Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression.

BACKGROUND: Plasma activity of dopamine beta-hydroxylase (DbetaH), the enzyme that converts dopamine to norepinephrine, is reportedly lower in patients with unipolar major depression with psychotic features (UDPF) than in those with nonpsychotic unipolar major depression (UD). Plasma DbetaH is under genetic control by the structural locus encoding DbetaH protein, DBH. This study tested the hypothesis that diagnosis-specific allelic variation at DBH accounts for lower plasma DbetaH in UDPF. METHODS: Plasma DbetaH activity was measured in samples from patients with UDPF (n = 33) and UD (n = 45). Genotypes were determined at several functional DBH polymorphisms, including C-1021T, a single nucleotide polymorphism (SNP) in the proximal 5' region that associates with variation in plasma DbetaH activity. RESULTS: Mean plasma DbetaH activity was significantly lower in UDPF than in UD. Genotyping at DBH did not reveal genetic associations distinguishing UDPF from UD. A two-way analysis of variance showed significant effects of genotype and diagnostic group but no significant interaction. CONCLUSIONS: Although the effects of the diagnosis of UDPF, and of DBH allele status, on plasma DbetaH activity were replicated, the lower plasma DbetaH in patients with UDPF was not accounted for by DBH genotype. Several explanations for this result are possible. First, other variants at DBH, or at other loci, could account for the findings. Second, nongenetic factors could account for the differences in plasma DbetaH. In this regard, we hypothesize that abnormal regulation of hypothalamic-pituitary-adrenal function in UDPF lowers expression of DbetaH protein, which could in turn alter the ratio of dopamine and norepinephrine in noradrenergic neurons, thereby promoting development of psychotic symptoms.     

Airway lesions caused by prolonged intubation with standard and with anatomically shaped tracheal tubes. A post-mortem study

Two groups of patients intubated for long periods were examined post mortem. In Group A (22 patients) the mean duration of intubation was 4.0 days and in Group B (19 patients) 5.7 days. The mean for the two groups was 4.8 days. In Group A a conventional endotracheal tube was used, and in Group B an anatomically shaped tube. Both tubes had cuffs of the intermediate-volume, low-pressure type. The larynx and trachea, from the epiglottis to the bifurcation, were removed in one piece at autopsy and the inner surface was photographed. The photographs were magnified and from these the size and estimated depth of any lesions were recorded. In the arytenoid and tracheal regions no significant difference was found between the two groups. In the cricoid region, on the other hand, the outcome was significantly more favourable following use of the anatomically shaped tube.     

Smoking and caffeine have a synergistic detrimental effect on aortic stiffness and wave reflections

OBJECTIVES: We investigated the acute and chronic combined effect of cigarette smoking and caffeine intake on aortic stiffness and wave reflections. BACKGROUND: We have shown that smoking and caffeine separately increase arterial stiffness. Aortic stiffness and wave reflections are important determinants of the efficient performance of the cardiovascular system and prognosticators of cardiovascular risk. METHODS: The acute effects of smoking (one cigarette), caffeine (200 mg, equivalent to 2 cups of coffee), and smoking plus caffeine were studied in 24 healthy subjects according to a randomized, placebo- and sham procedure-controlled crossover design. The chronic effect of smoking and caffeine was studied in a population study that enrolled 160 healthy subjects. RESULTS: Acute study: there was a significant interaction between caffeine and smoking with regard to pulse-wave velocity (p < 0.01) and augmentation index (p < 0.05). When smoking followed caffeine intake, pulse-wave velocity and augmentation index increased further by 0.52 m/s and 13.4%, respectively, reaching a total of 0.85 m/s and 17.4%, 0.17 m/s and 9.2% in excess of the mere sum of caffeine effect (0.33 m/s and 4%) alone and smoking effect alone (0.35 m/s and 4.2%). Population study: there was a significant interaction of chronic coffee consumption and smoking regarding pulse-wave velocity (p < 0.05) and augmentation index (p = 0.001). CONCLUSIONS: The present study shows, for the first time, that when smoking and caffeine intake are combined, they interact and exert a synergistic, unfavorable effect on aortic stiffness and wave reflections on both an acute and chronic basis.     

ST-segment depression during vasodilator stress is of minor clinical importance in women with normal myocardial perfusion imaging and low or intermediate risk of coronary artery disease

Purpose  

The prognostic value of electrocardiographic (ECG) ST-segment depression during vasodilator stress testing in patients with normal myocardial perfusion scintigraphy (MPS) is based on retrospective studies with controversial results. Moreover, the true incidence of obstructive coronary artery disease (CAD) in these patients is unknown.