Uric Acid and Cardiovascular Events: A Mendelian Randomization Study

Obesity and diets rich in uric acid–raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiovascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid–regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.     

Obesity, inflammation, and periodontal disease

The prevalence of obesity has increased substantially over the past decades in most industrialized countries. Obesity is a systemic disease that predisposes to a variety of co-morbidities and complications that affect overall health. Cross-sectional studies suggest that obesity is also associated with oral diseases, particularly periodontal disease, and prospective studies suggest that periodontitis may be related to cardiovascular disease. The possible causal relationship between obesity and periodontitis and potential underlying biological mechanisms remain to be established; however, the adipose tissue actively secretes a variety of cytokines and hormones that are involved in inflammatory processes, pointing toward similar pathways involved in the pathophysiology of obesity, periodontitis, and related inflammatory diseases. We provide an overview of the definition and assessment of obesity and of related chronic diseases and complications that may be important in the periodontist's office. Studies that have examined the association between obesity and periodontitis are reviewed, and adipose-tissue-derived hormones and cytokines that are involved in inflammatory processes and their relationship to periodontitis are discussed. Our aim is to raise the periodontist's awareness when treating obese individuals.     

Gingival crevicular fluid levels of calprotectin and myeloperoxidase during therapy for generalized aggressive periodontitis

BACKGROUND: Levels of the inflammation marker calprotectin in gingival crevicular fluid correspond to clinical and biochemical parameters of periodontal inflammation. Neutrophil granulocytes (polymorphonuclear neutrophils: PMNs) are supposed to be the main source of calprotectin in gingival crevicular fluid, but evidence is still lacking. The influence of periodontal therapy on gingival crevicular fluid levels of calprotectin has not yet been determined. OBJECTIVES: Gingival crevicular fluid levels of calprotectin were monitored during therapy for generalized aggressive periodontitis. Interrelations between calprotectin and the PMN marker myeloperoxidase (MPO) were evaluated. MATERIAL AND METHODS: Gingival crevicular fluid samples were collected from 23 patients with generalized aggressive periodontitis before and 3 months after non-surgical therapy with an adjunctive antimicrobial medication. Clinical parameters were recorded with a pressure-calibrated electronic probe. Levels of calprotectin and MPO in gingival crevicular fluid were analysed by enzyme-linked immunosorbent assay (ELISA) procedures. RESULTS: At baseline, levels of calprotectin and MPO were highly correlated. Bleeding and suppurating sites showed significantly higher levels of calprotectin and MPO than non-bleeding, non-suppurating sites. Therapy significantly decreased levels of both biomarkers. These changes of calprotectin and MPO were highly correlated and also related to probing-depth reduction. Three months after therapy, the levels of both markers still showed significant correlations in initially deep sites, whereas in initially shallow sites no significant correlation was found. After therapy, levels of markers in bleeding and non-bleeding sites were comparable. CONCLUSION: The correlations between calprotectin and MPO indicate that PMNs are a major contributor to the calprotectin content in gingival crevicular fluid of severely affected sites. Calprotectin levels in gingival crevicular fluid and their changes reflect periodontal inflammation as well as the clinical treatment outcome. A prognostic potential of this marker substance remains to be determined.     

Indikation,Prozedere und Outcome der präklinischen Notfallthorakotomie – eine systematische Literaturrecherche

Die Unfallchirurgie - Die präklinische Notfallthorakotomie (?prehospital resuscitative thoracotomy“, PHRT) ist eine von den aktuellen Reanimationsleitlinien des European...     

Overt and imagined singing of an Italian aria

Activation maps of 16 professional classical singers were evaluated during overt singing and imagined singing of an Italian aria utilizing a sparse sampling functional magnetic imaging (fMRI) technique. Overt singing involved bilateral primary and secondary sensorimotor and auditory cortices but also areas associated with speech and language production. Activation magnitude within the gyri of Heschl (A1) was comparable in both hemispheres. Subcortical motor areas (cerebellum, thalamus, medulla and basal ganglia) were active too. Areas associated with emotional processing showed slight (anterior cingulate cortex, anterior insula) activation. Cerebral activation sites during imagined singing were centered on fronto-parietal areas and involved primary and secondary sensorimotor areas in both hemispheres. Areas processing emotions showed intense activation (ACC and bilateral insula, hippocampus and anterior temporal poles, bilateral amygdala). Imagery showed no significant activation in A1. Overt minus imagined singing revealed increased activation in cortical (bilateral primary motor; M1) and subcortical (right cerebellar hemisphere, medulla) motor as well as in sensory areas (primary somatosensory cortex, bilateral A1). Imagined minus overt singing showed enhanced activity in the medial Brodmann's area 6, the ventrolateral and medial prefrontal cortex (PFC), the anterior cingulate cortex and the inferior parietal lobe. Additionally, Wernicke's area and Brocca's area and their homologues were increasingly active during imagery. We conclude that imagined and overt singing involves partly different brain systems in professional singers with more prefrontal and limbic activation and a larger network of higher order associative functions during imagery.     

Hepatic arterial flow volume and reserve in patients with cirrhosis: use of intra-arterial Doppler and adenosine infusion

BACKGROUND & AIMS: In cirrhosis, liver blood flow becomes increasingly dependent on the hepatic artery. The aim of this study was to investigate hepatic arterial blood flow volume and resistance and hepatic arterial flow reserve in relation to liver function and systemic hemodynamic alterations in patients with cirrhosis. METHODS: In 38 patients with cirrhosis, liver function, cardiac output, and systemic vascular resistance were studied, and hepatic arterial blood flow velocity, flow volume, and pulsatility index at baseline and during intra-arterial administration of adenosine (2-40 microg. min-1. kg body wt-1) were assessed by angiography combined with intravascular Doppler flowmetry. RESULTS: Hepatic arterial flow velocity was 21 +/- 11, 31 +/- 17, and 41 +/- 27 cm/s; flow volume was 266 +/- 246, 342 +/- 289, and 417 +/- 220 mL/min; and pulsatility index was 2.2 +/- 0.7, 1.7 +/- 0.6, and 1.5 +/- 0.5 in Child-Pugh classes A, B, and C, respectively (differences not statistically significant). Adenosine-induced changes in these parameters were more marked in Child-Pugh class A (68 +/- 15 cm/s, 1246 +/- 486 mL/min, and -1.14 +/- 0.5) than in class C (45 +/- 23, P < 0.05; 704 +/- 492, P = 0.02; and -0.58 +/- 0.38, P < 0.05). Using analysis of variance, cardiac index, systemic vascular resistance, and ascites, but not Child-Pugh class, were related to baseline values and adenosine-induced changes. CONCLUSIONS: Adenosine is a potent dilator of the hepatic artery in humans. The data suggest that hepatic arterial blood flow and adenosine-dependent flow reserve in patients with cirrhosis are under systemic hemodynamic or neurohormonal control.