Prevalence and axial length of hiatus hernia in patients, with nonerosive reflux disease: a prospective study

BACKGROUND AND AIMS: The relationship between hiatus hernia and reflux esophagitis is well established. However, there are conflicting reports regarding its effect on the development of nonerosive reflux disease (NERD). Our aim was to investigate the prevalence and axial length of hiatus hernia in patients with NERD, compared with patients with reflux esophagitis, Barrett esophagus, and controls. METHODS: Axial hernia length of the diaphragmatic hiatus was measured prospectively at endoscopy in controls and patients with typical reflux symptoms occurring at least weekly during the last month relieved by antacids. RESULTS: A final diagnosis of hiatus hernia was established in 21.2% of 249 controls, 60.4% of 346 patients with NERD, 78.1% of 251 patients with reflux esophagitis, and 88.2% of 17 patients with Barrett esophagus. Patients aged >59 years were most likely to have a hiatus hernia. There was an increased prevalence in patients with NERD as compared with controls (P<0.0001), and decreased prevalence as compared with those with reflux esophagitis and Barrett esophagus (P<0.0001 and 0.02, respectively). Axial length of hiatus hernia >3 cm was found more frequently in patients with reflux esophagitis and Barrett esophagus as compared with patients with NERD (P<0.0001 and 0.0052, respectively). There was no statistical significant difference between controls and patients with NERD regarding the prevalence of hiatus hernia >3 cm (P=0.0904). CONCLUSIONS: A small (<3 cm) hiatus hernia may contribute to the development of NERD, whereas an axial length >3 cm is associated with a more severe disease.     

Thyroid hormone synthesis and secretion in humans after 80 milligrams of iodine for 15 days and subsequent withdrawal

CONTEXT: In animals, acute iodine administration results in acute intrathyroidal inhibition of iodinations followed by escape of the inhibition if the excessive iodine intake continues. In humans, the intrathyroidal nonhormonal and hormonal iodine concentration after exposure to large doses of iodine for a relatively long period of time is not known. OBJECTIVE: To determine whether, in human thyroid, administration of large doses of iodine for a relatively long time results in alterations of intrathyroidal hormonal (HI) T4 and T3 and total iodine (TI) content, as well as whether changes in serum concentration of thyroid hormones and TSH would occur after iodine administration or discontinuation. DESIGN: In 33 euthyroid patients with single thyroid nodule or hyperparathyroidism, Lugol solution (80 mg iodine) was administered for 15 d before operation. Groups of six to eight patients underwent operation 0, 5, 10, and 15 d after iodine withdrawal. TI, HI in a sample of thyroid tissue, and serum concentration of T4, T3, and TSH were measured. In 21 normal euthyroid subjects who did not undergo operation, a similar protocol was used and serial blood measurements were taken. MAIN OUTCOME MEASURE: Intrathyroidal TI, HI, and serum thyroid hormone and TSH measurements were the main outcome measure. RESULTS: Intrathyroidal HI content and serum T4 and T3 were unchanged during and after iodine discontinuation. TI was increased during iodine administration and returned to control values 5 d after discontinuation of iodine. The ratio of HI/TI was decreased and returned to control values 15 d after the iodine was discontinued. Serum TSH was increased during iodine administration and returned to control values 10 d after iodine withdrawal. CONCLUSIONS: In humans, administration of iodine for a relatively long period of time was accompanied by increased intrathyroidal TI, but no changes in HI or demonstrable increases of serum T4 and T3 were observed. It is hypothesized that the maintenance of normal intrathyroidal HI is the result of the combined inhibitory effect of iodine on thyroid hormone synthesis and on the release of T4 and T3 from the thyroid.     

Insulin sensitivity assessment with euglycemic insulin clamp in adult beta-thalassaemia major patients

Objective: To assess insulin sensitivity in young adult normoglycemic β‐thalassaemia major patients. Methods: We measured insulin sensitivity with the euglycemic insulin clamp in 10 young adult (mean age 24.85 ± 2.45 yrs) normoglycemic β‐thalassaemia major patients and 10 sex‐ & age‐ matched controls. Liver iron accumulation was assessed by magnetic resonance imaging (MRI). Results: Glucose infusion rate (M) required to maintain euglycemia was significantly reduced in thalassaemic patients compared to controls (261.5 ± 63.5 mg/m²·min vs. 355.6 ± 35.3 mg/m²·min, P = 0.008). Consequently, significantly reduced in the thalassaemic group were also tissue sensitivity to insulin (M/I_s‐s) and glucose metabolic clearance rate (M/G_s‐s). There was significant negative correlation between ferritin levels and glucose infusion rate (r = ?0.918 P = 0.004). No significant correlations were observed between age, body mass index, daily transfusional iron accumulation, liver iron content and any of the euglycemic clamp parameters. Fasting insulin levels were significantly increased in patients with β‐thalassaemia major compared to controls (P = 0.01), and had significant negative correlation to MRI‐derived liver iron content (r = ?0.733, P = 0.03). Conclusions: Our data indicate that reduced insulin sensitivity resulting in hyperinsulinaemia precedes the manifestation of glucose intolerance in patients with β‐thalassaemia major. Insulin resistance seems to correlate with increased serum ferritin levels.     

Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy?

Adult-onset Still's disease is a rare systemic inflammatory disease of unknown etiology, characterized by daily high, spiking fevers, evanescent rash, and arthritis. There is no single diagnostic test for adult-onset Still's disease; rather, the diagnosis is based on clinical criteria and necessitates the exclusion of infectious, neoplastic, and other 'autoimmune' diseases. Proinflammatory cytokines such as interleukin (IL)-1, IL-6, and IL-18, interferon-gamma, tumor necrosis factor, and macrophage colony-stimulating factor are elevated in patients with adult-onset Still's disease and are thought to have a major role in the pathogenesis of the disease. Treatment consists of nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants (methotrexate, gold, azathioprine, leflunomide, cyclosporin, and cyclophosphamide), intravenous immunoglobulin, and cytokine (tumor necrosis factor, IL-1 and IL-6) inhibitors. Recent advances in basic immunology have enhanced our ability to hinder the pathogenic mechanisms associated with adult-onset Still's disease and have led to a paradigm shift where targeted treatments have an increasingly important role.     

Synchronous neural interactions assessed by magnetoencephalography: a functional biomarker for brain disorders

We report on a test to assess the dynamic brain function at high temporal resolution using magnetoencephalography (MEG). The essence of the test is the measurement of the dynamic synchronous neural interactions, an essential aspect of the brain function. MEG signals were recorded from 248 axial gradiometers while 142 human subjects fixated a spot of light for 45-60 s. After fitting an autoregressive integrative moving average (ARIMA) model and taking the stationary residuals, all pairwise, zero-lag, partial cross-correlations (PCC(ij)(0)) and their z-transforms (z(ij)(0)) between i and j sensors were calculated, providing estimates of the strength and sign (positive, negative) of direct synchronous coupling at 1 ms temporal resolution. We found that subsets of z(ij)(0) successfully classified individual subjects to their respective groups (multiple sclerosis, Alzheimer's disease, schizophrenia, Sj?gren's syndrome, chronic alcoholism, facial pain, healthy controls) and gave excellent external cross-validation results.