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Biomedical subjects

M Frieri

Publications and source records attributed to M Frieri.

At least 19 recordsLinked to original sources
PubMed1998

Osteoporosis in the corticosteroid-treated patient with asthma.

Osteoporosis affects 40% of white women older than 45 years of age and 15% of white men older than 50 years of age, resulting in approximately 1.5 million annual fractures in the United States. Systemic corticosteroid therapy increases the probability of osteoporosis, even with alternate-day dosing and with dosages sufficiently low so as not to affect the hypothalamic-pituitary-adrenal axis. Inhaled corticosteroid therapy may affect bone density if high-dose therapy is given to select individuals. The potential of increasing osteoporosis with inhaled corticosteroid asthma therapy is a concern because of the availability of more potent inhaled corticosteroid agents and recommendations that inhaled corticosteroid therapy be initiated earlier in the course of asthma. This article provides suggestions, on the basis of the medical literature and consensus of the authors when specific information was not available, for assessing and treating osteoporosis in subjects with asthma. Suggested risk categories are "low risk" (inhaled corticosteroid dosage of < or =800 microg of heclomethasone dipropionate [BDP]/day in adults or < or =400 microg BDP or equivalent in children), "moderate risk" (inhaled BDP >800 microg/day in adults or >400 microg/day in children), and "high risk" (systemic corticosteroid therapy 4 times a year or daily or alternate-day systemic corticosteroid therapy). Dosage of nasal corticosteroid probably should be added to the orally inhaled corticosteroid for total burden of inhaled corticosteroid. Potential treatment strategies based on risk factors and bone density if indicated are offered to assist physicians treating patients with asthma.

Adrenal Cortex Hormones↗
PubMed1998

Theophylline inhibits the production of nitric oxide by peripheral blood mononuclear cells from patients with asthma.

BACKGROUND: Nitric oxide (NO), a reactive free radical synthesized from L-arginine by the enzyme NO synthase (NOS), may play a role in many pathophysiologic conditions, including asthma. OBJECTIVE: The aim of this study was to investigate whether peripheral blood mononuclear cells (PBMCs) from asthmatics would spontaneously produce NO. A second objective was to ascertain whether commonly used asthma medications would modulate the production of NO. METHODS: PBMCs were isolated from 24 subjects (10 with asthma, 4 with allergic rhinitis and 10 healthy controls) and were incubated either alone or in the presence of an RNA polymerase inhibitor (actinomycin D, 1 microg/mL), a NOS inhibitor (L-NG-nitroarginine methyl ester [L-NAME], 1 mM), and L-NAME plus L-arginine (5 mM). Furthermore, PBMCs were incubated with or without addition of therapeutic concentrations of hydrocortisone (15 microg/mL), theophylline (15 microg/mL), albuterol (15 microg/mL) and ipratropium bromide (12 microg/mL). Culture supernatants were collected and assayed for NO production. RESULTS: NO production was significantly elevated in asthmatics compared with the control group (1.39+/-0.21 microM versus 0.46+/-0.01 microM; P < .05). L-NAME significantly reduced NO production in asthmatics (0.83+/-0.06 microM; P < .05), an effect completely reversed by L-arginine. Theophylline blocked NO production in asthmatics (1.39+/-0.21 microM to 0.92+/-0.11; P < .05). There was no significant effect with any of the other medications. CONCLUSION: This study suggests that theophylline may be antiinflammatory by inhibiting the L-arginine-dependent production of NO in patients with asthma.

Adult↗
PubMed1998

Allergen-stimulated leukotriene B4 and interleukin-8 levels in patients with asthma and allergic rhinitis-modulation by a lipid pathway inhibitor.

BACKGROUND: Leukotriene B4 (LTB4), a potent chemokinetic mediator for neutrophils, is enhanced by interleukin-8 (IL-8) and may play a key role in the inflammatory response of asthma. OBJECTIVE: The aim of the present study was to investigate whether zileuton, a 5-lipoxygenase antagonist known to inhibit LTB4 production and recruitment of eosinophils/neutrophils in bronchoalveolar fluid, could affect the production of LTB4 and IL-8 by allergen-stimulated peripheral blood mononuclear cells in vitro from patients with asthma and/or allergic rhinitis. METHODS: Peripheral blood mononuclear cells were isolated using Ficoll-Hypaque density gradient from 14 subjects (2 with asthma, 11 with asthma and allergic rhinitis, and 1 with allergic rhinitis) and were stimulated by selected allergens (grass, tree, mite, and mold) in the absence or presence of 1 and 10 microM of zileuton. Supernatants were collected and assayed for LTB4 and IL-8 levels using RIA and ELISA, respectively. RESULTS: Levels of LTB4 were significantly elevated in peripheral blood mononuclear cells stimulated with mold, grass, and tree compared with the unstimulated control group (P<.05). Levels of IL-8 were significantly elevated in all allergen-stimulated peripheral blood mononuclear cells, except mold, compared with the unstimulated control group (P<.05). Zileuton significantly reduced production of LTB4 by mold and tree-stimulated peripheral blood mononuclear cells. By contrast, no effect of zileuton on IL-8 production was observed in allergen-stimulated peripheral blood mononuclear cells. CONCLUSIONS: The zileuton-induced attenuation of LTB4 production by allergen-stimulated peripheral blood mononuclear cells from patients with asthma and/or allergic rhinitis occurs independently from the allergen-stimulated IL-8 production.

Adult↗
PubMed1998

Effect of mometasone furoate on early and late phase inflammation in patients with seasonal allergic rhinitis.

BACKGROUND: Mometasone furoate is a potent glucocorticoid that can markedly inhibit proinflammatory Th2 cytokines in vitro. An aqueous nasal spray formulation has been shown to be clinically active in reducing the symptoms of perennial and seasonal allergic rhinitis. OBJECTIVE: To determine whether pretreatment with mometasone furoate 200 microg once daily decreases specific indices of early and late phase nasal inflammation compared with placebo. METHODS: A randomized, double-blind, placebo-controlled crossover study was conducted using nasal provocation with ragweed antigen in 21 patients with ragweed-induced allergic rhinitis out of the ragweed season; the treatment period was 2 weeks. Symptom scores, rhinoprobe cytology, and nasal lavage fluid were collected during early and late phase periods for nasal cytokines (interleukin, 1, 4, 5, 6, and 8) and leukotriene B4 determinations using ELISA and RIA. RESULTS: Mean nasal symptom scores and sneezing frequency were consistently lower with mometasone furoate compared with placebo. Treatment was associated with a statistically significant early phase (30-minute time point) reduction in nasal lavage histamine levels compared with placebo (14.3 versus 20.2 ng/mL, P = .02). Within-treatment comparisons suggested that mometasone furoate reduced the antigen-induced late-phase response for IL-6, IL-8, and eosinophils compared with pretreatment. There were similar, but smaller, changes seen in the placebo group for these measurements. There were no statistically significant changes following antigen challenge in IL-1, IL-4, IL-5, LTB4, or in other nasal cytology parameters. CONCLUSION: These results suggest that the clinical activity of mometasone furoate nasal spray in seasonal allergic rhinitis is likely due, in part, to a reduction in the levels of histamine in nasal secretions related to the early phase response, and reductions in IL-6, IL-8, and eosinophils during the late phase response.

Adult↗
PubMed1995

Cerebral toxoplasmosis in childhood and adult HIV infection treated with 1-4 hydroxynaphthoquinone and rapid desensitization with pyrimethamine.

BACKGROUND: We describe a child and an adult infected with the human immunodeficiency virus (HIV) who developed cerebral lesions consistent with toxoplasmosis. A biopsy in the child and IgG ELISA in both patients confirmed the diagnosis of Toxoplasma gondii. The patients were initially treated with pyrimethamine, however, computerized tomography studies (CT scan) revealed progression of a left frontal and temporoparietal lesion. Therapy in the child was changed to pyrimethamine, clindamycin, and azithromycin. Repeat CT scan showed further disease progression and therapy was changed to high-dose pyrimethamine (3 mg/kg/d) and azithromycin. A subsequent CT scan disclosed further radiologic progression with increasing edema. The adult patient developed a maculopapular rash during attempted treatment with pyrimethamine. METHODS: Introduction of 2 (trans-4[4 chlorophenol] cyclohexy[3-hydroxy-1, 4 naphthoquinone] (HNPQ) an experimental antiparasitic compound previously used only in adult HIV clinical trials, was instituted in the child and rapid oral desensitization to pyrimethamine was initiated in the adult patient. RESULTS: HNPQ resulted in resolution of the cerebral lesion in the child and rapid oral desensitization to pyrimethamine produced an excellent clinical response in the adult. To our knowledge, these are the first cases of childhood and adult cerebral toxoplasmosis treated successfully with HNPQ and rapid oral desensitization to pyrimethamine. CONCLUSION: HNPQ and pyrimethamine desensitization should be considered as alternate modes of therapy in patients who become intolerant or fail to respond to traditional therapy for toxoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Augmented interleukin-6 secretion in collagen-stimulated peripheral blood mononuclear cells from patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis is an autoimmune disease that is associated with excessive fibroblast proliferation and collagen deposition in various tissues. Interleukin-6 (IL-6) is produced by fibroblasts, activated T and B lymphocytes, which maybe involved in the pathogenesis of systemic sclerosis. OBJECTIVE: This study was performed in order to determine whether IL-6 could be detected specifically in collagen-stimulated peripheral blood mononuclear cells from patients with systemic sclerosis. METHODS: We clinically evaluated seven patients with systemic sclerosis for disease duration and organ involvement and analyzed in vitro the ability of their peripheral blood mononuclear cells and those of disease-free controls, in the presence of concanavalin A, human type I collagen, and the mast cell mediator, heparin to secrete IL-6 spontaneously by a sensitive ELISA. RESULTS: Interleukin-6 production by nonspecific stimulation with concanavalin A did not differ between patients with systemic sclerosis and controls; however, collagen stimulation significantly increased IL-6 production in patients with systemic sclerosis; mean 1728 pg/mL versus a mean of 386 pg/mL in controls P = < .05). Collagen-stimulated IL-6 levels > 2000 pg/mL were obtained in 86% of patients with systemic sclerosis compared with none in the controls. In patients with systemic sclerosis with a shorter disease duration, greater spontaneous as well as collagen- and heparin-stimulated IL-6 production was observed, whereas decreased IL-6 levels were noted with longer disease duration (> 21 years). CONCLUSIONS: The results of this study suggest that peripheral blood mononuclear cells from patients with systemic sclerosis are specifically sensitized to human type I collagen to produce increased levels of IL-6, which may play a role in the pathogenesis in this fibrotic disorder.

Adult↗
PubMed1994

Increased interleukin-4 production in response to mast cell mediators and human type I collagen in patients with rheumatoid arthritis.

Mast cell synovial hyperplasia can occur in patients with rheumatoid arthritis. Histamine can accelerate synovitis and heparin can inhibit lymphocyte function. Since interleukin-4 (IL-4) can stimulate murine mast cell and IgE synthesis, we determined whether mast cell mediators and anti-IL-4 might effect lymphocyte proliferation from patients with rheumatoid arthritis. Twenty-four patients with rheumatoid arthritis and nine normal controls were evaluated by history, physical examination, physician and patient-assessed joint and allergic symptoms, and diary scores. An IL-2-driven-T cell (3H) Tdr proliferation assay with monoclonal anti-IL-4 and a sensitive ELISA were performed with isolated peripheral blood mononuclear cells (PBMC) with 10 micrograms/mL of either concanavalin A (Con A), type I human collagen, or heparin and 10(-6) M histamine. Increased lymphocyte proliferation indices with Con A (mean 21.69 +/- 4.9; 6.54 +/- 3.2 normal controls), type I human collagen (mean 2.17 +/- 0.52; 1.1 +/- .17, normal controls), histamine (mean 1.66 +/- .36; 0.62 +/- 0.08, normal controls), heparin (mean 1.61 +/- .38; 0.69 +/- .11, normal controls) occurred in peripheral blood mononuclear cells from all patients with rheumatoid arthritis compared with normal controls (P < .0236 to .0015) which was inhibited in 32% of peripheral blood mononuclear cells by anti-IL-4. Increased IL-4 ELISA levels in cultured supernatants were noted with heparin (P < .25) and collagen (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Systemic sclerosis. The role of the mast cell and cytokines.

This review of SSc has addressed the clinical features, pathophysiology involving the mast cell, T cell cytokines, and their interaction with other inflammatory cells (Figs 4 and 5). Therapeutic dilemmas and the future use of immunomodulatory therapy is also discussed. The allergist-immunologist may be the first physician to identify this insidious condition, since patients may present with cutaneous changes, swelling, pruritus, dyspnea, and with obstructive and restrictive findings on pulmonary function testing, or gastrointestinal symptoms, mimicking gastrointestinal hypersensitivity.

Cytokines↗
PubMed1991

Increased interleukin-2 production in response to human type I collagen stimulation in patients with systemic sclerosis.

Peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) produced increased amounts of interleukin-2 (IL-2), in a dose-dependent manner, in response to stimulation with human type I collagen, whereas PBMC from normal subjects did not. At a dose of 50 micrograms human type I collagen/10(6) PBMC, PBMC from SSc patients (n = 17) produced 8 times as much IL-2 as did PBMC from 16 normal subjects (P less than 0.005) and 3 times as much as did PBMC from a group of 13 rheumatoid arthritis patients (P less than 0.05). In contrast, IL-2 production by PBMC after nonspecific stimulation with the mitogen, phytohemagglutinin, did not differ among the SSc, rheumatoid arthritis, and normal control groups. Cell depletion experiments indicated that the IL-2-producing cells in SSc patients are CD4+. Thus, SSc patients have CD4 cells that are specifically sensitized to human type I collagen and can produce increased levels of IL-2. Measurement of IL-2 production stimulated by human type I collagen may be useful in evaluating disease activity, and further investigation of this process may contribute to the delineation of the pathogenesis of SSc.

Adult↗
PubMed1991

Altered T cell subpopulations and lymphocytes expressing natural killer cell phenotypes in patients with progressive systemic sclerosis.

Scleroderma (progressive systemic sclerosis [PSS]) is known to be associated with abnormal T cell immunoregulation. In the present study, we evaluated lymphocyte phenotypes in patients with PSS and normal control subjects by flow cytometry and monoclonal antibodies for total T (CD3), T suppressor (CD8), T helper (CD4), T helper-inducer (CDw29), T suppressor-inducer (CD45R), human leukocyte antigen, DR+B (CD19), DR+T, and natural killer subsets, HNK-1 (CD57) and NKH-1 (CD56) cells. Patients with PSS compared to normal subjects had significantly lower percentages of CD3+ (p less than 0.005) and CD8+ (p less than 0.05) (similar to several patients with rheumatoid arthritis also evaluated), as well as CD45R (p less than 0.05), T+DR+ (p less than 0.05), and NKH-1 (CD56) (p less than 0.0005) cells. Patients with PSS with late-limited or generalized disease had lower percentages of CD8+, CD19, NKH-1+, and CDw29, but higher percentages of CD4+, HNK-1, and CD45R cells compared to patients with early stage disease, but these results were not statistically significant. These unique alterations in patients with PSS may prove to be useful in monitoring the stage of disease activity for therapy and further define immunologic defects.

Adult↗
PubMed1991

Cellular immunity in preeclampsia: alterations in T-lymphocyte subpopulations during early pregnancy.

T-lymphocyte subpopulations were evaluated longitudinally in 62 primigravidas. Beginning early in the second trimester, women who later developed preeclampsia showed a significantly lower proportion of T-helper cells compared with those who remained normotensive (27.0 +/- 7.1 versus 34.7 +/- 7.9%; P less than or equal to .001). The decrease in the T-helper cell count occurred several weeks before the development of preeclampsia and reverted to normal 6-10 weeks postpartum.

Female↗