THE EUGLYCAEMIC HYPERINSULINAEMIC CLAMP: AN EVALUATION OF CURRENT METHODOLOGY

1. The recognition of the role of insulin resistance in disease states and the recent development of new drugs that modify insulin-dependent metabolism has led to increased use of the euglycaemic hyperinsulinaemic clamp to measure in vivo insulin sensitivity, but several key aspects of the technique are poorly documented in the literature. 2. We have evaluated the reproducibility and intersubject variation of measurements of insulin sensitivity in groups of insulin-sensitive and insulin-resistant subjects and assessed the effects of hand warming on haemodynamic and metabolic responses. 3. Subjects participated in one of two protocols: (i) 18 healthy male volunteers and 18 patients with hypertension and glucose intolerance were clamped on two occasions, 1 week apart with measurements of insulin sensitivity (M) derived after 120 and 180 min of hyperinsulinaemia; and (ii) six healthy volunteers were clamped on one occasion with simultaneous sampling of antecubital and ‘arterialized’ (dorsal hand) venous blood for comparison of plasma glucose concentrations and oxygen saturation and a further six volunteers were clamped on two occasions with and without the use of hand warming. 4. Measurements of M derived after 120 min (M120) and 180 min (M180) of hyperinsulinaemia were reproducible: the coefficients of repeatability (mg/kg per min) of M120 and M180 were 1.0 and 0.9 for volunteers and 1.0 and 1.0 for the patient group, respectively. The intersubject variation in insulin stimulus was high: coefficients of variation for M180 were 22% for volunteers compared with 38% for the patient group. In volunteers compared with the patient group, hand warming significantly increased venous oxygen saturations (95 ± 2 vs 79 ± 18%, respectively) and glucose concentrations (5.2 ± 0.2 vs 4.5 ± 0.4 mmol/L, respectively) and measurements of M were significantly higher using arterialized compared with antecubital venous blood. However, local hand warming was associated with systemic vasodilatation: blood pressure decreased (e.g. 6mmHg diastolic; P < 0.05) with a compensatory increase in heart rate (8 b.p.m.). 5. In conclusion, clamps of 120 and 180 min duration yielded measurements of M that were reproducible. The technique is much more robust when used in the context of a crossover design because of the significant (20–40%) intersubject variation in M, even among apparently homogeneous male volunteers. Hand warming effectively arterializes venous blood and gives significantly higher M values, but induces systemic vasodilatation, which may confound measurements of M.     

Effects of phosphatidylserine in Alzheimer's disease.

We studied 51 patients meeting clinical criteria for probable Alzheimer's disease (AD). Patients were treated for 12 weeks with a formulation of bovine cortex phosphatidylserine (BC-PS; 100 mg t.i.d.) or placebo, and those treated with the drug improved on several cognitive measures relative to those administered placebo. Differences between treatment groups were most apparent among patients with less severe cognitive impairment. Results suggest that phosphatidylserine may be a promising candidate for study in the early stages of AD.     

Once daily amlodipine in the treatment of mild to moderate hypertension.

1. The antihypertensive efficacy of once-daily amlodipine was studied in a group of 30 patients with mild to moderate hypertension in a double-blind, placebo controlled parallel group study. The dose range of amlodipine was 2.5-10 mg daily titrated at 2 weekly intervals for a total treatment period of 8 weeks. 2. Amlodipine produced a significant reduction in blood pressure compared with placebo, the mean difference between baseline and 8 weeks (corrected for placebo effect) being 16/12 mm Hg supine, 14/4 mm Hg standing. 3. Blood pressure returned to baseline values during a terminal 4 week washout period on placebo. 4. There were no significant effects on heart rate. 5. Two patients experienced slight ankle oedema while receiving amlodipine 10 mg daily but the active drug was otherwise well tolerated. 6. Plasma concentration of amlodipine, sampled 24 h after the preceding dose, increased as the dose titration sequence was followed, averaging 2.5 ng ml-1 on 2.5 mg, 4.9 ng ml-1 on 5 mg and 10.5 ng ml-1 on 10 mg.     

Treatment of age-associated memory impairment with guanfacine

Alpha2 adrenergic agonists have been shown to improve memory test performance in amnesic humans and aged nonhuman primates. In a group of drugs in this class that were tested for their effects on age-related memory impairments in aged monkeys, guanfacine was the most effective for improving mnemonic function at doses that were without significant side effects. These data prompted studies of guanfacine for its effect on learning and memory in persons with age-associated memory impairment (AAMI), the results of which are now reported. The data suggest that guanfacine may have modest mood-improving effects but had no significant effects on learning and memory in the subjects tested.     

Measuring health inequalities between genders and age groups with realization of potential life years (RePLY)

OBJECTIVE: We propose a new method to measure health inequalities caused by conditions amenable to policy intervention and use this to identify health differences between sexes and age groups. METHODS: The lowest observed mortality rates are used as a proxy of unavoidable mortality risks to develop a new measure of health outcome - realization of potential life years (RePLY). The RePLY distribution is used to measure avoidable health inequalities between sex and age groups respectively. FINDINGS: Using RePLY we find that even those countries with very high life expectancy at birth can have substantial health inequalities across different age groups. Also, gender inequality is more pronounced among those aged < 30. Among countries with a life expectancy < 60 years, there is a much larger prevalence of gender inequality against females; countries with life expectancy > 60 years have comparable numbers of cases of inequality among females and males. Finally, high avoidable health inequality is associated with low average income, high income inequality and high population fractionalization. CONCLUSION: It is important to distinguish between unavoidable and avoidable mortality when measuring health outcomes and their distribution in society. The proposed new measure (RePLY) enables policy-makers to focus on age-sex groups with low realization of potential life years and thus high avoidable mortality risks.     

Contaminants in Lesser and Greater Scaup Staging on the Lower Great Lakes

The decrease and subsequent lack of recovery of the North American scaup population has increased concerns about contaminants acquired during migration. We collected 189 fall- and spring-migrant lesser (Aythya affinis) and greater scaup (A. marila) on the lower Great Lakes (LGL) to determine if organic contaminants and trace elements in scaup livers were increased and to evaluate sources of variation in selenium (Se) burdens. We found that all organic contaminants were below toxic levels. Of 18 trace elements, only Se was detected at increased (>10-ppm dry-mass) levels. Se in lesser scaup increased but remained constant in greater scaup throughout fall; levels were increased in 14% of lesser scaup and 46% of greater scaup. During spring, Se increased in lesser scaup but decreased slightly in greater scaup; levels were increased in 75% of lesser scaup and 93% of greater scaup. We suggest that Se may be problematic for some breeding female scaup after departing the LGL, but more research is needed to determine the extent to which it affects scaup demographics.     

Reliability of peer and self-assessment scores compared with trainers' scores following third molar surgery

Context It is sometimes claimed that self‐assessment is inaccurate and that clinicians over‐rate their performance. There is a need to find out why this should be. Is poor self‐assessment caused by some clinicians' inability to accurately judge performance? Or does over‐scoring result from a desire to convey a more favourable impression? Peer assessment is widely advocated and is said to be of benefit to both assessor and assessee. Methods In this study, we wanted to see if postgraduates were able to peer‐assess and if this form of assessment was more reliable than self‐assessment when compared with assessment by a trainer. We used checklist and global rating scales to evaluate surgical skills in removing a mandibular third molar tooth. Results There was no statistically significant difference between peer‐assessed and trainer‐assessed scores. We found that, on average, peer assessment (especially global rating scales) reflected trainer scores more accurately than self‐assessment of surgical skills. Self‐assessment scores were significantly higher on average than those given in peer assessment. Discussion Although peers and trainee surgeons came from the same group, the surgeons were more likely to over‐score when measuring their own performances. The greatest variability (and over‐scoring) between assessor and trainee surgeon appeared to occur in those with lower mean scores. Formative peer assessment may be a useful and less stressful mechanism for encouraging reflection.