Immunodeficiency with hyper IgM after systemic lupus erythematosus.
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Biomedical subjects
Publications and source records attributed to K P Mathews.
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The distribution and clearance of aerosolized radioactive technetium 99m pertechnate in physiologic buffered saline was analyzed in four human adult asymptomatic volunteers following delivery into one nostril in the same manner as for nasal challenge testing (i.e., 0.1 ml via a 251 DeVilbiss atomizer powered by a compressor delivering 0.10 +/- 0.01 gm/spray). For comparison, squeeze bottles and spray bottles from commercial sources, a 114 and a 127 DeVilbiss atomizer, and a pipette were employed. Lateral imagery via minicomputer processing was used to determine both distribution and clearance of the radiotracer. The counts after 1 minute were lower following pipette delivery than with the other devices. None yielded discernable , wide-spread distribution of aerosol throughout the nasal cavity. Following delivery from the 251 atomizer, mean clearance at 17 minutes was 60.0%. Similar clearance rates were obtained with the other spraying methods except for lower values with the squeeze bottle. Analysis of six hour clearance studies by linear regression showed a relatively rapid initial phase, which is probably due largely to mucociliary clearance, and a prolonged late phase related to the very slow disappearance of residual material located far anteriorly in the nose. Achieving good initial retention and rapid clearance of material deposited anteriorly in the nose are desirable attributes of devices employed for administering materials intranasally.
Indomethacin inhibited rat liver glutathione S-transferases (EC 2.5.1.18). Its inhibition was non-competitive with respect to 3,4-dichloronitrobenzene with an apparent Ki of 5.3 X 10(-5) M and uncompetitive with respect to glutathione with an apparent Ki of 4.0 X 10(-5) M. 4-Chlorobenzoic acid and 5-methoxy-2-methylindole-3-acetic acid, two metabolites of indomethacin, were weak inhibitors of the enzymes. On the other hand, meclofenamic acid was a competitive inhibitor of the enzymes with an apparent Ki of 3.0 X 10(-4) M. Possible significance of these findings in arachidonic acid metabolism is discussed.
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Preliminary experiments indicated that solutions of aspirin (ASA) in buffered saline, pH 7.35, did not significantly change nasal airways resistance (NAR) when 0.1 ml of solution containing 22.5 mg (or less) per deciliter was sprayed into each nostril. Subsequently it was shown that this quantity of ASA administered intranasally did not significantly change NAR responses 15 min later to intranasal administration of increasing concentrations of histamine, methacholine, or an irritant (NH3 gas). However, the same atopic subjects demonstrated significantly decreased responses to intranasal challenge with short ragweed extract (SRW) after intranasal ASA. In addition, prior oral administration of ASA, Na salicylate, and indomethacin significantly inhibited nasal challenge responses to SRW in sensitive subjects under controlled conditions.
"Triad" asthmatics often have sinus disease, nasal polyps, and obstructive airways disease. This presentation is reminiscent of the symptoms of persons afflicted with various forms of ciliary dyskinesia. Therefore, we examined tissues from seven "triad" asthmatic patients for ciliary structural or functional abnormalities. Transmission and scanning electron microscopy revealed no specific abnormalities. Cultures of nasal epithelia were maintained for up to 20 weeks. They showed normal ciliary activity which was not influenced by perfusing the tissue with medium containing aspirin. In contrast, control tissue from a patient with situs inversus and sinusitis showed the expected structural and functional ciliary abnormalities. In culture, the ciliary function of tissue from this patient could be partly restored by perfusion with ATP or ATPase.
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IgE was measured by ELISA in tubes and in microtiter plates, the results being compared with PRIST data. The recommended readings of the tube contents in a spectrophotometer (SPM) were compared with results using a multi-channel photometer (MCP). Geometric mean values (International Units) and standard deviations of 44 normal sera examined by the 3 different methods were: PRIST 16.2 +/- 4.0; SPM 15.6 +/- 4.9 and MCP 18.4 +/- 4.4. Correlation coefficients were: PRIST-SPM r = 0.98; PRIST-MCP r = 0.98; and SPM-MCP r = 0.97. Intra- and inter-assay coefficients of variation were smaller for MCP than for SPM. In addition, reading in microtiter plates was much faster, while having little effect on sensitivity.
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Confirming previous work by Connell, it was shown that challenging nine subjects intranasally on successive days with short ragweed extract (SRW) resulted in a priming effect manifested by significantly augmented increases in nasal airways resistance as well as in increasing subjective symptoms. Priming was reproducible and transient. In contrast, significant priming to an irritant, ammonia gas (NH3), could not be unequivocally demonstrated over a similar period of time in these same subjects under the conditions employed. Also, priming these subjects with SRW extract failed to enhance responsiveness to NH3.
Theophylline is thought to improve asthma by increasing intracellular cyclic adenosine 3'-5'-monophosphate (cAMP) levels. It has been demonstrated in experimental animals that elevation of intracellular cAMP in the adrenal cortex causes an increased secretion of cortisol. We studied whether therapeutic doses of theophylline given intravenously and orally to human subjects over 3 days would increase cortisol secretion. A single-blind, 6-day protocol was employed in five normal and five asthmatic volunteers. Adrenal function was monitored by 8 A.M. and 4 P.M. serum cortisol and adrenocorticotropic hormone (ACTH) levels; daily 24-hr urine for urinary-free cortisol (UFF), 17-hydroxysteroids (17-OH), and 17-ketosteroids (17-KS); and alternate-day cortisol secretory rates (FSR) measured by isotope dilution after intravenous 14C-cortisol. Serum theophylline concentration also was monitored. Results in normal and asthmatic subjects were similar. Theophylline caused a significant but transient increase in UFF and 17-OH excretion. Urine volumes also increased significantly, suggesting that the renal effect of theophylline accounted for the increased UFF and 17-OH excretion. FSR increased during the first 24 hr after theophylline in eight of nine cases (p < 0.05 by sign test), mean values increasing from 14.2 to 19.3 mg, but this effect had dissipated by day 3 of theophylline administration. In contrast to these findings, theophylline had no effect on serum cortisol or ACTH or urinary 17-KS. It is likely that serum cortisol and ACTH remained unchanged because the increase in cortisol secretion was offset by a concomitant increase in cortisol clearance. It is concluded that theophylline produces a small, transient increase in cortisol secretion and clearance, and this effect is similar in asthmatic and normal subjects.
There is increasing evidence for the secretion of IgG and IgE, as well as IgA, antibodies by the nasal mucosa. Because the former immunoglobulins lack an identifiable secretory piece, estimates of their secretion have been on their ratio to albumin or to total immunoglobulin of the same type in the nasal secretion as compared with serum. It is shown, however, that use of the ratio to albumin will result in large errors if the amount of antibody secreted by the nose is relatively small, and ratios based on total secretory Ig will, at least hypothetically, lead to error if antibodies with multiple specificities are being secreted. It is suggested that a more valid quantitation will be obtained from the expression (Formula: see text) where INS is an index of nasal secretion, Ab = antibody, Alb = albumin, N = nasal secretion, and S = serum.
During 1978 a double blind study compared the efficacy of preseasonal short ragweed (RW) extract intranasal immunotherapy with a histamine placebo; in 1979 more prolonged treatment with a larger dose of polymerized ragweed (PRW) was evaluated. In neither year did the placebo-treated patients show significantly more severe disease as assessed by daily symptom diaries, examination in season, comparison of overall symptom severity with previous years or changes in nasal challenge tests. Following treatment in 1979 there was a significantly greater amount of secretory IgA and IgG ragweed antibodies secreted by the nose of the PRW-treated group, but these titers did not correlate with clinical results.
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If some clinical problems (e.g., radiographic contrast media reactions) arise from mediator release by circulating basophils, prednisone's capacity to prevent such is likely to be at least partly related to its suppressive effects on whole blood histamine and basophil levels. To establish an optimal dosage schedule, 15 healthy male volunteers entered a two-phased study to determine (1) the single dose of prednisone required to produce maximal suppression of histamine and basophil levels and (2) the effects of repeated prednisone doses. Parameters monitored were whole blood histamine, quantitative basophil counts, white blood cell (WBC) and differential counts, and plasma prednisone, prednisolone, and cortisol levels. Fifty milligrams prednisone suppressed whole blood histamine levels as much as a larger dose and also showed a marked effect on circulating basophils and other leukocytes. Three 50-mg prednisone doses given at 6-hr intervals had a greater effect on whole blood histamine and circulating leukocytes than fewer doses. Thus, the commonly used empirical prednisone dosage regimen is supported. One implication of the results of this study is that greater suppression of blood basophils and histamine levels might be obtained by administering the last prednisone dose about 6 hr before procedures in which a very rapid release of mediators from basophils is anticipated.