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Biomedical subjects

G Braunstein

Publications and source records attributed to G Braunstein.

At least 19 recordsLinked to original sources
PubMed1994

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↗
PubMed1994

[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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

[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↗
PubMed1991

[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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

Photodynamic therapy of choriocarcinoma transplanted to the hamster cheek pouch. I. Intraperitoneal photosensitization.

Human choriocarcinoma (JEG-3) cells were transplanted into the cheek pouch of hamsters and treated with photodynamic therapy. Twenty-four hours after intraperitoneal injection of the photosensitizer dihematoporphyrin ether (DHE), 20 tumors were illuminated with 100 J/cm2 of 630-nm light from an argon pumped dye laser. Contralateral tumors served as controls. Dihematoporphyrin ether alone had no effect on tumor growth, while laser light in the absence of DHE resulted in complete regression in 3 tumors (17%), and partial regression in 4 of 18 tumors (22%), possibly due to hyperthermia, P greater than 0.10. Using the combination of DHE plus light (photodynamic therapy) complete tumor regression was noted after a single treatment in 11 of 20 tumors (55%, mean tumor volume 279 mm3) and in 7 of 7 tumors (100%) after a second treatment. Two of 20 tumors were not retreated. Therefore, 18 of 20 tumors (90%) were grossly destroyed by one or two photodynamic treatments. Contralateral control tumors continued to grow to a median volume of 990 mm3 (chi 2 = 26.30, P less than 0.0001). Choriocarcinoma transplanted into the hamster cheek pouch is highly responsive to photodynamic therapy.

Animals↗
PubMed1988

[RU 41740: mode of action on the respiratory system].

Alveolar macrophages are issued from circulating monocytes and stand at the cross-road of all antixenic defences of the lung. They are obtainable for in vitro studies by alveolar lavage, and their properties have been determined during the last few years. Synthesis activity and secretion of inflammation mediators, enzymes, enzyme inhibitors, free radicals and factors of cell co-operation are responsible for the defence of the lungs. The phagocytic activities of alveolar macrophages and their ability to promote cell co-operation make them cells that are capable of antigenic presentation, a fundamental step in the development of immunological defence mechanisms. The effectiveness of RU 41740 in respiratory infections is due to its action on deep lung cells, and in particular alveolar macrophages. This compound has been shown to recruit cells (which is a sign of macrophage activation), to increase enzymatic activities, phagocytosis and release of free radicals and to promote interleukine 1 secretion. These activities have been demonstrated in in vitro studies as well as in animal and human studies.

Adjuvants, Immunologic↗
PubMed1988

Multiple markers for lung cancer diagnosis: validation of models for localized lung cancer.

Sera from 71 patients with localized lung cancer, from 70 normal controls, and from 73 patients with benign lung diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen (CEA). Individual markers were studied, and optimal combinations of markers were sought for discriminating patients with localized lung cancer from normal controls and from patients with benign lung disease. Both logistic regression and recursive partitioning methods for discrimination were tried. The best rules involved only CEA and ferritin for discriminating patients with lung cancer from normal controls, and CEA and age for discriminating patients with lung cancer from those with benign lung diseases. The performance of these rules was validated on an independent serum panel containing sera from 56 patients with localized lung cancer, 75 normal controls, and 75 patients with benign lung diseases. Three rules designed to achieve 95% specificity against normal controls attained 14%-36% sensitivity for localized lung cancer in the validation panels, whereas three rules designed to achieve 95% specificity against benign lung diseases attained 30%-39% sensitivity. Some aspects of potential clinical applications are discussed.

Age Factors↗
PubMed1988

Evidence that the histamine sensitivity and responsiveness of guinea-pig isolated trachea are modulated by epithelial prostaglandin E2 production.

1. Guinea-pig isolated tracheal preparations in which the epithelium had been removed exhibited a greater contractile response to histamine (intact: 1.91 +/- 0.12 g; n = 6 and rubbed: 2.76 +/- 0.15 g; n = 11; P less than 0.001). The histamine sensitivity (pD2 value) of these preparations was also significantly greater (intact: 4.80 +/- 0.04 and rubbed: 5.40 +/- 0.08; P less than 0.01). 2. Indomethacin suppressed the basal tone of both intact and rubbed preparations but was more effective in the former tissues (intact: -0.70 +/- 0.14 g; n = 22 and rubbed: -0.17 +/- 0.05 g; n = 12; P less than 0.02). 3. Arachidonic acid (AA; 10 microM) suppressed the basal tone of intact tissues but contracted such preparations following indomethacin treatment (1.7 microM; 30 min). However, in rubbed tissues AA (10 microM) induced a contraction which was attenuated following indomethacin treatment. 4. Prostaglandin E2 (PGE2; 0.01 and 0.1 microM) suppressed the basal tone of intact preparations and always evoked contraction of rubbed tissues. Following indomethacin treatment PGE2 (0.01 and 0.1 microM) generally evoked spasm of intact and rubbed tissues while at higher concentrations (1 microM) relaxant effects were observed. 5. Removal of the epithelium did not alter the relaxant effect of PGE2 (pD2 value) on histamine (50 microM)-contracted tissues (intact: 6.86 +/- 0.08 and rubbed: 7.10 +/- 0.3; n = 4; P greater than 0.1). 6. In rubbed preparations treated with indomethacin, PGE2 (0.01 and 0.1 microM) evoked spasm. However, when added to preparations contracted with 5 microM histamine, PGE2 always caused relaxation. 7. The release of immunoreactive PGE2 by rubbed preparations during histamine and/or AA stimulation was significantly less than that produced by intact stimulated tissues. 8. Exogenous PGE2 (0.01-1 microM) decreased the maximal response and sensitivity of rubbed tracheal preparations to histamine. 9. These results suggest that release of an epithelial derived cyclo-oxygenase product, namely PGE2, may regulate basal tone, histamine response and sensitivity of the guinea-pig isolated trachea.

Animals↗
PubMed1988

Local cellular and humoral responses to antigenic and distilled water challenge in subjects with allergic rhinitis.

We studied nasal responses to allergen, saline, and distilled water aerosol in 7 subjects with allergic rhinitis to determine whether they caused a similar release of mediators and influx of inflammatory cells into the nasal lumen. The subjects were challenged first with allergen and then with aerosols of distilled water and of normal saline in random order on separate days. We measured nasal airway resistance (Rn) by posterior rhinomanometry, measured the concentrations of protein, histamine, leukotrienes (LT) B4, C4, and D4, and platelet-activating factor (PAF-acether) and performed total and differential cell counts in nasal lavage fluid obtained before and after each challenge. Allergen challenge provoked a 2-fold or greater increase in nasal airway resistance in all subjects (mean increase = 12.2-fold). This response was associated with significant increases in protein, histamine, LTB4, and sulfidopeptide leukotrienes. 2-lyso-PAF-acether increased significantly, indicating activation of phospholipase A2, but PAF-acether was detected in only one subject. The total cell count increased from 55 +/- 44 x 10(3)/ml to 200 +/- 168 x 10(3)/ml; polymorphonuclear neutrophils increased from 11 +/- 22 x 10(3)/ml to 108 +/- 96 x 10(3)/ml, and eosinophils increased from 1.3 +/- 1.8 x 10(3)/ml to 10.6 +/- 15.3 x 10(3)/ml (p less than 0.05). Saline insufflation provoked insignificant changes in mean Rn, in the levels of protein and all inflammatory mediators, and in the number and types of cells in nasal lavage fluid. Distilled water insufflation also provoked an insignificant increase in mean Rn, but there was a 14-fold increase in one subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗