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Biomedical subjects

R D deShazo

Publications and source records attributed to R D deShazo.

At least 73 records · Page 4Linked to original sources

Hypersensitivity reactions to ingested crustacea: clinical evaluation and diagnostic studies in shrimp-sensitive individuals.

Adverse reactions to ingested crustacea are common and may be life-threatening. We studied 14 individuals with histories of such reactions to shrimp by immediate skin tests and RAST with extracts of shrimp, crab, crayfish, and lobster. Nine of these subjects (8/8 atopics and 1/6 nonatopics) had positive immediate skin tests (wheal greater than or equal to 2 mm) and RAST (ratios greater than 3.0) to shrimp. Their skin tests and RAST ratios to the other crustacea were also frequently positive even, in several cases, in the absence of prior exposure. In contrast, only 1/10 volunteers with no history of intolerance to crustacea had a weak positive skin test to raw shrimp. These studies suggest that both skin tests and RAST are useful in the confirmation of hypersensitivity to shrimp in atopic individuals and that cross-reactivity among crustacea may exist.

Adult↗

Persistent lymphadenopathy associated with hypertransfusion in sickle-cell disease.

We report the results of an immunologic evaluation of two hypertransfused (HT) patients with sickle-cell disease (SCD) who have developed persistent generalized lymphadenopathy. In order to interpret the results of this evaluation, we studied seven other HT patients with SCD and seven nonhypertransfused patients with SCD. Patients with SCD had decreased percentages of T-lymphocytes to include both helper and suppressor subsets in their peripheral blood. These decreases resulted in T helper/suppressor ratios not different from those of healthy normal control subjects. Lymphocyte proliferative responses to mitogen were decreased in the nonhypertransfused group, whereas mononuclear cell populations from both patient groups had higher levels of spontaneous suppressor cell activity than did control subjects. The patients with lymphadenopathy were distinguished from other HT sickle-cell anemia patients by immunologic abnormalities that included decreased percentages of T4+ lymphocytes, decreased T helper/suppressor ratios, and decreased lymphocyte responses to mitogen. Furthermore, the serum of these patients contained antibody specific for human T cell lymphotropic virus type III (HTLV-III). We believe that these two patients have developed acquired immunodeficiency syndrome-related lymphadenopathy as the result of transfusion-acquired HTLV-III. We propose that hypertransfusion treatment in SCD, possibly in association with phenytoin administration, places individuals at risk for HTLV-III-associated syndromes.

Adolescent↗

A longitudinal immunologic evaluation of hemophiliac patients.

Over an average span of one year, we performed a prospective clinical and immunologic evaluation of 30 patients with hemophilia. No patient developed life-threatening opportunistic infection or malignancy; however, the immunologic abnormalities and lymphadenopathy initially present in nine patients (lymphadenopathy group) persisted. In addition, five patients, representing 24% of the initial group without lymphadenopathy, developed generalized lymphadenopathy (converter group). One episode of idiopathic thrombocytopenia (ITP) and one episode of staphylococcal sepsis occurred in this "converter" group; one episode of ITP also occurred in the lymphadenopathy group. Sixteen patients remained asymptomatic. At the time of the follow-up evaluation, those differences in mononuclear cell (MNC) percentages and numbers noted initially among the three hemophiliac groups were no longer present. Natural killer cell function alone or in the presence of biologic response modifiers was not different among hemophiliac and control groups. Before developing lymphadenopathy, the converter group of patients had significantly better lymphocyte mitogenic function than did the other two groups of patients with hemophilia. However, lymphocyte mitogenic responses of all groups of patients with hemophilia significantly deteriorated over the course of the study. The abnormal mitogenic responses noted in these patients was explained in part by higher levels of spontaneous suppressor cell activity in mononuclear cell preparations from patients with hemophilia. We conclude that long-term immunologic studies of this patient population requires both quantitative and qualitative evaluations. Our data show that patients with hemophilia have progressive dysfunction of cell-mediated immunity.

Adolescent↗

Dermal hypersensitivity reactions to imported fire ants.

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.

Ants↗

Acquired immune deficiency syndrome (AIDS). Medical challenge of the 80's.

Although the pathophysiology of acquired immune deficiency syndrome (AIDS) is not completely understood, we know a great deal about its epidemiology, risk factors, clinical manifestations, course, and immunologic features. Clinicians caring for high-risk individuals, particularly those in endemic urban areas, should remain alert for signs and symptoms of opportunistic infections or neoplasms associated with immunosuppression. It is clear that research on AIDS has increased exponentially; both physicians and patients should be encouraged by the fact that the apparent cause of this syndrome has been identified (human T-lymphotropic retrovirus HTLV-III) and that this breakthrough should result in effective therapeutic strategies in the near future.

Acquired Immunodeficiency Syndrome↗

Studies of lymph nodes from patients with classical hemophilia.

Within the last 18 months, we have noted the development of unexplained lymph node enlargement in otherwise asymptomatic patients with hemophilia. Because such changes are poorly understood and, in some patient groups, may be related to the acquired immunodeficiency syndrome (AIDS), we studied the enlarged lymph nodes in four patients with severe factor VIII deficiency and abnormally low peripheral blood helper-inducer/suppressor cell (OKT4/OKT8) ratios. Surgically excised lymph nodes were studied for histopathologic, electron microscopic, and chromosomal changes. Cell suspensions from these and normal nodes were also studied using monoclonal antibodies. Excised lymph nodes showed follicular hyperplasia. Electron microscopy revealed no viral particles or vesicular rosettes. Chromosomal aberrations included an acrocentric marker chromosome in one patient and monosomy 21 in another. T lymphocyte ratios (OKT4/OKT8) in lymph node suspensions were lower than those in nodes from normal controls (1.2 v 6.1) and reflected the lymphocyte ratio in peripheral blood. Mature B cell percentages were increased in the lymph nodes from patients with hemophilia (38% v 27% in controls). Patients treated with factor VIII concentrates and male homosexuals have similarities in persistent lymph node enlargement, histologic features of follicular hyperplasia, and changes in lymph node and circulating lymphocyte subpopulations.

Adult↗

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.

Acquired Immunodeficiency Syndrome↗

Analysis of depressed cell-mediated immunity in asbestos workers.

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.

Asbestosis↗

Immunologic aberrations in asbestos cement workers: dissociation from asbestosis.

Immunoregulatory disorders have been implicated in the pathogenesis of asbestosis. We therefore compared the immunologic status of a well-characterized group of 31 current and former asbestos-cement workers with that of a group of 52 healthy controls, after adjustments had been made for the possible confounding effects of age, race, and smoking. The asbestos workers had significantly decreased percentages and numbers of both B and T lymphocytes in peripheral blood and a paradoxical IgG hypergammaglobulinemia. Analysis of T-lymphocyte subpopulations revealed that total T-cell numbers (OKT3+), helper-inducer T-cell numbers (OKT4+), and suppressor-cytotoxic T cell numbers (OKT8+) were decreased by similar proportions. These decreases were negatively correlated with time elapsing since the end of exposure to asbestos. In both workers and controls, lymphocyte proliferative responses to phytohemagglutinin (PHA) were correlated positively with the number of OKT4+ cells and negatively with age and serum IgG levels. When adjustments had been made for these confounding variables, no differences in PHA responses were noted between workers and controls. No relationship was detected in the workers between any of the immunologic aberrations noted and (1) radiographic category of pneumoconiosis, (2) estimates of cumulative asbestos exposure, or (3) abnormalities of pulmonary function. These data suggest that the immunologic perturbations we have noted in asbestos-exposed individuals are epiphenomena, unrelated to the pathogenesis of asbestosis itself.

Adult↗

Bronchoalveolar lavage cell--lymphocyte interactions in normal nonsmokers and smokers. Analysis with a novel system.

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.

Adult↗

An immunologic evaluation of hemophiliac patients and their wives. Relationships to the acquired immunodeficiency syndrome.

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.

Acquired Immunodeficiency Syndrome↗

Acquired immune deficiency syndrome: an update and interpretation.

It is clear that there is a distinct new clinical entity of acquired immune deficiency which manifests itself by opportunistic infections and KS. It occurs in selected groups of the population but with an ever increasing spectrum. The clinical presentation is extremely varied and the spectrum of disease runs a wide gamut. Health professionals should be aware that there is a large pool of individuals at risk for AIDS; also AIDS may manifest itself in the limited forms with mild initial signs which continue for months before serious disease becomes apparent. There is at present no specific diagnostic laboratory test to identify these patients or those at greatest risk. Present evidence indicates that once life-threatening opportunistic infections or KS have become obvious, although the disease process may wax and wane, most patients follow an inexorable downhill course. That process has not been reversed by presently applied therapies. In view of the failure of conventional and experimental therapies, the only treatment appears to be prevention of disease by avoiding risk factors. With the ever increasing number of possible risk factors identified, such avoidance becomes continually more difficult. The most pressing problem is to delineate the pathogenesis of AIDS. Until then optimal preventive and therapeutic interventions can not be instituted fully. There are a number of major unanswered questions, foremost of which is the nature of the transmittable agent. Moreover, it is not entirely clear who is susceptible to this agent. With the vast numbers at risk and growing numbers of AIDS cases, it is imperative to uncover the initial events responsible for this syndrome. From the public health point of view, it is also crucial to determine whether those individuals in the high risk groups which exhibit immunological abnormalities will, given a long enough latent period, eventually progress to AIDS/KS or whether the majority are merely a forme fruste of AIDS. Because of the major public health impact of AIDS, all physicians should be aware of and knowledgeable about this new disease process.

Acquired Immunodeficiency Syndrome↗

Dermal hypersensitivity reactions to insulin: correlations of three patterns to their histopathology.

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.

Animals↗

Evidence for histamine-mediated inhibition of monocyte chemotaxis in atopic dermatitis.

Leukocyte chemotaxis was studied in 11 patients with severe childhood onset atopic dermatitis at a time when their disease was relatively quiescent. Pyoderma had been an important complication of the dermatitis in these patients. The chemotactic responsiveness of patient neutrophils and monocytes was on the average not significantly different from that of healthy control subjects, although three patients were identified who had significantly impaired responses. No correlation between IgE levels and leukocyte chemotaxis was observed. Because excessive amounts of histamine have been recovered from the skin of patients with atopic dermatitis, we evaluated the effects of histamine on the chemotactic responsiveness of leukocytes from these patients. Histamine caused a small dose-related increase in chemotaxis of neutrophils from both patients and control subjects (10(-7)M to 10(-5)M histamine). In contrast, histamine had no effect on the chemotaxis of monocytes from control subjects but inhibited the chemotactic responsiveness of monocytes from atopic dermatitis patients. These findings suggest that an abnormal sensitivity of monocytes to histamine is an intrinsic feature of atopic dermatitis that may be detectable when the disease is quiescent. Furthermore, this abnormality may contribute to the impairment of monocyte chemotaxis that has been previously observed in patients with active atopic dermatitis.

Chemotaxis↗

Current concepts about the pathogenesis of silicosis and asbestosis.

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.

Animals↗