitivity angiitis, Schonlein-Henoch purpura, other disease-associated vasculitis), Wegener's granulomatosis, allergic granulomatosis (granulomatous angiitis), and giant cell arteritis.

Peripartum complications. Hemorrhage, embolism, hypertension, and infection.

Maternal peripartum complications continue to be a significant problem in the United States, even among previously healthy women. The problems include peripartum bleeding, infection, hypertension, and thromboembolic disease. Primary care physicians are often called upon to treat these conditions. An awareness of the approach to diagnosis and management helps to ensure optimal outcome.

Sinusitis. Its association with asthma.

Sinusitis may present as an indolent infection, without the classic symptoms and signs commonly expected, and will probably be missed in children who have only cough and persistent rhinorrhea unless this diagnosis is kept in mind. Plain radiography is the most commonly used diagnostic procedure for sinusitis, but computed tomography may be more sensitive. The contribution of sinusitis to the induction and exacerbation of asthma is still unresolved. The existence of a nasobronchial reflex is not clearly supported by available data, although it is a likely explanation for the observed relationship between the two processes. However, sinusitis appears to be an important underlying trigger for some cases of asthma and, therefore, should be suspected any time that acute or chronic asthma is difficult to control.