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Biomedical subjects

D E Maddox

Publications and source records attributed to D E Maddox.

At least 19 recordsLinked to original sources

Systemic reactions to allergy skin tests.

BACKGROUND: Skin testing is a common diagnostic tool in allergy. It is considered a safe procedure, although systemic reactions have been reported. OBJECTIVE: To identify the systemic reaction rates of allergy skin tests and to determine the clinical outcome of such reactions. METHOD: This retrospective study used a computerized database at the Mayo Clinic to identify patients who developed systemic reactions to skin tests. Altogether 497,656 skin tests were performed on 18,311 patients from January 1992 to June 1997. Skin puncture tests were performed on 16,505 patients. Skin puncture and intradermal skin tests were performed on 1,806 patients. Systemic reactions were evaluated and treated by physicians. RESULTS: There were 6 systemic reactions, an overall rate of 33 systemic reactions per 100,000 skin tests. All six patients had asthma. The systemic reaction rates for latex skin testing was 152 or 228 reactions per 100,000 latex skin tests, to penicillin and antibiotics 72 reactions per 100,000 penicillin and antibiotics skin tests, and to aeroallergens 15 or 23 reactions per 100,000 aeroallergen skin tests. The systemic reaction rate for skin puncture test was 30 reactions per 100,000 skin puncture tests, for skin puncture and intradermal skin tests, the rate was 55 reactions per 100,000 skin puncture and intradermal skin tests. All 6 patients were treated and dismissed within 1 hour after treatment. CONCLUSION: The systemic reaction rate to skin tests was very low. Systemic reactions were mild and all patients recovered fully within 1 hour.

Adult↗

Spells: in search of a cause.

OBJECTIVE: To determine the cause of spells, present clinical features, and discuss diagnostic approaches. DESIGN: Relevant medical literature is reviewed, and three illustrative cases are presented. RESULTS: Spells are a sudden onset of a symptom or symptoms that are stereotypic, self-limited, and recurrent. A spell involves both subjective perceptions and objective findings. In the assessment of patients who have spells, use of a systematic approach is important in determining the cause. The causes of spells include endocrine, cardiovascular, psychologic, pharmacologic, neurologic, and other miscellaneous disorders. A comprehensive history, physical examination, and basic laboratory studies are important in the initial assessment. Specialized testing is usually needed and directed by clinical suspicion based on the spell "phenotype" (for example, a pheochromocytoma, carcinoid syndrome, or mast cell disease) and the type of facial flush or pallor. CONCLUSION: In the assessment of the patient who has spells, the clinician should cast a wide but defensible diagnostic net. Initial studies should be directed by the clues obtained from the history and physical examination.

Adrenal Gland Neoplasms↗

Clinical pharmacodynamics of antihistamines.

Antihistamines act by competing with histamine for H1 or H2 histamine receptors on cell membranes. In addition, most of the common antihistamines bind other receptors and thus exert other pharmacologic actions. For all practical purposes, mast cells and basophils are the main physiologic sources of histamine, and the primary usefulness of antihistamines is in diseases characterized by excessive production and release of histamine by these two cell types. Experimental models have proven useful for evaluating antihistamine compounds in humans. In these model systems, a test drug may be employed to block one or more of the known effects of exogenously administered histamine or a histamine agonist. Or the release of endogenous histamine may be brought about in a controlled fashion by agents such as allergens, opiates, or compound 48/80, and the drug's effects on this process may then be measured. In the case of the central nervous system, unfortunately, such models are not available and other means of evaluation must be devised. The dose response and duration of action of orally administered antihistamines can be determined in a simple skin model by their blocking of the wheal and erythema (flare) resulting from an intradermal challenge with histamine, an allergen, or compound 48/80. Antihistamines can also be evaluated in urticaria induced by scratching or cold. Itching that commonly follows injection of histamine or an allergen into the skin is also inhibited by this class of drugs. Most of the commonly used antihistamines are effective in these models, which form the basis for evaluating antihistamines in the treatment of skin diseases. In the nose and conjunctiva, other model strategies are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Localization of a molecule immunochemically similar to eosinophil major basic protein in human placenta.

We have recently reported that human pregnancy is characterized by a 10- to 20-fold elevation of eosinophil major basic protein (MBP) immunoreactivity in maternal blood. Here we show, by immunofluorescence, that placental tissue specifically binds antibody to MBP in and around the placental X cells and placental-site giant cells and, using thin plastic sections, that placenta has no infiltrating eosinophils. The X cells line the inner aspects of placental septal cysts, and the cyst fluid, obtained by aspiration, contains immunoreactive MBP at concentrations of 100 micrograms/ml, a sixfold greater concentration than the highest levels measured in maternal blood. The soluble MBP immunoreactivities in placental homogenates and in maternal serum chromatograph identically on Sephadex G-50, and both these gestational MBP molecules migrate as though substantially larger than the MBP found in serum from patients with hypereosinophilic syndrome or purified from the eosinophil granule. Our inability to demonstrate eosinophils in maternal blood or placental tissue, coupled with the large quantities of immunoreactive MBP highly localized in placental cysts and the chromatographic behavior of this molecule, suggest that the MBP detected in human gestation is produced by placenta.

Animals↗

Elevated serum levels in human pregnancy of a molecule immunochemically similar to eosinophil granule major basic protein.

We have shown that serum levels of a molecule immunochemically similar to eosinophil granule major basic protein (MBP) are elevated in pregnant women throughout gestation. MBP levels increase during gestation and plateau at approximately 7,500 ng/ml by the 20th wk (greater than 10-fold above normal). Levels return to normal after delivery, with a T1/2 of 13.7 d. The MBP in pregnancy serum is remarkably similar to the eosinophil granule MBP in that: (a) pregnancy MBP fully inhibits the binding of radiolabeled MBP standard in a double antibody radioimmunoassay; (b) this inhibition reaction is specific for human MBP because pregnancy serum produces no inhibition of the binding of radiolabeled guinea pig MBP in the guinea pig MBP radioimmunoassay; (c) in a two-site immunoradiometric assay for MBP, slopes of dose-response curves for pregnancy serum, purified MBP, and serum from a patient with hypereosinophilic syndrome are identical, and maximal binding is comparable; (d) reduction and alkylation of pregnancy sera increases measured MBP 100-fold, as previously shown for eosinophil granule MBP in serum; and (e) the MBP in pregnancy serum demonstrates the same pattern of heat lability as has been previously reported for MBP. Four observations have raised the possibility that the eosinophil is not the source of the MBP in pregnancy serum: (a) no correlation between serum MBP level and peripheral blood eosinophil count exists in pregnant women, in contrast to previous studies of patients with eosinophilia; (b) levels of three other eosinophil-associated proteins are normal or low in pregnancy sera, whereas the serum levels of these proteins are elevated in patients with eosinophilia; (c) the slopes of dose-response curves for pregnancy sera and MBP standards differ in the double antibody radioimmunoassay; and (d) the molecule in pregnancy serum elutes from Sephadex G-50 columns at the void volume, while eosinophil granule MBP and the MBP in serum of patients with eosinophilia elute at a volume consistent with the previously established molecular weight of 9,300. These findings suggest that the MBP in pregnancy serum is derived from a source other than the eosinophil.

Animals↗

Differential expression of a lamininlike substance by high- and low-metastatic tumor cells.

High-metastatic murine fibrosarcoma cells readily attached to Type IV (basement membrane) collagen, whereas low-metastatic cells isolated from the same tumor did not. The addition of laminin--a glycoprotein that facilitates the adherence of epithelial cells to their basement membranes--enhanced the attachment of the low-metastatic cells, but not the high-metastatic cells. Using anti-laminin antibodies and a laminin-binding lectin as probes, the authors were able to identify by immunofluorescence a moiety associated with the high-metastatic cells, but not the low-metastatic cells, which cross-reacted with murine laminin purified from the EHS sarcoma. When extracts from the high-metastatic cells were separated by affinity chromatography, with the laminin-binding lectin as the affinity substrate, a substance was isolated that had an apparent molecular weight of 56,000 daltons. The affinity-purified material reacted strongly with anti-laminin antibodies by enzyme-linked immunosorbent assay.

Animals↗

Stimulated macrophages express a new glycoprotein receptor reactive with Griffonia simplicifolia I-B4 isolectin.

This paper presents data on reactions of murine macrophages with a variety of lectins, with special focus on Griffonia simplicifolia I-B4 isolectin, the only lectin we tried that distinguishes stimulated macrophages from resident populations. Specificity of Griffonia simplicifolia I reaction with carbohydrate determinants at the cell surface is shown by (i) ability of alpha-galactosidase treatment of intact cells to abolish all lectin binding whereas beta-galactosidase has no effect on lectin binding, (ii) ability of methyl alpha-D-galactopyranoside to completely inhibit lectin binding with methyl alpha-D-galactopyranoside having no effect on lectin binding, (iii) ability of brief treatment of intact cells with trypsin to liberate a glycopeptide but reacts with G. simplicifolia I to form a precipitate that is dissolved by addition of methyl-alpha-D-galactopyranoside or alpha-galactosidase, (iv) ability of methyl alpha-D-galactopyranoside (but no other monosaccharide) to completely inhibit avid binding of macrophages to G. simplicifolia I lectin immobilized on an insoluble support, and (v) ability of immobilized lectin to separate macrophages into highly pure subpopulations of lectin-reactive and lectin-unreactive cells, as shown by examination of fluorescein-labeled lectin-treated cells with phase-contrast/fluorescence microscopy.

Animals↗

Effect of Coronary Collateral Vessels on Regional Myocardial Blood Flow in Patients With Coronary Artery Disease.

The effect of radiographically graded coronary collateral vessels on regional myocardial blood flow was evaluated with intracoronary injection of xenon-1233 at rest and during contrast agent-induced coronary hyperemia in 24 patients with coronary artery disease. Eleven patients had no coronary collateral vessels demonstrated radiologically, whereas 13 had such vessels. In 7 of the 13 these were high grade and noncompromised, whereas in 6 they were of lesser grade. Regional myocardial blood flow at rest in patients with and without collateral channels was similar and increased during hyperemia. However, the increase in flow was significantly greater in the patients with high grade noncompromised collateral vessels than in those with lesser grade collateral vessels (80 +/- 16 versus 31 +/- 9 plercent, p < 0.05). To evaluate the functional significance of the high grade noncompromised collateral vessels against that of vessels of lesser grade, various indexes of global and regional ventricular function were compared in the 13 patients in the present study, as well as in 24 patients whose collateral vessels had been subjected to similar grading systems in previous studies of regional myocardial blood flow. There were no significant differences in degree of regional asynergy, ejection fraction or left ventricular end-diastolic pressure between the patients with high and lower grades of collateral vessels. Thus, high grade noncompromised collateral vessels do not appear to have a beneficial effect on resting left ventricular function despite their enhanced vasoldilatory reserve.

Collateral Circulation↗

Regional left ventricular function in acute myocardial infarction: evaluation with quantitative radionuclide ventriculography.

Regional and global left ventricular performance was noninvasively assessed with quantitative gated equilibrium radionuclide ventriculography in 43 patients an average of 40 hours after the onset of a first acute transmural myocardial infarction. In all 16 patients with anterior infarction, regional ejection fraction, a quantitative measure of regional left ventricular performance, was uniformly depressed in the infarcted zone. In patients with inferior infarction the abnormalities of regional performance were less severe. Fourteen of 20 patients (70 percent) with inferior infarction had depressed performance in the infarcted zone. Function in noninfarcted zones was abnormal in only 6 of the 20 patients (30 percent) with inferior infarction, but it was abnormal in 11 of the 16 patients (69 percent) with anterior infarction, particularly in those with severe pump failure. As a consequence, global left ventricular ejection fraction was significantly lower in patients with anterior than in those with inferior infarction (mean +/- standard error of the mean 31 +/- 3 percent versus 51 +/- 3 percent, less than 0.005). Prognosis and clinical functional class were related to performance not only in infarcted zones, but also in noninfarcted zones as assessed with electrocardiography. It is concluded that depressed function in apparently noninfarcted left ventricular zones contributes significantly to left ventricular dysfunction after acute myocardial infarction, particularly in patients with anterior infarction.

Animals↗

Significance of reduced regional myocardial blood flow in asynergic areas evaluated with intervention ventriculography. Results of studies combining washout of xenon-133 and postextrasystolic potentiation.

Nineteen patients with coronary artery disease were studied to determine the significance of reduced regional myocardial blood flow (50 ml/min per 100 g or less) in areas of abnormal wall motion. Regional myocardial blood flow was measured in four regions of the left ventricle with an Anger camera after the injection xenon-133 into the left main coronary artery. Abnormal wall motion was evaluated with biplane left ventriculography at rest and during postextrasystolic potentiation, a potent inotropic stimulus. Abnormal wall motion was defined as hemiaxis shortening of less than 20 percent. Four hemiaxes were designated as corresponding to the four regions of myocardial blood flow. Of 76 hemiaxes evaluated in the 19 patients, 54 manifested normal wall motion and 22 abnormal wall motion; 8 of the 22 hemiaxes had reduced regional myocardial bood flow. In these 8, hemiaxis shortening increased 6 +/- 2 percent (mean +/- standard error of the mean) above values at rest during postextrasystolic potentiation (with normalization of hemiaxis shortening in only 1 of the 8), compared with an increase of 19 +/- 4 percent (P less than 0.001) in the 12 hemiaxes with borderline regional myocardial blood flow (with normalization of hemiaxis shortening in 9 of the 12, P less than 0.05). These results indicate that the presence of reduced regional myocardial blood flow in areas of abnormal wall motion usually predicts a poor response to post-extrasystolic potentiation, whereas abnormal wall motion without reduced regional myocardial blood flow usually predicts a good response. The combination of reduced regional myocardial blood flow and abnormal wall motion suggests scarred and nonviable myocardium.

Adult↗

Regional ejection fraction: a quantative radionuclide index of regional left ventricular performance.

Radionuclide measurements of regional left ventricular ejection fraction were evaluated as a quantitative index of regional left ventricular function. Left ventricular regional ejection fractions were derived from background-corrected, time-activity curves in 43 patients assessed by both gated equilibrium radionuclide angiocardiography and left ventricular contrast angiography. From a single, modified left anterior oblique projection, the regional change in background corrected counts was determined in each of three anatomic regions. The normal range for regional radionuclide ejection fraction was determined in 10 patients with normal contrast ventriculograms and without obstructive coronary artery disease at coronary arteriography. Regional ejection fraction was compared with percent segmental axis shortening and extent of akinetic segments in corresponding regions of the contrast ventriculogram. Radionuclide and roentgenographic methods were in agreement as to the presence or absence of abnormal wall motion in 83 of 99 left ventricular regions (84%) in 33 patients evaluated prospectively. Comparison of regional ejection fraction demonstrated significant differences between regions with roentgenographically determined normokinesis (75 +/- 3%, mean +/- SEM), hypokinesis (44 +/- 3%, p less than 0.0005) and akinesis (24 +/- 5%, p less than 0.005). We conclude that the left ventricular regional ejection provides a reliable quantitative assessment of regional left ventricular performance.

Adult↗

Radionuclide left ventriculography with the slant hole collimator.

A 30 degrees slant-hole collimator was used during radionuclide ventriculography of the cardiac blood pool to improve imaging of the heart in both the modified left anterior oblique (MLAO) and right anterior oblique (RAO) views. In the MLAO view, with the holes slanted caudally, good separation between the left atrium and left ventricle was achieved, and the septum was displayed without foreshortening. In the RAO view with the collimator flat against the chest there was better resolution of the cardiac apex. The results of ejection fraction and wall motion analysis in these patients correlated well with contrast ventriculography (r=0.94). Combination of the slant-hole collimator, in vivo red blood cell labeling with stannous pyrophosphate, simultaneous collection of all phases of the cardiac cycle, and cine mode display, provide a practical system for the noninvasive measurement of left ventricular performance parameters.

Coronary Disease↗