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Biomedical subjects

W R Solomon

Publications and source records attributed to W R Solomon.

At least 19 recordsLinked to original sources

Immediate hypersensitivity reaction to cyclophosphamide.

We report a case of an acute anaphylactic reaction to intravenous cyclophosphamide in a patient with systemic lupus erythematosus. Skin testing for reactivity to cyclophosphamide and one of its metabolites, 4-hydroperoxycyclophosphamide, was performed on the patient and on 6 controls. The patient exhibited positive skin test responses; all controls had negative responses. The results suggest an acute hypersensitivity reaction related to sensitivity to cyclophosphamide and to 4-hydroperoxycyclophosphamide, through a shared antigenic determinant or dual sensitization.

Adult

Prevention of allergic disorders.

Allergic disease produces substantial pediatric morbidity and individual dysfunction, making its mechanisms an appropriate target for clarification and preventive strategies. Disease expression seems to reflect a constellation of determinants that controls IgE production variably, affects specific function of target organs, and determines exposure to putative allergens. Bases for the two former factors are being defined rapidly and appear to be controlled genetically. Therefore, although stronger eugenic motivation will be required to exploit even present information for effective prevention, parental phenotypes can provide a rough indication of postconceptive risk. Despite many divergent data, current evidence fails to support the value of gestational strategies undertaken to prevent allergic disease in the newborn; however, this risk apparently may be reduced by avoiding postnatal allergens. The protection afforded seems to be allergen-specific rather than somehow serving to abate "the allergic tendency." Evidence increasingly is persuasive that sensitization to pollens, foods, and possibly other agents is prone to occur in the first 6 to 12 months of life. Strategies that exclude potent food allergens from the diets of high-risk infants appear to reduce the occurrence of atopic dermatitis, but seem far less able to influence respiratory symptoms. Efforts to limit exposure to potent inhalant allergens (eg, dust mites, animal "danders") are now also feasible and offer quite effective secondary and, perhaps, primary prevention. Trials of these strategies and clarification of other domestic contaminant effects on child health offer "homely" but valid and potentially useful approaches to reducing the impact of allergic disease.

Animals

Particle penetration into the automotive interior. I. Influence of vehicle speed and ventilatory mode.

Penetration of particulate aeroallergens into the interiors of two, new, similar Chrysler Corporation passenger vehicles (having no evidence of intrinsic microbial contamination) was studied on a large circular test track during periods of high pollen and spore prevalence. Impactor collections were obtained at front and rear seat points and at the track center during periods with (1) windows and vents closed and air conditioning on, (2) windows closed, vents open, and no air conditioning, and (3) air conditioner off, front windows open, and vents closed. These conditions were examined sequentially during travel at 40, 50, 60, and 80 kph. Particle recoveries within the two, new, similar Chrysler Corporation passenger vehicles did not vary with the speed of travel, either overall or with regard to each of the three ventilatory modalities. In addition, collections at front and rear seat sampling points were comparable. Highest interior aeroallergen levels were recorded with WO, and yet, these levels averaged only half the concurrent outside concentrations at track center. Recoveries within the cars were well below recoveries obtained outside when windows were closed (both VO and AC modes). These findings suggest window ventilation as an overriding factor determining particle ingress into moving vehicles. Efforts to delineate additional determinants of exposure by direct sampling are feasible and would appear essential in formulating realistic strategies of avoidance.

Aerosols

The theophylline-enoxacin interaction: II. Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin.

The pharmacokinetics of theophylline and its three major metabolites, 3-methylxanthine, 1-methylurate, and 1,3-dimethylurate, were studied during intermittent administration of enoxacin. The addition of enoxacin (400 mg, twice daily) to a theophylline dosing regimen (150 mg, twice daily) resulted in an immediate fall in plasma theophylline metabolite concentrations. Mean steady-state theophylline concentration in plasma during the dosing interval increased from 3.17 to 8.23 micrograms/ml. The mean 12-hour recovery of total theophylline metabolite decrease from 76.3 to 38.6 mg. After the discontinuation of enoxacin, but not theophylline, the plasma theophylline metabolite levels immediately increased to near or above the concentrations observed before enoxacin coadministration. Concurrently, theophylline concentrations decreased to levels equivalent to those observed before enoxacin coadministration. In general, the changes in plasma theophylline concentrations observed after the addition of discontinuation of enoxacin were complete within 3 days.

Adult

Recommendations for the use of residential air-cleaning devices in the treatment of allergic respiratory diseases.

In an attempt to recommend standards for room air-cleaning devices, a committee reviewed (1) the types and performance characteristics of available domestic air-cleaning devices, (2) the available data on concentrations of allergens in the indoor air, and (3) the studies that have examined the health effects of the use of indoor air-cleaning devices. Absense of adequate data on the clinical relevance of indoor ambient allergen levels, as well as the effect of air-cleaning devices on these levels, plus a general lack of health effects by these devices in published double-blind studies precluded any firm recommendations for their use. It was clear, however, that use of room air-cleaning devices in the absence of other forms of environmental control was not reasonable.

Air

The theophylline-enoxacin interaction: I. Effect of enoxacin dose size on theophylline disposition.

Theophylline interacts pharmacokinetically with a variety of other drugs. Recently enoxacin was found to change theophylline's disposition. In a four-subject, four-way crossover study enoxacin was administered every 12 hours at four levels (0, 25, 100, and 400 mg) for 14 doses. With the ninth dose of enoxacin, 200 mg theophylline was coadministered. Blood and urine samples were assayed by sensitive and specific assays for the parent drugs and their metabolites. Significant reduction in the formation of theophylline's three major metabolites occurred on coadministration of enoxacin. At the 400 mg dose level, enoxacin caused a threefold decrease in theophylline's plasma clearance, a fourfold decrease in the urinary recovery of 3-methylxanthine and 1,3-dimethylurate, and a threefold decrease in the recovery of 1-methylurate.

Adult

Allergen carriage by atmospheric aerosol. II. Ragweed-pollen determinants in submicronic atmospheric fractions.

Outdoor air was drawn by a vacuum system through a 0.8 micron molecular membrane filter and a back-up, refrigerated condensor from 8 A.M. to 5 P.M. daily during the 1982 ragweed-pollen season. Sample sets from each day were collected and stored separately. Condensate was collected in a freezing jacket, thawed, refiltered through a 0.45 micron filter, and lyophilized. Reconstituted condensates evoked wheal-and-flare skin reactions in a ragweed-sensitive individual and produced significant inhibition in an IgG-ELISA system by use of ragweed-pollen protein or ragweed antigen E conjugated to polystyrene microtiter plates, pooled serum of patients on ragweed immunotherapy, and alkaline phosphatase-labeled anti-human IgG. Earlier, in 1983 in this JOURNAL, we reported the presence of airborne ragweed-pollen antigen in aerosol fractions below 5 micron. The present data demonstrate similar in filtrates well below the micronic range. Furthermore, these antigenic properties are substantially associated with atmospheric water vapor-either naturally or as a readily-induced result of the collection procedure. These results suggest that naturally occurring mists, although free of native particulates, may yet carry allergens of clinical significance.

Air Pollutants

Allergen carriage by atmospheric aerosol. I. Ragweed pollen determinants in smaller micronic fractions.

Outdoor air-bearing natural ragweed pollen burdens were drawn through 5 microns membrane filters during 24 hr periods; aerosols penetrating these barriers were collected on individual, in-line, 0.8 microns filters. The 0.8 microns filters were free of intact pollen grains and grain fragments when scanned in toto by transmitted light. Aqueous extracts of 0.8 microns filters were found to elicit wheal-and-flare skin test reactions in a ragweed pollen-sensitive subject but not in nonatopic controls. The same extracts produced significant inhibition of an IgG-ELISA system by use of ragweed pollen protein conjugated to polystyrene plate wells and pooled serum of patients on ragweed immunotherapy. No inhibition resulted from preincubation of serum with an unrelated allergen (hickory pollen extract). These data indicate the presence of airborne ragweed pollen allergen in aerosol fractions below 5 microns during seasonal periods of ragweed pollination, confirming the report of Busse et al. Potential sources of such aerosols are prominent in nature, and their occurrence may help explain existing dose-response disparities in pollinosis.

Aerosols

Evaluation of indoor plantings as allergen exposure sources.

The role of indoor plantings as allergen sources was assessed by direct sampling of interior air. Homes with 10 or more plants in one room and three University of Michigan greenhouses were studied by means of a dc-powered rotorod and separate Andersen viable sampler collections incubated at 23 degrees and 50 degrees C. Sequential 30 and 60 sec Andersen samples were obtained during 15 min rotorod collections before and during watering of plants as well as during disturbance of foliage by a small fan. Relative humidity averaged 51% in homes and 78% in greenhouses. Aspergillus fumigatus recoveries were rare. Thermophiles, primarily bacteria, were present at low-to-moderate levels in homes, did not increase with watering of fan in homes, and rose only slightly with disturbance at greenhouse sites. Cladosporium and Penicillium dominated Andersen collections. Watering and fan increased levels of these taxa as well as rotorod recoveries of Alternaria. Epicoccum, and Pithomyces slightly in homes and markedly at greenhouse sites. We conclude that modest numbers of undisturbed house plants contribute minimally to aeroallergen prevalence in homes. However, especially under greenhouse conditions, plantings can harbor abundant fungus growth that may become airborne, especially when agitated directly.

Allergens

Exclusion of particulate allergens by window air conditioners.

Effects of window air-conditioner operation on intramural particle levels were assessed in the bedrooms of 20 homes and in 10 outpatient clinic examining rooms during late summer periods. At each site, pollen and spore collections in the mechanically cooled room and a normally ventilated counterpart were compared using volumetric impactors. Substantially lower particle recoveries (median = 16/m3) were found in air-conditioned rooms than in those with open windows alone (median = 253 particles/m3). Furthermore, substantial exclusion of small (e.g., Ganoderma spores) as well as large (ragweed pollens) aerosol components were found by window units. Control studies within normally ventilated rooms and outside their open windows showed a marked but variable inward flux of particles. Window units appear to substantially reduce indoor allergan levels by maintaining the isolation of enclosed spaces from particle-bearing outdoor air.

Air Conditioning

Performance of adhesives for rotating-arm impactors.

Particle collections by paired rotoslide surfaces coated differentially with either of two silicone greases, white petrolatum or Lubriseal, were compared in two series of studies. Three samplers were employed, and adhesives were assigned randomly to the six available positions. Recovery differences were small but occasionally significant, with counts generally highest for silicone grease and lower with Lubriseal. During natural and simulated rainfall relative performances were similar, although differences were accentuated.

Adhesives