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   2014| April  | Volume 139 | Issue 4  
    Online since June 9, 2014

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A brief history of vaccines & vaccination in India
Chandrakant Lahariya
April 2014, 139(4):491-511
The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.
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Queyrat erythroplasia accompanied by bladder cancer in a circumcised male
Savas Ozturk, Haydar Ucak
April 2014, 139(4):650-651
  3,675 246 -
Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer
Shirish Shukla, Sutapa Mahata, Gauri Shishodia, Shailja Pande, Gaurav Verma, Suresh Hedau, Suresh Bhambhani, Archana Kumari, Swaraj Batra, Seemi F. Basir, Bhudev C. Das, Alok C. Bharti
April 2014, 139(4):531-543
Background & objectives: High-risk human papilloma virus (HR-HPV) infection and its integration in host genome is a key event in malignant transformation of cervical cells. HPV16 being a dominant HR-HPV type, we undertook this study to analyze if viral load and physical state of the virus correlated with each other in the absence of other confounding variables and examined their potential as predictors of progressive cervical lesions. Methods: Both, viral load and integration status of HPV16 were determined by real time URR PCR and estimation of E2:E6 ratio in a total of 130 PGMY-RLB -confirmed, monotypic HPV16-infected cervical DNA samples from biopsies of cytology-confirmed low grade (LSIL, 30) and high grade (HSIL, 30), and invasive carcinoma, (squamous cell carcinoma SCC, 70) cases. Results: Investigation of DNA samples revealed a gradual increase in HPV16 viral load over several magnitudes and increased frequency of integration from LSIL to HSIL and HSIL to invasive cancer in relation to the severity of lesions in monotypic HPV16-infected cervical tissues. In a substantial number of precancer (11/60) and cancer cases (29/70), HPV16 was detected in concomitant mixed form. The concomitant form of HPV16 genome carried significantly higher viral load. Interpretation & conclusions: Overall, viral load and integration increased with disease severity and could be useful biomarkers in disease progression, at least, in HPV16-infected cervical pre-cancer and cancer lesions.
  1,697 522 -
Role of neural modulation in the pathophysiology of atrial fibrillation
Shailesh Male, Benjamin J. Scherlag
April 2014, 139(4):512-522
Atrial-fibrillation (AF) is the most common clinically encountered arrhythmia affecting over 1 per cent of population in the United States and its prevalence seems to be moving only in forward direction. A recent systemic review estimates global prevalence of AF to be 596.2 and 373.1 per 100,000 population in males and females respectively. Multiple mechanisms have been put forward in the pathogenesis of AF, however; multiple wavelet hypothesis is the most accepted theory so far. Similar to the conduction system of the heart, a neural network exists which surrounds the heart and plays an important role in formation of the substrate of AF and when a trigger is originated, usually from pulmonary vein sleeves, AF occurs. This neural network includes ganglionated plexi (GP) located adjacent to pulmonary vein ostia which are under control of higher centers in normal people. When these GP become hyperactive owing to loss of inhibition from higher centers e.g. in elderly, AF can occur. We can control these hyperactive GP either by stimulating higher centers and their connections, e.g. vagus nerve stimulation or simply by ablating these GP. This review provides detailed information about the different proposed mechanisms underlying AF, the exact role of autonomic neural tone in the pathogenesis of AF and the possible role of neural modulation in the treatment of AF.
  1,772 428 -
Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats
Gajendra Kumar, Amita Srivastava, Surinder Kumar Sharma, Yogendra Kumar Gupta
April 2014, 139(4):610-618
Background & objectives: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. Results: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. Interpretation & conclusions: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney.
  1,552 432 -
Potter's syndrome - a fatal constellation of anomalies
MG Manoj, S. Kakkar
April 2014, 139(4):648-649
  1,439 331 -
Age related secretary pattern of growth hormone, insulin-like growth factor-I & insulin-like growth factor binding protein-3 in postmenopausal women
Akbar Aliasgarzadeh, Morteza Ghojazadeh, Reza Haji-Hoseini, Faezeh Mehanfar, Reza Piri, Mohammad Naghavi-Behzad, Nariman Nezami
April 2014, 139(4):598-602
Background & objectives: After menopause in women, loss of bone density increases rapidly with estrogen deficiency. Evidence has revealed that this deficiency may be directly correlated with growth hormone (GH) level declining with age. The present study was designed to evaluate the age dependant patterns of GH, insulin-like growth factor-1 (IGF1-1) and insulin-like growth factor binding protein-3 (IGFBP-3) endogenous secretion in postmenopausal women. Methods: During this prospective study in a 12-month period, 150 postmenopausal women were enrolled who were referred to the densitometry unit of bone research centre of Tabriz University of Medical Sciences for assessing bone mineral density. Serum levels of basal and clonidine stimulated GH were measured using radioimmunoassay while IGF-1 and IGFBP-3 were measured by ELISA. Post stimulation over 3 to 6 fold increase in GH over the baseline level was considered normal response and less increase was considered abnormal. Results: There were no significant differences in the mean levels of GH0, GH60 and GH90 in different age groups of postmenopausal women. No significant difference in the mean IGFBP-3 and IGF-1 levels was seen in different age groups of postmenopausal women. The number of postmenopausal women with abnormal response to stimulation by clonidine in 61-70 and > 70 yr age groups was higher than in other groups (P< 0.05). Interpretation & conclusions: Despite the higher rate of abnormal response to stimulation by clonidine in women aged more than 60 yr, the current study showed no significant correlation between age, and the basal and stimulated GH secretion rate and serum levels of IGF-1 and IGFBP-3 in postmenopausal women.
  1,470 286 -
An approach for conjugation of 177 Lu- DOTA-SCN- Rituximab (BioSim) & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients
Parul Thakral, Suhas Singla, Madhav Prasad Yadav, Atul Vashist, Atul Sharma, Santosh Kumar Gupta, C. S. Bal, Snehlata , Arun Malhotra
April 2014, 139(4):544-554
Background & objectives: The prerequisite of radioimmunotherapy is stable binding of a radionuclide to monoclonal antibodies, which are specific to the tumour-associated antigen. Most B-cell lymphomas express CD20 antigen on the surface of the tumour cells, making it a suitable target for therapeutic radioactive monoclonal antibodies. In the present study, the immunoconjugate of biosimilar Rituximab (Reditux™) and macrocyclic chelator, p-SCN-Bz-DOTA, was prepared and radiolabelled with Lutetium-177 followed by quality control procedures. Methods: Rituximab(BioSim) was desalted with sodium bicarbonate (0.1M, pH 9.0) and incubated with DOTA-SCN (1:50). The effectiveness of the conjugation was evaluated by determining the number of chelators per antibody molecule. This conjugate was radiolabelled with Lutetium-177 and purified using PD10 column. The quality control parameters like pH, clarity, radiochemical purity, in vitro stability and sterility were studied. Immunoreactivity of 177 Lu-DOTA-Rituximab (BioSim) was assessed using RAMOS cells. The radioimmunoconjugate (RIC) after stringent quality assurance was injected in three patients and the biodistribution profile was analysed. Results: An average of 4.25 ± 1.04 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab (BioSim).The radiochemical purity of the labelled antibody was > 95 per cent with preserved affinity for CD20 antigen. The final preparation was stable up to about 120 h when tested under different conditions. A favourable biodistribution profile was observed with liver showing the maximum uptake of the RIC. Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim) in patients of relapsed and refractory non Hodgkin's lymphoma can be considered.
  1,276 429 -
Tobacco cessation in India: A priority health intervention
K. R. Thankappan
April 2014, 139(4):484-486
  1,215 423 -
Polycystic ovary syndrome: Novel insights into causes and therapy
Alka Kriplani, Garima Kachhawa
April 2014, 139(4):653-654
  1,241 383 -
Phenotypic identification & molecular detection of bla NDM-1 gene in multidrug resistant Gram-negative bacilli in a tertiary care centre
K Anjana Shenoy, EK Jyothi, R. Ravikumar
April 2014, 139(4):625-631
Background & objectives: Carbapenemase-producing Enterobacteriaceae isolates have been increasingly identified worldwide. Though molecular data regarding New Delhi metallo-beta-lactamase-1 (NDM-1) producers are available, data regarding their rate of infection in a hospital setting and percentage among different clinical isolates are scarce. Hence, this study was undertaken to determine the occurrence of blaNDM-1 gene among clinical isolates of multidrug resistant Gram-negative bacilli (MDRGNB) in a tertiary care centre in Bangalore, Karnataka, India. Methods: A total of 74 MDRGNB isolates were studied. These were screened for MBL production by phenotypic assays such as double disk synergy test (DDST) and Modified Hodge's test (MHT). PCR was performed for the molecular detection of the gene and antibiograms were confirmed by automated bacteriology system. Results: Of the 74 MDRGNB isolates, 34 were positive for blaNDM-1 gene. All isolates were resistant to aztreonam and two isolates were resistant to tigecycline. Complete resistance to the tested carbapenems was seen in 28 (82.35%) of the positive isolates whereas variable carbapenem resistance was seen in six (17.64%) of the positive clinical isolates. Of the total 34 PCR positive isolates, 33 (97.05%) NDM-1 producers were identified by DDST and 26 (76.47%) by MHT as producers of MBL. Interpretation & conclusions: A high percentage of plasmid encoded NDM was noted in MDRGNB. Phenotypic and molecular screening should be employed along with routine antimicrobial susceptibility testing to reflect the true number of metallo-beta-lactamase producers.
  1,177 425 -
Pasteurization of bone for tumour eradication prior to reimplantation - An in vitro & pre-clinical efficacy study
Jyoti Kode, Prasad Taur, Ashish Gulia, Nirmala Jambhekar, Manish Agarwal, Ajay Puri
April 2014, 139(4):585-597
Background & objectives: In current era of limb-salvage therapy, pasteurization of bone sarcomas is receiving growing attention as a potential extracorporeal treatment and cost-effective alternative to allografts and radiation before surgical reimplantation. Detailed in vitro and in vivo pre-clinical study to evaluate efficacy of pasteurization to eradicate malignant cells has not been reported yet. The present study was carried out to assess the efficacy of pasteurization to kill tumour cells both in vitro and in vivo. Methods: Surgically resected specimens of osteosarcomas (n=4) were cut into equal halves and one section was pasteurized by heating at 60°C to 65°C for 40 min. Paired samples before and after pasteurization were studied in vitro for DNA ploidy, evaluation of histological change and elimination of mitotic activity. These tissues were transplanted in immune-deficient NOD-SCID mice to evaluate effect on tumour-generating ability, presence of human nuclei, osteopontin and cytokine/chemokines released in tumour-transplanted mice. Results: Non-pasteurized tumour samples had viable tumour cells which exhibited significant growth in culture, increased proliferative ability and clonogenic potential while respective pasteurized tumour tissues did not grow in culture and did not exhibit clonogenicity. Flow cytometry revealed that propidium iodide positive dead cells increased significantly (P< 0.01) post pasteurization. Seven of 12 non-pasteurized tumour transplanted mice demonstrated tumour-forming ability as against 0 of 12 in pasteurized tumour transplanted mice. Solid tumour xenografts exhibited strong expression of anti-human nuclei and osteopontin by immunohistochemistry as well as secretary human interluekin-6 (IL-6) while pasteurized mice failed to express these markers. Interpretation & conclusions : This study has provided a basis to establish pasteurization as being efficacious in ensuring tumour eradication from resected bone tumour specimens. Pasteurized tumour bearing bone can thus safely be used to reconstruct large defects after tumour resection.
  1,184 281 -
Tobacco cessation outcomes in a cohort of patients attending a chest medicine outpatient clinic in Bangalore city, southern India
P. K. Mony, D. P. Rose, P. Sreedaran, G. D'Souza, K. Srinivasan
April 2014, 139(4):523-530
Background & objectives: Nicotine dependence is a widely prevalent and harmful chronic addictive disorder. Quitting tobacco use is however, uncommon in India. We present long-term treatment outcomes of out-patient, tobacco cessation treatments from a specialty clinic setting in southern India. Methods: Patients seen in a tobacco cessation clinic were characterized for tobacco use, nicotine dependence and motivation for quitting and offered pharmacologic/non-pharmacologic treatment. They were subsequently contacted telephonically at a mean (±standard deviation) of 24 (±9.1) months to assess tobacco cessation outcome defined as 'point prevalence of 1-month abstinence' by self-reporting. Results: The mean age of participants was 48.0 ±14.0 yr. Tobacco use distribution was: beedis only (22%), cigarettes only (49%), beedis and cigarettes (18%), chewing only (2%), and smoking and chewing (9%). Two-thirds had high level of nicotine dependence. Of the 189 patients enrolled, only 15 per cent attended follow up clinics. Only 106 (56%) patients were successfully contacted telephonically and 83 (44%) were lost to follow up. Self-reported point prevalence abstinence was 5 per cent by 'intent-to-treat' analysis and 10 per cent by 'responder' analysis. Two clinical parameters - high level of nicotine dependence [estimated by the heaviness of smoking index (HSI)] and the absence of vascular or other chronic disease were found to be associated with successful quitting; these were however, not significant on multivariate analysis. Interpretation & conclusions: Our study has identified low quit-rates in a cohort of patients attending a hospital-based tobacco cessation clinic. In the absence of clear-cut predictors of cessation with low quit-rates, there should be continued efforts to improve cessation outcomes and identify predictors for action.
  1,063 387 -
Effect of active immunization against angiotensin II type 1 (AT1) receptor on hypertension & arterial remodelling in spontaneously hypertensive rats (SHR)
Liu-Dong Li, Miao Tian, Yu-Hua Liao, Zi-Hua Zhou, Fen Wei, Feng Zhu, Min Wang, Bin Wang, Yu-Miao Wei
April 2014, 139(4):619-624
Background & objectives: a0 ngiotensin II receptor type 1 (AT1) is known to be involved in the pathogenesis of hypertension. t0 his study was undertaken to explore the effect of active immunization against AT1 receptor on blood pressure and small artery remodelling in spontaneously hypertensive rat (SHR). Methods: Male SHR and Wistar rats aged two months were actively immunized with different peptides (ATR12185ͱͲATR10014 and ATR12181) corresponding to particular sequences of rat AT1 receptor, while another SHR group was given losartan (10 mg/kg/day) orally once a day. Anti-AT1 receptor antibodies were detected by ELISA and blood pressure was measured. The effect of the antibodies on the artery and vascular smooth muscle cells (VSMCs) proliferation was studied. Results: all immunized animals produced antibodies against the particular peptides. The systolic blood pressure was decreased in the SHR immunized with peptide-ATR12181 compared with the control. However, no changes were observed in the SHR immunized with other two peptides. The Wistar rats immunized with the three peptides did not show any changes in blood pressure. The media/lumen area ratio of the mesenteric artery was reduced in SHR immunized with ATR12181 and similar to that of the SHR treated with losartan. The antibody from SHR immunized with ATR12181 had no effect on the proliferation of VSMC. But it could inhibit the proliferation caused by angiotensin II and its effect at the titre of 1:40 was similar to that of 1µmol/l losartan. Interpretation & conclusions : Our findings demonstrated that the antibody from SHR immunized with ATR12181 had the effect of reducing blood pressure and target organ protection similar to losartan. Active immunization against AT1 receptor may be a promising strategy in future for the treatment of hypertension.
  946 350 -
Detection & characterization of necrotoxin producing Escherichia coli (NTEC) from patients with urinary tract infection (UTI)
Helina Rahman, Manab Deka
April 2014, 139(4):632-637
Background & objectives: Urinary tract infections (UTI) are a serious health problem affecting millions of people each year. Although appreciable work on various aspects of UTI including aetiology per se has been done, information on the emerging pathogens like necrotoxigenic Escherichia coli (NTEC) is largely lacking in India. In the present study E. coli isolates from patients with urinary tract infection from northeastern India were investigated for detection and characterization of NTEC. Methods: E. coli isolated and identified from urine samples of patients with UTI were serotyped. Antibiogram was determined by disc diffusion test. Plasmid profile was also determined. Virulence genes of NTEC (cnf1, cnf2, pap, aer, sfa, hly, afa) were detected by PCR assay. E.coli isolates carrying cnf gene (s) were identified as NTEC. Results: A total of 550 E. coli were isolated and tested for the presence of cnf genes. Of these, 84 (15.27%) belonged to NTEC. The cnf1 gene was present in 52 (61.9%) isolates, cnf2 in 23 (27.4%) and 9 (10.7%) carried both cnf1 and cnf2 genes. All the NTEC strains were found to harbour the pap and aer genes. Serogroup O4 was found to be the most common among the 12 serogroups identified amongst the NTEC isolates. Majority of the isolates (96.4%) were sensitive to furazolidone and were highly resistant to ampicillin. NTEC were found to harbour different numbers of plasmids (1 to 7). No association was observed between the number of plasmids and the antibiotic resistance of the isolates. Interpretation & conclusions: The results of the present study showed that about 15 per cent of E. coli isolates associated with UTI belonged to NTEC. More studies need to be done from other parts of the country.
  916 336 -
Downregulated inhibitor of growth 3 (ING3) expression during colorectal carcinogenesis
Wen-feng Gou, Hong-zhi Sun, Shuang Zhao, Zhe-feng Niu, Xiao-Yun Mao, Yasuo Takano, Hua-chuan Zheng
April 2014, 139(4):561-567
Background & objectives: ING3 (inhibitor of growth protein 3) overexpression decreased S-phase cell population and colony-forming efficiency, and induced apoptosis at a p53-mediated manner. The aim of this study was to investigate the clinicopathological and prognostic significance of ING3 expression in colorectal carcinogenesis and subsequent progression. Methods: ING3 expression was examined by immunohistochemistry on tissue microarray containing colorectal non-neoplastic mucosa (NNM), adenoma and adenocarcinoma. Colorectal carcinoma tissue and cell lines were studied for ING3 expression by Western blot or RT-PCR. Results: ING3 mRNA was differentially expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620 and WiDr cells. Carcinomas showed significantly lower ING3 expression than matched NNM at mRNA level (P< 0.05), but not at protein level. Immunohistochemically, ING3 expression was significantly decreased from NNM, adenoma to adenocarcinoma (P< 0.05). ING3 expression was not correlated with age, sex, tumour size, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumour- node- metastasis staging or differentiation. Kaplan-Meier analysis indicated that ING3 protein expression was not associated the prognosis of the patients with colorectal carcinoma (P< 0.05). Interpretation & conclusions: Our study showed that downregulated ING3 expression might play an important role in colorectal adenoma-adenocarcinoma sequence. Further studies are required to understand the mechanism.
  946 288 -
Blood count in new onset atrial fibrillation after acute myocardial infarction - A hypothesis generating study
Klaus Distelmaier, Gerald Maurer, Georg Goliasch
April 2014, 139(4):579-584
Background & objectives: Atrial fibrillation (AF) is a common complication after acute myocardial infarction (AMI) and associated with increased morbidity and mortality. Previous studies identified high white and red blood cell count as potential risk factors for new onset AF. The objective of this retrospective, nested case-control study was to examine the association of different parameters of the blood count with the development of new onset of AF after AMI. Methods: A total of 66 consecutive patients with new onset AF after AMI and 132 sex and age matched controls were enrolled into the study and analyzed whether parameters of the blood count, including leukocytes, platelets, haemoglobin, haematocrit or erythrocyte count, are associated with the occurrence of AF after AMI. All AMI patients had undergone coronary angiography. Results: Patients with post-AMI AF displayed significantly higher levels of haemoglobin (14.2 g/dl, IQR 12.4-15 vs. 12.9 g/dl, IQR 11.7-13.8; P< 0.001), haematocrit (41.7 %, IQR 36.6-44.3 vs. 38.7 %, IQR 34.7-41.5; P 0.0015), and erythrocyte count (4.6 T/l, IQR 4.1-5 vs. 4.2 T/l, IQR 3.9-4.65; P< 0.001). In the unadjusted and adjusted logistic regression analysis, the blood parameters most strongly associated with the outcome were serum haemoglobin (crude OR 2.20, 95% CI 1.40- 3.47, P 0.001; adjusted OR 3.82, 95% CI 1.71- 8.54, P 0.001) and erythrocyte count (crude OR 2.10, 95% CI 1.36-3.22, P 0.001; adjusted OR 3.79, 95% CI 1.73- 8.33, P 0.001), whereas haematocrit did not reach statistical significance. Interpretation & conclusions: This study shows a significant independent association between serum haemoglobin, haematocrit, erythrocyte count and occurrence of AF after AMI. However, the pathophysiologic mechanism underlying these associations and its potential clinical applicability need to be further elucidated.
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CYP4F2 1347 G > A & GGCX 12970 C > G polymorphisms: frequency in north Indians & their effect on dosing of acenocoumarol oral anticoagulant
Saurabh Singh Rathore, Surendra Kumar Agarwal, Shantanu Pande, Sushil Kumar Singh, Tulika Mittal, Balraj Mittal
April 2014, 139(4):572-578
Background & objectives: CYP4F2 and γ-glutamyl carboxylase (GGCX) have small but significant roles in the maintenance dose of coumarinic oral anticoagulants (COAs). CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms have been used in the pharmacogenetic dosing algorithms of warfarin for Caucasians and Chinese populations. India has a large population with multiple ethnic groups but there are no reports about the frequencies of these polymorphisms in north Indians. In the present study, we aimed to find out the allelic frequencies of CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms in a north Indian population and relate these to daily maintenance drug dose requirements of COA. Methods: CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms were genotyped by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) protocols and Taqman SNP discrimination assays in healthy volunteers (n=102) and patients (n=225) receiving acenocoumarol, an oral anticoagulant, after cardiac valve replacement surgery. Results: In healthy volunteers, the allele frequencies for CYP4F2 1347 G > A and GGCX 12970 C > G were 43.14 and 1.43 per cent, respectively. No significant differences in mean weight normalized doses of acenocoumarol were found for these CYP4F2 and GGCX genotypes. Binary logistic regression analysis revealed no significant association of any of the genotypes or alleles with the dosing phenotypes for both the SNPs. Interpretation & conclusions: We report distinct frequencies of CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms in north Indians but these polymorphisms did not have significant bearing on maintenance dose of acenocoumarol oral anticoagulant in cardiac valve replacement patients.
  839 335 -
Role of oxidative stress & antioxidant defence in ulcerative colitis patients from north India
S. V. Rana, S. Sharma, K. K. Prasad, S. K. Sinha, K. Singh
April 2014, 139(4):568-571
Background & objectives: Oxidative stress contributes to severity of ulcerative colitis (UC) but the status of erythrocyte antioxidant defence remains unknown. The present study was aimed to study the role of oxidative stress and antioxidant levels in erythrocytes of UC patients from north India. Methods: A total of 81 adult UC patients and 85 age and sex matched apparently healthy controls were included in this study. Levels of lipid peroxidation (LPO), reduced glutathione (GSH), catalase and superoxide dismutase (SOD) were measured in erythrocytes. Results: Mean age of UC patients was 43.5 yr (range 18-64 yr) while in the control group this was 45.3 yr (range 20-64 yr). LPO, catalase and SOD levels in UC patients were significantly increased (P< 0.05) compared to healthy controls, while GSH levels in UC patients were significantly decreased (P< 0.05) compared to healthy controls Ulcerative colitis activity score (UCAI) was 157.4±27.6 in UC patients. Interpretation & conclusions: Increased levels of LPO, SOD, catalase and a decreased level of GSH represent that oxidative stress plays a significant role in pathophysiology of UC. Further, the levels of LPO, GSH, catalase and SOD remained same during different UCAI.
  848 320 -
World Health Day 2014: an opportunity to promote research on vectors & vector-borne diseases
Leonard Ortega
April 2014, 139(4):481-483
  777 373 -
Predictors of quitting behaviour with special reference to nicotine dependence among adult tobacco-users in a slum of Burdwan district, West Bengal, India
Kamirul Islam, Indranil Saha, Rajib Saha, Sufi Abdul Samim Khan, Rupali Thakur, Swapnil Shivam
April 2014, 139(4):638-642
Background & objectives: Information on predictors of quitting behaviour in adult tobacco users is scarce in Indian context. Hence, this study was undertaken to assess the intention of tobacco-users towards quitting and its predictors with reference to nicotine dependence. Methods: A community-based observational, cross-sectional study was conducted on 128 adult tobacco-users (89.8% male) with mean age of 41.1 ± 15.7 yr selected by complete enumeration method. Data were collected by interview using pre-designed, pre-tested schedule. Nicotine dependence was assessed by Fagerstrφm Test for Nicotine Dependence (FTND) questionnaire. Result: Of the 128 users, 63.3 per cent had intention to quit. Majority of the tobacco users who did not intend to quit belonged to the age group of > 40 yr (66.0%), were illiterate (55.3%), started tobacco use at 11 - 15 yr of age (57.4%), had been using tobacco for 20 yr or more (70.2%), were daily tobacco users (91.5%), and highly dependent on nicotine (80.9%). Tobacco users having high FTND score and who started tobacco use early in life were 1.83 and 3.30 times more unintended to quit, respectively. Interpretation & conclusions:Suitable plan for quitting should be developed depending on the FTND score of an individual, the most important determinant of quitting that would be beneficial for categorization of the treatment leading to successful quitting.
  797 310 -
New HPV16 viral biomarkers to understand the progression of cervical lesions towards cancer
Jean-Luc Pretet, David Guenat, Didier Riethmuller, Christiane Mougin
April 2014, 139(4):487-489
  772 333 -
Multi-drug resistance in clinical isolates of Gram-negative bacilli in a tertiary care hospital of Assam
Himadri Dutta, Reema Nath, Lahari Saikia
April 2014, 139(4):643-645
  717 285 -
Covalent immobilization of lipase, glycerol kinase, glycerol-3-phosphate oxidase & horseradish peroxidase onto plasticized polyvinyl chloride (PVC) strip & its application in serum triglyceride determination
Nidhi Chauhan, Jagriti Narang, Chandra Shekhar Pundir
April 2014, 139(4):603-609
Background & objectives:Reusable biostrip consisting enzymes immobilized onto alkylamine glass beads affixed on plasticized PVC strip for determination of triglyceride (TG) suffers from high cost of beads and their detachments during washings for reuse, leading to loss of activity. The purpose of this study was to develop a cheaper and stable biostrip for investigation of TG levels in serum. Methods: A reusable enzyme-strip was prepared for TG determination by co-immobilizing lipase, glycerol kinase (GK), glycerol-3-phosphate oxidase (GPO) and peroxidase (HRP) directly onto plasticized polyvinyl chloride (PVC) strip through glutaraldehyde coupling. The method was evaluated by studying its recovery, precision and reusability. Results: The enzyme-strip showed optimum activity at pH 7.0, 35 o C and a linear relationship between its activity and triolein concentration in the range 0.1 to 15 mM. The strip was used for determination of serum TG. The detection limit of the method was 0.1 mM. Analytical recovery of added triolein was 96 per cent. Within and between batch coefficients of variation (CV) were 2.2 and 3.7 per cent, respectively. A good correlation (r=0.99) was found between TG values by standard enzymic colrimetric method employing free enzymes and the present method. The strip lost 50 per cent of its initial activity after its 200 uses during the span of 100 days, when stored at 4 o C. Interpretation & conclusions: The nitrating acidic treatment of plasticized PVC strip led to glutaraldehyde coupling of four enzymes used for enzymic colourimetric determination of serum TG. The strip provided 200 reuses of enzymes with only 50 per cent loss of its initial activity. The method could be used for preparation of other enzyme strips also.
  729 260 -
Bioevaluation of 125 I Ocu-Prosta seeds for application in prostate cancer brachytherapy
Archana Mukherjee, Haladhar Dev Sarma, Sanjay Saxena, Yogendra Kumar, Pradip Chaudhari, Jayant Sastri Goda, Pranjal Adurkar, Ashutosh Dash, Grace Samuel
April 2014, 139(4):555-560
Background & objectives: In recent years, brachytherapy involving permanent radioactive seed implantation has emerged as an effective modality for the management of cancer of prostate. 125 I-Ocu-Prosta seeds were indigenously developed and studies were carried out to assess the safety of the indigenously developed 125 I-Ocu-Prosta seeds for treatment of prostate cancer. Methods: Animal experiments were performed to assess the likelihood of in vivo release of 125 I from radioactive seeds and migration of seeds implanted in the prostate gland of the rabbit. In vivo release of 125 I activity was monitored by serial blood sampling from the auricular vein and subsequent measurement of 125 I activity. Serial computed tomography (CT) scans were done at regular intervals till 6 months post implant to assess the physical migration of the seeds. Results: The laser welded seeds maintained their hermeticity and prevented the in vivo release of 125 I activity into the blood as no radioactivity was detected during follow up blood measurements. Our study showed that the miniature 125 I seeds were clearly resolved in CT images. Seeds remained within the prostate gland during the entire study period. Moreover, the seed displacement was minimal even within the prostate gland. Interpretation & conclusions: Our findings have demonstrated that indigenously developed 125 I-Ocu-Prosta seeds may be suitable for application in treatment of prostate cancer.
  691 233 -
Clinical assessment and management of childhood psychiatric disorders
V Jayanthini
April 2014, 139(4):652-653
  563 223 -
Some Forthcoming Scientific Events

April 2014, 139(4):655-655
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  393 288 -
Susceptibility testing of Staphylococaus aureus
V. Anil Kumar
April 2014, 139(4):646-646
  417 255 -
Authors' response
Sheetal Chitnis, Gunjan Katara, Nanda Hemavani, Siddika Pareek, Dhananjay Sadashiv Chitnis
April 2014, 139(4):646-647
  412 199 -