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R Nickel

Publications and source records attributed to R Nickel.

At least 19 recordsLinked to original sources

Evaluation of the CD14 C-159 T polymorphism in the German Multicenter Allergy Study cohort.

BACKGROUND: Multiple genetic studies have shown linkage of atopy-related phenotypes to chromosome 5q31. In this region several candidate genes for atopy are localized such as the Th2 cytokines IL-4, IL-5 and IL-13, but also CD14, a receptor for LPS. Recently, a functional CD14 promoter polymorphism was related to total and specific IgE responsiveness. OBJECTIVE: The aim of our study was to evaluate the role of this single nucleotide polymorphism (SNP) in a large German birth cohort. METHODS: Atopy-related phenotypes were longitudinally carefully evaluated in over 800 children from birth to the age of 10 years. Yearly visits included standardized interviews, physical examinations and determination of total and specific IgE antibodies. Pulmonary function tests and histamine provocations were performed at the age of seven. Eight-hundred and seventy-two children of the Multicenter Allergy Study (MAS) cohort were genotyped using melting curve and restriction digest analyses. RESULTS: CD14-159 allele frequencies were consistent with previous reports, however, no association of the SNP with asthma, atopic dermatitis, allergic rhinitis, total or specific IgE levels could be observed. CONCLUSION: The CD14-159 SNP might not play a major role in the development of atopy in German children.

Follow-Up Studies↗

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↗

Comparison of bronchial responsiveness to histamine in asthma, allergic rhinitis and allergic sensitization at the age of 7 years.

BACKGROUND: Bronchial responsiveness (BR) to histamine or methacholin is a common finding in adult non-asthmatic patients with allergic rhinitis. OBJECTIVE: We tested whether BR is also present in children with a comparatively short history of allergic rhinitis in a paediatric cohort. METHODS: We performed pulmonary function tests and histamine challenges in a total of 654 children (age 7 years, participants of the German Multicenter Allergy Study) and compared PC20 FEV1 values in children with asthma, allergic rhinitis, asymptomatic allergic sensitization and non-atopic controls. RESULTS: Most pronounced BR to histamine was observed in allergic asthmatics (n = 28), irrespective of the presence or absence of allergic rhinitis. Furthermore, PC(20)FEV(1) values in non-asthmatic children with allergic rhinitis (n = 24) were not significantly different from those seen in asymptomatic atopic (n = 54) or non-atopic controls (n = 92). CONCLUSIONS: In contrast to adult study populations, 7-year-old non-asthmatic children with allergic rhinitis do not show a higher degree of BR than asymptomatic atopic or non-atopic controls. Therefore, secondary preventive measures in non-asthmatic children with allergic rhinitis (such as regular local anti-inflammatory therapy or specific immunotherapy) should be studied and applied more intensely to prevent bronchial hyper-responsiveness (BHR) and asthma in this high-risk group.

Asthma↗

Are childhood adversities relevant in patients with chronic low back pain?

Previous studies have found a high number of childhood adversities in patients with chronic low back pain, particularly in patients reporting persisting problems after back surgery. Our aim was to reproduce these results. Within the framework of a comprehensive diagnostic assessment and psychometric evaluation, 109 inpatients who had been treated for low back pain were examined in the orthopedics department of a German university hospital. Five risk factors investigated by Schofferman and his staff (Schofferman et al., 1993) were re-assessed in all of our patients using a structured biographical interview. The German chronic low back pain group was also compared with an age- and gender-matched control group of 109 non-chronic pain patients with respect to these childhood adversities and additional ones. Only approximately 11% of the German chronic low back pain sample demonstrated three or more risk factors, compared with more than 50% in Schofferman's sample, and 47.7% showed none of the five risk factors, compared to only 11% in the Schofferman sample. Moreover, no significant differences in distribution either in terms of the individual risk factors or their cumulative frequency were found in the German chronic low back pain group compared with an age and gender-matched control group without chronic pain. Childhood adversities do not occur frequently in a non-selected group of patients with chronic low back pain. Earlier results showing an increased likelihood of the occurrence of psychosocial risk factors could not be confirmed. As a consequence, further psychic or psychosomatic diagnostics of patients with chronic low back pain are needed to define diagnostic subgroups.

Absenteeism↗

[Coping in patients after liver transplantation with regard to their membership in a self-group].

BACKGROUND: Within the past 15 years, liver transplantation has proven itself to be the treatment of choice among patients with terminal liver disease. The one-year survival rate is about 80 %; after 8 years 61 % of the patients are still alive. The present study investigates the influence of active or depressive coping on the physical and mental quality of life in two different groups of patients after liver transplantation. METHODS: Members (n = 65) and non-members (n = 20) of a German self-help group were asked to fill out a postal survey. Patients were included if their liver transplantation was conducted 6 to 36 months ago. The health-related quality of life was surveyed using the SF-36 and coping strategies were investigated with the Freiburg questionnaire on coping with illness. RESULTS: All patients had a good physical and mental quality of life compared with a German normative sample. Members of the self-help group showed substantially higher active coping with illness (p < 0.0001), but only depressive coping correlates (negatively) with physical as well as with mental health-related quality of life (r between -0.24 and -0.68). This was true for both groups investigated. CONCLUSION: Based on an overall good health-related quality of life, depressive coping as well as aspects of the social environment contribute considerably in determining the well-being and quality of life in patients after liver transplantation.

Adaptation, Psychological↗

Somatisation predicts the outcome of treatment in patients with low back pain.

We have assessed the influence of somatisation on the outcome of treatment in 81 patients with chronic low back pain. All, irrespective of whether treatment was surgical or conservative, had a significantly better (p < 0.001) health-related quality of life at follow-up on all but one scale of the SF-36. Lower health-related quality of life at follow-up correlated significantly with a higher tendency to somatise before treatment and at follow-up. A logistic regression analysis yielded two factors which predicted the outcome; somatisation (p < 0.001) and 'doctor shopping' (the number of physicians consulted before the present inpatient treatment, p < 0.001). These factors accurately distinguished between patients with good and those with poor outcomes in 82%. Patients with somatisation and 'doctor shopping' were at a higher risk for a poor outcome. The results show the relevance of somatisation in the outcome of treatment in patients with low back pain.

Adult↗

Health-related quality of life and somatization in patients with long-term low back pain: a prospective study with 109 patients.

STUDY DESIGN: For this study, a prospective cohort of 109 patients was recruited consecutively at an orthopedic inpatient unit of a university hospital. Three self-report instruments were administered to patients with sciatica believed to be caused by a herniated lumbar disc to examine their quality of life and psychic stress at baseline and at the 1-year follow-up visit. OBJECTIVES: To investigate whether patients who have undergone a previous discectomy experience greater psychic stress than patients with no surgery, and to determine whether the groups differed regarding their health-related quality of life at the follow-up visit. SUMMARY OF BACKGROUND DATA: Previous studies have described psychic abnormalities in patients with long-term back pain, particularly patients with severe chronicity (i.e., history of surgeries and persistent problems) or those who underwent a previous discectomy. Additionally, a series of studies has shown that psychic and psychosocial parameters exert a significantly greater influence on the success of treatment than do clinical and imaging findings or the extent of disc abnormality. METHODS: The Short Form Health Survey 36, the Symptom Checklist 90, and Screening for Somatoform Disorders were administered to 109 patients consecutively treated in the authors' orthopedic university clinic, at baseline and at the 1-year follow-up visit. RESULTS: In all the patients examined, the physical and mental quality of life improved regardless of their group classification. The psychological distress, according to the Symptom Checklist 90, was clearly reduced in both groups at the follow-up visit, with the exception of somatization, as indicated by Symptom Checklist 90 and Screening for Somatoform Disorders. Whereas the patients who had undergone surgery remained nearly unchanged with regard to their somatization, the patients with no previous surgery improved significantly, as indicated by Screening for Somatoform Disorders and Symptom Checklist 90. Somatization, particularly that surveyed by the comprehensive Screening for Somatoform Disorders, proved to be quite a stabile factor over time in both groups. The extent of the physical impairment before treatment was nearly the same in both groups, as indicated by Short Form Health Survey 36. Despite a markedly higher chronicity of reported problems, patients who had undergone surgery were hardly more greatly impaired in terms of their mental quality of life and psychological distress, as indicated by Symptom Checklist 90, than those without a history of surgery. At the follow-up visit, the differences tended to be minimal as well. As compared with those who had no previous surgeries, the patients who had undergone surgery were significantly more heavily impaired in their physical quality of life despite significant improvements. CONCLUSIONS: Patients with sciatica demonstrated less abnormality in terms of the psychopathologic markers investigated than described in previous studies. Nevertheless, the predisposition to somatize influences health-related quality of life to a high degree.

Adult↗

Testing for gene-gene interaction controlling total IgE in families from Barbados: evidence of sensitivity regarding linkage heterogeneity among families.

Genetic heterogeneity has been proposed as a hallmark feature of allergic disease. To test the hypothesis that total IgE levels are jointly influenced by a locus on chromosome 12q21.1-q21.31 and a locus on 17q11.2-q21.2, we conducted multipoint allele-sharing analyses using nonparametric linkage (NPL) methods on Afro-Caribbean families from Barbados to test for evidence of gene-gene interactions. Significant correlations were observed between NPL scores at D12S1052 and both D17S1293 and D17S1299 for a dichotomized phenotype of total IgE. An analysis of family-specific NPL scores revealed that evidence for interaction was being driven largely by one multiplex pedigree (NPL = 12.01, 12.23, and 12.16 at D12S1052, D17S1293, and D17S1299, respectively). Using the programs SIMWALK (v2.0) and GOLD, a different set of haplotypes in this influential family was observed around D12S1052 and the 17q loci compared to the other Barbados pedigrees. Our findings are a classic example of founder effect, provide evidence for sensitivity of this type of linkage analysis to unusual pedigrees, and highlight an element of genetic heterogeneity that has been given little attention in the study of complex traits.

Asthma↗

[Chronic pain: epidemiology and health care utilization].

The prevalence of chronic pain in the general population ranges from 10% to over 40%, depending on the investigation and definition. Chronic pain is tied to high direct and indirect costs for the health care system on the one hand and considerable personal impairment of the quality of life on the other. The present paper provides an overview of the frequency and distribution of chronic pain in the general population and among those receiving treatment. The limitations of epidemiological investigations lie in the difficulty of validly assessing subjective internal experiences of the patients. Moreover, it is not possible to make diagnoses in the proper sense. In contrast, the examination of patients seeking and receiving treatment offers a further diagnostic differentiation and better assessment of the qualitative aspects of the pain experience. However, the meaningfulness of these studies is also limited due to the qualitative problems. Despite the methodological limitations of the studies investigated, the wide distribution and meaning of chronic pain becomes clear particularly when evaluating studies on the general population and populations receiving treatment.

Adult↗

Overexpression of cysteine proteinase 2 in Entamoeba histolytica or Entamoeba dispar increases amoeba-induced monolayer destruction in vitro but does not augment amoebic liver abscess formation in gerbils.

To study the role of cysteine proteinases in the pathogenicity of Entamoeba histolytica, we have attempted to overexpress the three main cysteine proteinases (EhCP1, EhCP2, EhCP5) of this parasite in trophozoites of E. histolytica as well as in non-pathogenic Entamoeba dispar by episomal transfection. Although each of the corresponding coding sequences were cloned in identical expression plasmids, we were unable to overexpress EhCP1 and EhCP5, respectively, but could substantially induce expression of EhCP2 in both amoeba species by sevenfold, leading to a threefold increase in total cysteine proteinase activity. Overexpression of EhCP2 did not influence expression of other cysteine proteinases and could be attributed to an increase of a single 35 kDa activity band in substrate gel electrophoresis. In contrast to previous findings, which indicated that amoeba cysteine proteinases are involved in erythrophagocytosis and liver abscess formation, cells overexpressing EhCP2 showed no difference in erythrophagocytosis or liver abscess formation compared with respective controls. However, overexpression of EhCP2 in both amoeba species resulted in a marked increase of in vitro monolayer destruction.

Animals↗

The pattern of atopic sensitization is associated with the development of asthma in childhood.

BACKGROUND: Even though atopic sensitization has been shown to be strongly associated with childhood asthma, asthma eventually develops in only one third of atopic children. OBJECTIVE: The aim of this study was to prospectively investigate the pattern of atopic sensitization typically associated with the development of asthma in childhood. METHODS: The German Multicenter Allergy Study followed 1314 children from birth to the age of 7 years. Parental questionnaires on asthma and asthmatic symptoms were completed 6 times up to the age of 2 years and from then on yearly. Determination of specific IgE to 9 food and inhalant allergens was performed yearly, and at the age of 7 years, a bronchial histamine challenge was conducted. RESULTS: Onset of atopic sensitization in atopic children with current asthma at the age of 7 years was significantly earlier than in atopic children without current asthma (39.4% before age 1 year vs 21.0%, P =.015). Early atopic sensitization without any sensitization to inhalant allergens at the age of 7 years conferred no increased risk for asthma at this age. Only those children sensitized to any allergen early in life and sensitized to inhalant allergens by the age of 7 years were at a significantly increased risk of being asthmatic at this age (odds ratio, 10.12; 95% CI, 3.81-26.88). However, even in this group of persistently sensitized children, the risk of being asthmatic at the age of 7 years was only increased if a positive parental history of asthma or atopy was present (odds ratio, 15.56; 95% CI, 5.78-41.83), with the effect being strongest for maternal asthma. CONCLUSION: Our results indicate that an underlying factor pertaining to asthma and maternal transmission may determine both a certain pattern of sensitization and the expression of asthma.

Age Factors↗

[Coping with conflict as pathogenetic link between psychosocial adversities in childhood and psychic disorders in adulthood].

OBJECTIVES: The present study explores the connection between neurotic or immature strategies for coping with conflict in the presence of specific psychosocial adversities during childhood and their cumulative effect. Here we test the hypothesis as to whether certain coping strategies can be viewed as a pathogenetic link between psychic illness in adulthood and adversities during childhood. METHODS: 407 consecutive patients referred to the outpatient unit of a psychosomatic university hospital were included in the study. The strategies for coping with conflict were assessed by means of two psychometric methods (FKBS, Hentschel et al., 1996; SBAK, Ehlers u. Peter, 1989), and the childhood adversities were assessed using the Mainz Structured Biographic Interview (Egle, 1993). RESULTS: Patients with sexual abuse and/or physical maltreatment during the first 14 years of life showed significantly higher values for immature coping mechanisms than patients without such traumatisation. Childhood adversities correlated negatively with mature coping strategies and positively with immature strategies. Significant differences also arise when patients with low risk are compared to those with a higher amount of childhood adversities. The latter group exhibits significantly higher scores for immature neurotic coping strategies, while the former exhibits mature ones. By means of a multivariate logistic regression analysis, 7 and 10% respectively of the variance of the predominant coping strategies within each group occurring in adulthood could be accounted for. CONCLUSIONS: The results suggest that in patients exposed to psychosocial stress during childhood an increased vulnerability for psychic disorders in adulthood is, in part, caused by the use of immature strategies for coping with conflict.

Adaptation, Psychological↗

Two novel calcium-binding proteins from cytoplasmic granules of the protozoan parasite Entamoeba histolytica.

We report on the molecular characterisation of two novel granule proteins of the protozoon and human pathogen Entamoeba histolytica. The proteins, which were named grainin 1 and 2, show a considerable structural similarity to calcium-binding proteins, particularly within EF-hand motifs. Each grainin possesses three of these putative calcium-binding sites. Based on careful inspection of known structures of protein families containing EF-hands, a domain of grainin 1 covering two EF-hand motifs was modeled by homology. Calcium-binding activity of grainins was demonstrated by two independent methods. These granule proteins may be implicated in functions vital for the primitive phagocyte and destructive parasite such as control of endocytotic pathways and granule discharge.

Amino Acid Motifs↗

Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers.

Atopic dermatitis is a chronic inflammatory skin disease that affects 10-20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31-33, 6p21.3, 12q15-24.1, 13q12-31, and 14q11.2/14q32.1-32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS'90), parental DNA was tested in 77 of 192 children with atopic dermatitis; (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12-14 and 5q31-33.

Child↗

An IL13 coding region variant is associated with a high total serum IgE level and atopic dermatitis in the German multicenter atopy study (MAS-90).

BACKGROUND: Allergic diseases are one of the major causes of morbidity in the developed countries today, and the prevalence of these diseases is increasing steadily. Study of total serum gE level is important in understanding the genetics of allergic iseases because IgE levels are considered to be a crucial pathogenic component. IL-13 plays an important role in the induction of IgE synthesis and in the pathogenesis of allergic diseases. OBJECTIVE: We sought to examine potential variation at the IL13 gene and estimate its effect on elevated IgE level and atopic dermatitis (AD). METHODS: We conducted mutational analyses of the IL13 gene by using single-stranded conformation polymorphism and DNA sequencing. Case control studies for high-IgE phenotype and AD were performed by using subjects from the German MAS-90 cohort. RESULTS: A novel IL13 coding region variant at 4257 bp (G to A, fourth exon) was identified. Case control studies of a German sample from the MAS-90 cohort showed significant associations between the presence of the A allele and two atopic phenotypes: high IgE (odds ratio, 2.38; 95% confidence interval, 1.35-4.21; P =.0026) and AD (odds ratio, 1.77; 95% confidence interval, 1.06-2.96; P =.03). CONCLUSION: This IL13 coding region variant may be involved in the pathogenesis of AD and high total serum IgE level in a study population of white subjects.

Chromosomes, Human, Pair 5↗

A genome-wide search for linkage to asthma. German Asthma Genetics Group.

Asthma is among the most frequent chronic diseases in childhood. Although numerous environmental risk factors have already been identified, the basis for familial occurrence of asthma remains unclear. Previous genome screens for atopy in British/Australian families and for asthma in different American populations showed inconsistent results. We report a sib pair study of a sample of 97 families, including 415 persons and 156 sib pairs. Following an extensive clinical evaluation, all participants were genotyped for 351 polymorphic dinucleotide markers. Linkage analysis for asthma identified four chromosomal regions that could to be linked to asthma: chromosome 2 (at marker D2S2298, P = 0.007), chromosome 6 (around D6S291, lowest P = 0.008), chromosome 9 (proximal to D9S1784, P = 0.007), and chromosome 12 (D12S351, P = 0.010). These linkage regions could be reproduced for all loci by analysis of total or specific immunoglobulin E (minimum P values at these regions were 0. 003, 0.001, 0.010, and 0.015, respectively).

Asthma↗

Ozone isotope enrichment: isotopomer-specific rate coefficients

Six rate coefficients of relative ozone formation contradict the role of molecular symmetry in the process that results in the enrichment of heavy ozone isotopomers. The results show that collisions between light atoms, such as 16O, and heavy molecules, such as 34O2 and 36O2, have a rate coefficient advantage of about 25 and 50 percent, respectively, over collisions involving heavy atoms and light molecules. These results suggest that the observed isotope effect for each isotopomer may be caused by the preponderance of a single reaction channel and not through molecular symmetry selection.

Journal Article↗