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1.  Clinical decision-making augmented by simulation training: neural correlates demonstrated by functional imaging: a pilot study 
BJA: British Journal of Anaesthesia  2013;112(1):124-132.
Background
Investigation of the neuroanatomical basis of clinical decision-making, and whether this differs when students are trained via online training or simulation training, could provide valuable insight into the means by which simulation training might be beneficial.
Methods
The aim of this pilot prospective parallel group cohort study was to investigate the neural correlates of clinical decision-making, and to determine if simulation as opposed to online training influences these neural correlates. Twelve third-year medical students were randomized into two groups and received simulation-based or online-based training on anaphylaxis. This was followed by functional magnetic resonance imaging scanning to detect brain activation patterns while answering multiple choice questions (MCQs) related to anaphylaxis, and unrelated non-clinical (control) questions. Performance in the MCQs, salivary cortisol levels, heart rate, and arterial pressure were also measured.
Results
Comparing neural responses to clinical and non-clinical questions (in all participants), significant areas of activation were seen in the ventral anterior cingulate cortex and medial prefrontal cortex. These areas were activated in the online group when answering action-based questions related to their training, but not in the simulation group. The simulation group tended to react more quickly and accurately to clinical MCQs than the online group, but statistical significance was not reached.
Conclusions
The activation areas seen could indicate increased stress when answering clinical questions compared with general non-clinical questions, and in the online group when answering action-based clinical questions. These findings suggest simulation training attenuates neural responses related to stress when making clinical decisions.
doi:10.1093/bja/aet326
PMCID: PMC3854551  PMID: 24065729
computer simulation; magnetic resonance imaging, functional; stress, psychological
2.  Adrenal imaging (Part 2): Medullary and secondary adrenal lesions 
Adrenal malignancies can be either primary adrenal tumors or secondary metastases, with metastases representing the most common malignant adrenal lesion. While imaging cannot always clearly differentiate between various adrenal malignancies, presence of certain imaging features, in conjunction with appropriate clinical background and hormonal profile, can suggest the appropriate diagnosis. The second part of the article on adrenal imaging describes adrenal medullary tumors, secondary adrenal lesions, bilateral adrenal lesions, adrenal incidentalomas and provides an algorithmic approach to adrenal lesions based on current imaging recommendations.
doi:10.4103/2230-8210.146859
PMCID: PMC4287762  PMID: 25593821
Adrenal imaging; adrenal incidentalomas; adrenal lymphoma; adrenal medulla; adrenal metastases; bilateral adrenal masses; pheochromocytoma
3.  Adrenal imaging (Part 1): Imaging techniques and primary cortical lesions 
Adrenal glands can be affected by a variety of lesions. Adrenal lesions can either be primary, of adrenal origin, or secondary to other pathologies. Primary adrenal lesions can further be either of cortical or medullary origin. Functioning adrenal lesions can also give clues to the histologic diagnosis and direct workup. Over the years, various imaging techniques have been developed that have increased diagnostic accuracy and helped in better characterization of adrenal lesions non-invasively. In the first part of the two part series, we review adrenal imaging techniques and adrenal cortical tumors such as adenomas, adrenocortical tumors, adrenal hyperplasia and oncocytomas.
doi:10.4103/2230-8210.146858
PMCID: PMC4287786  PMID: 25593820
Adrenal adenoma; adrenal cancer; adrenal imaging; adrenocortical carcinoma
4.  Study of hypothalamic pituitary adrenal axis in patients of membranous nephropathy receiving modified Ponticelli regimen 
Indian Journal of Nephrology  2015;25(1):12-15.
Pulse methyl prednisolone followed by oral prednisolone and abrupt switch to chlorambucil/cyclophosphamide (Ponticelli/modified Ponticelli regimen) is used in patients with idiopathic membranous nephropathy. This therapy where steroids are stopped abruptly is unphysiologic and expected to have hypothalamic pituitary adrenal (HPA) axis suppression; however, this has not been evaluated. A total of 13 consecutive adult patients with idiopathic membranous nephropathy who had completed modified Ponticelli regimen were studied. The regimen included administration of pulse methylprednisolone 1 g for 3 days followed by oral prednisolone 0.5 mg/kg/day for 27 days followed by oral cyclophosphamide at a dose of 2 mg/kg/day for the next month. This was repeated for three courses. Patients who had received corticosteroids prior to therapy were excluded. The HPA axis was evaluated after 1 month of completing the last course of steroid therapy. The evaluation was done using a low-dose adrenocorticotropic hormone stimulation test. A single intravenous bolus dose of synacthen (1 μg) was given at 9.00 am and the serum cortisol levels were estimated by radioimmunoassay at 0, 30, and 60 min. A peak cortisol level of 550 nmol/L or higher was considered as normal. Mean baseline cortisol levels was 662.3 ± 294.6 nmol/L and peak cortisol level was 767 ± 304.4 nmol/L. A total of 6 patients (46.2%) had low basal cortisol levels, only 3 (23%) had both basal and peak cortisol levels < 550 nmol/L suggestive of HPA axis suppression. To conclude, 23% of patients had suppression of HPA axis after modified Ponticelli regimen.
doi:10.4103/0971-4065.136884
PMCID: PMC4323906
Adrenal insufficiency; adrenocorticotropic hormone stimulation; membranous glomerulonephritis; nephritic syndrome; pulse methyl prednisolone
5.  Rapidly progressive renal failure in a patient with extranodal non-Hodgkin's lymphoma 
Indian Journal of Nephrology  2015;25(1):43-45.
A 60-year male was admitted with advanced renal failure and bilaterally enlarged kidneys. Kidney biopsy revealed diffuse interstitial infiltration by CD20 + lymphomatous cells suggestive of diffuse large B-cell, non-Hodgkin's lymphoma. Bone marrow examination was negative for malignant cells. Positron emission tomography-computed tomography showed uniformly diffuse and avid flurodeoxy glucose uptake in both kidneys, multiple hypodense areas of both lobes of liver, and axial and appendicular skeleton. Patient was treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone, became afebrile and serum creatinine normalized.
doi:10.4103/0971-4065.140723
PMCID: PMC4323911
Primary renal lymphoma; complication; rapidly progressive renal failure
6.  Successful induction of granulomatosis with polyangiitis with tacrolimus 
Indian Journal of Nephrology  2015;25(1):46-49.
We report a 50-year-old female who presented with inflammatory arthritis, upper respiratory tract symptoms, and microscopic hematuria with nephrotic range proteinuria. Antineutrophil cytoplasmic antibodies (ANCA) were detectable and kidney biopsy showed pauci-immune focal necrotizing crescentic glomerulonephritis. She was treated with pulse intravenous cyclophosphamide (CYC) and prednisolone. Patient developed severe leucopenia after the first dose and subsequently had leucopenia to low dose CYC, mycophenolate mofetil and azathioprine were also tried. However, patient developed leukopenia with all the above agents. Initiation of tacrolimus (TAC) was followed by dramatic response: Proteinuria decreased, serum albumin normalized and C-ANCA and anti-PR3 ANCA assays became negative. This is the first successful case of TAC as an induction agent in a patient with GPA (ANCA associated vasculitis with renal involvement).
doi:10.4103/0971-4065.136885
PMCID: PMC4323912
Antineutrophil cytoplasmic antibodies; associated vasculitis; granulomatosis with polyangiitis
7.  Morphine stimulates platelet-derived growth factor receptor-β signalling in mesangial cells in vitro and transgenic sickle mouse kidney in vivo 
BJA: British Journal of Anaesthesia  2013;111(6):1004-1012.
Background
Pain and renal dysfunction occur in sickle cell disease. Morphine used to treat pain also co-activates platelet-derived growth factor receptor-β (PDGFR-β), which can adversely affect renal disease. We examined the influence of morphine in mesangial cells in vitro and in mouse kidneys in vivo.
Methods
Mouse mesangial cells treated with 1 μM morphine in vitro or kidneys of transgenic homozygous or hemizygous sickle or control mice (n=3 for each), treated with morphine (0.75, 1.4, 2.14, 2.8, 3.6, and 4.3 mg kg−1 day−1 in two divided doses during the first, second, third, fourth, fifth, and sixth weeks, respectively), were used. Western blotting, bromylated deoxy uridine incorporation-based cell proliferation assay, reverse transcriptase-polymerase chain reaction, immunofluorescent microscopy, and blood/urine chemistry were used to analyse signalling, cell proliferation, opioid receptor (OP) expression, and renal function.
Results
Morphine stimulated phosphorylation of PDGFR-β and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) to the same extent as induced by platelet-derived growth factor-BB (PDGF-BB) and promoted a two-fold increase in mesangial cell proliferation. The PDGFR-β inhibitor, AG1296, OP antagonists, and silencing of μ- and κ-OP abrogated morphine-induced MAPK/ERK phosphorylation and proliferation by ∼100%. Morphine treatment of transgenic mice resulted in phosphorylation of PDGFR-β, MAPK/ERK, and signal transducer and activator of transcription 3 (Stat3) in the kidneys. Morphine inhibited micturition and blood urea nitrogen (BUN) clearance and increased BUN and urinary protein in sickle mice.
Conclusion
Morphine stimulates mitogenic signalling leading to mesangial cell proliferation and promotes renal dysfunction in sickle mice.
doi:10.1093/bja/aet221
PMCID: PMC3828056  PMID: 23820675
morphine; nephropathy; pain; platelet-derived growth factor; sickle cell disease
8.  Acute pyelonephritis in diabetes mellitus: Single center experience 
Indian Journal of Nephrology  2014;24(6):367-371.
Diabetes mellitus is a common cause of pyelonephritis. Both emphysematous pyelonephritis (EPN) and non-EPN (NEPN) are associated with poor outcome. This study was aimed at analyzing the clinical features, microbiological profile, prognostic factors, and treatment outcome of pyelonephritis in diabetic patients. A total of 105 diabetic patients with pyelonephritis were admitted from July 2010 to June 2012. Patients were treated with appropriate antibiotics and percutaneous drainage (PCD) as indicated. Nephrectomy was carried out in patients of EPN who were refractory to conservative measures. NEPN and EPN were seen in 79 (75.2%) and 26 (24.7%) patients, respectively. Escherichia coli was the most common organism. Pyelonephritis was associated with renal abscess and papillary necrosis in 13 (12.4%) and 4 (3.8%) patients with EPN and NEPN, respectively. Worsening of renal functions were seen in 92 and 93% of patients with EPN and NEPN, respectively. Class 1 EPN was seen in 2 (7.7%), Class II in 8 (30.7%), IIIa in 7 (27%), IIIb in 5 (19.3), and IV in 4 (15.4%) patients. Antibiotics alone were sufficient in 38.5% of EPN versus 62% in NEPN; additional PCD was required in 42.3% in EPN and 21.4% in NEPN. Nephrectomy was required in 5 (19.2%) EPN patients with Class IIIB or IV. A total of 13 patients (12.4%) expired, 4 (15.4%) in EPN, and 9 (11.4%) in NEPN group. Patients with EPN had a higher incidence of shock (6% vs. 0; P < 0.05) and poorly controlled blood sugar (26% vs. 50%; P < 0.05) compared with NEPN. Presence of shock and altered sensorium were associated with poor outcome in patients with EPN. Diabetics with pyelonephritis have severe disease. Patients of EPN have poorer treatment outcome compared with those with NEPN. However, there is no difference in the mortality, but a greater need of nephrectomy in EPN compared with NEPN patients. Presence of shock and altered sensorium at presentation were poor prognostic factors in EPN.
doi:10.4103/0971-4065.135347
PMCID: PMC4244716  PMID: 25484530
Diabetes mellitus; emphysematous pyelonephritis; nonemphysematous pyelonephritis
9.  Modeling of Grid Cell Activity Demonstrates in Vivo Entorhinal ‘Look-Ahead’ Properties 
Neuroscience  2013;247:10.1016/j.neuroscience.2013.04.056.
Recent in vivo data show ensemble activity in medial entorhinal neurons that demonstrates ‘look-ahead’ activity, decoding spatially to reward locations ahead of a rat deliberating at a choice point while performing a cued, appetitive T-Maze task. To model this experiment's look-ahead results, we adapted previous work that produced a model where scans along equally probable directions activated place cells, associated reward cells, grid cells, and persistent spiking cells along those trajectories. Such look-ahead activity may be a function of animals performing scans to reduce ambiguity while making decisions. In our updated model, look-ahead scans at the choice point can activate goal-associated reward and place cells, which indicate the direction the virtual rat should turn at the choice point. Hebbian associations between stimulus and reward cell layers are learned during training trials, and the reward and place layers are then used during testing to retrieve goal-associated cells based on cue presentation. This system creates representations of location and associated reward information based on only two inputs of heading and speed information which activate grid cell and place cell layers. We present spatial and temporal decoding of grid cell ensembles as rats are tested with perfect and imperfect stimuli. Here, the virtual rat reliably learns goal locations through training sessions and performs both biased and unbiased look-ahead scans at the choice point. Spatial and temporal decoding of simulated medial entorhinal activity indicates that ensembles are representing forward reward locations when the animal deliberates at the choice point, emulating in vivo results.
doi:10.1016/j.neuroscience.2013.04.056
PMCID: PMC3848600  PMID: 23660194
entorhinal cortex; grid cells; look-ahead; persistent spiking; Bayesian decoding; place cells
10.  Treatment of Ruptured Saccular Aneurysms of the Fenestrated Vertebrobasilar Junction with Balloon Remodeling Technique 
Interventional Neuroradiology  2013;19(3):289-298.
Summary
Fenestration of the intracranial arteries is a relatively common occurrence. This anatomic variation may predispose to aneurysm formation at certain sites. Treatment of such aneurysms is difficult as it may occlude one of the limbs of fenestration with resultant deficit. Thus, preservation of both the limbs with adequate exclusion of the aneurysm from the circulation should be the aim of any treatment. We describe a series of four cases of ruptured aneurysms arising from a fenestrated vertebrobasilar junction treated with endovascular balloon remodeling technique.
PMCID: PMC3806003  PMID: 24070077
aneurysm, vertebrobasilar junction, fenestration, coiling
11.  p28, A first in class peptide inhibitor of cop1 binding to p53 
British Journal of Cancer  2013;108(12):2495-2504.
Background:
A 28 amino-acid (aa) cell-penetrating peptide (p28) derived from azurin, a redox protein secreted from the opportunistic pathogen Pseudomonas aeruginosa, produces a post-translational increase in p53 in cancer cells by inhibiting its ubiquitination.
Methods:
In silico computational simulations were used to predict motifs within the p53 DNA-binding domain (DBD) as potential sites for p28 binding. In vitro direct and competitive pull-down studies as well as western blot and RT-PCR analyses were used to validate predictions.
Results:
The L1 loop (aa 112–124), a region within the S7–S8 loop (aa 214–236) and T140, P142, Q144, W146, R282 and L289 of the p53DBD were identified as potential sites for p28 binding. p28 decreased the level of the E3 ligase COP1 >80%, in p53wt and p53mut cells with no decrease in COP1 in p53dom/neg or p53null cells. Brief increases in the expression of the E3 ligases, TOPORS, Pirh2 and HDM2 (human double minute 2) in p53wt and p53mut cells were in response to sustained increases in p53.
Conclusion:
These data identify the specific motifs within the DBD of p53 that bind p28 and suggest that p28 inhibition of COP1 binding results in the sustained, post-translational increase in p53 levels and subsequent inhibition of cancer cell growth independent of an HDM2 pathway.
doi:10.1038/bjc.2013.266
PMCID: PMC3694247  PMID: 23736031
p53; COP1; cell penetrating peptide; cell cycle; ubiquitination; E3 ligases
12.  Ethnic and Sex Differences in Visceral, Subcutaneous, and Total Body Fat in Children and Adolescents 
Obesity (Silver Spring, Md.)  2013;21(6):1251-1255.
Objective
This study investigated ethnic and sex differences in the distribution of fat during childhood and adolescence.
Design and Methods
A cross-sectional sample (n=382), aged 5 to 18 years, included African American males (n=84), White males (n=96), African American females (n=118), and White females (n=84). Measures for total body fat (TBF) mass and abdominal adipose tissue (total volume and L4–L5 cross-sectional area) for both subcutaneous (SAT) and visceral (VAT) depots were assessed by DXA and MRI, respectively. ANCOVAs were used to determine ethnic and sex differences in TBF (adjusted for age) and ethnic and sex differences in SAT and VAT (adjusted for both age and TBF).
Results
Age-adjusted TBF was greater in African Americans (p=0.017) and females (p<0.0001) compared to Whites and males, respectively. In age- and TBF-adjusted ANCOVAs, no differences were found in the SAT. The VAT volume was, however, greater in Whites (p<0.0001) and males (p<0.0001) compared to African Americans and females, respectively. Similar patterns were observed in SAT and VAT area at L4–L5.
Conclusions
The demonstrated ethnic and sex differences are important confounders in the prevalence of obesity and in the assignment of disease risk in children and adolescents.
doi:10.1002/oby.20210
PMCID: PMC3735659  PMID: 23670982
14.  Seasonal prevalence of gastrointestinal helminths in sheep and goats of middle agro-climatic zone of Jammu province 
A total of 1920 faecal samples of sheep (960) and goats (960) of stationary flocks of the middle agro-climatic zone of Jammu province were examined, out of which 67.24 % animals were positive for helminthic infections. The different nematodes observed were strongyles (50.1 %), trichurids (12.1 %) and Strongyloides spp. (4.2 %). Trematode ova recorded were of amphistomes (8.3 %), Fasciola spp. (8.2 %) and Dicrocoelium spp. (5.4 %). No significant difference was observed between the infection level in sheep (68.54 %) and goats (65.94 %) which could be attributed to mixed grazing and sharing of pastures/sheds. Significantly (p < 0.05) higher infection was observed in monsoon as compared to winter. Strongyles were predominant during all the seasons, but significantly (p < 0.05) higher infection was observed in monsoon as compared to winter. Coproculture studies revealed that Haemonchus contortus (61.18 %) predominated during all the seasons, followed by Trichostrongylus spp. (13.67 %), Ostertagia spp. (12.17 %), Strongyloides spp. (4.14 %), Oesophagostomum spp. (3.84 %) and Bunostomum spp. (3.83 %). Eggs per gram of faeces (EPG) were the highest (sheep 1883.33 ± 117.6 and goats 1800 ± 110.21) during monsoon and the lowest during winter (sheep 640 ± 41.29 and goats 556.67 ± 33.01). Two peaks of EPG (the first in May and the second in August) were recorded during the 1 year study period. Infection was significantly (p < 0.05) higher in young (73.22 %) as compared to adults (61.25 %). Females showed a higher infection (73.33 %) as compared to males (61.14 %). The effect of prevailing agro-climatic conditions on the prevalence of gastrointestinal helminths has been discussed.
doi:10.1007/s12639-012-0122-3
PMCID: PMC3590375  PMID: 24431535
Sheep; Goats; Prevalence; Helminths; Jammu
15.  Pathological alterations in natural cases of Capillaria hepatica infection alone and in concurrence with Cysticercus fasciolaris in Bandicota bengalensis 
The present study reports the natural occurrence and pathomorphological alterations of Capillaria hepatica infection alone and in concurrence with Cysticercus fasciolaris infection in the liver of Bandicota bengalensis. Out of the eighteen mature male B. bengalensis autopsied, livers of eight rats (44.4 %) were found infected with parasites comprising two (11.1 %) rats infected with C. hepatica alone, four (22.2 %) infected with C. fasciolaris alone and two (11.1 %) infected with C. hepatica in concurrence with C. fasciolaris. Gross lesions comprising of pale cystic areas or streaks on the surface of liver in rats revealed the presence of eggs of C. hepatica scattered in the parenchyma of the liver. Histologically, granulomatous reaction around the eggs, adult worms and dead components of parasites were observed.
doi:10.1007/s12639-012-0121-4
PMCID: PMC3590378  PMID: 24431534
Bandicota bengalensis; Capillaria hepatica; Concurrent infection; Cysticercus fasciolaris; Rodents
16.  Acrocyanosis with intrahepatic carcinoid tumor 
doi:10.4103/2229-5178.131139
PMCID: PMC4030363  PMID: 24860770
17.  A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours 
British Journal of Cancer  2013;108(5):1061-1070.
Background:
This first-in-human, phase I clinical trial of p28 (NSC745104), a 28-amino-acid fragment of the cupredoxin azurin, investigated the safety, tolerability, pharmacokinetics and preliminary activity of p28 in patients with p53+ metastatic solid tumours.
Methods:
A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3+3 dose escalation design until either a grade 3-related adverse event occurred or the maximum tolerated dose (MTD) was reached. Single-dose and steady-state serum pharmacokinetics were characterised. Assessments included toxicity, best objective response by RECIST 1.1 Criteria, and overall survival.
Results:
No patients exhibited any dose-limiting toxicities (DLTs), significant adverse events or exhibited an immune response (IgG) to the peptide. The No Observed Adverse Effect Level (NOAEL) and MTD were not reached. Seven patients demonstrated stable disease for 7–61 weeks, three a partial response for 44–125 weeks, and one a complete response for 139 weeks. Three patients are still alive at 158, 140, and 110 weeks post therapy completion.
Conclusion:
p28 was tolerated with no significant adverse events. An MTD was not reached. Evidence of anti-tumour activity indicates a highly favourable therapeutic index and demonstrates proof of concept for this new class of non-HDM2-mediated peptide inhibitors of p53 ubiquitination.
doi:10.1038/bjc.2013.74
PMCID: PMC3619084  PMID: 23449360
p28; p53; metastatic solid tumours
18.  Heavy-ion (56Fe) irradiation leads to impaired aortic relaxation prior to atherosclerotic plaque formation in ApoE−/− mice 
Journal of Radiation Research  2014;55(Suppl 1):i42-i43.
Terrestrial radiation exposure is a well-established risk factor for cardiovascular disease. For example, coronary artery disease and stroke are both well-established adverse effects of therapeutic radiation, especially for breast and head-and-neck cancers [ 1]. Similarly, atomic bomb survivors were significantly more likely to die of cardiovascular disease than their countrymen [ 2]. Even radiation technologists, prior to 1950 (when regulations governing shielding and occupational exposure were less rigorous), had an increased risk of clinically significant atherosclerosis [ 3]. Although the character of the radiation in interplanetary space is very different from that encountered on Earth, there is concern that exposure to this cosmic radiation might pose a similar risk for astronauts. Decreased endothelium-dependent vasodilation is thought to predispose humans to the development of structural vascular changes that precede development of atherosclerosis. Therefore, in this study, we examined the effect of 56Fe, an important component of cosmic radiation, on vascular relaxation. At the NASA Space Radiation Laboratory at Brookhaven National Laboratory, 10-week-old apoE−/− mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe, a dose in the range that was shown previously to accelerate the development of atherosclerotic plaques in this mouse model at 13 weeks post-exposure [ 4]. The mice were then transferred to the University of Alabama at Birmingham, where they were housed under standard conditions and fed a normal diet. At 4–5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation in irradiated mice was compared with that of age-matched controls from un-irradiated apoE mice and from un-irradiated wild-type mice of the same C57BL/6 genetic background. Aortic relaxation was not significantly different between un-irradiated apoE−/− mice and un-irradiated wild-type C57BL/6 mice, consistent with previous studies. 56Fe radiation, however, resulted in significantly impaired relaxation in response to acetylcholine. This suggests that heavy-ion radiation exposure leads to impairment of normal vascular reactivity prior to the appearance of atherosclerotic plaques, suggesting that it may be a driving force, rather than a consequence, of radiation-induced accelerated atherosclerosis.
doi:10.1093/jrr/rrt190
PMCID: PMC3941542
cardiovascular; atherosclerosis; 56Fe; mouse; aorta; heavy ions
19.  Changing histologic spectrum of adult nephrotic syndrome over five decades in north India: A single center experience 
Indian Journal of Nephrology  2014;24(2):86-91.
Glomerular diseases are an important cause of chronic renal failure in developing countries. The spectrum of diseases causing nephrotic syndrome is changing globally in the last few decades. The aim of this prospective study was to look at this spectrum at a tertiary care center in North India and to analyze the changing trends over the last five decades. Patients in the age group 18-60 years with nephrotic syndrome were consecutively included in the study. Renal biopsies were performed in all patients and were subjected to light microscopy, immunofluorescence (IF) and electron microscopy (EM). While the IF was performed in 78% of cases, EM was available in one-fourth of cases. During 2002-2007, 364 patients (60.2% males) were included in the study. The mean age was 31.5 years. Primary glomerular diseases accounted for 89% of cases while lupus nephritis was the most common secondary glomerular disease. Focal segmental glomerulosclerosis (FSGS) accounted for 30.6% of primary glomerular diseases making it the most common cause of nephrotic syndrome. It was followed by membranous glomerulonephritis (MGN) in 24.4%, mesangiocapillary glomerulonephritis in 17.9% and minimal change disease in 14.8%. In the age group >40 years, MGN was the most common lesion (32.5%) followed by FSGS (27.7%). Over the last five decades, there was a nearly five-fold increase in the incidence of FSGS, 3-fold increase in MGN and a 10-fold reduction in diffuse proliferative glomerulonephritis while there was no major change in incidence of other diseases. The biopsy diagnosis of FSGS has increased considerably in last few decades and it is now the most common cause of nephrotic syndrome in adults in North India. MGN is the most common lesion in patients over 40 years of age.
doi:10.4103/0971-4065.127892
PMCID: PMC3968615  PMID: 24701040
Chronic kidney disease; focal segmental glomerulosclerosis; idiopathic nephrotic syndrome; membranous nephropathy; minimal change disease; renal biopsy
20.  Vitrectomy for epiretinal membrane secondary to treatment for juvenile Coats' disease 
Eye  2012;27(2):278-280.
doi:10.1038/eye.2012.275
PMCID: PMC3574262  PMID: 23258308
21.  The role of stem cells in osteoarthritis 
Bone & Joint Research  2014;3(2):32-37.
Introduction
Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair.
Methods
In this study, we used scaffold-free mesenchymal stem cells (MSCs) obtained from bone marrow in an experimental animal model of OA by direct intra-articular injection. MSCs were isolated from 2.8 kg white New Zealand rabbits. There were ten in the study group and ten in the control group. OA was induced by unilateral transection of the anterior cruciate ligament of the knee joint. At 12 weeks post-operatively, a single dose of 1 million cells suspended in 1 ml of medium was delivered to the injured knee by direct intra-articular injection. The control group received 1 ml of medium without cells. The knees were examined at 16 and 20 weeks following surgery. Repair was investigated radiologically, grossly and histologically using haematoxylin and eosin, Safranin-O and toluidine blue staining.
Results
Radiological assessment confirmed development of OA changes after 12 weeks. Rabbits receiving MSCs showed a lower degree of cartilage degeneration, osteophyte formation, and subchondral sclerosis than the control group at 20 weeks post-operatively. The quality of cartilage was significantly better in the cell-treated group compared with the control group after 20 weeks.
Conclusions
Bone marrow-derived MSCs could be promising cell sources for the treatment of OA. Neither stem cell culture nor scaffolds are absolutely necessary for a favourable outcome.
Cite this article: Bone Joint Res 2014;3:32–7.
doi:10.1302/2046-3758.32.2000187
PMCID: PMC3926293  PMID: 24526748
MSC; Mesenchymal stem cells; OA; Osteoarthritis; Rabbit model; Repair
22.  Strategic planning and designing of a hospital disaster manual in a tertiary care, teaching, research and referral institute in India 
BACKGROUND:
As per the “Disaster Management Act, 2005” of India, it is mandatory for government hospitals in India to prepare a disaster plan. This study aimed to prepare a disaster manual of a 1 900 bed tertiary care hospital, in consultation and involvement of all concerned stakeholders.
METHODS:
A committee of members from hospital administration, clinical, diagnostic and supportive departments worked on an initial document prepared according to the Act and gave their inputs to frame a final disaster manual.
RESULTS:
The prepared departmental standard operating procedures involved 116 people (doctors and paramedical staff), and were then synchronized, in 12 committee meetings, to produce the final hospital disaster manual.
CONCLUSIONS:
The present disaster manual is one of the few comprehensive plans prepared by the stakeholders of a government hospital in India, who themselves form a part of the disaster response team. It also helped in co-ordinated conduction of mock drills.
doi:10.5847/wjem.j.issn.1920-8642.2014.01.006
PMCID: PMC4129869  PMID: 25215145
Disaster Management Act; Disaster manual; Hospital administration; Stakeholders; Mock drills
23.  Outcomes of spousal versus related donor kidney transplants: A comparative study 
This study was designed to compare the outcomes of spousal donor (SD) with related donor (RD) kidney transplants performed at our center between January 2010 and October 2012. A total of 323 adult, ABO-compatible kidney transplants (SD 150 [46.4%], RD 173 [53.6%]) were included. Data on outcomes at 6 months post-transplant was collected retrospectively (2010-2011) and prospectively (January-October 2012). Majority of the donors (SD 88%, RD 72.2%) were females. In the SD group, donors were younger (SD 35.6 ± 8.2 years, RD 45.2 ± 11.5 years; P < 0.0001), whereas recipients were older (SD 42.2 ± 8.3 years, RD 30.0 ± 9.5 years; P < 0.0001). A significantly higher proportion of patients in the SD group were given induction therapy (43% vs 12%; P < 0.001). Biopsy proven acute rejections were more common in the RD group (16% vs 28.3%; P = 0.01). Majority (80.8%) of the acute rejections occurred in the first 2 weeks post-transplant in both groups. Isolated acute cellular rejections (ACRs) and isolated antibody mediated rejections constituted 50% and 25% of rejection episodes in both groups, whereas the remainder had histological evidence of both. The proportion of steroid responsive ACRs was similar in both groups (SD 83.3%, RD 65.4%; P = 0.2). The number of patients with abnormal graft function at the end of the study was higher in the RD group (2.3% vs. 12.3%; P = 0.001). Patient survival and infection rates were similar in the two groups. We conclude that short-term outcomes of SD transplants are not inferior to RD transplants. Lesser use of induction therapy in the RD group may explain the poorer outcomes as compared to the SD group.
doi:10.4103/0971-4065.125046
PMCID: PMC3927188  PMID: 24574623
Kidney transplant; outcomes; related donor; spousal donor
24.  Idiopathic Calcinosis Cutis over Elbow in a 12-Year Old Child 
Case Reports in Orthopedics  2013;2013:241891.
Calcinosis cutis is an uncommon disorder caused by an abnormal deposit of calcium phosphate in the skin in various parts of the body. Four main types of calcinosis cutis have been recognized according to etiology: associated with localized or widespread tissue changes or damage (dystrophic calcification), that associated with an abnormal calcium and phosphorus metabolism (metastatic calcification), not associated with any tissue damage or demonstrable metabolic disorder (idiopathic calcification), and Iatrogenic. Very few cases of idiopathic calcinosis cutis are reported in early childhood in the literature. We report one such case of idiopathic calcinosis cutis over elbow in a 12-year-old female child. Histological examinations of the lesions resected in this case reveal calcium deposits in the dermis, surrounded by foreign body giant cells. Idiopathic calcinosis cutis is a rare phenomenon and occurs in the absence of known tissue injury or systemic metabolic defect. It is important to delineate it from other calcification disorders for further plan of management. Medical therapy in calcinosis cutis is of limited benefit in pediatric age group and poses a challenging problem of postsurgical management.
doi:10.1155/2013/241891
PMCID: PMC3835332  PMID: 24294531
25.  Pathological studies on experimental Trypanosoma evansi infection in Swiss albino mice 
The pathology of Trypanosoma evansi infection was studied in Swiss albino mice using cattle isolate of the parasite. Sixteen Swiss albino mice were used in the experiment and were divided into two groups viz. infected group (I) and uninfected healthy control group (II) comprising 12 and four mice, respectively. Twelve mice from group I were infected with 1 × 105 purified trypanosomes. Systematic necropsy examination specifically of the infected mice (group I) as well as of healthy control (group II) was performed and pathological changes were recorded. The different tissue samples were collected in 10 % neutral buffered formal saline and were used to study the histopathological changes. Gross post-mortem examination revealed enlargement of spleen, petechial haemorrhages in liver in the terminal stages of disease. Tissue sections revealed presence of numerous trypanosomes in blood vessels of liver, spleen, brain and kidneys. Microscopically, liver revealed lesions varying from vacuolar degeneration, coagulative necrosis along with congestion and haemorrhages. Spleen showed extensive haemorrhages in red pulp area, haemosiderosis and aggregation of histiocytes resulting in multinuclear giant cell formation. Lungs revealed oedema, congestion and mild inflammatory changes. Brain revealed mild degenerative changes along with congestion of meningeal blood vessels. Kidneys showed tubular degeneration, congestion and cellular infiltration. Heart revealed mild degenerative changes along with interstitial oedema. All changes were consistent with trypanosome infection and were confirmed by presence of trypanosomes in most of the tissue sections examined.
doi:10.1007/s12639-012-0120-5
PMCID: PMC3427679  PMID: 24082539
Albino mice; Pathology; Trypanosoma evansi; Trypanosomosis

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