Influence of aortic elastic properties on pulse pressure changes induced by rapid ventricular pacing

The mechanism of aortic pulse pressure decline induced by acute rapid ventricular pacing remains incompletely understood. It has been ascribed to changes in stroke volume or aortic compliance. This becomes more complicated by the dependence of aortic compliance on the level of the mean aortic pressure as well as the aortic wall properties. To test the role of such mechanical factors, aortic pressure-diameter hemodynamics, derived from simultaneous tip-micromanometer aortic pressure recordings and high-fidelity ultrasonic intravascular aortic diameter recordings, were measured in 15 normal subjects during and after abrupt cessation of rapid ventricular pacing (up to 160 bpm). Immediately after terminating the pacing, diastolic aortic pressure declined (–9%, from 87.4±1.2 to 79.5±1.7 mmHg,P<0.0001) while systolic aortic pressure increased (+19%, from 109.5±1.6 to 130.1±2.8 mmHg,P<0.0001). Thus, pulse pressure increased from 22.1±2.2 to 50.6±3.1 mmHg,P<0.0001. To quantify systolic and diastolic aortic pressure differences we compared the first postpaced beat (a) and the last paced beat (b). To estimate what the aortic pressure would have been for the paced beats had the aortic diameter differences due to the different heart rate not occurred we calculated the theoretical pressure of the paced beat P_b=E_b·D_a, where E_b was the instantaneous aortic elastance of the paced beat and D_a was the aortic diameter for the postpaced beat. The corrected pressure difference was then calculated by the following: P_cor=(D_a·E_b)–P_a. It was found that systolic P_cor was 25% of systolic P_raw and diastolic P_cor was 89% of diastolic P_raw. P_raw was the pressure difference between paced and spontaneous beat measured from the raw data. P_cor indicates the portion of P_raw that results from a change in aortic stiffness as a consequence of viscous behavior or aorto-ventricular coupling. These data indicate that the majority of diastolic pressure decline after pacing was terminated, may reflect a change in aortic stiffness while the majority of systolic pressure rise, and may be attributable to differences in hemodynamics alone.     

Hypercoagulable States in Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) patients have an increased risk for venous thromboembolism, mainly portal venous thrombosis (PVT). The aim of this study was to assess the role of acquired and hereditary thrombotic risk factors in HCC patients. Thirty-one patients with HCC, 30 patients with cirrhosis but without HCC or PVT, and 48 matched healthy controls were studied. Mean levels of plasma protein C, protein S, antithrombin, and serum lipoprotein (a) were significantly lower in patients with HCC and in the cirrhotic group compared to the healthy controls. Mean serum homocysteine levels were significantly higher in patients with HCC compared to cirrhotics and healthy controls. The prevalence of activated protein C resistance, factor V Leiden mutation, prothrombin gene mutation G20210GA, and C677T methylenetetrahydrofolate reductase polymorphism was not significantly different among the three groups. In conclusion, thrombophilic defects are common in HCC patients and they might contribute to the observed thrombotic complications in this malignancy.     

Melanin-concentrating hormone receptor 1 activates extracellular signal-regulated kinase and synergizes with G(s)-coupled pathways

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays a key role in energy homeostasis. Like many neuropeptides, it signals through two G protein-coupled receptors. MCH receptor 1 (MCHR1) is the sole receptor expressed in rodents and couples to G(i) and G(q) proteins. Little is known about the intracellular pathways engaged by MCH and its receptor. Using HEK293 cells stably expressing MCHR1, we demonstrate that MCH, acting through MCHR1, antagonizes the action of forskolin, an adenylate cyclase activator that increases intracellular levels of cAMP. MCH also inhibits cAMP induction by the G(s)-coupled beta-adrenergic receptor. Activation of either the G(i)- or G(s)-dependent pathway typically results in ERK phosphorylation in HEK293 cells. In contrast to opposing actions on cAMP synthesis, simultaneous MCH and forskolin treatment results in synergistic activation of ERK. This synergy proceeds through pertussis toxin-independent pathways and requires several enzymatic activities such as protein kinase A, protein kinase C, phospholipase C, and Src kinase. Finally, we provide evidence that such positive interactions are not limited to cell lines but can also be observed in the brain.     

Hemodynamics of Stent Implantation Procedures in Coronary Bifurcations: An <Emphasis Type="Italic">In Vitro</Emphasis> Study

Stent implantation in coronary bifurcations presents unique challenges and currently there is no universally accepted stent deployment approach. Despite clinical and computational studies, the effect of each stent implantation method on the coronary artery hemodynamics is not well understood. In this study the hemodynamics of stented coronary bifurcations under pulsatile flow conditions were investigated experimentally. Three implantation methods, provisional side branch (PSB), culotte (CUL), and crush (CRU), were investigated using time-resolved particle image velocimetry to measure the velocity fields. Subsequently, hemodynamic parameters including wall shear stress, oscillatory shear index (OSI), and relative residence time (RRT) were calculated. The pressure field through the vessel was non-invasively quantified and pressure wave speeds were computed. The effects of each stented case were evaluated and compared against an un-stented case. CRU provided the lowest compliance mismatch, but demonstrated detrimental stent interactions. PSB, the clinically preferred method, and CUL maintained many normal flow conditions. However, PSB provided about a 300% increase in both OSI and RRT. CUL yielded a 10 and 85% increase in OSI and RRT, respectively. The results of this study support the concept that different bifurcation stenting techniques result in hemodynamic environments that deviate from that of un-stented bifurcations, to varying degrees.     

ST-segment depression during vasodilator stress is of minor clinical importance in women with normal myocardial perfusion imaging and low or intermediate risk of coronary artery disease

Purpose  

The prognostic value of electrocardiographic (ECG) ST-segment depression during vasodilator stress testing in patients with normal myocardial perfusion scintigraphy (MPS) is based on retrospective studies with controversial results. Moreover, the true incidence of obstructive coronary artery disease (CAD) in these patients is unknown.     

Perineal rectosigmoidectomy for gangrenous rectal prolapse

Incarceration rarely complicates the chronically progressive form of the full thickness rectal prolapse.Even more rarely,it becomes strangulated,necessitating emergency surgery.We describe an extremely rare case of incarcerated acute rectal prolapse,without a relevant previous history or symptoms of predisposing pathology.The patient underwent emergency perineal proctosigmoidectomy,the Altemeier operation,combined with diverting loop sigmoid colostomy.The postoperative course was quite uneventful with an ex...     

Differences in the suppression of distortion product otoacoustic emissions by contralateral white noise between patients with acute or chronic tinnitus

Objective: The mechanisms underlying the shift from acute tinnitus to chronic remain obscure. An association between tinnitus and medial olivocochlear bundle (MOCB) reflex dysfunction has been hypothesised by several studies. The differences between participants with acute and chronic tinnitus have not yet been investigated. Design: Participants were examined with distortion product otoacoustic emissions (DPOAEs) suppression elicited by contralateral white noise. They were compared in terms of frequency regions with non-recordable DPOAEs, suppression amplitudes and the presence of DPOAE enhancement. Study sample: Eighteen participants with acute tinnitus, 40 age-matched adults with chronic tinnitus and 17 controls were included. All participants (aged 34.7?±?9.6years; mean?±?Standard deviation) had normal hearing. Tinnitus was bilateral in 22 participants and unilateral in 36. Results: Ears with chronic tinnitus presented significantly lower DPOAE suppression amplitudes than ears with acute tinnitus (p?p?p?=?0.0002, respectively). Non-recordable DPOAEs were significantly more frequent in the chronic than in the acute tinnitus and control groups (p?Conclusions: The differences between study groups indicate that when tinnitus becomes chronic, DPOAEs suppression presents changes that might reveal corresponding steps in tinnitus pathophysiology. Treatment implications are discussed.     

Anticoagulation for atrial fibrillation in active cancer

Atrial fibrillation (AF) may often pre-exist in patients with newly diagnosed cancer or occur with increased frequency shortly after cancer diagnosis. Patients with active cancer and AF have a particularly high risk of thromboembolic complications, as both conditions carry a risk of thrombosis. Thromboembolic risk is determined by several factors, including advanced age, sex (females), cancer histology (adenocarcinomas), location (e.g., pancreas, stomach), advanced stage, anticancer regimens (e.g., platinum compounds, anti-angiogenic therapies, immune modulators), comorbidities (e.g., obesity, kidney disease) and concurrent therapies (e.g., surgery, central catheters). Physicians are often reluctant to prescribe anticoagulants to patients with active cancer and AF, mainly due to fear of bleeding complications, which is partly related to the paucity of evidence in the field. Decision making regarding anticoagulation for the prevention of ischemic stroke and systemic embolism in patients with active cancer and AF may be challenging and should not simply rely on the risk prediction scores used in the general AF population. By contrast, the administration and choice of anticoagulants should be based on the comprehensive, individualized and periodic evaluation of thromboembolic and bleeding risk, drug-drug interactions, patient preferences and access to therapies.     

Increased serum CA-15.3 levels in patients with megaloblastic anemia due to vitamin B12 deficiency

OBJECTIVES: To estimate the usefulness of serum tumor markers' monitoring, as predictors of gastric cancer in patients with pernicious anemia. PATIENTS AND METHODS: We investigated serum levels of carcinoembryonic antigen (CEA), alpha-fetal protein, cancer antigen (CA)-19.9, CA-125 and CA-15.3 in 50 patients with pernicious anemia and in 24 healthy controls, matched for age and sex. In 38 patients, the evaluation was repeated 1-6 months after the correction of cobalamin deficiency. RESULTS: All patients and controls had normal serum CEA and alpha-FP, and the levels of these markers as well as those of CA-125 and CA-19.9 did not differ between the two groups. All 50 patients, but only 2 controls exhibited increased serum CA-15.3, and the difference between the two groups was very significant (129.4 +/- 84.9 vs. 19.8 +/- 7.3 IU/ml, p < 0.001), while no difference between males and females was found. A thorough clinical examination of all patients, and mammographic study in 18 females did not reveal any finding suspicious of breast cancer. CA-15.3 levels were positively correlated with serum lactate dehydrogenase, and negatively with B(12) and hemoglobin, but they were substantially decreased after the correction of anemia, in all 38 patients tested, and in 33 of them they were restored to normal. After a median follow-up of 34 months, one patient developed a colon cancer, but none showed any sign suspicious of breast cancer. CONCLUSIONS: Serum CA-15.3 shows an aberrant increase in untreated patients with pernicious anemia, which is reversed after the correction of the anemia. The possible origin seems unrelated to mammary tissue, and may be released by the apoptosing bone marrow megaloblastic erythroblasts.