Abnormal Vascular Responses to Exercise in Patients with Aortic Stenosis

We tested the hypothesis that the normal forearm vasoconstrictor response to leg exercise is inhibited or reversed in patients with aortic stenosis, possibly because of activation of left ventricular baroreceptors. Forearm vascular responses to supine leg exercise were measured in 10 patients with aortic stenosis and in 2 control groups of 6 patients with mitral stenosis and 5 patients without valvular heart disease.Forearm vasoconstriction occurred during exercise in the control groups. In contrast, forearm blood flow increased and forearm vascular resistance did not change in patients with aortic stenosis. In six patients with aortic stenosis and a history of exertional syncope, forearm vasodilatation occurred during the second minute of leg exercise. Inhibition or reversal of forearm vasoconstrictor responses in aortic stenosis was asscociated with significant increases in left ventricular pressure.In three patients with aortic stenosis and exertional syncope, forearm vasodilator responses to exercise changed to vasoconstrictor responses after aortic valve replacement.The results indicate that forearm vasoconstrictor responses to leg exercise are inhibited or reversed in patients with aortic stenosis, possibly because of activation of left ventricular baroreceptors. The observations suggest that reflex vasodilatation resulting from activation of left ventricular baroreceptors may contribute to exertional syncope in patients with aortic stenosis.     

A descriptive and comparative study of the prevalence of depressive and anxiety disorders in low-income adults with type 2 diabetes and other chronic illnesses

OBJECTIVE: To determine whether type 2 diabetes contributes to the presence of depressive and anxiety disorder diagnoses in low-income adults with hypertension, asthma, and/or arthritis. RESEARCH DESIGN AND METHODS: Using a cross-sectional design, this study administered a structured diagnostic interview to low-income primary care patients diagnosed with type 2 diabetes, hypertension, arthritis, and asthma, as well as to those with no chronic illness (n = 326), to determine the 12-month prevalence of depressive and anxiety disorders. A logistic regression (LR) model was used to assess whether a diagnosis of depression and/or anxiety was associated with type 2 diabetes after adjusting for known risk factors. RESULTS: A high prevalence rate of depressive and/or anxiety disorders was found in the total sample (29%) and in all three illness groups: type 2 diabetes (36%), other chronic illnesses (24%), and no chronic illness (31%). Using LR, a main effect was detected for illness group when age and education were controlled (chi(2) = 22.66, df 4, P = 0.000). Specifically, the odds of occurrence of a depressive and/or anxiety disorder in those with comorbid type 2 diabetes were twice that in the nondiabetic, chronically ill comparison group (odds ratio 2.26, 95% CI 1.28-4.01, P = 0.005). CONCLUSIONS: These results suggest a positive contribution of type 2 diabetes to increased rates of depressive and/or anxiety disorders in patients with hypertension, asthma, and/or arthritis and support prior research that type 2 diabetes may serve as an indicator of depression and anxiety in low-income adults treated in primary care clinics.     

On the adaptation in potassium excretion associated with nephron reduction in the dog

An effort to examine certain aspects of the adaptation in potassium excretion associated with nephron reduction was made in dogs with unilateral remnant kidneys. A constant intake of potassium was maintained by tube feeding and studies were performed before and after removal of the intact control kidney. The removal of the intact kidney created the need for the remaining nephrons of the remnant kidney to increase their rate of potassium excretion markedly. Sodium intake was held constant either at a normal or a low level. Mineralocorticoid hormone activity was maintained either at a high level by the administration of 0.2 mg 9-α-fluorohydrocortisone daily or at a low level by performing bilateral adrenalectomy and administering a minimal maintenance dose of deoxycorticosterone acetate (DOCA) and cortisol. Potassium excretion per nephron increased strikingly within 18 hr of contralateral nephrectomy and by 7 days, excretion rates were 600% of control values for the remnant kidney. More potassium was excreted in the first 5 hr after administration of a test dose of potassium by the remnant kidney alone in the postnephrectomy state than by both the remnant and intact kidneys in the prenephrectomy state. 24 hr excretion of potassium by the remnant kidney postnephrectomy averaged 92% of the administered load of potassium. The adaptation in potassium excretion was independent of the concurrent rate of sodium excretion and of mineralocorticoid hormone activity and persisted during constriction of the renal artery, a stimulus which presumably decreased distal delivery of sodium. The adaptation and the continued modulation of potassium excretion could not be explained adequately by an increase in impermeant anion excretion per nephron. Finally, known changes in hydrogen ion excretion per nephron associated with nephron reduction are in a direction opposite to those which would explain the acquired kaliuresis per nephron.     

Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells

Tobacco-related diseases such as lung cancer cause over 4.2 million deaths annually, with approximately 400,000 deaths per year occurring in the US. Genotoxic effects of tobacco components have been described, but effects on signaling pathways in normal cells have not been described. Here, we show activation of the serine/threonine kinase Akt in nonimmortalized human airway epithelial cells in vitro by two components of cigarette smoke, nicotine and the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Activation of Akt by nicotine or NNK occurred within minutes at concentrations achievable by smokers and depended upon alpha(3)-/alpha(4)-containing or alpha(7)-containing nicotinic acetylcholine receptors, respectively. Activated Akt increased phosphorylation of downstream substrates such as GSK-3, p70(S6K), 4EBP-1, and FKHR. Treatment with nicotine or NNK attenuated apoptosis caused by etoposide, ultraviolet irradiation, or hydrogen peroxide and partially induced a transformed phenotype manifest as loss of contact inhibition and loss of dependence on exogenous growth factors or adherence to ECM. In vivo, active Akt was detected in airway epithelial cells and lung tumors from NNK-treated A/J mice, and in human lung cancers derived from smokers. Redundant Akt activation by nicotine and NNK could contribute to tobacco-related carcinogenesis by regulating two processes critical for tumorigenesis, cell growth and apoptosis.     

Predictors of Mortality in Patients with Delirium Tremens

Objectives:  The objectives were to identify factors that may help predict mortality for patients with delirium tremens (DT).
Methods:  The authors conducted a 1:1 gender- and age-matched case–control study of patients hospitalized for DT. Using McNemar chi-square tests and conditional logistic regression (CLR), risk factors for death, including demographics, location of diagnosis, vital sign derangements, treatment methods, and comorbid conditions, were evaluated. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) are reported.
Results:  Thirty-five patients with DT died between January 2000 and June 2006. The majority (31; 88.6%) were male with a mean (±standard deviation [SD]) age of 51.7 (±7.6) years. Hyperthermia in the first 24 hours of DT diagnosis (OR = 10.0, 95% CI = 2.3 to 42.7), persistent tachycardia (OR = 24.0, 95% CI = 3.3 to 177.4), and use of restraints (OR = 7.50, 95% CI = 1.7 to 32.8) were associated with increased mortality by univariate analysis, while an emergency department (ED) diagnosis of DT (OR = 0.18, 95% CI = 0.05 to 0.6) and use of clonidine (OR = 0.10, 95% CI = 0.01 to 0.78) were associated with decreased mortality. In the CLR model, restraint use and hyperthermia were the only variables that remained significant (OR = 5.8, 95% CI = 1.0 to 32.2; and OR = 6.1, 95% CI = 1.2 to 30.4, respectively).
Conclusions:  The use of restraints and hyperthermia is associated with increased odds of death for patients with DT. This study highlights the need for further research into modifiable factors influencing mortality from DT.     

The diagnostic value of oral glucose tolerance test and combined B-cell stimulation in chronic pancreatitis

The secretory capacity of the B-cells in 40 patients with chronic or chronic relapsing pancreatitis was examined by means of the oral glucose tolerance test (100 g of glucose, orally) and combined stimulation (100 g of glucose, orally, 1 mg of glucagon, and 0.5 g of tolbutamide intravenously. Under both the test conditions, the immunologically measurable insulin was significantly reduced compared to that of controls. The maximal insulin differences and the insulinogenic index (35-minute value) of the combined stimulation method were most satisfactory for the diagnosis of the secretory B-cell insufficiency. In addition to these parameters, the constancy of insulin levels in the period between 35 and 60 minutes indicated a dysfunction of the endocrine pancreas.Presented in part at the Seventh Congress of the German Diabetic Society, Bad Nauheim, 4–6 May 1972.     

A randomized placebo-controlled trial of pre-treatment and short- or long-term maintenance therapy with amiodarone supporting DC cardioversion for persistent atrial fibrillation.

AIMS: The efficacy of cardioversion (DCCV) for restoration of sinus rhythm (SR) in persistent atrial fibrillation (AF) is limited by a high relapse rate. Relapse may be reduced by amiodarone but no placebo-controlled trials of efficacy have been performed and the appropriate duration of therapy is unknown. METHODS AND RESULTS: In this double-blind study, 161 subjects with persistent AF were randomized to one of three groups-placebo (n=38); amiodarone 400mg BD for 2 weeks prior to DCCV and 200mg daily for 8 weeks followed by placebo for 44 weeks (n=62, short-term amiodarone); amiodarone 400mg BD for 2 weeks then 200mg daily for 52 weeks (n=61, long-term amiodarone). Spontaneous reversion to SR occurred before DCCV in 21% (26/123) patients on amiodarone and none of the 38 patients on placebo (absolute difference 21%, 95% confidence interval (CI): 10 to 29%, P=0.002). At 8 weeks following DCCV, 51% (63/123) patients on amiodarone remained in SR compared to 16% (6/38) taking placebo (difference-35% 95% CI: -48 to -18%, P<0.001). At 1 year, 49% (30/61) patients on long-term amiodarone were in SR compared to 33% (21/62) taking short-term amiodarone (difference-15%, 95% CI: -31 to 2%, P=0.085). There was no difference in adverse event rate or quality of life scores between groups. CONCLUSIONS: Amiodarone pre-treatment before electrical DCCV for persistent AF allows chemical conversion in one-fifth of patients without altering the efficacy of subsequent DC conversion. Amiodarone is more effective than placebo in the maintenance of SR when continued for 8 weeks following successful DCCV. More patients taking long-term amiodarone remained in SR at 52 weeks, but more had serious adverse effects requiring discontinuation of therapy. Eight weeks of adjuvant therapy with amiodarone following successful DCCV may be the preferred option.     

Effect of the somatostatin analogue lanreotide on meal-stimulated portal blood flow in patients with liver cirrhosis

BACKGROUND: Lanreotide, a new long-acting somatostatin analogue, has been shown to inhibit the meal-stimulated increase of splanchnic blood flow in healthy volunteers. To date, similar data in patients with liver cirrhosis have not been available. We have examined the effect of lanreotide compared with placebo on meal-stimulated portal blood flow in patients with liver cirrhosis using Doppler ultrasound. METHODS: 20 cirrhotic patients (placebo n = 12, lanreotide n = 8) with proven portal hypertension were studied after an overnight fast. Lanreotide, at a dose of 100 microg/h, was infused intravenously over 7 h after a 1-hour basal period. In parallel to the intravenous infusion, a liquid test meal (Ensure plus, 1.5 kcal/min) was perfused for 7 h through an intraduodenal tube at a rate of 3 ml/min. Blood pressure, heart rate and portal vein blood flow (PVF, ml/min, Doppler technique) were determined at regular intervals. RESULTS: Baseline PVF amounted to 725 +/- 182 ml/min in the placebo and to 917 +/- 252 ml/min in the lanreotide group (n.s.). The meal-stimulated increase in PVF was blunted by lanreotide (AUC, % x min): 62,709.6 +/- 6,817 (placebo) vs. 45,237 +/- 2,507 (lanreotide), p < 0.05. Lanreotide also blunted the postprandial increase in heart rate for the first 2 h of meal perfusion. CONCLUSIONS: Because of potent inhibition of postprandial splanchnic hyperemia in patients with liver cirrhosis, lanreotide may be useful in the treatment of complications of portal hypertension.