Risk factors for primary prevention of cardiovascular disease and risk reduction by lipid control: the OMEGA study risk factor sub-analysis

To identify risk factors for cardiovascular disease (CVD) in hypertensive patients with no history of CVD being treated with antihypertensive drugs, we examined subgroup data (n?=?13?052) from the prospective, observational Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement (OMEGA) study. Risk factors for CVD, stroke and coronary heart disease (CHD) were examined using a Cox proportional hazards model. In addition, the effect of statin therapy at baseline on CHD prevention was analyzed in dyslipidemic patients. The factors significantly related to CVD were female (hazard ratio [HR]?=?0.637, 95% confidence interval [CI] 0.428–0.948), older age (65–69 years: HR?=?2.165, 95% CI 1.214–3.861; 70–74 years: HR?=?2.324, 95% CI 1.294–4.174; ≥75 years: HR?=?2.448, 95% CI 1.309–4.578), family history of CHD (HR?=?1.993, 95% CI 1.249–3.179), diabetes (HR?=?2.287, 95% CI 1.700–3.078), current smoking (HR?=?2.289, 95% CI 1.512–3.466) and alcohol drinking socially (HR?=?0.589, 95% CI 0.379–0.913). Diabetes was a risk factor for both stroke and CHD, while age, family history of CHD, and sodium intake score were risk factors for stroke alone. Sex, dyslipidemia, smoking and exercise habits were risk factors for CHD alone. The risk of CHD in dyslipidemic patients on statin treatment was comparable to the risk in patients without dyslipidemia (HR?=?1.134, 95% CI 0.604–2.126). However, in dyslipidemic patients not on statin treatment, the HR increased to 1.807 (95% CI 1.156–2.825). In conclusion, some risk factors for CVD in hypertensive patients being treated with antihypertensive drugs with no history of CVD differed between CHD and stroke. These results suggest the importance of managing dyslipidemia with a statin for primary prevention of CHD, as well as the importance of hypertension therapy.     

Long-term safety,efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with severe uncontrolled asthma

Background

Omalizumab is effective and well-tolerated in children with moderate to severe allergic asthma. However, the effects of long-term treatment with omalizumab in this population haven't been well investigated. The objective of this study is to evaluate the long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with uncontrolled severe asthma.

Histological diagnosis of gastric submucosal tumors: A pilot study of endoscopic ultrasonography-guided fine-needle aspiration biopsy vs mucosal cutting biopsy

AIM: To compare the usefulness of endoscopic ultrasonography-guided fine-needle aspiration biopsy(EUS-FNAB) without cytology and mucosal cutting biopsy(MCB) in the histological diagnosis of gastric submucosal tumor(SMT).METHODS: We prospectively compared the diagnostic yield, feasibility, and safety of EUS-FNAB and those of MCB based on endoscopic submucosal dissection. The cases of 20 consecutive patients with gastric SMT ≥1 cm in diameter. who underwent both EUS-FNAB and MCB were investigated.RESULTS: The histological diagnoses were gastrointestinal stromal tumors(n = 7), leiomyoma(n =6), schwannoma(n = 2), aberrant pancreas(n = 2), and one case each of glomus tumor, metastatic hepatocellular carcinoma, and no-diagnosis. The tumors' mean size was 23.6 mm. Histological diagnosis was made in 65.0% of the EUS-FNABs and 60.0% of the MCBs, a nonsignificant difference. There were no significant differences in the diagnostic yield concerning the tumor location or tumor size between the two methods. However, diagnostic specimens were significantly more frequently obtained in lesions with intraluminal growth than in those with extraluminal growth by the MCB method(P = 0.01). All four SMTs with extraluminal growth were diagnosed only by EUSFNAB(P = 0.03). No complications were found in either method.CONCLUSION: MCB may be chosen as an alternative diagnostic modality in tumors showing the intraluminal growth pattern regardless of tumor size, whereas EUSFNAB should be performed for SMTs with extraluminal growth.     

Maximum value of home blood pressure: a novel indicator of target organ damage in hypertension

The maximum office systolic blood pressure (SBP) has been shown to be a strong predictor of cardiovascular events, independently of the mean SBP level. However, the clinical implications of maximum home SBP have never been reported. We investigated the association between the maximum home SBP and target organ damage (TOD). We assessed the left ventricular mass index (LVMI) and carotid intima-media thickness (IMT) using ultrasonography and the urinary albumin/creatinine ratio (UACR) as measures of TOD in 356 never-treated hypertensive subjects. Home BP was taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. The maximum home SBP was defined as the maximum mean triplicate BP reading in the 14-day period for each individual and was significantly correlated with LVMI (r=0.51, P<0.001), carotid IMT (r=0.40, P<0.001), and UACR (r=0.29, P<0.001). The correlation coefficients with LVMI and carotid IMT were significantly larger for the maximum home SBP than the mean home SBP. In multivariate regression analyses, the maximum home SBP was independently associated with LVMI and carotid IMT, regardless of the mean home BP level. In the prediction of left ventricular hypertrophy and carotid atherosclerosis, the goodness-of-fit of the model was significantly improved when the maximum home SBP was added to the sum of the mean office and home BPs (P=0.002 and P<0.001, respectively). These findings indicate that assessment of the maximum home SBP, in addition to the mean home SBP, might increase the predictive value of hypertensive TOD in the heart and artery.     

Relationship Between Swallowing Function and Gas Exchange During Day and Night in Patients with Obstructive Sleep Apnea Syndrome

Patients with obstructive sleep apnea syndrome (OSAS) are likely to exhibit an impaired swallowing reflex. However, mechanisms of disturbed swallowing reflex have not been determined. Because the upper-airway function is inhibited by hypoxia and hypercapnia, we examined the relationship between the swallowing function and gas exchange during day and night in patients with OSAS. Twenty-four patients with OSAS and 24 age-matched controls were studied. OSAS was diagnosed from overnight polysomnography. The swallowing reflex was judged by the latent time (LT) for swallowing following bolus injection of distilled water at the suprapharynx, the inspiratory suppression time (IST) from swallowing termination to the next onset of inspiration, and the threshold for evoking the swallowing response in terms of a volume of water (TV). Whereas the LT values are positively correlated with PaCO2 but not with PaO2 during the day, the values of IST and TV were not associated with daytime PaCO2 or PaO2. Nocturnal nadir SaO2 was correlated with LT, IST, and TV. These results indicate that oxyhemoglobin desaturation and hypercapnia may be associated with one of the mechanisms of the impaired swallowing function in patients with OSAS.     

FGF-2 regulation of neurogenesis in adult hippocampus after brain injury

Fibroblast growth factor-2 (FGF-2) promotes proliferation of neuroprogenitor cells in culture and is up-regulated within brain after injury. Using mice genetically deficient in FGF-2 (FGF-2(-/-) mice), we addressed the importance of endogenously generated FGF-2 on neurogenesis within the hippocampus, a structure involved in spatial, declarative, and contextual memory, after seizures or ischemic injury. BrdUrd incorporation was used to mark dividing neuroprogenitor cells and NeuN expression to monitor their differentiation into neurons. In the wild-type strain, hippocampal FGF-2 increased after either kainic acid injection or middle cerebral artery occlusion, and the numbers of BrdUrd/NeuN-positive cells significantly increased on days 9 and 16 as compared with the controls. In FGF-2(-/-) mice, BrdUrd labeling was attenuated after kainic acid or middle cerebral artery occlusion, as was the number of neural cells colabeled with both BrdUrd and NeuN. After FGF-2(-/-) mice were injected intraventricularly with a herpes simplex virus-1 amplicon vector carrying FGF-2 gene, the number of BrdUrd-labeled cells increased significantly to values equivalent to wild-type littermates after kainate seizures. These results indicate that endogenously synthesized FGF-2 is necessary and sufficient to stimulate proliferation and differentiation of neuroprogenitor cells in the adult hippocampus after brain insult.     

Neurokinin-1 and neurokinin-2 antagonism inhibits long-term acid fog-induced airway hyperresponsiveness

BACKGROUND: We recently reported that airway hyperresponsiveness (AHR) induced by a 6-h exposure to sulfuric acid (H(2)SO(4)) was inhibited by either the neurokinin (NK)-1 receptor antagonist, FK888, or the NK-2 receptor antagonist, SR48968, when administered immediately before the exposure. The aims of this study were to determine whether these antagonists have any therapeutic efficiency against AHR after long-term H(2)SO(4) inhalation and to elucidate the mechanisms in ovalbumin sensitized guinea pigs. METHODS: Specific airway resistance (sRaw), AHR, and BAL fluid were analyzed after an 8-week exposure to H(2)SO(4) aerosol (82 mg/m(3), pH 1.7, 40 mOsm) or hypotonic saline solution (pH 5.9, 40 mOsm) as a control. The H(2)SO(4) group then received a 2-week treatment with FK888, SR48968, or vehicle. RESULTS: The AHR and the eosinophil count in BAL fluid were significantly increased in the H(2)SO(4) group compared to control animals, while sRaw was significantly elevated in both groups after the 8-week exposure. Treatment with both FK888 and SR48968 significantly reduced the AHR and tended to inhibit eosinophilia in BAL fluid, but sRaw did not change. The degree of AHR improvement with SR48968 was much larger than with FK888. CONCLUSION: Our results show that both NK-1 and NK-2 receptor antagonists inhibited long-term H(2)SO(4)-induced AHR in sensitized guinea pigs, and the effect was much greater with an NK-2 antagonist. We suggest that NK-1 or NK-2 antagonism might partially inhibit the H(2)SO(4)-induced influx of eosinophils into the lung.