Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial.

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Association of methylenetetrahydrofolate reductase gene polymorphisms & colorectal cancer in India.

BACKGROUND & OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, 677 C-->T and 1298 A-->C have shown to impact several diseases including cancer. This case-control study was undertaken to analyse the association of the MTHFR gene polymorphisms 677 C-->T and 1298 A-->C and risk of colorectal cancer (CRC). METHODS: One hundred patients with a confirmed histopathologic diagnosis of CRC and 86 age and gender matched controls with no history of cancer were taken for this study. DNA was isolated from peripheral blood samples and the genotypes were determined by PCR-RFLP. The risk association was estimated by compounding odds ratio (OR) with 95 per cent confidence interval (CI). RESULTS: Genotype frequency of MTHFR 677 CC, CT and TT were 76.7, 22.1 and 1.16 per cent in controls, and 74, 25 and 1.0 per cent among patients. The 'T' allele frequency was 12.21 and 13.5 per cent in controls and patients respectively. The genotype frequency of MTHFR 1298 AA, AC, and CC were 25.6, 58.1 and 16.3 per cent for controls and 22, 70 and 8 per cent for patents respectively. The 'C' allele frequency for 1298 A-->C was 43.0 and 45.3 per cent respectively for controls and patients. The OR for 677 CT was 1.18 (95% CI 0.59-2.32, P = 0.642), OR for 1298 AC was 1.68 (95% CI 0.92-3.08, P = 0.092) and OR for 1298 CC was 0.45 (95% CI 0.18-1.12, P = 0.081). The OR for the combined heterozygous state (677 CT and 1298 AC) was 1.18 (95% CI 0.52-2.64, P =0.697). INTERPRETATION & CONCLUSION: The frequency of the MTHFR 677 TT genotype is rare as compared to 1298 CC genotype in the population studied. There was no association between 677 C-->T and 1298 A-->C polymorphisms and risk of CRC either individually or in combination. The homozygous state for 1298 A-->C polymorphism appears to slightly lower risk of CRC. This needs to be confirmed with a larger sample size.

Percutaneous pericardio-peritoneal shunt (PPP)--a novel palliative treatment for recurrent cardiac tamponade.

The management of pericardial effusion with recurrent cardiac tamponade in disseminated malignancy is a therapeutic challenge. Treatment options include repeated aspirations, balloon pericardiostomy and surgical pericardial window with variable success at symptom palliation. We describe a safe and novel percutaneous technique of pericardio-peritoneal shunt for palliative treatment of malignancy associated massive pericardial effusion ina patient who declined surgery and had refractory pericardial effusion despite repeated pericardiocentesis, chemical pericardiodesis and balloon pericardiostom

Association between plasma homocysteine and riboflavin status in Acute Lymphoblastic Leukemia in children.

Remethylation of homocysteine to methionine is dependent on an adequate supply of one or more of the B vitamins like folate, vitamin B(12) and vitamin B(6). Plasma total homocysteine (tHcy) is also influenced by genetic factors such as polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. MTHFR is a flavo enzyme and a key player in folate metabolism and changes in its activity could modify the susceptibility to Acute Lymphoblastic Leukemia (ALL). In this case - control study we have examined the effect of riboflavin status as measured by erythrocyte glutathione reductase activation coefficient (EGRAC) on homocysteine levels along with vitamin B(12) and folate in pediatric ALL. Folate and B(12) levels were significantly lower among cases as compared to controls while EGRAC and tHcy did not differ significantly among the groups. The multivariate regression analysis revealed that in the ALL group EGRAC significantly influences tHcy levels suggesting that riboflavin availability may be a predictor of tHcy levels in patients with ALL. This finding may have implications for tHcy lowering therapy.

Homocysteine, vitamin B12 and folate status in pediatric acute lymphoblastic leukemia.

OBJECTIVE: The cause of majority of acute leukemias is unknown, but likely to involve interaction of environment, hematopoitic development and weak susceptibility loci within an individual's genetic constitution. The present study evaluates the association between plasma levels of homocysteine, folate and vitamin B12 and acute lymphoblastic leukemia. METHODS: Plasma levels of homocysteine, folate and vitamin B12 were compared between cases of acute lymphoblastic leukemia and age and sex matched normal controls. Homocysteine levels were measured by solid immunoassay, while folate and vitamin B12 levels were determined by radioassay. RESULTS: Folate levels were significantly among cases as compared to control group (8.56 +/- 4.35) vs (14.04 +/- 2.62) ng/ml, P< 0.001). Although individually vitamin B12 and homocysteine were not significant different between cases and controls, the combined effect of all three parameters was significantly different (P< 0.001), with 83.3% of correct classification of cases and controls was obtained by discriminate function analysis. CONCLUSION: The data provide evidence for the role of folate, vitamin B12 and homocysteine levels in acute lymphoblastic leukemia, suggesting that gene-environment interaction may be an important factor in the development of acute lymphoblastic leukemia.

Effect of Vitamin B(12) and Folate on Homocysteine levels in colorectal cancer.

Folate and cobalamin (Vitamin B(12)) are two essential micronutrients involved in one-carbon metabolism, which affects heart disease, neural tube defects and cancer. Methylenetetrahydrofolate reductase, the key enzyme involved in one carbon metabolism produces methyl tetrahydrofolate from methylene tetrahydrofolate, which in turn donates methyl group to homocysteine to generate methionine. There exist two common low function polymorphic variants of the methylenetetrahydrofolate reductase gene involving nucleotides 677 C→T and 1298 A→C, which are associated with hyperhomocysteinemia. These polymorphisms are also linked with increased risk for certain cancers such as breast cancer and at the same time providing a protective effect on colorectal cancer. In this case control study, we have evaluated levels of folic acid, vitamin B(12) and homocysteine in patients with colorectal cancer. Folate and homocysteine levels did not differ significantly between the two groups; however an increasing trend was noticed with increase in homocysteine levels. Vitamin B(12) levels were increased in cases compared to control group.

Audit of radiation dose to patients during coronary angiography.

BACKGROUND: There is widespread concern about radiation doses imparted to patients during cardiology procedures in the medical community. The current study intends to audit and optimize radiation dose to patients undergoing coronary angiography (CA) performed using two dedicated cardiovascular machines. MATERIALS AND METHODS: One hundred and forty nine patients who underwent CA are reported in this study. Dose auditing was done by implementing dose reduction strategies using spectral filters and by evaluating work practices of operators involved in performing CA. STATISTICAL ANALYSIS: A Student's 't' test was used to analyze the statistical significance. RESULTS AND CONCLUSION: The radiation dose imparted to patients was measured using dose area product (DAP) meter. The mean DAP values during CA before optimization was 55.86 Gy cm2 and after optimization was 27.71 Gy cm2. No ill-effects of radiation were reported for patients who underwent CA. Use of copper filtration may be recommended for procedures performed using cardiovascular machines.

Feasibility of angioplasty and stenting for abdominal aortic lesions adjacent to previously stented visceral artery lesions in patients with Takayasu arteritis.

Two young female patients with Takayasu arteritis presented with symptomatic long-segment abdominal aortic stenosis in the vicinity of previously deployed celiac and renal artery stents that projected markedly into the narrowed aortic lumen. Crushing or distortion of the visceral artery stents during aortic angioplasty was avoided by performing simultaneous or alternating balloon dilatations in the aorta and in the visceral artery stents. Consequently, the visceral artery stents remained patent and shortened longitudinally, allowing unhindered deployment of Wallstents in the adjacent aorta and abolition of a pressure gradient across the aortic lesions. Access to side branches covered by the Wallstent was obtained without difficulty, enabling the performance of balloon dilatation in multiple side branches and ostial stent deployment in a renal artery. These techniques could increase the scope of endovascular therapy in the treatment of patients with Takayasu arteritis.

Optimization and audit of radiation dose during percutaneous transluminal coronary angioplasty.

The percutaneous transluminal coronary angioplasty (PTCA) is one of the interventional procedures which impart high radiation doses to patients compared to the other cardiologic procedures. This study intends to audit and optimize radiation dose imparted to patients undergoing PTCA. Forty-four patients who underwent PTCA involving single or multiple stent placement guided under cardiovascular X-ray machine were included in the study. Radiation doses were measured using dose area product (DAP) meter for patients undergoing single and multiple stent placements during PTCA. A dose reduction of 27-47% was achieved using copper filters and optimal exposure parameters. The mean DAP values before optimization were 66.16 and 122.68 Gy cm(2) for single and multiple stent placement respectively. These values were 48.67 and 65.44 Gy cm(2) respectively after optimization. In the present scenario, due to the increase in the number of PTCAs performed and the associated risk from radiation, periodical audit of radiation doses for interventional procedures are recommended.

Audit of radiation dose during balloon mitral valvuloplasty procedure.

Radiation doses to patients during cardiological procedures are of concern in the present day scenario. This study was intended to audit the radiation dose imparted to patients during the balloon mitral valvuloplasty (BMV) procedure. Thirty seven patients who underwent the BMV procedure performed using two dedicated cardiovascular machines were included in the study. The radiation doses imparted to patients were measured using a dose area product (DAP) meter. The mean DAP value for patients who underwent the BMV procedure from one machine was 19.16 Gy cm(2) and from the other was 21.19 Gy cm(2). Optimisation of exposure parameters and radiation doses was possible for one machine with the use of appropriate copper filters and optimised exposure parameters, and the mean DAP value after optimisation was 9.36 Gy cm(2).

Loss of anti-aggregatory effects of aortic valve tissue in patients with aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Patients with aortic stenosis (AS) exhibit increased platelet aggregability, and thrombus formation has been documented on calcific and severely stenosed valves. Isolated porcine and canine aortic valves (AV) release nitric oxide (NO) and prostacyclin, which exert local antithrombotic effects; to date, this has not been studied in humans. In the present study the possible interaction of AV tissue with platelet aggregation was examined, using fragments of AV obtained from patients with AS and aortic regurgitation (AR). METHODS: Fragments of AV tissue, excised from patients undergoing AV replacement, were co-incubated with blood samples obtained from normal subjects. The direct effects of valve tissue from patients with AS (n = 14) or with predominant AR (n = 13) on ADP-induced platelet aggregation and intraplatelet cGMP and cAMP content were compared. RESULTS: In whole blood, non-calcified AV fragments from AR patients inhibited platelet aggregation by 57 +/- 6% (p < 0.01); in platelet-rich plasma results were analogous. In order to determine whether this anti-aggregatory effect could be attributed to the valvular release of NO or prostacyclin, intraplatelet cGMP and cAMP formation was assessed, respectively. While there were no significant changes in cGMP content, cAMP increased by 26 +/- 4% (p < 0.02). Both, anti-aggregatory and cAMP-stimulating effects were similar to those produced by 10 nM prostaglandin E1, a prostacyclin mimetic. Fragments from stenotic valves did not inhibit aggregation and did not affect cGMP or cAMP. Furthermore, fragments from heavily calcified regions potentiated aggregation and, in some cases, induced spontaneous aggregation. CONCLUSION: Minimally calcified aortic valves (i.e., AR) and, therefore, presumably also normal valves, exert anti-aggregatory effects, most likely via prostacyclin release. AS is associated with a loss of this effect, thus potentially contributing to thrombotic risk.

Prevalence of coronary artery disease in patients with rheumatic heart disease in the current era.

BACKGROUND: This study was undertaken to determine the prevalence of coronary artery disease in patients with rheumatic heart disease undergoing valve surgery. METHODS AND RESULTS: Consecutive patients with rheumatic heart disease (n=376) who were above the age of 40 years, and scheduled for valve surgery underwent diagnostic coronary angiogram to delineate coronary arteries. The patients were divided into three groups based on valve involvement (mitral valve, aortic valve, and combined aortic and mitral valve). Significant coronary artery disease was considered to be present if one or more coronaries showed 50% or more luminal stenosis. There were 287 (76.3%) males and 89 (23.7%) females. The mean age of the study population was 51.2+/-8.2 years. Eighty-nine (23.8%) patients had typical chest pain, 116 (30.6%) patients had atypical chest pain and 171 (45.5%) patients had no chest pain. Hypertension was noted in 88 (23.4%) patients, 65 (17.3%) patients had diabetes, 98 (26.1%) patients were smoker, and 66 (17.6%) patients had dyslipidemia, and 15 (4.0%) patients gave past history of myocardial infarction. Of the total 376 patients, 46 (12.2%) patients were found to have significant coronary artery disease. In patients with mitral vale disease the prevalence was 13.5% (13/96), while it was 15.3% (19/124) in patients with aortic valve disease and 9% (14/156) in those with combined mitral and aortic valve disease. CONCLUSIONS: Our results suggest that the overall prevalence of coronary artery disease in a group of patients with rheumatic heart disease undergoing valve surgery in the current era is 12.2%. This prevalence is much lower than the figures reported earlier in the Western literature.