Occupational asthma caused by stainless steel welding fumes: a clinical study.

The aim of the present study was to describe the cases of occupational asthma (OA) due to stainless steel welding fumes diagnosed at the Finnish Institute of Occupational Health during the period 1994-2003. OA was diagnosed according to patient history, lung function examinations and welding challenge tests with measurements of the forced expiratory volume in one second (FEV(1)) and peak expiratory flow (PEF) values. The present series comprised 34 patients, all male, with a mean age of 44.7 yrs (range 22-57), mainly working as welders. The mean duration of exposure was 22.4 yrs, and the mean duration of exposure before the onset of respiratory symptoms was 18 yrs. Dyspnoea was the most frequently reported work-related respiratory symptom. During the inhalation challenge tests, the mode of the asthmatic FEV(1)/PEF reaction was delayed in 16 (47%) patients, immediate in nine (26%) patients and dual (both immediate and delayed) in nine (26%) patients. In the follow-up assessment 6 months later, only six patients were considered able to continue performing welding tasks, whereas occupational injury pension was recommended for seven, and measures of vocational rehabilitation for 14 patients. In most cases, after the diagnosis of occupational asthma, the continuation of welding work was not possible.     

Occupational IgE-mediated allergy to Tribolium confusum (confused flour beetle)

BACKGROUND: We report on IgE-mediated allergy in a worker caused by Tribolium confusum (confused flour beetle). These beetles lived in the "old" flour to which he was exposed in his work. CASE REPORT: A 35-year-old, nonatopic mechanic in a rye crispbread factory developed rhinitis, conjunctivitis, and asthmatic symptoms, as well as urticaria on his wrists, lower arms, hands, neck, and face, during the maintenance and repair of machines contaminated by flour. This flour had been in and on the machines for a long time, and it contained small beetles. The patient did not suffer any symptoms when handling fresh, clean flour. RESULTS: Skin prick tests with standard environmental allergens, storage mites, enzymes, flours, and molds were negative. A prick test with flour from the machines gave a 10-mm reaction. An open application of the same flour caused urticarial whealing on the exposed skin. Prick tests with fresh flour from the factory were negative. A prick test with minced T. confusum from the flour in the machines gave a 7-mm reaction. Histamine hydrochloride 10 mg/ml gave a 7-mm reaction. Specific serum IgE antibodies to T. confusum were elevated at 17.2 kU/l. Prick tests with the flour from the machines were negative in five control patients. CONCLUSIONS: The patient had occupational contact urticaria, rhinitis, conjunctivitis, and asthmatic symptoms from exposure to flour. His symptoms were caused by immediate allergy to the beetle T. confusum. Immediate allergy to this beetle has rarely been reported in connection with respiratory symptoms, but it may be more common. Contact urticaria from this source has not been reported before.     

The human brain processes visual changes that are not cued by attended auditory stimulation

Event-related potentials (ERPs) to visual stimuli were recorded from the scalp of eight adult humans performing a task in which they counted vowels from a heard story. In the oddball condition, a repeated (standard) light bar of 50 ms in duration was rarely (P = 0.1) replaced by a (deviant) one differing in orientation from the standard. In the control condition, standards were simply omitted from the series and only (alone-) deviants retained. In both conditions, visual stimuli were asynchronous with auditory-task-relevant stimuli. ERPs to deviants significantly differed in amplitude from those to standards in the midline electrodes centrally, parietally and occipitally at 160-200 ms from stimulus onset. Occipitally, such a difference was absent between ERPs to alone-deviants and those to standards. The occipital differential ERPs to deviants, which thus could be found only when standards were present in the series, are discussed in the context of the mismatch negativity (MMN).     

Molecular and biological analysis of echovirus 9 strain isolated from a diabetic child

The full-length infectious cDNA clone was constructed and sequenced from the strain DM of echovirus 9, which was recently isolated from a 6-week-old child at the clinical onset of type 1 diabetes. Parallel with the isolate DM, the full-length infectious cDNA clone of the prototype strain echovirus 9 Barty (Barty-INF), was constructed and sequenced. Genetic relationships of the sequenced echo 9 viruses to the other members of the human enterovirus type B species were studied by phylogenetic analyses. Comparison of capsid protein sequences showed that the isolate DM was closely related to both prototype strains: Hill and Barty-INF. The only exception was the inner capsid protein VP4 where serotype specificity was not evident and the isolate DM clustered with the strain Hill and the strain Barty-INF with echovirus 30 Bastianni. Likewise, the nonstructural protein coding region, P2P3, of isolate DM was more similar to strain Hill than to strain Barty-INF. However, like echovirus 9 Barty, the isolate DM contained the RGD-motif in the carboxy terminus of capsid protein VP1. By blocking experiments using an RGD-containing peptide and a polyclonal rabbit antiserum to the alpha(v)beta(3)-integrin, it was shown that this molecule works as a cellular receptor for isolate DM. By using primary human islets, it was shown that the isolate DM is capable of infecting insulin-producing beta-cells like the corresponding prototype strains did. However, only isolate DM was clearly cytolytic for beta-cells. The infectious clones that were made allow further investigations of the molecular features responsible for the diabetogenicity of the isolate DM.     

Phylogenetic analysis of rhinovirus isolates collected during successive epidemic seasons

Human rhinoviruses (HRV) have been shown to be the major causative agent for mild respiratory infections, but also associated with more serious diseases, such as acute otitis media and pneumonia in children, and asthma. Despite the economical and medical importance of HRV, little is known about the circulation and genetic diversity of HRV during a given season. The aim of this study was to genetically characterize HRV strains causing acute respiratory infections in a cohort of small children during a 2 years follow-up time. Genetic relationships between 61 HRV field isolates were studied using partial genomic sequencing in the VP4/VP2 region (420 nt) and phylogenetic analysis of these sequences. Sequences from the clinical isolates clustered in the two previously known phylogenetic clades, the designated genetic group 2 (including HRV 14) being more predominant. The maximum genetic variation within group 1 was 32.3% and within group 2 it was 32.7%. Several distinct clusters could be observed, some of which were strictly seasonal, whereas some other variants were detected during several seasons. The results of this study show striking genetic diversity of the HRV strains circulating in a given community during a short time.     

Lack of Autoimmune Serological Reactions in Rodent Models of Insulin Dependent Diabetes Mellitus

Spontaneous insulitis with insulin-dependent diabetes mellitus (IDDM) in rodent models, the BB rat and NOD mouse, has clarified the pathogenesis of and guided decisions on interventional therapy for human IDDM. However, the occurrence in such models of a standard marker of human IDDM, autoantibodies to β islet cell constituents, has been controversial. Hence we assessed diabetes-prone rodents for the frequencies of raised levels of auto-antibodies to glutamic acid decarboxylase GAD (anti-GAD), insulin and heat shock protein 65 (HSP-65) in relation to levels in non-diabetes-prone animals and levels in human diabetic sera. Assays were performed sequentially at various ages of life. The immunoassays used for anti-GAD and anti-insulin were those validated for sensitivity and specificity for detection of the corresponding autoantibodies in human IDDM sera at international workshops. Positive controls included human IDDM sera with reactivity with GAD or insulin and, for mouse anti-GAD, the highly reactive monoclonal antibody, GAD-6. The results were that levels of autoantibodies in diabetes-prone BB rats or NOD mice to the ‘IDDM-relevant’ autoantigens in our panel did not exceed levels in control rats or mice, and were much lower than levels in humans with IDDM. We conclude that the BB rat and NOD mouse represent a model, but not a facsimile, of human IDDM and that therapeutic successes in such models should be interpreted with caution in relation to interventional therapy for human IDDM.     

Cardiorespiratory and thermal effects of wearing gas protective clothing

Summary Six healthy men aged 25 to 37 walked on a treadmill at work levels of 21 and 41% of their for 25 to 30 min wearing gas protective clothing (GPC) consisting of an impermeable suit with a self-contained breathing apparatus (total weight 25 kg) or shorts (control tests, CT) in a temperate environment (t _a 24.3°C ± 1.0°C, rh 30–50%). When the GPC was worn at 21 and 41% , the most prominent increases, compared with the CT, were noted in the heart rate ( ± SE, 120 ± 5 vs 76 ± 3 beats min^–1 and 171 ± 5 vs 103 ± 3 beats min^–1), mean skin temperature (36.1 ± 0.2 vs 31.3° C ± 0.1°C and 36.9 ± 0.3 vs 30.9°C ± 0.4°C) and sweat rate (473 ± 51 vs 70 ± 23 g m^–2 h^–1 and 766 ± 81 vs 135 ± 18 g m^–2 h^–1) indicating a high cardiovascular and thermoregulatory strain, which was not decreased by ventilating the suit with an air flow of 281 min^–1 at 41% . The ventilation, oxygen consumption and production of carbon dioxide increased in relation to the extra weight of the GPC, partly dependent on the dynamic work level. It was concluded that the increase in the physiological load caused by the GPC was so high that the work-rest regimens, workers' level of physical fitness, cardiovascular health and heat tolerance should be considered whenever gas protective clothing is used.     

Overweight,obesity and the risk of LADA: results from a Swedish case–control study and the Norwegian HUNT Study

Aims/hypothesis

Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies.

Methods

Analyses were based on incident cases of LADA (n?=?425) and type 2 diabetes (n?=?1420), and 1704 randomly selected control participants from a Swedish case–control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984–2008). We present adjusted ORs and HRs with 95% CI.

Results

In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD.

Conclusions/interpretation

Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.