Improvements in cognition, mood and behaviour following commencement of continuous subcutaneous insulin infusion therapy in children with type 1 diabetes mellitus: a pilot study.

AIMS/HYPOTHESIS: Anecdotally, parents and teachers of children with type 1 diabetes mellitus report improvements in behaviour and learning following the commencement of continuous subcutaneous insulin infusion (CSII). This study aimed to investigate changes in cognition, mood and behaviour following commencement of CSII in children with type 1 diabetes. METHODS: Children (n = 32) with type 1 diabetes aged 6-16 years and starting CSII at two Australian centres underwent behavioural, cognitive and glycaemic assessments prior to the commencement of CSII and 6-8 weeks after its start. A comprehensive cognitive test battery was administered, comprising measures of intelligence, attention, processing speed and executive skills. Behaviour and mood were assessed using the Behaviour Assessment System for Children--Second Edition. Continuous glucose monitoring was performed over a 72 h period and HbA(1c) was measured at both time-points. RESULTS: After commencement of CSII, there were significant improvements in HbA(1c), a reduction in hyperglycaemia and blood glucose variation and an increase in normoglycaemia. Significant improvements were observed in perceptual reasoning, selective attention, divided attention, cognitive flexibility and working memory. Fewer mood-related symptoms were reported (parent, teacher and self-report) and fewer behavioural problems (parent reports) CONCLUSIONS/INTERPRETATION: In this uncontrolled pilot study, children with type 1 diabetes demonstrated significant improvements in measures of metabolic control, mood and behaviour and in some complex cognitive skills after commencing CSII therapy.

Cardiovascular effects of a novel enkephalin analogue, 443C81, in humans.

The cardiovascular effects of a novel enkephalin analogue, 443C81 (Tyr-D-Arg-Gly-Phe(4NO2)-Pro.NH2), were studied in healthy volunteers. According to a double-blind, cross-over, randomised, balanced design, six men received two different doses of 443C81 or saline as intravenous (i.v.) infusions on three occasions. Mean +/- SD plasma concentrations achieved at steady state were 0.46 +/- 0.11 microgram/ml after low-dose 443C81 and 1.0 +/- 0.2 microgram/ml after high-dose 443C81. In the supine position, low and high doses produced mean transient increases in diastolic blood pressure (DBP) of 5 and 4 mm Hg and heart rate (HR) of 5 and 12 beats/min, respectively. With the higher dose, these changes were followed by a mean decrease in DBP of 8 mm Hg while HR returned to control values. When the subjects were tilted, the pressor effect was not observed, and hypotension occurred earlier and was more pronounced. Both doses reduced forearm and systemic vascular resistance, and there was a dose-related increase in supine forearm venous capacitance; venoconstriction associated with tilting was unaffected by 443C81. Plasma renin activity and elevation of epinephrine concentrations on tilting were increased by the enkephalin, which also caused a diuresis through an increase in free water clearance.

The adjunctive effect of telmisartan in patients with hypertension uncontrolled on current antihypertensive therapy.

This prospective, double-blind, randomised, parallel-group, multicentre study assessed the adjunctive effect of telmisartan monotherapy versus placebo in controlling blood pressure during the last six hours of the 24-hour dosing period. After a two-week run-in phase, 375 patients with essential hypertension uncontrolled on existing therapy were randomised to either placebo or telmisartan (40 mg uptitrated to 80 mg after four weeks, if needed) for eight weeks. Ambulatory blood pressure monitoring (ABPM) was conducted at randomisation (baseline) and treatment end. The change from baseline in diastolic blood pressure (DBP) over the last six hours (primary endpoint) was significantly greater with telmisartan than placebo (adjusted mean treatment difference in favour of telmisartan: -3.7 mmHg, 95% confidence interval (CI) -5.5, -1.9 mmHg, p < or = 0.001, n = 350), as was the reduction in 24-hour DBP (adjusted mean treatment difference: -5.0 mmHg, 95% CI -6.5, -3.5 mmHg, p < or = 0.001). Telmisartan also reduced mean systolic blood pressure significantly more than placebo over the last six hours and the entire 24-hour dosing interval. Responder rates (ABPM DBP, seated DBP, and overall [seated SBP/DBP]) at 8 weeks were significantly higher with telmisartan than with placebo (p < or = 0.01). All treatments were well tolerated. When added to existing antihypertensive regimens, telmisartan offers additional effectiveness while maintaining placebo-like tolerability.

Dipipanone and nifedipine in cold induced pain; analgesia not due to skin warming.

The mechanism of the pain relief produced by opiates in normal volunteers in the cold induced pain test has been investigated. In a double-blind placebo controlled study, hand skin temperature during a 3 min immersion in water at 1 degree C was not affected by either the opioid dipipanone 8 mg or the vasodilator nifedipine 10 and 20 mg. During this immersion, dipipanone produced significant pain relief. Nifedipine reduced pre-immersion blood pressures and raised heart rates, however, it did not significantly alter pain scores. It is concluded that vasodilatation and local warming do not play a role in the relief of pain by opiates in the cold immersion test.

Carbamazepine and lamotrigine in healthy volunteers: relevance to early tolerance and clinical trial dosage.

This study was conducted to examine the effects of acute doses of lamotrigine (LTG) and carbamazepine (CBZ) in healthy subjects and determine whether the low tendency to impairment with LTG observed in animals applied to humans. Twelve healthy men participated in a placebo-controlled, balanced, double-blind comparison of the drugs on a series of psychomotor, autonomic, sensory, and subjective variables. Variables were analyzed by analysis of variance, and p < 0.05 was considered significant. Adaptive tracking and body sway were impaired by CBZ 600 mg. CBZ 400 and 600 mg impaired smooth pursuit eye movements and also reduced mean peak saccadic velocity. No differences from placebo occurred after LTG. CBZ 600 mg increased heart rate (HR), but no drug-related changes were noted in pupil size, salivary secretion, visual near point, or subjective effects. During the controlled study, mean plasma CBZ concentrations at 2 and 6.5 h after the 600-mg dose were 5.28 and 5.36 micrograms/ml; after LTG 300 mg, they were 3.16 and 3.00 micrograms/ml. Increased CBZ saliva concentrations were significantly associated (p < 0.01) with impaired adaptive tracking, smooth and saccadic eye movements and increased HR, and plasma concentrations were associated with impaired eye movements and body sway.