A rapid method for microarray cross platform comparisons using gene expression signatures

Microarray technology has become highly valuable for identifying complex changes in global gene expression patterns. The inevitable use of a variety of different platforms has compounded the difficulty of effectively comparing data between projects, laboratories, and public access databases. The need for consistent, believable results across platforms is fundamental and methods for comparing results across platforms should be as straightforward as possible. We present the results of a study comparing three major, commercially available, microarray platforms (Affymetrix, Agilent, and Illumina). Concordance estimates between platforms was based on mapping of probes to Human Gene Organization (HUGO) gene names. Appropriate data normalization procedures were applied to each dataset followed by the generation of lists of regulated genes using a common significance threshold for all three platforms. As expected, concordance measured by directly comparing gene lists was relatively low (an average 22.8% for all platforms across all possible comparisons). However, when statistical tests (gene set enrichment analysis--GSEA, parametric analysis of gene enrichment--PAGE) which align gene lists with continuous measures of differential gene expression were applied to the cross platform datasets using significant gene lists to poll entire datasets, the relatedness of the results from all three platforms was specific, obvious, and profound.     

Doppler Assessment of Hepatic Venous Waves for Predicting Large Varices in Cirrhotic Patients

Background/Aim:

Color Doppler examination of changes in hepatic venous waveforms is being evaluated as a means of prediction of severity of portal hypertension and presence of esophageal varices. Normal hepatic venous waveform shows a triphasic pattern. In cirrhosis, this pattern changes to a biphasic or monophasic pattern. We aimed to study the sensitivity of loss of normal hepatic venous waveforms in predicting large varices in a cross-sectional analysis.

Materials and Methods:

All patients, admitted or attending the outpatient department, with a diagnosis of cirrhosis were included in the study. All patients were subjected to oesophagogastroduodenoscopy and Color Doppler examination, and waveform patterns in hepatic vein were recorded. The sensitivity and specificity of changes in waveform in detecting large varices were studied.

Results:

A total of 51 cases were examined. Triphasic waves were seen in 4 (7.8%) cases, biphasic in 26 (51%) cases, and monophasic in 21 (41.2%) cases. Small varices were seen in 30 (58.8%) cases and large varices in 21 (41.2%) cases. The sensitivity of loss of the triphasic wave pattern in detecting significant varices (Grade 3 or 4) was very high (95.23%) and negative predictive value was also high (75%). Severity of liver disease as indicated by Child-Pugh and MELD scores did not correlate with changes in hepatic venous waveforms.

Conclusion:

Loss of triphasic hepatic venous waveform is highly sensitive in predicting significant varices in patients with cirrhosis.     

A floating right heart thrombus in transit across tricuspid valve causing an endocardial friction rub

We report a 42-year-old lady on combined oral contraceptive pills with deep venous thrombosis and mild pulmonary embolism, who developed shock, while being treated with heparin. On auscultation, there was an unexpected loud, superficial, squeaky, triphasic friction rub over the left lower parasternal area. Simultaneous echocardiogram revealed a large serpiginous, freely floating mass in right atrium, prolapsing freely to right ventricular inlet across the tricuspid valve. The endocardial friction rub persisted for about 24 h as long as the thrombus was intracardiac and disappeared when the thrombus disappeared from right heart, occluding the proximal left pulmonary artery. She died due to shock awaiting surgery. We highlight that such a rub in a patient with deep venous thrombosis, though rare, may be an important clue to impending pulmonary embolism.     

Immunoglobulin G-mediated regulation of the murine immune response to transfused red blood cells occurs in the absence of active immune suppression: implications for the mechanism of action of anti-D in the prevention of haemolytic disease of the fetus and newborn?

Anti-D has been widely and effectively used in Rhesus blood group D negative mothers for the prevention of haemolytic disease of the fetus and newborn; its mechanism of action however, often referred to as antibody-mediated immune suppression (AMIS), remains largely unresolved. We investigated, in a murine model, whether active immune suppression or clonal deletion mediated by anti-red blood cell (RBC) immunoglobulin G (IgG) could explain the phenomenon of AMIS. Transfusion of IgG-opsonized foreign RBCs (i.e. AMIS) strongly attenuated antibody responses compared to transfusion of untreated foreign RBCs. When the AMIS-mice were subsequently transfused with untreated RBCs, no immune suppression was observed at 5 and 35 days after AMIS induction; in fact, the mice responded to retransfusion with untreated RBCs in a manner that was characteristic of a secondary immune response. When IgG-opsonized RBCs were transfused concurrently with untreated RBCs, a dose-dependent reduction of the antibody response was observed. This work suggests that the attenuation of the antibody responsiveness by anti-RBC IgG is not associated with active immune suppression or clonal deletion at either the T-cell or B-cell level; rather, the effect appears more characteristic of B-cell unresponsiveness to IgG-opsonized RBCs. These results may have implications for the understanding of the mechanism of action of anti-D in haemolytic disease of the fetus and newborn.     

Brugada syndrome simulating acute myocardial infarction

Successful recanalisation of a chronic coronary occlusion may result in survival advantage. This report describes a 61-year-old man with an initially chronic occluded right coronary artery. A follow-up angiography 2 years later revealed a spontaneous recanalisation.     

Ultra Long Stent in an Aberrant Right Coronary Artery

The prevalence of anomalous origin of right coronary artery from the left sinus is about 0.92%. A percutaneous coronary intervention (PCI) in such a vessel is challenging especially when maneuvering long stents. We report a case of 75-year old female patient with recent acute coronary syndrome. The angiogram showed significant lesions in the left anterior descending coronary artery and the left circumflex coronary artery with an aberrant RCA originating from the left sinus close to the origin of LMCA with multiple tight lesions. The aberrant RCA was stented with a 50 mm long stent. To the best of our knowledge, the placement of such a long stent in an aberrant coronary artery has hitherto never been reported in the literature.     

Echocardiographic assessment of right ventricular function in inferior wall myocardial infarction and angiographic correlation to proximal right coronary artery stenosis

BackgroundPresence of right ventricular (RV) infarction imposes a higher risk of adverse events in inferior wall myocardial infarction (IWMI). In this study, we attempted to correlate various indices of RV function assessed by echocardiography with presence of a proximal right coronary artery (RCA) stenosis in patients with first episode of acute IWMI.MethodsIn a prospective study, patients with first episode of acute IWMI underwent echocardiographic assessment within 24 h of symptom onset and indices of RV function viz. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI) and tissue Doppler velocities from RV free wall were measured. Patients who underwent coronary angiogram (CAG) within one month and they were classified into group 1 and group 2 based on the presence or absence, respectively, of a significant proximal RCA stenosis.ResultsThere were 90 patients with first episode of IWMI of which 67 patients underwent CAG. There was significant difference between group 1 (n = 26) and group 2 (n = 41) in TAPSE (13.5 ± 1.3 vs 21.3 ± 1.7, p < 0.001), MPI by tissue Doppler (0.87 ± 0.1 vs 0.55 ± 0.2, p < 0.001) and in tissue Doppler systolic velocity from RV free wall (S′ 9.8 ± 1.1 vs 15.0 ± 1.5, p < 0.001). There was a good interobserver correlation for TAPSE, MPI by TDI, and S′ velocity. TAPSE ≤ 16 (sensitivity 93%, specificity 100%), MPI-TDI ≥ 0.69 (sensitivity 94.7%, specificity 93.5%), S ≤ 12.3 (sensitivity 90.3%, specificity 94.3%) were useful in predicting presence of proximal RCA stenosis.ConclusionRV function indices like TAPSE, MPI-TDI and S′ velocity are useful in predicting proximal RCA stenosis in first episode of acute IWMI.     

Coronary sinus filling time: A novel method to assess microcirculatory function in patients with angina and normal coronaries

ObjectiveDysfunction of the coronary microcirculation is considered as one of the factors responsible for symptoms and abnormal stress tests in patients with angina and normal coronaries (syndrome X). We sought to evaluate the usefulness of coronary sinus filling time (CSFT) to assess coronary microcirculation in this group of patients.MethodsWe compared the CSFT of patients having definite angina or atypical angina with positive treadmill electrocardiography test (angina group), with that of patients undergoing coronary angiogram (CAG) prior to balloon mitral valvuloplasty (control group). During CAG, coronary sinus was visualized in appropriate views and CSFT in seconds was derived from frame count. Thrombolysis In Myocardial Infarction (TIMI) flow grade, corrected TIMI (cTIMI) frame count, TIMI Myocardial Perfusion grade (TMP) were assessed.ResultsThere were 41 patients in angina group and 16 in control group. Among the angina group 68.8% were females as against 81.8% in the control group. 87.8% (n = 36) had typical angina. Mean CSFT was 4.25 ± 0.72 s and 3.46 ± 0.99 s in the angina group and control group respectively (p = 0.001). No significant differences were found between the groups with respect to TMP (p = 0.68) & cTIMI frame count (p = 0.22).ConclusionCSFT is a simple method to assess the transit time through coronary microcirculation. CSFT was significantly delayed in patients with angina and normal coronaries. TMP and cTIMI frame count were not significantly different between groups.