Should angiotensin-converting enzyme-inhibitors be used to improve outcome in patients with coronary artery disease and 'preserved' left ventricular function?

Early clinical studies investigating the role of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure unexpectedly demonstrated a possible reduction in coronary heart disease endpoints. Two large scale clinical trials, HOPE and EUROPA, both studies in patients with coronary artery disease (CAD) but without clinical evidence of heart failure, showed a highly significant improvement in coronary heart disease outcomes on treatment with ramipril and perindopril, respectively, in contrast, in a similar population, PEACE was unable to demonstrate such benefit with trandolapril. Meta-analyses of all trials involving ACE-inhibitors showed a highly significant improvement in coronary heart disease endpoints. Current ESC guidelines recommend ACE-inhibitor therapy in CAD patients with co-existing indications for ACE-inhibitors, such as hypertension, heart failure, left ventricular dysfunction, prior MI was left ventricular dysfunction, or diabetes (class I, level of evidence A). These guidelines also recommend ACE-inhibitor therapy in all patients with angina and proven coronary disease (class IIa, level of evidence B). However, in angina patients without independent indication for ACE-inhibitor treatment, the anticipated benefit should be weighted against the costs and risks of side effects; in these patients, only agents and doses of proven efficacy for secondary prevention should be employed.     

Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage

BACKGROUND: Gastro-oesophageal reflux is often associated with cough. Patients with reflux show an enhanced tussive response to bronchial irritants, even in the absence of respiratory symptoms. AIM: To investigate the effect of mucosal damage (either oesophageal or laryngeal) and of oesophageal acid flooding on cough threshold in reflux patients. PATIENTS: We studied 21 patients with reflux oesophagitis and digestive symptoms. Respiratory diseases, smoking, and use of drugs influencing cough were considered exclusion criteria. METHODS: Patients underwent pH monitoring, manometry, digestive endoscopy, laryngoscopy, and methacholine challenge. We evaluated the cough response to inhaled capsaicin (expressed as PD5, the dose producing five coughs) before therapy, after five days of omeprazole therapy, and when oesophageal and laryngeal damage had healed. RESULTS: In all patients spirometry and methacholine challenge were normal. Thirteen patients had posterior laryngitis and eight complained of coughing. Twenty patients showed an enhanced cough response (basal PD5 0.92 (0.47) nM; mean (SEM)) which improved after five and 60 days (2.87 (0.82) and 5.88 (0.85) nM; p<0.0001). The severity of oesophagitis did not influence PD5 variation. On the contrary, the response to treatment was significantly different in patients with and without laryngitis (p = 0.038). In patients with no laryngitis, the cough threshold improved after five days with no further change thereafter. In patients with laryngitis, the cough threshold improved after five days and improved further after 60 days. Proximal and distal oesophageal acid exposure did not influence PD5. Heartburn disappeared during the first five days but the decrease in cough and throat clearing were slower. CONCLUSIONS: Patients with reflux oesophagitis have a decreased cough threshold. This is related to both laryngeal inflammation and acid flooding of the oesophagus but not to the severity of oesophagitis. Omeprazole improves not only respiratory and gastro-oesophageal symptoms but also the cough threshold.     

Effect of pancreas transplantation on life expectancy, kidney function and quality of life in uraemic Type 1 (insulin-dependent) diabetic patients

The aim of our study was to evaluate the effects of haemodialysis, kidney transplantation and simultaneous kidney and pancreas transplantation on survival of diabetic subjects and on kidney function. 40 Type 1 (insulin-dependent) diabetic patients received a kidney transplantation: in 31 cases the kidney was transplanted simultaneously to a pancreas graft from the same donor (KP group), while in 9 cases the pancreas was not available (K group). 44 uraemic Type 1(insulin-dependent) diabetic patients on dialysis and in waiting list for kidney transplantation, constituted the control group (HD group). Patient survival rate 1, 3 and 5 years following transplantation was better in KP group (93%, 89%, 89%, respectively) than in K group (88%, 88%, 73%, respectively) and in HD group (88%, 62%, 51%, respectively). Kidney graft survival at 1, 3 and 5 years post-transplant was better in KP group (93%, 72%, 72%, respectively) than in K group (76%, 61%, 31%, respectively). 1 year after transplantation, patients of the KP group who had lost the pancreas for technical reasons (thrombosis) were included in the K group so as to evaluate the effect of the transplanted pancreas on long-term patient and kidney survival. Patient survival rate in the KP group (17 patients) at 2 and 4 years was 100%, while at the same intervals it was 78% in the K group (13 patients). Kidney graft function rate at 2 and 4 years was 93% in the KP group (17 grafts) and 54% and 27% respectively in the K group (14 grafts). Evaluation of quality of life in patients receiving a kidney and pancreas transplantation showed an improvement in psychological well-being, when compared to patients receiving a kidney transplantation alone. Physical well-being was similar in patients transplanted with kidney and pancreas or with kidney alone.     

Influence of acoustic stress by noise on gastrointestinal motility in dogs

The effects of acoustic stress (AS) on gastrointestinal motility and their prevention by previous treatment with naloxone, phentolamine, propranolol, muscimol, and diazepam were investigated in intact and vagotomized fasted dogs fitted with chronically implanted strain gauges on the antrum at 10 cm from pylorus and on the jejunum at 70 and 140 cm from the pylorus. These effects were compared to those produced by intracerebroventricular administration of ovine corticotropin releasing factor (oCRF). Beginning 40–50 min after the occurrence of a gastric migrating motor complex (MMC), a 1-hr hearing of prerecorded intense music through earpieces (<100 dB) delayed the occurrence of the next gastric MMC observed after 2.8±1.2 hr, while jejunal MMC were still present at a normal frequency. During AS, heart rate and plasma cortisol were significantly increased by 32.7 and 215%, respectively, 10–15 min after the beginning of hearing. The AS-induced lengthening of the gastric MMC cycle as well as cortisol increase were abolished after previous administration of diazepam (0.5 mg/kg intramuscular) or muscimol (10 g/kg intravenous), while they were still present after naloxone (0.1 mg/kg intravenous), phentolamine (0.2 mg/kg intravenous), or propranolol (0.1 mg/kg intravenous). CRF administered intracerebroventricularly (100 ng/kg) also delayed the occurrence of gastric MMC without affecting jejunal motility, and this effect was not antagonized by previous treatment with diazepam or muscimol. Both the effects of AS and CRF were abolished after bilateral thoracic vagotomy. These results suggest that the selective inhibition of gastric motility induced by noise in dog is due to the CNS release of CRF which affects, in turn, the vagal output to the stomach. The suppressive action of diazepam or GABA agonist on noise-induced gastric hypomotility may be related to blockade of the AS-induced CRF release.     

Recommendations of the National Heart, Lung, and Blood Institute Nanotechnology Working Group

Recent rapid advances in nanotechnology and nanoscience offer a wealth of new opportunities for diagnosis and therapy of cardiovascular, pulmonary, and hematologic diseases and sleep disorders. To review the challenges and opportunities offered by these nascent fields, the National Heart, Lung, and Blood Institute convened a Working Group on Nanotechnology. Working Group participants discussed the various aspects of nanotechnology and its applications to heart, lung, blood, and sleep (HLBS) diseases. This report summarizes their discussions according to scientific opportunities, perceived needs and barriers, specific disease examples, and recommendations on facilitating research in the field. An overarching recommendation of the Working Group was to focus on translational applications of nanotechnology to solve clinical problems. The Working Group recommended the creation of multidisciplinary research centers capable of developing applications of nanotechnology and nanoscience to HLBS research and medicine. Centers would also disseminate technology, materials, and resources and train new investigators. Individual investigators outside these centers should be encouraged to conduct research on the application of nanotechnology to biological and clinical problems. Pilot programs and developmental research are needed to attract new investigators and to stimulate creative, high-impact research. Finally, encouragement of small businesses to develop nanotechnology-based approaches to clinical problems was considered important.     

Reperfusion Injury: Does It Exist and Does It Have Clinical Relevance?

Although reperfusion is an absolute prerequisite for the survival of ischemic tissue, it is not necessarily without hazard. Many (but not all) cardiologists are of the opinion that some components of reperfusion may be detrimental and able to inflict injury over and above that attributable to the ischemia. In this article we define four sequelae of reperfusion that might be designated as reperfusion injury. We identify possible underlying mechanisms and consider whether any of these forms of reperfusion injury are of clinical relevance.     

The epidemiological modelling of dysthymia: Application for the Global Burden of Disease Study 2010

Background

In order to capture the differences in burden between the subtypes of depression, the Global Burden of Disease 2010 Study for the first time estimated the burden of dysthymia and major depressive disorder separately from the previously used umbrella term ‘unipolar depression’. A global summary of epidemiological parameters are necessary inputs in burden of disease calculations for 21 world regions, males and females and for the year 1990, 2005 and 2010. This paper reports findings from a systematic review of global epidemiological data and the subsequent development of an internally consistent epidemiological model of dysthymia.

Methods

A systematic search was conducted to identify data sources for the prevalence, incidence, remission and excess-mortality of dysthymia using Medline, PsycINFO and EMBASE electronic databases and grey literature. DisMod-MR, a Bayesian meta-regression tool, was used to check the epidemiological parameters for internal consistency and to predict estimates for world regions with no or few data.

Results

The systematic review identified 38 studies meeting inclusion criteria which provided 147 data points for 30 countries in 13 of 21 world regions. Prevalence increases in the early ages, peaking at around 50 years. Females have higher prevalence of dysthymia than males. Global pooled prevalence remained constant across time points at 1.55% (95%CI 1.50–1.60). There was very little regional variation in prevalence estimates.

Limitations

There were eight GBD world regions for which we found no data for which DisMod-MR had to impute estimates.

Conclusion

The addition of internally consistent epidemiological estimates by world region, age, sex and year for dysthymia contributed to a more comprehensive estimate of mental health burden in GBD 2010.