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Biomedical subjects

A Rios

Publications and source records attributed to A Rios.

At least 73 records · Page 4Linked to original sources
PubMed1988

Plasma fibronectin values in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex.

The authors studied the circulating fibronectin concentrations in the plasma of 24 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) and of 74 age- and sex-matched healthy blood donors. They adapted a commercially available turbidimetric immunoassay for use with a centrifugal analyzer. The assay showed within-run precision of 2.1%, 2.3%, 1.8%, and 1.1%, and an accuracy of 90%, 99%, 98%, and 98% at fibronectin concentrations of 126 mg/L, 200 mg/L, 293 mg/L, and 317 mg/L, respectively. Between-run precision was 5%, 3%, and 2% for 66 mg/L, 218 mg/L, and 283 mg/L concentrations, respectively. Plasma fibronectin values obtained from the healthy blood donors were in good agreement with those values reported by other investigators using various methods. No significant differences between the plasma fibronectin values of the patient population (mean +/- 2 SD = 294 mg/L +/- 110 mg/L) and of the control group (mean +/- 2 SD = 311 mg/L +/- 130 mg/L) were noted. The authors conclude that the measurement of fibronectin concentrations in patients with AIDS or ARC does not contribute significantly to the diagnosis and therapeutic management of these patients.

AIDS-Related Complex↗
PubMed1987

Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group.

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5, 1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 mumol/L or higher (greater than or equal to 2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemo-pneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS.

AIDS-Related Complex↗
PubMed1987

Hematologic response of four patients with smoldering acute myelogenous leukemia to partially pure gamma interferon.

In vitro and in vivo studies were conducted to obtain basic information on the activity of gamma interferon (IFN-gamma) in acute myelogenous leukemia (AML). In a selected case of AML, recombinant IFN-gamma, but not IFN-alpha, induced differentiation of primary leukemic blasts in vitro. Similarly, IFN-gamma inhibited leukemic colony formation in vitro. This contrasted with IFN-alpha which was inactive. In one case of AML (M2), partially purified IFN-gamma given intravenously caused a shift of the WBC profile from immature blasts to maturing myeloid cells and neutrophil granulocytes. Intravenous IFN-gamma treatment of another patient who had AML as a second malignancy resulted in a complete hematologic remission, normalization of marrow granulocyte-macrophage colony-forming cell in vitro growth, and conversion of marrow cytogenetics from 95% hyperdiploid clone with complex abnormalities into 100% diploid. The results indicate a potential use of IFN-gamma in the treatment of selected patients with AML and the possibility of in vitro pretreatment evaluation of these patients' leukemic response to IFNs.

Adult↗
PubMed1987

Acquired immunodeficiency syndrome-associated psoriasis and Reiter's syndrome.

Human immunodeficiency virus (HIV) causes a spectrum of immunodysfunction, the most severe of which is the acquired immunodeficiency syndrome (AIDS). We have followed the course of psoriasis in 13 patients over 2 1/2 years in a population of more than 1000 HIV-positive individuals. Four patients had a history of mild psoriasis that became severe and uncontrollable as symptoms of immunodeficiency developed. Psoriasis and HIV positivity, AIDS-related complex, or AIDS simultaneously developed in nine patients. In addition to psoriasis, Reiter's syndrome (arthritis, urethritis, and conjunctivitis) developed in one patient in the first group and three patients in the second group. Opportunistic infections, especially candidiasis and Staphylococcus, drugs, and an altered immune system may contribute to the development or flare of psoriasis in these patients. The appearance of severe psoriasis (especially in a patient with other risk factors for HIV) should prompt evaluation for HIV, and may be a poor prognostic indicator in HIV-positive patients, since nine of our 13 patients have died. Immunosuppressive therapy with methotrexate is contraindicated in this group of patients. Newer forms of drug therapy including etretinate show promising results for the management of AIDS-associated psoriasis.

AIDS-Related Complex↗
PubMed1986

Effects of propranolol, clonidine and hydrochlorothiazide treatment and abrupt discontinuation on central and peripheral noradrenergic activity in essential hypertension.

This study was undertaken to investigate further the CNS actions of commonly employed antihypertensive drugs. Measurements of cerebrospinal fluid (CSF) and plasma catecholamines (CA) were made in an attempt to estimate the activity of central and peripheral noradrenergic neurons during treatment with or after abrupt discontinuation of treatment with clonidine (CLO), propranolol (PRO), hydrochlorothiazide (HCTZ) or placebo, in patients with essential hypertension. A randomized, parallel, placebo-controlled, single-blind design was employed. BP reductions equal to or greater than 10 mmHg were observed with CLO (0.36 +/- 0.07 mg daily), PRO (160 mg +/- 0 mg daily) or HCTZ (70 +/- 12 mg daily). CLO reduced plasma norepinephrine (NE) by 64% and PRO increased it by 25%. Neither HCTZ nor placebo modified plasma NE. Plasma renin activity (PRA) was reduced by PRO (51%, P less than 0.01) and CLO (35%, P less than 0.05). CSF-NE levels (pg/ml) were significantly lower in the CLO group (CLO: 175 +/- 23; PRO: 278 +/- 35; HCTZ: 255 +/- 34; placebo: 203 +/- 7).

Adrenergic Fibers↗
PubMed1986

Relationship of exposure to human T lymphotropic virus and T helper cells in homosexual men.

The detection of serum antibodies (Ab) against HTLV-III in individuals with AIDS and related symptoms (ARC) has unambiguously defined the association of the virus infection to AIDS. This study was done to determine the extent of exposure to HTLV-III in homosexual men by measuring (Ab) and relating it to the stage of disease and T cell subsets. We found Ab in 89.5% of the 492 men with the median titers by stage of disease being 1600 for symptom-free, 6400 for ARC or Kaposi's sarcoma, and 4800 for opportunistic infection (OI), respectively. There was no correlation between Ab titers and either absolute or relative T helper cells (T4+), even though these cells decreased with disease severity. More specifically, however, symptom free patients had a normal distribution of the helpers of suppression (T4+/Leu8+), whereas, in symptomatic men, there was a significant decrease suggesting that the target cell for the virus is a subpopulation of the T helper cell.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Coexpression of T- and B-markers in a lymphoproliferative disorder.

An atypical case of lymphoproliferative disorder in which T- and B-cell antigens were coexpressed in the neoplastic cells is described. The disease was characterised by hepatosplenomegaly, lymphadenopathy, a low WBC (5 X 10(9)/l) and bone marrow infiltration. The predominant cell population (greater than 70%) comprised lymphoid cells with a range of nuclear irregularities and included some blast cells. 90% of the peripheral blood lymphocytes showed a mature T-helper phenotype (E+, T11+, T3+, T4+, T8-, T6-, TdT-) with coexpression of the specific B-markers B1 and FMC7, in 90% and 50% of cells, respectively. HLA-DR antigens were present in 55% of cells while surface and cytoplasmic immunoglobulins (Ig) were detected in less than 10% of cells. Molecular investigations with appropriate probes showed evidence of T-cell receptor gene rearrangement but no rearrangement for the genes of the Ig-heavy and -light chains. Cytogenetic studies revealed a translocation t(10;19) (p12; q13) in all the metaphases analyzed. This case demonstrates that the study of neoplastic cells with a battery of monoclonal antibodies may disclose the existence of a hitherto unrecognised lymphoid cell population with atypical expression of B- and T-cell antigens. On the other hand, the presence of T-cell receptor gene rearrangement indicates that this is a T-cell disorder with the aberrant co-expression of specific B-cell markers.

Aged↗
PubMed1986

Clinical toxicity of interferons in cancer patients: a review.

All major types of human interferons (IFNs) have been purified and clinically administered as antitumor agents. We summarize here experience to date with toxicity of IFNs in cancer patients. The acute syndrome consists of fever, chills, myalgias, arthralgias, and headache, with some variation according to type of IFN, route of administration, schedule, and dose. Fatigue, perhaps reflecting CNS toxicity, is the most prevalent nonacute symptom. At high doses, IFNs are neurotoxic; the abnormalities seen by EEG resemble those in diffuse encephalitis. Hematologic toxicity consists mainly of leukopenia, but anemia and thrombocytopenia occur in some patients. Nausea, vomiting, and diarrhea are the main gastrointestinal symptoms. Elevation of serum transaminases seems to reflect liver toxicity. Renal function is well preserved, except for rare instances of acute renal failure. Cardiac toxicity remains questionable, although heart failure and arrhythmias have been associated with the administration of IFNs. Most, if not all, of these effects are reversible or can be ameliorated. With IFN alpha, the type most widely used in clinical studies, doses of 1 million to 9 million units (MU) are generally well tolerated, but doses greater than or equal to 18 MU yield moderate to severe toxicity. Doses greater than or equal to 36 MU can induce severe toxicity and significantly alter the performance status of the patient.

Antibody Formation↗
PubMed1986

Phase I study of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP), an oral interferon inducer, in cancer patients.

2-Amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) was given to 59 patients in a Phase I study. The agent was selected because it is an interferon inducer and an immunotherapeutic agent in animal tumor models. The study was conducted in two phases. In the first phase, the drug was administered as a single oral dose of 25-2,000 mg/m2. In the second part, the highest tolerated dose reached during part one was used as the initial dose in a multiple-dose scheme of treatment. Patients were treated weekly. The dose was escalated each week, starting with a dose of 2 g/m2 and escalating to 3, 4, and 5 g/m2. No cardiac, hematologic, hepatic, or renal toxicity was observed. The most common toxicity was nausea and vomiting, which occurred in 18% of the patients; others were headache (8%), abdominal pain (8%), and diarrhea (6%). No consistent induction of interferon and no major modification of host defense parameters occurred. One patient with malignant melanoma showed evidence of tumor regression. Pharmacologic studies demonstrated a significant decrease in the bioavailability of the drug as it was administered in this study. Further studies of ABPP with a preparation that has good availability are indicated to determine the potential antitumor activity of this agent or this class of agents in humans.

Adult↗
PubMed1986

Initial clinical studies with copovithane.

Copovithane is a new copolymer of low molecular weight and with a significant in vivo antitumor activity in preclinical trials. The mechanism of action is unknown. Ninety-one patients with various metastatic neoplasms beyond the curable stage were treated with copovithane by weekly intravenous administration. Dose levels ranged from 1 to 33 g/m2/week. No dose-limiting toxicity was reached. Tolerance was excellent, with minor fatigue, occasional nausea, and intermittent proteinuria as the only significant side effects in less than 25% of patients. Two patients achieved a partial remission, and five patients reached minor responses during therapy. Antitumor effects were noted only in cutaneous and subcutaneous metastases. Extensive immunologic evaluation revealed some improvement in helper:suppressor T cell ratio, in vitro cytotoxicity tests, and lymphocyte blastogenic responses in patients treated at intermediate levels. The immunologic testing also suggested that the higher dose levels (22-33 g/m2 weekly) might adversely affect the immune response. The clinical relevance of these changes is uncertain. Phase II clinical trials are recommended utilizing weekly doses between 10 and 15 g/m2.

Adult↗
PubMed1985

Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma.

Fifty-six patients with metastatic renal cell carcinoma (RCC) were treated with recombinant DNA-derived interferon alpha (rIFN alpha A). The first 30 patients were randomized between doses of 2 X 10(6) U/m2 and 20 X 10(6) U/m2 intramuscularly daily. No complete (CR) or partial (PR) remissions were achieved in 15 patients receiving the low dose. In contrast, 27% of those receiving the high dose achieved CR or PR. Subsequently, 26 additional patients were given the high dose and achieved a 31% response rate. Remissions lasted from 1 to more than 12 months (median, 3 months). Responses occurred predominantly in lung parenchyma or mediastinal node metastases. Toxicity of the high dose required dose reduction in 50% of the patients. Neutralizing antibodies to rIFN alpha A developed in seven of 12 responsive (58%) and nine of 29 (31%) nonresponsive patients (P = greater than .5). The median duration of remission among the antibody-positive and antibody-negative patients were 2 and 10 months, respectively (P = .009). The clinical significance of the antibodies to rIFN alpha A remains unclear, but the coincidence between the detection of antibodies and the early relapse of the disease in some responsive patients suggests that these antibodies may abrogate the biologic activity of rIFN alpha A. This effect, however, was not associated with adverse clinical sequelae.

Adult↗
PubMed1985

Treatment of acquired immunodeficiency syndrome--related Kaposi's sarcoma with lymphoblastoid interferon.

Twelve homosexual patients with Kaposi's sarcoma associated with the acquired immune deficiency syndrome (AIDS) were treated with a preparation of purified human lymphoblastoid interferon (Wellferon [Burroughs Wellcome, Research Triangle Park, NC]). They were given a dose of 20 X 10(6) U/m2 intramuscularly daily for approximately two months. Responders continued their treatment on a maintenance schedule of 20 X 10(6) U/m2 three times a week. Four patients experienced complete remissions, and four experienced partial remissions that resulted in a total response rate of 67%. The median duration of treatment was 14 weeks (7 to 28+ weeks), and the median response duration was 28+ weeks (19 to 29+ weeks). Of the four patients in complete remission, one relapsed at 25 weeks and one at 26 weeks; the other two remained in complete remission at 28 and 29+ weeks. The clinical toxicity consisted of chills, fever, fatigue, and asthenia. Hematologic toxicity was similar to that previously described for other preparations of alpha-interferon and consisted of moderate leukopenia and thrombocytopenia. Asthenia, a condition present in all 12 patients, was severe in 50%. A minimal tumor burden, the absence of circulating interferon before treatment, and a performance status of greater than or equal to 90% on the Karnofsky scale were related to an improved response rate. Measurement of immunologic parameters showed significant declines in the already impaired T cell levels, lymphocyte blastogenic response to concanavalin A, monocyte-mediated antibody-dependent cellular cytotoxicity, and monocyte-adherence. Activation of natural killer cells was not noted, and no life-threatening infections occurred during treatment. These data suggest that human lymphoblastoid interferon is an active agent in the treatment of Kaposi's sarcoma, and its use warrants further study in a larger number of patients.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Pharmacokinetics, single-dose tolerance, and biological activity of recombinant gamma-interferon in cancer patients.

We report a clinical study of the pharmacokinetics, toxicity, and biological activity of i.v.- and i.m.-administered recombinant gamma-interferon (rIFN-gamma) consisting of 143 amino acids. Ten patients with metastatic cancer were given rIFN-gamma at doses of 0.01 to 2.5 mg/sq m by alternating i.m. and i.v. bolus injections with a minimum intervening period of 72 h. After i.v. administration, rIFN-gamma was cleared monoexponentially with a short half-life of 25 to 35 min as determined by bioassay and enzyme immunoassay. After i.m. injection, a longer half-life of 227 to 462 min was measured by enzyme immunoassay. Serum titers were detected by bioassay only at high doses, suggesting partial loss of antiviral activity at the i.m. site. However, other biological effects were retained as evidenced by fever, chills, and fatigue after both routes of administration and granulocytopenia after i.m., but not i.v., doses. Two of ten patients showed objective evidence of tumor regression. These data suggest that further studies with i.m. as well as prolonged i.v. infusions of rIFN-gamma are indicated.

Half-Life↗