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Biomedical subjects

B Niggemann

Publications and source records attributed to B Niggemann.

At least 19 recordsLinked to original sources

Remifentanil and propofol for sedation in children and young adolescents undergoing diagnostic flexible bronchoscopy.

Flexible fibreoptic bronchoscopy (FOB) has become a useful diagnostic and therapeutic procedure in children. We investigated 26 patients (3-14 years) for FOB using a new sedation strategy. All patients received oral premedication and inhalation of topical anaesthetic. Sedation for bronchoscopy was achieved with a continuous infusion of remifentanil and intermittent boluses of propofol. Propofol injection was repeated if sedation was inadequate. Sedation could be successfully performed in all children without adverse effects. Endtidal CO2 concentration and arterial oxygen saturation remained stable throughout the study. All children were awake 5+/-1.3 min after stopping remifentanil infusion. Sedation with remifentanil/propofol is a new sedation strategy for diagnostic flexible paediatric bronchoscopy in children with spontaneous ventilation.

Adolescent

Atopy, the use of condoms, and a history of cesarean delivery: potential predisposing factors for latex sensitization in pregnant women.

OBJECTIVE: Our purpose was to assess the prevalence of latex sensitization among women admitted for delivery and the relevant risk factors. STUDY DESIGN: In a prospective study 333 consecutive patients admitted for delivery were screened for specific immunoglobulin E antibodies to latex and for atopic status. A questionnaire was filled in and included questions about the obstetric and surgical history, known contact with latex, and previous use of condoms. RESULTS: Nine of 333 (2.7%) women showed latex-specific immunoglobulin E. All 9 women had atopy (100% vs 26. 2% in the latex-negative group; P <.00001). Of 8 patients with specific immunoglobulin E who gave details about the use of condoms, 6 had had frequent contact with latex condoms (75% vs 51%). Previous cesarean delivery was more frequent in latex-sensitized patients (33% vs 8.4%; P <.05), whereas previous pregnancies, previous deliveries, and total number of operations had no influence. CONCLUSION: Given a prevalence of 2.7% of latex sensitization, all obstetric patients should be questioned about known immediate allergic reaction to latex, a predisposition to atopy, previous intra-abdominal operations, and the regular use of condoms in the past. Patients with atopy and additive risk factors should be treated in a latex-free environment.

Adolescent

Cloning, expression, and characterization of recombinant Hev b 3, a Hevea brasiliensis protein associated with latex allergy in patients with spina bifida.

BACKGROUND: Two natural rubber latex proteins, Hev b 1 and Hev b 3, have been described in spina bifida (SB)-associated latex allergy. OBJECTIVE: The aim of this study was to clone and express Hev b 3 and to obtain the immunologic active and soluble recombinant allergen for diagnosis of SB-associated latex allergy. METHODS: A complementary DNA (cDNA) coding for Hev b 3 was amplified from RNA of fresh latex collected from Malaysian rubber trees (Hevea brasiliensis). PCR primers were designed according to sequences of internal peptide fragments of natural (n) Hev b 3. The 5'-end sequence was obtained by specific amplification of cDNA ends. The recombinant (r) Hev b 3 was produced in Escherichia coli as a 6xHis tagged protein. Immunoblotting and inhibition assays were performed to characterize the recombinant allergen. RESULTS: An Hev b 3 cDNA clone of 922 bp encoding a protein of 204 amino acid residues corresponding to a molecular weight of 22.3 kd was obtained. In immunoblots 29/35, latex-allergic patients with SB revealed IgE binding to rHev b 3, as did 4 of 15 of the latex-sensitized group. The presence of all IgE epitopes on rHev b 3 was shown by its ability to abolish all IgE binding to nHev b 3. Hev b 3 is related to Hev b 1 by a sequence identity of 47%. Cross-reactivity between these 2 latex allergens was illustrated by the large extent of inhibition of IgE binding to nHev b 1 by rHev b 3. CONCLUSION: rHev b 3 constitutes a suitable in vitro reagent for the diagnosis of latex allergy in patients with SB. The determination of the full sequence of Hev b 3 and the production of the recombinant allergen will allow the epitope mapping and improve diagnostic reagents for latex allergy.

Adolescent

Colcemid but not taxol modulates the migratory behavior of human T lymphocytes within 3-D collagen lattices.

T cell migration within tissue requires engagement of the cytoskeleton, however, little is known about the functional role of both actin- and tubulin-based cytoskeleton in this process. We investigated the direct effect of microtubule disruption and stabilization using colcemid and taxol, respectively, on the locomotion of peripheral human T cells within three-dimensional (3-D) collagen lattices. Microtubules network disassembly very potently enhanced T cell migration, nearly doubling the fraction of locomoting cells. Both a recruitment of previously sessile cells as well as an increase in the mean duration of active locomotion contributed to the promigratory effect. The stimulatory effect was correlated with the loss of the integrity of the tubulin cytoskeleton. Reassembly of microtubules, subsequent to the removal of colcemid from the cells, resulted in the successive return of the migratory activity to baseline levels. On the contrary, taxol failed to modulate T cell migration in our in vitro assay despite its potency to assemble tubulin into compact clots. Our observations underscore the view that tubulin-dependent cellular deformability is not the rate-limiting factor for locomotion and provide evidence that the increase in migratory activity subsequent to colcemid-treatment is due to a secondary phenomenon, most likely the activation of the actin cytoskeleton.

Cell Movement

Effect of pre- and postnatal tobacco smoke exposure on specific sensitization to food and inhalant allergens during the first 3 years of life. Multicenter Allergy Study Group, Germany.

BACKGROUND: The study aimed to assess the effect of pre- and postnatal tobacco smoke exposure on specific sensitization to food allergens and inhalant allergens during the first 3 years of life. METHODS: A total of 342 children of a prospective and observational birth cohort study on atopy (MAS) were included on the basis of a complete follow-up of specific IgE measurements at the ages of 1, 2, and 3 years with available questionnaire information about the parental smoking habit at birth, 18 months, and 3 years of age. Study children were grouped into four exposure categories representing in utero and postnatal environmental tobacco smoke (ETS) exposure, and according to the number of cigarettes smoked by the parents. The effect on the development of allergic sensitization to food, outdoor, and indoor allergens by 3 years of age was determined by multiple logistic regression analyses. RESULTS: At the age of 3, children who were pre- and postnatally exposed to tobacco smoke had a significantly higher risk of sensitization to food allergens (odds ratio: 2.3, 95% C.I.: 1.1-4.6) than unexposed children. Children who were only postnatally exposed by a smoking mother also had a 2.2 times higher risk (95% C.I.: 0.9-5.9) of sensitization than unexposed children. These two categories (pre- and/or postnatal exposure) contribute to the significant overall effect of the tobacco smoke exposure (P< or =0.02). No significant association between tobacco smoke exposure and specific sensitization to inhalant allergens was observed. The determining risk factors for this type of sensitization were atopic family history and mite- and cat-allergen exposure levels. CONCLUSIONS: During the first 3 years of life, both prenatal and postnatal tobacco smoke exposure has an adjuvant effect on allergic sensitization which seems to be restricted to allergens to which children are mainly exposed, in combination with the peak of the ETS exposure around the first birthday.

Child, Preschool

Evaluation of the risk of anaphylactic reactions by wasp venom-extract challenges in children.

Diagnostic sting challenges have been shown to provide information on the risk of further anaphylactic reactions to bee stings. We present a follow-up study in wasp venom-hypersensitive children after diagnostic venom extract challenges to analyze their risk of further anaphylactic reactions. Responses were obtained from 104 patients with wasp venom hypersensitivity out of 115 former patients. Only one of the 104 patients showed more than a severe local reaction to the sting challenge irrespective of the performance of a single or sequential challenge; therefore, only one patient received venom immunotherapy. The performance of a diagnostic sting challenge with wasp venom extract in children had a high negative predictive value of 94.6% for the risk of further systemic reactions. This was shown by analysis of later field stings, since 37 children experienced further field stings and only two of these children(5.4%) developed a mild systemic reaction (urticaria) equal to or less severe than the index sting. The value of the venom extract challenge can be interpreted in two ways: either it is less sensitive than a native sting challenge since the rate of systemic reactions to the challenge was very low, or the prognosis of wasp venom hypersensitivity in children is extremely favorable. Since the latter hypothesis is supported by the low incidence of systemic field sting reactions, we postulate that venom immunotherapy is necessary only in a minority of children with wasp venom hypersensitivity with an index sting reaction of Mueller grade I or II. However, the value of venom extract challenges as a general diagnostic instrument in children with Mueller I and II reactions due to wasp venom hypersensitivity may be questioned. It may have a place as a safe procedure in demonstrating to parents and physicians the often self-limiting natural course in most of these children.

Adolescent

Outcome of double-blind, placebo-controlled food challenge tests in 107 children with atopic dermatitis.

BACKGROUND AND OBJECTIVE: Little is known about late phase clinical reactions during oral food challenges and the value of specific IgE in terms of sensitivity and specificity. METHODS: We therefore analysed retrospectively the clinical outcome of 387 oral provocations during double-blind, placebo-controlled food challenge tests in 107 children with atopic dermatitis. RESULTS: Eighty-seven (81%) children showed a positive clinical reaction to at least one challenge. The vast majority of children (94%) showed clinical symptoms to one or two allergens. One hundred and thirty-one of 259 (51%) of verum challenges and 1/128 (0.8%) placebo challenge were assessed as positive. Oral provocations with hen's egg showed the highest percentage of positive reactions (70%). Sensitivity of specific IgE to the four allergens tested was 90%, specificity 30%. Sensitivity of the parental history as a predictive factor was 48%, specificity 72%. Ninety-two of 131 (70%) children with positive verum provocations showed early reactions, 33 (25%) late and six (5%) combined early and late reactions. In 84/131 (64%) positive provocations one organ system was involved, while in 44 (34%) provocations two and in three (2%) challenges three organ systems were involved. Skin reactions were the most frequent clinical manifestation leading to positive reactions followed by gastro-intestinal and respiratory symptoms. There was no correlation between titration dose and specific IgE. The subgroup of non-sensitized children did not differ in terms of sex, age or titration dose from the total study population. CONCLUSION: Double-blind, placebo-controlled oral food challenges are helpful in distinguishing children with clinically manifested symptoms from those with food sensitization. Accurately identifying children with a clinical relevant food allergy may help to prescribe specific diets on a scientific basis, avoiding dietary limitations which may be unnecessary or even harmful.

Administration, Oral

In vivo and in vitro studies on the residual allergenicity of partially hydrolysed infant formulae.

AIM: Because allergen-reduced formulae are widely used in the prevention and treatment of cow's milk allergy in children and because anaphylactic reactions have been reported for some hydrolysed formulae, it is of clinical relevance to know about the residual allergenicity of so-called hypoallergenic formulae. METHOD: We therefore studied the reactions of 20 children (mean age 1.6 years) with proven cow's milk allergy to a variety of formulae, using skin prick test, specific IgE in serum, protein content and RAST inhibition. RESULTS: Whereas all but two children with a clinically relevant cow's milk allergy had a positive skin prick test to cow's milk, some children still showed positive responses to the partially hydrolysed formulae. No child had a positive skin test to the amino acid formula. Specific IgE to the partially hydrolysed whey formula (median 0.28 U/ml) was significantly lower (p < 0.003) than to cow's milk. Specific IgE to the partially hydrolysed whey/casein formula, soy/pork collagen hydrolysate and the amino acid formula was in a low range (median values 0.19, 0.23 and 0.21 U/ml, respectively). While determination of the protein content of the formulae gave no valid information, RAST/EAST inhibition was highest for cow's milk, followed by the partially hydrolysed whey formula, partially hydrolysed whey/casein formula, soy/pork collagen formula, and the amino acid formula. CONCLUSION: Skin prick test and RAST inhibition test are suitable methods for determining the residual allergenicity of hydrolysed infant formulae, while determination of protein content using the applied modified Lowry method is not helpful.

Amino Acids

Functional hierarchy of simultaneously expressed adhesion receptors: integrin alpha2beta1 but not CD44 mediates MV3 melanoma cell migration and matrix reorganization within three-dimensional hyaluronan-containing collagen matrices.

Haptokinetic cell migration across surfaces is mediated by adhesion receptors including beta1 integrins and CD44 providing adhesion to extracellular matrix (ECM) ligands such as collagen and hyaluronan (HA), respectively. Little is known, however, about how such different receptor systems synergize for cell migration through three-dimensionally (3-D) interconnected ECM ligands. In highly motile human MV3 melanoma cells, both beta1 integrins and CD44 are abundantly expressed, support migration across collagen and HA, respectively, and are deposited upon migration, whereas only beta1 integrins but not CD44 redistribute to focal adhesions. In 3-D collagen lattices in the presence or absence of HA and cross-linking chondroitin sulfate, MV3 cell migration and associated functions such as polarization and matrix reorganization were blocked by anti-beta1 and anti-alpha2 integrin mAbs, whereas mAbs blocking CD44, alpha3, alpha5, alpha6, or alphav integrins showed no effect. With use of highly sensitive time-lapse videomicroscopy and computer-assisted cell tracking techniques, promigratory functions of CD44 were excluded. 1) Addition of HA did not increase the migratory cell population or its migration velocity, 2) blocking of the HA-binding Hermes-1 epitope did not affect migration, and 3) impaired migration after blocking or activation of beta1 integrins was not restored via CD44. Because alpha2beta1-mediated migration was neither synergized nor replaced by CD44-HA interactions, we conclude that the biophysical properties of 3-D multicomponent ECM impose more restricted molecular functions of adhesion receptors, thereby differing from haptokinetic migration across surfaces.

Antibodies, Monoclonal

CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize beta1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion.

Cell migration may depend on integrin-mediated adhesion to and deadhesion from extracellular matrix ligands. This concept, however, has not yet been confirmed for T lymphocytes migrating in three-dimensional extracellular matrices. We investigated receptor involvement in T cell migration combining a three-dimensional collagen matrix model with time-lapse videomicroscopy, computer-assisted cell tracking and confocal microscopy. In collagen lattices, the migration of CD4+ T cells (1) involved interactions with collagen fibers at the leading edge and uropod likewise, (2) occurred independently of the co-clustering of beta1, beta2, or beta3 integrins with F-actin, focal adhesion kinase, and phosphotyrosine at interactions with collagen fibers, (3) was counteracted by high-affinity beta1 integrin binding induced by antibody TS2/16; however, (4) the migration could not be blocked by a combination of adhesion-perturbing anti-beta1, -beta2, -beta3, and alpha v integrin antibodies. Integrin blocking neither affected cell polarization, interaction with fibers, beta1 integrin distribution, migration velocity, path structure, nor the number of locomoting cells in spontaneously migrating or concanavalin A-activated cells. Hence, T lymphocytes migrating in three-dimensional collagen matrices may utilize highly transient interactions with collagen fibers of low adhesivity, thereby differing from focal adhesion-dependent migration strategies employed by other cells.

Antibodies, Monoclonal

Latex provocation tests in patients with spina bifida: who is at risk of becoming symptomatic?

BACKGROUND: Although there is accepted information on the prevalence rates of sensitization to latex in patients with spina bifida, little is known about the clinical relevance of this sensitization. METHODS: We performed provocation tests with latex gloves in 159 patients with spina bifida (median age, 10 years). RESULTS: Eighty-eight patients (55.3%) were sensitized to latex in terms of a positive skin prick test response, specific IgE to latex in serum, or both. Fifty-five patients (34.6% of all patients or 62.5% of latex-sensitized patients) showed clinical symptoms on provocation. Specific IgE to latex was significantly higher in patients with a positive provocation test response (P <.0001). The total number of operations and degree of sensitization showed a significant correlation. More than 8 operations significantly increased the risk of sensitization (P <.0001), and more than 9 operations increased the risk of allergy to latex (P <.0001). One hundred seventeen (75%) patients had a ventricular shunt system. Specific IgE in these patients was significantly higher than in patients without (P <.0001), and the odds ratio for the existence of a shunt system in terms of a positive provocation was 3.9. Patients with a shunt system were significantly more often sensitized and had positive provocation results (P <.0001). Seventy-two patients (45.3%) were classified as atopic; they were significantly more often sensitized and clinically symptomatic (P <.0001), and the odds ratio for having a positive provocation response was 3.2 for atopic subjects. History of symptoms on contact with material containing latex had a sensitivity of 53.7% and specificity of 94.2%. CONCLUSIONS: Our results indicate that an atopic disposition, number of operations, and presence of a shunt system increase the risk of becoming not only sensitized but also allergic to latex. Our results strongly support the necessity that patients with spina bifida as a high-risk group for latex allergy should remain latex-free from the first day of life.

Adolescent

Prospective, double-blind, placebo-controlled, multicentre study on the effect of high-dose, intravenous immunoglobulin in children and adolescents with severe bronchial asthma.

OBJECTIVE: In order to study the effect of high-dose, intravenous immunoglobulin (i.v.IG) in severe childhood asthma, we investigated 31 children and adolescents (15 girls, 16 boys) aged 9-22 years (median age of 14 years) suffering from severe bronchial asthma. METHODS: In a prospective, double-blind fashion, patients received either four doses of i.v.IG (1 g/kg body weight) or identical doses of intravenous human serum albumin. The first two doses were given on two consecutive days, followed by two further doses at 4 week intervals. RESULTS: There was no statistical difference in the actively treated group when compared with the placebo group in symptom-score, bronchial hyperreactivity or peak-flow-variability. There was a trend for fewer total days of upper respiratory tract infections and also symptom-scores in the i.v.IG group but these did not reach statistical significance. CONCLUSION: Our data indicate that treatment with i.v.IG in asthmatic children did not show a significant reduction in the incidence of upper respiratory tract infections, but the patients who did have upper respiratory infections in the i.v.IG-group appear to have less protracted infections. Severity and bronchial hyperreactivity do not seem to be affected by the treatment as performed in our study.

Adolescent

Prediction of sensitization to inhalant allergens in childhood: evaluating family history, atopic dermatitis and sensitization to food allergens. The MAS Study Group. Multicentre Allergy Study.

BACKGROUND: A family history of atopy is a poor predictor of sensitization to inhalant allergens and allergic disease during childhood. We recently identified early sensitization to food allergens, especially hen's egg, as a valuable predictor of subsequent sensitization to inhalant allergens. OBJECTIVE: (1) Whether prediction will be improved by in vitro allergy tests at 1 year of age in combination with family history and medical history data. (2) Comparison with the capacities of in vitro tests to predict sensitization to aeroallergens. METHODS: Of an observational birth cohort study (MAS) 49 children who were sensitized to inhalant allergens at 5 years of age and 116 non-sensitized controls were included in the present study. For the prediction of sensitization to inhalant allergens the following prognostic factors were evaluated: atopic family history (FH), atopic dermatitis (AD) during the first year of life, two in vitro allergy tests for specific IgE to common food allergens at 1 year of age (fx5 [Pharmacia] and single allergen specific tests (sIgE) for four allergens) and 'high' total serum IgE, defined by three different cut off points. RESULTS: The combination of medical history data and laboratory tests resulted in the best predictive discrimination. The positive predictive values (PPV) were higher if sensitization to food was detected by single allergen specific tests (PPV: 66%/75%/100% corresponding to the three evaluated risk groups) than by the qualitative fx5 (PPV: 46%/65%/100%). The negative predictive values were equal for both tests (69 and 92% for the two low risk groups). High total serum IgE had low predictive capacity. CONCLUSION: During infancy the prediction of sensitization to inhalant allergens should be based on medical history data and allergy tests determining sensitization to food allergens. The in vitro tests improve the predictive discrimination, but the individual risk profile of the child must be considered for a reliable and valid prediction.

Allergens

Direct and rapid induction of migration in human CD4+ T lymphocytes within three-dimensional collagen matrices mediated by signalling via CD3 and/or CD2.

Specific activation of T cells requires stable cell-cell interaction; however, little is known how the transition from a previously motile state into a sessile state following activation is achieved. We investigated the direct effect of T-cell receptor (TCR)/CD3 complex engagement and/or stimulation of the accessory molecule CD2 on the locomotion of peripheral human T cells within three-dimensional (3-D) collagen lattices. Simultaneous engagement of CD3 and CD2 very potently stimulated T-cell migration, resulting in the recruitment of previously sessile cells (about 24% of the total population was additionally recruited) as well as an increase in the mean duration of active locomotion. This induction of migration was accompanied by an increased tyrosine phosphorylation of a 125 000 MW substrate corresponding to the focal adhesion kinase. Using confocal laser scanning microscopy we detected antibody-induced receptor capping into the uropod of migrating T cells whereas untreated control cells displayed an even distribution of CD3 and CD2 on the cell surface. Less pronounced induction of locomotion was achieved following triggering of CD3 or CD2 alone. Thus, in 3-D collagen lattices specific T-cell activation did not lead to cessation of cellular migration but rather induced cytoskeletal activity that ultimately resulted in vigorous locomotory activity.

Antibodies, Monoclonal

Role of nonallergic hypersensitivity reactions in children with chronic urticaria.

BACKGROUND: IgE-independent (pseudoallergic) reactions to food and food ingredients are common in a subgroup of adult patients with chronic urticaria, who have daily spontaneous occurrence of wheals. However, for children with chronic urticaria (duration longer than 6 weeks, no physical influence), no data on the importance of pseudoallergen-induced chronic urticaria are available. Therefore, we investigated the role of nonallergic hypersensitivity to food in all children seen with chronic continuous urticaria in our two clinics over the last 2 years (n = 16). METHODS: All patients were given a low-pseudoallergen diet for 3 weeks followed by provocation with food rich in pseudoallergens. To identify the main eliciting agents, a subgroup of responders was exposed to food additives by double-blind, placebo-controlled food challenges. RESULTS: Pseudoallergen-induced urticaria was diagnosed in 12 cases (75%). Reactions occurred mainly to coloring agents and preservatives, but also to monosodium glutamate and a sweetener (saccharin/cyclamate). CONCLUSIONS: These results confirm that nonallergic hypersensitivity reactions play a role in children with chronic urticaria, although the latter disease is rare at that age. In children, food additives, especially coloring agents and preservatives, appear to play a more important role in eliciting nonallergic hypersensitivity reactions than in adult patients, where naturally occurring pseudoallergens in fruits and vegetables are mainly responsible.

Adolescent

Development of latex allergy in children up to 5 years of age--a retrospective analysis of risk factors.

The aim of the study was to investigate possible associations between the time course of early sensitization to latex and various life style factors. Of the 398 children from a prospective birth cohort study, 20 (5%) showed specific serum IgE to latex at the age of 5 years. Sensitization started beyond the first year of life and 19 out of 20 sensitized children showed increasing specific IgE-values over time. All 20 sensitized children were atopic (p < 0.00000). Total IgE was significantly higher in the sensitized group (median 394.5 kU/I) than in the non-sensitized group (median 39.2 kU/l) (p < 0.00001). Comparing the latex-sensitized group with the non-sensitized children, there were significantly more operations in the latex group (p < 0.05) during the first 5 years of life. Medical history, certain foods, the use of pacifiers, mattress composition and socio-economic data proved not to be significant risk factors. From our study we conclude that besides the number of operations and an atopic predisposition--no other definite risk factor for developing sensitization or allergy to latex (such as everyday household objects) can be identified in children up to 5 years of age.

Age Factors