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Biomedical subjects

A Rios

Publications and source records attributed to A Rios.

At least 91 records · Page 5Linked to original sources

Polymicrobial brain abscess in a homosexual man with Kaposi's sarcoma.

A progressive visual field defect and fever occurred in a 39-year-old homosexual man with acquired immunodeficiency syndrome and Kaposi's sarcoma. Computerized tomography of the brain documented a left parieto-occipital abscess. A specimen obtained at the time of surgical excision of the lesion revealed organisms with morphologic features of Toxoplasma gondii and Candida. Culture of this material grew Staphylococcus epidermidis. Appropriate therapy for this polymicrobial infection resulted in resolution of the fever and clinical improvement. The visual deficit remained unchanged despite antimicrobial therapy.

Acquired Immunodeficiency Syndrome↗

Immunologic studies of the acquired immune deficiency syndrome: relationship of immunodeficiency to extent of disease.

Immunologic and conventional laboratory studies were done in 135 previously untreated subjects including 28 (20.7%) symptom-free homosexuals and 74 (54.8%) with ARC and 33 (24.5%) with AIDS. More than half of all patients had abnormal percentages of lymphocytes, percentages of T3+ cells, percentage and absolute number of T4+ cells, percentage of T8+ cells, T4/T8 ratio, monocyte adherence, and serum thymosin alpha 1. Most immune variables worsened with progressive disease. Low lymphocyte 5'nucleotidase increased suppressor cell activity, and impaired IL-2 and alpha interferon production and response suggest diminished mature and increased immature peripheral blood and tissue T cells. These findings suggest approaches to staging, prognostication, and treatment for AIDS.

Acquired Immunodeficiency Syndrome↗

New avenues in the use of cyclosporine for transplantation. Graft and donor pretreatment.

Modification of graft immunogenicity using graft (GPTX) and donor pretreatment (DPTX) has been pursued in an attempt to modify allograft immunogenicity using various immunosuppressive agents. The murine skin allograft and canine renal allograft models were used to study the efficacy of Cyclosporine (Cy A) as a DPTX and GPTX prior to transplantation. Tail skin allografts from C3HHeN male mice were grafted to Balb/c female mouse recipients. Minimal immunosuppression was given to all skin graft recipients. Skin allograft were either GPTX with Cy A, DPTX with either Cy A, methylprednisolone (MP), or cyclophosphamide (CP), or Cy A GPTX and DPTX with the three drugs alone or in combination. Cy A GPTX alone of skin allografts did not significantly prolong survival. DPTX with Cy A significantly prolonged skin graft survival, however, CP or MP alone did not. The various combinations of MP, Cy A, and CP as DPTX and MP, Cy A, and CP DPTX used together with Cy A GPTX also significantly prolonged murine skin allograft survival. Kidney allografts used unrelated mongrel dogs as donors or recipients. Renal transplant experimental groups were either: Non-pretreated and immediately transplanted, nonpretreated and hypothermically stored (HS) for 24 hours in Collins (C-2) solution, GPTX with 12.5 mg Cy A during 24 hr. HS in C-2, DPTX with Cy A (25 mg/Kg), or Cy A DPTX (15 mg/kg) and GPTX during 24 hrs. HS in C-2. Cy A GPTX during HS was sometimes effective in prolonging kidney allograft survival greater than 30 days using only minimal immunosuppression with azathioprine. Cy A DPTX prolonged survival somewhat, but not significantly. Improved results were seen, however, when Cy A DPTX was used together with Cy A graft pretreatment. These results indicate the potential for the successful use of Cy A as a donor and/or graft pretreatment, however, further studies will be necessary to optimize the use of Cy A in these modalities.

Animals↗

Bacteremia caused by Campylobacter-like organisms in two male homosexuals.

Bacteremia caused by newly described Campylobacter-like organisms occurred in two immunosuppressed homosexual patients with tuberculosis. Although these organisms grow well in aerobic bottles using a radiometric blood culture system, they are not readily seen in gram-stained smears and are easily missed if routine subculture methods are used. Microscopic examination of wet preparations and subculture to brucella agar base supplemented with 10% sheep blood and incubated in microaerophilic conditions are useful for identification and isolation. The recovery of Campylobacter-like organisms from the blood suggests that these organisms, formerly known only to be associated with proctocolitis or asymptomatic rectal infection in homosexual men, can also cause systemic infection in these patients.

Adult↗

Immunological characterizations of patients with acquired immune deficiency syndrome, acquired immune deficiency syndrome-related symptom complex, and a related life-style.

Immunological, hematological, and biochemical studies were done at the time of referral in 135 homosexual subjects, 28 of whom were symptom free (SF), 74 of whom had the acquired immune deficiency syndrome (AIDS)-related symptom complex (ARC), and 33 of whom had AIDS with Kaposi's sarcoma, opportunistic infection, or both. Of 38 laboratory parameters, 11 were significantly different than controls in the SF patients, 19 in the ARC patients, and 20 in the AIDS patients. In SF patients, delayed hypersensitivity was significantly suppressed for 6 of 12 recall antigens. In addition, the percentage of circulating lymphocytes, the percentage of T3+ cells, the percentage and absolute number of T4+ cells, the T4/T8 ratio, the blastogenic responses to phytohemagglutinin, pokeweed mitogen, and concanavalin A were depressed significantly in this group. In contrast, the percentage and absolute granulocyte count, the serum lysozyme, and the serum thymosin alpha 1 were significantly elevated in these patients. In patients with more advanced disease (ARC and AIDS), immunological and hematological parameters tended to worsen. Thus, in the AIDS patients the white blood cell count, percentage, and absolute T11+ cells, absolute T3+ cells, percentage of T4+ cells and absolute level of B-cells, as well as the monocyte adherence and delayed hypersensitivity responses to 12 of 12 recall antigens were depressed. Serum levels of thymosin alpha 1 were equally elevated in all three groups. Serum interferon was found in 15 of 18 opportunistic infection patients with or without Kaposi's sarcoma, in 3 of 9 Kaposi's sarcoma patients without opportunistic infection, but in none of the ARC or SF patients. This study has demonstrated that SF sexually active homosexuals have a characteristic pattern of immune deficiency and that immunodeficiency worsens as one compares SF to ARC to AIDS patients. The study has provided a data base for the development of prognostic criteria and for characterization and evaluation of immunorestorative and immunomodulatory therapy.

Acquired Immunodeficiency Syndrome↗

Pharmacokinetic study of partially pure gamma-interferon in cancer patients.

A pharmacokinetic study was performed with partially pure immune (gamma) interferon (IFN-gamma) in patients with metastatic cancer. Nine patients were given IFN-gamma by the i.m. route in doses ranging from 1.5 X 10(5) to 9.6 X 10(6) antiviral units. There was no detectable antiviral activity in patients' serum, and only minimal side effects were observed. Fifteen patients were given IFN-gamma by i.v. bolus infusion in doses ranging from 1.5 X 10(5) to 54 X 10(6) units. Serum clearance of antiviral activity was described by a monoexponential disappearance curve. The serum half-life was dose dependent (3 min at the lower doses and 34 min at the highest doses). There were few consistent biological effects observed in the patients. Based on these pharmacokinetic data, eight patients were treated by a 6-hr continuous infusion consisting of 3 X 10(6) units by i.v. bolus followed by 4 X 10(6) units/hr for 6 hr. This regimen resulted in consistent serum levels of IFN-gamma ranging from 40 to 60 units over the 6-hr period. Marked granulocytopenia occurred within 24 hr and was sustained during the 10-day infusion period. There was marked increase in serum beta 2-microglobulin. We conclude that, in order to induce consistent serum antiviral activity, partially pure IFN-gamma, because of its rapid serum disappearance curve, must be administered by continuous i.v. infusion.

Drug Evaluation↗

Nonbacterial thrombotic endocarditis in a male homosexual with Kaposi's sarcoma.

Nonbacterial thrombotic endocarditis (NBTE), or marantic endocarditis, was found at autopsy in a young male homosexual with Kaposi's sarcoma. Vegetations were seen in the mitral and aortic valves. Embolic phenomena and cytomegalovirus infection were noted in the brain, spleen, liver, lung, gastrointestinal tract, and bone marrow. To our knowledge, this is the first reported case of NBTE in a young immunosuppressed homosexual man with Kaposi's sarcoma.

Adult↗

Human cryptosporidiosis: spectrum of disease. Report of six cases and review of the literature.

Although once regarded exclusively as an animal parasite, Cryptosporidium has emerged during the last decade as a cause of diarrhea in humans. Of the 43 cases of human cryptosporidiosis reported, 27 patients in whom either humoral or cell-mediated immune defects were present had chronic protracted diarrhea that was almost invariably unresponsive to therapy and culminated in death. In contrast, 16 patients with intact immune systems had either self-limited disease or were asymptomatic. Animal exposure was almost exclusively recorded in the latter group. During the last six months at University of Texas M. D. Anderson Hospital and Tumor Institute, Houston, gastrointestinal (GI) tract cryptosporidiosis developed in six homosexual men with acquired immune deficiency syndrome (AIDS). The diagnosis of cryptosporidiosis was established histologically in five patients. In four, cryptosporidial oocysts were detected in the stool. In addition to extensive GI tract cryptosporidiosis, two patients had biliary tract involvement. Multiple chemotherapeutic agents failed to control the disease, and five patients eventually died. Cryptosporidiosis should be considered in the differential diagnosis of diarrhea, in animal handlers or in the severely compromised patient, especially one with AIDS, who has chronic protracted diarrhea.

Acquired Immunodeficiency Syndrome↗

Immunological studies of male homosexuals with the prodrome of the acquired immunodeficiency syndrome (AIDS).

Homosexual patients who mainly had the prodrome of the syndrome of opportunistic infection and Kaposi's sarcoma were studied immunologically. Patients showed diminished delayed hypersensitivity to recall antigens, diminished lymphocyte blastogenic responses, a suppressor cell for lymphocyte proliferative responses, low helper cells and an inverted helper:suppressor ratio. The patients had low levels of adherent monocytes. NK cell activity and antibody dependent cellular cytotoxicity were normal. Virtually all patients showed elevated serum thymosin alpha 1 levels and elevated serum lysozyme levels. The most consistent findings were the low helper cells, inverted helper:suppressor ratio and elevated serum thymosin alpha 1 and lysozyme. The patients with the prodrome should be subjected to therapeutic research with immunorestorative drugs.

Acquired Immunodeficiency Syndrome↗

Leukocyte subset analysis and related immunological findings in acquired immunodeficiency disease syndrome (AIDS) and malignancies.

Cell surface marker analyses conducted on human peripheral blood lymphoid cells have proven extremely useful in the diagnosis of immunodeficiency and the diagnosis and staging of malignancies. In this paper we have focused on the ratio of helper to suppressor cells in patients with the acquired immune deficiency syndrome and in patients with malignancy. In thirty-three patients with the acquired immune deficiency syndrome, the majority showed an inverted helper:suppressor ratio, elevated serum thymosin alpha 1, and elevated serum lysozyme levels. The inverted ratio was due to a deficiency in T-helper cells. The inverted helper:suppressor ratio was associated with functional suppressor cell activity that was seen in 12 out of 21 patients examined. Patients' lymphocytes were found to suppress the PHA, pokeweed mitogen, and concanavalin-A responses of normal subjects' lymphocytes. The suppression also correlated with impaired lymphocyte proliferative responses among the patients' cells themselves. Because of these findings, the helper:suppressor ratio was studied in patients with solid tumors, lymphoma, acute leukemia, chronic lymphocytic leukemia, and hairy cell leukemia. Approximately 30% of these patients have an inverted helper:suppressor ratio. However, in ten out of 30 patients with chronic lymphocytic leukemia and in three out of 45 patients with lymphoma, the helper:suppressor ratio was elevated, being greater than 3.0. The significance of these findings is as yet to be explored, but it is suggested that an inverted helper:suppressor ratio in patients with malignancy may relate to an advanced stage of disease or a poor prognosis. Documentation of this point will require further study.

Acquired Immunodeficiency Syndrome↗

Immunological characterization of homosexual males.

To help clarify the nature and pathogenesis of the syndrome of severely opportunistic infection associated with immune deficiency in young homosexual males, we investigated the immunological characteristics of a group of 33 young homosexual men. These young men all had the prodrome to the syndrome which included a history of multiple sexual partners and multiple sexually transmitted diseases. In addition, they all had a past history of mild to moderate viral, bacterial, parasitic, or fungal infections and had used recreational drugs. Within this group of patients, there were five men who had Kaposi's sarcoma. Compared to the 21 normal heterosexual individuals, the homosexual men were found to be anergic to a battery of recall antigens (52% versus 19%); to be hyporesponsive to mitogen stimulation (pokeweed, 30.7 x 10(-3) versus 65.3 x 10(-3) cpm, p less than or equal to 0.005; concanavalin A, 32.2 x 10(-3) versus 60.1 x 10(-3) cpm, p less than or equal to 0.006); and to have lower helper T-cells (18% versus 34.6%, p less than or equal to 0.01), inverted helper:suppressor T-cell ratios (0.85 versus 1.92, p less than or equal to 0.01), and an elevated serum thymosin alpha 1 level (1473 versus 524 pg/ml, p less than or equal to 0.001). These data suggest that the immunological defect precedes the syndrome. The mechanism of this phenomenon is unclear; however, the repeated viral infection combined with drug usage may be responsible. The five patients with Kaposi's sarcoma were compared as a group to the other patients without cancer and found to be more severely immunodeficient. This suggests that the immune suppression by the malignant disease is superimposed on the preexisting deficiency.

Adult↗

Phase I study of MVE-2 therapy in human cancer.

MVE-2, a polymer of maleic anhydride and divinyl-ether (molecular weight, 15,500), was given to 57 patients in a phase I study. The agent was selected for study because it was a potent macrophage activator, interferon inducer, and immunotherapeutic agent in animal tumor models. The drug was administered by iv infusion over a 1-hour period using three schedules of administration: (a) weekly at doses of 25-650 mg/m2, (b) every other week at doses of 500-1200 mg/m2, and (c) every 3 weeks at doses of 1200-1500 mg/m2. No cardiac, pulmonary, hematologic, or hepatic toxicity was observed. There were 25 episodes of asymptomatic proteinuria in 26 patients who received MVE-2 dose levels of greater than or equal to 500 mg/m2. It was not associated with changes in BUN or creatinine. The proteinuria began approximately 4 weeks after the start of therapy and lasted approximately 4-6 weeks after the therapy was terminated. Proteinuria resolved in all patients followed. At present, proteinuria appears to be the major dose-limiting toxicity. None of the patients had a partial or complete response although there was evidence of biologic activity with measurable tumor regression in five patients. No major modification of host defense parameters was noted. Further studies should be directed towards determining the nature of the proteinuria and whether changes in the rate or schedule of administration can modify the proteinuria or increase the host defense modification.

Blood Urea Nitrogen↗