Depressant effect of digoxin on atrioventricular conduction in man.

We examined the effect of chronically administered digoxin on atrioventricular (A-V) conduction in nine cardiac transplant recipients. We assessed A-V conduction by measuring the duration from the pacing stimulus to the onset of the QRS complex (S'R interval) and by determining the occurrence of Wenckebach periodicity during rapid atrial pacing. We made measurements during a control period and during a period of digoxin administration of up to 37 days. During the digoxin period, the cycle length at which Wenckebach block occurred was prolonged by 14% of the control value and the S'R interval was significantly prolonged at paced rates of 110 beats per minute and faster. After digoxin was discontinued, the Wenckebach periodicity and S'R interval returned to control values. Atropine and propranolol did not alter digoxin's effect on A-V conduction. We conclude that digoxin exerts a direct (or non-neurally mediated) depressant effect upon A-V conduction in man, although the stress of tachycardia is necessary to demonstrate the effect.     

Demonstration of the formation of hydroxyl radicals in acute myocardial infarction in man using salicylate as probe.

Dihydroxybenzoic acid (DHBA) derivatives of acetylsalicylic acid (ASA) are formed in vivo by the action of the hydroxyl radical (OH.). In order to evaluate the possible formation of OH(.) in acute myocardial infarction (AMI) in man, 9 consecutive patients with a first episode of AMI (8 males, 1 female, mean age 50.3 years), treated with rt-PA, and 8 healthy volunteers (7 males, 1 female, mean age 29.8 years) were studied. All subjects received 100 mg ASA p.o. daily; venous blood samples were taken 30 min after the first dose (time 0) and then at 3-, 6-, 12-, 24- and 48 h and 5 days. Serum was analyzed by HPLC and electrochemical detection for 2,3- and 2,5-DHBA contents. 2,3-DHBA was present in all subjects with AMI and undetectable in healthy volunteers at all time points studied. Serum levels of 2,5-DHBA did not show statistically significant differences between AMI patients and healthy volunteers. These data support the hypothesis that hydroxyl radicals are formed during AMI in man.     

A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery disease

Insulin resistance is associated with increased risk of atherosclerosis. Insulin receptor substrate-1 (IRS-1) plays a key role in tissue insulin sensitivity. A common mutation (G972R) of the IRS-1 gene has been shown to impair IRS-1 function, and it has been associated with reduced insulin sensitivity and lipid abnormalities. This led us to investigate the role of the G972R mutation in predisposing individuals to coronary artery disease (CAD). The DNA of 318 subjects with angiographically documented coronary atherosclerosis (>50% stenosis) and 208 population control subjects was analyzed for the presence of the G972R mutation. This mutation was detected by nested polymerase chain reaction and BstNI restriction enzyme digestion. The frequency of the G972R mutation was significantly higher among patients with CAD than controls (18. 9% versus 6.8%, respectively; P<0.001). After controlling for other coronary risk factors, the relative risk of CAD associated with the G972R mutation was 2.93 (95% CI 1.30 to 6.60; P<0.02) in the entire cohort. This risk was found to be even higher in the subgroups of obese subjects (odds ratio [OR] 6.97, 95% CI 2.24 to 21.4; P<0.001) and subjects with clinical features of insulin resistance syndrome (OR 27.3, 95% CI 7.19 to 104.0; P<0.001). The IRS-1 gene variant was associated with a higher frequency of diabetes mellitus (14.9% among carriers versus 6.5% among noncarriers; P<0.01) and with a 60% increase of plasma total triglycerides (P<0.001). Also, plasma concentrations of total cholesterol and the ratio of total cholesterol to HDL cholesterol were significantly (P<0.001) higher among carriers than noncarriers, although to lesser a extent. These effects were independent of CAD status. The G972R mutation in the IRS-1 gene was found to be a significant independent predictor of CAD. Moreover, this mutation greatly increased the risk of CAD in obese subjects and in patients with the cluster of abnormalities of insulin resistance syndrome. Besides the increased frequency of diabetes, carriers showed a more atherogenic lipid profile, suggesting a potential role of the IRS-1 gene in the pathogenesis of lipid abnormalities associated with CAD.     

Diagnostic Accuracy of a Bedside Screening Tool for Dysphagia (BSTD) in Acute Stroke Patients

Background and purposean estimated 40-80% of acute ischemic stroke patients have dysphagia and about 14% develop stroke-associated pneumonia. However, it may be difficult to detect swallowing problems at admission. Moreover, there might not be an on-duty specialist skilled in the diagnosis of this condition. This study aimed at developing a user-friendly bedside examination to identify the risk of dysphagia in stroke patients at hospital admission.Methodsa diagnostic accuracy study was carried out to assess the concurrent validity of a simple Bedside Screening Tool for Dysphagia (BSTD) in acute stroke. All the consecutive stroke patients admitted between January and April 2018 were enrolled. Sensitivity, specificity, positive (PPV), negative predictive values (NPV) and the Cohen K concordance index scores, reported by nurses and speech-pathologists, were assessed.Resultsa total of 67/120 patients (55.8%) were male; overall average age was 67.4 (range 45-91) and 80.8% of the whole population had a history of ischemic stroke. The nursing staff identified 33.3% of dysphagia cases at admission and the speech pathologists 30%. The Cohen K was 0.92 (optimal concordance when K was > 0.8), sensitivity was 100%, specificity 95.2%, PPV 90% and NPV 100%.Conclusionsour BSTD had a 100% negative predictive value, indicating that this screening test is very useful in ruling out/confirming dysphagia in acute stroke patients