Trends in prevalence and risk factors of allergic rhinitis symptoms in primary schoolchildren six years apart in Budapest.

BACKGROUND: Few data are available concerning the time trends and risk factors associated with allergic rhinitis (AR) in schoolchildren in Hungary. METHODS: At an interval of six years, parents of 6-12-year-old children completed identical ISAAC-based and additional questionnaires related to possible risk factors. RESULTS: Response rate was 62.8% with 6335 questionnaires distributed in 2007, and 52.9% with 6441 questionnaires in 2013. The prevalence of current AR symptoms (subjects presenting clinical symptoms of AR in the past 12 months, but had yet to be diagnosed by physician) increased significantly from 14.9% to 23.5% (p<0.001). There was no significant change in the prevalence of physician-diagnosed AR (11.6-11.2%). In multivariate analysis, gender (OR 0.733; CI 0.642-0.931), a family history of atopy (OR 2.017; CI 1.669-2.436), frequent upper respiratory tract infections (OR 2.033; CI 1.659-2.492), long-lasting disease before the appearance of the allergy (OR 2.119; CI 1.311-3.428), feather bedding (OR 0.773; CI 0.599-0.996) and living in a green area (OR 1.367; CI 1.133-1.650) were found to be significant risk factors of cumulative AR in 2013. In both of the groups with (p<0.000) or without (p<0.003) AR the families with a history of atopy used feather bedding less frequently than families without atopy. CONCLUSION: Although the prevalence of physician-diagnosed AR has not shown significant changes during the studied interval, the significant increase of the current AR symptoms suggests growing prevalence of AR among children in Budapest. Our results revealed new aspects of bedding customs in atopic families.

Work status in patients with early rheumatoid arthritis: emphasis on shoulder function and mechanical exposure.

OBJECTIVES: The aim of this study was to investigate work status and associated factors in patients with early rheumatoid arthritis (RA), with the emphasis on shoulder function, work-related mechanical exposure, and activity limitations related to the shoulder-arm-hand. METHOD: Patients with early RA were provided with self-report questionnaires quantifying work-related mechanical exposure and activity limitations. Shoulder function (i.e. isometric muscle strength, shoulder-arm movement, and shoulder pain), hand-grip force, and number of tender and swollen joints were assessed. RESULTS: The study comprised 135 patients (103 women and 32 men), with a mean age of 48 (SD 9.6) years, a mean disease duration of 21 (SD 9.6) months, and a mean Disease Activity Score using 28 joint counts (DAS28) of 3.7 (SD 1.4). The majority (75.6%) were working full- or part-time. Work hours correlated with work-related mechanical exposure (rs = -0.34, p < 0.001) and with physical work load (rs = 0.26, p = 0.0036). Work hours also correlated with shoulder function, that is shoulder-arm movement (rs = 0.34, p < 0.0001), shoulder strength (rs = 0.25, p = 0.0032), and activity-induced shoulder pain (rs = -0.45, p < 0.0001). Significant correlations were found between work hours and hand-grip force (rs = 0.45, p < 0.0001), activity limitations related to the shoulder-arm-hand (using the Disabilities of the Arm, Shoulder and Hand Questionnaire, DASH) (rs = -0.61, p < 0.0001), and DAS28 (rs = -0.43, p < 0.0001). DASH was found to be the only significant (p < 0.001) variable to independently explain the ability of working full-time [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.29-0.55 per 10 increments, area under the receiver operating characteristic (ROC) curve (AUC) 0.81, 95% CI 0.74-0.89]. CONCLUSIONS: Work status in early RA is associated with shoulder function and activity limitations related to the shoulder-arm-hand accentuated by work-related mechanical exposure.

The c.-133A > G polymorphism in NPC1L1 gene influences the efficacy of ezetimibe monotherapy on apolipoprotein A1 in hyperlipidemic patients.

Niemann-Pick C1-like 1 protein (NPC1L1) plays a critical role in intestinal cholesterol absorption. Previous studies found that the NPC1L1 c.-133A > G SNP, but not other NPC1L1 SNPs, was associated with response to statin treatment and statin-ezetimibe combinations. To date effect of NPC1L1 c.-133A > G SNP on ezetimibe monotherapy has not been studied. Our objective was to examine whether SNP c.-133A > G at the NPC1L1 gene has effects on lipid levels and on the efficacy of 3, 6 and 12 months of 10 mg daily ezetimibe monotherapy in hyperlipidemic patients with statin induced adverse effects. One hundred and one type IIa and IIb hyperlipidemic patients (72 females, 29 males; age: 61.23 +/- 9.87 ys; BMI: 28.18 +/- 4.29 kg/m2) were enrolled. The genotype frequencies were conformed to Hardy-Weinberg equilibrium. We could not find significant differences in initial lipid levels between AA and AG + GG patients. While plasma levels of apolipoprotein A1 (ApoA1) did not significantly decrease after ezetimibe treatment (1.96; 3.39 and 2.74%) in AA patients, a significant elevation in ApoA1 levels has been found after treatment in AG + GG patients (9.15; 8.54 and 13.58%). The effect of NPC1L1 c.-133A > G on the ApoA1 levels was found significant (p < 0.05). Efficacy of treatment with ezetimibe on other plasma lipid parameters after 3, 6 or 12 months did not differ significantly. NPC1L1-133A > G SNP influences the ApoA1 response to ezetimibe monotherapy, therefore, may alter the effect of ezetimibe on the structure and function of the high-density lipoprotein particles.

Rationalisation in public dental care--impact on clinical work tasks and mechanical exposure for dentists--a prospective study.

Swedish dentistry has been exposed to frequent rationalisation initiatives during the last half century. Previous research has shown that rationalisation often results in increased risk of developing work-related musculoskeletal disorders, thus reducing sustainability in the production system. In this prospective study, we assessed mechanical exposures among Swedish dentists in relation to specific rationalisations of clinical dental work during a six-year period. Body postures and movements of 12 dentists were assessed by inclinometry synchronised to video recordings of their work. No rationalisation effects could be shown in terms of a reduction in non-value-adding work ('waste'), and at job level, no major differences in mechanical exposure could be shown between baseline and follow-up. CONCLUSION: The present rationalisation measures in dentistry do not seem to result in rationalisation at job level, but may potentially be more successful at the overall dental system level. PRACTITIONER SUMMARY: In contrast to many previous investigations of the mechanical exposure implications of rationalisation, the present rationalisation measures did not increase the level of risk for dentists. It is highlighted that all occupations involved in the production system should be investigated to assess production system sustainability.

Working conditions, health and productivity among dentists in Swedish public dental care--a prospective study during a 5-year period of rationalisation.

In recent decades, comprehensive rationalisations have been implemented in public dentistry in Sweden. How rationalisations affect working conditions, health and production from a long-term perspective has been poorly investigated. This study aims to analyse changes and associations in dentists' working conditions, health and productivity during a 5-year period. In 2003 and 2008, 65 dentists responded to questionnaires measuring work conditions and health. Treatment times for patients and productivity were tracked in electronic registers. Paired t-tests showed that the number of treated adult patients per dentist increased, and perceived physical working conditions improved while perceived work control and leadership deteriorated. Structural equation modelling showed that physical factors were important for health and productivity. When assessing risks in the work environment, there is a need to understand the interaction of effects on working conditions and health due to rationalisations so as to increase the sustainability of production systems. PRACTITIONER SUMMARY: Dentistry in Sweden has undergone considerable change. Questionnaire surveys with dentists, undertaken in 2003 and 2008, found that the present rationalisations resulted in improved perceived physical working conditions. Aspects of the psychosocial working environment had deteriorated, however. This is a concern as health and workability are important for workplace efficiency.

Molecular Diagnostic Challenges and Complex Management of Consecutive Twin Pregnancies in a Family with CD40 Ligand Deficiency.

X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency disorder (PID) caused by mutation in the gene encoding the CD40 ligand (CD40L) expressed on activated T cells. Prenatal genotyping in carriers with twin pregnancies is more challenging than in women with singleton pregnancies. In addition, women with twin pregnancies may decide on selective termination for which the risk of loss of the healthy foetus may exceed 7%. We report here on a family affected by XHIGM. Diagnosis of the disease was made in a male patient as late as 33 years of age. After family screening, the sister of the proband conceived male twins in two consecutive pregnancies. In the first pregnancy, one of the male foetuses was hemizygous for the c.521A>G (Q174R) mutation in the CD40L gene. In the second pregnancy, ultrasound scan showed one foetus to have exencephaly and karyotyping revealed this foetus to have trisomy 18. Several options were discussed, but the parents decided on selective termination in both pregnancies. The interventions were successful in both cases, and the mother now has two healthy sons. This report demonstrates the way in which advanced technologies in molecular medicine and obstetric interventions may assist families with decisions about possible selective termination in case of life-threatening molecular or chromosomal disorders. Diagnosis of CD40L deficiency at the age of 33 years in the proband was striking and indicated that PIDs are still neglected as disease entities in the evaluation of patients with recurrent severe infectious diseases.

Mechanical exposure among general practice dentists in Sweden and possible implications of rationalisation.

The present study investigates the dental work in terms of time distribution and mechanical exposure in value-adding work (VAW) and non-VAW. Further rationalisation of dental work would typically involve an increase in the proportion of VAW. Information on mechanical exposure within the classes of VAW and non-VAW may be used to predict possible implications of rationalisation. Sixteen dentists were investigated. Using a data logger, postures and movements were continuously recorded for each subject during the 4 h of work, which included the 45 min of video recording. Time distribution and mechanical exposure for the six different work activities identified were evaluated from the video recordings, using a loss analysis technique. VAW, which comprised 54% of the total working time, generally implied significantly more constrained mechanical exposures as compared with non-VAW. The results suggest that future rationalisation of dental work, involving a reduction of non-VAW, may increase the risk of developing musculoskeletal disorders. Statement of Relevance: The present study illustrates the potential effects of rationalisation on biomechanical exposures for dentists. The results highlight the significance of integrating ergonomic issues into the rationalisation process in dentistry in addition to ordinary workstation and tool design improvements performed by ergonomists.

A fully automated system with an optical immersion probe (OIP) for high-precision spectrophotometric measurements.

A new and fully automated system with the interconnection of an Optical Immersion Probe (OIP) - pH meter - peristaltic pump was used to study the spectral and protolytic properties of carbocyanine the dyes 1,1',3,3,3',3'-hexamethylindocarbocyanine chloride (HIC); 1,1',3,3,3',3'-hexamethylindodicarbocyanine iodide (HIDC); and 3,3'-diethyloxadicarbocyanine iodide (DODC). This system can measure a large number of experimental points in a short time period. The effect of 32 various organic solvents on the UV-ViS spectra of the dyes was studied. The solvatochromic behaviour of studied dyes was characterized by positive solvatochromism for HIDC and negative solvatochromism for HIC and DODC. Through the application of a large number of experimental points, the protonation and hydrolysis constants of dyes were determined with high precision, where the confidence interval of the рK values is ±(0.001-0.005), compared with a confidence interval of ±(0.04-0.10) for standard procedures. The fully automated system presented is accurate, fast, environmentally friendly and promising for multiple analytical applications.

Precision of measurements of physical workload during standardised manual handling. Part II: Inclinometry of head, upper back, neck and upper arms.

For measuring the physical exposure/workload in studies of work-related musculoskeletal disorders, direct measurements are valuable. However, the between-days and between-subjects variability, as well as the precision of the method per se, are not well known. In a laboratory, six women performed three standardised assembly tasks, all of them repeated on three different days. Triaxial inclinometers were applied to the head, upper back and upper arms. Between-days (within subjects) and between-subjects (within tasks) variance components were derived for the 10th, 50th and 90th percentiles of the angular and the angular velocity distributions, and for the proportion of time spent in predefined angular sectors. For percentiles of the angular distributions, the average between-days variability was 3.4 degrees , and the between-subjects variability 4.0 degrees . For proportion of time spent in angular sectors, the variability depended on the percentage of time spent in the sector; the relative variability was scattered and large, on average 103% between days and 56% between subjects. For the angular velocity percentiles, the average between-days variability was 7.9%, and the average between-subjects variability was 22%. The contribution of the measurement procedure per se to the between-days variability, i.e., the imprecision of the method, was small: less than 2 degrees for angles and 3% for angular velocity.

The importance of work organization on workload and musculoskeletal health--Grocery store work as a model.

We have evaluated the consequences of work organization on musculoskeletal health. Using a postal questionnaire, answered by 1600 female grocery store workers, their main work tasks were identified and four work groups were defined (cashier, picking, and delicatessen work, and a mixed group, who performed a mix of these tasks). The crude odds ratios (ORs) for neck/shoulder complaints were 1.5 (95% CI 1.0-2.2), 1.1 (0.7-1.5) and 1.6 (1.1-2.3), respectively, compared to mixed work. Adjusting for individual and psychosocial factors had no effect on these ORs. For elbows/hands, no significant differences were found. Technical measurements of the workload showed large differences between the work groups. Picking work was the most strenuous, while cashier work showed low loads. Quantitative measures of variation revealed for mixed work high between minutes variation and the highest between/within minutes variation. Combining work tasks with different physical exposure levels increases the variation and may reduce the risk of musculoskeletal complaints.

Anti-factor V auto-antibody in the plasma and platelets of a patient with repeated gastrointestinal bleeding.

Development of autoantibody against coagulation factor V (FV) is a rare clinical condition with hemorrhagic complications of varying severity. The aim of this study was to establish the pathomechanism of an acquired FV deficiency and characterize the FV inhibitor responsible for the clinical symptoms. A 78-year-old female was admitted to hospital with severe gastrointestinal bleeding. General clotting tests and determination of clotting factors were performed by standard methods. FV antigen and FV containing immune complexes were measured by ELISA. The FV molecule was investigated by Western blotting and by sequencing the f5 gene. The binding of patient's IgG to FV and activated FV (FVa) was demonstrated in an ELISA system and its effect on the procoagulant activity of FVa was tested in clotting tests and in a chromogenic prothrombinase assay. Localization of the epitope for the antibody was performed by blocking ELISA. FV activity was severely suppressed both in plasma and platelets. FV antigen levels were normal by ELISA using polyclonal anti-FV antibody or monoclonal antibody against the connecting region of FV, but depressed when HV1 monoclonal antibody against the C2 domain in the FV light-chain was used as capture antibody. The FV molecule was found intact. An IgG reacting with both FV and FVa was present in the patient's plasma and its binding to FV was inhibited by HV1 antibody. FV-containing immune complexes were detected in the patient's plasma and platelet lysate. The patient's IgG inhibited the procoagulant function of FVa. An anti-FV IgG was present in the patient's plasma and platelets. The autoantibody reacted with an epitope in the C2 domain of FV light chain and neutralized the procoagulant function of FVa.

Factor XIII of blood coagulation as a nuclear crosslinking enzyme.

Intracellular localization and distribution of Factor XIII subunit A (FXIIIA) was investigated in association with monocyte-macrophage differentiation in a long term culture of human monocytes by light- and electron microscopical as well as biochemical and immunobiochemical techniques. To allow the detection of FXIIIA in cells with well-preserved ultrustructure, immunosera against glutaraldehyde-derivatized recombinant FXIIIA were developed in rabbits, then characterized and used in this study. In the early phase of macrophage differentiation intranuclear accumulation of FXIIIA was detected as a transient phenomenon in cells of the 2nd day culture by optical sectioning with 0,7 microm steps in laser scanning confocal microscopy and immunoblotting technique. FXIIIA could be detected by immunoelectron microscopic postembedding staining over electrodense DNA-containing areas. Fluoresceinated monodansylcadaverine incorporation assay was used to demonstrate that FXIIIA is not only present in the nuclei, but also expresses its transglutaminase activity. Our finding of the nuclear accumulation of FXIIIA in differentiating human macrophages is also unique in that a blood clotting factor has, for the first time, been localized in nuclei and has been shown to be an intracellular crosslinking enzyme. The possible role of nuclear FXIIIA in association with cellular processes involving chromatin structure remodeling, such as cell death, cell differentiation or cellular proliferation requires further in-depth investigation.

Effect of Val34Leu polymorphism on the activation of the coagulation factor XIII-A.

Coagulation factor XIII (FXIII) is a protransglutaminase involved in the last step of the coagulation cascade by stabilising the fibrin clot. Recently, a common variation (FXIII Val34Leu) has been associated with a decreased risk of myocardial infarction and deep venous thrombosis. Val34Leu is critically located near the thrombin activation site of FXIII-A. In this study we investigated its effects on the activation of FXIII. Both recombinant and platelet-derived FXIII Val34Leu variants were shown to be more susceptible to thrombin cleavage than the wild type FXIII. The rate of enzymatic activation of FXIII Val34Leu was found increased, however, the specific activity of fully activated wild type FXIII and the Val34Leu mutant did not differ. During the course of thrombin-induced activation of FXIII fibrin gamma-chain dimerisation and alpha-chain polymerisation developed more rapidly with the Val34Leu mutant. The increased rate of fibrin stabilisation brought about by the Val34Leu FXIII seems to be paradoxically associated with a protective effect against pathological thrombosis.

Membranous glomerulonephritis in a patient with inherited activated protein C resistance.

We present a patient with membranous glomerulonephritis, several clinical complications of the antiphospholipid syndrome and ulcerative colitis, but without lupus anticoagulant and antiphospholipid/cofactor antibodies. Immunological studies--other antibodies--were negative and failed to show enough criteria for any autoimmune diseases. Evaluation of her laboratory tests for hereditary thrombophilia revealed a heterozygous form of the Leiden mutation that might be associated with widespread vasculopathy. An interesting possibility is that the inherited activated protein C resistance could be an additional risk factor for vaso-occlusive manifestations appearing as a clinical sign of cardiovascular diseases and nephropathy.

The role of platelet-activating factor (PAF) antagonists and nitric oxide in cardiac actions of PAF. Electrophysiological and morphological study.

Electrophysiological and ultrastructural effects of platelet-activating factor (PAF) antgonists, WEB 2086 and BN 52021 were compared in isolated guinea-pig hearts preparations. We studied the possible role of nitric oxide (NO) in electromechanical actions of PAF. Isometric twitches and intracellular action potentials (APs) were recorded from guinea-pig right ventricular papillary muscles and left atria. For electron microscopic study the hearts were perfused according to Langendorff technique. WEB 2086 (5 x 10(-9)-5 x 10(-7) M) significantly shortened the duration of atrial AP without changing the ventricular one, however, BN 52021 decreased both of them. The shortening of atrial and ventricular AP duration (APD) by both PAF antagonits were abolished by 4-aminopyridine (10(-3) M), a blocker of one type of K+ channels (IKto). Glibenclamide (10(-6) M) the blocker of ATP-dependent K channels prevented the shortening effect of BN 52021 (10(-6) M) on ventricular APD. Electron microscopic study of myocardial samples from hearts subjected to 30 min hypoxia/reoxygenation showed intracellular oedema, intramitochondrial swelling and fragmentation of mitochondrial christae, separation of intercalated disc. Pretreatment with WEB 2086 (5 x 10(-7) M) warded off nearly all damage caused by hypoxia/reoxygenation. Both WEB 2086 and NO synthase inhibitor NG-nitro-L-arginine methyl esther (L-NAME) (10(-3) M) abolished the negative inotropic effect of PAF (10(-7), 10(-6) M). L-NAME prevented the shortening of APD induced by 10(-7) M PAF. These results suggest that PAF may be responsible for myocardial ischemia and the beneficial effects of PAF antagonists in this pathological process could be due to their possible K+ channel stimulator property. These data support the possibility that NO contributes to the cardiac electromechanical alterations induced by PAF.

Interindividual variation of physical load in a work task.

OBJECTIVES: This study analyzed the variation in physical work load among subjects performing an identical work task. METHODS: Electromyographs from the trapezius and infraspinatus muscles and wrist movements were recorded bilaterally from 49 women during a highly repetitive industrial work task. An interview and a physical examination were used to define 12 potential explanatory factors, namely, age, anthropometric measures, muscle strength, work stress, and musculoskeletal disorders. RESULTS: For the electromyographs, the means of the 10th percentiles were 2.2% and 2.8% of the maximal voluntary electrical activity (%MVE) for the trapezius and infraspinatus muscles, respectively. However, the interindividual variations were very large [coefficients of variation (CV) 0.75 and 0.62, respectively]. Most of the variance could not be explained; only height, strength, and coactivation of the 2 muscles contributed significantly (R2(adj)0.20-0.52). The variation was still large, though smaller (CV < or =0.63), for values normalized to relative voluntary electrical activity (RVE). For the wrist movements, the median velocity was 29 degrees per second, and the interindividual variations were small (CV < or =0.24). Six factors contributed to the explained variance (R2(adj)0.12-0.55). CONCLUSIONS: The interindividual variation is small for wrist movements when the same work tasks are performed. In contrast, the electromyographic variation is large, even though less after RVE normalization, which reduces the influence of strength, than when MVE is used. Because of these variations, several electromyographs are needed to characterize the exposure of a specific work task in terms of muscular load, and individual electromyographs are preferable when the worker' s risk of myalgia is being studied.

Finger receptor dysfunction in dental technicians exposed to high-frequency vibration.

The effects of high-frequency vibration (up to 40 kHz) on digital nerve function were studied in ten dental technicians and ten age-matched referents. Nerve conduction velocities, including fractionated antidromic measurements over the carpal tunnel, showed no difference between the groups. In the group of dental technicians the difference between the response latency of the mechanical and electric stimuli in the median nerve distally on the fingers of the right hand was slightly higher than in the reference group, and therefore distal nerve or receptor dysfunction was suggested. Vibration warming and cooling thresholds were significantly increased and thus revealed damage to both myelinated and unmyelinated fibers in the fingers of subjects exposed to high-frequency vibration.

Questionnaire-based mechanical exposure indices for large population studies--reliability, internal consistency and predictive validity.

OBJECTIVES: This study attempts to construct valid indices for mechanical exposure of the shoulder-neck region with relation to the development of shoulder-neck pain in a 1-year perspective study of a general population. METHODS: A comprehensive questionnaire was presented to 14 556 subjects aged 45 or 65 years and repeated after 12 months. Twenty-four questions concerning positions, movements, and manual materials handling were registered on a 3-point impact scale. Musculoskeletal problems were reported on a slightly modified version of the Standardized Nordic Questionnaire for the Analysis of Musculoskeletal Symptoms. Test-retest stability after 2 weeks was calculated for 232 consecutive participants. Based on mechanistic theories, 4 exposure indices were formed. Another 5 constructs were obtained by factor analysis. RESULTS: All the indices showed good test-retest stability, and 5 of them had very good internal consistency. Due to overlaps between the indices, 2 indices stood out as having unique properties. One of them concerned mainly postures and the other dealt primarily with measured lifting. However, the latter was not related to the shoulder-neck pain outcome when adjusted for the posture index. The posture index showed an exposure-effect relationship with the outcome. The job titles implied a large degree of exposure misclassification. CONCLUSIONS: The posture index is recommended as a mechanical exposure index for analyses of interaction with other possible determinants of shoulder-neck pain (ie, psychosocial factors). The use of such an index instead of job titles in large population studies will reduce the risk of misclassification.

Questionnaire versus direct technical measurements in assessing postures and movements of the head, upper back, arms and hands.

OBJECTIVES: This study compares questionnaire-assessed exposure data on work postures and movements with direct technical measurements. METHODS: Inclinometers and goniometers were used to make full workday measurements of 41 office workers and 41 cleaners, stratified for such factors as musculoskeletal complaints. The subjects answered a questionnaire on work postures of the head, back, and upper arms and repeated movements of the arms and hands (3-point scales). The questionnaire had been developed on the basis of a previously validated one. For assessing worktasks and their durations, the subjects kept a 2-week worktask diary. Job exposure was individually calculated by time-weighting the task exposure measurements according to the diary. RESULTS: The agreement between the self-assessed and measured postures and movements was low (kappa = 0.06 for the mean within the occupational groups and kappa = 0.27 for the whole group). Cleaners had a higher measured workload than office workers giving the same questionnaire response. Moreover, the subjects with neck-shoulder complaints rated their exposure to movements as higher than those without complaints but with the same measured mechanical exposure. In addition, these subjects also showed a general tendency to rate their postural exposure as higher. The women rated their exposure higher than the men did. CONCLUSIONS: The questionnaire-assessed exposure data had low validity. For the various response categories the measured exposure depended on occupation. Furthermore, there was a differential misclassification due to musculoskeletal complaints and gender. Thus it seems difficult to construct valid questionnaires on mechanical exposure for establishing generic exposure-response relations in epidemiologic studies, especially cross-sectional ones. Direct technical measurements may be preferable.