Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Subclinical hypothyroidism is a condition characterized by increased levels of thyroid-stimulating hormone (TSH) associated with normal levels of free triiodothyronine (FT3) and free thyroxine (FT4). The exact prevalence of this condition in Italy is not known. The aim of this study was to assess the presence of subclinical hypothyroidism in 1001 subjects living in the Milan area (age 17-89) and apparently free from thyroid pathology. This sample which had applied to a large laboratory centre (Centro Diagnostico Italiano, Milano) for a routine check-up was seen from April to July 1996. A serum TSH assay was performed using a highly sensitive immunoenzymatic method, while an FT3 and FT4 assay was performed by means of a radioimmunologic method using commercial kits. The prevalence of subclinical hypothyroidism in the total population proved to be 4.7% (95% CI-Confidence Interval: 3.4-6.0). Sex stratification showed a prevalence of 6.1% in females and 3.4% in males. Prevalence in patients up to 65 was 4.2%. This value increased up to 8.0% in subjects over 65. By combining these variables, in females >65 prevalence increased to 11.3%. Overall, symptoms typical of overt hypothyroidism were found in 58.3% of patients suffering from subclinical hypothyroidism and in 39.9% of healthy subjects (p<0.02). The results of this study show that there is a significant presence (about 5%) of subclinical hypothyroidism in this population and that its frequency is more than doubled in women over 65. Early treatment might reduce the progression to overt hypothyroidism. The benefits of such a procedure were recently suggested by a decision making modelling approach applied to the Italian environment.
A double-blind, randomized trial is described which was designed to compare the clinical effect of 600 mg daily of carbamazepine (Tegretol) and of tiapride (Sereprile) in hospitalized patients with pre-delirium tremens. Physicians' assessment of patients' progress was made following 2, 4 and 7 days of treatment. Of the sixty patients admitted to the study, five dropped out for various reasons, leaving fifty-five patients who completed the study. Both drugs were effective in the treatment of alcohol withdrawal symptoms; no significant difference was found between the two treatments with respect to total symptoms, score and visual analogue scale assessment. Carbamazepine gave faster relief of symptoms and demonstrated a preferential action on symptoms like fear and hallucinations. No case of delirium tremens was observed in those patients who completed the trial.
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