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Biomedical subjects

R Patterson

Publications and source records attributed to R Patterson.

At least 217 records · Page 12Linked to original sources

Desensitization of human basophils with suboptimal concentrations of agonist. Evidence for reversible and irreversible desensitization.

Leucocytes from allergic donors were preincubated with suboptimal concentrations of ragweed or anti-IgE and then challenged with increasing concentrations of the homologous or heterologous agonist. The initial incubation resulted in desensitization, as judged by a reduced reactivity relative to controls preincubated without agonist but challenged similarly. Both homologous and heterologous desensitization were observed and were dose dependent. Evidence was obtained for both a reversible and irreversible component of desensitization, which was also agonist-concentration related. Reversibility occurred to a similar degree either by incubation of suboptimally desensitized cells with optimal concentrations of agonist or by removal of IgE and resensitization. This could implicate IgE-agonist aggregation on the basophil surface as a mechanism of desensitization. Histamine release from desensitized cells was highly correlated with degranulation, suggesting that individual cells were desensitized in an all-or-none manner.

Antibodies, Anti-Idiotypic

Prenatal lead exposure and its potential significance for developmental disabilities: a preliminary study of umbilical cord blood lead levels.

It has been reported that between 1976-1980 the mean blood lead level in American preschool children was 16 micrograms/dl. The Centers for Disease Control (CDC) recently set a blood level of 25 micrograms/dl as the highest acceptable level for children. However, current research findings have provided evidence that detrimental effects on development can occur when lead levels are below this acceptable value. In particular, recent work has shown a relationship between early (prenatal) exposure to lead and delayed cognitive development. Because the developing fetus is particularly vulnerable to insult, it is of critical importance to obtain information about the developmental effects of prenatal exposure to lead and about those factors that may influence this exposure. This report presents initial findings of an ongoing investigation pertaining to issues surrounding early lead exposure. To date umbilical cord blood samples have been measured in 802 infants born at Children's Hospital of Buffalo between November 1987 and April 1988. These infants' residence span approximately 50 townships with most residing in Buffalo proper. Approximately 60 percent of the infants had measurable cord blood lead levels in the range of 4 to 20 micrograms/dl.

Cognition Disorders

Limiting concentrations of human basophil-bound IgE antibody required for histamine release.

Human blood basophils were treated to remove resident IgE, and passively sensitized with mixtures of ragweed antigen E-specific and non-specific IgE under receptor-saturating conditions. At a ratio of about 0.005 (0.5%) specific IgE or higher, maximal histamine release was observed, but below this a progressive decrease occurred. With leucocytes of four donors, minimal ratios producing mediator release above background varied from 0.001 to 0.00034, which was roughly inversely related to the number of IgE receptors per basophil. This indicated that for these donors' cells a similar number of specific IgE molecules was required for histamine release, and calculation showed the numbers to be 30-55, despite a five-fold difference in total numbers of IgE receptors between different donor basophils. Therefore, it could be estimated that the minimal number of bridges required for basophil activation was to the order of 10-15, depending on whether divalent or trivalent bridges were involved. Since percentage histamine release and percentage degranulated cells were highly correlated after suboptimal sensitization, individual cells or subsets of basophils were apparently differentially responsive. This is consistent with other evidence of functional heterogeneity and that histamine release by individual cells is an all or none process.

Allergens

Trimellitic anhydride exposure in a 55-gallon drum manufacturing plant: clinical, immunologic, and industrial hygiene evaluation.

Nine workers at a 55-gallon drum manufacturing plant had history of exposure to a paint powder that contained trimellitic anhydride (TMA). Environmental monitoring revealed airborne levels of TMA to be over 100 times the OSHA permissible exposure limit of 0.04 mg/m3. The exposed workers were evaluated in a cross-sectional study by questionnaire, physical examination, screening pulmonary function tests, serial peak expiratory flow rates (PEFR), and serum antibody levels. Four workers had symptoms consistent with TMA-induced irritant effects. Three had symptoms and IgG levels consistent with TMA late respiratory systemic syndrome (LRSS). Two of these three had PEFR changes that showed significant drops (greater than 20%) 12-18 hours after the end of a work shift. The material safety data sheet for the paint powder failed to list TMA as an ingredient. Despite the well-described toxic effects of TMA, the present study documents that TMA-related illness may continue to be a problem in situations where workers and management are not properly notified of the potential hazards. The measurement of PEFR may be useful in identifying TMA-exposed workers with LRSS.

Adult

What causes stereoscopic tilt from spatial frequency disparity.

A controversy still exists concerning whether the tilt created with interocular spatial frequency disparity arises from a computation of spatial frequency differences or from cumulative positional disparity. In a first experiment, we examined the influence of positional disparity on tilt created with frequency disparity, reasoning that if tilt were computed from spatial frequency differences, the perceived angle should remain unaltered since adding a positional disparity does not change the harmonic content of the stimulus. The results indicated that positional disparity weakened perceived tilt. In a second experiment, we tested the idea that tilt results from the calculation of increasing positional disparity across the display, arguing if local matches of features in the two eyes are made in computing tilt, then the solution to binocular correspondence may be less ambiguous if the same number of cycles was displayed for both spatial frequencies. Perceived tilt increased when the number of cycles was equal, although the angle of tilt still decreased with positional disparity. In Experiment 3, we further reduced potential sources of ambiguity for the binocular matching process by employing D10s (the tenth derivative of a Gaussian) instead of grating patterns. Positional disparity exerted essentially no influence on the perceived angle of tilt of the D10s. Taken together, the results of these experiments suggest that tilt from frequency disparity can be explained solely on the basis of positional disparity.

Depth Perception

Mechanism of leukotriene D4-induced bronchoconstriction in normal subject.

Leukotriene (LT) D4 is a potent constrictor of human airways and a putative mediator of asthma. However, its mechanism of action in man has not been established. In the present study we sought to determine the role of upper airway reflexes, cholinergic pathways, and cyclooxygenase products of arachidonic acid metabolism in mediating LTD4-induced bronchoconstriction in man. Six normal subjects underwent bronchoprovocation testing with LTD4 after pretreatment with either aerosolized phosphate-buffered saline, aerosolized atropine (1.5 mg), aerosolized lidocaine (80 to 160 mg), or oral indomethacin (50 mg three times daily for 10 doses). Specific airway conductance (SGaw), the flow rate at 30% of vital capacity from a partial forced expiratory maneuver (V30P), and the FEV1 were measured at each concentration of LTD4. We calculated the provocative concentration of LTD4 required to produce a 35% fall in SGaw (PC35SGaw) or a 30% fall in V30P (PC30V30P) and the slope of the LTD4 dose-response curve. Atropine increased baseline SGaw 49% (p less than 0.01) and V30P 43% (p less than 0.005). Atropine also increased the PC35SGaw and PC30V30P and increased the slope of the LTD4 dose-response curve. However, neither of these opposing effects was significant. Lidocaine had no effect on either baseline function or the airway response to LTD4. Indomethacin produced small decreases in baseline V30P (12%) and FEV1 (3%) (p less than 0.05 for both), but it too had no effect on the airway response to LTD4. These results indicate that the bronchoconstriction produced by aerosolized LTD4 in normal subjects is not mediated by cyclooxygenase products of arachidonic acid metabolism or irritant receptors in the upper airways. Although cholinergic pathways may play some role, the data suggest that bronchoconstriction results, at least in part, from a direct effect of LTD4 on airway smooth muscle.

Adult

Six-year clinical and immunologic follow-up of workers exposed to trimellitic anhydride.

We report a 6-year study from 1979 through 1985 of workers exposed to trimellitic anhydride (TMA) in three groups of volunteers. Twenty-nine percent of workers (5/17) originally studied had immunologically induced respiratory disease. Subsequent to this evaluation, increased environmental control of TMA exposure was instituted. Since that time, there have been decreasing clinical symptoms and decreasing levels of antibody against TMA conjugated to human serum albumin. These long-term studies originally used radioimmunoassays, but enzyme-linked immunoassays against TMA-conjugated proteins are now demonstrated to be equally appropriate and are more cost-effective. With appropriate clinical and immunologic studies, immunologic airway reactions to TMA may be identified and then prevented by environmental control to decrease inhalation exposure to TMA. This is likely applicable to certain other chemical antigens that immunize by inhalation.

Air Pollutants, Occupational

The safety and activity of polymerized ragweed: a double-blind, placebo-controlled trial in 81 patients with ragweed rhinitis.

Eighty-one patients with ragweed pollinosis were recruited for a double-blind, histamine placebo-controlled study of the safety, immunogenicity, and efficacy of 15 weekly injections of polymerized ragweed (PRW) immunotherapy totaling 1359 allergy units. Patients were paired on the basis of cutaneous end point titration to RAST standardized extracts of giant and short ragweed. One patient of each pair was randomized to receive PRW, and the other patient, a caramelized glucose histamine placebo. Symptom and medication score diaries were completed by 68 patients. All 68 patients received the full maintenance dose. No patient dropped out because of adverse reactions, and there were no systemic reactions. Except for one patient receiving placebo who developed mildly elevated liver function tests, there were no clinically significant changes in routine laboratory tests associated with injections. By Student's test on log-transformed values, blocking antibody rose significantly in the patients receiving PRW but was unchanged in those receiving placebo. By Wilcoxon paired signed-rank test, the symptom and medication scores in the patients receiving PRW were significantly lower than scores in the patients receiving placebo. This study demonstrates the safety, immunogenicity, and activity of PRW in the treatment of ragweed pollinosis.

Adult

Levels and specificity of antibody in bronchoalveolar lavage (BAL) and serum in an animal model of trimellitic anhydride-induced lung injury.

A study was undertaken to characterize the antibody response in rats exposed to trimellitic anhydride (TMA) by inhalation. Total antibody levels directed to trimellitic rat serum albumin (TM-RSA) from TMA-exposed rats were assayed by an ammonium sulfate technique. Total antibody levels in bronchoalveolar lavage (BAL) and the matched serum were compared by correction for the albumin content of each. An ELISA was developed to detect IgG, IgA, and IgM directed toward TM-RSA in BAL and serum and to compare class-specific antibody levels in BAL and serum by normalizing for albumin content. The specificity of the rat IgG response was determined by ELISA inhibition with TM-RSA and TM-human serum albumin (TM-HSA) and compared with reciprocal inhibition studies with serum from TMA-exposed workers. The levels of total antibody in BAL were three to 15 times greater than the levels found in the matched serum pair. IgG, IgA, and IgM antibodies were detected in the BAL and the serum of TMA-exposed rats but not in control rats. In each of the four rats tested, all antibody classes were present in equal or greater amounts in the BAL than in the serum. Complete inhibition of the rat IgG binding in ELISA was observed when TM-RSA or TM-HSA were added as inhibitors. Human IgG was inhibited in ELISA only by TM-HSA. In an animal model of human lung disease, the levels of total antibody as well as class-specific antibodies directed against TM-RSA were greater in BAL than in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Provocative challenge with local anesthetics in patients with a prior history of reaction.

Possible allergic sensitivity to local anesthetic agents remains problematic for some patients who could benefit from their use. We retrospectively reviewed all our consultations for evaluation of local anesthetic allergy from 1965 to 1985 to assess the safety and efficacy of skin testing and provocative test dosing with a variety of local anesthetic agents. Fifty-nine patients reported 70 reactions from the administration of six different local anesthetics. Fifty-four patients could name one or more local anesthetic agents they believed were responsible, and five patients named only "caine" drugs. Multiple reactions of the same type to the same agent were considered as one reaction. On the basis of their history of reaction, the patients were categorized as follows: anaphylactoid reactions (urticaria, angioedema, wheezing, or hypotension within 1 to 2 hours of exposure), possible anaphylactoid reactions (tachycardia, dizziness, syncope, breathlessness, or pruritus occurring within 1 to 2 hours of exposure), contact dermatitis (a typical eczematous skin eruption after appropriate cutaneous sensitization), and other reactions (nonanaphylactoid reactions other than those already described or those occurring more than 2 hours after exposure). Fifty-nine patients were administered local anesthetics after skin testing and provocative test dosing, including two patients who required intravenous lidocaine (Xylocaine; Astra Pharmaceutical Products, Inc., Westboro, Mass.) acutely to control cardiac arrhythmias. These two patients had reported anaphylactoid reactions to oral antiarrhythmic drugs of the local anesthetic class. Despite the history of previous reactions, there were no positive skin tests or positive provocative drug challenges in any patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis

Evaluation and management of corticotropin allergy.

Subsequent use of an adrenocorticotropic hormone (ACTH) preparation may be considered in some instances in a patient who has demonstrated a suspected or proven allergic reaction to corticotropin on prior administration. We describe a patient with multiple sclerosis with a history of anaphylaxis to porcine ACTH in whom another course of treatment with ACTH was being considered. The patient had immediate cutaneous reactivity to porcine ACTH but not to the synthetic ACTH peptide, cosyntropin. With a test-dose schedule, we were able to uneventfully administer cosyntropin to the patient. The presence of serum IgE antibody directed against porcine ACTH and absence of IgE antibody against cosyntropin were demonstrated by ELISA technique, corroborating the skin test results. These studies are consistent with previous evidence that immediate hypersensitivity reactions to corticotropin are IgE mediated and support the value of skin testing in the clinical evaluation and management of known or suspected corticotropin hypersensitivity.

Adrenocorticotropic Hormone

Prolonged evaluation of patients with corticosteroid-dependent asthma stage of allergic bronchopulmonary aspergillosis.

Eight cases with stage IV allergic bronchopulmonary aspergillosis (ABPA) (corticosteroid-dependent asthma stage) were observed for a total of 82 patient years with individual patients observed for 7 to 19 years (mean 10.2) years. One case is the first case of ABPA diagnosed in the United States in 1967. A second case has been observed through four stages of ABPA. None of these eight cases has demonstrated pulmonary deterioration by clinical, chest roentgenogram, or pulmonary function analysis. After diagnosis, the maintenance dose of prednisone in seven of eight cases was a low to moderate dose alternate-day prednisone. These results suggest that continuous observation and management of episodes of pulmonary consolidation or asthma exacerbations may prevent the progression of ABPA to stage V (fibrotic end stage). The total IgE may remain elevated in these patients, and therapy should not attempt to reduce total serum IgE to normal levels. After prolonged therapy with prednisone for asthma and control of ABPA, the IgE and IgG antibody indices against Aspergillus fumigatus may remain elevated or may be below the levels that are of diagnostic value.

Adolescent

Management of drug allergy in patients with acquired immunodeficiency syndrome.

Management of patients with acquired immunodeficiency syndrome (AIDS) is complicated by a high frequency of adverse drug reactions to trimethoprim-sulfamethoxazole and pentamidine. Because of the lack of suitable alternative antiparasitic drugs, some patients who have experienced previous allergic-type reactions to antimicrobial agents may require readministration with incriminated drugs. We report the outcome of seven drug-allergic patients with AIDS evaluated from 1982 to 85. Readministration of pentamidine was carried out without repeated reactions in three patients, and sulfadiazine and sulfamethoxazole-trimethoprim were readministered after very cautious test dosing in two other patients. A generalized maculopapular rash developed after 10 days of sulfadiazine therapy for Toxoplasma chorioretinitis but has been managed with prednisone, 20 to 30 mg/day for 3 months, and sulfadiazine has been continued. The administration of prednisone, 100 to 200 mg daily for treatment of severe cutaneous vasculitis from azulfidine in another patient, did not result in suprainfection. The complexities and potential legal risk of readministration of drugs in the drug-allergic patient with AIDS are emphasized in that coincidental deaths occurred in two patients 48 and 96 hours after readministration of pentamidine.

Acquired Immunodeficiency Syndrome

Iatrogenic pseudoanaphylaxis.

A nurse exposed accidentally to chymopapain by ocular exposure was treated vigorously for chymopapain anaphylaxis. Retrospective analysis of the case indicates that there was no evidence of IgE antibody against chymopapain, and the clinical events were inconsistent with anaphylaxis and could be explained by a vasovagal reaction and the cardiorespiratory effects of repeated intravenous epinephrine. Our assessment is that the nurse is currently in a state of good health; however, she did not accept our absence of allergic disease diagnosis and has sought "clinical ecology therapy." Although no litigation in this case has arisen, the legal implications of this case report are reviewed.

Adult

Allergic bronchopulmonary candidiasis: case report and suggested diagnostic criteria.

A patient with an illness consistent with allergic bronchopulmonary candidiasis is described. The patient had asthma, atelectatic pulmonary infiltrates on three occasions, immediate cutaneous reactivity as low as 10(-7) (wt/vol) to Candida albicans extract, and precipitating antibody to this organism. C. albicans was the only organism cultured from two bronchial lavage specimens. Total serum IgE was elevated to 5745 ng/ml and decreased rapidly with corticosteroid therapy. Serologic studies were not consistent with allergic bronchopulmonary aspergillosis. Serum IgE to C. albicans, measured by ELISA after adsorption of IgG from the serum samples by incubation with staphylococcal protein A, was found to be 575% to 650% above control values. The serum IgE antibody activity against Candida decreased with clinical improvement after corticosteroid therapy.

Adolescent