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Biomedical subjects

R Patterson

Publications and source records attributed to R Patterson.

At least 307 records · Page 17Linked to original sources
PubMed1986

Outcome of pregnancy in women requiring corticosteroids for severe asthma.

We report on the outcome of 56 pregnancies in 51 women with severe asthma requiring prednisone and/or beclomethasone dipropionate. There were no malformations, neonatal deaths, or maternal deaths. The overall incidence of premature (less than 37 weeks gestational age) and low birth-weight infants (less than or equal to 2500 gr) was slightly higher than would be expected in the general population. These findings appeared attributable in part to infants of gravidas whose asthma was complicated by emergency room visits or status asthmaticus. There was a statistically increased incidence of low birth weight and small size for gestational age infants in the eight infants born to women who experienced status asthmaticus when these infants were compared to the 41 infants born to women who did not require emergency room therapy or develop status asthmaticus. Our data confirm that prednisone and beclomethasone dipropionate are appropriate therapy for pregnant women with severe asthma and suggest that the prevention of status asthmaticus may result in a favorable outcome for the fetus. The current study confirms previous evaluations of pregnant women with severe asthma conducted by Northwestern University Allergy Service and extends the series to 171 pregnancies.

Adrenal Cortex Hormones↗
PubMed1986

Ethylene oxide (ETO) as a possible cause of an allergic reaction during peritoneal dialysis and immunologic detection of ETO from dialysis tubing.

An infant with end-stage renal disease requiring continuous ambulatory peritoneal dialysis (CAPD) had a cutaneous eruption with eosinophilia. This reaction was not associated with any drug administration. An analysis for antibodies against ethylene oxide-human serum albumin (ETO-HSA) was conducted because IgE antibodies have been correlated with allergic reactions during hemodialysis. IgE and IgG antibodies against ETO-HSA were demonstrated in one of two serum samples available. Serologic evidence is presented that ETO may be eluted from the dialysis tubing, react with HSA in the peritoneum, and immunize the dialyzed host. This may be a possible explanation for allergic manifestations in our patient and others undergoing peritoneal dialysis.

Antibodies↗
PubMed1986

Comparison of prednisolone kinetics in patients receiving daily or alternate-day prednisone for asthma.

Prednisolone pharmacokinetics were compared in seven patients with asthma managed by alternate-day prednisone therapy and in seven patients with asthma requiring daily doses of prednisone. Steroid requirements of these patients were carefully characterized and had been stable for at least 12 months. Prednisolone volume of distribution, elimination clearance, and elimination t1/2 averaged 0.606 +/- 0.061 and 0.553 +/- 0.162 L/kg, 2.28 +/- 0.43 and 1.93 +/- 0.54 ml/min/kg, and 204 +/- 44 and 214 +/- 19 minutes in patients receiving alternate-day or daily prednisone therapy, respectively. These results indicate that differences in these pharmacokinetic parameters do not account for the well-established clinical observation that some patients require daily prednisone doses and that their disease cannot be managed with alternate-day steroid therapy.

Adult↗
PubMed1986

Human antibodies against formaldehyde-human serum albumin conjugates or human serum albumin in individuals exposed to formaldehyde.

Sera from patients undergoing hemodialysis with formaldehyde (F)-sterilized dialyzers were studied to determine if antibodies against F conjugated to human serum albumin (HSA) could be detected. F-human serum albumin (F-HSA) conjugates were prepared using ratios of F to HSA that did not precipitate the HSA. The F-HSA conjugates migrate differently electrophoretically than HSA with an increased negative charge of F-HSA as compared with HSA. The F-HSA was used in an ELISA. The results demonstrated that in certain sera, IgG, IgM, IgA and IgE antibodies against F-HSA could be measured. In the highest titered sera, it was shown that the IgG antibody was not directed against F alone or F-lysine but against an antigenic grouping of F-HSA. No correlation of either IgG or IgE antibodies with immune complex or allergic reactions was found in this series of dialysis patients. Some sera from dialysis patients had antibody activity against HSA. Sera from 2 physicians with rhinitis after F exposure had no antibody activity against F-HSA or HSA. Two nurses with a history of F-induced asthma had no IgG antibodies but did have IgE antibodies against F-HSA and HSA. This spectrum of immunologic responses is analogous to responses in dogs immunized with F or F dog albumin. We have not been able to identify anti HSA antibodies in patients reactive to other hapten-HSA compounds and it is suggested that anti HSA antibodies in F-exposed humans may relate to the F exposure.

Antibody Specificity↗
PubMed1986

Allergic bronchopulmonary aspergillosis in asthmatic patients presenting with allergic rhinitis.

The early diagnosis of allergic bronchopulmonary aspergillosis (ABPA) is is important because it may allow prevention of evolution to the fibrotic lung disease stage (stage V). In two immunotherapy studies of 62 patients recruited for allergic rhinitis, we conducted studies to exclude ABPA in any subject with asthma and positive immediate skin reactivity to Aspergillus fumigatus. The evaluation included serum precipitating antibodies against A. fumigatus, total serum IgE, blood eosinophilia, serum IgE and IgG antibody indices against A. fumigatus, and chest X-rays. Three of the 62 patients (5%) had features indicative of ABPA. This finding underscores the importance of excluding the diagnosis of ABPA in all asthmatics with skin reactivity to A. fumigatus, even if the patients major initial complaint is allergic rhinitis.

Adult↗
PubMed1986

Inhibition of rhesus monkey airway and cutaneous responses to platelet-activating factor (PAF) (AGEPC) with the anti-PAF agent SRI 63-072.

Previous studies with synthetic platelet-activating factor (PAF) (AGEPC) showed that aerosol challenges in rhesus monkeys resulted in airway responses simulating acute antigen-induced responses and immediate-type skin reactions [1]. The current studies evaluated whether an antagonist of PAF (SRI 63-072) could inhibit the airway and cutaneous reactivity to PAF. Under the conditions of these experiments, the antagonist partially inhibited PAF activity in both experimental systems. Inhibition of endpoint cutaneous reactivity to PAF may be a suitable system for comparing potency of pharmacologic antagonists in primate skin.

Aerosols↗
PubMed1986

Aging changes in Bruch's membrane of monkeys: an electron microscopic study.

Bruch's membrane from monkeys of various ages was studied by electron microscopy. In monkeys under 15 years of age, Bruch's membrane rarely contained a small amount of polymorphous material that did not appear to increase with advancing age up to 15 years. However, the polymorphous material did increase over 20 years of age. The accumulation of vesicular, granular, tubular and linear polymorphous material in Bruch's membrane was though to be a result of evagination of a minimal portion of a retinal pigment epithelial (RPE) cell between adjacent basal infoldings, and its subsequent degeneration. The plasma membrane of the evagination seemed to be the primary source of the tubular or linear material, vesicles the main source of vesicular material, and cytosol and basement membranes to be the source of the granular material. The fibrous long-spacing collagen was associated with the basement membrane of the choriocapillaris and RPE cells. The granular deposits between the plasma infoldings and the basement membrane of RPE cells may originate from the basement membrane of the RPE, and could be the initial lesion of basal linear deposits.

Aging↗
PubMed1986

Characterization of the airway response to inhaled leukotriene D4 in normal subjects.

To better understand the role of leukotriene D4 (LTD4) in the pathogenesis of airway hyperreactivity, we administered aerosolized LTD4 on multiple occasions to 6 normal subjects and measured specific airway conductance (SGaw) by body plethysmography and the flow rate at 30% of vital capacity from partial forced expiratory maneuvers (V30P). Dose-response curves generated from standard bronchoprovocation tests revealed that LTD4 was 280 to 590 times more potent as a bronchoconstrictor than was methacholine. The airway response to single bronchoconstricting doses of LTD4 administered on separate days was reproducible for SGaw (r = 0.86, p less than 0.05) and V30P (r = 0.95, p less than 0.005). The response to 3 consecutive single-dose LTD4 challenges performed on the same day, allowing SGaw and V30P to return to greater than 90% of the control value between challenges, demonstrated tachyphylaxis: the response to the third dose was significantly less than the response to the first dose for SGaw (p less than 0.001) and for V30P (p less than 0.01). A single bronchoconstricting dose of LTD4, given before a standard methacholine dose-response challenge, lowered the concentration of methacholine needed to decrease V30P 30% (p less than 0.05) and SGaw 35% (p = 0.09). A single bronchoconstricting dose of methacholine preceding a standard methacholine challenge did not have this effect. LTD4 and methacholine demonstrated a cumulative dose-effect when progressively higher concentrations were inhaled. In summary, the airway response to LTD4 is reproducible, exhibits tachyphylaxis, and a cumulative dose-effect occurs. As well, LTD4 increases the responsiveness of normal airways to methacholine.

Adult↗
PubMed1986

Pathogenesis of drusen in the primate.

Two monkey eyes that showed clinical evidence of drusen were studied by light and electron microscopy. The drusen-like spots had several different morphological patterns: the appearance of typical drusen, budding retinal pigment epithelial (RPE) cells, and vacuolation of retinal pigment epithelial cells. Several stages of budding were seen. In some lesions, part of the RPE cell protruded into the sub-RPE space. The upper portion of the budding cell was connected to the cytoplasm of the parent RPE cell and was surrounded by basement membrane of the RPE cell. These budding cells had plasma membranes, cytoplasm that contained organelles, and a nucleus. Disconnected buds, separate from the parent RPE cell, were also seen; these showed degeneration. Finally, an accumulation of vesicular, granular, tubular and linear material was found in the nodular space beneath the RPE cell. It is suggested that this budding of RPE cells is the initial event in drusen-formation.

Animals↗
PubMed1986

Binding constants of IgE receptors on human blood basophils for IgE.

The ability to remove receptor-bound IgE but maintain functional integrity of human blood basophils allowed measurement of several parameters of binding of IgE. Non-specific binding was determined by a modification of the standard technique and was found to be only about 10% of specific binding. The number of free receptors varied inversely with the serum IgE of the donor. Forward rate constants were readily measured at 0 degree but were considerably higher at 37 degrees, and a rough estimate of the activation energy for binding was calculated to be 6700 calories/mol. Saturation of basophil receptors with IgE occurred in 1-3 h using 3.6 micrograms 125I-IgE/ml at 37 degrees. For seven donors, the forward rate constant, k1, ranged from 2.9 to 7.25 X 10(4) M/sec with a mean of 5.2 X 10(4)/M/sec. This is about one-third the reported value for cultured cord blood basophils. The backward rate constant, k-1, ranged from 1.4 to 3.9 X 10(-5)/sec with a mean of 2.5 X 10(-5)/sec. This is less than half that of cord blood basophils. The equilibrium association constant, Ka, ranged from 1.4 to 2.7 X 10(9)/M with a mean of 2.1 X 10(9)/M. This is comparable to the high affinity binding reported for cord blood and other basophils. There was no great difference in binding constants among the four atopic and three non-atopic donors studied. The affinity of monoclonal mouse 125I-IgE for IgE receptors on human basophils was about four-fold lower than that of human IgE. Sensitization of human basophils for histamine release with mouse IgE anti-DNP was confirmed. Non-specific human IgE but not IgG inhibited sensitization by mouse IgE, indicating that the same receptors were involved and that they were specific for IgE.

Basophils↗
PubMed1986

Modified antigens in the treatment of allergic disease.

In summary, effects at improvement upon conventional immunotherapy by antigen modification have taken three major directions. First, methods designed primarily to impede allergen release from the site of deposition have been only modestly successful. An example is alum-precipitated extracts which require somewhat fewer injections. Second, attempts to suppress specific IgE production have been unsuccessful in human trials, although antigen-specific IgG levels have increased in a manner similar to that produced by conventional allergen immunotherapy. The third major avenue of antigen modification, to reduce allergenicity while retaining immunogenicity, appears, at present, to be the most promising. Clinical studies of polymerized allergens summarized above have shown that patients can be given a course of polymerized allergen immunotherapy in a few weeks, while a course involving a comparable quantity of unmodified allergen would require years. With the use of polymerized pollen extracts, degree of symptom reduction, persistence of benefit, and magnitude of IgG-blocking antibody induction are comparable to that achieved with unmodified allergens, while the incidence of systemic reactions is greatly reduced. The development of polymerized allergens appears to represent a significant advance which may be expected to expand the clinical utility of allergen immunotherapy.

Allergens↗
PubMed1986

Comparison of cutaneous and bronchial reactivity to leukotriene D4 in humans.

To establish whether a relationship exists between cutaneous and bronchial reactivity to leukotriene D4 (LTD4), endpoint cutaneous reactivity and bronchial reactivity were determined in six patients with asthma, six patients with seasonal allergic rhinitis, and six nonatopic men. In all subjects, increasing doses of LTD4 produced decreases in specific airway conductance (SGaw) and flow at 30% of vital capacity measured from a partial forced expiratory maneuver (V30P). Intracutaneous injections of LTD4 and histamine resulted in immediate wheal and erythema reactions in all patients. Serial 10-fold dilutions of LTD4 and histamine were injected to establish the lowest dose capable of producing a 4 mm wheal with erythema. Endpoint cutaneous reactivity to LTD4 ranged from 1 mumol to 100 pmol in controls and from 100 nmol to 1 fmol in patients with asthma, but statistically significant differences between groups were not apparent even with inclusion of six additional subjects. No meaningful correlations were found between the quantity of LTD4 producing the threshold cutaneous reaction and the dose of inhaled LTD4 that produced a 35% decrease in SGaw and 30% decrease in V30P. In contrast to the bronchi, where subjects in all three groups were 264 to 840 times more sensitive to LTD4 than to methacholine, 11/18 subjects (3/6 with asthma) were less sensitive to LTD4 than to histamine in terms of endpoint cutaneous reactivity. However, seven of 18 subjects who were more sensitive to LTD4 than to histamine had relative potencies ranging from 5 to 500,000.

Asthma↗
PubMed1986

A comparison of the immune response to immunotherapy with polymerized grass allergen and monomeric grass allergen.

This study compares the immune response of ten patients treated with polymerized grass (PG) immunotherapy with that of 12 patients treated with conventional monomer grass (MG) immunotherapy. The patients treated with PG immunotherapy received a mean cumulative dose of 44,840 protein nitrogen units (PNU), and those treated with MG immunotherapy received a mean cumulative dose of 46,083 PNU. Total antibody binding of perennial rye grass groups I, II, and III (RGGI, RGGII, and RGGIII) was measured in the serum of each individual. In addition, IgG titers to partially purified extracts of Bermuda, timothy, and orchard grass were also determined. A significant increase in the total antibody binding of RGGI, as well as an increase in the mean IgG titer to Bermuda, timothy, and orchard grass was demonstrated after treatment in the patients who had received PG immunotherapy. The mean total antibody binding of RGGII and RGGIII also increased in these patients, although not significantly. No significant difference in the mean total antibody binding of RGGI, RGGII, or RGGIII nor in the mean IgG titer to the three grass extracts was found in the sera of the two groups of patients. This study demonstrates a comparable immune response between immunotherapy with PG and MG, and retention of antigenic determinants during the polymerization process.

Allergens↗
PubMed1986

Natural history of asthma in patients requiring long-term systemic corticosteroids.

To study the natural history of corticosteroid-dependent asthma, we evaluated 40 randomly selected adult patients with severe asthma who were refractory to management with inhaled corticosteroids and bronchodilators and who required long-term prednisone therapy (mean duration, 6.2 +/- 5.1 years). During long-term observation, 13 patients (32.5%) significantly improved; ten (25%) of these tolerated discontinuation of long-term prednisone use and three (7.5%) had decreased prednisone requirements. Three patients (7.5%) had increased requirements for prednisone. Twenty-four patients (60%) had generally unchanged, long-term prednisone requirements; of note, eight of these had significant, but temporary intervals (mean, 3.2 years) when they could be managed without prednisone. Patients with mixed asthma were more likely to tolerate discontinuation of long-term prednisone; no other factors studied were predictive of the course of asthma. Although prior to our care many patients had a history of numerous emergency room visits and hospitalizations (some for life-threatening episodes of status asthmaticus), there were few emergency room visits and hospitalizations while under strict management by our service. Variations observed in the natural history of corticosteroid requirements in asthma must be considered in designing studies seeking to evaluate efficacy of new experimental therapies for asthma.

Administration, Inhalation↗
PubMed1986

Identification of patients at risk for anaphylaxis due to streptokinase.

To identify patients at risk for immediate-type allergic reactions to streptokinase, we performed streptokinase skin tests on patients immediately before planned administration of intravenous streptokinase for treatment of acute myocardial infarction. Forty-five patients had negative skin tests and received streptokinase without allergic reaction. One patient had a positive skin test and was given urokinase instead, without incident. Positive skin tests were also present in a patient who had recently had an anaphylactic reaction to streptokinase, and in two physician volunteers who had been sensitized to streptokinase during initial determination of the optimal skin testing dose. Immunoassays for IgE to streptokinase were performed on serum samples from skin-tested patients and volunteers, and on 16 other patients who had not been skin tested but had previously received streptokinase without allergic reactions. The skin test was a sensitive and specific indicator of elevated levels of IgE to streptokinase. We propose that skin testing immediately before streptokinase administration is a practical approach for identifying patients at risk for immediate-type allergic reactions to streptokinase, and its use may possibly prevent anaphylaxis and death.

Anaphylaxis↗