Presence of Spontaneous Nystagmus, Benign Paroxysmal Positional Vertigo, and Tumarkin Fall in Patients With Primary Headache and Their Responses to Caloric and Video Head Impulse Tests.

Background: Migraine, vestibular migraine (VM) and tension-type headache (TTH) are the most common disorders in dizziness and headache clinics, associated with dizziness or vertigo and postural imbalance, causing a substantial burden on the individual and the society. The objective of this research was to examine the presence of spontaneous nystagmus, comorbidity of benign paroxysmal positional vertigo (BPPV), and Tumarkin fall in patients; additionally, the study focused on assessing the patients' responses to bithermal caloric irrigation and video head impulse test (vHIT). Methods: Consecutive patients diagnosed with migraine, VM, and TTH according to the International Classification of Headache Disorders, third edition (beta version (ICHD-3ß)), who were referred to Dizziness and Headache Clinic were enrolled. BPPV and Tumarkin fall were assessed by questionnaires. The presence of BPPV was further evaluated through Dix-Hallpike or head roll maneuver, while spontaneous nystagmus was monitored using video-oculography during interictal period. Lastly, patients' responses to bithermal caloric irrigation and vHIT were analyzed. Results: There was a significantly higher incidence of spontaneous nystagmus in VM compared to both migraine and TTH. The drop attack episodes were slightly more frequent in VM than in TTH and migraine, though not statistically significant. The prevalence of BPPV was significantly higher in VM than in migraine and TTH. Unilateral vestibular paresis was more common in the VM group than in migraine and TTH. There was profound unilateral weakness (UW) in VM patients than in migraine, but no significant difference was found between VM and TTH. In VM, the percentage of saccades along with reduced vHIT gain was significantly higher than in migraine. Lastly, the percentage of abnormal response in vHIT was significantly lower than the percentage of abnormal UW in caloric irrigation across all groups. Conclusions: In VM patients, the prevalences of decompensated peripheral damage and BPPV were higher than in migraine and TTH patients as disclosed by the presence of peripheral spontaneous nystagmus and abnormal vHIT during the interictal period. Our findings suggest that the peripheral vestibular system acts as a significant mechanism in the pathogenesis of VM, and it might also be involved in migraine and TTH cases without vertigo symptoms.

Prognostic value of plasma ghrelin in predicting the outcome of patients with chronic heart failure.

BACKGROUND AND AIMS: Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue receptor and is closely associated with chronic heart failure (CHF). We undertook this study to investigate the relevance of ghrelin in CHF prognosis. METHODS: A total of 145 in-patients with CHF in NYHA class II, III or IV despite optimized therapy were prospectively included in the study, grouped according to NYHA class and compared with 55 healthy control subjects. Ghrelin and N-terminal pro-B-type natriuretic peptide (Nt pro-BNP) were measured in plasma by ELISA. Echocardiographic information was also measured, including left atrial dimension, left ventricular end-diastolic diameter, LV volume and left ventricular ejection fraction (LVEF). Patients were followed for 2 years or until major adverse cardiac events. RESULTS: Plasma ghrelin levels were significantly lower in patients with CHF than in control subjects (p = 0.014). In addition, plasma ghrelin levels differed significantly with the severity of CHF. Notably, survival analysis showed that high ghrelin levels were an indicator of a favorable prognosis for CHF. Our results also showed that ghrelin correlated inversely with plasma Nt pro-BNP levels (r = -0.562, p <0.001) and positively with LVEF (r = 0.620, p <0.001) in patients with CHF. Furthermore, multivariate analysis showed that ghrelin levels were independently associated with adverse cardiac events (hazard ratio: 0.72; 95% CI: 0.64-0.81, p = 0.03). CONCLUSIONS: Ghrelin is a new biomarker of CHF severity as well as a new prognostic predictor for patients with CHF. Future experimental and clinical studies are warranted to evaluate ghrelin as a novel prognostic tool and for its therapeutic potential in patients with CHF.

Role of Genetic Polymorphism of Angiotensin-Converting Enzyme, Plasminogen Activator Inhibitor-1 and Endothelial Nitric Oxide Synthase in the Prognosis of Coronary Artery Disease.

BACKGROUND: This study was to investigate the effects of multiple genetic polymorphisms and conventional risk factors in the prognosis of coronary artery disease (CAD). METHODS: One hundred and fifty five patients with CAD were prospectively recruited, they were subgrouped as single vessel disease (SVD) and multiple vessel disease (MVD). All patients were detected I/D polymorphism of angiotensin-converting enzyme (ACE) gene, 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene, and G894→T mutation of endothelial nitric oxide synthase (eNOS) gene. The patients were followed up for 10-65 months, mean 35 months. End points were major adverse cardiovascular events (MACE), including angina, myocardial infarction, and cardiac sudden death. RESULTS: During the follow-up period, MACE developed in 81 patients, 73 patients with angina, seven with myocardial infarction, and one with cardiac sudden death. CAD patients with MVD were more probable of developing MACE during follow-up. Distribution of PAI-1 gene polymorphism was significantly different between SVD and MVD patients, p < 0.001. The frequency of DD genotype of ACE and 4G/4G genotype of PAI-1 in patients with MACE were significantly higher than those in patients without MACE, p < 0.001 and p = 0.002, respectively. Incidence of diabetes mellitus was significantly higher in patients with MACE than in patients without MACE, P = 0.03. Cox regression analysis showed that diabetes mellitus (HR 2.36, 95% CI 1.33-4.46, p = 0.003), 4G/4G polymorphism of PAI-1 gene (HR 3.45, 95% CI 1.71-6.56, p = 0.009), and D/D polymorphism of ACE gene (HR 2.99, 95% CI 1.84-5.76, p = 0.005), were independent predictors of the MACE. CONCLUSIONS: Our results showed that the conventional risk factors and genetic polymorphisms have significant influence on prognosis of CAD patients. CAD patients with diabetes mellitus, DD genotype of ACE, and 4G/4G genotype of PAI-1 suggested poor prognosis.

U19/Eaf2 binds to and stabilizes von hippel-lindau protein.

Studies have firmly established a key regulatory role for the tumor suppressor pVHL in the regulation of the vascular system and normal spermatogenesis. Here, we report that knockout of the newly identified tumor suppressor U19/Eaf2 also caused vascular system abnormalities and aspermatogenesis, suggesting a potential link between U19/Eaf2 and pVHL. Coimmunoprecipitation and in vitro binding assays showed an association between U19/Eaf2 and pVHL, whereas deletion mutagenesis revealed the requirement of the NH(2) terminus of U19/Eaf2 and both the alpha and beta domains of pVHL for this binding. U19/Eaf2 stabilizes pVHL, as shown by protein stability and pulse-chase studies. Testes and mouse embryonic fibroblasts (MEF) derived from U19/Eaf2 knockout mice expressed reduced levels of pVHL, indicating that full in vivo expression of pVHL indeed requires U19/Eaf2. As expected, U19/Eaf2 knockout MEF cells exhibited an increased level and activity of hypoxia-inducible factor 1alpha (HIF1alpha), a protein typically regulated via a pVHL-mediated degradation pathway. Furthermore, angiogenesis in a Matrigel plug assay was significantly increased in U19/Eaf2 knockout mice. The above observations argue that U19/Eaf2 can modulate HIF1alpha and angiogenesis, possibly via direct binding and stabilization of pVHL.

Carotid atherosclerosis in ischemic cerebrovascular patients.

BACKGROUND: Cerebral emboli resulting from atherosclerosis at the carotid bifurcation is a major cause of ischemic stroke. A convenient and prompt evaluation is necessary for secondary prevention and treatment. METHODS: In this study, one hundred and thirty eight patients with cerebral ischemic events were enrolled; 100 patients with nonischemic cerebral diseases were enrolled as controls. Noninvasive ultrasound was used to measure the atherosclerotic plaques and intima-media thickness (IMT) of carotid and femoral artery. RESULTS: Our results showed that patients in study group had higher incidence and severity of carotid and femoral plaques, and higher mean intima-media thickness (IMT) at both the carotid and femoral sites compared with that of controls (p < 0.01). Carotid atherosclerosis were highly prone to have instability plaques in study group(p < 0.001). CONCLUSIONS: This cross-sectional study showed that, the prevalence of carotid atherosclerosis and the unstable plaques were higher in cerebral ischemic patients. KEYWORDS: Carotid artery; Atherosclerosis; Intima-media thickness; Cerebral ischemic stroke.

[Association of PAI-1 gene polymorphism with prognosis of coronary artery disease].

OBJECTIVE: To investigate the association of the 4G/5G polymorphism located in the promoter region of plasminogen activator inhibitor-1(PAI-1) gene with prognosis of coronary artery disease (CAD) in Chinese Hans. METHODS: One hundred and fifty five patients with CAD and 190 unrelated healthy control individuals were included in the study. The 4G/5G polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A follow-up survey of major adverse cardiovascular event (MACE) and analysis of the relationship between the severity of coronary vessels and PAI-1 gene polymorphism were carried out. RESULTS: (1) The frequency of 4G/4G genotype of PAI-1 gene was higher in CAD patients than in controls (58/155, 37.42% vs 52/190, 27.37%, P< 0.01). (2) The frequency of 4G/4G genotype of PAI-1 in patients with MACE was higher than that in patients without MACE (40/81, 49.38% vs 18/74, 23.42%; P< 0.01). (3) The frequency of 4G/4G genotype in patients with multivessel disease was higher than that in patients with single-vessel disease (30/47, 44.77% vs 9/37, 24.32%; P< 0.05). CONCLUSION: The 4G/5G polymorphism located in the promoter region of PAI-1 gene was associated with prognosis of CAD patients, and may be regarded as a biomarker of the severity of the involved vessels.

[Association between angiotensin-converting enzyme and endothelial nitric oxide synthase gene polymorphism and risk of coronary artery disease].

OBJECTIVE: To observe the association between angiotensin-converting enzyme (ACE) gene polymorphism and endothelial nitric oxide synthase (eNOS) gene polymorphism and risk of coronary artery disease (CAD) in Han Chinese. METHODS: The polymorphism in the ACE and eNOS gene were detected by using polymerase chain reaction-restriction fragment length polymorphism analysis, blood pressure (BP), blood lipids, blood glucose (BS), body mass index (BMI) and left ventricle eject fraction (LVEF) were determined 236 patients with CAD and 190 healthy individuals. RESULTS: The frequencies of DD genotype of ACE were higher and the II genotype were lower in CAD patients than in controls (P < 0.05). CAD patients with DD genotypes were related with higher serum TG, lower HDL-C, higher BS levels, higher BWI and lower LVEF compared to CAD patients with II and ID genotypes of ACE (all P < 0.05), while SBP, DBP, TC and LDL-C levels were similar among CAD patients and controls with different genotypes of ACE (P > 0.05). The genotype distributions of ACE and eNOS were also similar among CAD patients with or without diabetes mellitus/ACS, with single or multiple vessel diseases (P > 0.05). The frequency of GT genotype of eNOS was higher in CAD patients than in controls (P < 0.01) while the frequency of GG genotype in CAD patients and controls was similar (P > 0.05) and eNOS genotypes were not related to TC, TG, HDL-C, LDL-C, BS, BMI, SBP, DBP and LVEF levels among CAD patients and controls (P > 0.05). The risk of suffering from CAD in population with ACE DD genotype is 1.74 times higher than that with II genotype (P < 0.01) and 1.73 times higher in population with eNOS GT genotype than that with GT genotype (P < 0.05). The risk of suffering from CAD is 37.9% with II and GG genotypes and 77.8% with DD and GT genotypes. CONCLUSION: The ACE and eNOS genotype polymorphisms were associated with risk of CAD and persons with DD and GT genotypes take higher risk of suffering from CAD.