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Biomedical subjects

S R Findlay

Publications and source records attributed to S R Findlay.

At least 19 recordsLinked to original sources
PubMed1992

Ipratropium bromide aqueous nasal spray for patients with perennial allergic rhinitis: a study of its effect on their symptoms, quality of life, and nasal cytology.

Ipratropium bromide is an anticholinergic agent with topical activity that has been studied as a freon-propelled aerosol spray for therapy of nonallergic rhinitis. This is the first report of its use both as an aqueous nasal spray and in perennial allergic rhinitis. In this study 123 patients who had symptoms of perennial allergic rhinitis were randomized to receive ipratropium bromide 21 micrograms or 42 micrograms or placebo, one spray per nostril three times a day for 4 weeks. Patients maintained daily diaries of duration and severity of nasal symptoms and were evaluated weekly. Mean duration and severity of rhinorrhea was decreased in both ipratropium bromide treatment groups by comparison with placebo, with consistently greatest improvement in the group treated with ipratropium bromide 42 micrograms per nostril three times a day. No statistically significant differences occurred among treatment groups in duration or severity of postnasal drip, congestion, or sneezing. Seventy percent of patients treated with 42 micrograms of ipratropium bromide thought it had good or excellent effect on rhinorrhea (p less than 0.05 vs placebo); significantly more patients thought that it had improved the quality of life (p = 0.02). No changes occurred in nasal cytology, and no significant local or systemic adverse events occurred. These data indicate that ipratropium bromide significantly decreases the rhinorrhea of perennial allergic rhinitis.

Administration, Intranasal↗
PubMed1992

Effect of the oral leukotriene antagonist, ICI 204,219, on antigen-induced bronchoconstriction in subjects with asthma.

We studied the effect of a single oral dose of ICI 204,219 on subject response to bronchoprovocation and quantitative skin testing with standardized allergen (cat dander). Cat-allergic male subjects with asthma entered the double-blind, randomized, placebo-controlled, crossover study. Each subject received a 40 mg dose of ICI 204,219 or placebo on study days separated by at least 10 days. After dosing, each subject underwent bronchoprovocation with cat allergen until a provocative dose of allergen caused a 20% decrease in FEV1 or a maximum dose of 30,000 AU/ml was reached. Fifteen subjects entered and 13 completed the study. No significant shift in the dose-response curve of the quantitative skin test occurred in any subject. A mean tenfold increase in the interpolated provocative concentration causing a 20% decrease in FEV1 was observed between ICI 204,219 (6996 +/- 3204 AU/ml) and placebo (460 +/- 98 AU/ml). Eight of 12 subjects required more antigen to provoke a bronchoprovocation response after dosing with ICI 204,219 than that required with placebo (range, threefold to 30-fold), three demonstrated no difference (less than twofold), and one subject required less antigen after ICI 204,219 (sevenfold less). Area under the curve measurements were significantly different (p less than 0.05) between ICI 204,219 and placebo for the fixed time from the end point of the allergen bronchoprovocation to 5 hours after provocation. In conclusion, this trial demonstrates that a single oral dose of ICI 204,219 antagonizes the bronchoconstriction induced by inhaled cat allergen.

Administration, Oral↗
PubMed1992

Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily.

Fluticasone propionate was compared with beclomethasone dipropionate for the treatment of allergic rhinitis in a multicenter, double-blind, randomized, placebo-controlled study during the mountain cedar (Juniperus ashei) pollination season in central Texas. Adults (n = 313) with moderate to severe symptoms were treated with fluticasone propionate aqueous nasal spray 200 micrograms once a day or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice a day or placebo for 2 weeks. Fluticasone propionate administered once daily and beclomethasone dipropionate administered twice daily were equally effective as assessed by clinician- and patient-rated scores for nasal obstruction, rhinorrhea, sneezing, and nasal itching throughout the treatment and follow-up periods. Both regimens were more effective than placebo. Adverse events were related to topical administration and were similar in frequency and nature in all three treatment groups. Fluticasone propionate and beclomethasone dipropionate displayed a similar safety profile that did not differ from placebo. We conclude that fluticasone propionate aqueous nasal spray administered as 200 micrograms once daily in the morning is as safe and effective as beclomethasone dipropionate aqueous nasal spray administered as 168 micrograms twice daily for seasonal allergic rhinitis.

Administration, Topical↗
PubMed1992

Adrenal function in adult asthmatics during long-term daily treatment with 800, 1,200, and 1,600 micrograms triamcinolone acetonide. Multicenter study.

A study to assess the effect of the long-term use of triamcinolone acetonide (TA) on adrenal function was conducted with 143 male and female patients with asthma who were randomly assigned to receive 800, 1200, or 1,600 micrograms of TA daily for six months. Adrenal function was assessed prior to treatment and after two weeks and one, three, and six months of TA use. The effect of TA was evaluated by measuring plasma cortisol levels just prior to and 30 min after a bolus IV injection of 0.25 mg cosyntropin. Adrenal suppression was assumed if the plasma concentration of cortisol did not increase by at least 7 micrograms/dl from the prestimulation value, and remained below 18 micrograms/dl 30 min after the cosyntropin injection. Urine collected for 24 h prior to each cosyntropin stimulation was assayed for free cortisol and related metabolites to confirm suppression. Although all treatment regimens caused some reduction in the 24-h excretion of corticosteroid products, none of the mean values was below the normal ranges. The mean data indicate that TA had no significant effect on adrenal function at any dose or at any time for the patients overall. Individually, three patients exhibited some reduction in adrenal function.

17-Hydroxycorticosteroids↗
PubMed1986

Comparison of histamine release effects of ionic and non-ionic radiographic contrast media.

Histamine release may underline the side effects (particularly anaphylactoid) of radiographic contrast media. To study the histamine-releasing properties of radiographic contrast media, this study measured the in vitro release of histamine from human basophils incubated with diatrizoate, a standard ionic radiographic contrast agent, and with iopamidol, a newly developed non-ionic contrast agent. The basophils were separated from blood obtained from 16 patients scheduled for coronary angiography. For both diatrizoate and iopamidol, the concentration of histamine released varied as the concentration of radiographic contrast agent was increased from 0.075 M to 0.50 M. At the higher concentrations tested, the percent of histamine released by iopamidol was about half that released by diatrizoate (p less than 0.05). These data suggest that the use of non-ionic contrast media may involve less patient risk from the histamine-mediated allergic and/or hemodynamic side effects associated with radiographic contrast procedures.

Diatrizoate↗
PubMed1984

Radiographic contrast media-induced noncardiogenic pulmonary edema: case report and review of the literature.

Adverse reactions are a frequent complication of exposure to radiographic contrast media (RCM). These reactions are most often anaphylactoid in nature and are characterized by the occurrence of urticaria, angioedema, bronchospasm, and shock. In patients who have had an anaphylactoid reaction to RCM and in whom reexposure is indicated, various pretreatment protocols have been developed to mitigate the risk for recurrence. We report the case of a 46-year-old man who, while undergoing cardiac catheterization, developed noncardiogenic pulmonary edema. This is the first reported case of the occurrence of noncardiogenic pulmonary edema secondary to RCM documented with Swan-Ganz data. In addition, our patient developed noncardiogenic pulmonary edema despite pretreatment with prednisone and diphenhydramine, administered because of a past history of a similar reaction. Potential mechanisms for such a reaction are discussed.

Cardiac Catheterization↗
PubMed1984

Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses.

The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol. Nine active-treatment subjects who received a mean cumulative dose of cat allergen, 1 of 10.9 units, and eight placebo-treatment subjects completed the study. Active treatment resulted in significant reductions in bronchial sensitivity (p less than 0.05) and prick test titer (p less than 0.01). In addition, active treatment resulted in a significant delay in the onset of ocular (p less than 0.05) and pulmonary (p less than 0.02) symptoms on exposure to living cats. Significant increases in IgG antibody to cat allergen 1 (p less than 0.001) and cat albumin (p less than 0.01) also occurred with active treatment. There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils. These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations.

Allergens↗
PubMed1984

In vitro basophil histamine release induced by mannitol in a patient with a mannitol-induced anaphylactoid reaction.

Anaphylactoid reactions in man are associated with the infusion of diagnostic and therapeutic agents. The etiology of such reactions remains unknown, but clinically they have the signs and symptoms that mimic those associated with in vivo histamine release. We report that the leukocytes of a patient who suffered an anaphylactoid reaction associated with the infusion of mannitol repeatedly released histamine in vitro when the leukocytes were challenged with low concentrations of mannitol (less than 0.1 M). In 44% deuterium oxide buffer, the patient's cells were tenfold more reactive to mannitol as compared to normal leukocytes and were pharmacologically modulated in a fashion similar to IgE-dependent release. The temperature optimum for this nonhyperosmolar (less than 0.1M) mannitol-induced, deuterium oxide-dependent release was the same as that for IgE-dependent release. Desensitization of the patient's cells with anti-IgE completely suppressed release induced by low concentrations of mannitol but did not affect the hyperosmolar (greater than 0.1M) mannitol-induced release of basophil histamine. These studies suggest that patients experiencing anaphylactoid reactions may be identified by use of in vitro basophil histamine release.

Anaphylaxis↗
PubMed1984

Anti-immunoglobulin induced histamine release from naturally abundant basophils in the snapping turtle, Chelydra serpentina.

The dose response, temperature sensitivity, time course and calcium dependency of histamine release from snapping turtle basophils treated with rabbit anti-turtle immunoglobulin (RATIg) sera was explored. This investigation indicated that the level of histamine release induced by RATIg was dependent upon the concentration of RATIg with concentrations of 350 mcg/ml inducing optimal release. In addition, release was temperature dependent with release increasing over a temperature range of 10 degrees C to maximal at 27 degrees C. Release was also dependent on the length of exposure to RATIg. Release increased steadily over a time period of 0 to 30 minutes with the higher concentrations of RATIg inducing the most rapid release. Basophil-histamine release was also found to be calcium dependent. This study indicates that the snapping turtle basophil possesses similar characteristics to that of its mammalian counterparts. It is proposed that the very wide temperature range over which turtle basophils release histamine is an important feature in he immune resistance of this ectothermic animal.

Animals↗
PubMed1983

Purification of human basophils by negative selection.

Enriched populations of human basophils were prepared using a combination of negative selection techniques. First, a 2-step discontinuous gradient was made using 65% and 55% isotonic Percoll. Purification of plasma basophils by centrifugation through the gradient increased basophils from 0.96 +/- 0.55% to 14.6 +/- 7.9% (n = 9). In 5 other experiments a second step was added in which contaminating mononuclear cells were removed using a panning technique. In this technique, Percoll separated cells were treated with anti-T-cell antibodies. Contaminating T-cells were selectively removed by adherence to a petri dish coated with affinity purified goat anti-mouse IgG. Basophil purity was increased to 34 +/- 15% using this step. These experiments demonstrated that negative selection techniques can yield an increase in basophil purity 50-100-fold. The purified basophils contained the expected quantity of histamine (1.36-1.54 pg/basophil) and released the same amount of histamine in response response to different concentrations of goat anti-human IgE Fc as did unpurified cells.

Antibodies, Monoclonal↗
PubMed1983

Allergens detected in association with airborne particles capable of penetrating into the peripheral lung.

Extrinsic asthma is caused by exposure to airborne allergens. The diameter of airborne particles influences the depth of penetration and deposition fraction in the lung. In this study, we used an Andersen sampler to collect 9 different size ranges of airborne particles from a cat-containing and a cat-free room. We detected cat allergen 1 (CA1), the major cat allergen, using a rocket immunoelectrophoretic technique in larger particle size ranges (more than 5 mu). Using in vitro cat allergic donor basophil histamine release, cat-associated allergen activity was detected in particle size ranges from 10 to less than 1 mu in aerodynamic diameter. Control collections of airborne particles from a cat-free room showed little or no allergen activity, and nonatopic donor basophils did not release histamine in response to any of these samples. The P-K test (positive transfer test) confirmed findings of the other assays. We conclude that cat-derived allergens are associated with a large range of airborne particle sizes that penetrate into the peripheral lung.

Air↗
PubMed1983

Naturally abundant basophils in the snapping turtle, Chelydra serpentina, possess cytophilic surface antibody with reaginic function.

Basophils constitute 50 to 63% of the blood leukocytes in Chelydra serpentina, the snapping turtle. Immunoglobulin (Ig) on the surface of the turtle basophil was detected by indirect immunofluorescence by using an IgG fraction from rabbit anti-turtle Ig serum (RATIg) and a fluoresceinated goat anti-rabbit antibody incubated at 4 degrees C. However, when the cells were incubated with RATIg at 22 degrees C, the basophil number, as determined by Wright's stain and neutral red counts, decreased dramatically. This morphologic evidence of degranulation was directly proportional to the antiserum concentration. Degranulation also correlated with cell histamine release (r = 0.73). In other experiments, turtle basophils were found to express antigen-specific surface Ig after immunization with sheep red blood cells (SRBC). Washed basophils from immunized turtles formed basophil-SRBC rosettes in vitro. Basophils from control turtles did not. Basophil-SRBC rosettes could also be induced by in vitro passive sensitization by preincubation of normal turtle basophils in the SRBC immune turtle sera. This study shows clearly that the turtle basophil has an immune capacity analogous to the mammalian basophil/mast cell. This study also contains the first direct evidence for the existence of reaginic antibody (or antibodies) in an ectothermic vertebrate. Finally, C. serpentina is proposed as a unique animal model for the study of basophil function.

Animals↗
PubMed1983

Direct effect of complement factor C5a on the contractile state of isolated smooth muscle cells.

The complement-(C) derived factor C5a has long been recognized as a potent contractile agonist in smooth muscle (1,2); however, controversy remains as to whether the effects of this anaphylatoxin are direct or secondary to the release of histamine (3) and/or other mediators (4-8) from nonmuscle cells within the tissue. To resolve this controversy, we have assessed the contractile effects of purified human C5a and C5a des Arg in a homogeneous preparation of enzymatically dispersed smooth muscle cells derived from the stomach of the toad, Bufo marinus. This preparation, which is insensitive to histamine at concentrations as high as 10(-4) M, responds normally to a variety of electrical (9), mechanical (10), and pharmacologic (11, 12) stimuli. These smooth muscle cells also respond to purified human anaphylatoxin; exposure to the cells to purified human C5a or C5a des Arg produce contractions of the smooth muscle cells that are accompanied by increased Ca2+ influx. The contractile response was unaffected by antagonists to histamine or acetylcholine but was reduced by 30% by pretreatment with the leukotriene antagonist FPL55712. A direct contractile effect of C5a on amphibian smooth muscle cells is suggested.

Animals↗
PubMed1982

Pneumocystis carinii and cytomegalovirus pneumonia in a previously healthy adult.

A case of Pneumocystis carinii pneumonia and cytomegalovirus infection occurring in a previously healthy adult male homosexual who was not receiving known immunosuppressive therapy is described. This 35-year-old man had been treated with metronidazole and tetracycline for an intermittent diarrheal illness of 5 months' duration. He was then admitted to the hospital where he was found to have a small infiltrate in the left lower lobe, and this process soon involved both lungs. Initially, Pneumocystis carinii infection and later cytomegalovirus infection were diagnosed by lung biopsy and culture. Peripheral blood lymphopenia was present and he had in vivo and in vitro abnormalities of his cellular immune responses. He was unresponsive to Bactrim as well as pentamidine and pyrimethamine therapy and died 7 wk after hospitalization.

Adult↗
PubMed1981

Local heat urticaria/angioedema: evidence for histamine release without complement activation.

A 42-yr-old white woman reported onset in 1976 of local pruritus, burning, erythema, and edema within minutes after exposure in heat. With more extensive exposure, she occasionally had transient headaches and nausea. In order to investigate the etiology of this condition, her forearm was exposed to water at 44 degree C for 4 min. Within a few minutes, a lesion identical to her spontaneously induced ones developed only at the area exposed to heat. Samples of venous blood from this extremity demonstrated a transient rise in plasma histamine levels without any significant change in serum hemolytic complement activity or in C3, C4, or factor B. These findings suggest that this rare syndrome involves local activation of mediator release from mast cells, without participation of the complement system.

Adult↗
PubMed1981

Hyperosmolar triggering of histamine release from human basophils.

Idiopathic reactions occurring during the infusion of hyperosmolar solutions, such as radiocontrast dyes, cause a significant number of deaths each year. These reactions are similar to those which follow mediator release during allergen-induced anaphylaxis. In attempting to explain these nonimmunologic reactions, we examined the direct effect of hyperosmolarity on normal human basophils with emphasis on release induced by mannitol. The cells of all donors released histamine in vitro in response to hyperosmolar (0.2-0.7 M) solutions of a number of solutes including mannitol. That this was not a toxic process was supported by a number of criteria, including inhibition of release by excess stimulus at 37 degrees C and a lack of release at 4 degrees C. Furthermore, electron microscopic studies revealed that hyperosmolar stimulation did not disrupt the cell membrane or lead to any signs of cytotoxicity. In contrast to antigen-stimulated release, where granules fuse only with the cell membrane, granules in mannitol-stimulated cells, in addition to fusing with the cell membrane, may also be extruded into a common intracellular sac before exteriorization. Characteristics similar to antigen-induced histamine release included the time-course for release, inhibition by drugs that modify phospholipid metabolism, p-bromophenacyl bromide, and eicosa-5,8,11,14-tetraynoic acid, and augmentation of release by deuterium oxide (D(2)O). The release process differed from antigen-induced release by a number of criteria, including independence from immunoglobulin (Ig)E-related mechanisms, insensitivity to agonists that elevate intracellular cyclic AMP, minimal dependence on extracellular calcium, lack of inhibition by 2-deoxyglucose and theophylline, and a temperature optimum of 32 degrees C. We conclude that this noncytotoxic hyperosmolar release process is different from IgE-mediated secretory events and may well play a role in the idiopathic reactions which occur secondary to the infusion of hyperosmolar solutions in man.

Adult↗