Clinical profile,management and outcome of pulmonary embolism in Shahid Gangalal National Heart Centre,Kathmandu, Nepal

Background and aims

Pulmonary embolism (PE) is associated with a significant mortality and morbidity. We aim to study clinical profile, management and outcome of PE at Shahid Gangalal National heart Centre, Kathmandu, Nepal.

AUF1 is upregulated by angiotensin II to destabilize cardiac Kv4.3 channel mRNA

Expression of cardiac myocyte Kv4 channels (Kv4.3 for human, Kv4.2 and Kv4.3 for rodents) is downregulated with hypertrophy in vivo leading to a decrease in the transient outward current (Ito). This effect is recapitulated in vitro with rat neonatal cardiac myocytes treated with angiotensin II (Ang II), which acts via AT₁ receptors, NADPH oxidase and p38 MAP kinase to destabilize the 3′ untranslated region (3′UTR) of the Kv4.3 channel messenger RNA (mRNA). Here deletion analysis and mutagenesis identify an AU-rich element (ARE) in the Kv4.3 3′UTR that is required for Ang II-induced destabilization. Overexpression of AUF1 (ARE/poly-(U)-binding/degradation factor 1), an RNA destabilizing protein, mimics and occludes the Ang II effect, while RNA interference targeted against AUF1 blocks the Ang II effect on the Kv4.3 3′UTR. Ang II upregulates AUF1 by activating AT₁ receptors, NADPH oxidase and p38 MAP kinase. Finally, pull-down assays establish that Ang II increases AUF1 binding to the ARE required for destabilization, while binding of the mRNA stabilizing protein HuR is unaffected. Hence, Ang II acts via AT₁ receptors, NADPH oxidase and p38 MAP kinase to upregulate AUF1, which in turn binds to an ARE in the Kv4.3 3′UTR to destabilize the channel mRNA.     

Chlamydia pneumoniae exposure and inflammatory markers in acute coronary syndrome (CIMACS)

Previous studies have shown higher levels of Chlamydia pneumoniae (C. pneumoniae, CP) antibody titers (CPIgG), C-reactive protein (CRP), and fibrinogen in patients with coronary artery disease. The role of these infectious and inflammatory markers in precipitating acute coronary syndrome (ACS) is unclear. We conducted a cross-sectional study on patients (n = 830, mean age 63 +/- 15 years, 57% male) admitted to the chest pain center of our institution. The differences in the CPIgG, CRP, and fibrinogen levels in patients who were diagnosed with ACS versus those who were not (non-ACS) were evaluated. CPIgG titers tended to be higher in the ACS group than in the non-ACS group. However, when different titers were used to define seropositivity, the difference achieved statistical significance only at the titer of > or =1:1,024 (35% vs 26%, p = 0.004). CRP (median 0.48 vs 0.33 mg/dl, p <0.0001), fibrinogen (median 317 vs 293 mg/dl, p <0.0001), and leukocyte count (median 7.7 vs 6.9 10(9)/L, p <0.0001) were higher in the ACS group. On multivariate analysis, CPIgG > or =1:1,024 (odds ratio [OR] 1.62), diabetes (OR 1.91), hypertension (OR 1.46), prior myocardial infarction (OR 1.78), smoking (OR 1.70), Caucasian race (OR 1.7), high-density lipoprotein (OR 0.98), and elevated troponin-T (OR 12.44) were the only factors independently associated with ACS. Thus, we found a strong association between high level seropositivity to CP and ACS. This may indicate recent re-infection or an exaggerated immune response to CP as an etiologic factor for ACS. This study also suggests that therapeutic interventions may need to be specifically targeted to these patients.     

Density and function of inward currents in right atrial cells from chronically fibrillating canine atria

OBJECTIVE: To determine whether I(Na) and I(CaL) are altered in function/density in right atrial (RA) cells from dogs with chronic atrial fibrillation (cAF dogs, episodes lasting at least 6 days) and whether the changes that occur differ from those in dogs with nonsustained or brief episodes of fibrillation (nAF dogs). METHODS: Using whole cell voltage clamp, sodium and calcium current density and function were determined in disaggregated RA cells from nAF, cAF and control atria (Con). Ca(2+) currents were studied with either Ca(2+) or Ba(2+) as charge carrier, as well as with either EGTA or BAPTA as the internal solution Ca(2+) chelator. RESULTS: After rapid atrial pacing, dogs can either fibrillate for short periods of time (nAF) or longer, more sustained periods (cAF). Both the Na(+) and Ca(2+) current decrease in cells of the nAF atria. Na(+) current density remains reduced in cAF cells with some slowing of recovery kinetics. Ca(2+) current density does not further decrease with persistent atrial fibrillation (cAF cells) remaining significantly different from Con cells. However, the difference in density of Ca(2+) currents between nAF and Con cells is negligible when Ba(2+) is charge carrier and when Ca(i) is quickly and effectively chelated with BAPTA. On the contrary, cAF I(BaL) densities remain significantly reduced compared to Con and nAF values when Ba(2+)/BAPTA conditions are used. CONCLUSIONS: Na(+) current density/function does not recover to Con values in cAF. Further these enhanced Ca(2+)-dependent inactivation processes contribute significantly to the reduction of I(CaL) density observed in nAF cells while reduction of Ca(2+) currents in cAF atria is probably by another mechanism     

Evaluation of Factors in Relation with the Non-Compliance to Curative Intent Radiotherapy among Patients of Head and Neck Carcinoma: A Study from the Kumaon Region of India

Introduction:

Radiotherapy (RT)-based curative regimens for head and neck squamous cell carcinomas (HNSCC) deliver a dose of 66–70 Gray (Gy) over a period of 6–7 weeks, and incomplete treatments are unlikely to result in cure. Non-compliance to RT is major contributory factor to treatment failure.

Aims:

To assess the proportion of patients who do not complete planned treatment after initiation of curative RT. This study also aims to explore a possible relationship of non-compliance due to socio-economic, disease-related and treatment-related factors.

Materials and Methods:

The records of HNSCC patients treated from January 2012–December 2013 were audited. Data from the treatment records were to collect patient-related, disease-related, and social demographic parameters. Of the patients who had not completed treatment, the reasons behind the same were investigated.

Results:

Of the 324 patients of HNSCC who were initiated on radical RT, a total of 76 patients were found to have discontinued treatment without authorization of the treating clinician. There was no significant predilection for treatment non-compliance with regards to patient age, educational status, religion, site of the disease, use of neoadjuvant chemotherapy, or use of concurrent chemotherapy. There tended to be a higher association of treatment non-compliance among patients residing >100 km away from the treatment center, patients hailing from hilly regions, patients without the below poverty line (BPL) card, unemployed patients, and patients with stage IV-A/B disease. Of the 76 patients who did not complete treatment, telephonic questionnaire could be obtained from 54 patients. Causes for non-compliance included preference for traditional healers (22.2%), fear of toxicity (7.4%), logistic reasons (18.5%), financial reasons (24.1%), and lack of interest/faith in RT (5.6%).

Conclusion:

There is a high incidence of treatment default among patients of HNSCC during RT in this region. The revelation of the higher propensity for treatment default among patients from distant, hilly regions, unemployed, patients without BPL cards, and stages-IVA/IVB highlights the need for specific interventions for these special populations.     

Phytoplankton nutrient dynamics and flow cytometry based population study of a eutrophic wetland habitat in eastern India,a Ramsar site

Phytoplankton diversity, their abundance based on flow cytometric (FCM) analysis and seasonal nutrient dynamics were investigated from a waste water fed wetland of Eastern India (88° 24.641′E and 22° 33.115′N). The primary objective of the study was to correlate the seasonal fluctuations in phytoplankton abundance to the environmental variables. Total chlorophyll content and FCM based cell counts were used to characterize and quantify the phytoplankton population. Multivariate statistical methods were employed in predicting the possible relationships between biotic and abiotic variables. Distinct seasonal variations characterized by high abundance during the pre-summer period compared to other seasons were detected. The results indicated that environmental factors like water temperature and nutrients, such as various forms of nitrogen and phosphate, influenced the seasonal phytoplankton accumulation. Cluster analysis and non-metric multidimensional scaling helped analyze the seasonal distribution of phytoplankton based on their composition. The dominant genera among the entire phytoplankton community were Scenedesmus spp. of Chlorophyta, followed by Merismopedia spp. of Cyanoprokaryota. Around 3.7 × 10⁵ phytoplankton mL⁻¹ were recorded during the study period. Due to the very high count of individual species in the community, FCM based counting was applied for determination of Species Diversity Index. The entire population was divided into 13 subpopulations based on the cell sorting method and the seasonal abundance in each sub-population was illustrated.

Phytoplankton diversity, their abundance based on flow cytometric (FCM) analysis and seasonal nutrient dynamics were investigated from a waste water fed wetland of Eastern India (88° 24.641′E and 22° 33.115′N).     

Diastolic Assessment: Application of the New ASE Guidelines

Purpose of Review

The purpose of this review is to summarize the new guidelines from the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) for the diagnosis and grading of diastolic dysfunction (DD), with commentary on the rationale behind the use of the recommended individual parameters.

Recent Findings

Previous guidelines for assessment of diastolic function have been criticized for being too complex with modest diagnostic performance and inter-observer variability.

Summary

The new ASE/EACVI diastology guidelines aim to simplify the diagnosis and gradation of DD by using a limited set of echocardiographic variables. The robustness of these recommendations has been subsequently validated in several trials. Understanding the physiological principles that govern changes in echocardiographic parameters during normal and abnormal diastolic function is critical for the appropriate application of these recommendations.