Effects of a peripherally acting alpha 2-adrenoceptor antagonist (L-659,066) on hemodynamics and plasma levels of catechols in conscious rats

L-659,066 is a new alpha 2-adrenoceptor antagonist which does not enter the central nervous system after systemic administration and therefore can be used to examine effects of blockade of peripheral alpha 2-receptors on hemodynamics and plasma levels of catechols. After i.v. administration to conscious rats, L-659,066 produced dose-related, small decreases in mean arterial pressure (MAP) and large increases in heart rate (HR), arterial plasma levels of norepinephrine (NE), and levels of the intraneuronal NE metabolite, dihydroxyphenylglycol (DHPG). After administration of L-659,066, HR, but not MAP, was strongly correlated with NE levels (r = 0.93, P less than 0.001). Levels of DHPG and dihydroxyphenylalanine (DOPA) also were strongly correlated with NE levels (r = 098 and r = 0.71). After comparison with responses during hypotension induced by the vasodilator, nitroprusside, the results indicated that L-659,066 increases sympathetically mediated NE release and catecholamine turnover due to inhibition of presynaptic alpha 2-receptors as well as due to reflexive sympathetic activation related to blockade of alpha 2-receptors on arterial smooth muscle cells.     

Comparison of noradrenaline and isoprenaline removal in the canine hindlimb and kidney

Because isoprenaline is not a substrate for neuronal uptake (Uptake-1, U-1), the difference in regional removal of isoprenaline from regional removal of the sympathetic neurotransmitter noradrenaline has been proposed as an index of regional U-1 activity. U-1 activity has not been assessed in the kidney, where decreased U-1 may account for increased renal spillover of noradrenaline into plasma in disorders such as essential hypertension. Tracer-labelled noradrenaline and isoprenaline were simultaneously infused intravenously into anaesthetized dogs, and the regional removal of noradrenaline and isoprenaline was measured in the hindlimb and kidney after administration of the U-1 blocker desipramine, hydrocortisone, which inhibits extra-neuronal uptake of noradrenaline (Uptake-2, U-2), or no drug. Hindlimb removal of noradrenaline (51%) exceeded that of isoprenaline (36%). Desipramine abolished this difference by decreasing removal of noradrenaline without affecting removal of isoprenaline. Renal removal of isoprenaline exceeded that of noradrenaline (74% vs 54%) even after U-1 blockade. Hydrocortisone did not affect removal of noradrenaline or isoprenaline in either bed. The results suggest that differences in removal of noradrenaline and isoprenaline reflect U-1 activity in the hindlimb but not in the kidney; U-1 is much more important than U-2 in the regional removal of noradrenaline; and one mechanism of noradrenaline removal in the kidney is by neuronal uptake.     

Decreased flow accuracy from volumetric infusion pumps

Accurate flow from infusion pumps should be maintained when exposed to a variety of clinical conditions. The intent of this study was to evaluate in vitro flow rate accuracy of three infusion pumps subjected to the influences of variable back-pressure, solution viscosity, and infusion rates. A factorial study design was selected to determine the influence of three flow rates (5, 10, and 20 ml/h), three back-pressures (100, 200, and 300 mm Hg), and two solution viscosities (5%, 25% dextrose in water) on flow rate accuracy from three infusion pumps (Abbott 4P, IVAC 560, and Travenol 6200) using a standard gravimetric technique. Mean +/- SD accuracy values were -9.4 +/- 6.4% (range -29.1 to -0.7), 0.5 +/- 2.2% (range -4.2 to 6.3), and -0.5 +/- 4.7% (range -8.5 to 9.9) of the desired rate for the Abbott, IVAC, and Travenol devices, respectively. Back-pressure was the only factor to influence significantly flow accuracy for the Abbott device (r = .81). All factors significantly influenced accuracy for the Travenol device (r = .55). No factor influenced accuracy for the IVAC infusion pump. Both the IVAC 560 and Travenol 6200 have acceptable flow accuracy values within the range of study factors examined. The Abbott 4P had significant decreases in flow accuracy in response to increasing back-pressure.     

Development and Validation of the Congestion Quantifier Seven-Item Test (CQ7): A Screening Tool for Nasal Congestion

ObjectiveThis study aimed to develop and validate a short, simple, patient-completed instrument for identifying patients with congestion in a 15-day study. Allergic rhinitis (AR) is the most common allergic condition worldwide, with congestion as one of the most salient symptoms. Nevertheless, there is no short screening tool designed specifically to identify congestion that can help patients make decisions about seeking treatment.MethodsPatients (N = 354) received a clinical exam to confirm congestion and assess its possible causes including confirmation of AR. They completed the 13-item draft of the Congestion Quantifier (CQ) and five additional patient-reported outcome instruments.ResultsThe 13-item draft CQ was reduced to a seven-item version, the CQ7. Internal consistency reliability was 0.93; test–retest reliability = 0.85. Construct validity wasdemonstrated by significant correlations with the Medical Outcomes Study Sleep Scale, the Work Productivity and Activity Impairment Questionnaire—Allergy Specific, and the Positive Affect and Negative Affect Scale Fatigue subscale (r = 0.23–0.67). The CQ7 can discriminate between controls and patients (AUC > 0.9). Moreover, it can discriminate between different levels of severity of symptoms of AR. A score of 7 provided optimum balance of sensitivity (91%), specificity (86%), and correct classification (90%) for detecting congestion.ConclusionThe CQ7 is reliable, valid, and responsive to differences in severity of nasal congestion. The CQ7 can identify patients with congestion that may need to be evaluated by a clinician.     

Prognostic endpoint yield of high-level versus low-level graded exercise testing

The prognostic endpoint yield (PEY) of a low-level (less than or equal to 4.6 METS) vs a high-level graded exercise test administered soon after myocardial infarction was evaluated with 184 patients. Test endpoints considered prognostically significant for future cardiac events were (1) ST segment depression greater than or equal to 1mm, (2) angina pectoris, and (3) complex ventricular beats. Test endpoints were assigned to both low-level and high-level tests if they occurred less than or equal to 4.6 METS; test endpoints greater than 4.6 METS were assigned to the high-level test only. Allowing the 145 patients who were asymptomatic during the low-level test to continue into the high-level protocol revealed a 2.5 times greater occurrence of angina pectoris (38 vs 15), a 3.4 times greater occurrence of ST segment depression (27 vs 8), and twice the occurrences of ventricular beats (4 vs 2). This substantial increase in prognostic endpoint yield was demonstrated in the presence of a significantly longer exercise time with the high-level test (9.0 vs 5.1 min), with no significant difference between protocols for peak heart rate or systolic blood pressure. Therefore, a high-level graded exercise test appears to increase the yield of test endpoints with known prognostic importance.     

Effect of growth hormone on height, weight, and body composition in Prader-Willi syndrome

AIMS: To evaluate the effect of the administration of growth hormone on stature, body weight, and body composition in children aged between 4 and 10 years with Prader-Willi syndrome. METHODS: Height, weight, and skinfold thickness were recorded in 25 children using standard anthropometric techniques at recruitment, and six months later, shortly before the start of daily subcutaneous injections of growth hormone. Body composition was assessed via a measurement of total body water using stable isotopes. Measurements were repeated at the end of the six months of growth hormone administration. Measurements of height, weight, and skinfold thickness were expressed as standard deviation scores (SDSs). RESULTS: There was a significant reduction in the percentage of body fat after growth hormone treatment; height velocity doubled during treatment; body weight did not change significantly when expressed as an SDS. Skinfold thickness at both the triceps and subscapular site decreased in absolute terms and when expressed as an SDS. CONCLUSIONS: These results indicate sufficient potential benefit to justify a more prolonged trial of growth hormone treatment and an exploration of different dosage regimens in children with Prader-Willi syndrome.