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   2013| June  | Volume 137 | Issue 6  
    Online since July 4, 2013

 
 
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EDITORIAL
Adolescent drug abuse - Awareness & prevention
Bharath Chakravarthy, Shyam Shah, Shahram Lotfipour
June 2013, 137(6):1021-1023
PMID:23852281
  2,956 1,442 -
CENTENARY REVIEW ARTICLE
Indian childhood cirrhosis (ICC) & ICC-like diseases: The changing scenario of facts versus notions
NC Nayak, AR Chitale
June 2013, 137(6):1029-1042
PMID:23852284
Indian childhood cirrhosis (ICC), a disease considered to have been endemic in and unique to India has now been documented in children of non-Indian origin from other countries. More recently available findings from a large multicentre study sponsored by the Indian Council of Medical Research (ICMR) have dispelled some of the generally accepted notions and have established several new facts on different aspects of the disease. All relevant reports on ICC and ICC-like diseases, till date, were reviewed to obtain a proper perspective on the current state of our understanding on this non-Wilsonian copper overload liver disease. A primary role of exogenous copper in causing the disease was earlier debated on the basis of studies in India but investigators abroad studying some sporadic cases and a series of endemic ICC-like diseases supported a hepatotoxic injury by ingested copper in genetically susceptible infants and children in ICC- like disease and in ICC. Epidemiologic and morphologic findings in the well controlled ICMR study based on 225 cases of ICC and 426 controls, all confirmed on liver biopsy, have however, convincingly refuted this concept. Additionally, this study revealed that unlike what has been believed earlier, older children more than 3 yr age can get the disease and that in its natural course the hepatic histology can transform between the characteristic one considered diagnostic and some other patterns, any one of which can be the morphologic manifestation at first presentation of the patient. Older children and cases with milder morphologic changes at presentation had longer survival. The overall inference from critical analysis of all available data is that ICC and ICC-like diseases clinically manifest in a child of any age though common in younger ones, and a clinical diagnosis must be made in any child with so-called 'cryptogenic cirrhosis'. Exposure to exogenous copper in food, milk and water should not be a prerequisite for this consideration. A liver biopsy whenever feasible should be mandatory for confirmation with the understanding that the morphologic changes in liver can present a few other patterns besides the characteristic one currently taken to be diagnostic. The ascribed current decline in encountering ICC is likely to be due partly to missing a diagnosis and partly to a true reduction in incidence consequent on time related economic and socio-cultural changes.
  2,082 413 -
ORIGINAL ARTICLES
Low dose mifepristone in medical management of uterine leiomyoma - An experience from a tertiary care hospital from north India
Vidushi Kulshrestha, Alka Kriplani, Nutan Agarwal, Neetu Sareen, Pradeep Garg, Smriti Hari, Jyoti Thulkar
June 2013, 137(6):1154-1162
PMID:23852296
Background & objectives: Uterine myoma is a common indication for hysterectomy in India. An effective medical treatment option may reduce hysterectomy associated morbidity. This study was undertaken to evaluate efficacy and safety of low dose mifepristone in medical management of myoma and to compare two doses - 10 vs. 25 mg/day. Methods: In this randomized clinical trial, women with symptomatic myoma or myoma>5cm were included. Uterine size >20 wk, fibroids >15 cm were excluded. Pictorial blood loss assessment chart (PBAC) score was used to assess menstrual-blood-loss and visual analog scale (VAS) for other symptoms. Haemogram, liver function test, ultrasound with doppler and endometrial histology was performed. Patients were randomized and were given oral mifepristone as 25 mg/day in group 1 and 10 mg/day in group 2 for 3 months. Patients were followed at 1, 3 and 6 months. Results: Seventy patients in group 1 and 73 in group 2 completed treatment. Mean PBAC score reduced from 253 to 19.8 and from 289.2 to 10.4 at 1 and 3 months in groups 1 and 2, respectively. At 3 months, 67 of 70 (95.7%) patients of group 1 and 66 of 73 (90.4%) of group 2 developed amenorrhoea which reverted after median 34 (range 4-85) days. Mean myoma volume decreased by 35.7 per cent (from 176.8 to 113.7cm 3 ) and 22.5 per cent (from 147.6 to 114.4 cm 3 ) at 3 months in groups 1 and 2, respectively. Side effects seen were leg cramps in 7 of 70 (10%) and 5 of 73 (6.8%) and hot-flushes in 5 of 70 (7.1%) and 5 of 73 (6.8%) in groups 1 and 2, respectively. Repeat endometrial-histopathology did not reveal any complex hyperplasia or atypia in either group. Interpretation & conclusions: Mifepristone (10 and 25 mg) caused symptomatic relief with more than 90 per cent reduction in menstrual blood. Greater myoma size reduction occured with 25 mg dose. Amenorrhoea was developed in 90-95 per cent patients which was reversible. It can be a reasonable choice for management of uterine leiomyoma as it is administered orally, cost-effective and has mild side effects.
  1,907 514 -
CLINICAL IMAGES
Cullen's sign for acute haemorrhagic pancreatitis
Rohan P Parikh, Kamlesh J Upadhyay
June 2013, 137(6):1210-1210
PMID:23852306
  2,047 263 -
ARTICLES
Arsenical dermatosis from tubewell water in West Bengal

June 2013, 137(6):1229-1237
Full text not available  [PDF]  [Mobile Full text]  [EPub]
  1,794 163 -
ORIGINAL ARTICLES
Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone
Shamsul Bin Sulaiman, Tan Kok Keong, Chen Hui Cheng, Aminuddin Bin Saim, Ruszymah Bt. Hj Idrus
June 2013, 137(6):1093-1101
PMID:23852290
Background & objectives: Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering. Methods: HA-SMC and TCP/HA-SMC constructs were induced in the osteogenic medium for three weeks prior to implantation in nude mice. The HA-SMC and TCP/HA-SMC constructs were implanted subcutaneously on the dorsum of nude mice on each side of the midline. These constructs were harvested after 8 wk of implantation. Constructs before and after implantation were analyzed through histological staining, scanning electron microscope (SEM) and gene expression analysis. Results: The HA-SMC constructs demonstrated minimal bone formation. TCP/HA-SMC construct showed bone formation eight weeks after implantation. The bone formation started on the surface of the ceramic and proceeded to the centre of the pores. H&E and Alizarin Red staining demonstrated new bone tissue. Gene expression of collagen type 1 increased significantly for both constructs, but more superior for TCP/HA-SMC. SEM results showed the formation of thick collagen fibers encapsulating TCP/HA-SMC more than HA-SMC. Cells attached to both constructs surface proliferated and secreted collagen fibers. Interpretation & conclusions: The findings suggest that TCP/HA-SMC constructs with better osteogenic potential compared to HA-SMC constructs can be a potential candidate for the formation of tissue engineered bone.
  1,438 473 -
REVIEW ARTICLES
Current concepts in the management of small cell lung cancer
Apar Kishor Ganti, William W West, Weining Zhen
June 2013, 137(6):1043-1051
PMID:23852285
Small cell lung cancer (SCLC) has a clinical course that is distinct from its more common counterpart non-small cell lung cancer. SCLC continues to be a major clinical problem, with an aggressive clinical course and short disease-free duration after initial therapy. Current optimal treatment consists of chemotherapy with platinum-etoposide, given concurrently with thoracic irradiation in patients with limited stage disease and chemotherapy alone in those with extensive stage. Prophylactic cranial irradiation (PCI) is recommended for patients who have responded to initial therapy, as it not only decreases the risk of brain metastases and but also improves overall survival. Newer targeted agents are currently being evaluated for this disease.
  1,258 617 -
ORIGINAL ARTICLES
Carrier detection in Duchenne muscular dystrophy using molecular methods
SM Sakthivel Murugan, C Arthi, N Thilothammal, BR Lakshmi
June 2013, 137(6):1102-1110
PMID:23852291
Background & objectives: Duchenne and Becker muscular dystrophies are X-linked allelic disorders which are caused by mutations in the DMD gene. Carrier analysis in DMD is complicated due to the heterozygous nature of the X chromosome. Several techniques have been tried for carrier analysis in families where the mutation is identified including quantitative multiplex PCR (qmPCR), Southern blot, and now multiplex ligation-dependent probe amplification (MLPA). Linkage analysis is used in cases without identifiable mutations. The present study was undertaken to determine the status of probable carriers in families where the DMD deletion/duplication has been identified for the affected index cases. Methods: Carrier status was present in 150 probable carriers from 110 apparently unrelated families where the patients' mutations were known. Of these 110 families, 100 were deletions, 9 duplications and 1 point mutation. Multiplex ligation-dependent probe amplification (MLPA) was used to assess the copy number changes and direct sequencing was used for the case with the point mutation. Results: Of the 150 cases, 49 were found to be carriers. Among the sporadic cases, it was observed that the rate of de novo mutations was very high (71%) as compared to the hereditary cases (29%), which was higher than the calculated rate (30%). It was observed that this difference was more apparent in deletion mutations than in duplications. Interpretation & conclusions: Identifying the DMD carrier rates in the families with unidentified deletions and duplications and where the causative mutation could be small insertions/deletions or point mutations could throw more light into this observation. MLPA was found to be useful in detecting copy number changes in DMD carriers and this could be the method of choice for DMD carrier analysis, when the mutation is detected in the affected child.
  1,359 459 -
Adaptation of heart to training: A comparative study using echocardiography & impedance cardiography in male & female athletes
Dilek Cicek Yilmaz, Belgin Buyukakilli, Serkan Gurgul, Ibrahim Rencuzogullari
June 2013, 137(6):1111-1120
PMID:23852292
Background & objectives: Intensive regular physical exercise training is associated with a physiological changes in left ventricular (LV) morphology and functions. This cardiac remodeling observed in the athletes is associated with the specific haemodynamic requirements of the exercise undertaken. The main objective of this study is to evaluate the effect of endurance training on cardiac morphology, systolic and diastolic LV functions and haemodynamic parameters both in male and female athletes. Methods: Seventy nine healthy athletes (age 20.0 ± 2.6 yr; 49% male) and 82 healthy sedentary adolescent (age 20.8 ± 2.2 yr, 49% male) volunteered to participate in this study. All subjects underwent transthoracic echocardiography and impedance cardiography. Results: Both female and male athletes had greater LV end-diastolic cavity sizes, LV mass and stroke volume (SV) values when compared with controls. Also, in male athletes, LV mass index was higher than in female athletes. While male athletes had lower resting heart rate compared to female athletes, they had higher mean arterial blood pressure. In male athletes, basal septal and mid septal strain values were higher compared to controls. There were no significant differences in strain and peak systolic strain rate values between female athletes and controls. In male athletes, there was a weak positive correlation between SV and LV mass, basal lateral and septal strain values. In female athletes, only a weak positive correlation was found between SV and basal septal strain values. Interpretation & conclusions: Endurance-trained male and female athletes had higher LV mass, LV cavity dimensions and SV compared to sedentary controls. Although there was no difference in diastolic cardiac functions between athletes and controls, local enhanced systolic function was found with increase of SV. Both morphologic and haemodynamic differences were more evident in male athletes.
  1,358 440 -
COMMENTARIES
Are mobile phones the key to HIV prevention for mobile populations in India?
Dallas Swendeman
June 2013, 137(6):1024-1026
PMID:23852282
  562 1,132 -
ORIGINAL ARTICLES
Contact with HIV prevention programmes & willingness for new interventions among truckers in India
SG Prem Kumar, G Anil Kumar, Ramesh Poluru, John A Schneider, Lalit Dandona, Lakshmi Vemu, T Sudha, Kenneth H Mayer, Rakhi Dandona
June 2013, 137(6):1061-1071
PMID:23852287
Background & objectives: Systematic data on existing coverage and willingness for HIV prevention strategies among truckers are not readily available in India. The present study aimed to further the understanding on contact of truckers with existing HIV prevention services and to assess willingness for new HIV prevention strategies. Methods: A total of 1,800 truck drivers and helpers aged 16-65 yr passing through Hyderabad were approached to assess contact made with HIV prevention programmes, history of previous HIV testing and their acceptance for circumcision, oral HIV testing, new medications to control HIV (PrEP) and telephonic counselling. Dried blood samples were collected on filter paper and tested for HIV. Multiple logistic regression was performed for analysis of association between contact with HIV prevention programme and socio-demographic, sexual risk behaviour variables and work characteristics. Results: A total of 1,602 (89%) truckers gave interview and provided blood sample. Forty five truckers tested positive for HIV resulting in HIV prevalence of 2.8 per cent (95% CI 2.0-3.6%). Only 126 truckers (7.9%; 95% CI 6.5-9.2%) reported ever being contacted by staff providing HIV prevention interventions. Previous HIV testing was reported by19 per cent (95% CI 17.3-21.2%). Those reporting contact with HIV prevention programmes ever were more likely to have undergone HIV testing (odds ratio 3.6, 95% CI 2.4-5.4). The acceptance for pre-exposure prophylaxis (PrEP) was 87 per cent, oral HIV testing 98 per cent, and telephonic counselling 82 per cent, but was only 9 per cent for circumcision.Truckers who reported having sex with a man and those who halted regularly at dhabas were significantly more willing to undergo circumcision for HIV prevention (odds ratios 2.7, 95% CI 1.4-5.4 and 2.1, 95% CI 1.3-3.2, respectively). Interpretation & conclusions: Our findings showed that truckers had low contact with HIV prevention programmes, suggesting a need for urgent measures to reach this population more effectively. The willingness for new HIV interventions was high except for circumcision. These findings could be used for further planning of HIV prevention programmes for truckers in India.
  1,300 369 -
A pilot study on real-time transvaginal ultrasonographic elastography of cystic ovarian lesions
Nazan Ciledag, Kemal Arda, Elif Aktas, Bilgin Kadri Aribas
June 2013, 137(6):1089-1092
PMID:23852289
Background & objectives: This study was carried out to determine the appearance of various cystic ovarian lesions on transvaginal real-time ultrasonographic elastography and to investigate its potential in the differential diagnosis of cystic ovarian lesions. Methods: Twenty six women (age range, 27-71 yr; mean age 42 ± 16 yr) with cystic ovarian masses underwent transvaginal B-mode and Doppler ultrasonography, and transvaginal real-time ultrasonographic elastography. Those having ovarian cysts with solid components underwent to biopsy or surgical excision. The elasticity colour code (pattern 1-5), and strain index of cystic ovarian lesions were analyzed and associated with histopathological diagnosis. Results: Eleven of 26 ovarian cysts (42%) (diameter range, 3.2-4.5 cm) without solid component were not colour coded with blue or colour coded with blue-red-green heterogenous mosaic pattern. Fifteen of 26 cystic ovarian lesions (58%) (diameter range, 3.5-6.5 cm) had solid components. Among these, two had colour pattern 5, their strain indexes were 3.7 and 4, and their histopathologic diagnosis were germ cell carcinoma. One had colour pattern 5, with strain index 13.6, and histopathologic diagnosis was clear cell carcinoma. Interpretation & conclusions: Transvaginal real-time ultrasonographic elastography has potential role in the differential diagnosis of cystic ovarian lesions and this technique may be useful in differentiation of the benign lesions from those of malignant.
  1,268 327 -
A retrospective analysis of dermatological lesions in kidney transplant patients
Michela Castello, Marilena Gregorini, Teresa Rampino, Francesca Bosio, Giulia Bedino, Giovanni Piotti, Grazia Soccio, Pasquale Esposito, Catherine Klersy, Massimo Abelli, Giovanni Borroni, Antonio Dal Canton
June 2013, 137(6):1188-1192
PMID:23852300
Background & objectives: Kidney transplantation is the best option for patients with end-stage renal disease (ESRD) failure. Prolonged use of immunosuppressive drugs often causes opportunistic infections and malignancies of skin and mucosae, but due to lack of a careful dermatological screening in several transplantation centers the diagnosis and the treatment of dermatological lesions in kidney transplant patients are underestimated. In addition after the introduction of interleukin (IL)-2 -receptor antagonists (basiliximab/daclizumab), mTOR inhibitors and mycophenolate mofetil (MMF)/mycophenolic acid (MPA) in new immunosuppressive protocols only a few studies have analyzed the skin and mucosal lesions in kidney transplant patients. This study was undertaken to evaluate the cutaneous and mucosal diseases after kidney transplantation, and to investigate the association between these and different immunosuppressive protocols and/or demographic features. Methods: A retrospective analysis was done using medical records of kidney transplantation between 2000 and 2009 at the Transplant Unit of Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. The study included 183 patients (M 57.3%, F 42.7%) aged 51.5±11.8 yr) with transplant age 52.3±34.9 months. Induction therapy was basiliximab and steroids based; maintenance therapy included combination-regimes from cyclosporine, tacrolimus, steroids, mycophenolate mofetil (MM), mycophenolic acid (MPA), rapamycin, everolimus. Anti-rejection therapy was steroid and/or thymoglobulines based. Diagnosis of cutaneous disease was made through examination of skin, mucous membranes, nails and hair evaluation. Skin biopsies, specific cultures and serological tests were done when required. Results: Skin and mucosal diseases were reported in 173 (95.7%) of patients; 88 (50.81%) showed viral lesions; 92 (53.01%) immunosuppression-related lesions; 28 (16.39%) benign tumours; 26 (15.3%) precancers /neoplastic lesions; 24 (14.21%) mycosis; 16 (9.29%) cutaneous xerosis, 15 (8.74%) dermatitis, while absence of cutaneous disease was evident only in 8 (4.37%) cases. An association between drug side effects and anti-rejection treatment ( P≤0.01) and/or calcineurin-inhibitors (CNI) exposure ( P≤0.01) was found. Longer exposure to immunosuppressive drugs (>60 months) was associated with pre-malignancy and malignancy lesions. Interpretation & conclusions: Cutaneous diseases are frequent in kidney transplanted patients. Continuous skin monitoring is necessary to make an early diagnosis and to start appropriate treatment.
  1,098 483 -
Effect of a deacyl gymnemic acid on glucose homeostasis & metabolic parameters in a rat model of metabolic syndrome
Shobhit Bhansali, Nusrat Shafiq, Promila Pandhi, Amrit Pal Singh, Inderjeet Singh, Pawan Kumar Singh, Sadhna Sharma, Samir Malhotra
June 2013, 137(6):1174-1179
PMID:23852298
Background & objectives: Metabolic syndrome (MS) comprises several cardio-metabolic risk factors, which include obesity, hypertension, hyperglycaemia, hypertriglyceridaemia and decreased HDL cholesterol. Leaf extract of Gymnema sylvestre has been shown to possess glucose lowering activity in animal models. This study was carried out to evaluate the efficacy of deacyl gymnemic acid (DAGA), active constituent of G. sylvestre, in a rat model of MS. Methods: Six groups consisting of six wistar rats in each, were studied. Group I received the normal diet, while the remaining five groups received high fructose diet (HFD ) for 20 days to induce MS. HFD was continued in these five groups for the next 20 days along with group II received vehicle solution, group III received pioglitazone and groups IV- VI received DAGA in variable doses. Systolic blood pressure (SBP) was measured using tail-cuff method. Oral glucose tolerance test (OGTT) was done at baseline and at days 20 and 40. Blood samples were collected for glucose, insulin and lipid profile. Results: Administration of HFD for 20 days resulted in weight gain (>10%), increase in SBP, fasting plasma glucose (FPG) and triglycerides fulfilling the criteria for MS. Administration of DAGA (200 mg/kg) reduced SBP and significantly improved the FPG and HOMA-IR (homeostatis model assessment-insulin resistance) with modest improvement in lipid profile without decrease in body weight similar to pioglitazone. Interpretation & conclusions: Our findings show that DAGA decreases SBP and improves parameters of glucose-insulin homeostasis in a rat model of MS induced by HFD. Further studies are required to elucidate the mechanism of action.
  984 510 -
Pre-clinical toxicity & immunobiological evaluation of DNA rabies vaccine & combination rabies vaccine in rhesus monkeys (Macaca mulatta)
B Dinesh Kumar, P Uday Kumar, T Prasanna Krishna, S Kalyanasundaram, P Suresh, V Jagadeesan, S Hariharan, A Nadamuni Naidu, Kamala Krishnaswamy, PN Rangarajan, VA Srinivasan, GS Reddy, B Sesikeran
June 2013, 137(6):1072-1088
PMID:23852288
Background & objectives: Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine [DRV (100 μg)] and combination rabies vaccine [CRV (100 μg DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys. Methods: As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters. Results: In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28 th day. Interpretation & conclusions: The information generated by this study not only draws attention to the need for national and international regulatory agencies in formulating guidelines for pre-clinical safety evaluation of biotech products but also facilitates the development of biopharmaceuticals as safe potential therapeutic agents.
  1,088 364 -
REVIEW ARTICLES
Hidden magicians of genome evolution
C Sandeep Kumar, Sameera Fatima Qureshi, Altaf Ali, ML Satyanarayana, Advithi Rangaraju, A Venkateshwari, Pratibha Nallari
June 2013, 137(6):1052-1060
PMID:23852286
Transposable elements (TEs) represent genome's dynamic component, causing mutations and genetic variations. Transposable elements can invade eukaryotic genomes in a short span; these are silenced by homology-dependent gene silencing and some functional parts of silenced elements are utilized to perform novel cellular functions. However, during the past two decades, major interest has been focused on the positive contribution of these elements in the evolution of genomes. The interaction between mobile DNAs and their host genomes are quite diverse, ranging from modifications of gene structure to alterations in general genome architecture and can be regarded as hidden magicians in shaping evolution of genomes. Some of the prominent examples that impressively demonstrate the beneficial impact of TEs on host biology over evolutionary time include their role in structure and functions of eukaryotic genomes.
  1,014 371 -
ORIGINAL ARTICLES
Evident stabilization of the clinical profile in HIV/AIDS as evaluated in an open label clinical trial using a polyherbal formulation
Mangaiarkarasi Asokan, Imtiaz Nisar Lone, Anil Babu Mukthey, Paul Siddhartha, Gayathri Mariappa, Praveen Kumar Kotehal, Bhuthiah Satish, Eugene Wilson, Savariraj Sahayam, Gopinath Velayutham, Rajalakshmi Perumal, Karthikeyan Baskaran, Devanathan Rengarajan, Ravichandran Muthusamy, Mariamma Philip, KC Ravindra, Jeelan N Basha, Pushpak Mizar, Gurvinder Kaur, Narinder K Mehra, Tapas K Kundu, DK Subbakrishna, Kadappa Shivappa Satish, Udaykumar Ranga
June 2013, 137(6):1128-1144
PMID:23852294
Background & objectives: The complementary and alternative medicines (CAM) have not been systematically evaluated for the management of HIV/AIDS patients. In a prospective, single-site, open-label, non-randomized, controlled, pilot trial, we evaluated a polyherbal formulation (PHF) for its safety and efficacy in treating subjects with HIV-AIDS. Methods: A total of 32 and 31 subjects were enrolled under the PHF and highly active antiretroviral treatment (HAART) arms, respectively, and followed up for a period of 24 months. Plasma viral RNA, CD4 cell count and blood chemistry were monitored at 3-month intervals. Following mid-term safety evaluation, 12 subjects from the PHF arm were shifted to HAART and were followed separately as PHF-to-HAART arm, for the rest of the period. Results: The HAART arm was characterized by significant improvements in CD4 cell count (154.4 cells/μl/year, P<0.001) and reduction in plasma viral load within 3 to 6 months (-0.431+ 0.004 log 10 IU/month, P<0.001). In contrast, the PHF arm showed a profile of CD4 cell loss at remarkably slower kinetics (14.3 cells/μl/year, P=0.021) and insignificant reduction in the viral load. The PHF and HAART arms did not differ significantly in the occurrence of AIDS-related illnesses over the study period of 24 months. In the PHF-to-HAART arm, the rates of CD4 count and reduction in viral load were significant and comparable to that of the HAART group. In the PHF arm, at 1 month, a significant increase in CD4 cell count and a concomitant decrease in viral load were seen. Interpretation & conclusions: The PHF appears to have provided protection by delaying the kinetics of CD4 cell reduction. Given the several study limitations, drawing assertive inferences from the data is challenging. Future studies with a stringent study design are warranted to confirm these findings.
  966 332 -
Inhibitory effect of polyunsaturated fatty acids on apoptosis induced by Streptococcus pneumoniae in alveolar macrophages
Archana Saini, Kusum Harjai, Sanjay Chhibber
June 2013, 137(6):1193-1198
PMID:23852301
Background & objectives: Apoptosis is considered as a major defense mechanism of the body. Multiple pathogens induce macrophage apoptosis as a mode of immune evasion. In earlier studies, n-3 polyunsaturated fatty acids (PUFA) have been reported to be protective against neuronal apoptosis and neuronal degeneration, seen after spinal cord injury. In this study, we tried to evaluate the role of n-3 polyunsaturated fatty acids on the process of macrophage phagocytic activity and apoptosis in mice. Methods: Mice were divided into three groups (n=60); Group I was fed on sea cod oil; Group II on flaxseed oil supplementation for 9 wk along with standard laboratory chow diet. Group III was fed on standard diet and served as control. After supplementation, phagocytic and apoptotic (morphological staining: acridine orange plus ethidium bromide; H-33342 plus propidium iodide staining and DNA ladder formation) activities of mouse alveolar macrophages were assessed. Results: Alveolar macrophages (obtained from sea cod oil and flaxseed oil fed group mice) showed significant increase in bacterial uptake as well as intracellular killing (P 0.05) of Streptococcus pneumoniae. Significant decrease (P<0.05) in apoptotic cells was observed among alveolar macrophages from sea cod and flaxseed oil fed mice whereas maximum apoptosis was observed in control alveolar macrophages on interaction with bacteria in vitro which was confirmed by DNA laddering. Interpretation & conclusions: These findings suggest that dietary supplementation with n-3 polyunsaturated fatty acids to mice led to enhanced phagocytic capability of their alveolar macrophages as well as provided protection against apoptosis upon challenge with S. pneumoniae.
  945 283 -
Epidemiological trends of RF/RHD in school children of Shimla in north India
Prakash Chand Negi, Anubhav Kanwar, Renu Chauhan, Sanjeev Asotra, Jarnail Singh Thakur, Ashok Kumar Bhardwaj
June 2013, 137(6):1121-1127
PMID:23852293
Background & objectives: There are no active surveillance studies reported from South East Asian Region to document the impact of change in socio-economic state on the prevalence of rheumatic fever/rheumatic heart disease (RF/RHD) in children. Therefore, we conducted a study to determine the epidemiological trends of RF/RHD in school children of Shimla city and adjoining suburbs in north India and its association with change in socio-economic status. Methods: Active surveillance studies were conducted in 2007-2008 in urban and rural areas of Shimla, and 15145 school children, aged 5-15 yr were included and identical screening methodology as used in earlier similar survey conducted in 1992-1993 was used. The study samples were selected from schools of Shimla city and adjoining rural areas by multistage stratified cluster sampling method in both survey studies. After a relevant history and clinical examination by trained doctor, echocardiographic evaluation of suspected cases was done. An updated Jones (1992) criterion was used to diagnose cases of acute rheumatic fever (ARF) and identical 2D-morphological and Doppler criteria were used to diagnose RHD in both the survey studies. The socio-economic and healthcare transitions of study area were assessed during the study interval period. Results: Time trends of prevalence of RF/RHD revealed about five-fold decline from 2.98/1000 (95% C.I. 2.24-3.72/1000) in 1992-1993 to 0.59/1000 (95% C.I. 0.22-0.96/1000) in 2007-2008. (P<0.0001). While the prevalence of ARF and RHD with recurrence of activity was 0.176/1000 and 0.53/1000, respectively in 1992-1993, no case of RF was recorded in 2007-2008 study. Prevalence of RF/RHD was about two- fold higher in rural school children than urban school children in both the survey studies (4.42/1000 vs. 2.12/1000) and (0.88/1000 vs. 0.41/1000), respectively. The indices of socio-economic development revealed substantial improvement during this interim period. Interpretation & conclusions: The prevalence of RF/RHD has declined by five-fold over last 15 yr and appears to be largely contributed by improvement in socio-economic status and healthcare delivery systems. However, the role of change in the rheumatogenic characteristics of the streptococcal stains in the study area over a period of time in decline of RF/RHD cannot be ruled out. Policy interventions to improve living standards, existing healthcare facilities and awareness can go a long way in reducing the morbidity and mortality burden of RF/RHD in developing countries.
  801 383 -
Diphenylmethyl selenocyanate attenuates malachite green induced oxidative injury through antioxidation & inhibition of DNA damage in mice
Jayanta Kumar Das, Sibani Sarkar, Sk Ugir Hossain, Pramita Chakraborty, Rajat Kumar Das, Sudin Bhattacharya
June 2013, 137(6):1163-1173
PMID:23852297
Background & objectives: Malachite green (MG), an environmentally hazardous material, is used as a non permitted food colouring agent, especially in India. Selenium (Se) is an essential nutritional trace element required for animals and humans to guard against oxidative stress induced by xenobiotic compounds of diverse nature. In the present study, the role of the selenium compound diphenylmethyl selenocyanate (DMSE) was assessed on the oxidative stress (OS) induced by a food colouring agent, malachite green (MG) in vivo in mice. Methods: Swiss albino mice (Mus musculus) were intraperitoneally injected with MG at a standardized dose of 100 μg/ mouse for 30 days. DMSE was given orally at an optimum dose of 3 mg/kg b.w. in pre (15 days) and concomitant treatment schedule throughout the experimental period. The parameters viz. ALT, AST, LPO, GSH, GST, SOD, CAT, GPx, TrxR, CA, MN, MI and DNA damage have been evaluated. Results: The DMSE showed its potential to protect against MG induced hepatotoxicity by controlling the serum alanine aminotransferase and aspartate amino transferase (ALT and AST) levels and also ameliorated oxidative stress by modulating hepatic lipid peroxidation and different detoxifying and antioxidative enzymes such as glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and also the selenoenzymes such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) and reduced glutathione level which in turn reduced DNA damage. Interpretation & conclusions: The organo-selenium compound DMSE showed significant protection against MG induced heptotoxicity and DNA damage in murine model. Better protection was observed in pretreatment group than in the concomitant group. Further studies need to be done to understand the mechanism of action.
  830 277 -
Development of ELISA based detection system for lethal toxin of Clostridium sordellii
Preetika Arya, S Ponmariappan, Lokendra Singh, Om Kumar
June 2013, 137(6):1180-1187
PMID:23852299
Background & objectives: Clostridium sordellii and its toxins are associated with diseases in animals as well as human. C. sordellii produces two protein toxins (lethal toxin and haemorrhagic toxin). Lethal toxin has gained more importance due its high toxicity. The present study was carried out to develop a sandwich ELISA for detection of lethal toxin of C. sordellii. Methods: The catalytic domain (1.6kb) of lethal toxin of C. sordellii was PCR amplified, cloned into pQE30 UA vector and transformed into Escherichia coli SG 13009. Expression conditions were optimized and the recombinant protein was purified under native condition using Ni-NTA affinity chromatography, confirmed by SDS-PAGE and Western blot. Antibody was generated against the purified recombinant protein using Freund's complete and incomplete adjuvants (FCA and FIA) in BALB/c mice and rabbit. A sandwich ELISA was optimized for the detection of lethal toxin. Results: The maximum recombinant protein expression was achieved at 0.5 mM IPTG (isopropylthiogalactoside) induction 4.0 h of post-induction. The polyclonal antibody raised in mice and rabbit showed a titre up to 1:512000. The produced antibody was highly sensitive with the detection limit of 0.3 ng/ml of lethal toxin at 1:4000 dilutions of mice (capturing) and rabbit (revealing) antibody. Interpretation & conclusions: An ELISA based detection system was developed for the detection of lethal toxin of C. sordellii. The developed detection system was found to be specific as there was no cross-reactivity with any other clostridial toxins. It will be useful for the detection of lethal toxin of C. sordellii in clinical and environmental samples.
  797 266 -
CORRESPONDENCE
Chemokine receptor 5 (CCR5) polymorphism in chronic hepatitis B patients treated with three different nucleos(t)ide analogues
Varun Goel, Purabi Deka Bose, Manash P Sarma, Rajib K Hazam, Bhudev C Das, Ranjana Gondal, Premashis Kar
June 2013, 137(6):1208-1209
PMID:23852305
  634 244 -
STUDENT IJMR
Current analgesic use predicts low emotional quality of life in youth: A cross-sectional survey among university students in Sikkim, North East India
Shurmala Ahongshangbam, Amit Chakrabarti
June 2013, 137(6):1199-1203
PMID:23852302
Background & objectives: Occurrence of chronic physical pain is increasingly identified among youth, and medically unsupervised analgesic use is a possible risk factor for opioid dependence and other mental diseases in later life. Therefore, the present study was carried out in young student population in Sikkim, India, to explore predictors (including current chronic pain and current analgesic use) of low QoL in youth to identify a subset of population vulnerable to substance use and mental diseases in later life. Methods: The study was conducted in a health university setting in Sikkim, North East India. In this cross-sectional study, 156 participants were enrolled with almost equal number of males and females. Generic instruments for demographics and current analgesic use and SF - 36, for assessment of quality of life (QoL), were used. QoL was measured in general, physical and emotional domains. Presence of chronic physical pain during past four weeks was captured using SF - 36. Results: Almost two-third participants reported presence of current physical pain (69%, n=108); and (14%, n=22) reported current analgesic use for pain. In logistic regression model controlled for age, ethnicity, gender and residence, higher body mass index (BMI) (β=-0.16, P=0.02) and current analgesic use (β=1.6, P=0.006) predicted low QoL in emotional domain (less accomplishment due to emotional problem). Current analgesic use also predicted low QoL in another measure of emotional domain (depressed β=2.0, P=0.001). Interpretation & conclusions: This study identified a subset of participants in their youth with low QoL in emotional domain predicted by current analgesic use and possible overweight problem. Low QoL in more than one emotional domain also identifies possibility of later psychiatric impairment. However, chronic pain did not emerge as a significant predictor of low QoL in emotional domain.
  578 291 -
ORIGINAL ARTICLES
Immunologic response among HIV-infected patients enrolled in a graduated cost-recovery programme of antiretroviral therapy delivery in Chennai, India
Sunil Suhas Solomon, Aylur K Ganesh, Shruti H Mehta, Tokugha Yepthomi, Kavitha Balaji, Santhanam Anand, Joel E Gallant, Suniti Solomon
June 2013, 137(6):1145-1153
PMID:23852295
Background & objectives: Sustainability of free antiretroviral therapy (ART) roll out programmes in resource-limited settings is challenging given the need for lifelong therapy and lack of effective vaccine. This study was undertaken to compare treatment outcomes among HIV-infected patients enrolled in a graduated cost-recovery programme of ART delivery in Chennai, India. Methods: Financial status of patients accessing care at a tertiary care centre, YRGCARE, Chennai, was assessed using an economic survey; patients were distributed into tiers 1- 4 requiring them to pay 0, 50, 75 or 100 per cent of their medication costs, respectively. A total of 1754 participants (ART naοve = 244) were enrolled from February 2005-January 2008 with the following distribution: tier 1=371; tier 2=338; tier 3=693; tier 4=352. Linear regression models with generalized estimating equations were used to examine immunological response among patients across the four tiers. Results: Median age was 34; 73 per cent were male, and the majority were on nevirapine-based regimens. Median follow up was 11.1 months. The mean increase in CD4 cell count within the 1 st three months of HAART was 50.3 cells/μl per month in tier 1. Compared to those in tier 1, persons in tiers 2, 3 and 4 had comparable increases (49.7, 57.0, and 50.9 cells/μl per month, respectively). Increases in subsequent periods (3-18 and >18 months) were also comparable across tiers. No differential CD4 gains across tiers were observed when the analysis was restricted to patients initiating ART under the GCR programme. Interpretation & conclusions: This ART delivery model was associated with significant CD4 gains with no observable difference by how much patients paid. Importantly, gains were comparable to those in other free rollout programmes. Additional cost-effectiveness analyses and mathematical modelling would be needed to determine whether such a delivery programme is a sustainable alternative to free ART programmes.
  577 231 -
COMMENTARIES
DNA vaccines: Getting closer to becoming a reality
Kaushik Bharati, Sudhanshu Vrati
June 2013, 137(6):1027-1028
PMID:23852283
  505 291 -
CORRESPONDENCE
Induced pluripotent stem cells: A new futuristic era towards orodental disorders
Preetinder Singh
June 2013, 137(6):1207-1207
PMID:23852304
  581 195 -
Report on institutions rankings - Where our medical institutions stand? Our big neighbour & the way forward
Madan M Godbole, Ramnath Misra, Chandra Mani Pandey, Surendra Srivastava
June 2013, 137(6):1204-1206
PMID:23852303
  463 280 -
BOOK REVIEWS
Controversies in acute kidney injury
RK Sharma
June 2013, 137(6):1213-1215
  440 185 -
CLINICAL IMAGES
Recurrent iris cyst following pencil tip injury
Harsha Bhattacharjee, Dipankar Das
June 2013, 137(6):1211-1211
PMID:23852307
  406 193 -
BOOK REVIEWS
WHO Expert Committee on Biological Standardization, 59 th Report
NK Ganguly
June 2013, 137(6):1212-1213
  299 180 -
BOOKS RECEIVED
Book Received

June 2013, 137(6):1215-1215
  222 147 -
MOST CITED ARTICLES
Most Cited Article

June 2013, 137(6):1227-1228
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  136 163 -
SOME FORTHCOMING SCIENTIFIC EVENTS
Some Forthcoming Scientific Events

June 2013, 137(6):1216-1216
Full text not available  [PDF]  [Mobile Full text]  [EPub]
  123 166 -
IJMR CLASSIC
Pathological lessions in HIV positive petients

June 2013, 137(6):1219-1226
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  124 159 -
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