Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease

OBJECTIVES: To test whether the addition of melatonin to bright-light therapy enhances the efficacy in treating rest–activity (circadian) disruption in institutionalized patients with Alzheimer's disease (AD).
DESIGN: Randomized, controlled trial.
SETTING: Two nursing homes in San Francisco, California.
PARTICIPANTS: Fifty subjects (mean age 86) with AD.
INTERVENTION: Experimental subjects received 1 hour of morning light exposure (≥2,500 lux in gaze direction) Monday to Friday for 10 weeks and 5 mg melatonin (LM, n=16) or placebo (LP, n=17) in the evening. Control subjects (n=17) received usual indoor light (150–200 lux).
MEASUREMENTS: Nighttime sleep variables, day sleep time, day activity, day:night sleep ratio, and rest–activity parameters were determined using actigraphy.
RESULTS: Linear mixed models were employed to test the primary study hypotheses. No significant differences in nighttime sleep variables were found between groups. At the end of the intervention, the LM group showed significant improvement in daytime somnolence as indicated by a reduction in the duration of daytime sleep, an increase in daytime activity, and an improvement in day:night sleep ratio. The LM group also evidenced a significant increase in rest–activity rhythm amplitude and goodness of fit to the cosinor model.
CONCLUSION: Light treatment alone did not improve nighttime sleep, daytime wake, or rest–activity rhythm. Light treatment plus melatonin increased daytime wake time and activity levels and strengthened the rest–activity rhythm. Future studies should resolve the question of whether these improvements can be attributed to melatonin or whether the two zeitgebers interact to amplify efficacy.     

Hyperhomocysteinemia exacerbates the development of intimal hyperplasia in Sprague-Dawley rats: Alleviation by rosiglitazone

The amino acid intermediate homocysteine (Hcy) is formed during the metabolism of methionine to cysteine. Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for coronary atherosclerosis. The circulating levels of total Hcy (tHcy) can increase due to intake of foods rich in methionine or deficiencies of vitamins such as folate, pyridoxine and cyanocobalamin, which are required for the metabolism of Hcy. In addition, mutations in the genes coding for Hcy metabolizing enzymes can contribute to an increase in tHcy levels. Clinical and epidemiological studies have shown that an elevated level of tHcy measured in serum or plasma is a strong predictor of cardiovascular disease risk, which appears to be greatest in patients who have HHcy following a methionine load. Intimal hyperplasia (IH) (intima/media [I/M] ratio) is the universal response of a vessel to injury and may result in vasoconstriction when left unattended. The effect of dietary HHcy on balloon catheter-injured carotid artery and its modulation (if any) by the peroxisome proliferator-activated receptor agonist gamma rosiglitazone was evaluated in 12-week-old female Sprague-Dawley rats fed either a control diet or a diet containing 1% L-methionine. Once the rats were established on the diet, the group that was fed 1% L-methionine was further subdivided and either given an aqueous preparation of 3 mg/kg/day rosiglitazone or the vehicle via oral gavage for one week. This was followed by surgically injuring the left carotid artery using a Maverick Over-The-Wire catheter (2.0 mm × 20 mm, 3.2F; Boston Scientific, USA). The rats were continued on their respective diets and drug regimen for 21 days postsurgery. On day 22 of the procedure, the rats were sacrificed for collection of blood, the carotid arteries and liver for biochemical and histological evaluation. Compared with controls there was a significant increase in both tHcy levels and I/M ratio in the rats fed 1% L-methionine (5.4±0.28 μM versus 32.8±3.01 μM, P<0.002; and 0.175±0.05 versus 1.05±0.23, P<0.005, respectively). The effect of rosiglitazone in rats fed the control diet was not prominent. On the other hand, administration of rosiglitazone to the rats on the 1% L-methionine diet significantly reduced the levels of serum tHcy (16.6±2.1 μM versus 32.8±3.01 μM, P<0.001); however, the tHcy levels remained significantly elevated compared with animals on the control diet (P<0.002). The group receiving the L-methionine diet plus rosiglitazone had an inhibition in the development of IH compared with those receiving the L-methionine diet alone (I/M of 0.278±0.041 versus 1.05±0.23, P<0.01). Moreover, the development of IH in the group receiving the L-methionine diet plus rosiglitazone treatment was not significantly different from that observed in the group on the control diet without rosiglitazone (0.278±0.041 versus 0.175±0.05, respectively). These findings may have important implications in deciphering the molecular mechanisms involved in the augmentation of IH in HHcy and modulation of this process by rosiglitazone.     

European reference values for Doppler indices of left ventricular diastolic filling

The European Study Group on diastolic heart failure requires objective evidence of abnormal left ventricular diastolic function to establish the diagnosis of diastolic heart failure, which is common in older people. Reference values for Doppler indices of transmitral flow, used to assess left ventricular diastolic function, have not been reported for people 70 years and over in Europe. The aim of this study was to establish reference values for these Doppler indices of transmitral flow in older people. A random sample of 355 subjects aged 70 and over, living in the community underwent clinical assessment and echocardiography. Asymptomatic subjects with no cardiovascular disease and cardiovascular risk factors were identified. Measurements of five commonly used Doppler indices of transmitral flow from these subjects were obtained and reference range expressed as mean+/-2 standard deviations and as percentiles. We have therefore generated reference Doppler values of transmitral flow for people aged over 70 in a British population.     

Role of the coronary sinus in maintenance of atrial fibrillation

INTRODUCTION: Bursts of tachycardia arising in the pulmonary veins may play an important role in perpetuating atrial fibrillation (AF). However, the role of the coronary sinus (CS) in the perpetuation of AF has been unclear. The aim of this study was to determine whether the CS plays a role in perpetuation of AF. METHODS AND RESULTS: Pulmonary vein isolation was performed by segmental ostial ablation with radiofrequency energy in 22 consecutive patients with paroxysmal AF. Bipolar and unipolar electrograms recorded in the left atrium and CS were analyzed during atrial pacing from the mitral annulus and during AF. There was a mean of 2.5 +/- 0.5 electrical connections between the CS and the left atrium. The electrical connections between the left atrium and CS were ablated with a mean of 6.2 +/- 2.7 minutes of radiofrequency energy applied along the atrial side of the inferior mitral annulus. During AF, episodes of intermittent tachycardia alternated between the left atrium and the CS. Among the 22 patients, sustained AF was still inducible in 9 after pulmonary vein isolation. After electrical disconnection of the CS from the left atrium, sustained AF was inducible in only 3 of these 9 patients. CONCLUSION: The CS may be a source of rapid repetitive electrical activity during AF. The lower probability of inducible sustained AF after electrical disconnection of the CS from the left atrium suggests that the CS may play a role in perpetuating AF.     

Atrial Burst Pacing with Biphasic and Monophasic Waveforms for Atrial Fibrillation

Background: Biphasic pacing is a novel mode of pacing that was suggested to increase cardiac conduction velocity as compared with cathodal monophasic pacing. We aimed to evaluate the safety and efficacy of rapid atrial pacing to convert atrial fibrillation (AF) to normal sinus rhythm. Methods: Multiple biphasic (anodal/cathodal), reverse biphasic (cathodal/anodal), and monophasic (cathodal) atrial pacing therapies were performed among 12 patients undergoing left atrial catheter ablation for AF. The efficacy end point was successful conversion of AF to sinus rhythm, and safety end point no induction of ventricular arrhythmias. Patients were paced at three cycle lengths (100, 200, and 333 msec) for 60 seconds at three locations (right and left atrial appendages and coronary sinus). Results: Among the 66 biphasic (anodal/cathodal) pacing procedures one procedure in a patient with chronic AF, which involved pacing at the left atrial appendage with a cycle length of 200 msec, led to conversion of AF to sinus rhythm. None of the 66 monophasic pacing procedures or the 66 reverse biphasic (cathodal/anodal) pacing procedures was associated with AF termination. None of the biphasic pacing procedures was associated with induction of ventricular arrhythmias. Conclusions: Rapid atrial pacing using a variety of waveforms at the cycle length and output used in the current study was found to be safe. There was a single success in converting a chronic AF to sinus rhythm. Ann Noninvasive Electrocardiol 2012;17(1):22–27     

Perspectives on eating disorders and service provision: A qualitative study of healthcare professionals

The study examined healthcare professionals' perspectives of eating disorder patients and services. Qualitative semi‐structured interviews were conducted with 18 healthcare professionals resulting in two themes. First, the practical difficulties of meeting the complex service needs of people with eating disorders were illustrated. Second, staff recognised patient diversity and the consequent need for individualised interventions. Services are frustrated in meeting patient needs due to complex resource limitations, which do not amount only to lack of funding. Rather than eating disordered patients being viewed as ‘difficult’, as reported in previous qualitative research, they are only difficult in a context of limited resources. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association.     

Undiagnosed and untreated wheezing in a cohort of adolescents with a family history of allergic disease.

Wheezing is a common symptom among adolescents. A cross-sectional survey was undertaken of a prospective cohort of teenagers with a close family history of allergy. The results demonstrate the prevalence of wheezing, the diagnosis of asthma, and the treatment of symptoms in this group. The findings suggest that undiagnosed and inadequately or untreated wheezing is as common among adolescents with a family history of allergic disease as in the general adolescent population, and can be associated with severe symptoms.