Does Hemodilution by the Crystalloid Priming Solution Derange the Efficacy of Anticoagulation During Cardiopulmonary Bypass?

BACKGROUND AND AIM: Recent studies suggest the development of a procoagulant state with hemodilution. We conducted this study to investigate the effect of hemodilution, by the priming solution in a cardiopulmonary bypass (CPB) circuit, on "point of care" coagulation assays (activated clotting time [ACT] and thromboelastography [TEG]). METHODS: Twenty patients undergoing cardiac surgery with crystalloid priming of CPB circuit were evaluated. Confounding variables arising from contact activation were eliminated by minor modifications. Ten milliliter per kilogram body weight of priming solution (lactated Ringer's) was infused via the aortic cannula. ACT and TEG were performed, both prior to and immediately after hemodilution. In case of latter, four variables, reaction time (r), coagulation time (k), maximum amplitude (MA), and clot formation rate (angle alpha), were estimated and considered for the results. To see if these results are duplicated "in vitro," prebypass blood samples from eight heparinized patients, diluted (4:1) with priming solution from the venous reservoir, were also analyzed. RESULTS: Falls in ACT, from a mean of 659.7 (+/-260.6) seconds to 251.5 (+/-103.2) seconds (p < 0.01), r time (678.1 [+/-318.1] sec to 468.7 [+/-152.7] sec) (p < 0.01), and k time (211.7 [+/-161.7] sec to 123.8 [+/-32.1] sec) (p < 0.05) on TEG were noted upon hemodilution. Angle alpha and MA increased, but were not statistically significant. Results from the in vitro study closely matched the results from our in vivo analysis. CONCLUSION: The study suggests that hemodilution by crystalloid priming solution may impair the efficacy of anticoagulation during CPB. The mechanism for this phenomenon remains to be elucidated.     

Delayed Presentation of Iatrogenic Left Ventricular Pseudoaneurysm

Abstract Occurrence of left ventricular aneurysm outside the realm of ischemic heart disease is uncommon and one following an iatrogenic trauma is very rare. We describe one such case of left ventricular pseudoaneurysm developing following pericardiocentesis and presenting one year after the procedure, and its successful surgical management . (J Card Surg 2010;25:284‐287)     

Should barium enema be the next step following an incomplete colonoscopy?

Introduction  

Double contrast barium enema (DCBE) is used to screen and diagnose colorectal disease and is often recommended following an incomplete colonoscopy. The purpose of this study was to determine the value of DCBE following an incomplete colonoscopy.     

Two new species of Myxobolus (Myxozoa: Myxosporea: Bivalvulida) infecting Indian freshwater fishes in Punjab Wetlands (India)

A survey of parasites of freshwater fishes in Harike and Ropar Wetlands of Punjab (India) revealed the presence of two new myxosporean species belonging to the genus Myxobolus Butschli 1882. Spores of the first species, M. duodenalis sp. nov. parasitize the inner wall of the duodenum of Wallago attu (Bloch and Schneider) (Cypriniformis: Cyprinidae) vern. mulli are characterized by a broad, pyriform shape with a blunt anterior end and measures 9.0 × 3.20 μm. Spore valves are thin, smooth, and symmetrical with no parietal folds. There are two polar capsules, prominently unequal and pyriform in shape, with a narrow anterior end and a rounded posterior end. The larger polar capsule measures 4.70 × 1.76 μm and the smaller 2.76 × 1.06 μm. The larger polar capsule occupies more than half, while the smaller one occupies one third of the spore body cavity. An intercapsular process is absent. Spores of the second species, Myxobolus patialensis sp. nov. parasitize the caudal fin of Labeo rohita (Ham. 1822) (Cypriniformis: Cyprinidae) vern. rohu are pyriform in valvular view, measuring 11.28 × 6.67 μm. The two shell valves are asymmetrical and contain five parietal folds along the posterior end of the spore. Two anteriorly situated polar capsules, elongated and oval in shape are prominently unequal in size. The larger polar capsule measures 4.8 × 3.1 μm and smaller one 1.70 × 1.51 μm. The larger polar capsule lies obliquely to the spore axis and the smaller one is at the same level but pointing outward anteriolaterally. An intercapsular process is absent. This species is characterized by having a prominent ridge on the shell surface anteriolaterally on the side of the smaller polar capsule.     

Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles

Although gain of chromosome 5p is one of the most frequent DNA copy-number imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its selection remain poorly understood. In a previous cross-sectional clinical study, we showed that the microRNA processor Drosha (located on chromosome 5p) demonstrates frequent copy-number gain and overexpression in cervical SCC, associated with altered microRNA profiles. Here, we have conducted gene depletion/overexpression experiments to demonstrate the functional significance of up-regulated Drosha in cervical SCC cells. Drosha depletion by RNA interference (RNAi) produced significant, specific reductions in cell motility/invasiveness in vitro, with a silent RNAi-resistant Drosha mutation providing phenotype rescue. Unsupervised hierarchical clustering following global profiling of 319 microRNAs in 18 cervical SCC cell line specimens generated two groups according to Drosha expression levels. Altering Drosha levels in individual SCC lines changed the group into which the cells clustered, with gene depletion effects being rescued by the RNAi-resistant mutation. Forty-five microRNAs showed significant differential expression between the groups, including four of 14 that were differentially expressed in association with Drosha levels in clinical samples. miR-31 up-regulation in Drosha-overexpressing samples/cell lines was the highest-ranked change (by adjusted p value) in both analyses, an observation validated by northern blotting. These functional data support the role of Drosha as an oncogene in cervical SCC, by affecting expression of cancer-associated microRNAs that have the potential to regulate numerous protein-coding genes.     

64 Slice multi-detector row cardiac CT

Cardiac imaging is feasible with multi-detector row (MDCT) scanners. Coronary arterial anatomy and both non-calcified and calcified plaques are depicted at CT coronary angiography. Vessel wall pathology and luminal diameter are depicted, and secondary myocardial changes may also be seen. Diagnostic capacity has increased with technological advancement, and preliminary investigations confirm the utility of 64-MDCT in low- and intermediate-risk patients who present to the emergency department with acute chest pain. The clinical indications, 64-MDCT technique, and MDCT findings in coronary artery disease are reviewed.     

Gated cardiac imaging of the aortic valve on 64-slice multidetector row computed tomography: preliminary observations

PURPOSE: To conduct a pilot study to determine the feasibility of evaluating aortic valve morphology and motion on electrocardiogram-gated 64-slice cardiac MDCT. METHODS: Four-dimensional images of the aortic valve were reviewed in 20 consecutive patients who underwent computed tomography (CT) coronary angiography. A consensus reading of 3 readers was performed of valve visibility, number of leaflets, valve motion, and calcification. Visibility of the valve leaflets and visualization of opening and closing of the valve leaflets were graded as well seen or suboptimally seen. The number of valve leaflets (3 or 2) and presence of valvular calcification were noted. RESULTS: The aortic valve was well seen in all 20 patients. Three leaflets were identified in all cases, and no calcifications were seen. Valve movement with opening and closure of the leaflets during the cardiac cycle was also well seen in all cases. CONCLUSIONS: Visualization of the aortic valve and valvular motion during the cardiac cycle is feasible on CT studies performed for coronary angiography. CT has a potential role in the assessment of aortic valvular pathology.     

Prostaglandin E2 Receptor,EP3, Is Induced in Diabetic Islets and Negatively Regulates Glucose- and Hormone-Stimulated Insulin Secretion

BTBR mice develop severe diabetes in response to genetically induced obesity due to a failure of the β-cells to compensate for peripheral insulin resistance. In analyzing BTBR islet gene expression patterns, we observed that Pgter3, the gene for the prostaglandin E receptor 3 (EP3), was upregulated with diabetes. The EP3 receptor is stimulated by prostaglandin E₂ (PGE₂) and couples to G-proteins of the G_i subfamily to decrease intracellular cAMP, blunting glucose-stimulated insulin secretion (GSIS). Also upregulated were several genes involved in the synthesis of PGE₂. We hypothesized that increased signaling through EP3 might be coincident with the development of diabetes and contribute to β-cell dysfunction. We confirmed that the PGE₂-to-EP3 signaling pathway was active in islets from confirmed diabetic BTBR mice and human cadaveric donors, with increased EP3 expression, PGE₂ production, and function of EP3 agonists and antagonists to modulate cAMP production and GSIS. We also analyzed the impact of EP3 receptor activation on signaling through the glucagon-like peptide (GLP)-1 receptor. We demonstrated that EP3 agonists antagonize GLP-1 signaling, decreasing the maximal effect that GLP-1 can elicit on cAMP production and GSIS. Taken together, our results identify EP3 as a new therapeutic target for β-cell dysfunction in T2D.Signaling through G-protein–coupled receptors (GPCRs) on β-cells modulates the effects of glucose and other nutrients on β-cell function. The most studied GPCR of relevance to type 2 diabetes (T2D) is the glucagon-like peptide 1 (GLP-1) receptor. It is coupled to a stimulatory G-protein, G_s, which activates adenylate cyclase, increasing cAMP production and potentiating glucose-stimulated insulin secretion (GSIS) (1). Agents that stabilize or mimic GLP-1 are now widely used in the treatment of T2D (2). Not all patients respond to these treatments (3–5), raising the possibility that endogenous negative regulatory pathways suppress full GLP-1 action.The BTBR mouse strain, when made obese with the leptin^ob/ob mutation, is highly susceptible to diabetes (6). We previously profiled gene expression in multiple tissues, including pancreatic islets, of lean and obese BTBR mice before and after the onset of diabetes (7). Ptger3 expression was markedly elevated in islets from BTBR mice after the onset of diabetes. Ptger3 encodes a GPCR for prostaglandin (PG)E2, termed prostaglandin E receptor 3 (EP3), the only one of four PGE₂ receptors that couples to G-proteins of the G_i subfamily, all of which negatively regulate cAMP production (8). We confirmed increased Ptger3 expression by quantitative real-time (qRT) PCR, and further, we explored the expression patterns of genes in the synthetic pathway of PGE₂, the endogenous ligand for EP3. Interestingly, several PGE₂ synthetic genes, including prostaglandin-endoperoxidase synthase 2 (Ptgs2, i.e., cyclooxygenase-2 or COX-2) and prostaglandin E synthase (Ptges) were also upregulated, correlating with increased PGE₂ production in pancreatic islets from both diabetic mice and humans. We hypothesized that increased PGE₂ production, coupled with increased EP3 receptor expression, mediates a negative autocrine/paracrine signaling pathway in diabetic islets. Our results identify a mechanism by which this pathway antagonizes therapeutic agents that act through GLP-1 and suggest that this pathway contributes to the β-cell dysfunction of T2D patients.