Intolerance to Cereals Is Not Specific for Coeliac Disease

Background: While dyspeptic patients in primary care often receive empirical treatment with antisecretory drugs, a substantial number suffer from motility disturbances which may be associated with their complaints. We aimed to compare the effectiveness of treatment with antisecretory treatment with a prokinetic agent in uninvestigated dyspepsia. Methods: 563 patients presenting dyspeptic complaints to the general practitioner with a low likelihood of organic (ulcer, reflux or malignant) disease, i.e. absence of alarm symptoms or a history of peptic ulcer disease or gastro-oesophageal reflux disease were included. They entered a randomized, double-blind trial of 4 weeks of ranitidine 150 mg bid compared with 4 weeks of cisapride 10 mg bid, with 3 months follow-up. Treatment failure was defined as no response to treatment or a relapse of symptoms within the follow-up period. Also studied were the effect on dyspepsia severity, response to treatment after 4 weeks, and time to relapse. Results: For all randomized patients, the incidence of overall treatment success after 3 months follow-up with antisecretory treatment was 107/271 (39.5%) and with a prokinetic agent 122/282 (43.3%); the risk difference was 3.8% (95% CI-4.4% to 12.0%); the difference in symptom severity score after 4 weeks of treatment was 0.3; 95% CI-0.4% to 1.0%. For patients responding to 4 weeks of treatment, relapsefree time was 86 days in the prokinetic group and 79 days in the acid suppression group (P = 0.005). Conclusions: Antisecretory and prokinetic therapies are equally effective in primary care patients with uninvestigated dyspeptic complaints, though relapse rates are lower in patients treated with prokinetic treatment.     

Enzymatic detoxification of gluten by germinating wheat proteases: Implications for new treatment of celiac disease

Introduction. Currently the only treatment for celiac disease is a lifelong gluten-free diet. The diet is, however, often burdensome, and thus new treatment options are warranted. We isolated proteases from germinating wheat grain naturally meant for total digestion of wheat storage proteins and investigated whether these enzymes can diminish toxic effects of gluten in vitro and ex vivo.

Methods. Pepsin and trypsin digested (PT) gliadin was pretreated with proteases from germinating wheat, whereafter the degradation was analyzed by HPLC-MS (high-performance liquid chromatography and mass spectroscopy) and sodium dodecyl sulphate polyacrylamide gel electrophoresis. The toxicity of cleaved PT-gliadin products was assessed in Caco-2 epithelial cells, celiac patient-derived T cells, and in human small intestinal mucosal organ culture biopsies.

Results. Proteases from germinating wheat degraded gliadin into small peptide fragments, which, unlike unprocessed PT-gliadin, did not increase epithelial permeability, induce cytoskeletal rearrangement or changes in ZO-1 expression in Caco-2 cells. Pretreated gliadin did not stimulate T cell proliferation in vitro or enhance the production of autoantibodies to culture supernatants and the activation of CD25+ lymphocytes in the organ culture to the same extent as unprocessed PT-gliadin.

Discussion. Germinating wheat enzymes reduce the toxicity of wheat gliadin in vitro and ex vivo. Further studies are justified to develop an alternative therapy for celiac disease.     

Plasma renin substrate and oestrogens in normal pregnancy

Relationship between concentrations of serum oestrogens, plasma renin substrate and plasma renin activity were studied in six women throughout pregnancy. There was a significant positive correlation between serum oestradiol-17β and plasma renin substrate concentrations (r=0.60). Serum oestriol concentrations also correlated significantly with plasma renin substrate concentrations (r=0.68). Correlation coefficients calculated separately for each subject throughout pregnancy were higher than those for the whole group. Also, there was much individual variation in dose-response of serum oestrogens to plasma renin substrate concentrations. There was no significant correlation between serum oestrogens and plasma renin activity.

Our results support the view that oestrogens cause the increase in plasma renin substrate concentration during pregnancy, and emphasize the individual variation in response of renin substrate concentration to serum level of oestrogens.     

Post-traumatic meningioma: three case reports of this rare condition and a review of the literature

We present three cases of meningiomas developing at the site of an old head trauma. We then review the literature regarding the controversies on the development of post-traumatic brain tumors and, finally, we emphasize the medico-legal characteristics of post-traumatic meningiomas, particularly with respect to their cell type which is frequently atypical or anaplastic and which have a poor outcome.     

Clonal Analysis of Regulatory T Cell Defect in Patients with Autoimmune Polyendocrine Syndrome Type 1 Suggests Intrathymic Impairment

Mutations in the autoimmune regulator gene disrupt thymic T cell development and negative selection, leading to the recessively inherited polyendocrine autoimmune disease autoimmune polyendocrine syndrome type 1 (APS‐1). The patients also have a functional defect in the FOXP3⁺ regulatory T cell population, but its origin is unclear. Here, we have used T cell receptor sequencing to analyse the clonal relationship of major CD4⁺ T cell subsets in three patients and three healthy controls. The naive regulatory T cells showed little overlap with helper T cell subsets, supporting divergence in the thymus. The activated/memory regulatory T cell subset displayed more sharing with helper T cells, but was mainly recruited from the naive regulatory T cell population. These clonal patterns were very similar in both patients and controls. However, naive regulatory T cells isolated from the patients had a significantly longer T cell receptor complementarity‐determining region 3 than any other population, suggesting failure of thymic selection. These data indicate that the peripheral differentiation of regulatory T cells in APS‐1 patients is not different from that in healthy controls. Rather, the patients' naive regulatory T cells may have an intrinsic defect imprinted already in the thymus.     

Osteoarthritis of finger joints in Finns aged 30 or over: prevalence,determinants, and association with mortality

BACKGROUND: Prevalence and risk factors of osteoarthritis (OA) in finger joints have been amply explored in previous studies. However, no study has focused on finger joint OA as a predictor of mortality. OBJECTIVE: To investigate finger joint OA for its associations with alleged risk factors and with life expectancy in an extensive health survey. METHODS: From 1978 to 1980 a representative population sample of 8000 Finns aged 30 years or over was invited to participate in a comprehensive health examination; 90% accepted. Hand radiographs were taken from 3595 subjects. By the end of 1994, 897 of these had died. RESULTS: The prevalence of OA of Kellgren's grade 2 to 4 in any finger joint and in at least two symmetrical pairs of distal interphalangeal joints (DIPs) was 44.8% and 16.0%, respectively. Age and body mass index were significant determinants for OA both in any finger joint and in symmetrical DIP OA. The history of physical workload in women showed a positive association with OA in any finger joint. Smoking in men seemed to protect against symmetrical DIP OA. As adjusted for the determinants above, symmetrical DIP OA predicted mortality in women (relative risk (RR), 1.23; 95% confidence interval (95% CI) 1.01 to 1.51), but not in men (RR 0.89; 95% CI 0.68 to 1.16). In men, however, OA in any finger joint significantly predicted cardiovascular deaths (RR 1.42; 95% CI 1.05 to 1.92). CONCLUSION: OA in any finger joint and symmetrical DIP OA have different risk factor profiles and predict mortality in different patterns between men and women.     

Nationwide trends in molecular epidemiology of methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>, Finland, 1997–2004

Background  

In Finland, the annual number of MRSA notifications to the National Infectious Disease Register (NIDR) has constantly increased since 1995, and molecular typing has revealed numerous outbreak isolates of MRSA. We analyzed the data on MRSA notifications of the NIDR, and MRSA isolates were identified mainly by pulsed-field gel electrophoresis (PFGE) at the National Reference Laboratory (NRL) in Finland during 1997–2004. One isolate representative of each major PFGE type was further characterized by multilocus sequence (MLST)-, staphylococcal cassette chromosome mec (SCCmec)-, and Panton-Valentine leukocidin (PVL)-typing.     

Hereditary hemochromatosis gene (HFE) mutations C282Y, H63D and S65C in patients with idiopathic dilated cardiomyopathy

BACKGROUND: Hereditary hemochromatosis (HH), a common autosomal recessive disease, leads to excessive iron accumulation in some organs, including the heart. It is therefore not surprising that cardiomyopathy is one of the most severe complications of HH. The HFE gene defects have been thought to contribute to idiopathic dilated cardiomyopathy (IDCM) in some patients, even though the results of genotype analyses have so far been contradictory. Hence we set out here to evaluate the prevalence and potential role of HFE mutations in patients with IDCM. METHODS: A total of 91 IDCM patients and 102 controls were subjected to HFE mutation analyses, in which C282Y, H63D and S65C mutations were determined for each patient. We also analyzed the impact of the C282Y and H63D mutations on the left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional classes. RESULTS: The prevalences of heterozygosity for the C282Y, H63D and S65C mutations in the IDCM patients were 13.2%, 22.0% and 2.2%, respectively. LVEDD was significantly higher (P=0.037) in those with the C282Y mutation at the end of the follow-up period than in those with no mutation. CONCLUSIONS: Our data showed no significant deviations in C282Y, H63D and S65C mutation frequencies between the IDCM patients and controls, suggesting that these mutations do not increase the risk of IDCM. Heterozygosity for the C282Y mutation may nevertheless be a modifying factor contributing to LV dilatation and remodeling.