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Biomedical subjects

G Shapiro

Publications and source records attributed to G Shapiro.

At least 37 records · Page 2Linked to original sources
PubMed1998

Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid-dependent, persistent asthma.

BACKGROUND: Inhaled glucocorticosteroids are indicated for the treatment of persistent asthma; however, many young children are unable to effectively use currently available inhalers. OBJECTIVE: We sought to evaluate the efficacy and safety of 3 different twice daily doses of budesonide inhalation suspension (Pulmicort Respules) in inhaled steroid-dependent asthmatic children. METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group study involving 178 children (age range, 4 to 8 years) at 17 centers in the United States. Budesonide inhalation suspension doses of 0.25 mg, 0.50 mg, or 1.0 mg twice daily were administered by means of a jet nebulizer and air compressor system. Efficacy was assessed by recording at home nighttime and daytime asthma symptom scores, use of rescue medication, pulmonary function tests, and treatment discontinuation because of worsening symptoms. Safety was assessed by reported adverse events and changes in baseline and adrenocorticotrophic hormone-stimulated plasma cortisol levels in a subset of patients. RESULTS: Baseline demographics, symptom scores, and pulmonary function data were similar across treatment groups. All doses of budesonide inhalation suspension were superior to placebo in improving nighttime and daytime asthma symptom scores (P </=.026), reducing use of breakthrough medication (P </=.032), and improving morning peak expiratory flow (P </=.030). The number of dropouts because of worsening asthma was also significantly fewer in the budesonide groups (P </=.015). There were no differences between doses of budesonide. Adverse events and basal and adrenocorticotrophic hormone-stimulated cortisol responses were not different between budesonide and placebo groups. CONCLUSION: Budesonide inhalation suspension, 0.25 mg, 0.50 mg, and 1.0 mg twice daily, is an effective and safe treatment for young children with inhaled steroid-dependent, persistent asthma.

Administration, Inhalation↗
PubMed1998

Participation of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation in patients with essential hypertension.

Oxidative stress and inflammation have recently been linked to endothelial damage in essential hypertension (EH). Activated peripheral polymorphonuclear leukocytes (PMN) damage surrounding tissue by releasing reactive oxygen species (ROS) and proteolytic enzymes before self-necrosis. PMN necrosis further exacerbates inflammation and promotes chemotaxis and PMN recruitment. The number and properties of PMN from untreated EH patients is the focus of the present study. Oxidative stress was assessed by measuring the rate of superoxide anion release from separated, phorbol ester-stimulated PMN and the redox state of plasma glutathione. Inflammation was estimated indirectly by determining PMN number and their in vitro survival. PMN from EH patients (n = 37) released superoxide anion faster (P < .0001) than those of normotensives (NC, n = 37), 17.7 +/- 1.14 v 9.54 +/- 0.51 nmol/10 min/10(6) cells. The redox state of glutathione was twofold higher in EH plasma (P < .02) indicating systemic oxidative stress. PMN survival in vitro correlates linearly with the rate of superoxide release (r2 = 0.60, P < .02) and PMN count of EH patients, although in the normal range, were significantly higher (P < .0001), indicating necrosis and recruitment. Hypertensive plasma significantly reduced NC PMN viability, whereas normal plasma significantly increased EH PMN viability. What our studies show is that EH is accompanied by a primed state PMN that does not correlate with the levels of blood pressure. PMN priming in EH patients reflects an in vivo exposure to a constant stimulus ending in oxidative stress, increased self-necrosis, and cell recruitment. Oxidative stress and inflammation will result in endothelial damage and atherosclerosis in the long run.

Adult↗
PubMed1997

Combined Fmoc-Alloc strategy for a general SPPS of phosphoserine peptides; preparation of phosphorylation-dependent tau antisera.

A block method for the solid phase synthesis (SPPS) of serine phosphopeptides has been developed using a combination of Fmoc and Alloc strategies. Alloc-Ser[PO(OCH2CH CH2)2] OH2, prepared in a one pot procedure from Alloc-Ser-OH, was introduced at the N-terminus of a sequence prepared by standard Fmoc-SPPS. Global cleavage of the allyl ester based protecting groups, followed by coupling of a tripeptide fragment, led to the tau phosphopeptide, 1. Using tau phosphopeptides a series of phosphorylation state-dependent antisera to human tau protein have been raised. These antisera are valuable tools for studying the tau protein which is found in an abnormal, hyperphosphorylated form in Alzheimer's disease brain.

Amino Acid Sequence↗
PubMed1996

Evaluating sol-gel ceramic thin films for metal implant applications. I. Processing and structure of zirconia films on Ti-6AI-4V.

Thin ceramic films or coatings over metallic bone-interfacing implant surfaces have the potential to improve implant performance with respect to implant fixation, wear, or corrosion. In this study, zirconia (ZrO2) thin films formed on Ti-6AI-4V using a polymeric alkoxide-based solgel process were investigated. ZrO2 films of uniform thickness on the order of 100 nm were obtained by dip coating Ti-6AI-4V samples into a zirconium propoxide containing solution using a substrate withdrawal speed ranging from 2 to 8 cm/min and a sol of nominal viscosity approximately 6 cps. These films were essentially free of surface macrodefects but had random submicron "pinholes." X-ray diffraction studies suggested that the films were at least partially crystalline, with some "metastable" cubic and/or tetragonal phases after annealing for 1 h at 500 degrees C. The demonstrated reproducibility of this approach for producing good quality ZrO2 films on Ti-6AI-4V warrants further studies to optimize processing conditions for implant applications.

Alloys↗
PubMed1996

Fluticasone propionate aqueous nasal spray compared with terfenadine tablets in the treatment of seasonal allergic rhinitis.

BACKGROUND: Comparative studies with topical corticosteroids and antihistamines for treatment of allergic rhinitis have not always demonstrated clear distinctions between the two on the basis of therapeutic efficacy. OBJECTIVE: This study was designed to compare the efficacy and tolerability of fluticasone propionate aqueous nasal spray with those of terfenadine in the treatment of seasonal allergic rhinitis. METHODS: Three hundred forty-eight patients with allergic rhinitis were given fluticasone propionate aqueous nasal spray (200 micrograms once daily), terfenadine tablets (60 mg twice daily), or placebo for 4 weeks in a multicenter, randomized, double-blind, double-dummy, parallel-group study. RESULTS: Clinician-rated total nasal symptom scores after 1, 2, 3, and 4 weeks of therapy and patient-rated total nasal symptom scores throughout treatment were significantly (p <0.05) lower in the fluticasone propionate group compared with the terfenadine group or the placebo group. Terfenadine was not statistically different from placebo on the basis of clinician-related nasal symptom scores, except for sneezing. Total nasal airflow, measured by rhinomanometry, significantly (p <0.05) improved in the fluticasone propionate group compared with the terfenadine group or the placebo group. More fluticasone propionate-treated patients compared with placebo-treated patients had reduced nasal mucosal eosinophil counts after 4 weeks of therapy (p <0.05). No serious or unusual drug-related adverse events were reported. Morning plasma cortisol concentrations after 4 weeks of therapy did not differ among groups. CONCLUSION: Fluticasone propionate aqueous nasal spray is more effective than terfenadine tablets for treatment of seasonal allergic rhinitis.

Administration, Intranasal↗
PubMed1996

Extended-release albuterol in the treatment of 6- to 12-year-old asthmatic children.

BACKGROUND: Albuterol sulfate, in the syrup and tablet form for oral administration, has been an effective treatment for adults and children with bronchial asthma. Extended-release albuterol sulfate tablets (Proventil Repetabs, Schering Corp.) provide a convenient, twice-daily dosing regimen, but are indicated only for patients > or = 12 years of age. OBJECTIVE: This study was undertaken to determine whether patients 6 to 12 years of age could be effectively and safely treated with extended-release albuterol tablets. METHODS: This was a randomized, double-blind, placebo-controlled, parallel group study of 157 patients in five centers. Patients were randomized to 4 weeks' treatment with extended-release albuterol tablets, 4 mg twice daily (q 12h), increasing up to 12 mg q 12h, or placebo. Efficacy was evaluated based on pulmonary function tests (PFTs), physician and patient evaluations, and data collected from patients' diaries on PEFR, asthma symptoms, number of nighttime awakenings, and number of tablets taken. The primary efficacy parameter was area under the curve (AUC) for FEV1, evaluated for 8 to 12 hours post-dosing. Safety was evaluated based on vital signs, electrocardiograms, and adverse events. RESULTS: Mean AUCs for FEV1 were significantly greater in the albuterol group at days 1 and 8 (P < or = .03). The albuterol group showed consistently lower severity scores for asthma symptoms. Physicians' and patients' global evaluations favored the albuterol group over the placebo group. No serious, treatment-related adverse events were reported. There were no clinically meaningful changes from baseline in either treatment group for vital signs or electrocardiograms. CONCLUSIONS: Extended-release albuterol tablets (4 mg), administered to children 6 to 12 years old in divided doses of up to 24 mg/day, improved pulmonary function and asthmatic symptoms and were well tolerated.

Adolescent↗
PubMed1996

Heparin induces apoptosis in human peripheral blood neutrophils.

Programmed cell death, by apoptosis, has been shown to play an important role in the regulation of haemopoiesis. Using trypan blue exclusion for distinguishing intact membranes, flow cytometry for detection of sub G1 peak and in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL), this study shows that heparin induces apoptosis in vitro in human peripheral blood neutrophils. The known anti-proliferative effect of heparin in several in vitro cell systems has therefore to be interpreted in the light of apoptosis. In addition, apoptosis may help explain the anti-inflammatory effects resulting from the interaction between vessel wall heparan sulphate and chemoattracted peripheral blood neutrophils.

Apoptosis↗
PubMed1996

Short-term effect of erythropoietin on T-cell mitogenic proliferation in chronic renal failure patients.

Uremic patients undergoing hemodialysis (HD) are known to be highly susceptible to infections. Recent data indicate that in addition to its well-known stimulating effects on red cell production, erythropoietin (EPO) may also have immunomodulating properties. The aim of this study was to examine the effect of EPO on lectin-induced T-lymphocyte transformation in uremic patients, as part of its effect on the immune response. Sixteen HD patients and 20 age- and sex-matched healthy controls were compared before and after 6 and 20 weeks of EPO treatment. T lymphocytes were analyzed for their mitogenic activity following treatment with phytohemagglutinin (PHA), concanavalin A (CON A) and anti-CD3 by measuring 3H-thymidine incorporation. HD patients showed reduced mitogenic responses to all mitogens tested, compared to healthy controls. During the 6 weeks of EPO administration, a significant increase in T-lymphocyte activity could be demonstrated following exposure to all three mitogens (PHA, from 32 +/- 2 to 45 +/- 8; CON A, from 11 +/- 3 to 25 +/- 9; anti-CD3, from 11 +/- 3 to 22 +/- 5, means +/- SD). This increase was augmented after 5 months of EPO treatment. We conclude therefore that EPO improves in vitro T-cell mitogenic proliferation, even after short periods of treatment.

Adjuvants, Immunologic↗
PubMed1995

Temporal variation in nasal and oral breathing in children.

The purpose of this study was to measure several variables associated with respiratory function at repeated intervals. The temporal variation of these variables was assessed within persons and within the sample population. Twenty-nine children, 18 boys and 11 girls, between the ages of 7 and 13 years of age, participated. Each subject attended three separate appointments. At each appointment, the percentage nasal breathing was measured three times with inductive plethysmography. The nasal resistance and smallest nasal cross-sectional area were measured once at each appointment with posterior rhinomanometry. The findings suggest a significant amount of variation in repeated measurements of respiratory variables. More variation was noted in measurements taken on different days than within 1 day. No correlation was present between either nasal resistance or nasal cross-sectional area in relation to percentage of nasal breathing. All subjects had a nasal component of respiration; no one was a 100% oral breather. No correlation was observed between age or gender of the subjects and any of the respiratory variables measured.

Adolescent↗
PubMed1995

The effect of nedocromil sodium on childhood asthma during the viral season.

Viral-induced symptomatic respiratory infections (SRI) frequently cause exacerbations of asthma in children. This study investigated the protective effects of 0.5% nedocromil sodium nebulizer solution given three times a day in preventing asthma exacerbations associated with SRI. Ninety-three mild-moderate asthmatic children (6 to 12 yr of age) received either 0.5% nedocromil sodium or placebo for 24 wk during the viral season. The nedocromil sodium group was symptom-free 58% of the days, and the placebo-treated patients were symptom-free 45% of the days (p = 0.027). During Weeks 1-12, significant differences favored nedocromil sodium for asthma summary score (means: nedocromil sodium = 0.61, placebo = 0.92; p = 0.026), and daytime asthma (nedocromil sodium = 0.78, placebo = 1.22; p = 0.03). Significant differences were noted during monthly intervals for cough (Weeks 1-4: nedocromil sodium = 0.61, placebo = 0.92, p = 0.027) and peak expiratory flow rate (PEFR) (nedocromil sodium 262, placebo = 254 L/min, p = 0.041 Weeks 9-12). Patients in the active treatment group reduced their need for rescue inhaled beta 2-agonist by 10%, whereas patients treated with placebo demonstrated a 24% increase. There was a strong correlation between asthma symptoms and SRI symptoms (r = 0.47; p < 0.001). During SRIs, patients in the nedocromil sodium group demonstrated more rapid resolution of asthma symptoms immediately following infection (p = 0.033 summary score, p = 0.039 sleep difficulty). No serious adverse events were noted. Nedocromil sodium did not prevent the infection or exacerbation of asthma symptoms during SRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Asthmatic Agents↗
PubMed1994

Nonradioactive assay for protein phosphatase 2B (calcineurin) activity using a partial sequence of the subunit of cAMP-dependent protein kinase as substrate.

Currently, protein phosphatase 2B (calcineurin) activity is assayed based on release of [32P]phosphate from a 19-amino acid peptide (partial sequence of the regulatory subunit of cAMP-dependent protein kinase) following its [32P]ATP phosphorylation using the catalytic subunit of cAMP-dependent protein kinase. This sensitive method consumes a large amount of radioactivity and is therefore problematic as a screening method for calcineurin inhibitors. We have developed an alternative nonradioactive enzyme assay in which both phosphorylation by protein kinase and dephosphorylation by calcineurin are monitored by the simultaneous quantitative determination of phosphorylated and non-phosphorylated peptide using HPLC on an RP18 column with uv detection. The method allows the measurement of enzyme kinetics as well as the characterization of potential inhibitors. The method is comparable in sensitivity to the radioactive assay. Since calcineurin is commercially available and the substrate can be prepared in a sufficient amount, this method can be used for screening purposes. An important advantage of this new method, due to the obviation of radioactivity, is the facilitation of kinetic determinations at high substrate concentrations and the increased specificity (better identification of substrate and product). The nonradioactive substrate is very stable and can be stored for months in comparison with the 32P-peptide, which has to be freshly prepared every few weeks due to the decay of the nuclid.

Amino Acid Sequence↗
PubMed1993

SDZ ENS 163 a novel pilocarpine like drug: pharmacological in vitro and in vivo profile.

The thiolactone analogue of pilocarpine, SDZ ENS 163, acts in vitro and in vivo as a partial agonist at M1/M3 and as an antagonist at M2 muscarinic receptors. In vitro, the properties of SDZ ENS 163 have been investigated in several functional models for muscarinic receptors: it is a full agonist at M1 (rat superior cervical ganglion, carbachol = 100%) and a partial agonist at M3 receptors (guinea pig ileum). However, the drug shows antagonistic properties at M2 receptors (rat atria). Radioligand binding studies with 3H-N-methylscopolamine (3H-NMS) using CHO cells expressing m1 or m3 receptors indicate that SDZ ENS 163 does not discriminate between m1 and m3 receptors (Ki 1.5 and 2.4 microM respectively). Regarding phosphoinositide (PI) turnover in A9L cells, SDZ ENS 163 is a partial agonist at m1 receptors. In ex vivo neurochemical studies in rats SDZ ENS 163 displays effects characteristic of muscarinic antagonists regarding the turnover of ACh which is increased in the brain. At a similar dose-range SDZ ENS 163 accelerates PI metabolism in the rat brain in vivo and increases the energy of the low frequency band (2-5 Hz) in the rat hippocampal EEG. These effects observed in vivo are consistent with postsynaptic M1 agonistic and presynaptic M2 antagonistic activities. Since SDZ ENS 163 at centrally active doses exerts no peripheral cholinergic effects, it may be useful for the symptomatic treatment of Alzheimer's disease.

Acetylcholine↗