Binita Goswami

Atherosclerosis Pathophysiology and the Role of Novel Risk Factors: A Clinicobiochemical Perspective:

Atherosclerosis is the root cause of the biggest killer of the 21st century. Mechanisms contributing to atherogenesis are multiple and complex. A number of theories—including the role of dyslipidemia, hypercoagulability, oxidative stress, endothelial dysfunction, and inflammation and infection by certain pathogens—have been propounded from time to time explain this complex phenomenon. Recently it has been suggested that atherosclerosis is a multifactorial, multistep disease that involves chronic inflammation at every step, from initiation to progression, and that all the risk factors contribute to pathogenesis by aggravating the underlying inflammatory process. A better understanding of the pathogenesis of atherosclerosis will aid in devising pharmaceutical and lifestyle modifications for reducing mortality resulting from coronary artery disease (CAD). A comprehensive literature search was conducted using the Web sites of the National Library of Medicine (http:// www.ncbl.nlm.nih.gov/) and PubMed Central, the US National Library of Medicines digital archive of life sciences literature (http:// www.pubmedcentral.nih.gov/). The data were accessed from books and journals in which relevant articles in this field were published. The whole spectrum of coronary artery disease evolves through various events that lead to the formation and progression of atherosclerotic plaque and finally its complications. Atherosclerosis is the culprit behind coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The pathogenic mechanisms are varied and complex. Of late, the role of lipoprotein (a), homocysteine, and inflammation and infection as prime culprits in pathogenesis of CAD is the subject of intense research and debate. The appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework to understand the clinical benefits of newer therapeutic strategies, and a better understanding of pathogenesis aids in formulating preventive and therapeutic strategies in reducing mortality resulting from CAD. An in-depth knowledge of the various pathogenic mechanisms involved in atherosclerosis can help in substantiating the current existing knowledge about the CAD epidemic. This knowledge will help clinicians to better manage the disease, which affects Indians in its most severe form.

Paraoxonase: a multifaceted biomolecule.

BACKGROUND Paraoxonase enzyme was first identified as a protective barrier against organophosphorus poisoning. After painstaking research spanning the last three decades, the knowledge about this enzyme has increased immensely. The present review attempts to elaborate the role of paraoxonase enzyme in normal physiology as well as provide an overview of the various disorders in which the enzyme may have a role in etiopathogenesis. METHODS The literature was searched from the websites of the National Library of Medicine (http://www.ncbi.nlm.nih.gov/) and Pub Med Central, the U.S. National Library of Medicines digital archive of life sciences journal literature. RESULTS Paraoxonase acts as an important antioxidant enzyme against oxidative stress. The enzyme has been implicated in the pathogenesis of a number of disorders including cardiovascular disorders, cancers etc. CONCLUSIONS A better understanding of the molecular mechanism of the enzyme along with the regulatory circuits will help us to utilize agonists to potentiate the anti oxidant actions of the enzyme.

Evaluation of errors in a clinical laboratory: a one-year experience

Abstract Background: Efficient laboratory service is the cornerstone of modern health care systems. Scientific innovations have contributed to substantial improvements in the field of laboratory science, but errors still prevail. These errors are classified as preanalytical, analytical and postanalytical, depending upon the time of presentation. Methods: The data for 67,438 routine venous blood specimens were scrutinized, and errors were documented over the period of 1 year in the clinical biochemistry laboratory of Govind Ballabh Pant Hospital in Delhi, India. Results: Preanalytical errors were most common, with a frequency of 77.1% followed by postanalytical 15% and analytical 7.9%, respectively. Conclusions: Our study illustrates the importance of proper venipuncture procedures, analytical expertise and correct transcription of numerical data for precise and accurate reporting of results to clinicians. There is an urgent need for close inter-departmental cooperation to meet the goal of ensuring patient well being. Clin Chem Lab Med 2010;48:63–6.

Vitamin D as a predictor of insulin resistance in polycystic ovarian syndrome.

INTRODUCTION Polycystic Ovary Syndrome (PCOS) is the most common endocrinological disorder in women in the reproductive age group. The salient features of this condition include hyperandrogenic features, infertility and insulin resistance among others. Mechanisms behind these features are a matter of debate. Vitamin D has been implicated lately in the etiology of many disorders. The aim of our study was to assess the role of vitamin D as an etiological and predictive factor in PCOS. MATERIALS AND METHODS The study comprised 60 proven cases of PCOS diagnosed on the basis of Rotterdam criteria. The parameters assessed include HOMA-IR, vitamin D besides the routine anthropometric and biochemical parameters. RESULTS The study population was divided into 3 groups according to vitamin D status. Insulin resistance was most severe in the sub group with vitamin D deficiency. Multiple regression analysis established the role of vitamin D as the best predictor of insulin resistance in our study. CONCLUSION Vitamin D has an important role in the pathogenesis of insulin resistance in PCOS.

TNF-α/IL-10 ratio and C-reactive protein as markers of the inflammatory response in CAD-prone North Indian patients with acute myocardial infarction

BACKGROUND Cytokines are responsible for the modulation of immunological and inflammatory processes and play a significant role in the pathogenesis of coronary artery disease (CAD). Tumor necrosis factor (TNF)-alpha is the major pro-inflammatory cytokine while interleukin-10 (IL-10) is the major anti-inflammatory cytokine in patients with CAD. We determined the significance of the TNF/IL-10 ratio and C-reactive protein (CRP) in patients of acute myocardial infarction as a marker for CAD in the atherosclerosis-prone North Indian population. METHODS The study group comprised of 100 patients of acute myocardial infarction (AMI) and 100 age and sex matched healthy controls. Lipid profile, apolipoprotein-A (Apo-A), apolipoprotein-B (Apo-B) and CRP concentrations were estimated using commercially available kits in all patients and control subjects. TNF-alpha, lipoprotein (a) (Lp(a)) and IL-10 concentrations were assayed by using commercially available ELISA kits. RESULTS The TNF-alpha concentrations were significantly higher in patients with acute myocardial infarction (86.9+/-4.7 pg/ml), as compared to control subjects (7.1+/-0.67 g/ml). AMI patients also exhibited higher serum concentrations of IL-10 (5.74+/-0.82 pg/ml), in comparison to the controls (1.22+/-0.06 pg/ml). The ratio of TNF-alpha to IL-10 was significantly increased in cases (15.2+/-1.13), in comparison to healthy subjects (5.8+/-0.64). CONCLUSIONS These cytokines underline the role of the immune processes during unstable atherosclerosis and in the pathogenesis of coronary artery disease in the Indian context.

Apo-B/apo-AI ratio: a better discriminator of coronary artery disease risk than other conventional lipid ratios in Indian patients with acute myocardial infarction.

Background — Coronary artery disease (CAD) is a leading cause of morbidity and mortality in the developed world and is rapidly assuming epidemic proportions in developing countries including India.This has led to extensive research to determine the risk factors unique to this group which may predispose to the elevated risk of this disease. Important amongst them are lipoproteins, homocysteine, lipoprotein (a), pro-inflammatory cytokines etc. The following study was undertaken to evaluate the role of the apolipoprotein-B100 (apo-B)/apolipoprotein-AI (apo-AI) ratio as a predictor of CAD risk in the atherosclerosis-prone Indian population, as compared to other conventional lipid ratios. Material and methods — The study group comprised 100 clinically assessed patients with acute myocardial infarction (AMI) diagnosed on electrocardiographic and biochemical criteria and 100 agematched healthy control subjects. Apo-B and apo-AI levels were estimated by the immunoturbidimetric method, using kits from Randox, UK. Lipid profile was determined using standard enzymatic methods. The exponential regression coefficient β was calculated for total cholesterol/high-density lipoprotein cholesterol (TC/HDL), TC-HDL/HDL, low-density lipoprotein (LDL) cholesterol/HDL and apo-B/apo-AI ratios. Results — The TC/HDL ratio was 5.15 ± 1.7 and 3.45 ± 0.87 in patients with AMI and control subjects, respectively (P < 0.001).The TC-HDL/HDL ratio was 4.61 ± 2.6 and 2.22 ± 1.14 in the patients with AMI and the control subjects (P< 0.001).The LDL/HDL ratio was 3.32 ± 1.5 in the AMI patients and 1.84 ± 0.78 in the control subjects (P< 0.001); whilst the apo-B/apo-AI ratio in the patients with AMI was 0.96 ± 0.30 and 0.71 ± 0.20 in the control subjects (P< 0.001).The exponential value of the regression coefficient β (Exp [β]) for apo-B/apo-AI ratio was 111.9, as compared to 4.4 for the LDL/HDL ratio, 3.5 for the TC/HDL ratio and 2.2 for the TC-HDL/HDL ratio, though all the lipid ratios were significantly higher in cases than in control subjects. Conclusion — Our findings suggest that the apo-B/apo-AI ratio is a better discriminator of CAD risk in the atherosclerosis-prone Indian population, than any of the conventional lipid ratios.The reduction of value of the apo-B/apo-AI ratio may drastically decrease the risk for CAD. Hence, the apo-B/apo-AI ratio may be suggested as an alternative to other lipid ratios for risk assessment in patients with CAD.

Identification of the Types of Preanalytical Errors in the Clinical Chemistry Laboratory: 1-Year Study at G.B. Pant Hospital

Objective: To evaluate the leading causes of preanalytical errors in a clinical chemistry laboratory. Methods: A retrospective analysis of the results obtained from the clinical chemistry laboratory for errors in the preanalytical phase has been carried out to summarize data regarding the frequency of the main factors affecting the preanalytical quality of results. Laboratory personnel were asked to register rejections, and causes for rejection of ward as well as out-patient samples collected in the laboratory. Results: Of the 96,328 tubes received during the data collection period, 1469 samples were found unsuitable for further processing. This accounted for 1.52% of all samples collected in the laboratory. Rejections arose as a result of the following reasons: 0.74% were rejected due to hemolysis; 0.47% were specimens without proper requisition slips; and 0.23% had insufficient sample quantity. Conclusion: Of all the samples received in the lab, the overall percentage of rejection is 1.52%.

Validation of a scoring system to predict difficult laparoscopic cholecystectomy

INTRODUCTION Laparoscopic cholecystectomy (LC) is one of the most common laparoscopic procedures being performed by general surgeons all over the world. Preoperative prediction of the risk of conversion or difficulty of operation is an important aspect of planning laparoscopic surgery. The purpose of our prospective study was to analyze various risk factors and to predict difficulty and degree of difficulty preoperatively by the use of a scoring system. MATERIALS This prospective study was conducted in the department of surgery, Lady Hardinge Medical College and associated Dr Ram Manohar Lohia Hospital, Delhi, India. The parameters considered in the preoperative scoring method were old age, male sex, history of hospitalization, obesity, previous abdominal surgery scar, palpable gall bladder, wall thickness of gall bladder, pericholecystic collection and impacted stone. A total of 210 patients were included in the study. RESULTS We found that history of hospitalization, palpable gall bladder, impacted stone and gall bladder wall thickness were statistically significant factors for prediction of difficult laparoscopic cholecystectomy. Sensitivity and specificity of this preoperative scoring method were found to be 95.74% and 73.68% respectively. Positive predictive values of this scoring method were 90% and 88% for easy and difficult cases respectively. Area under ROC curve was 0.86. Conversion rate from laparoscopic to open cholecystectomy was found to be 4.28%. CONCLUSION With the help of accurate prediction, high risk patient may be informed before hand regarding the probability of conversion and hence they may have a chance to make arrangements accordingly. On the other hand, surgeons also may have to schedule the time and team for the operation appropriately. Surgeons can also be aware about the possible complications that may arise in high risk patients.

Association between insulin resistance and hypothyroidism in females attending a tertiary care hospital

The effect of thyroid status on insulin sensitivity is of great interest but despite various studies there is conflicting data on this subject. The study group comprised of 25 female subjects each with subclinical hypothyroidism, overt hypothyroidism and euthyroid controls. Serum samples of all the patients were assayed for thyroid profile, Insulin and lipid profile. Homeostasis model of assessment (HOMA-IR) was employed to assess the level of insulin resistance. Patients with hypothyroidism demonstrated insulin resistance and dyslipidemia as observed by the higher HOMA-IR and cholesterol and triglyceride levels respectively as compared to the controls. A significantly positive correlation between TSH and HOMA-IR level was also observed in the hypothyroidism group. Thyroid dysfunction leads to alterations in glucose and lipid metabolism which is an important risk factor for cardiovascular diseases. The dyslipidemia and insulin resistance should be managed aggressively to reduce the impending risk.

Evaluation of the Role of Magnetic Resonance Spectroscopy in the Diagnosis of Follicular Malignancies of Thyroid

OBJECTIVES To evaluate role of magnetic resonance spectroscopy in differentiating benign from malignant follicular nodules. DESIGN Prospective study. SETTING Department of Surgery in collaboration with Department of Radio Diagnosis, Maulana Azad Medical College, Delhi, India. PATIENTS Twenty-five patients with a solitary thyroid nodule with follicular etiology. INTERVENTIONS Magnetic resonance spectroscopy was carried out in all the cases, and its findings were compared with the final diagnosis based on histopathological examination of sample obtained at surgery. MAIN OUTCOME MEASURES Choline peak detected on MRS. RESULTS There were 17 benign cases, 16 follicular adenomas, and 1 colloid goiter. Of the 17 benign cases, only 1 showed choline peak; however, all 8 follicular carcinoma cases showed prominent choline peak. Hence, the sensitivity is 100% while the specificity is 94.11%. CONCLUSION Magnetic resonance spectroscopy may prove to be a sensitive diagnostic tool in differentiating follicular adenomas from carcinomas.