[Optimization of asthma control with fluticasone/salmeterol (seretide) combination: new clinical data].
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Albuterol↗
Biomedical subjects
G Braunstein
Publications and source records attributed to G Braunstein.
Evidence for multidrug resistance-1 P-glycoprotein-dependent regulation of cellular ATP permeability.
The mechanisms responsible for regulating epithelial ATP permeability and purinergic signaling are not well defined. Based on the observations that members of the ATP-binding cassette (ABC)1 family of proteins may contribute to ATP release, the purpose of these studies was to assess whether multidrug resistance-1 (MDR1) proteins are involved in ATP release from HTC hepatoma cells. Using a bioluminescence assay to detect extracellular ATP, increases in cell volume increased ATP release approximately 3-fold. The MDR1 inhibitors cyclosporine A (10 microm) and verapramil (10 microm) inhibited ATP release by 69% and 62%, respectively (p < 0.001). Similarly, in whole-cell patch-clamp recordings, intracellular dialysis with C219 antibodies to inhibit MDR1 decreased ATP-dependent volume-sensitive Cl- current density from -33.1 +/- 12.5 pA/pF to -2.0 +/- 0.3 pA/pF (-80 mV, p < or = 0.02). In contrast, overexpression of MDR1 in NIH 3T3 cells increased ATP release rates. Inhibition of ATP release by Gd3+ had no effect on transport of the MDR1 substrate rhodamine-123; and alteration of MDR1-substrate selectivity by mutation of G185 to V185 had no effect on ATP release. Since the effects of P-glycoproteins on ATP release can be dissociated from P-glycoprotein substrate transport, MDR1 is not likely to function as an ATP channel, but instead serves as a potent regulator of other cellular ATP transport pathways.
3T3 Cells↗
The pressurized metered dose inhaler (pMDI) remains the most commonly prescribed device for the delivery of inhaled asthma medications.
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Administration, Inhalation↗
What internists need to know: core competencies in women's health. ABIM Subcommittee on Clinical Competence in Women's Health.
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Age Factors↗
Selective recruitment of eosinophils by substance P after repeated allergen exposure in allergic rhinitis.
We have investigated the nasal response to substance P after pollen exposure in seasonal allergic rhinitic patients. Seven patients with strictly seasonal allergic rhinitis were studied during the pollen season, 24 h after nasal challenge with pollen. They received increasing doses of nebulized substance P (0 to 80 nmol) in each nostril. Responses were assessed by measurement of nasal airway resistance by posterior rhinomanometry and quantification of albumin, histamine, and inflammatory cells in the nasal lavage fluid. Nasal airway resistance increased in a dose-dependent manner after substance P challenge. Protein and albumin in nasal lavage fluids increased after administration of substance P: from 2.6 +/- 0.3 to 6.8 +/- 1.1 mg for protein (P < 0.01) and from 0.2 +/- 0.1 to 3.1 +/- 0.6 mg for albumin (P < 0.02). Expressed as a percentage of total protein, albumin increased from 10.5 +/- 3.6% to 39.9 +/- 3.5% (P < 0.02), suggesting occurrence of plasma leakage. No histamine release was observed after challenge with substance P. Total cell counts significantly increased from 11.4 +/- 2.4 to 41.8 +/- 17.3 x 10(3) cells/ml after substance P (P < 0.05). Eosinophils were already numerous before substance P challenge (2.1 +/- 0.7 x 10(3) cells/ml), and the number of eosinophils markedly increased in all patients after substance P (for the whole group, 25.8 +/- 13.3 cells/ml, P < 0.05). In contrast, the number of neutrophils only slightly increased in five patients, and changes did not reach significance for the group as a whole. Our results show that substance P induces nasal obstruction and albumin extrusion in allergic rhinitic patients after repeated pollen exposure. These vascular phenomena are associated with recruitment of eosinophils. Since substance P is known to be released after nasal allergen challenge, our data suggest a role for substance P in the chronic eosinophilic inflammation of the nasal mucosa observed in symptomatic allergic rhinitis.
Administration, Intranasal↗
Performance on the internal medicine second-year residency in-training examination predicts the outcome of the ABIM certifying examination.
For 223 residents from eight teaching hospitals, the results of the second-year in-training examination and the first-sitting certifying examination of the American Board of Internal Medicine were highly correlated. The results of the in-training examination can serve residents as an important measure of their preparedness for certification and can be useful in identifying the need for more intensive self-study strategies during the subsequent one and a half years.
Certification↗
Do nasal mast cells release histamine on stimulation with substance P in allergic rhinitis?
The effects of nasal administration of increasing doses of exogenous substance P have been studied in patients with allergic rhinitis treated with placebo or with the H1 antagonist cetirizine (10 mg twice daily for 3 days). Responses to substance P were assessed by posterior rhinomanometry (measuring nasal airway resistance) and by measure of histamine, protein and albumin production and cell recovery in nasal lavage fluids before and after challenge. Substance P induced a dose-dependent increase in nasal airway resistance which was similar after treatment with either cetirizine or placebo (maximal increase in nasal airway resistance was 4.2-fold greater than the baseline with the placebo and 4.7-fold greater than the baseline with cetirizine). No histamine release was observed. Similar increases in protein and albumin production were observed after stimulation with substance P along with the placebo (protein: from 0.35 +/- 0.11 to 3.31 +/- 0.62 mg and albumin: from 0.09 +/- 0.04 to 2.08 +/- 0.39 mg) and when combined with cetirizine treatment (proteins: from 0.42 +/- 0.09 to 3.62 +/- 0.77 and albumin: from 0.17 +/- 0.04 to 2.19 +/- 0.51 mg). After stimulation with substance P, percentages of neutrophils recovered in nasal fluids increased from 26.2 +/- 11.5 to 54.5 +/- 9.5 with the placebo and from 35.5 +/- 11.0 to 53.6 +/- 9.5 with cetirizine. Eosinophils were inconsistently found after substance P stimulation during both treatments. In conclusion, nasal response to substance P is not modified by cetirizine which suggests that the effect of substance P is not secondary to histamine release in the nose in man.
Adult↗
[Inhaled corticotherapy sparing effect by sodium nedocromil in moderate to severe asthma].
BACKGROUND: The increased use of high dose inhaled steroid in the treatment of asthma has revealed the risk of dose-dependent side effects. Nedocromil sodium is a non steroidal agent with anti-inflammatory properties. OBJECTIVE: To demonstrate whether nedocromil sodium may have some therapeutic benefit in asthmatic patients treated with high dose inhaled steroids and whether it has an inhaled steroid sparing effect. PATIENTS: 134 adults with moderate to severe asthma not adequately controlled with high dose inhaled steroids (750 to 1,500 micrograms/day). METHOD: After a two week baseline period, patients were randomized to receive either nedocromil sodium (4 mg qid) or placebo for 24 weeks in a double blind fashion. During the first 12 weeks of treatment, the dose of inhaled steroid was maintained constant whereas it was altered during the last 12 weeks according to asthma scores. RESULTS: Among 108 patients reaching the reduction phase, a decrease of 250 micrograms of inhaled steroid or more was possible in 79% of patients on nedocromil sodium and in 60% of patients on placebo (p < 0.03). Symptoms scores were improved on both treatments during the 12 first weeks, more on nedocromil sodium than on placebo, treatment difference reaching significance for daytime asthma (p < 0.02). FEV1 improved during the trial for patients on nedocromil (from 69 +/- 18% to 74 +/- 21%; p < 0.005) whereas it did not for those on placebo. CONCLUSION: Nedocromil sodium is effective in improving moderate to severe asthma in addition to inhaled steroid and has some steroid sparing effect in patients treated with high dose inhaled steroid.
Administration, Inhalation↗
Inhibition of histamine-induced nasal obstruction by cetirizine in allergic rhinitis.
This double-blind randomized crossover placebo-controlled study was designed to assess objectively the nasal antihistamine effect of cetirizine in patients with allergic rhinitis and control subjects. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0; 0.04 to 1.28 mg/nostril) in six patients with allergic rhinitis and six control subjects on cetirizine (2 x 10 mg daily for 3 days) or placebo. Sneezings were counted and nasal obstruction was assessed by subjective scoring and by objective measurement of nasal airway resistance by posterior rhinomanometry. Histamine induced sneezing and a dose-dependent increase in nasal airway resistance and in perceived sensation of obstruction. Responses were greater in patients with allergic rhinitis compared with controls, although of borderline significance for nasal obstruction. Cetirizine totally abolished sneezing and significantly reduced increase in nasal airway resistance and perceived sensation of nasal obstruction both in normal and rhinitic subjects. Our results demonstrate by an objective measurement the nasal antihistamine effect of cetirizine. We propose this simple provocation test to assess the time-course of the effect of antihistamines and to compare the relative potency of related compounds.
Adult↗
[The Turbuhaler].
Metered-dose inhalers have several caveats. They contain fluorocarbons which are considered to be responsible for the depletion of the ozone layer in the stratosphere. Inhalation through metered-dose inhalers can cause cough and bronchospasm. Moreover, metered-dose inhalers are difficult to handle. Errors in using these devices have been described in 30% to 70% of subjects, the incoordination between the actuation of the device and the inhalation being the most common. The author describes the Turbuhaler made of three parts (a reservoir for the powder, the dosing chamber and the inhalation channel) and the way it works. It has been shown that the efficacy of terbutaline (in mg/mg) is equivalent with the Turbuhaler and the metered-dose inhaled. Several studies that are reviewed by the author show that the Turbuhaler is the inhalation device that is the easiest to use.
Adult↗
Cubic phase in the Y-Ba-Cu-O system.
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Journal Article↗
Isoproterenol activation of prostaglandin production in guinea-pig airway muscle preparations from immature and mature animals.
The aim of this study was to evaluate the capacity of isoproterenol to activate the cyclooxygenase pathway in tracheal and bronchial tissues derived from immature (198 +/- 4 g, N = 12) and mature (997 +/- 28 g, N = 12) guinea-pigs. Immunoreactive PGE2 and PGF2 alpha were measured in bath samples obtained during resting tone and when tissues had been maximally contracted or relaxed. Results from these experiments showed that histamine contractions were significantly greater in tracheal than in bronchial preparations, an effect which was independent of age. Isoproterenol and theophylline were equiactive in relaxing basal tone of tracheal and bronchial tissues when data for each tissue type was compared with results in the different age groups. This effect was also independent of age. When results were normalized for tissue wet weights, the quantities of prostaglandins produced in tissues from mature guinea-pigs were less than those generated in similar tissues derived from immature animals. These data indicate significant modifications in basal prostaglandin production in tissues from immature and mature guinea-pigs. In addition, isoproterenol stimulated prostaglandin production in airways from immature and mature animals whereas theophylline did not alter the basal production.
Aging↗
Terbutaline powder in asthma exacerbations.
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Administration, Inhalation↗
Clinical and inflammatory responses to exogenous tachykinins in allergic rhinitis.
Our purpose was to characterize the tachykinin receptor type involved in nasal obstruction to exogenous substance P in rhinitic patients. We also attempted to assess biochemical and cellular events associated with this response. Nasal challenges were performed in seven patients with allergic rhinitis. They received increasing doses (10 to 80 nmol) of substance P, of neurokinin A, of the N-terminal fragment of substance P, substance P(1-9), and of saline on 4 different days separated by 14 days. Nasal airway resistance (NAR) increased in a dose-dependent manner on substance P. Maximal increase reached 4.5-fold basal NAR. Response to neurokinin A was significantly lower (less than 2-fold basal NAR). No effect was observed on substance P(1-9) and saline. This order of activity [substance P much greater than neurokinin A greater than substance P(1-9) = saline] indicates an NK1 receptor-mediated mechanism inducing local vasodilation. No histamine release was found after any of the four challenges. Proteins significantly increased in nasal lavage fluid on both substance P and neurokinin A, whereas substance P(1-9) and saline had no effect. The percentage of albumin increased in nasal lavage fluid from 30 to 50% of total proteins on substance P and neurokinin A, indicating microvascular leakage. Polymorphonuclear cells significantly increased from 9 to 36% on substance P, from 13 to 49% on neurokinin A, and from 13 to 55% on substance P(1-9). Eosinophils increased in five patients on substance P (from 0.1 to 5% for the group), in three patients after neurokinin A, and in two after substance P(1-9).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Randomized evaluation of two teaching methods using aerosol dosers].
The administration of antiasthmatic drugs by pressurised aerosols is limited by the difficulties of the inhalation technique. The development of teaching aids may help their use. The aim of this study was to assess and to compare 2 educational methods of inhalation: a standardised inhalation card and a video film. Forty five asthmatic patients who were poor coordinators were separated randomly into 3 groups: education by card, education by video film and a third group served as a positive control and had been educated by video film and also an additional education in a room set aside for teaching inhalation techniques. The FEV1 (VEMS) had been read before the education session and 15 days after, and on each occasion before and after inhalation of a beta-2-mimetic. An inhalation score was measured on the same date. The 2 educational methods enabled an improvement in the score to be shown which was more marked in the video group than in the card group. The VEMS (mean + or - one standard deviation) before inhalation of beta-2-mimetics was significantly superior to J15 in relation to J1 in the video group (2.38 +/- 0.84 and 1.89 +/- 0.61 respectively) and in the control group (2.05 +/- 0.81 and 1.71 +/- 0.66 respectively) whilst the values did not differ in the card group (2.09 +/- 0.63 and 2.01 +/- 0.7 respectively). This study suggests the value of education of these patients and the superiority of video education in relation to reading a standardised card in the optimisation of treatment administered by the inhaled route.
Adolescent↗
[Inhalation chambers].
Since the last 30 years metered-dose pressurised aerosols have largely contributed to the treatment of asthma with inhaled beta-2 stimulants and corticosteroids. Two problems, however, are associated with these aerosols: (1) small amounts of active substance are deposited in the lungs and larger amounts in the mouth and pharynx; (2) aerosols are uneasy to use because of lack of coordination between actuation and inhalation and absence of apnoea at the end of inspiration. An elegant solution of these problems is the inhalation chamber: a reservoir inserted between the patient's mouth and the aerosol, which increases the lung deposition, reduces the ENT deposition and makes coordination unnecessary. The inhalation chamber is primarily indicated for patients with poor coordination. When beta-2 stimulants are inhaled the therapeutic benefit can be measured by a gain of efficacy in poor coordinators. When corticosteroids are inhaled the benefit is measured by a better local tolerance and, to some extent, by a gain in therapeutic effectiveness; the inhalation chamber here is indicated for patients with ENT complications (e.g. candidiasis, dysphonia) or for the most severe cases requiring high-dose therapy. The introduction of inhalation chamber must be regarded as an improvement in the management of asthma, taking into account the potential risk of poor compliance, and in such cases the development of powder inhalers may be envisaged.
Administration, Inhalation↗
Thallium-201 scintigraphy in differentiated thyroid cancer: comparison with radioiodine scintigraphy and serum thyroglobulin determinations.
The role of thallium-201 (201TI) scintigraphy in the follow-up evaluation of differentiated thyroid carcinoma (DTC) is controversial. Desirable characteristics of 201TI scintigraphy including the potential for no thyroid hormone withdrawal, immediate imaging postinjection, and low radiation burden relative to iodine-131 (131I) suggests it is logistically superior to 131I scintigraphy. Fifty-two patients with DTC were evaluated with 201TI and 131I neck and chest images, and serum thyroglobulin measurements. In post-thyroidectomy and pre-131I ablation therapy patients, very little 201TI accumulation was noted within the thyroid bed, with discordantly increased 131I activity and normal serum thyroglobulin measurements. Twenty-nine percent of patients evaluated after 131I ablative therapy had elevated serum thyroglobulin levels and localized neck and chest abnormalities on 201TI scan that were not seen on 131I studies. Our data suggest that 201TI is more sensitive than 131I diagnostic (5 mCi) studies for detection of DTC, while 131I is more sensitive in detecting normal residual thyroid tissue postoperatively.
Adenocarcinoma↗
Cytogenetic characterization of renal cell carcinoma in von Hippel-Lindau syndrome.
We report the case of a 26-year-old man with von Hippel-Lindau syndrome (VHL) and two renal cell carcinomas (RCC), one of which was studied cytogenetically. Chromosomal analysis of the RCC showed a translocation that involved chromosomes 3 and 8 with subsequent loss of the derivative chromosome 8. The patient's peripheral lymphocytes showed a normal karyotype that indicated that there was not a constitutional chromosomal translocation. This is the third reported case of RCC in a patient with VHL in which loss of a portion of the short arm of chromosome 3 (3p) has occurred. Similar chromosomal changes that involve 3p have been reported in both familial and sporadic cases of RCC and have led to speculation that a tumor suppressor gene may be located in this region. Cytogenetic characterization of renal tumors could assume increasing significance in the diagnosis and classification of RCC and potentially may guide therapy. These studies may also lead to a better understanding of the biologic behavior of RCC and result in more informed patient evaluation and counseling.
Adult↗