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Biomedical subjects

N A Pawlowski

Publications and source records attributed to N A Pawlowski.

At least 19 recordsLinked to original sources
PubMed2001

Anaphylaxis to raw potato.

BACKGROUND: Potato allergy has been described rarely, generally in relation to the Oral Allergy Syndrome (OAS). Adults with seasonal allergic rhinitis have been reported in whom peeling of raw potatoes causes oculonasal symptoms, wheezing, and contact urticaria. Skin testing with fresh fruits and vegetables has been recommended in cases of OAS, although the sensitivity of commercial potato extract is reportedly equal to that of fresh potato. CASE REPORT: This report describes a 4-year-old with raw potato-induced anaphylaxis. He rapidly developed urticaria, angioedema, respiratory distress, vomiting and diarrhea after biting into a raw potato that was being used for painting in preschool. Review of systems is significant for viral-induced wheezing, but no symptoms suggestive of seasonal allergic rhinitis were evident. His mother has a history of seasonal allergic rhinitis and contact urticaria with raw potato. Skin testing to commercial potato extract was negative and skin testing to fresh potato by the prick + prick method was markedly positive. Skin testing to birch tree was negative. An open challenge to a small amount of cooked potato was negative. Food challenge to raw potato was not considered indicated in this case of immediate anaphylaxis to a single food. CONCLUSIONS: This patient had clinical and skin test reactivity to raw and uncooked potato in the absence of OAS. The patient will be followed for the development of seasonal allergic rhinitis.

Administration, Oral↗
PubMed2000

Resolution of childhood peanut allergy.

BACKGROUND: Peanut allergy creates great fear in many families because it is one of the leading causes of fatal and near-fatal food-induced allergies. Earlier reports suggested that peanut allergy was life-long, but a recent study described resolution of peanut allergy in some children. OBJECTIVE: Tolerance to peanut allergy in childhood was studied. Examination of the natural history of childhood peanut allergy was explored. METHODS: A retrospective review of all children with peanut allergy seen at the Children's Hospital of Philadelphia in a 3-year period (n = 293). Children with histories of peanut allergy were challenged at the mean age [3.8 years; range 1.5 to 8 year] which was 1.8 years [range: 0.5 to 6.8 years], following their last known clinical reaction. Food allergy or tolerance was confirmed by open challenges. RESULTS: Thirty-three patients with histories of peanut allergy and a positive skin test to peanut underwent oral challenges. Not one patient (n = 5) with a history of peanut anaphylaxis developed tolerance to peanuts. In comparison, 9 of 17 patients with history of urticaria upon ingestion to peanuts developed tolerance. Also, 4 of 10 patients with flaring of their atopic dermatitis upon ingestion to peanuts developed tolerance. The 14 patients with a negative challenge to peanut had a significantly smaller wheal and flare reaction than the 19 patients with positive challenges. Tolerance to peanut was documented by a positive challenge reverting to a negative challenge in one patient. Oral challenge of 13 additional patients with positive skin tests and histories of only refusing to eat peanut resulted in 5 (39%) positive challenges. CONCLUSION: A selected group of peanut-allergic children, who do not have a history anaphylaxis to peanut, may develop tolerance to peanuts.

Arachis↗
PubMed2000

Prevention of asthma morbidity: recent advances.

Asthma prevalence has risen substantially in recent decades and is an increasing cause of disability for American children. Concern about the rise in morbidity has led to treatment guidelines and a growing body of clinical research. Recent trials continue to support the role of inhaled corticosteroids as the most effective therapy to control airway inflammation associated with persistent asthma. Growth suppression due to inhaled corticosteroids has also been well documented, although the long-term effects and relative potencies of different agents require further study. Other anti-inflammatory agents such as cromolyn and the new class of leukotriene receptor antagonists have demonstrated benefit in milder patients. Leukotriene receptor antagonists and long-acting beta2-agonists may allow for reduction of inhaled steroid doses. Control of environmental allergens and irritants is essential. New evidence suggests an increasingly important role for allergen immunotherapy.

Administration, Inhalation↗
PubMed1998

Routine and influenza vaccination rates in children with asthma.

BACKGROUND: Children with asthma may be at increased risk for low immunization rates given that they have recurrent illnesses that often result in acute care visits to their pediatrician, visits to the emergency room, admissions to the hospital, and visits to subspecialists, where immunizations are not routinely administered. OBJECTIVES: To assess immunization rates for routine and influenza vaccines in children with asthma and assess factors that may contribute to delay. METHODS: We conducted a cross-sectional survey of 117 children aged 6 to 48 months with onset of asthma within the first 15 months of life. Subjects were recruited from an allergy and immunology clinic at an urban, tertiary care center. Those judged to have immunization delay did not have the required 4 DTP, 3 OPV, and 1 MMR vaccine by age 24 months (4:3:1 series). Receipt of influenza vaccine was determined for eligible children with moderate to severe asthma. RESULTS: Seventy-four (80%) children had up-to-date immunizations at age 24 months. Those with delay had fewer visits to a subspecialist than those who were up-to-date (1 versus 2 visits P = .010). Twenty-two (25%) of 87 eligible subjects received influenza vaccine. Recipients were more likely to have been hospitalized than nonrecipients (77% versus 49%, P = .022). CONCLUSIONS: Though the majority of young children with asthma were up-to-date for routine immunizations, only 25% of children with moderate to severe asthma received influenza vaccine. Greater efforts must be made by pediatricians and asthma subspecialists to ensure that children with moderate to severe asthma are immunized against influenza virus.

Asthma↗
PubMed1996

Latex allergy in pediatric emergency department personnel.

Allergy to natural latex proteins has been recently recognized as a dangerous entity among health care professionals. Cutaneous symptoms related to latex glove use vary from the redness and scaling of contact dermatitis to urticaria. In addition, anaphylactic reactions have been reported. We report the spectrum of reactions to latex glove use in 93 members of our emergency department (ED) staff during a one-month study period. In addition, we attempt to correlate these symptoms with serologic evidence of atopy and latex allergy. Eighty-four of these subjects underwent total serum immunoglobulin E and latex-specific radioallergosorbent test (RAST) testing. Fifty-four percent of subjects reported symptoms relating to latex glove use, categorized as either contact dermatitis (48.4%) or urticaria (5.4%). Of the urticaria group, two subjects reported additional symptoms related to latex glove use such as rhinitis, conjunctivitis, or sneezing. All three groups of subjects (asymptomatic, contact dermatitis, and urticaria) were alike with respect to age, sex, and race. The urticaria group reported a higher incidence of environmental allergies (chi 2, P = 0.02). Serum total immunoglobulin E levels and latex-specific RAST results did not differ among the three groups. The one subject with a positive latex-specific RAST reported urticarial and nasoocular symptoms when exposed to latex gloves. Seventeen percent of symptomatic subjects reported decreased use of latex gloves because of these symptoms. It was concluded that many members of our pediatric ED staff exhibit a sensitivity to latex antigens. Clinical symptoms, rather than serologic testing, must be used to identify latex-sensitive individuals in this setting. Recommendations are offered to assist in the identification and management of hospital personnel who exhibit allergy to latex-containing products.

Adult↗
PubMed1996

A comparison of electrochemiluminescence and flow cytometry for the detection of natural latex-specific human immunoglobulin E.

In vitro correlates of type 1 hypersensitivity to natural latex (NL) proteins continue to be limited by both sensitivity and specificity. Methods which have detection limits in the picogram range, namely, radioallergosorbent assays (RAST) and enzyme-linked immunosorbent assays (ELISA), are inadequate for the identification of NL hypersensitivity in certain at-risk groups, such as health care workers. A flow cytometry assay (FCA), previously shown to be comparable to RAST and ELISA in the identification of NL-sensitized pediatric patients with spina bifida, was compared with electrochemiluminescence (ECL) in the evaluation of pediatric patients with spina bifida and NL-sensitized adult health care workers. As with RAST and ELISA, ECL is capable of detecting picogram amounts of specific analyte. The ECL assay detected NL-specific immunoglobulin E (NL-IgE) in three of six health care workers with strong histories of NL hypersensitivity. All six patients were negative by FCA. Further, 2 of 11 spina bifida patients found to be NL-IgE negative by FCA were NL-IgE positive by ECL. These findings suggest that in sensitivity the ECL assay is an improvement over the FCA for the identification of NL-sensitive individuals.

Adult↗
PubMed1995

Physician-targeted program on inhaled therapy for childhood asthma.

BACKGROUND: Inhaled medications are the mainstay of asthma therapy, but significant deficiencies exist in the knowledge and skills of physicians regarding use of metered-dose inhalers (MDI) and spacer devices. OBJECTIVE: We developed, implemented, and evaluated the effects of a physician-targeted educational program on inhaled therapy in a group of pediatric residents in our institution. METHODS: Patient-directed instruction sheets on aerosol therapy were developed on the basis of literature review and expert guidelines. These served to establish a consistent foundation for the educational curriculum. The program was delivered through one-on-two teaching sessions (45 minutes). Residents were provided with a summary of theoretical and practical information and with devices for practice (a placebo MDI, InspirEase and AeroChamber holding chambers, and the AeroChamber device with mask). Each session included review of an educational monograph, demonstration of proper technique, and practice with the different devices. The program was evaluated by a randomized-control design. Assessment of practical skills included number of correct steps for the use of MDI (maximum score, 7), InspirEase (maximum, 7) and AeroChamber (maximum, 6). Theoretical knowledge was assessed with 25 multiple-choice questions. RESULTS: Pretest scores in the experimental group (n = 24) were 3.7 of 7, 1.9 of 7, and 0.3 of 6 steps correct for MDI, InspirEase, and AeroChamber devices, respectively, and 13 of 25 for the theoretical knowledge assessment. The control group (n = 26) had similar pretest scores. After the program the experimental group significantly improved in all parameters: 6.3 of 7, 5.9 of 7, and 4.5 of 6 steps correct for MDI, InspirEase, and AeroChamber devices, respectively, and 18 of 25 questions correct (p < 0.01 for all parameters). CONCLUSIONS: Implementation of a simple educational program among pediatric residents can significantly increase their skills in the use of inhalational therapy.

Administration, Inhalation↗
PubMed1995

Latex hypersensitivity in children: clinical presentation and detection of latex-specific immunoglobulin E.

OBJECTIVE: To better understand the clinical characteristics, diagnosis, and possible prevention of immediate hypersensitivity reactions to latex in a hospitalized, pediatric patient population. METHODS: We performed a retrospective case analysis of the first 35 patients with latex allergy evaluated by our service over a 2-year period at our institution. Characteristics of patients and clinical reactions were analyzed and the presence of latex-specific immunoglobulin E was assessed using in vitro methods. In a limited group of patients, the success of strict environmental control and premedication with steroids and antihistamines was evaluated for the prevention of latex allergic reactions. RESULTS: The majority of our patients had life-threatening reactions. In previous reports, most pediatric patients underwent reactions in the perioperative period and belonged to two well-recognized "high-risk" patient groups (spina bifida and genitourinary malformations). In our series, 21 patients (60%) had reactions outside of the operating room setting, and 14 patients (40%) had primary diagnoses outside of the previously recognized "high-risk" groups. Many patients had a history of multiple surgical procedures, and a history of a surgical procedure in the first year of life was very common. A pre-existing clinical history of latex allergy was present in only 18 of the 35 patients, and a severe or life-threatening allergic reaction was the presenting feature of latex allergy in 11 of the 35 patients. Using in vitro assays, we were able to detect latex-specific immunoglobulin E in the sera of all but two of our patients. Latex gloves and latex-containing intravenous sets were common triggers for reactions. When exposure to latex occurs systemically, as through an intravenous line, premedication with steroids and antihistamines may fail to protect against anaphylaxis. CONCLUSIONS: Our experience indicates that the incidence of latex hypersensitivity in children is increasing, that the circumstances (patient profile, hospital location, route of exposure) in which life-threatening reactions may occur are more broad than previously reported, and that a better understanding of both environmental sources of latex antigens and host responses to latex exposure are needed for improved prevention of serious reactions.

Adolescent↗
PubMed1994

What do pediatricians in training know about the correct use of inhalers and spacer devices?

Most patients with asthma in the United States are cared for by nonspecialist physicians. Because inhaled medications are the mainstay of asthma therapy and their successful use requires both practical skills and theoretic knowledge, we wondered how much nonspecialist physicians know about the use of metered-dose inhalers and spacer devices. Fifty pediatricians in training were interviewed individually. Practical knowledge was assessed by asking each to demonstrate correct use of a placebo inhaler and a spacer device (Inspirease [Key Pharmaceuticals, Inc., Miami, Fla.] and Aerochamber with mask [Monaghan Medical Corp., Plattsburgh, N.Y.]). Of the seven recommended steps for use of metered-dose inhalers, the residents demonstrated an average of 3.8 steps correctly. The most common errors included not shaking the metered-dose inhaler before use (18% of residents correct) and insufficient breath holding (28% correct). In testing spacer use, the most common errors included not shaking the canister (16% correct) and incorrect number of activations and inhalations (12% correct). Many residents were not familiar with correct assembly of the spacer (48% correct). Theoretic knowledge of metered-dose inhaler and spacer use was evaluated by a written questionnaire. The most common deficiencies in theoretic knowledge related to the purpose of slow inspiration and breath holding. Most of the participants had been treating children with asthma and had prescribed metered-dose inhalers (45 of 50, 90%) and spacer devices (76%) in the past.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗
PubMed1994

Flow cytometric measurement of immunoglobulin E to natural latex proteins.

Immediate hypersensitivity to natural latex (NL) occurs in sensitized individuals after repeated exposure to products or devices containing NL components. Since allergic reactions to NL proteins are quite frequent and may be quite serious, diagnostic assays are needed to identify individuals at risk. A number of latex proteins have been considered the major antigens, but they have been incompletely characterized. There is no standard material available for skin testing. In vitro diagnostic tests, such as the radioallergosorbent test (RAST), are time consuming and their sensitivity and specificity remain to be proven. We have developed a rapid microsphere-based, fluorescence-activated flow cytometry assay for the measurement of NL protein-specific human immunoglobulin E and have compared it with both the enzyme-linked immunosorbent assay and radioallergosorbent test methods. By using the total purified NL protein fraction isolated from raw ammoniated NL sap as the antigen, the flow cytometry assay was both sensitive and specific for the detection of NL protein-specific human immunoglobulin E in the sera of sensitized pediatric patients.

Adolescent↗
PubMed1992

Role of endothelin-1 in regulating proliferation of cultured rabbit airway smooth muscle cells.

Increased expression of the potent vasoconstrictor and bronchoactive peptide, endothelin-1 (ET-1), has recently been demonstrated in airway epithelial and endothelial cells of asthmatic patients. To identify its potential role in contributing to airway smooth muscle (ASM) hyperplasia, a characteristic feature of asthmatic airways, the mitogenic action of ET-1 was investigated in cultured rabbit ASM cells. ET-1 elicited significant dose-dependent (10(-12)-10(-6) M) increases in ASM cell number, with a mean potency (i.e., -log mean effective dose) of action of 9.82-log M. ET-1 also acutely stimulated intracellular inositol 1,4,5-trisphosphate accumulation. The latter response was blocked by phospholipase C inhibition with neomycin; however, neomycin had no effect on the promitogenic action of ET-1. By contrast, the ASM cell proliferative response to ET-1 was independently inhibited by pertussis toxin, inhibitors of phospholipase A2, cyclooxygenase, and thromboxane A2 (TxA2) synthesis, as well as blockade of the TxA2 receptor. Moreover, in complementary studies, we found that administration of the stable TxA2 mimetics, carbocyclic TxA2 (CTA2) and U-46619, induced ASM cell proliferation and that ET-1 evoked the release of endogenous TxA2 from the ASM cells. Collectively, these observations provide new evidence that 1) ET-1 is a potent mitogen of ASM cells, 2) the promitogenic effect of ET-1 is associated with activation of a pertussis toxin-sensitive G protein coupled to stimulation of phospholipase A2, and 3) the latter mediates ASM cell proliferation via the release and autocrine mitogenic action of TxA2. The findings support a potential role for ET-1 in mediating the characteristic hyperplasia of ASM in asthma.

Animals↗
PubMed1991

Role of endothelin 1 in regulating rabbit airway contractility.

Endothelin 1 (ET-1) is a potent vasoconstrictor peptide recently isolated from vascular endothelial cells. Because its role and mechanisms of action in regulating airway contractility remain to be identified, we examined the contractile effects of ET-1 in isolated rabbit tracheal smooth muscle (TSM) segments. In TSM under passive tension, ET-1 elicited dose-dependent contractions with a mean +/- SE -log 50% of maximal response value of 7.82 +/- 0.13 vs. a value of 5.61 +/- 0.07 -log M for acetylcholine (ACh). In TSM half-maximally contracted with ACh, however, ET-1 exerted dual and opposing contractile effects. Lower doses of ET-1 (less than or equal to 10(-9) M) produced a 74.2 +/- 16.6% decrease in active TSM tension. This relaxant response to ET-1 was associated with an accelerated accumulation of prostaglandin (PG) I2 and PGE2 and was attenuated by cyclooxygenase inhibition with indomethacin (10(-5) M). The combination of indomethacin and removal of the airway epithelium completely inhibited the TSM relaxant response to ET-1. In contrast, higher doses of ET-1 (greater than 10(-9) M) induced airway contractions that were attenuated by the Ca2+ channel blockers nifedipine (10(-5) M) and diltiazem (10(-5) M) and ablated in Ca2(+)-free buffer. Moreover, ET-1-induced TSM contractions were inhibited by the protein kinase C (PK-C) antagonists 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, and staurosporine.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Mechanisms of action of endothelin 1 in maturing rabbit airway smooth muscle.

Maturational differences in the effects and mechanisms of action of endothelin 1 (ET-1) on airway contractility were investigated in tracheal smooth muscle (TSM) segments isolated from 2-wk-old and adult rabbits. In TSM under passive tension, ET-1 elicited dose-dependent contractions, with a potency of action that was significantly greater (P less than 0.001) in the 2-wk-old vs. adult tissues (i.e., mean +/- SE - log 50% of maximal response values: 8.59 +/- 0.17 vs. 7.79 +/- 0.15 - log M, respectively). In TSM half-maximally contracted with acetylcholine (ACh), however, ET-1 elicited dual and opposing dose-dependent effects. At lower doses (less than or equal to 10(-9) M), ET-1 induced TSM relaxation that was significantly greater in the adult vs. 2-wk-old TSM segments (i.e., approximately 100 vs. 26.5% decrease in active tension, respectively). The relaxant responses were associated with significantly enhanced (P less than 0.001) ET-1-induced release of prostaglandins E2 and I2 in the adult tissues. At higher doses (greater than 10(-9) M), ET-1 induced TSM contractions that were 1) attenuated to a relatively greater extent by the Ca2+ channel blocker, nifedipine (10(-5) M) in the 2-wk-old tissues and 2) associated with significantly (P less than 0.001) enhanced ET-1-stimulated accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in the immature TSM. Moreover, the TSM contractions were inhibited by the protein kinase C (PKC) antagonist, H-7, and the latter effect was more potent in the immature TSM. Collectively, these findings demonstrate that ET-1 exerts a potent duality of action in rabbit TSM which varies significantly with maturation, wherein 1) age-dependent differences in airway relaxation are associated with changes in the evoked release of bronchodilatory prostaglandins and 2) maturational differences in airway contraction are associated with changes in Ins(1,4,5)P3 accumulation and extracellular Ca2+ mobilization, coupled to differences in PKC activation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

The selective binding and transmigration of monocytes through the junctional complexes of human endothelium.

Human monocytes show a high affinity for vascular endothelium both in vitro and in vivo. To explore monocyte-endothelial interaction in greater detail, we have developed a new in vitro model for growth of human endothelial cells (EC). Human umbilical vein EC (HUVEC) cultured upon collagen gels form confluent monolayers of EC that bind silver at their intercellular border similar to cells in situ. Intercellular junctional structures, both adherens and tight junctions, were identified. In contrast, HUVEC grown on plastic surfaces did not stain with silver. The silver-staining characteristic of EC-collagen monolayers was reversible and related to their in vitro maturation and senescence. Silver staining of EC borders provided a grid by which the location of monocyte binding to the luminal surface of individual EC could be assessed. Using this technique, we found that monocytes preferentially bound to the margins of EC, in approximation to the silver-staining junctions. These results suggest that EC determinants recognized by monocytes occur in a unique topographical distribution on the apical face of EC. After binding, monocytes migrated through the EC monolayers at high basal rates. The lack of penetration of collagen gels in the absence of an EC monolayer suggested the generation of EC-specific chemotactic signal(s). Monocytes were observed to pass between EC without evidence of disruption of the monolayer. Silver stain remained present during all phases of migration, and under transmission electron microscopy, junctional complexes were found proximal to monocytes that had just completed their passage through the monolayer. After orientation to the basal surface of the EC monolayer, monocytes migrated randomly into the underlying collagen gel. Monocyte adherence, penetration, migration, and long term survival can be studied under these conditions.

Cell Adhesion↗
PubMed1985

Human monocyte-endothelial cell interaction in vitro.

We have examined the interaction of freshly isolated human blood monocytes with cultured human umbilical vein endothelial cells in vitro. Purified monocytes incubated with confluent primary or passaged endothelial cells (EC) for 90 min at 37 degrees C bound at maximal densities of 6.5-7.0 X 10(3)/mm2 (8 or 9 per EC) without causing disruption of the monolayer. Monocyte-EC binding proceeded in the presence of plasma proteins or optimal phagocytic doses of opsonized zymosan particles. The avidity of attachment was not diminished by alternative monocyte isolation techniques. Monocyte attachment to EC was dependent upon the presence of divalent cations (magnesium greater than calcium) and was inhibited at 4 degrees C. Monocytes selectively bound to EC when incubated with monolayers composed of smooth muscle cells and EC. Neither EC monolayer confluence nor a variety of EC culture conditions affected the high levels of monocyte binding. In contrast, human neutrophils (less than 1 per EC) and lymphocytes (less than 2-3.5 per EC) bound at lower maximal densities under the same conditions, while platelet reactivity remained minimal. The distinctively higher affinity of human blood monocytes relative to other circulating white cells for binding to cultured human EC may have relevance to their function in vivo.

Cell Adhesion↗
PubMed1984

Stimulation of human endothelial cell prostacyclin synthesis by select leukotrienes.

Cultured endothelial cells from human umbilical cord labeled with [3H]20:4 release radiolabel when exposed to leukotrienes C or D (LTC or LTD). The major radiolabeled 20:4 metabolite recovered in the culture medium was prostacyclin. Both leukotrienes produced a dose-dependent synthesis of prostacyclin, with a maximal response at 10(-7) M leukotriene. LTC promoted a twofold greater response than did LTD at all concentrations tested (10(-9) to 10(-7) M). In contrast, no release of radiolabel above basal levels was evident with a challenge of LTE or LTB at the same concentrations. Endothelial cells metabolize approximately 40-50% of exogenously supplied LTC to LTD and LTE in 60 min. Levels of alpha-glutamyltranspeptidase (gamma-GTPase), the ectoenzyme reported to convert LTC or LTD, were detected in intact endothelial cells with the chromogenic substrate L-gamma-glutamyl-p-nitroanilide at levels sufficient to account for the observed rate of LTC metabolism. High concentrations of the gamma-GTPase inhibitors, glutathione and AT-125, blocked the metabolism of LTC by endothelium. These results suggest that degradation of leukotrienes by endothelium may be one mechanism for inactivation of these lipid mediators.

Arachidonic Acid↗