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Floating-Harbor syndrome (FHS) is a rare autosomal dominant syndrome characterized by short stature with delayed bone age, retarded speech development, intellectual disability and dysmorphic facial features. Recently, dominant mutations almost exclusively clustered in the final exon of the Snf2-related CREBBP activator protein (SRCAP) gene were identified to cause FHS. Here, we report a boy with short stature, speech delay, mild intellectual disability, dysmorphic features, and with genetically confirmed FHS. To the best of our knowledge, this is the first molecularly confirmed case with this syndrome reported in Romania. An intensive program of cognitive and speech stimulation, as well as yearly neurological, psychological, ophthalmological, otorhinolaryngological, pediatric and endocrinological monitoring for our patient were designed. We propose a checklist of clinical features suggestive of FHS, based on the main clinical features, in order to facilitate the diagnosis and clinical management of this rare condition. [ABSTRACT FROM AUTHOR]

Hypertension in the elderly is a major risk factor for cardiovascular disease. We aimed to analyze determinants of blood pressure (BP) control across different age groups. Population of a large global survey on hypertension treatment and control including 18 927 patients was analyzed. A logistic regression analysis was conducted to estimate BP control rates and the prevalence of antihypertensive drug usage according to age. Systolic BP control decreased from 29.6% (95% confidence intervals (CI) 26.0;33.5) at 18-40 years to 22.4% (20.8;24.2) at >75 years (P<0.0001), and diastolic BP control increased from 31.6% (27.9;35.6) to 57.3% (55.2;59.3), respectively (P<0.0001). BP control was worse in diabetic patients, but did not differ substantially with co-morbid conditions, except for a better control in patients with myocardial infarction (MI) (P<0.05). The use of 3 antihypertensive drugs increased with age from 16.1 to 37.8% (P<0.0001) due to a more frequent use of loop diuretics (P<0.0001), thiazides (P<0.0001), angiotensin-converting enzyme (ACE) inhibitors (P<0.0001) and calcium channel blockers (P<0.0001). About one third of patients received non-guideline-recommended drug-drug combinations. BP control is largely unsuccessful with increasing age. Owing to frequent inadequacies in the combination of antihypertensive drugs, future guidelines and educational programs should devote increased attention to the choice of optimal drug-drug combinations in the elderly. [ABSTRACT FROM AUTHOR]

Background: Microalbuminuria (MAU) is a marker of endothelial dysfunction and a predictor of cardiovascular events. The effects of cigarette smoking on the prevalence of MAU in a high-risk population with arterial hypertension are unclear. Methods: The International Survey Evaluating Microalbuminuria Routinely by Cardiologists in patients with Hypertension (I-SEARCH) documented the clinical profile of 20,364 patients with arterial hypertension and cardiovascular risk factors. In this population, 13,690 patients had no history of smoking, 4,057 patients were former smokers and 2,617 patients were current smokers. Results: The prevalence of MAU was associated with the smoking status. Consumption of 1-20 cigarettes per day leads to an increase of 6.8% in the prevalence of MAU compared to non-smokers ( P < 0.001). Smoking of >20 cigarettes per day was associated with a 12.5% higher prevalence of MAU compared to non-smokers, while former smokers had a 4.7% higher prevalence of MAU. Multivariable analysis revealed that smoking was independently associated with MAU [odds ratio (OR) smoking vs. non-smoking 1.16; 95% confidence interval (CI) 1.01-1.33; P < 0.05]. Particularly, a consumption of >20 cigarettes per day was associated with high odds for MAU (OR 1.33; CI 1.01-1.75; P < 0.05). Interestingly, independently of blood pressure, the use of an angiotensin receptor blocker and an ACE was associated with significantly reduced odds ratio for MAU in the smoking group, while there was no significant association in the non-smoking group. Conclusion: The prevalence of MAU in hypertensive patients is higher in smokers than in non-smokers with a strong dose dependency. [ABSTRACT FROM AUTHOR]

Cardiovascular death represents the single largest cause of mortality in women with 70% of deaths attributable to modifiable risk factors, such as hypertension. This analysis aims at evaluating, whether there are gender disparities in antihypertensive drug usage and blood pressure (BP) control. We included 18 017 patients with arterial hypertension from the International Survey Evaluating Microalbuminuria Routinely by Cardiologists in patients with Hypertension (I-SEARCH). The study was conducted between September 2005 and March 2006 in 26 countries, and data on patient demographics, cardiovascular disease and risk factors, BP, and cardiovascular drug treatment were collected. Mean systolic blood pressure (SBP) was 2.1 mm Hg higher in women (150.6±0.35 mm Hg, n=8357/18 017) than in men (148.5±0.35 mm Hg; P<0.0001, n=9526/18 017), whereas no difference in diastolic BP was seen (88.2±0.20 vs 88±0.20 mm Hg; P=0.198). Gender differences in SBP were more pronounced in diabetic as compared with non-diabetic patients (3.5 vs 1.7 mm Hg, n=4272 vs n=13 611; P<0.0001) and became evident at an age 55 years old. Overall BP-control rate was 33.6% in men and 30.6% in women (P<0.0001) and was lower in diabetic as compared with non-diabetic patients. In all, 30% of patients used one, 40% used two and 30% used 3 drugs without gender differences. Response rates to different drug regimens appeared to be similar. However, women received more frequently thiazides and β-blockers, and less frequently ACE-inhibitors as monotherapy. Major efforts are required to improve BP-management, especially in women. [ABSTRACT FROM AUTHOR]

Background: Niacin is an agent that significantly increases high-density lipoprotein cholesterol (HDL-C), but its effects on surrogate markers of atherosclerosis and inflammatory markers are less clear. We studied the effects of niacin on carotid intimal media thickness (IMT), brachial artery reactivity as well as markers of inflammation and the metabolic profile of patients with metabolic syndrome. Methods and results: Fifty patients with the metabolic syndrome (Adult Treatment Panel (ATP) III criteria) were randomised to either extended-release niacin (1000 mg/day) or placebo. After 52 weeks of treatment, there was a change of carotid IMT of +0.009 ± 0.003 mm in the placebo group and −0.005 ± 0.002 mm in the niacin group (p = 0.021 between groups). Endothelial function improved by 22% in the group treated with niacin (p < 0.001), whereas no significant changes were seen in the placebo group. High sensitivity C-reactive protein decreased by 20% in the group treated with niacin for 52 weeks (p = 0.013). Niacin increased HDL-C (p < 0.001) and decreased low-density lipoprotein cholesterol and triglycerides (p < 0.001) significantly, and there were no adverse effects on fasting glucose levels after 52 weeks of treatment. Conclusion: Extended-release niacin therapy effects a regression in carotid intimal medial thickness and improvement in metabolic parameters (increased HDL and reduced triglycerides). Furthermore, extended-release niacin may demonstrate an anti-atherogenic effect in the metabolic syndrome by improving endothelial function and decreasing vascular inflammation. [ABSTRACT FROM AUTHOR]

Objective: High blood pressure (BP) is a leading risk factor for cardiovascular morbidity and mortality. Effective antihypertensive pharmacotherapy is available but recognition and proper management of hypertension and BP goal achievement is still poor. Therefore, it was hypothesized that physicians' attitude towards high BP, as well as patients' perception and knowledge, may influence actual management of hypertension.Research Design and Methods: Telephone interviews were carried out with a random sample of 1259 primary care physicians in 17 countries worldwide from 12 December 2005 to 13 January 2006 using a central computer assisted telephone interview methodology (CATI).Results: (1) Physicians believed that 62 +/- 21% of their patients had their BP controlled. (2) They were mostly in line with guideline recommended BP goals and 96% were aware of the elevated cardiovascular risk of hypertension, but 41% aimed to reduce BP to acceptable levels only. (3) Physicians indicated that in 41% of patients monotherapy controls BP and 71% would escalate to combination therapy after monotherapy failure. (4) 54% regard hypertension management as difficult. (5) Physicians estimated that between 60 and 70% of patients know their BP goal but thought that there was still room for improvement of hypertension management on the patient side.Conclusion: Although many effective treatment options for arterial hypertension exist, BP goal achievement worldwide is suboptimal, leaving patients at an unnecessary cardiovascular risk. An increase in patients' awareness and compliance together with an increased adherence of physicians to current guidelines should help in reducing the long term cardiovascular consequences of hypertension. [ABSTRACT FROM AUTHOR]

Release of bacterial endotoxin and cytokines induce cardiac failure during sepsis. We investigated the direct effects of E. coli endotoxin (lipopolysaccharide, LPS) and cytokines induced by LPS on the cardiac myocyte gene program. For in vivo-experiments adult Wistar rats were given 600 µg/day LPS i.v. for 24 h or 7 days. In addition, cultured adult rat cardiac myocytes were treated with LPS, interleukin-1β (IL-1β), tumour necrosis factor-α (TNFα), interferon-γ (IFNγ) or IL-6 for 24 h. mRNA expression was evaluated for cardiac-α-actin (cAct), skeletal-α-actin (skAct), β- and α-myosin heavy chain (MHC). LPS induced βMHC-mRNA 3.6-fold and repressed αMHC 2.7-fold and cAct 2.5-fold after 24 h in vivo. Up-regulation of βMHC (3-fold) and repression of cAct (2.5-fold) were still observed after 7 days LPS infusion, whereas αMHC-mRNA levels had returned to normal. At the protein level, increased expression of βMHC by LPS treatment occurred already after 24 h and was maintained thereafter. LPS had no influence on skAct-mRNA. Similar changes in contractile protein mRNA expression were observed in LPS-treated cardiomyocytes in culture, whereas the tested cytokines either activated (IL-1β, IFNγ) or repressed (TNFα, IL-6) both MHC-isoforms and cAct. In conclusion, LPS and pro-inflammatory cytokines induce changes in contractile protein expression that may contribute to the acute heart failure observed during endotoxaemia. [ABSTRACT FROM AUTHOR]

The biological significance of the differential expression of cytokeratin (CK) polypeptides in breast carcinomas is unclear. We examined the CK profiles of 101 primary infiltrating ductal breast carcinomas using monoclonal antibodies directed against 11 different CKs and against vimentin. Two major CK phenotypes were distinguished: first, a phenotype expressing only the simple-epithelial CKs 7 (variably), 8, 18 and 19, and secondly, a bimodal phenotype co-expressing significant amounts of one or more of the stratified-epithelial CKs 4, 14 and 17. The vast majority of G1 and G2 carcinomas had the simple-epithelium phenotype, as did a subgroup of G3 carcinomas. Interestingly, the majority (62%) of G3 carcinomas exhibited the bimodal phenotype, with the expression of CKs 4, 14 and 17 being statistically correlated with poor histological differentiation and absence of steroid hormone receptors. The distribution of vimentin only partially overlapped with that of these stratified-epithelial CKs. Prognostic analyses suggested that the presence of CKs 4, 14 and/or 17 was associated with short overall and disease-free survival in subgroups comprising G3, oestrogen-receptor-negative and vimentin-negative tumours. In node-positive tumours the correlation between these CKs and a shorter disease-free interval attained statistical significance (log rank, 0.0096). Thus, abnormal CK profiles in ductal breast carcinomas appear to reflect disturbed regulation of differentiation-related gene expression programmes and may prove to be of clinical value. [ABSTRACT FROM AUTHOR]