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Biomedical subjects

B Niggemann

Publications and source records attributed to B Niggemann.

At least 37 records · Page 2Linked to original sources
PubMed2005

Controlled oral food challenges in children--when indicated, when superfluous?

The diagnostic work-up of suspected food allergy includes the skin prick test (SPT), the measurement of food specific immunoglobulin E (IgE) antibodies using serologic assays, and more recently the atopy patch test (APT). For specific serum IgE and the SPT, decision points have been established for some foods allowing prediction of clinical relevance in selected cases. The APT may be helpful, especially when considered in combination with defined levels of specific IgE. Controlled oral food challenges still remain the gold standard in the diagnostic work-up of children with suspected food allergy. Most food allergic children will lose their allergy over time. As there is no laboratory parameter, which can accurately predict when clinical tolerance has been developed, controlled oral food challenges are the measure of choice. In this article, the current knowledge of predictors for the outcome of oral food challenges is reviewed and proposals for the daily practical work-up in the case of suspected food related clinical symptoms are presented.

Algorithms↗
PubMed2005

Specific oral tolerance induction with food in children: transient or persistent effect on food allergy?

BACKGROUND: The standard treatment of food allergy is elimination of the incriminated food from the diet. Specific oral tolerance induction (SOTI) seems to be a promising approach for a causal treatment; however, it is unclear whether the tolerance achieved is transient or persistent. We report on a subset of three patients of a larger ongoing study who were treated successfully with SOTI treatment, but experienced a secondary loss of tolerance after a period of allergen avoidance. METHODS: The patients suffered from IgE-mediated allergy either to cow's milk (CM) (patient A) or hen's egg (HE) (patients B and C), confirmed by double-blind, placebo-controlled food challenge (DBPCFC). SOTI treatment was performed at home on a daily basis until tolerance to a maximum of 250 ml CM or 4.5 g lyophilized HE protein was achieved. The daily maintenance dose was 100 ml CM or 2.5 g HE protein. RESULTS: Patients A, B and C reached tolerance to the maximum dose after 37, 41 and 52 weeks, respectively. According to the protocol, patients A and B performed a strict secondary elimination diet for 2 months prior to a follow-up DBPCFC after a maintenance phase of 27 and 39 weeks, respectively. Patient C discontinued treatment for 2 days after 4 weeks on the maintenance dose. Despite previous tolerance, on re-exposure to the allergen all patients experienced moderate systemic allergic reactions. CONCLUSIONS: We conclude that SOTI can induce transient tolerance in food allergy, but does not necessarily lead to its permanent abrogation. Regular allergen intake seems necessary to maintain the established tolerance.

Administration, Oral↗
PubMed2005

Anaphylactic reactions in children--a questionnaire-based survey in Germany.

BACKGROUND: Severe anaphylactic reactions are medical emergencies requiring immediate recognition and treatment. Despite this, little is known on their clinical features, especially in infants and children. OBJECTIVE: To evaluate trigger factors, patterns of clinical reaction, site of occurrence and treatment modalities of reported reaction in infants and children below 12 years of age in Germany. METHODS: Paediatricians throughout Germany were asked by questionnaire to report accidental anaphylactic reactions over the previous 12 months. Severity of reported reactions was classified in grades I-IV according to reported symptoms. RESULTS: Hundred and three cases of anaphylaxis were evaluated. Median age was 5 years, 58% were boys. Site of occurrence was the child's home in the majority of cases (58%). Foods were the most common causative allergen (57%), followed by insect stings (13%) and immunotherapy (SIT) (12%); in 8% anaphylactic agent was unknown. Among foods, peanuts and tree nuts were the most frequent allergens (20% of food allergens in each case). Severe reactions with cardiovascular involvement occurred in 24% of cases. No fatal reaction was observed. Recurrent episodes of anaphylaxis were reported in 27% of cases, half of these caused by the same allergen again. For treatment, 20% of children received adrenaline, in 8% of cases intravenously. Thirty-six per cent of patients with grade-IV reactions received adrenaline, 24% intravenously. In 17% of all children an adrenaline self-injector was prescribed after the episode. CONCLUSION: Our data: (i) shows an uncertainty of physicians in diagnosing anaphylaxis, (ii) reveals remarkable under-treatment of the majority of children with anaphylaxis, (iii) reflects the need for guidelines and training for physicians in managing children with anaphylaxis and (iv) should encourage the development of self-management programmes for patients and families.

Adrenergic Agonists↗
PubMed2004

Antitumour effects of PLC-gamma1-(SH2)2-TAT fusion proteins on EGFR/c-erbB-2-positive breast cancer cells.

Due to its pivotal role in the growth factor-mediated tumour cell migration, the adaptor protein phospholipase C-gamma1 (PLC-gamma1) is an appropriate target to block ultimately the spreading of EGFR/c-erbB-2-positive tumour cells, thereby minimising metastasis formation. Here, we present an approach to block PLC-gamma1 activity by using protein-based PLC-gamma1 inhibitors consisting of PLC-gamma1 SH2 domains, which were fused to the TAT-transduction domain to ensure a high protein transduction efficiency. Two proteins were generated containing one PLC-gamma1-SH2-domain (PS1-TAT) or two PLC-gamma1-SH2 domains (PS2-TAT). PS2-TAT treatment of the EGFR/c-erbB-2-positive cell line MDA-HER2 resulted in a reduction of the EGF-mediated PLC-gamma1 tyrosine phosphorylation of about 30%, concomitant with a complete abrogation of the EGF-driven calcium influx. In addition to this, long-term PS2-TAT treatment both reduces the EGF-mediated migration of about 75% combined with a markedly decreased time locomotion of single MDA-HER2 cells as well as decreases the proliferation of MDA-HER2 cells by about 50%. Due to its antitumoral capacity on EGFR/c-erbB-2-positive breast cancer cells, we conclude from our results that the protein-based PLC-gamma1 inhibitor PS2-TAT may be a means for novel adjuvant antitumour strategies to minimise metastasis formation because of the blockade of cell migration and proliferation.

Adenoma↗
PubMed2004

Prevalence of adverse reactions to food in Germany - a population study.

OBJECTIVE: A population study was performed to identify the prevalence of all kinds of adverse reactions to food. METHODS: In a representative cross-sectional survey performed in 1999 and 2000 in Berlin, 13 300 inhabitants of all ages were addressed by questionnaire. This questionnaire was answered by 4093 persons. All respondents mentioning any sign of food intolerance or the existence of allergic diseases (n = 2298) were followed up by telephone and, in case food intolerance could not be ruled out by patient history, were invited to attend to the clinic for personal investigation including double-blind, placebo-controlled food challenge tests (DBPCFC). RESULTS: The self-reported lifetime prevalence of any adverse reaction to food in the Berlin population (mean age 41 years) was 34.9%. Eight hundred and fourteen individuals were personally investigated according to the guidelines. The point prevalence of adverse reactions to food confirmed by DBPCFC tests in the Berlin population as a mean of all age groups was 3.6% (95% confidence interval [3.0-4.2%]) and 3.7% in the adult population (18-79 years, 95% confidence interval [3.1-4.4.%]). Two and a half percent were IgE-mediated and 1.1% non-IgE-mediated, females were more frequently affected (60.6%). Based on a statistical comparison with available data of adults from the nationwide German Health Survey from 1998, adverse reactions to food in the adult population of Germany (age 18-79) were calculated with 2.6% [2.1-3.2%]). CONCLUSIONS: The study gives for the first time information about the point prevalence of both immunological and nonimmunological adverse reactions to food and underlines the relevance of this issue in public health. The data also show that an individualized stepwise approach including provocation tests is mandatory to confirm the diagnosis.

Adolescent↗
PubMed2004

Food allergy and non-allergic food hypersensitivity in children and adolescents.

BACKGROUND: Previous studies have shown a 10-fold discrepancy of self-reported food-induced symptoms and physician-diagnosed food hypersensitivity. Little information is available on the prevalence of food hypersensitivity in unselected paediatric populations. No data were available for German children. OBJECTIVE: To study the perception of food-induced symptoms in the paediatric population, to investigate the allergens accused, to objectify patients' reports, and to identify subgroups at risk of having food-induced allergy (FA) or non-allergic food hypersensitivity (NAFH) reactions. METHODS: This paper presents the data of the paediatric group (0-17 years) of a representative, randomly sampled, cross-sectional population-based survey studying 13 300 inhabitants of the German capital city Berlin regarding food-related symptoms. Instruments included mailed questionnaires, structured telephone interviews, physical examination, skin-prick tests, specific serum IgE and standardized, controlled and blinded oral food challenges. RESULTS: Two thousand three hundred and fifty-four individuals were contacted by mailed questionnaire, 739 (31.4%) responses could be fully evaluated. Four hundred and fifty-five (61.5%) participants reported symptoms related to food ingestion, 284 (38.4%) affirmed reproducible symptoms in the standardized telephone interview. One hundred and eighty-four (24.8%) individuals were fully examined. Reproducible symptoms to food were found in 31 (4.2%) children and adolescents: 26 (3.5%) showed symptoms of FA and five (0.7%) of NAFH. The oral allergy syndrome was most often observed. Foods most commonly identified by oral challenges were apple, hazelnut, soy, kiwi, carrot and wheat. CONCLUSION: The perception of food-related symptoms is common among children and adolescents from the general population. Self-reports could be confirmed in around one out of 10 individuals, still resulting in 4.2% of proven clinical symptoms. However, most reactions were mild and mainly because of pollen-associated FA, while NAFH reactions were less common. Severe IgE-mediated FA was observed in individuals with pre-existing atopic disease, who should be fully investigated for clinically relevant FA.

Adolescent↗
PubMed2004

Unproven diagnostic procedures in IgE-mediated allergic diseases.

A considerable body of literature on therapeutic aspects of complementary and alternative medicine has been published in recent years, but little is known on diagnostic procedures. This short review lists complementary and alternative diagnostic procedures for the diagnosis of allergic diseases and presents an assessment of their usefulness for the daily practice. The review of the literature revealed that neither the determination of specific immunoglobulin G-antibodies in serum, the hair-analysis, the cytotoxic test, kinesiology, iridology, or electrodermal testing represent useful tests for the daily practice. To date, no complementary or alternative diagnostic procedure can be recommended as a meaningful element in the diagnostic work-up of allergic diseases. This is especially true for food allergy: properly performed oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals. Ineffective diagnostic approaches may be costly for the consumer and delay appropriate therapy.

Animals↗
PubMed2004

Role of oral food challenges in the diagnostic work-up of food allergy in atopic eczema dermatitis syndrome.

The diagnosis of food allergy in infants and children is still a challenging task for the pediatrician. While immediate-type allergic reactions to foods can be diagnosed quite easily, late-phase reactions, e.g. in atopic dermatitis, often represent a diagnostic challenge. Once classical diagnostic procedures such as history, skin prick tests, atopy patch test, and specific immunoglobulin E in serum have been exhausted, double-blind, placebo-controlled food challenges represent the state of the art. After an oligo-allergenic diet, suspected foods or placebo are given in a titrated manner until a clear clinical reaction or the highest dose. The observation period should be 48 h in the case of atopic dermatitis. Constant clinical monitoring is mandatory. Dietetic recommendations are given for 12 months. The effort involved in such a procedure is justified because it can help to avoid clinically relevant food allergens in some cases and in others can prevent children from being exposed unnecessarily to diets that may be harmful to them.

Allergens↗
PubMed2004

A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen.

BACKGROUND: Especially in childhood, sublingual immunotherapy (SLIT) could offer advantages over subcutaneous therapy. However, limited data on its efficacy is available. METHODS: In four German centres 97 children (age 3-14 years) with allergic rhinoconjunctivitis to grass pollen were enrolled in a prospective, double-blind trial comparing SLIT (Pangramin SLIT; ALK-SCHERAX, 0.5 microg major allergens, three times per week, 32 months) with placebo. Primary endpoint was a multiple symptom-medication score for changes in seasonal diary entries between the first and third year of the study (SLIT n=39; placebo n=38). RESULTS: The multiple symptom-medication score was significantly reduced by SLIT to 77.3% of the placebo group (P=0.0498). The subsequent analysis of the single endpoints did not reveal significant differences for symptom scores in favour of SLIT (85.1% of placebo group; P=0.22). However, the medication score improved significantly (67.1% of placebo group; P=0.0025). Furthermore, secondary endpoints assessing in vivo immune responses did not differ significantly between the groups. However, retrospective analysis showed some inhomogeneity for clinical and in vitro parameters at the beginning of the study. Allergic side effects with possible relation to the study drug were reported in both groups (SLIT 49%, placebo 27%, P=0.026). CONCLUSION: Our study indicates that SLIT had a positive effect on the reduction of a multiple symptom-medication score, mainly by significantly reducing rescue medication use, but had no significant effect on symptoms alone in children with rhinoconjunctivitis to grass pollen compared with a placebo.

Administration, Sublingual↗
PubMed2004

Specific IgE levels do not indicate persistence or transience of food allergy in children with atopic dermatitis.

BACKGROUND: Food allergy in early childhood usually resolves with time; however, little is known about predictors for persistence or transience of food allergy in children with atopic dermatitis. The aim of the study was to evaluate whether specific IgE levels in serum could be a useful predictor of the outcome of oral re-challenges. METHODS: In 74 children, 99 oral food challenges were performed (cow milk n = 48, hen egg n = 37, and wheat n = 14) and repeated after a median time interval of 16 months. In 15 of the 74 children, a third challenge (n = 22) could be performed, with a median time interval from second challenge to third challenge of 15 months. RESULTS: There were 37 children with transient food allergy (positive first challenge and negative second challenge), while 62 children had persistent food allergy (positive first challenge and negative second challenge). Comparison of the two groups showed that specific IgE as well as total IgE in serum was significantly higher in the latter group. However, looking at the time course, specific IgE did not decrease significantly during elimination diet. CONCLUSION: Our results indicate that specific IgE in serum--although very helpful at the time of the first diagnosis--cannot predict whether a chid will become tolerant after a period of avoidance. Therefore, oral re-challenges remain mandatory.

Dermatitis, Atopic↗
PubMed2003

Molecular cloning and immunological characterisation of potential allergens from the mould Fusarium culmorum.

BACKGROUND: High quality and stability are essential requirements of commercial allergen preparations. Recently we have demonstrated the very low stability of protein allergens in an extract of the ubiquitous mould Fusarium culmorum. OBJECTIVE: The present study was performed to identify, isolate and characterise allergens of F. culmorum as a basis for a stable allergenic reference material. In addition, the significance of IgE binding to carbohydrate structures in the natural allergen source was investigated. METHODS: Sera of 52 subjects with suspected mould allergy were used to determine the IgE binding capacity of a commercial F. culmorum extract and an in-house extract by immunoblotting and enzyme allergo sorbent test (EAST). Binding of IgE-antibodies to putative carbohydrate structures located on glycoproteins was verified by periodate treatment of blot strips prior to immunodetection. A complementary (c)DNA expression library of F. culmorum was prepared and screened for IgE-binding clones using sera from F. culmorum-sensitive individuals. Positive clones were isolated, and the open reading frames were subcloned into expression vectors to produce recombinant proteins in E. coli. The recombinant proteins were tested for their IgE reactivity by immunoblotting and EAST. RESULTS: Using the in-house extract for EAST and immunoblot experiments 44% (23/52) of the sera were found to contain F. culmorum-specific IgE antibodies. Compared to the in-house extract, nearly all IgE-reactivties in the range of 15-30kD were lacking in the commercial preparation as examined by immunoblot analysis and only 10% (5/52) of the sera were found to contain F. culmorum-specific IgE by EAST. IgE binding to putative carbohydrate structures was observed in the high molecular weight range in approximately 50% (12/23) of the IgE-positive sera by both extracts. Three IgE binding clones were isolated from the cDNA-library. One clone (Fus c 1) is homologous to the highly conserved 60S acidic ribosomal protein P2 described as minor allergen in other moulds. The second (Fus c 2) shows high similarity (64%) to a respiratory allergen from the basidiomycete Coprinus comatus (Cop c 2). The third clone (Fus c 3) was not related to known proteins. With sera from 26 individuals sensitised to F. culmorum the IgE prevalence of recombinant proteins rFus c 1, rFus c 2 and rFus c 3 was found to be 35, 50, and 15%, respectively. CONCLUSIONS: F. culmorum may represent an underestimated source of aeroallergens. In contrast to highly labile and poorly standardised F. culmorum extracts, the new recombinant allergens may serve as stable allergenic reference material. A combination of rFus c 1 and rFus c 2 is suitable to diagnose 81% of F. culmorum-sensitised subjects. IgE reactivity to putative carbohydrate structures is relatively frequent, and can not be detected by these allergens.

Allergens↗
PubMed2003

Effects of neurotransmitters on the chemokinesis and chemotaxis of MDA-MB-468 human breast carcinoma cells.

Most patients suffering from breast carcinoma do not die due to the primary tumor but from the development of metastases. Active migration of cancer cells is a prerequisite for development of these metastases. We used time-lapse videomicroscopy and computer-assisted cell tracking of MDA-MB-468 human breast carcinoma cells, which were incorporated into a three-dimensional collagen matrix, in order to analyze the migratory activity of these cells in response to different neurotransmitters. Our results show that met-enkephalin, substance P, bombesin, dopamine, and norepinephrine have a stimulatory effect on the migration of the breast cancer cells; moreover, these cells show positive chemotaxis towards norepinephrine as was analyzed by the directionality and persistence on a single-cell basis. Gamma-aminobutyric acid (GABA) however has an inhibitory effect. Endorphin and leu-enkephalin, as well as histamin and acetylcholine, had no influence on the migratory activity of the cells. In summary, we provide evidence for a strong regulatory involvement of neurotransmitters in the regulation of breast cancer cell migration, which might provide the basis for the use of the pharmacological agonists and antagonists for the chemopreventive inhibition of metastasis development.

Antineoplastic Agents↗
PubMed2003

Side-effects of complementary and alternative medicine.

Complementary and alternative medicine are increasingly used to diagnose or treat allergic diseases, and numerous studies have reported benefits of this type of medicine. This article presents a review of the literature on risks of these methods. The potential sensitizing capacity of numerous herbal remedies may lead to allergic contact dermatitis and more rarely to IgE-mediated clinical symptoms. Mechanical injuries may be observed following acupuncture leading to pneumothorax, cardiac tamponade or spinal injury. Infectious complications after acupuncture include hepatitis and bacterial endocariditis. Organ toxicity has been observed associated with various herbal preparations involving the liver, kidneys, and the heart. Some herbs may have cancerogenic properties. Severe nutritional deficiencies can occur in infants and small children given strict alternative diets, resembling 'kwashiorkor'. Finally, among other miscellaneous adverse effects, adulteration with steroids, and herbal and drug interactions are discussed. The pattern of side-effects is similar to that observed by the use of conventional medicine. Therefore, caution may be justified using both conventional and unconventional methods. Only if the benefit is proven and the side-effects are established, should a given method be chosen.

Acupuncture Therapy↗
PubMed2003

A novel function for chemokines: downregulation of neutrophil migration.

Migration is a key function of stem cells during ontogenesis, of fibroblasts in wound healing and of immune cells in host defence. The signals that initiate migration are as important as signals that terminate migration, once the destination has been reached. We now show that formyl-methionyl-leucyl-phenylalanine (fMLP)-induced migration of neutrophils was inhibited by increasing concentrations of interleukin-8 (IL-8). IL-8 dose dependently increased the frequency and the duration of stop-periods, whereas the percentage of cells of a population that was locomotory active remained constant. The stop-signal delivered by IL-8 was intracellularly transduced by a dichotomic pathway: (i) the activation of the adenylyl cyclase leads to an increase of cytosolic cyclic adenosine monophosphate, which results in an activation of the sarcoplasmatic/endoplasmatic reticulum calcium ATPase pump and a calcium sequestration; (ii) the activation of the phospholipase Cbeta (PLCbeta) generates inositol-1,4,5-phosphate (IP3) and diacylglycerol (DAG), which results in IP3-mediated release of intracellularly stored calcium in the endoplasmatic reticulum and DAG-mediated activation of protein kinase C. Thus, we show for the first time that a chemokine, IL-8, in concert with fMLP, downregulates the neutrophil migration through the regulation of the intracellular calcium concentration via the adenylyl cyclase and the PLCbeta2.

Bucladesine↗
PubMed2003

Transient early wheeze is not associated with impaired lung function in 7-yr-old children.

The aim of the present study was to analyse determinants of lung function in 7-yr-old children with different wheezing patterns (early, persistent and late onset) in a prospective cohort study. The German Multicentre Allergy Study (MAS) followed 1,314 children from birth onwards. Annual assessments included clinical check-ups, a structured interview and repeated measurement of specific immunoglobulins Ig(E) directed against food and inhalant allergens. At the age of 7 yrs, lung function was measured by body plethysmography in 800 children. Episodes of wheezing in the past 12 months ("current wheeze") were strongly associated with reduced lung function at age 7 yrs. Children with wheezing episodes only during the first 3 yrs of life showed a slight impairment in maximal expiratory flow when 50% of the forced vital capacity remains to be exhaled (98.9 +/- 24.2 versus 103.2 +/- 22.8% of the predicted value in children who never wheeze). Separate analysis of determinants of pulmonary function within these subgroups resulted in distinctly different patterns. Determinants of impaired lung function in the group of current wheezers were: time in years since first wheeze, a parental history of atopy, current sensitisation to indoor allergens, elevated cord blood IgE levels and a low ponderal index at birth. In the group of transient early wheezers, frequent lower respiratory tract infections early in life and maternal smoking during pregnancy were significant but weak determinants of impaired lung function. The present results indicate that determinants of pulmonary function in 7-yr-old children differ with respect to different wheezing phenotypes, demanding different therapeutic strategies. Although transient early wheezers were found to have normal-to-subnormal lung function, children with asthmatic symptoms (persistent and late-onset disease) at age 7 yrs already show significant impairment of expiratory flow volumes.

Age Factors↗