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Biomedical subjects

J Grossman

Publications and source records attributed to J Grossman.

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

Alterations in heart failure of cyclic AMP-dependent inotropic and lusitropic properties of cardiac and skeletal muscle.

A central working hypothesis in our laboratory is that deficient cellular cyclic AMP concentrations may be responsible, at least in part, for striated muscle dysfunction, both cardiac and skeletal, in heart failure. These results suggest that therapy aimed at restoring cyclic AMP to normal levels may be effective with regard to improving systolic and diastolic function in the heart and may decrease the development of fatigue in skeletal muscle of patients with failure. The use of cyclic AMP-dependent drugs in clinical practice has been limited by side effects associated with raising total cellular content of this cyclic nucleotide. However, evidence suggesting that separate pools of cyclic AMP may exist within the cell raises the possibility that those pools associated with excitation/contraction coupling could serve as more specific therapeutic targets.

Animals↗
PubMed1998

Continuing competence in the health professions.

The health professions are confronted with external pressures to assure the public of the continuing competence of health care providers and internal pressures for self-regulation. This article describes the forces driving continuing competence, the difficulty defining the scope of professional competencies for experienced practitioners, the difficulty creating valid measures to evaluate continuing competence, and the need for shared responsibility and collaboration among regulatory boards, professional associations, and specialty certification programs. The article presents findings from the Study of Professions, which was based on literature review, document review, and telephone interviews with key informants from 13 regulated health professions.

Certification↗
PubMed1997

Efficacy and safety of loratadine plus pseudoephedrine in patients with seasonal allergic rhinitis and mild asthma.

BACKGROUND: Antihistamines have been shown to have a variety of therapeutic effects in asthma. Although nasal obstruction may play an important role in modulating lower airway function, no prior trial has used a decongestant in combination with an antihistamine in patients with allergic rhinitis and concomitant asthma. OBJECTIVE: We sought to determine the efficacy and safety of loratadine (5 mg) plus pseudoephedrine (120 mg) (L/P) twice daily in patients with seasonal allergic rhinitis and mild asthma. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of L/P in 193 subjects during the fall allergy season. Nasal and chest symptoms, albuterol use, and peak expiratory flow rates were recorded daily for 6 weeks. Spirometry was measured at baseline and after 1, 2, 4, and 6 weeks of therapy, and health-related quality of life was rated at the beginning and end of the study. RESULTS: Total rhinitis and asthma symptom severity scores were significantly reduced in patients receiving active therapy compared with those receiving placebo throughout the 6-week study. Peak expiratory flow rates improved significantly in patients treated with L/P during weeks 2 through 6 (peak effect [mean +/- SEM]: L/P, 26.23 +/- 4.64 L/min vs placebo, 8.52 +/- 3.53 L/min, p = 0.002) as did FEV1 (peak effect [mean +/- SEM]: L/P, 170 +/- 53 ml vs placebo, 20 +/- 40 ml, p = 0.01) at all clinic visits. In addition, select measures of asthma-specific quality of life improved significantly relative to placebo. CONCLUSIONS: L/P significantly improved nasal and asthma symptoms, pulmonary function, and quality of life in patients with seasonal allergic rhinitis and concomitant mild asthma.

Adolescent↗
PubMed1997

Human T-cell leukemia virus type 1 Tax releases cell cycle arrest induced by p16INK4a.

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein causes cellular transformation by deregulating important cellular processes such as DNA repair, transcription, signal transduction, proliferation, and growth. Although it is clear that normal cell cycle control is deregulated during HTLV-1-induced cellular transformation, the effects of Tax on cell cycle control are not well understood. Flow cytometric analyses of human T cells indicate that cell cycle arrest in late G1, at or before the G1/S restriction point, by p16INK4a is relieved by Tax. Furthermore, Tax-dependent stimulation of 5-bromo-2'-deoxyuridine incorporation and transcriptional activation is inhibited by p16INK4a. This result suggests that p16INK4a is able to block Tax-dependent stimulation of DNA synthesis and cell cycle progression into S phase. In vitro binding assays with recombinant glutathione S-transferase fusion proteins and [35S]methionine-labeled proteins indicate that Tax binds specifically with p16INK4a but not with either p21cip1 or p27kip1. Furthermore, sequential immunoprecipitation assays with specific antisera and [35S]methionine-labeled cell lysates subsequent to coexpression with Tax and p16INK4a indicate that the two proteins form complexes in vivo. Immunocomplex kinase assays with cyclin-dependent kinase 4 antiserum indicate that Tax blocks the inhibition of cdk4 kinase activity by p16INK4a. This study identifies p16INK4a as a novel cellular target for Tax and suggests that the inactivation of p16INK4a function is a mechanism of cell cycle deregulation by Tax.

Animals↗
PubMed1997

One airway, one disease.

The prevalence of asthma and allergic rhinitis is increasing in the general population, and a high proportion of new patients have coexisting upper and lower airway disease. Estimates show that 60 to 78% of patients who have asthma have coexisting allergic rhinitis. During the past decade, our understanding of asthma and allergic rhinitis has evolved. The historic perspective of these allergen-induced disorders as distinct and separate entities is being displaced by current thinking that they are described better as a continuum of inflammation involving one common airway. Therefore, traditional therapies originally indicated for allergic rhinitis and asthma are being reassessed to explore their potential utility in both upper and lower airway diseases. Recently, there has been a renewed interest in the role that histamines play in lower airway disease, and interest is increasing in the theory that leukotrienes, which are far more potent inflammatory mediators than histamines, play a role in upper airway disease. Given the pivotal role that leukotrienes play as potent inflammatory mediators in the pathophysiologic state of inflammation of both airways, leukotriene receptor antagonists recently have emerged as important therapeutic advances that have potential clinical utility in both asthma and allergic rhinitis.

Asthma↗
PubMed1997

Results of the first U.S. double-blind, placebo-controlled, multicenter clinical study in asthma with pranlukast, a novel leukotriene receptor antagonist.

Pranlukast (SB 205312; ONO-1078), a potent, orally active selective cysteinyl-leukotriene receptor antagonist (LTRA), was developed in Japan for the treatment of asthma. This article reports results of the initial U.S. clinical evaluation of pranlukast. The primary objective of this multicenter study was to evaluate the safety and tolerability of pranlukast administered at doses of 337.5 mg b.i.d. and 450 mg b.i.d. in 65 patients with mild to moderate asthma. Pranlukast, a novel LTRA, is safe and well tolerated at doses of 337.5 mg b.i.d. and 450 mg b.i.d. Pranlukast has demonstrated clinical activity in patients with asthma.

Adult↗
PubMed1997

Randomized trial of zileuton in patients with moderate asthma: effect of reduced dosing frequency and amounts on pulmonary function and asthma symptoms. Zileuton Study Group.

This 6-month, randomized, multicenter study was designed to determine whether patients who had been treated with the leukotriene pathway inhibitor zileuton 600 mg four times daily (QID) for 2 months could be maintained at the same level of pulmonary function, symptom control, and beta-agonist use with less frequent dosing--first 600 or 800 mg three times daily (TID) and then twice daily (BID). A total of 278 patients with chronic asthma, ages 16 to 70, participated at 25 US centers. All had a 1-second forced expiratory volume (FEV1) of 35%-75%, reversible airway disease, and a nonsmoking history of 1 year. An 8-week open-label period (zileuton 600 mg QID) was followed by a 16-week double-blind period, in which patients who responded to the QID treatment were randomized to receive zileuton 600 or 800 mg TID for 8 weeks and then rerandomized to receive zileuton 600 or 800 mg BID for another 8 weeks. Primary outcomes were FEV1 and asthma symptom scores; secondary outcomes were peak expiratory flow rate, beta-agonist use, and asthma exacerbations requiring steroid rescue. Patients who showed improvements in lung function when treated with zileuton 600 mg QID demonstrated minimal decreases in FEV1 and comparable peak expiratory flow rates, symptom control, beta-agonist use, and systemic corticosteroid rescue when being treated with lower doses and/or less frequent doses of zileuton. Patients who demonstrate improved asthma control with zileuton 600 mg QID may be able to reduce their daily dosage and/or frequency while still maintaining the same level of symptom control.

Adolescent↗
PubMed1996

Comparative study of cetirizine and terfenadine versus placebo in the symptomatic management of seasonal allergic rhinitis.

BACKGROUND: Cetirizine is a new antihistamine with greater selectivity for the histamine H1 receptor and a low rate of hepatic metabolism. Cetirizine once daily is effective in the symptomatic treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: The efficacy and safety of cetirizine 10 mg qd, terfenadine 60 mg bid, and placebo were compared in patients with seasonal allergic rhinitis. METHODS: A multicenter, prospective, double-blind, randomized, parallel study was conducted for 2 weeks during the ragweed pollen season in patients with documented allergic rhinitis. Total symptom complex and total symptom complex plus nasal congestion scores, global efficacy, overall satisfaction, and adverse events were assessed at baseline and after 1 and 2 weeks of treatment. RESULTS: Of the 311 patients randomized to treatment, 283 completed the study. Cetirizine produced a marked improvement in symptoms scores compared with placebo after 1 week of therapy (P = .001). By the end of week 1, total symptom complex scores were improved by 37% with cetirizine compared with 29% for terfenadine, and 23% for placebo. An overall treatment effect was evident at week 1 (P = .0019), with marked differences between cetirizine and both placebo (P = .0004) and terfenadine (P = .0464) but not between terfenadine and placebo (P = .1215). A more marked treatment effect was evident during the first week of the study; this appeared to be related to spontaneous resolution of symptoms, since mean pollen counts derived for each patient declined significantly each week of the study. Therapy was generally well tolerated. Headache was the most common side effect in each group. Four patients on cetirizine, one on terfenadine, and two on placebo withdrew because of side effects. Somnolence was reported in 12 patients on cetirizine (P < .05), 2 on terfenadine, and 3 on placebo. CONCLUSION: Cetirizine produced a greater improvement in symptoms of seasonal allergic rhinitis than terfenadine or placebo.

Adolescent↗
PubMed1996

Speed of onset of action of Tilarin.

Two studies have been carried out specifically to examine the speed of onset of action of intranasal nedocromil sodium 1% (Tilarin) for the relief of symptoms due to ragweed allergic rhinitis. One, a multicentre placebo-controlled comparative study using a QID regimen, 1 spray per nostril, was designed to assess the speed of onset of action of nedocromil sodium during the first week of treatment in patients with rhinitis symptoms, and to evaluate the efficacy and safety of nedocromil sodium during 6 weeks of treatment (1). A 1-week baseline, the start of which was timed to coincide with the start of the ragweed season, was followed by 6 weeks double-blind trial treatment; only patients (n = 166) who were symptomatic at the end of baseline were included in the double-blind phase. Non-parametric analyses of all variables including a summary score (stuffy nose, runny nose, itchy nose and sneezing) showed that the onset of action of nedocromil sodium occurred on the first day of treatment. Further, patients using nedocromil sodium had less symptoms during the 10 days of peak pollen, at which time physician assessment showed reduced mucosal oedema and nasal discharge, and both patient and clinician opinions favoured nedocromil sodium. No significant adverse events were reported during this 6-week study. In the second study (2), 104 patients were randomly allocated to receive either nedocromil sodium or placebo, QID. They then spent 10 hours per day for 2 consecutive days in Iowa City Park during the peak of the ragweed season. Only patients showing significant symptoms of seasonal allergic rhinitis (SAR) during 3 hourly baseline assessments were included. Over the 2-day period, symptom scores for stuffy nose, runny nose, itchy nose and sneezing, and global symptom summary scores, were recorded at 19 hourly time points. At home in the evening, patients recorded symptom scores for the post-exposure period. In comparison with placebo, nedocromil sodium significantly improved rhinitis symptoms within 2 hours, and this reduction in SAR symptoms was maintained throughout the 2-day exposure period. Post exposure symptom summary scores were also significantly lower in patients treated with nedocromil sodium than in those patients treated with placebo. Overall, very few adverse events were reported, none of them serious. In conclusion, nedocromil sodium 1% nasal spray acts rapidly, within 2 hours on the first day of treatment, to reduce ongoing symptoms of SAR. Relief of rhinitis symptoms is maintained throughout the peak pollen period with nedocromil sodium QID, which appears to be a safe and well tolerated treatment for ragweed SAR.

Adolescent↗
PubMed1996

Corticosteroid-sparing effect of azelastine in the management of bronchial asthma.

The objective of this double-blind trial was to evaluate the corticosteroid-sparing effect of azelastine in patients with chronic bronchial asthma. A total of 193 subjects received either 6 mg of azelastine twice per day or placebo (in a 2:1 ratio) in combination with beclomethasone dipropionate (6 to 16 inhalations per day). The number of daily inhalations of the corticosteroid was reduced until maximum reduction or elimination was achieved. Patients then entered a 12-wk maintenance period, during which patients were maintained on their lowest possible dose of inhaled corticosteroid. Compared with placebo, the azelastine group had a statistically significantly greater overall median reduction in inhaled corticosteroids (4.9 puffs/day for azelastine versus 3.1 puffs/day for placebo; p < or = 0.010) during the maintenance period. The azelastine group also had a statistically significantly higher percentage of patients with reductions of > or = 50% and > or = 75% from the baseline level (53 and 31%, respectively, for azelastine versus 34 and 14%, respectively, for placebo; p < or = 0.028). The results demonstrated that azelastine, 6 mg twice per day, can reduce the need for inhaled corticosteroids in patients with chronic bronchial asthma and not lead to a deterioration in pulmonary function.

Administration, Inhalation↗
PubMed1996

Assessment of knowledge gains in proactive training for postvention.

This paper describes the development of a knowledge measure for the evaluation of a proactive training program for suicide postvention and analyses of its psychometric properties. The 25-item true-false knowledge test was administered before and after each of 12 training sessions; a total of 205 school personnel participated in the training and evaluation. Participants showed significant improvement in overall test scores and on several individual items following the training. Analyses suggested that the measure has construct validity, and that it taps a single underlying dimension. Strengths and weaknesses of the measure, and measurement issues in program evaluation are discussed.

Adaptation, Psychological↗
PubMed1995

Cetirizine in patients with seasonal rhinitis and concomitant asthma: prospective, randomized, placebo-controlled trial.

OBJECTIVE: This study explored the safety and efficacy of cetirizine for treatment of allergic rhinitis and asthma. METHODS: Daily treatment for 6 weeks with cetirizine 10 mg (93 patients) was compared with placebo treatment (93 patients) in a randomized, double-blind parallel study of patients with allergic rhinitis and asthma. This multicenter study was started just before onset of the fall pollen season. Rhinitis and asthma symptoms were assessed twice daily; spirometry was performed weekly. RESULTS: Placebo-treated patients experienced a worsening of rhinitis symptoms from baseline throughout the study, whereas cetirizine-treated patients had a significant improvement in rhinitis symptoms at week 1, which was maintained after onset of the pollen season. Asthma symptoms in the cetirizine group improved from baseline at week 1; symptoms were significantly better than in the placebo group for 5 of 6 weeks of the study. Pulmonary function did not worsen in patients taking cetirizine or placebo; there were no differences between treatments as determined by spirometry. Albuterol use was less frequent in the cetirizine-treated patients for every week of the study, but differences did not reach significance. Pseudoephedrine use was similar in both groups. More cetirizine-treated patients (90%) completed the trial than did placebo-treated patients (74%). Both treatments were well tolerated. CONCLUSION: Cetirizine 10 mg daily is safe and effective in relieving both upper and lower respiratory tract symptoms in patients with seasonal allergic rhinitis and concomitant asthma.

Adolescent↗
PubMed1995

Product characteristics and pharmacokinetics of intranasal ipratropium bromide.

The in vivo absorption potential of ipratropium bromide nasal spray was evaluated in studies involving healthy volunteers (0.03%, 0.06%, and 0.12% dosage strengths) and patients with perennial rhinitis (0.03% and 0.06%) and the common cold (0.06%). The dose used was two sprays per nostril, corresponding to a total dose of 84 micrograms, 168 micrograms, and 336 micrograms for the three dosage strengths. These studies indicate that 10% or less of active drug is absorbed systemically after nasal administration based on the amount of unchanged drug excreted in urine in a 24-hour interval. In most instances, the plasma drug concentrations were undetectable. In none of these studies did plasma ipratropium concentrations reach a level where systemic anticholinergic effects are known to occur.

Absorption↗
PubMed1995

Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications.

To study the long-term safety and effectiveness of ipratropium bromide nasal spray 0.03% in the treatment of nonallergic perennial rhinitis, we administered this medication for 1 year in an open-label trial involving 285 patients. Our intention was to maintain the highest protocol dose possible to gain a clearer picture of the long-term side effect profile of the compound. Ipratropium bromide was well tolerated with no serious side effects in this patient population. It provided a significant improvement in rhinorrhea throughout the year-long trial; only 17 of 285 patients (6%) were considered treatment failures. There was an improvement in patient quality of life, as well as a substantial reduction in the need for other medications (antihistamines, decongestants, and nasal steroids) used to treat perennial rhinitis symptoms.

Adult↗
PubMed1995

Long-term treatment of perennial allergic rhinitis with ipratropium bromide nasal spray 0.06%.

The purpose of this study was to assess the safety and efficacy of ipratropium bromide nasal spray 0.06% (aqueous solution), 84 micrograms per nostril three times a day, in reducing nasal hypersecretion in the long-term treatment of patients with perennial allergic rhinitis (PAR). This was an open-label 1-year trial. In the first 6 months all patients were treated with two puffs ipratropium bromide nasal spray 0.06%, 84 micrograms per nostril three times per day, unless they were unable to tolerate the dose. In the last 6 months the dose could be reduced to the lowest amount required to control rhinorrhea. Ninety-six patients entered the trial, and 47 completed it. Sixty-three patients completed more than 6 months of treatment. Patient and physician global evaluation suggested that ipratropium bromide nasal spray 0.06% is effective in controlling rhinorrhea associated with PAR and can contribute to control of congestion, postnasal drip, and sneezing. There was also a trend toward reduction of mucosal edema and improvement in quality of life. The most common drug-related adverse events were nasal dryness, epistaxis/nose bleed, and increased rhinitis. Most adverse events were mild and resulted in drug discontinuation in less than 10% of patients. Ipratropium bromide nasal spray was well tolerated and not associated with serious drug-related adverse events or clinically significant anticholinergic side effects. Use of ipratropium bromide nasal spray alone or with other standard medications should be considered in treating patients with PAR.

Adolescent↗
PubMed1995

A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the common cold.

Rhinorrhea is an annoying symptom of the common cold for which effective therapy is not currently available. Ipratropium bromide (IB) is an anticholinergic drug that has been shown to decrease glandular secretion when applied topically to the nasal mucosa. The purpose of this study was to compare the efficacy and safety of three doses of IB nasal spray versus either vehicle or no treatment in relieving rhinorrhea in patients with naturally acquired colds. Rhinorrhea severity was measured objectively by determining nasal discharge weights and subjectively by means of visual analog scale scores. Compared with either vehicle or no treatment, IB nasal spray produced a significant decrease in the severity of rhinorrhea. A dose of 84 micrograms (two sprays of a 0.06% solution in buffered saline solution) in each nostril was more efficacious than a 42 microgram per nostril dose and only marginally less efficacious than a 168 micrograms per nostril dose. The 84 micrograms per nostril dose also was associated with fewer adverse events than was the higher dose. None of the adverse events related to intranasal IB therapy was of a serious nature. The use of IB nasal spray appears to be a rational and safe approach to relieving rhinorrhea associated with the common cold.

Adolescent↗
PubMed1995

Strategies for school-based response to loss: proactive training and postvention consultation.

The suicide of a student or staff member is one of the most difficult crisis confronting a high school. This article describes the first year of a school-based postvention program to train and consult with crisis personnel in a structured response to this crisis. Responding to Loss (RTL) is one program offered by Community Action for Youth Survival, a project of the Ronald McDonald Children's Charities. Serving a contiguous three county urban area, this program integrates public health, epidemiological, psychiatric, and prevention paradigms to provide a comprehensive approach to the aftermath of adolescent suicide. RTL provides an interdisciplinary model for comprehensive, school-based postvention programs based on the guidelines developed by the Centers for Disease Control and national and local psychological autopsy data. It highlights the significance of responding to increased rates of suicide in minority youth, suicide witnessed by peers, and suicide victims who have dropped out of school. Organizational issues, such as systematic school entry, development of a computerized school database, proactive training, and collaboration with the offices of medical examiners and coroners, are described. Initial evaluation data from year 1 indicate significant gains in participants' knowledge and skills, as well as a high rate of consumer satisfaction.

Adolescent↗