Serotonin transporter polymorphism modifies the association between depressive symptoms and sleep onset latency complaint in elderly people: results from the ‘InveCe.Ab’ study

Previous studies have documented the involvement of the central nervous system serotonin in promoting wakefulness. There are few and conflicting results over whether there is an actual association between bearing the short allele of serotonin transporter promoter polymorphism (5‐HTTLPR) and worse sleep quality. This study examined whether sleep onset latency complaint is associated with the 5‐HTTLPR triallelic polymorphism in the SLC6A4 gene promoter and whether this polymorphism influences the relationship between sleep onset latency complaint and depressive symptoms in elderly people. A total of 1321 community‐dwelling individuals aged 70–74 years were interviewed for sleep onset latency complaint and for sleep medication consumption. Participants’ genomic DNA was typed for 5‐HTTLPR and rs25531 polymorphisms. Depressive symptoms were evaluated with the Geriatric Depression Scale Short form and general medical comorbidity was assessed by the Cumulative Illness Rating Scale. The presence of a past history of depression was recorded. The S′ allele of the 5‐HTTLPR triallelic polymorphism was associated with sleep onset latency complaint. This association was maintained after adjusting for depressive symptoms, sex, age, history of depression and medical comorbidity. After stratification for 5‐HTTLPR/rs25531, only in S′S′ individuals high depressive symptoms were actually associated with sleep onset latency complaint. These data indicate that the low‐expressing 5‐HTTLPR triallelic polymorphism is an independent risk factor for sleep onset latency disturbance. Furthermore, the 5‐HTTLPR genotype influences the association between depressive symptoms and sleep onset latency complaint.     

Advances in stem cell therapy for amyotrophic lateral sclerosis

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a progressive, incurable neurodegenerative disease that targets motoneurons. Cell-based therapies have generated widespread interest as a potential therapeutic approach but no conclusive results have yet been reported either from pre-clinical or clinical studies.

Areas covered: This is an integrated review of pre-clinical and clinical studies focused on the development of cell-based therapies for ALS. We analyze the biology of stem cell treatments and results obtained from pre-clinical models of ALS and examine the methods and the results obtained to date from clinical trials. We discuss scientific, clinical, and ethical issues and propose some directions for future studies.

Expert opinion: While data from individual studies are encouraging, stem-cell-based therapies do not yet represent a satisfactory, reliable clinical option. The field will critically benefit from the introduction of well-designed, randomized and reproducible, powered clinical trials. Comparative studies addressing key issues such as the nature, properties, and number of donor cells, the delivery mode and the selection of proper patient populations that may benefit the most from cell-based therapies are now of the essence. Multidisciplinary networks of experts should be established to empower effective translation of research into the clinic.     

Intramyocardial dissecting hematoma in anterior wall ST elevation myocardial infarction: impact on left ventricular remodeling and prognosis

Intramyocardial dissecting hematoma is an uncommon complication of myocardial infarction potentially leading to cardiac rupture. The aim of the present study was to investigate coronary reperfusion results, left ventricular (LV) function recovery and remodeling and clinical outcomes in patients with anterior STEMI complicated by intramyocardial hematoma. We prospectively studied 87 patients (mean age 59?±?10 years; 88% male) with anterior STEMI (42 with intramyocardial hematoma) in order to evaluate coronary reperfusion results, LV remodeling (≥15% increase in end-systolic volume) and clinical outcomes (cardiac death, non-fatal reinfarction, and hospitalization for congestive heart failure) at 24 months. Thrombolysis in myocardial infarction (TIMI) flow score and myocardial blush grade (MBG) were assessed both pre- and post-percutaneous coronary intervention (PCI) and speckle-tracking echocardiography was performed post PCI and at 6-month follow-up. Patients with hematoma had lower post-PCI TIMI score and MBG, higher heart rate, worse LV ejection fraction and longitudinal or rotational function than their counterparts. LV remodeling occurred in 33 (78.6%) patients with hematoma and 11 (24.4%) patients without (p?<?0.001). Independent predictors of LV remodeling were heart rate (p?=?0.018), MBG (p?=?0.036) and presence of hematoma (p?<?0.001). Hematoma (log-rank test, χ²?=?9.849; p?=?0.002) and LV remodeling (log-rank test, χ²?=?13.770; p?<?0.001) were associated to a higher rate of adverse events. Cox analysis identified LV remodeling as the only independent predictor of adverse events (hazard ratio?=?3.912; 95% confidence interval, 1.429–10.714; p?=?0.008). Intramyocardial dissecting hematoma complicating anterior STEMI is an independent determinant of LV remodeling and is associated to poor prognosis.     

Risk of Exclusion From Stroke Rehabilitation in the Oldest Old

Objective

To investigate whether oldest-old age (≥85y) is an independent predictor of exclusion from stroke rehabilitation.

Baroreflex sensitivity in the elderly with silent myocardial ischemia

In order to assess high-pressure barocepture sensitivity and parasympathetic function in elderly patients with silent myocardial ischemia, we selected 45 inpatients in our geriatric unit for a prospective cohort study of patients with coronary heart disease. All patients were over 65 years of age (37 men and 8 women) and had coronary heart disease, documented by an angiographic study and electrocardiographic evidence of myocardial ischemia during exercise stress testing, performed according to the Bruce protocol. The subjects were divided in three subgroups: group 1 (22 patients) with electrocardiographic and echocardiographic history of myocardial infarction but no angina chest pain during exercise testing; group 2 (13 patients) with no exercise induced chest pain; and group 3 (10 patients) with exercise-induced chest pain. Baroceptor sensitivity was assessed in all subjects, by evaluating heart rate changes expressed in RR interval on the basis of changes in the mean arterial pressure during intravenous infusion of stepwise doses (50-100 and 150 mug) of phenylephrine hydrochloride. Heart rate changes were also evaluated during overshoot of the Valsalva maneuver (Valsalva max.), providing an index of parasympathetic activity. Our results showed that group two patients (only silent ischemia) had significantly (P>0.001) greater baroceptor sensitivity than the other two groups (group 2; 15.2+/-1.9 ms/mmHg; group 1: 10.0+/-1.7 ms/mmHg; and group 3: 9.8+/-1.7 ms/mmHg). Group two also showed a significant positive correlation (r=0.58; P<0.05) between baroceptor sensitivity and end-diastolic pressure and a significant inverse correlation (r=-0.672; P<0.05) between baroceptor sensitivity and the ejection fraction. Group 2 patients had a significantly longer RR interval than group 1 (P<0.05) and group 3 (P<0.05); a significant positive correlation (r=0.620; P<0.05) between Valsalva max. and end-diastolic pressure; and a significant inverse correlation (r=0.694; P<0.05) between Valsalva max. and the ejection fraction. Valsalva max. and baroceptor sensitivity correlated significantly in all three groups (group 1, r=0.707; P<0.001; group 2, r=0.94; P<0.001; and group 3; r=0.833; P<0.05). In conclusion our data suggest that elderly patients with silent ischemia appear to have an increased capacity for evoking parasympathetic reflexes that could inhibit pain perception.     

Safety and efficacy of therapy with botulinum toxin in obesity: a pilot study

Background Botulin toxin (BTX) has been proposed as a potential obesity treatment.Methods In a pilot study, the short-term efficacy and safety of BTX was assessed in eight subjects (four men, four women; median age, 46 years; range, 35–57 years) with severe obesity (median body mass index [BMI], 47.1 kg/m²; range 38.2–56.7 kg/m²) and multiple dietary treatment failures. In a single endoscopic session, 500 UI of BTX-A was injected in the gastric antral region.Results No clinically significant side effects were observed. In all patients, despite their not being on a specific diet, a reduction of body weight was observed at 1 month (median baseline weight, 124.4 kg vs 121.8 kg at 1 month; P < 0.05). Two treatment-unrelated dropouts were observed. At 4 months, three of the six patients had a further weight loss. The treatment effect was apparently independent of changes in hunger or satiety, or of changes in fasting and postprandial plasma ghrelin and serum leptin, thus suggesting a different pharmacological mechanism.Conclusions BTX-A treatment appears to be safe and well tolerated by obese patients, while its short-term efficacy varied widely.     

Losartan treatment and left ventricular filling during volume loading in patients with dilated cardiomyopathy

Background Patients with mild heart failure show a reduction in preload reserve mechanism during volume expansion. At this time, the effects of volume expansion on left ventricular (LV) diastolic filling in this subset of patients have not been well characterized. Methods We evaluated the effects of acute volume loading on Doppler parameters of LV filling in 10 healthy control subjects and in 12 patients with idiopathic dilated cardiomyopathy (DCM). In patients with DCM, the effects of losartan on diastolic adaptation to volume load were also investigated. Results During volume loading, the healthy control subjects showed a decrease in isovolumic relaxation time (F = 5.3, P < .05) but an increase in the LV peak filling rate (F = 52.9, P < .001) and velocity time integral of both systolic (F = 72.8, P < .001) and diastolic (F = 4.6, P < .05) pulmonary venous flow. In patients with DCM, isovolumic relaxation time decreased more than in control subjects (F = 8.1, P < .01), and the deceleration time of the early mitral wave was reduced (F = 26.3, P < .001). Furthermore, the duration of pulmonary venous flow reversal exceeded that of mitral flow at atrial contraction (F = 28.5, P < .001). After treatment with losartan, the deceleration time of early mitral wave remained unchanged, and the duration of pulmonary venous flow reversal at atrial contraction did not exceed that of mitral flow; thus, a significant treatment effect was detectable (F = 5.6, P < .05; and F = 6.6, P <.05, respectively). Conclusions Control subjects respond to volume load with enhancement in early LV filling, whereas patients with DCM show an increase of LV filling pressure. Diastolic adaptation to volume load improves in patients with DCM after treatment with losartan. (Am Heart J 2002;143:433-40)     

Absence of somatic mutations in natriuretic peptide receptor type A gene in human aldosterone-secreting adenomas

Somatic mutations of genes codifying for key regulatory proteins are the cause of different types of hormone-secreting adenomas. Natriuretic peptides (NP) are the strongest inhibitors of aldosterone secretion but aldosterone-secreting adenomas (aldosteronomas) are resistant to this inhibition and have reduced binding sites for NPs. The objective of this study was to sequence the entire coding region of the NP receptor type A (NPRA, codified by the Npr1 gene) to find loss-of-function somatic mutations. Total RNA was extracted from eight aldosteronomas and cDNA was synthesized. NPRA mRNA expression was evaluated by Northern blot analysis and compared with beta-actin mRNA as the housekeeping gene. Twelve primer couples were designed on the basis of the Npr1 gene organization to amplify, by PCR, all 22 coding exons of the gene. The two strands of amplified DNAs were purified and directly sequenced by automated capillary sequencer. NPRA mRNA expression did not differ among aldosteronomas. Npr1 open reading frame sequences obtained from eight aldosteronomas did not contain any mutation. The coding sequences of all 22 exons were identical in all samples and identical to published sequences. In the 3'-untranslated region (3'-UTR) a new length difference 3C/4C polymorphism was found at position 15 129 (three adenomas were 3C/4C and two were 3C/3C). Such a 3C/4C polymorphism was present in genomic DNA from 80 control subjects (25, 4C/4C; 40, 3C/4C; 15, 3C/3C). Mutations in the coding exons of the Npr1 gene do not appear to be a common cause of aldosteronomas. Moreover, the exons of Npr1 encoding for the translated portion of mRNA do not appear to be prone to polymorphisms. The polymorphism identified in the 3'-UTR might affect mRNA stability resulting in lower receptor synthesis, but it is not likely to confer a predisposition to the development of aldosteronomas.