Atenolol in Migraine Prophylaxis a Double-blind Cross-over Multicentre Study

SYNOPSIS
The prophylactic anti-migraine effect of atenolol was compared to placebo in a multicentre study on 63 patients with classical and/or common migraine. The study design was double-blind cross-over and patients were given atenolol 100 mg o.d. or matching placebo during a study treatment period of 24 weeks. The effect of atenolol was significantly better than that of placebo: integrated headache values were reduced in 70% of the patients (p = 0.004) and the proportion of days with headache was reduced in 59% of the patients (p = 0.010). Few side effects were reported with both atenolol and placebo. This study shows atenolol to be safe and effective in the prophylactic treatment of migraine.     

Use of a novel double-antibody technique to describe the pharmacokinetics of rapid-acting insulin analogs

OBJECTIVE: To measure the contribution of bedtime intermediate-acting human insulin on the morning plasma insulin profiles after injection of the rapid-acting insulin analogs lispro and aspart in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 14 patients with type 1 diabetes, aged 35 +/- 13 years (mean +/- SD), participated in this single-blind, randomized crossover study. After taking their usual injection of human intermediate-acting insulin the night before, they were given insulin aspart or insulin lispro (10 units) before a standardized breakfast. The contribution of continuing absorption of the human insulin was measured using a monoclonal antibody not cross-reacting with insulin aspart or lispro, whereas the contribution of the analogs was estimated by subtraction after measurement of all plasma free insulin using an antibody cross-reacting equally with human insulin and both analogs. RESULTS: The correlation coefficient of the fasting free insulin concentrations measured with both insulin methods was 0.95. Fasting free insulin was 95 +/- 25 pmol/l before administration of insulin aspart, when determined with enzyme-linked immunosorbent assay detecting only human insulin, and 71 +/- 20 pmol/l before administration of insulin lispro (NS). Both insulin analogs gave marked peaks of free insulin concentrations, lispro at 40 +/- 3 min and aspart at 55 +/- 6 min after injection (P = 0.01). The later part of the profiles, from 4.5 to 5.5 h after injection, were similar and showed almost no contribution of the insulin analogs. CONCLUSIONS: The combination of insulin assays that detect human insulin only or both human insulin and analogs provides a new tool for studying insulin pharmacokinetics. Using this technique, we showed that 4.5 h after administration of the rapid-acting insulin analogs lispro and aspart, the free insulin levels are almost only attributable to the intermediate-acting insulin given at bedtime.     

Ultrasound nucleolysis: an in vitro study

Thermal intradiscal therapy for chronic low back pain, using a catheter inserted into the intervertebral disc, is becoming more popular in the treatment of low back pain. The aim of this study was to investigate the possibility of heating the nucleus pulposus of the intervertebral disc with high-intensity focused ultrasound (US) or HIFU. Two specific situations were considered, invasive transducers that would be in contact with the annulus fibrosus of the disc, and noninvasive transducers that could be used externally. Theoretical simulations were performed to find the optimal parameters of US transducers and then experimental studies were done using transducers made to these specifications. These experiments confirmed that it was possible to heat the discs with HIFU. Two orthogonal transducers resulted in a superior temperature distribution than using just one transducer. It is, therefore, feasible to consider thermal treatment of the nucleus pulposus of the disc using noninvasive US.     

Sublingual Nitroglycerin Delays Arterial Wave Reflections Despite Increased Aortic “Stiffness” in Patients with Hypertension: A Doppler Echocardiography Study

Venodilatation with consequent reduction in left ventricular filling and end-diastolic wall stress is an important mechanism for the beneficial effects of nitroglycerin in ischemic heart disease and in left ventricular failure. The effects of sublingual nitroglycerin on arterial pulsatile hemodynamics are less well defined. Doppler echocardiography and the calibrated subclavian artery pulse tracing were used to assess hemodynamics in subjects with sustained arterial hypertension (n = 25) before and 5 to 10 minutes after sublingual deposition of 0.5 mg glyceryl trinitrate. Aortic characteristic impedance was calculated by averaging the modulus of the input impedance (ratio of pressure to flow) at high frequencies and by calculating the ratio of pressure and flow increments during upstroke. The pressure wave was split into forward and backward components, and the reflection coefficient (the ratio of backward to forward pressures) was calculated. Parameters of the arterial bed were estimated by using 2- and 3-element Windkessel models. Nitroglycerin delayed the return of arterial wave reflections by 17% (P =.02) and increased aortic characteristic impedance by 20% (P =. 01), but it did not influence total arterial compliance. Mean arterial pressure decreased 7% (P =.0001), but pulse pressure did not change. Stroke volume and the acceleration time of aortic root flow decreased by 13% (P =.0001) and 8% (P =.01), respectively. Cardiac output decreased 7% (P =.01), despite an increase in heart rate of 10% (P =.0001). Peripheral resistance tended to decrease (4%, P =.06). Thus, in subjects with sustained hypertension, sublingual nitroglycerin dilates peripheral, predominantly muscular arteries with a subsequent delayed return of reflected pressure waves. Reflex activation of the sympathetic nervous system with consequent increased acceleration of left ventricular ejection seems to counteract the effect of reduced mean arterial pressure (distending pressure) with respect to the "stiffness" of the aorta.     

International survey of self-reported medicine use among adolescents

OBJECTIVE: To examine gender, age, and country variations in adolescents' self-reported medicine use. DESIGN: Cross-sectional school surveys of representative samples of 11- to 15-year-old girls and boys were used. The 1997/1998 Health Behaviour in School-aged Children study was referenced. A standardized questionnaire was completed during school hours. SETTING: Canada, US, Greenland, Israel, and 24 European countries. PARTICIPANTS: 123 227 participants equally distributed by gender and by 3 age groups (mean 11.7, 13.6, 15.6 y). MAIN OUTCOME MEASURES: Self-reported medicine use for headache, stomachache, difficulties in getting to sleep, and nervousness during the past month. RESULTS: The magnitude of the adolescents' medicine use for headache, stomachache, difficulties in getting to sleep, and nervousness varied substantially across countries. In each of the 28 countries, more girls than boys used medicine for pain. Use of medicine for headache increased by age; use of medicine for stomachache increased by age among girls, but decreased among boys; and use of medicine for difficulties in getting to sleep and nervousness decreased from the age of 11 to 15 years. There was an increase in the crude girl versus boy ratios for medicine use by age for all 4 symptoms. Multivariate logistic regression analyses, adjusting for age group and country, revealed the following odds ratios (95% CI) for girls' versus boys' medicine use: headache 1.56 (1.53 to 1.60), stomachache 2.16 (2.10 to 2.22), difficulties in getting to sleep 0.96 (0.91 to 1.00), and nervousness 1.04 (0.99 to 1.08). CONCLUSIONS: Substantial proportions of adolescents used medicine for common health problems. The prevalence of use differed between type of symptom for which the medicine was used, between countries, and between gender and age groups. We suggest that young people's medicine use should be addressed in public health policy.     

Recent-onset rheumatoid arthritis: a 1-year observational study of correlations between health-related quality of life and clinical/laboratory data.

OBJECTIVE: To analyse correlations within and between clinical/laboratory assessments and health-related quality of life variables for recent-onset rheumatoid arthritis at the time of diagnosis and 12 months later. METHODS: A total of 297 patients with recent-onset (< or =12 months) rheumatoid arthritis were included at diagnosis and followed up for 12 months. Clinical/laboratory assessment was performed by erythrocyte sedimentation rate, C-reactive protein, 28-joint count of tender/swollen joints, physician's global assessment, grip force, grip ability, functional impairment and walking speed. The self-reported health-related quality of life included symptoms (pain, morning stiffness), patients estimated general health, Health Assessment Questionnaire and SF-36. RESULTS: All tested variables improved within 6 months of diagnosis and then remained stable but still affected at the 12-month follow-up. Multivariate correlations between clinical/laboratory variables and health-related quality of life were weak. At inclusion, clinical/laboratory assessments explained 18% of health-related quality of life at the same time-point and predicted 7% of the variation in health-related quality of life after 12 months. CONCLUSION: The time-course followed similar patterns for most variables, but only a small part of the variation in health-related quality of life was explained or predicted by the clinical/laboratory variables. This implies that health-related quality of life adds important information to clinical/laboratory assessments in clinical practice and should be considered in goal setting together with clinical/laboratory assessment in order to optimize healthcare and outcome.