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Biomedical subjects

K P Mathews

Publications and source records attributed to K P Mathews.

12 recordsLinked to original sources

Cold-dependent activation of complement: recognition, assessment, and mechanism.

Cold-dependent activation of complement (CDAC) is a phenomenon characterized by low hemolytic complement activity in chilled serum. Complement component levels are normal when measured immunologically, and there is normal hemolytic activity in EDTA plasma or serum maintained at 37 degrees C. Little attention has been paid to CDAC except in Japan, and current unfamiliarity with it, even by clinical immunologists, can lead to confusion and unnecessary laboratory tests. A 66-year-old patient with a complex medical history is described whose complement tests showed abnormalities characteristic of CDAC. Evidence for classical complement pathway activation in the cold was obtained by CH50 measurements, by hemolytic C4 determinations, by C4a, C3a, and C4d generation, and by quantitating C1s-C1r-(C1 inhibitor)2 complexes. A good correlation was observed among these parameters. Cryoprecipitates were absent. CDAC activity has persisted for over 5 years and is greater at 13 than at 4 degrees C. Activation is ablated by heating at 56 degrees C and restored by the addition of C1 to the heated serum. Adsorption by streptococcal protein G-Sepharose and precipitation by 2.5% polyethylene glycol support the hypothesis that CDAC is caused by aggregated IgG. The CDAC factor(s) also induces complement activation in normal serum but has not interfered with Raji cell or C1q binding tests or with FACS analysis. More limited studies of a second individual experiencing CDAC yielded similar results.

Adult

Effect of histamine and methacholine on nasal airway resistance in atopic and nonatopic subjects. Comparison with bronchial challenge and skin test responses.

Serial nasal, intracutaneous, or bronchial challenges were carried out with solutions containing 2- or 3-fold increments in histamine (H) or methacholine (Meth) concentration until nasal airway resistance (NAR) increased by more than 100%, a large intracutaneous reaction was elicited, or FEV1 decreased by 20% or more. Thirty nonatopic and 48 asymptomatic atopic subjects were studied, the latter group divided into rhinitic patients with and without asthma. Several types of data analysis demonstrated there was no significant difference in the nasal or cutaneous effects of H or Meth between the atopic and nonatopic groups. Comparable results were obtained in a subgroup of 39 subjects (13 normal, 13 atopic, and 13 atopic with asthma) who underwent all six test sequences (i.e., nasal, cutaneous, and bronchial with both drugs). As expected, the asthmatics showed significantly increased bronchial reactivity to both agents. In comparison with Meth, H had a much greater effect on the nasal mucosa and skin than on the bronchi. It is concluded that, contrary to bronchial responses, but in accord with cutaneous reactivity, the nasal responses of nonatopic subjects, atopic persons with allergic rhinitis alone, and subjects with both allergic rhinitis and asthma show no intergroup differences on testing with H or Meth.

Airway Resistance

An improved technique for nasal inhalation challenge tests.

An improved technique for nasal inhalation challenge tests is described. It includes an improved delivery system utilizing a Maxi-Myst air compressor delivering a flow of room air controlled by an in-line, electroncially timed solenoid which precisely controls the duration of compressor activity. A No. 251 DeVilbiss atomizer will deliver 0.1 + 0.01 gm/spray when the flow rate is 11.5 L/min, the duration of atomizer activity is approximately 0.1 sec, and the amount of liquid in the atomizer insert is kept between 0.75 and 2.0 ml. Nasal aerosol challenge of 0.1 ml of isotonic phosphate-buffered saline per nostril produced less variability in nasal airway resistance (NAR) response than 0.2 ml, and the smaller volume proved satisfactory for 6 consecutive saline challenges at 15-min intervals. A new face mask, which did not impinge on the bridge of the nose or paranasal structures, yielded lower baseline values of nasal airway resistance and much less variability in these measurements. Techniques employed in objectively quantitating nasal responses to various exogenous substances are briefly but critically reviewed.

Administration, Intranasal

The effects of topical saline and isoproterenol on nasal airway resistance.

Following determination of baseline nasal airway resistance (NAR) in human subjects, phosphate-buffered saline (PBS) was aerosolized into each nostril and NAR measurements repeated 8 times in 15 minutes. The mean maximal NAR increase in 102 subjects was 22.5% (SD +/- 24.5%) with no significant difference between atopic and nonatopic persons. Hay fever patients did not show significantly increased responsiveness to PBS while symptomatic. During 242 repeat challenges with PBS in 67 asymptomatic subjects, NAR increased over 50% in 24 tests. Following a series of 6 PBS challenges at 15-minute intervals, 10 of 71 subjects had more than a 100% increase in NAR over initial baseline values. Administration of PBS on cotton pledgets, pipetting PBS into the nose, or even just inserting a nasal speculum produced greater increases in NAR than the usual aerosol method. Intranasal atropine effectively blocked PBS-induced increases in NAR, suggesting parasympathetic stimulation as a mechanism. Isoproterenol increased NAR over 100% in 27 of 53 subjects, with no significant difference among rhinitic, asthmatic, and nonatopic individuals. This effect was inhibited by propranolol. Isoproterenol administration to 12 ragweed-sensitive subjects 15 minutes prior to ragweed challenge produced a variable inhibition in NAR responses or no protection at all. Thus the direct effects of isoproterenol on the nasal vasculature tend to outweigh those expected from inhibition of mediator release under the conditions of this study.

Administration, Intranasal

Immunotherapy for allergic disease.

Although immunotherapy initially was purely empirical, immunologic studies of treated patients in more recent years have shown several types of responses that might be beneficial to patients. Likewise, double-blind clinical trials have documented some clinical improvement if sufficiently large doses of certain allergens are administered to properly selected patients. The selection of patients for possible immunotherapy depends upon a large number of considerations, including the severity of their disease and response to simpler forms of treatment. More slowly absorbed allergen preparations may make immunotherapy less cumbersome and reduce risks. It is impressive that so many patients persist with such an inconvenient form of treatment. Perhaps this indicates that allergies are trivial only for those who don't have them.

Clinical Trials as Topic

Immediate-type hypersensitivity to a bean lectin source with commentary on occupational allergy in allergy-immunology laboratory and research workers.

A case of acute, severe allergic conjunctivitis is reported in a biochemist who had been grinding Bandeiraea simplicifolia, the source of an anti-B lectin. A crude extract of these beans produced immediate-type skin test reactivity, and reaginic antibodies were demonstrated in her serum. Several other examples of occupationally induced allergy in laboratory and research workers in the field of allergy-immunology are briefly cited. Exposure to potential allergens in a dry, powdered form seems particularly hazardous.

Adult

Comparative nasal absorption of allergens in atopic and nonatopic subjects.

Based on sensitization following intranasal antigen administration, previous investigations have suggested greater absorption of allergens through the nasal mucous membranes of atopic than of nonatopic subjects. In this study mucosal absorption was assessed more directly by determining the capacity of allergens applied intranasally to elicit cutaneous Prausnitz-Küstner (P-K) reactions in nonatopic persons as compared with asymptomatic atopic subjects sensitive to other allergens. Two series of reaginic human serum dilutions were injected intracutaneously in recipients backs, and 48 hours later one series was challenged intracutaneously with test allergen. After the responses had been recorded, concentrated allergenic extract was sprayed into the nose and the second series of P-K sites observed for reactivity. Sometimes these P-K sites were rechallenged intracutaneously the following day to determine passive transfer neutralization. Two allergens were studied: bovine ribonuclease (RNase) and peanut extract. Two sera containing peanut reagins and one with RNase antibodies were each used in 10 to 11 atopic and 9 to 11 nonatopic recipients. The atopic group failed to show greater or more rapid absorption of either allergen through the nose based on the highest serum dilution reacting after nasal challenge. the speed of the reaction, the ratio of the titer by nasal challenge to the intracutaneous titer, or passive transfer neutralization. Controls showed that the results were not influenced by systemic absorption of allergen employed for intracutaneous tests. Drinking the amount of peanut extract applied intranasally did not elicit P-K reactions.

Administration, Intranasal

Effect of ammonia on nasal resistance in atopic and nonatopic subjects.

Nasal airway resistance (NAR) was assessed from the slope of pressure-glow curves obtained during normal nasal breathing. Volunteers were classified as atopic or nonatopic according to strict critera. 100 ppm NH3 was introduced into each nostril for periods ranging from 5 to 30 seconds with frequent NAR monitoring. A progressive increase in NAR responses was obtained with incremental NH3 exposure, but no significant difference was noted between the mean response of atopic and nonatopic subjects. Control exposures to compressed air under the same pressure generally produced only a small change in NAR, while aerosolized buffered saline increased NAR more than compressed air. The nasal response to NH3 was effectively inhibited by intranasal atropine administration but not by chlorpheniramine. The nasal response to NH3 was effectively inhibited by intranasal atropine administration but not by chlorpheniramine. The described procedure provides a safe and simple method for studying semiquantitatively the short-term effects of inhaled irritants on the nose.

Air