Mycobacterium avium-M. intracellulare and Acquired Immunodeficiency Syndrome.
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Journal Article↗
Biomedical subjects
C R Horsburgh
Publications and source records attributed to C R Horsburgh.
Response to therapy of pulmonary Mycobacterium avium-intracellulare infection correlates with results of in vitro susceptibility testing.
Seventy-five patients with pulmonary infection caused by Mycobacterium avium-intracellulare were studied to determine whether results of therapy correlated with in vitro susceptibility testing of mycobacterial isolates. Fifty patients responded to therapy and 25 were nonresponders. The total number of drugs received by responders did not differ significantly from the total number of drugs received by nonresponders. However, responders received significantly more drugs to which their isolate was susceptible in vitro than did nonresponders (2.4 +/- 1.2 versus 1.4 +/- 1.0, p less than 0.001). We conclude that patients with pulmonary M. avium-intracellulare infection should receive chemotherapeutic agents to which their isolate is susceptible in vitro.
Antitubercular Agents↗
Altered immunity in hemophilia correlates with the presence of antibody to human T-cell lymphotropic virus type III (HTLV-III).
Twenty-nine heterosexual patients with hemophilia were investigated with histories, physical examinations, laboratory evaluations of immune function, delayed hypersensitivity skin tests, and assays for antibody to human T-cell lymphotropic virus type III (HTLV-III). Sixteen patients were HTLV-III antibody positive and 13 were HTLV-III antibody negative. No patient had the acquired immune deficiency syndrome (AIDS). Patients who had antibody to HTLV-III had received significantly more units and lots of factor concentrates in the preceding 5 years than those who did not have antibody. HTLV-III antibody-positive patients had significantly fewer total T cells (Leu-1 positive) and significantly fewer helper T cells (Leu-3 positive) than HTLV-III negative patients. Antibody-positive patients also had increased amounts of IgG and decreased thymidine incorporation in response to concanavalin A in vitro. There were no differences in in vitro lymphocyte responses to phytohemagglutinin (PHA), pokeweed mitogen, Candida, tetanus, or purified protein derivative (PPD), no significant impairments of gamma interferon or interleukin-2 (IL-2) production, and no anergy. Ten patients with antibody to HTLV-III had immunologic studies repeated 1 year after the original evaluation. A significant increase was seen in suppressor (Leu-2-positive) T cells but not in total T-cell or helper T-cell numbers, helper/suppressor ratios, or T-cell functional assays. We conclude that the immune abnormalities in hemophiliacs are the result of contact with HTLV-III but that these abnormalities may remain stable over prolonged periods.
Adult↗
Pathologic findings in disseminated Mycobacterium avium-intracellulare infection. A report of 11 cases.
The pathology of disseminated Mycobacterium avium-intracellulare (MAI) was studied in 20 specimens from 11 patients. The patients ranged from 28 to 65 years and included 8 immunosuppressed and 3 immunocompetent hosts. Specimens of lymph node (five), spleen (one), liver (four), bone (three), pulmonary tissue (three), skin (three), and an aortic aneurysm were included. All cultured specimens grew MAI, but only two-thirds of these showed acid-fast bacilli (AFB) on staining. Some tissues (liver, spleen) showed granulomas similar to those seen in tuberculosis. Other tissues (skin, bone, bronchus) showed necrotizing acute and chronic inflammation with histiocytes but no definite granulomas. Lymph nodes showed a variety of nonnecrotizing and necrotizing granulomatous lesions. In skin, bone, and some lymph nodes, MAI infection appears to be histopathologically distinguishable from tuberculosis. The cases reported here are distinct from those reported in some children and patients with the acquired immunodeficiency syndrome who have massive histiocytic infiltrates with innumerable intracellular AFB. This difference may be due to a specific defect in host response involving T-cell macrophage interaction.
Adult↗
Mycobacterium avium-M. intracellulare isolates from patients with or without acquired immunodeficiency syndrome.
Susceptibility testing and serotyping were performed on 57 isolates of Mycobacterium avium-M. intracellulare from patients with acquired immunodeficiency syndrome (AIDS) and 75 isolates from patients without AIDS. Susceptibility patterns and serotypes of AIDS isolates were significantly different from those of non-AIDS isolates. These results may partially explain the poor therapeutic response of M. avium-M. intracellulare infections in AIDS patients.
Acquired Immunodeficiency Syndrome↗
Mycobacterium avium complex and the acquired immunodeficiency syndrome.
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Acquired Immunodeficiency Syndrome↗
Altered excretion of modified nucleosides and beta-aminoisobutyric acid in subjects with acquired immunodeficiency syndrome or at risk for acquired immunodeficiency syndrome.
Urinary excretion of modified nucleosides and beta-aminoisobutyric acid, subsequently referred to as markers, was determined in populations of patients with acquired immunodeficiency syndrome (AIDS) or at risk for development of AIDS. Our results show that asymptomatic adult male homosexuals excreted elevated amounts of markers as compared to male heterosexuals. This aberrant excretion was more pronounced in asymptomatic adult male homosexuals with antibodies to HTLV-III. Significantly greater excretion of 1-methylinosine, N4-acetylcytidine, and N2-methylguanosine was observed in asymptomatic adult male homosexuals with antibodies to HTLV-III than in asymptomatic male homosexuals without antibodies to HTLV-III. Increased amounts of markers were also excreted by subjects with the generalized or chronic lymphadenopathy syndrome, AIDS related complex (ARC), or AIDS. In these subjects, the most pronounced differences between groups were between subjects with chronic lymphadenopathy syndrome and those with ARC; subjects with ARC excreted greater amounts of seven of the ten urinary markers. There were few differences between subjects with ARC and those with AIDS, Kaposi's sarcoma, or AIDS with opportunistic infections. This observation may be useful for identifying subjects who are at risk of developing AIDS. A prospective study to test this hypothesis is under way.
Acquired Immunodeficiency Syndrome↗
Interleukin-2 production by persons with the generalized lymphadenopathy syndrome or the acquired immune deficiency syndrome.
We measured production of interleukin-2 (IL-2) by phytohemagglutinin-stimulated peripheral blood mononuclear cells from 27 heterosexual persons, 43 asymptomatic homosexual men, 34 homosexual men with generalized lymphadenopathy syndrome (GLS), and 21 patients with acquired immune deficiency syndrome (AIDS). Asymptomatic heterosexual and homosexual subjects produced comparable amounts of IL-2, but 8 of 11 AIDS patients with opportunistic infections and two of three AIDS patients with both opportunistic infections and Kaposi's sarcoma failed to produce detectable amounts of IL-2; all seven AIDS patients with only Kaposi's sarcoma produced IL-2. The titer of IL-2 produced by the AIDS patients correlated with the percentage of helper T lymphocytes (Leu 3a+ cells) but not with the percentage of suppressor T lymphocytes (Leu 2a+ cells). This observation is interpreted as indicating that failure to produce IL-2 by AIDS patients is most likely due to depletion of IL-2-producing cells, although an abnormality of T-cell function has not been excluded. In addition, three of eight AIDS patients who did not produce IL-2 produced supernatants that inhibited growth of IL-2-dependent cells in the presence of IL-2. These observations suggest that measurement of endogenous IL-2 production may be important in selecting patients for therapy with IL-2.
Acquired Immunodeficiency Syndrome↗
The bone marrow in disseminated Mycobacterium avium-intracellulare infection.
Thirteen cases of disseminated Mycobacterium avium-intracellulare (MAI), representing a total of 27 bone marrow specimens, were studied. The patients ranged from 25 to 46 years of age and included ten immunocompromised and three immunocompetent hosts. Peripheral blood findings included anemia in all patients, leukopenia in 73%, thrombocytopenia in 45%, and pancytopenia in 45%. Fourteen of the specimens (52%) showed granulomas ranging from small, subtle lymphohistiocytic aggregates to larger lymphohistiocytic lesions and clusters of epithelioid histiocytes; almost half of these lesions were missed initially. Rare acid-fast bacilli were seen in only one case, but 53% grew MAI on culture. In one case of the acquired immunodeficiency syndrome, culture was positive in the absence of inflammation or AFB on staining. These findings are not significantly different from those reported in disseminated Mycobacterium tuberculosis infection.
Adult↗
Disseminated infection with Mycobacterium avium-intracellulare. A report of 13 cases and a review of the literature.
Thirteen cases of disseminated infection with Mycobacterium avium-intracellulare (MAI) seen at the National Jewish Hospital and Research Center and 24 cases from the literature were analyzed to define clinical and therapeutic features of the disease. Disseminated MAI infection was a disease of immunocompromised and apparently normal hosts. It was acquired from the environment by unknown mechanisms, usually entering the body through the lungs and spreading to include the reticuloendothelial system, bones, and less commonly, the skin. Diagnosis was often delayed and required culture of tissue or secretions. Medical personnel must maintain a high index of suspicion for MAI disease, especially in immunocompromised hosts. These patients should be monitored carefully for evidence of MAI with frequent cultures of blood and bone marrow. Blood culture systems able to recover MAI promptly and reliably should be employed (52, 64). New diagnostic aids, such as the standardized preparation of PPD-B currently being prepared or tests for antibody to MAI, will help in differentiating MAI from other processes. If MAI is recovered, broad-spectrum therapy should be instituted. Response to combination antimicrobial chemotherapy in the patients surveyed in this report was gratifying. Over two-thirds of treated patients responded to therapy. New antimycobacterial agents such as ansamycin and thienamycin have been shown to have activity against MAI in vitro (40, 81, 92) and may further improve therapeutic efficacy. Studies of in vitro synergy, currently in progress in our laboratory, will also help define the optimal therapeutic regimen for each individual patient. While the patients presented in this report had a reassuring response to therapy, those who had many bacilli in the tissues had a poorer outcome. Patients with AIDS often have this lepromatous histology (37) and thus may respond more poorly than the patients in this report even when optimal therapy is employed. Careful monitoring of AIDS patients for MAI infection may permit earlier institution of therapy and improve the chances for control of the infection. Studies to assess the relationship of in vitro sensitivity to therapeutic response in these patients are currently underway in our laboratory. It is hoped that early institution of therapy and optimization of regimens according to in vitro sensitivity data will lead to decreased morbidity and mortality in all patients with MAI infection.
Acquired Immunodeficiency Syndrome↗
A microtiter assay for human monocyte activation by lymphokines.
This report describes a microtiter assay of human lymphokine activity based on lymphokine-induced increases in monocyte adherence to plastic surfaces. Supernatants were generated by stimulation of peripheral blood mononuclear cells with streptokinase/streptodornase or purified protein derivative. Monocyte adherence was measured by a 51chromium radioassay. The increased adherence was shown to be due to a soluble factor that was produced by antigen-stimulated mononuclear cells from donors who were responsive to the antigen but not by mononuclear cells from donors who were unresponsive. The factor was not dialyzable. The assay requires only 20 ml of peripheral blood and is easily automated and quantifiable, making it suitable for clinical laboratory use.
Cell Adhesion↗
Fibronectin deposition in delayed-type hypersensitivity. Reactions of normals and a patient with afibrinogenemia.
During development of delayed hypersensitivity (DH) skin reactions, fibronectin accumulates in two distinct sites: (a) the dermal interstitium in a pattern similar to fibrin and with a time course similar to that of fibrin deposition and mononuclear cell infiltration, and (b) blood vessel walls in a pattern suggestive of basement membrane staining and with a time course similar to that of endothelial cell proliferation. In vitro fibronectin can bind to monocytes or endothelial cells and simultaneously bind to fibrin or collagen matrices; by such interaction in vivo it may affect cell migration or proliferation. Thus, fibronectin deposition in DH reactions may facilitate cell-matrix interactions; however, the possibility exists that extravascular fibronectin accumulation may be only secondary to interstitial fibrin clot formation, and that blood vessel-associated fibronectin may be only a function of adsorption onto basement membrane (type IV) collagen. To address these possibilities, we investigated the association of fibronectin with fibrin, type IV collagen, and mononuclear cell infiltrates in DH reactions. Skin sites of DH reactions in normal volunteers were biopsied at 24, 48, and 72 h after intradermal challenge and examined by immunofluorescence technique. At all time points most of the interstitial fibronectin coincided with fibrin; however, some interstitial fibronectin was coincident with mononuclear cells positive for HLA-DR or monocyte-specific antigen. The coincidence of fibronectin with mononuclear cells was more apparent in a 48-h DH reaction from a patient with congenital afibrinogenemia. Vessel wall fibronectin was increased by 48 h after challenge and appeared as a fine linear band on the luminal side of a much thicker band of type IV collagen. Thus, the coincidence of extravascular fibronectin with mononuclear cells, its appearance without fibrin in the site from a patient with afibrinogenemia, and incomplete correspondence of vessel wall fibronectin with type IV collagen suggest that fibronectin localization in DH reactions involves endothelial cell and mononuclear cell binding as well as adsorption to fibrin and/or type IV collagen.
Afibrinogenemia↗
The acquired immunodeficiency syndrome and a trimethoprim-sulfamethoxazole adverse reaction.
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Acquired Immunodeficiency Syndrome↗
Long-term therapy of chronic mucocutaneous candidiasis with ketoconazole: experience with twenty-one patients.
Our experience in the treatment of chronic mucocutaneous candidiasis with ketoconazole is reviewed. Of 21 patients, 15 have evidence of deficient cellular immunity and eight have endocrine abnormalities. Six patients had concurrent dermatophytosis or chromomycosis. All patients responded to treatment. Mucosal lesions improved in 6.7 +/- 0.5 days and cutaneous lesions responded to 22.7 +/- 5.1 days. The responses by infected nails were more variable (mean response time 92.4 +/- 14.4 days). Concurrent dermatophytoses did not prolong response times. Adverse effects were infrequent: one patient had drug-induced hepatitis and two patients became hypertensive. The relationship of hypertension to ketoconazole treatment is unclear. One patient was able to remain in remission after treatment was discontinued. Two patients had relapses while on treatment. Candida albicans isolated from these patients was highly resistant to ketoconazole in vitro. We conclude that ketoconazole is an effective and well-tolerated drug for the treatment of the infectious component of chronic mucocutaneous candidiasis.
Adolescent↗
Treatment of fungal infections in the bones and joints with ketoconazole.
Seven patients with fungal infections in the bones and joints were treated with ketoconazole. One patient had aspergillosis, two had sporotrichosis, and four had coccidioidomycosis. All of the organisms that were tested demonstrated in vitro sensitivity to ketoconazole. Patients were treated with 200-600 mg of oral ketoconazole per day for a minimum of six months. Initially four of seven patients responded to therapy, but only one was cured. The other three patients did not respond. Treatment failure may be due to poor penetration of ketoconazole into bone. Ketoconazole will not cure fungal osteomyelitis, but it may be useful in conjunction with surgical debridement. Chronic suppressive therapy with ketoconazole is well tolerated but may not prevent metastatic fungal infection.
Adult↗
Acquired immunodeficiency syndrome in a patient with hemophilia.
A patient with hemophilia A developed T-cell deficiency characterized by infection with several opportunistic pathogens. Immunologic investigation showed cutaneous anergy, lymphocyte unresponsiveness to mitogens and antigens, an abnormal ratio of T-helper and T-suppressor cells with absolute lymphopenia and elevated IgA. The clinical and immunologic characteristics of this patient fit the recently described syndrome of opportunistic infections or Kaposi's sarcoma in patients with acquired T-cell deficiency; however, this patient does not have any of the associated underlying risk factors such as homosexuality, intravenous drug or amyl nitrite use, or positive serologic tests for syphilis. We conclude that the patient's acquired T-cell deficiency can be explained by exposure to a virus or other transmissible agent during factor VIII transfusions.
Acquired Immunodeficiency Syndrome↗
In vitro studies on bile acid deconjugation and lipolysis inhibition by Giardia lamblia.
In vitro studies were conducted to determine whether Giardia lamblia can be deconjugate bile acids or inhibit lipolysis. Cultured G. lamblia trophozoites failed to deconjugate either glycine- or taurine-conjugated cholic acid, deoxycholic acid, or chenodeoxycholic acid. However, sonicated trophozoites significantly inhibited the hydrolysis of tributyrylglycerol by porcine pancreatic lipase. This inhibition was not dependent upon the presence of bile acids but was dependent upon the concentration of G. lamblia sonicate. Heating the sonicate for 20 min at 60 degrees C abolished the inhibitory effect; dialysis of the sonicate did not affect inhibition. We conclude that cultured G. lamblia trophozoites do not deconjugate bile acids and that sonicated G. lamblia inhibit lipolysis in vitro.
Bile Acids and Salts↗
The global distribution of human immunodeficiency virus type 2 (HIV-2) infection.
We reviewed published reports of infection with human immunodeficiency virus type 2 (HIV-2) to provide a picture of its geographic distribution, pathogenicity, modes of transmission, and risk to the blood supply. Since the first reports in 1986, 627 HIV-2-seropositive persons have been reported; 604 of these were in natives of West Africa. Acquired immunodeficiency syndrome (AIDS) had developed in 42 patients, while 8 patients had AIDS-related complex. Transmission by sexual intercourse was the usual reported mode of spread. The modes of transmission of HIV-2 are thought to be the same as those for HIV-1, but perinatal transmission and transmission by sharing of needles among intravenous drug abusers have not yet been reported. The virus has not been identified in blood donors in the United States or West Germany, but two HIV-2-infected blood donors were reported in France. Further epidemiologic studies are needed to define the spectrum of disease, modes of transmission, and risk of HIV-2 to the blood supply.
Acquired Immunodeficiency Syndrome↗