Myocardial Perfusion Scan Study before and after On-Pump Coronary Artery Bypass Grafting Surgery - A Single-Center Study.

Aim: Ischemic cardiac disease is the most common adult heart disease. The primary aim of the study was to analyze the myocardial perfusion status of the patients undergoing coronary artery bypass graft using sestamibi scan and assess the improvement in perfusion status of the myocardium after the surgery. Materials and Methods: This study was a descriptive study consisting of a single group of patients undergoing elective surgery for coronary artery disease. The patients underwent myocardial perfusion scan before surgery. Another myocardial perfusion scan was performed 3 months after the surgery. The change in myocardial perfusion status was analyzed. Results: Totally, 49 patients were initially included in this study. Seven patients lost their follow-up. Among the 17 patients who had severely reduced tracer uptake preoperatively, 3 (7.1%) had a good outcome, while 14 (33.3%) had a poor outcome, which was statistically significant (P < 0.001). Eighteen cases who belonged to the category of moderately reduced tracer uptake while analyzed, it was found that 16 (38.1%) had a good outcome while only 2 (4.8%) had a poor outcome; the difference in proportion among these two groups was statistically significant (P < 0.001). The patients who had mildly reduced tracer uptake preoperatively, all 3 (7.1%) had a good outcome, but it was not statistically significant (P = 0.23). Four patients had adequate tracer uptake preoperatively, out of which 3 (7.1%) had a good outcome, while the other 1 (2.4%) had a poor outcome and was not statistically significant (P = 0.63). Conclusion: Surgical revascularization improves perfusion in a selective group of patients.

Step-by-Step Guide for Synthesis and Delamination of Ti3 C2 Tx MXene.

To advance the MXene field, it is crucial to optimize each step of the synthesis process and create a detailed, systematic guide for synthesizing high-quality MXene that can be consistently reproduced. In this study, a detailed guide is provided for an optimized synthesis of titanium carbide (Ti3 C2 Tx ) MXene using a mixture of hydrofluoric and hydrochloric acids for the selective etching of the stoichimetric-Ti3 AlC2 MAX phase and delamination of the etched multilayered Ti3 C2 Tx MXene using lithium chloride at 65 °C for 1 h with argon bubbling. The effect of different synthesis variables is investigated, including the stoichiometry of the mixed powders to synthesize Ti3 AlC2 , pre-etch impurity removal conditions, selective etching, storage, and drying of MXene multilayer powder, and the subsequent delamination conditions. The synthesis yield and the MXene film electrical conductivity are used as the two parameters to evaluate the MXene quality. Also the MXenes are characterized with scanning electron microscopy, x-ray diffraction, atomic force microscopy, and ellipsometry. The Ti3 C2 Tx film made via the optimized method shows electrical conductivity as high as ≈21,000 S/cm with a synthesis yield of up to 38 %. A detailed protocol is also provided for the Ti3 C2 Tx MXene synthesis as the supporting information for this study.

Influence of CYP2C9 Polymorphisms on Plasma Concentration of Warfarin and 7-Hydroxy Warfarin in South Indian Patients.

BACKGROUND: Warfarin is primarily metabolized by cytochrome P450 2C9 (CYP2C9) enzyme, which is encoded by the CYP2C9 gene. CYP2C9*2 and CYP2C9*3 variants significantly influence warfarin metabolism and subsequently the required dose of warfarin. OBJECTIVES: The current retrospective study was aimed to determine the influence of CYP2C9 variants on warfarin metabolic ratio (MR, warfarin/7-hydroxy warfarin) and warfarin maintenance therapy in 210 patients (mean age 44.6±11.6 (SD) years; male to female ratio 81:129). METHODS: High-performance liquid chromatography (HPLC) with UV detector was used to measure plasma concentrations of warfarin and 7-hydroxy warfarin. Plasma samples were collected 12 h after the previous dose of warfarin was administered. CYP2C9 variants (rs1799853 and rs1057910) were identified using real-time polymerase chain reaction allele-discrimination method. RESULTS: The mean daily maintenance dose of warfarin was 4.6±1.8 (SD) mg. The mean plasma warfarin and 7-hydroxy warfarin concentrations were 3.7±1.6 (SD) µg/mL and 1.1±0.54 (SD) µg/mL, respectively. Patients carrying other CYP2C9 variants required 39% lower warfarin maintenance dose 3.3±1.2(SD)mg than CYP2C9*1*1 carrier 4.9±1.8(SD)mg, (p<0.0001). MRs differed significantly between CYP2C9 variant carriers (8.1±5.1) and normal genotype carriers (4.8±3.9) (p<0.0001). Probit analysis identified an MR value of 7.6 as the anti-mode (sensitivity of 84% and specificity of 55%) to differentiate poor and intermediate metabolizers (carriers of any CYP2C9*2 or CYP2C9*3 variants) from normal metabolizers (CYP2C9*1*1 genotype). CONCLUSION: The present study results provide, insights on the effect of CYP2C9 genetic polymorphisms on inter-individual variability in warfarin metabolism and emphasizes utility of phenotyping in a setting of genotype-guided dosing of warfarin in South Indian population.

Periodontal ligament cells in adolescents and adults: Genetic level responses to orthodontic forces.

INTRODUCTION: Periodontal ligament cells (PDLC) respond to the application of mechanical forces by releasing various molecules that participate in bone remodeling. Whether these cellular reactions take place at the same rate in adolescent and adult patients is not known. In this study, we aimed to evaluate differences in genetic expression, if any, between the release of various inflammatory mediators from PDLC in adolescent and adult patients before and after the application of orthodontic forces. METHODS: Forty subjects with bimaxillary dentoalveolar protrusion requiring extraction of first premolars for orthodontic treatment were selected and divided into 2 groups. Group A included 20 adolescents (aged 12-20 years), and group B included 20 adults (aged 35-50 years). Then, 35-50 g of force were applied to the maxillary first premolars, and teeth were extracted at different periods: pretreatment (control group), 7 days, 14 days, and 28 days (experimental group). The periodontal ligament was scraped from the middle third of the root, and the beta-galactosidase assay was performed in the control group. RNA extraction, DNase treatment, quantitative polymerase chain reaction, and complementary DNA synthesis were performed in the experimental group. RESULTS: Adult PDLC exhibited senescent changes through increased beta-galactosidase activity. The increase in the inflammatory response and bone resorption in adult patients was evident by increased prostaglandin E2, IL1B, and acid phosphatase mRNA expression levels. Controlled bone formation response by adolescent PDLC was evident from increased ALP and BGLAP mRNA levels and a balanced receptor activator of nuclear factor kappa-Β ligand/OPG ratio. CONCLUSIONS: The study could identify the reasons behind the differential response of adolescent and adult PDLC to orthodontic mechanics.

Relationship between transesophageal echocardiography-derived pulmonary artery systolic pressure measurements and early morbidity in patients undergoing coronary artery bypass grafting.

Context: We studied the relationship between intraoperative transesophageal echocardiography-derived (TEE-derived) pulmonary artery systolic pressure (PASP) measurements with early morbidity in on-pump coronary artery bypass grafting (CABG) surgery. Aims: The objective of the study was to assess whether TEE-derived elevated PASP is independently predictive of significant morbidity. Settings and Design: Prospective observational study in a university hospital. Materials and. Methods: Around 54 patients who underwent CABG under cardiopulmonary bypass (CPB) were divided into two groups; with PASP ≥35 mmHg and PASP <35 mmHg, assessed by intraoperative TEE. Outcomes studied were poor coronary revascularization, postoperative arrhythmias, myocardial infarction, respiratory failure, intra-aortic balloon pump use, pacemaker dependence, significant inotrope use, prolonged intensive care unit stay, and the total length of stay in the hospital. Mortality analysis was not a part of this study since expected sample sizes were low. Results: Patients with PASP ≥35 mmHg had a higher risk of respiratory failure, increased inotrope use and prolonged hospital stay, although multivariate analysis failed to demonstrate an independent association of PASP with these outcomes. Diabetes mellitus (DM), peripheral vascular disease, low cardiac output and elevated mitral annular E/e' ratio were significantly associated with higher pulmonary arterial pressures. Multivariate analysis showed that PASP was independently associated with higher mitral annular E/e' ratio. Conclusions: Our study, therefore, suggests that higher PASP may predict higher left ventricular filling pressures, and although elevated PASP ≥35 mmHg may be associated with DM; peripheral vascular disease, lower intraoperative cardiac output, postoperative respiratory failure, higher inotrope use, and delayed hospital discharge, it is not an independent predictor of any of these variables.

Management of aortic aneurysm presenting during pregnancy: A case report.

Aortic aneurysm in pregnancy is associated with higher risk of complications due to the stress induced by the physiologic changes in pregnancy. Many of the reports are concentrated on those with catastrophic outcomes or who underwent surgical repair during pregnancy/puerperium. We report a case of aortic aneurysm, who presented during the second trimester and had a successful pregnancy outcome, and discuss the various issues concerning the management during pregnancy.

Alfvénic velocity spikes and rotational flows in the near-Sun solar wind.

The prediction of a supersonic solar wind1 was first confirmed by spacecraft near Earth2,3 and later by spacecraft at heliocentric distances as small as 62 solar radii4. These missions showed that plasma accelerates as it emerges from the corona, aided by unidentified processes that transport energy outwards from the Sun before depositing it in the wind. Alfvénic fluctuations are a promising candidate for such a process because they are seen in the corona and solar wind and contain considerable energy5-7. Magnetic tension forces the corona to co-rotate with the Sun, but any residual rotation far from the Sun reported until now has been much smaller than the amplitude of waves and deflections from interacting wind streams8. Here we report observations of solar-wind plasma at heliocentric distances of about 35 solar radii9-11, well within the distance at which stream interactions become important. We find that Alfvén waves organize into structured velocity spikes with duration of up to minutes, which are associated with propagating S-like bends in the magnetic-field lines. We detect an increasing rotational component to the flow velocity of the solar wind around the Sun, peaking at 35 to 50 kilometres per second-considerably above the amplitude of the waves. These flows exceed classical velocity predictions of a few kilometres per second, challenging models of circulation in the corona and calling into question our understanding of how stars lose angular momentum and spin down as they age12-14.

Highly structured slow solar wind emerging from an equatorial coronal hole.

During the solar minimum, when the Sun is at its least active, the solar wind1,2 is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvénic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind3 of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain4; theories and observations suggest that they may originate at the tips of helmet streamers5,6, from interchange reconnection near coronal hole boundaries7,8, or within coronal holes with highly diverging magnetic fields9,10. The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfvén-wave turbulence11,12, heating by reconnection in nanoflares13, ion cyclotron wave heating14 and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe15 at 36 to 54 solar radii that show evidence of slow Alfvénic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities10,16 that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind.

Are Congenital Arteriovenous Malformations of Proximal Upper Extremity, More on the Right: Case Report and Literature Review.

This is a case of a 9-year-old boy with a congenital arteriovenous malformation (AVM) of the right upper extremity arising from the right subclavian artery. He underwent open surgical excision of the vascular tumor. Upon reviewing the literature, a high incidence of right-sided congenital AVM of the proximal upper extremity was identified. It has been suggested that this high incidence may be related to the complexity of the embryologic development of the right subclavian artery.

Contrast Enhanced Computed Tomographic Study on the Prevalence of Duodenal Diverticulum in Indian Population.

INTRODUCTION: Duodenal diverticulum (DD) is the second most common diverticulum, yet its incidence varies widely from 1-22% based on the mode of investigation. Computed Tomography (CT) of abdomen is the preferred modality to diagnose acute abdomen including those of complications of DD. Moreover, the prevalence of DD in Indian population is not yet been studied using CT. AIM: The current study aim to look for the prevalence of DD in Indian population using Contrast Enhanced Computed Tomography (CECT) abdomen. MATERIALS AND METHODS: A retrospective study was done to assess the presence of DD using the CECT abdomen of 565 patients. The number, size, location, wall thickness and the contents of the diverticulum were noted. The data obtained was analysed using SPSS version 17.0. The mean, percentage of frequency of each variable and the association of DD with pancreatitis, cholelithiasis and colonic diverticulum were also looked for. Frequencies and percentages were calculated for all categorical variables. Spearman's rho correlation was done for age, diameter and content of DD. RESULTS: The prevalence of DD in Indian population was 8.3% with the mean diameter of 17.13mm+7.26. The prevalence increased with age with no sex predilection. 89.3% were solitary and 10.64% were multiple. It was predominantly seen in the second part of duodenum (90.38%) and juxtapapillary type was the commonest. As the diameter of DD increased, fluid became its content. No significant association was observed between the presence of DD with pancreatitis, cholelithiasis or colonic diverticulum. A case of periampullary carcinoma arising from DD, a rare entity is being reported in this study. CONCLUSION: The prevalence of DD in Indian population is high compared to western population. DD has been attributed to the cases of acute abdomen and fluid alone as a content of DD with an incidence of 1.92% can be mistaken for a cystic neoplasm of pancreas. Rarely, a periampullary carcinoma can also arise from the wall of the pre-existing DD. This knowledge should be emphasised upon by the radiologist, surgeons and gastroenterologist who will be dealing with cases of acute abdomen and periampullary carcinoma.

Combined nephrectomy and aortic valve replacement: perioperative decision-making.

Open heart surgery and urologic surgery may be required for patients with coincident diseases. We report a patient who suffered from aortic valve stenosis which was asymptomatic barring atrial fibrillation. He was prescribed warfarin and then developed a large perinephric hematoma. The perioperative considerations focused on whether to conduct aortic valve replacement for this patient and, if such surgery was indicated, the appropriate time to conduct it. Traditionally, severe cardiac disease is addressed first before conducting elective noncardiac surgery; however, this option was not available since the patient already had a perinephric hematoma which could bleed more when subjected to systemic heparinization for cardiopulmonary bypass. Here, we describe the process of perioperative decision-making involving multiple specialities and re-examine several guidelines.

The FIELDS Instrument Suite for Solar Probe Plus: Measuring the Coronal Plasma and Magnetic Field, Plasma Waves and Turbulence, and Radio Signatures of Solar Transients.

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.

Frequency of Epstein--Barr virus infection as detected by messenger RNA for EBNA 1 in histologically proven gastric adenocarcinoma in patients presenting to a tertiary care center in South India.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric carcinoma is a relatively uncommon entity detected in approximately 10% of gastric adenocarcinoma. OBJECTIVE: The purpose of this study is to estimate the frequency of EBV-associated gastric carcinoma and also to assess the nature of presentation, any significant difference between this subgroup and EBV-negative gastric adenocarcinomas with respect to age and sex predilection, lymph nodal status, site of presentation. MATERIALS AND METHODS: We prospectively analyzed 100 cases of gastric adenocarcinoma who underwent either a partial or total gastrectomy during the period from March 2010 to August 2011. The tumour and the corresponding normal gastric tissue from the same patient were analyzed for the presence of Epstein-Barr nuclear antigen 1 (EBNA1) messenger ribonucleic acid (mRNA) by real-time polymerase chain reaction (PCR). RESULT: EBV was detected in 6% cases of gastric adenocarcinoma. All the positive patients were males. The majority of cases involved the proximal stomach and there was variable lymph nodal involvement. CONCLUSION: Our study endorses that there is an association between EBV infection and gastric adenocarcinoma in the Indian population. There was no significant difference between this subgroup and EBV-negative gastric adenocarcinomas with respect to age and sex predilection, lymph nodal status and site of presentation. Short-term follow-up of this subgroup of patients seems to indicate a good overall prognosis after appropriate treatment. However, a larger study with long-term follow-up is needed to further establish the role of EBV in gastric adenocarcinoma in this study population.

Gastrointestinal Stromal Tumours: Review of 150 Cases from a Single Centre.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. They constitute a significant percentage ranging from 1-2 % of all the gastrointestinal neoplasms [11]. Knowledge on the molecular biology and behavior of these tumours is still not very clear. The clinicopathologial features are variable and surgical resection with chemotherapy is the main modality of treatment. We have retrospectively analyzed the clinicopathological features, treatment and prognosis of 150 patients managed in the Department of Surgery. Retrospective review of the records of 150 patients diagnosed with gastrointestinal stromal tumours and managed during the period January 2006 to December 2011. Clinicopathological features, immunohistochemistry, mitotic index, surgical resection adjuvant chemotherapy and survival analyzed. One hundred and fifty patients diagnosed with GIST and treated were reviewed. Ninety five of them were males (63.3 %). The tumour was most commonly seen during the fourth and fifth decades of life. Abdominal pain (52 %), intestinal bleeding (40 %) and abdominal mass (25 %) were the common clinical symptoms. Sixty percent of the tumours (90/150) were located in the stomach followed by small bowel (20 %) and duodenum (14.6 %). One hundred and thirty-five patients underwent excision of the tumour and five patients had multi organ resection of the adjacent organs like spleen, tail of the pancreas and kidney. Fifteen patients (10 %) received neoadjuvant Imatinib for down staging of the tumour prior to surgery. The tumour size ranged from 1 to 34 cm. One third of the tumours (42/150) belonged to the high-grade category. KIT protein (CD117) was positive in 90 %( 135/150), while CD34 was positive in 50 % (74/150) of tumours. Majority of the patients with high and intermediate-risk category received adjuvant Imatinib (65/77). Seventeen patients (11.3 %) developed recurrence of the tumour on follow-up and rest of the patients had stable disease. Eight of the 15 patients (53 %) who had advanced disease developed recurrence of the disease over 6 months to 1 year. Fifteen patients died on follow-up between 2 and 5 years. Gastrointestinal tumours are the most common non epithelial tumour of the GIT. GISTS are found to show a male preponderance and are common during the fourth and fifth decades. Abdominal pain and intestinal bleeding are the most common clinical presentation. Most of the tumours were located in the stomach. Surgical resection is the best modality of treatment for operable lesions. Tyrosine kinase receptor (KIT) inhibitor like imatinib is used for adjuvant treatment. Regular follow-up with ultra sonogram or computed tomogram helps in diagnosing disease recurrence.

An acenocoumarol dosing algorithm exploiting clinical and genetic factors in South Indian (Dravidian) population.

OBJECTIVE: The objective of this study was to determine the influence of CYP2C9, VKORC1, CYP4F2, and GGCX genetic polymorphisms on mean daily dose of acenocoumarol in South Indian patients and to develop a new pharmacogenetic algorithm based on clinical and genetic factors. METHODS: Patients receiving acenocoumarol maintenance therapy (n = 230) were included in the study. Single nucleotide polymorphisms (SNP) of CYP2C9, VKORC1, CYP4F2, and GGCX were genotyped by real-time polymerase chain reaction (RT-PCR) method. RESULTS: The mean daily acenocoumarol maintenance dose was found to be 3.7 ± 2.3 (SD) mg/day. The CYP2C9 *1*2, CYP2C9 *1*3, and CYP2C9 *2*3 variant genotypes significantly reduced the dose by 56.7 % (2.0 mg), 67.6 % (1.6 mg), and 70.3 % (1.5 mg) than wild-type carriers 4.1 mg, p < 0.0001. The genetic variants of CYP2C9 and GGCX (rs11676382) were found to be associated with lower acenocoumarol dose, whereas CYP4F2 (rs2108622) was associated with higher doses. Age, body mass index (BMI), variation of CYP2C9, VKORC1, CYP4F2, and GGCX were the major determinants of acenocoumarol maintenance dose, accounting for 61.8 % of its variability (adjusted r (2) = 0.615, p < 0.0001). Among the VKORC1 variants, rs9923231 alone contributed up to 28.6 % of the acenocoumarol dose variation. CONCLUSION: VKORC1 rs9923231 polymorphism had the highest impact on acenocoumarol daily dose. A new pharmacogenetic algorithm was established to determine the acenocoumarol dose in South Indian population.

Phosphatase and tensin analog expression in arterial atherosclerotic lesions.

CONTEXT: Phosphatase and tensin analog (PTEN) gene mutation has been proven for pro-inflammatory property and proliferative potential through tyrosine kinase pathway. We studied mutated PTEN for its pathogenetic association in arterial atherosclerosis. AIMS: The objective was to study mutation of PTEN by immunohistochemical method in arterial atherosclerotic lesions and correlate with grades of atherosclerosis, smooth muscle migration in intima, degree of inflammation and Framingham heart study risk factors. SETTINGS AND DESIGN: Human, Prospective Clinical study. MATERIALS AND METHODS: We studied patients with arterial occlusive disease diagnosed by Doppler ultrasonography over a 2-year period. Immunohistochemistry was performed with mouse monoclonal antibodies for PTEN and smooth muscle actin (SMA). STATISTICAL ANALYSIS USED: Chi-square test. RESULTS AND CONCLUSION: Aorta was the single most common vessel affected (21%). Mean age of patients studied was 48.6 years and 80% were male. Mutant PTEN was associated with higher grades of atherosclerotic lesions (P < 0.0001) graded by American Heart Association classification and with smooth muscle proliferation and migration in intima (P < 0.0001). No statistically significant association with the vessel wall inflammation and other risk factors of atherosclerosis.

Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on warfarin maintenance dose and explicating a new pharmacogenetic algorithm in South Indian population.

OBJECTIVE: To determine the influence of genetic polymorphisms on warfarin maintenance dose and to explicate an algorithm using the pharmacogenetic and clinical factors to determine the maintenance and/or starting dose of warfarin in South Indian patients receiving warfarin therapy. METHODS: Patients receiving stabilized warfarin therapy (n=257) were included in the study. Single nucleotide polymorphisms (SNPs) of CYP2C9 (rs1799853 and rs1057910), VKORC1 (rs9923231, rs7196161, rs2884737, rs9934438, rs8050894, rs2359612 and rs7294), CYP4F2 (rs2108622) and GGCX (rs11676382) were genotyped by the quantitative real time-PCR method. RESULTS: The mean daily maintenance dose of warfarin was found to be 4.7 ± 2.1 mg/day. Patients with the CYP2C9*1/*2, *1/*3 and *2/*3 variant genotypes required a 51.0 (2.8 mg), 60.9 (2.3 mg) and 62.2 % (2.2 mg) lower daily maintenance dose of warfarin, respectively, than those patients with the CYP2C9*1/*1 wild-type genotype (5.2 mg) (p<0.0001). The genetic variants of CYP2C9, VKORC1 and GGCX were associated with decreased warfarin dose, except for rs7196161, rs7294 and rs2108622 which were associated with an increased warfarin dose. Genetic variations of CYP2C9 (*2 and *3), VKORC1 (rs9923231, rs7294, rs9934438 and rs2359612), CYP4F2, GGCX and non-genetic factors such as age, body weight, clinical status (post mechanical valve replacement) could explain up to 62.1 % of the overall variation (adjusted r (2) 60.2 %, p<0.0001) in warfarin maintenance dose. CONCLUSION: Genetic polymorphisms of CYP2C9, VKORC1, CYP4F2 and GGCX are important predictive factors of warfarin maintenance dose, and the developed algorithm will be useful to predict the required maintenance and/or starting warfarin dose in South Indian populations.

Estimation of plasma levels of warfarin and 7-hydroxy warfarin by high performance liquid chromatography in patients receiving warfarin therapy.

Warfarin is one of the most commonly prescribed oral anticoagulant for prevention of thromboembolic events. The effect of this drug is measured by monitoring prothrombin time expressed as International Normalized Ratio (INR). In some cases, however, the measurement of plasma concentration of warfarin was emphasized. In the present study, reversed phase high performance liquid chromatography (HPLC) was used to estimate the plasma drug levels. A total of 185 patients were enrolled in this study. Five milliliter of venous blood was collected using sodium EDTA tubes for pharmacokinetic analysis. Solid phase extraction was used to recover the warfarin and it's metabolite from plasma using isopropanol and potassium phosphate buffer (40:60) mobile phase. Warfarin, 7-hydroxy warfarin and carbamazepine (internal standard) were separated on a C18 column and had the retention time 3.6 min, 2.9 min and 5.9 min, respectively. The assay was linear in warfarin concentration ranges of 0.1-5 µg/ml. The extraction recovery was found to be ≃85%. The mean plasma concentrations of warfarin and 7-hydroxy warfarin were found to be 3.47 ± 1.87 (SD) µg/ml, 1.25 ± 0.81 (SD) µg/ml, respectively. Through the present study the plasma concentrations of warfarin, 7-hydroxy warfarin and their metabolic ratio was determined. The assay was sensitive to follow warfarin pharmacokinetics in a patient with warfarin therapy for 3 months and above.

Effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients.

AIM: To determine the effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients with heart valve replacement. MATERIALS AND METHODS: The study was conducted in 170 patients on therapy with acenocoumarol following heart valve replacement surgery. Single nucleotide polymorphisms (SNP) namely CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), and VKORC1 (rs9923231) were identified by quantitative Real-Time Polymerase Chain Reaction (RT-PCR) method. RESULTS: Patients with at least one variant allele of CYP2C9 (*1*2 or *1*3) required 44% and 28.2% lower daily maintenance dose of acenocoumarol (2.0mg and 2.5mg, respectively) than the normal CYP2C9*1*1 genotype group (3.4mg) (p<0.05). Patients with VKORC1 GG genotype required higher dose (3.3mg) as compared to those with genotype VKORC1 GA (2.3mg) and VKORC1 AA (1.0mg) (p<0.001). Patients with both CYP2C9*1*2/*1*3 and VKORC1 GA genotype required 38% lower dose (2.46mg) than patients with CYP2C9*1*1 and VKORC1 GG genotype (3.52mg) (p<0.0001). The clinical (age, body mass index) and genetic variables (VKORC1-1639 G>A, CYP2C9*2, CYP2C9*3) contribute together to predict 30.4% of the required maintenance dose of acenocoumarol. CONCLUSION: The genetic polymorphisms of CYP2C9 and VKORC1 results in decreased requirement of daily maintenance dose of acenocoumarol. The polymorphism VKORC1 (-1639 G>A) was found to be the major predictor of acenocoumarol dose requirement in South Indian population.

Extended multiorgan resection in locally advanced gastric cancer: a single centre experience from south India.

BACKGROUND: The prognostic and survival benefit of extended multiorgan resection for locally advanced gastric adenocarcinoma remains controversial. The morbidity associated with additional organ resection has been found to be higher when compared to patients undergoing gastrectomy alone. The aim of our study was to evaluate the morbidity, mortality and survival benefit associated with extended multiorgan resection for locally advanced gastric adenocarcinoma. METHODS: From January 2004 to December 2011, 721 patients underwent resectional surgery for gastric adenocarcinoma at the Christian Medical College, Vellore, India. Out of this group, 36 patients underwent primary resection and had one or more organs resected in addition to the stomach. A retrospective analysis of the case records of all these patients was performed. The Kaplan-Meier survival probability was estimated. Cox regression analysis was used to evaluate the clinico-pathological variables affecting the survival of these patients. RESULTS: The perioperative morbidity and mortality rates were 25% and 5.5% respectively. The most common organs resected were colon and spleen. The incidence of pathologically confirmed T4b cancers was only 50%. The median survival of these patients was 28 months. The survival was influenced by a R0 or curative resection. However, it was not statistically significant. CONCLUSION: Extended multiorganresection in locally advanced gastric cancer can be performed with acceptable morbidity and mortality. In our study, overstaging was found in 50% of the patients and hence, when the real nature of invasion is unclear, the surgeon may proceed with en bloc resection of the stomach with the involved adjacent organs. As long as an R0 resection can be achieved, extended multiorgan resection can be performed for carcinoma stomach.