Publications by authors named "Kulwant Singh"

63 Publications

Impact of COVID-19 Pandemic on Neurosurgical Practice in a Tertiary Care Center in India.

J Neurosci Rural Pract 2021 Jan 4;12(1):24-32. Epub 2020 Sep 4.

Department of Neurosurgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

 The aim of the study is to determine the magnitude of repercussions of coronavirus disease 2019 (COVID-19) pandemic on neurosurgical specialty and formulate a management approach.  This combined retrospective and prospective study was done in neurosurgical specialty of IMS-BHU, Varanasi, India, a tertiary care center, between January 1, 2020 and May 31, 2020. Analysis of impact on neurosurgical emergency and electives was done over before pandemic, during lockdown 1 and 2 and during lockdown 3 and 4 timelines. Effects of COVID-19 pandemic on psychology of neurosurgical team (50 members) and on patient party (88) were also evaluated. Virtual learning and webinars as a substitute to residential neurosurgical training were analyzed by a questionnaire given to 13 neurosurgeons of our department.  Ordinary one-way ANOVA (analysis of variance) and unpaired -test were used according to data analyzed. < 0.05 was considered statistically significant. GraphPad Prism software was used for this analysis.  On an average 8.22 admissions per day were done in neurosurgical emergency before pandemic. After lockdown these figures reduced to 3.2 admissions per day during lockdown 1 and 2 and to 5.36 admissions per day during lockdown 3 and 4. There was significant reduction in neurotrauma admission rate during lockdown ( < 0.0001) at our center. There was 76% reduction in emergency neurosurgical operated cases during pandemic. There was significant reduction in outpatient department (OPD) attendance per day, OPD admissions per day ( < 0.0001), and total elective surgeries ( < 0.0001) during lockdown. Of 50 neurosurgical team members (neurosurgeons, nursing, and ground staff) interviewed, 90% of them had the fear of contacting the COVID-19 disease, fear of well-being of family and children, and difficulty in transport. Three out of 13 neurosurgeons (23.1%) agreed on change in practice based on what they learned from virtual teaching and webinars and only two of them (15.4%) accepted improvement of skills based on virtual learning.  The COVID-19 pandemic is causing a significant impact on health care systems worldwide. For conserving resources elective surgical procedures should be limited. This pandemic has a negative impact on neurosurgical resident training program and psychology of both neurosurgical unit and patients.
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http://dx.doi.org/10.1055/s-0040-1716455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846333PMC
January 2021

Rare, Yet Emerging Cause of Graft Dysfunction-ALECT 2 Amyloidosis.

Indian J Nephrol 2020 May-Jun;30(3):204-206. Epub 2020 Feb 11.

Department of Transplant Surgery, Surya Kidney Hospital, Mohali, Punjab, India.

Amyloidosis is characterized by pathological deposition of abnormal protein aggregates in various tissues, AL protein being the commonest. Amyloidosis derived from leukocyte cell-derived chemotaxin 2 (LECT2) is a recently recognized form of amyloidosis in the United States with predominant involvement of kidney and liver. We present a case of ALECT2 renal amyloid in a transplant recipient who presented with gradual worsening of graft function and subnephrotic proteinuria. To our knowledge, this is first case of LECT2 amyloidosis from Northern India in a transplant recipient. There is no effective therapy for amyloidosis derived from leukocyte cell-derived chemotaxin 2.
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http://dx.doi.org/10.4103/ijn.IJN_258_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470195PMC
February 2020

Clinical, operative, and outcome analysis of giant extradural hematoma: A retrospective study in tertiary care center.

Surg Neurol Int 2020 8;11:236. Epub 2020 Aug 8.

Department of Neurosurgery, Institute of Medical Sciences, Banaras Hindu University, Lanka, Varanasi, Uttar Pradesh, India.

Background: This study is aimed to find a critical volume of operated giant or massive extradural hematoma (EDH) that affects outcome significantly and analyze them with respect to their clinical, surgical, and outcome perspective.

Methods: This retrospective study includes 253 patients operated for EDH in emergency in the Department of Neurosurgery of IMS BHU, Varanasi, India, a tertiary care center, between August 1, 2018, and November 1, 2019. Giant EDH critical volume was evaluated. Twenty-nine patients with giant EDH with clot volume ≥ 80 ml were further analyzed for clinical, surgical, and outcome predictive factors. Statistical analysis was done using Prism GraphPad ver. 8.0.0. value was taken at 0.05.

Results: Dichotomized group analysis with Glasgow Outcome Score (GOS) 4-5 versus GOS 1-3 for testing clot volume revealed significance difference with < 0.001. Mean volume of GOS 1-3 came out to be 79.68 ml. Hence, we took clot volume >80 ml for further analysis. The most common age group was 20-40 (55.17%). M2 (31.03%) was the most common best motor response in operated giant EDH cases. Most of them were having severe (79.31%) head injury. Glasgow Coma Scale (GCS) at admission ( < 0.0001), pupillary changes ( = 0.0032), and best motor response ( < 0.0001) was significantly ( < 0.05) associated with outcome following surgery for giant EDH.

Conclusion: Giant EDH with volume ≥ 80 ml is associated with poorer outcome. GCS at admission, pupillary changes, and best motor response is predictors for surgical outcome of giant EDH.
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http://dx.doi.org/10.25259/SNI_128_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451170PMC
August 2020

Clinical Profile and Outcome of Brain Abscess in Children from a Tertiary Care Hospital in Eastern Uttar Pradesh.

Ann Indian Acad Neurol 2020 May-Jun;23(3):303-307. Epub 2020 Jun 10.

Department of Paediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Background And Aims: Brain abscess is a serious and dreadful disease presenting at tertiary centre. The objective of this study was to look into the clinical profile, predisposing conditions, microbiology and outcome of children suffering from brain abscess.

Methods: 30 children up to 18 years with clinical and imaging evidence of brain abscess were taken for study. Patients were stabilized as per unit protocol. Necessary investigations were carried out. Neuroimaging (CT or MRI) was used to confirm the diagnosis. All parameters (clinical, investigation, outcome) were recorded in predesigned performa. Neurosurgery consultation was sought in patients with multiple abscesses, posterior fossa abscesses, abscess with air-fluid level and causing midline shift.

Results: There were 16 males with 13 patients in age group (5-10 years). Mean duration of stay in hospital was 14.8 days. Most common predisposing factor was chronic suppurative otitis media (n-15). Typically, patients presented with fever, headache and seizures. On examination, motor deficits were the most common followed by signs of meningitis. Computerized tomography confirmed the diagnosis in most cases. Temporal lobe (n-11) was the commonest intracranial site for the abscess. and were the common pathogen isolated from blood and pus. Blood culture positivity rate was 16.7% and pus culture positivity rate was 25%. All cases were managed with intravenous antibiotics and aspiration (n-10) and excision (n-6). There were 5 deaths. There was complete immediate recovery in 13 cases with residual motor deficit in 12 cases.

Conclusion: Brain abscess is a rare but serious entity in children. Late diagnosis and improper management leads to poor outcome. Early surgical intervention is helpful. Threshold for diagnosis should be low in children with chronic ear infection and congenital heart diseases.
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http://dx.doi.org/10.4103/aian.AIAN_425_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313559PMC
June 2020

Hyperkalemia Unveiled: A Case of Barakat Syndrome.

Indian J Nephrol 2020 Mar-Apr;30(2):135-136. Epub 2020 Jan 3.

Department of Nephrology, Institute of Renal Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India.

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http://dx.doi.org/10.4103/ijn.IJN_132_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132841PMC
January 2020

Abrasive Wear Behavior of Cryogenically Treated Boron Steel (30MnCrB4) Used for Rotavator Blades.

Materials (Basel) 2020 Jan 16;13(2). Epub 2020 Jan 16.

Mechanical Engineering Department, University of Birmingham, Birmingham B15 2TT, UK.

Rotavator blades are prone to significant wear because of the abrasive nature of sand particles. The aim of this research work is to investigate the effect of cryogenic treatment and post tempering on abrasive wear behavior, in the presence of angular quartz sand (grain size of 212-425 μm), of rotavator blade material of boron steel (30MnCrB4). Cryogenic treatment has caused an improvement in the abrasive wear resistance and microhardness of 30MnCrB4 by 60% and 260.73%, respectively, compared to untreated material due to enhancement in hardness, the conversion of retained austenite into martensite, and the precipitation of secondary carbides in boron steel after exposure to cryogenic temperature. Economic analysis justifies the additional cost of cryogenic treatment.
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http://dx.doi.org/10.3390/ma13020436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013460PMC
January 2020

Correction to "MEMS impedance flow cytometry designs for effective manipulation of micro entities in health care applications" [Biosens. Bioelectron], 2019, 142, 111526.

Biosens Bioelectron 2020 02 13;149:111850. Epub 2019 Nov 13.

Department of Electronics & Communication Engineering, Manipal University Jaipur, 303007, Rajasthan, India. Electronic address:

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http://dx.doi.org/10.1016/j.bios.2019.111850DOI Listing
February 2020

MEMS impedance flow cytometry designs for effective manipulation of micro entities in health care applications.

Biosens Bioelectron 2019 Oct 23;142:111526. Epub 2019 Jul 23.

Department of Electronics & Communication Engineering, Manipal University Jaipur, 303007, Rajasthan, India. Electronic address:

Efficient manipulation of micro biological cells has always been a very important task in healthcare sector for which a Micro Electro Mechanical System (MEMS) based impedance flow cytometry has been proven to be a promising technique. This technique utilise the advantage of dielectrophoresis (DEP) force which is generated by non-uniform electric field in a microfluidic channel using an appropriate external AC supply at certain frequency range. The DEP forces generated in micro-channel depend upon various biological and physical parameters of cell and suspending medium. Apart from that design parameters of microfluidic channel and dimension of electrodes used for generating DEP action also plays major role in micro cell/bead manipulation. This article give remarks on the operating parameters which affects the cell manipulation and interrogates the currently accepted various electrode orientations in microfluidic MEMS flow cytometer technologies for effective manipulation of micro entities like healthy human cells (T-lymphocytes, B- lymphocytes, Monocytes, Leukocytes erythrocytes and human kidney cells HEK293), animal cells (neuroblastoma N115 and sheep red blood cells), cancer cells (MCF-7, MDA-435 and CD34), yeast cells (saccharomyces cerevisiae, listeria innocua and E. coli) and micro particles (polystyrene beads) based on their dielectric properties using DEP action. Article focuses on the key electrode orientations for generation of non-uniform electric field in microfluidic flow cytometer like tapered electrodes, trapezoidal electrode arrays, Interdigitated electrodes, curved microelectrode and 3D electrode orientations and give remarks on their advantages and limitations. The cell manipulation with current MEMS impedance flow cytometry orientations targeting possibilities of implementation of the lab-on-chip devices has been discussed.
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http://dx.doi.org/10.1016/j.bios.2019.111526DOI Listing
October 2019

New insight on 8-anilino-1-naphthalene sulfonic acid interaction with TgFNR for hydrophobic exposure analysis.

Int J Biol Macromol 2019 Feb 31;122:636-643. Epub 2018 Oct 31.

Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow PIN 226 031, INDIA. Electronic address:

The exposed hydrophobic patches of protein are widely detected through the binding by the fluorescent probes such as 1-anilino-8-naphthalene sulfonate (ANS), Nile Red (NR) and 1-(N-phenylamino) naphthalene, N-(1-Naphthyl) aniline (1NPN). Interestingly, at pH4, where the Toxoplasma gondii Ferredoxin-NADP(+) reductase (TgFNR) is stable, an exclusive binding and fluorescence emission was observed for ANS. To understand the underlying difference in the binding of ANS, NR and 1NPN; their effect on the protein structure was studied in detail. ANS was found to interact with TgFNR via electrostatic as well as hydrophobic interactions at pH4. NR and 1NPN did not show any such binding to TgFNR in the similar conditions, however showed strong hydrophobic interaction in the presence of NaCl or DSS (2, 2-dimethyl-2-silapentane-5-sulfonate). The subsequent structural studies suggest that ANS, NaCl and DSS induced partial unfolding of TgFNR by modulating ionic interactions of the enzyme, leading to the exposure of buried hydrophobic patches amicable for the binding by NR and 1NPN. The induced unfolding of TgFNR by ANS is unique and thus cautions to use the fluorescent dye as simple indicator to probe the exposed hydrophobic patches of the protein or its folding intermediates.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.10.208DOI Listing
February 2019

Bilateral Mirror Image Cervical Neurofibroma in an Adult with Neurofibromatosis Type 1.

Malays J Med Sci 2017 Mar 24;24(1):117-120. Epub 2017 Feb 24.

Department of Pathology, Sir Sunder Lal Hospital, IMS BHU, Varanasi, Uttar Pradesh-221005, India.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterised by various phenotypic features like hyperpigmented spots, neurofibromas, Lisch nodules, skeletal abnormalities and tendency to develop neoplasms. Only few cases of Non-Familial Spinal Neurofibromatosis-1 (Non-FSNF1) have been described in literature with tumors involving the spinal roots at every level being even rarer. We reported an interesting case of bilateral symmetrical cervical neurofibroma with multiple spinal neurofibromas appearing as mirror image on CT, associated with non familial NF-1 as a rare presentation in a 25-year-old adult male.
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http://dx.doi.org/10.21315/mjms2017.24.1.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346010PMC
March 2017

Bilateral Traumatic Intracranial Hematomas and its Outcome: a Retrospective Study.

Indian J Surg 2017 Feb 16;79(1):19-23. Epub 2015 Dec 16.

Department of Radio diagnosis, Sir Sunder Lal Hospital, IMS, BHU, Varanasi, Uttar Pradesh 221005 India.

The objective of this study was to evaluate the age distribution, mode of injury, type of hematomas, and their surgical outcome in patients with bilateral traumatic head injuries. The present study included 669 cases of traumatic head injury who presented at the neurosurgery emergency out of which 94 cases had bilateral head injuries from the period of August 2009 to April 2014. The data from the hospital computerized database were retrospectively analysed. Cases of bilateral traumatic head injury included 94 patients out of which 88.29 % ( = 83) were males and 11.70 % ( = 11) were females. Commonest mode of injury was road traffic accident in 56.38 % ( = 53) followed by fall from height in 29.78 % ( = 28). In our study, 25.53 % patients had epidural hematoma (EDH) with intracerebral hematoma (ICH) or contusion ( = 24), followed by EDH with subarachnoid hemorrhage (SAH) in 18.08 % ( = 17). At the time of discharge, all those patients managed conservatively had good Glasgow outcome scale (GOS) while with surgical intervention 58 % patients had good GOS, 19 % had moderate disability, and 9 % remained with severe disability. In cases of bilateral hematomas, EDH is most common and should be managed in neurosurgical emergency. Other combinations of bilateral intracranial hematomas should be managed according to the surgical indication and serial CT imaging.
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http://dx.doi.org/10.1007/s12262-015-1416-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346077PMC
February 2017

A prospective pilot study on serum cleaved tau protein as a neurological marker in severe traumatic brain injury.

Br J Neurosurg 2017 Jun 15;31(3):356-363. Epub 2017 Mar 15.

d Department of Anatomy , Sir Sunder Lal Hospital, IMS BHU , Varanasi , Uttar Pradesh , India.

Objective: Neurotrauma has been labelled as a "silent epidemic" affecting both the developed and the developing nations. To date, no single brain-specific biomarker has been unanimously accepted for routine clinical use in TBI. Our study aims to determine the correlation of "cleaved-tau protein" in severe traumatic brain injury (TBI) with Glasgow Coma Scale (GCS) at the time of admission, mode of injury, CT findings and outcome at discharge.

Methods: The study has been approved by the institutional ethical committee. 40 cases with severe TBI and 40 randomly selected healthy controls were included in this prospective study. Venous blood samples were collected and serum cleaved tau protein levels were measured and correlated with gender, mode of injury, CT findings GCS score and GOS score at discharge.

Results: In the severe TBI group, the mean serum cleaved tau protein levels in males were 91.65 ± 41.34 pg/ml (mean ± S.D.), and females were 104.43 ± 53.08 pg/ml (mean ± S.D.), (p = 0.27). Mean serum C-tau level in study group was 95.48 ± 44.87 pg/ml (range 36.44-192.34), 95% C.I. (81.13-109.83) and in controls was 33.82 ± 13.65 pg/ml (range 2.48-66.54), 95% C.I. (29.46-38.19) (p < 0.001). The distribution of serum C-tau was in severe TBI group varied in all categories of GCS at 0th day (p < 0.001). Serum cleaved tau protein levels in the good outcome group were 74.26 ± 25.43 pg/ml (mean ± S.D.), range 36.44-144.54, 95% C.I. (63.52-85.00) and the poor-outcome group were 127.32 ± 49.40 pg/ml, range 66.65-192.34, 95% C.I. (100.99-153.64) (p = 0.001).

Conclusion: In severe TBI, serum cleaved tau protein levels were significantly higher as compared to the controls in this prospective study. However, results of this study are preliminary in nature and there is a need to undertake larger prospective studies to reach a definitive conclusion.
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http://dx.doi.org/10.1080/02688697.2017.1297378DOI Listing
June 2017

Perspectives on hypertension outcomes after single-stage clearance of a complete staghorn renal calculus.

Saudi J Kidney Dis Transpl 2017 Jan-Feb;28(1):170-173

Department of Obstetrics and Gynecology, People's College of Medical Sciences, Bhopal, Madhya Pradesh, India.

A 55-year-old male presented, in June 2013, with left flank pain. Investigations revealed a complete staghorn stone. He had undergone two sittings of extracorporeal shock wave lithotripsy (ESWL) in 2008 for left renal stone. One year subsequent to this, he was diagnosed with hypertension and diabetes. The management of complete staghorn stones in a single sitting is a difficult proposition. Percutaneous nephrolithotomy (PCNL) is the gold standard to manage such stones. The patient was subjected to PCNL, and complete clearance was achieved in one sitting. On one-year follow-up, there was a significant reduction in blood pressure (BP) and better glycemic control. Although there are several reports where hypertension has been reported after multiple sittings of ESWL, whether ESWL contributed to the genesis of hypertension and diabetes in this patient or it was simply incidental, cannot be stated with certainty. There was a significant reduction in the BP after complete stone removal, but there is uncertainty over the effect of total clearance of renal stones on hypertension, and we need to await the results of more controlled trials studying this phenomenon. A better glycemic control was perhaps achieved secondary to the eradication of recurrent urinary tract infections due to complete stone clearance.
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http://dx.doi.org/10.4103/1319-2442.198244DOI Listing
August 2019

High incidence of neural tube defects in Northern part of India.

Asian J Neurosurg 2016 Oct-Dec;11(4):352-355

Department of Anatomy, Sir Sunder Lal Hospital, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Background: In the absence of primary care and prevailing associated social stigma, many patients of neural tube defects (NTDs) from remote areas die without getting any treatment. The high number of such untreated cases and unregistered deaths in these areas made us ponders to the fact that tertiary care center-based studies do not represent the true incidence of NTDs.

Materials And Methods: We did a population-based survey for NTDs births of rural areas from Jaunpur to Ghazipur district in Eastern Uttar Pradesh. These districts are among the least developed areas of Northern India in Uttar Pradesh among other 17.

Results: The data show an incidence of 7.48 per 1000 live births.

Conclusion: Besides of unawareness regarding periconceptional folate supplementation, intensive effort is required to design adequately powered studies to search other key factors responsible for high prevalence of NTDs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974957PMC
http://dx.doi.org/10.4103/1793-5482.175628DOI Listing
October 2016

Clear cell sarcoma of the paraspinal ligament - A rare tumor at an unusual location: A review.

Neurol India 2016 Jul-Aug;64(4):802-5

Department of Orthopedics, Trauma Centre, Sir SunderLal Hospital, IMS, BHU, Varanasi, Uttar Pradesh, India.

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http://dx.doi.org/10.4103/0028-3886.185353DOI Listing
October 2018

Uncommon presentation of choroid plexus papilloma in an infant.

J Pediatr Neurosci 2016 Jan-Mar;11(1):61-3

Department of Neuro Surgery, Sir Sunderlal Hospital, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Choroid plexus tumors are relatively rare primary brain tumors that arise from the epithelial differentiated tissue, majority being well-differentiated papillomas. In adults, fourth ventricle and in children, lateral ventricles are the most common site of these tumors. We reported a case of choroid plexus papilloma in the temporal horn of lateral ventricle in a female child who presented with the uncommon symptoms of sudden intraventricular hemorrhage and multiple episodes of seizure without symptoms of raised intracranial tension.
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http://dx.doi.org/10.4103/1817-1745.181254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862292PMC
May 2016

Is size really a contraindication for laparoscopic resection of giant adrenal myelolipomas?

BMJ Case Rep 2016 Mar 17;2016. Epub 2016 Mar 17.

LN Medical College and Research Centre, Bhopal, Madhya Pradesh, India.

A 55-year-old non-diabetic, normotensive man presented with dull aching pain in the left upper abdomen of 2-year duration. He had no significant medical, surgical or family history. Relevant blood tests and chest skiagram were normal. 24 h urinary vanillylmandelic acid levels and serum electrolyte levels were normal. Ultrasonogram and CT findings were suggestive of a 15 × 11 cm giant left adrenal myelolipoma. A left adrenalectomy was performed using a laparoscopic transperitoneal approach employing three ports. Pneumoperitoneum was achieved by this closed method. After successful excision, the internal contents were suctioned and the capsule was retrieved through a 2.5 cm incision. The operating time was 210 min and total blood loss 50-60 mL; no blood transfusions were needed. The patient was discharged on the third postoperative day. Histopathology confirmed an adrenal myelolipoma. The cited case is of the largest adrenal myelolipoma resected entirely using a laparoscopic approach.
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http://dx.doi.org/10.1136/bcr-2016-215048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800226PMC
March 2016

UTX inhibition as selective epigenetic therapy against TAL1-driven T-cell acute lymphoblastic leukemia.

Genes Dev 2016 Mar;30(5):508-21

The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8L6, Canada; Ottawa Institute for Systems Biology, Ottawa, Ontario K1H 8L6, Canada;

T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures, and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and, as such, T-ALL treatments are uniformly applied across subtypes, leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL by which a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in the dosage and activity of the histone 3 Lys27 (H3K27) demethylase UTX/KDM6A. Specifically, we identify UTX as a coactivator of TAL1 and show that it acts as a major regulator of the TAL1 leukemic gene expression program. Furthermore, we demonstrate that UTX, previously described as a tumor suppressor in T-ALL, is in fact a pro-oncogenic cofactor essential for leukemia maintenance in TAL1-positive (but not TAL1-negative) T-ALL. Exploiting this subtype-specific epigenetic vulnerability, we propose a novel therapeutic approach based on UTX inhibition through in vivo administration of an H3K27 demethylase inhibitor that efficiently kills TAL1-positive primary human leukemia. These findings provide the first opportunity to develop personalized epigenetic therapy for T-ALL patients.
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http://dx.doi.org/10.1101/gad.276790.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782046PMC
March 2016

Dorsal spinal epidural psammomatous meningioma in an adult male.

J Neurosci Rural Pract 2016 Jan-Mar;7(1):125-7

Department of Anaesthesia, Sir Sunderlal Hospital, Institute of Medical Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Meningiomas are benign in nature and arise from the arachnoid cells. They are mostly situated in the intracranial compartment, whereas spinal meningiomas are rare. Approximately, in 10% of cases, an extradural component is seen but an exclusively extradural meningioma is quite uncommon. However, WHO Grade II (atypical) and Grade III (anaplastic) tumors can behave aggressively. We reported a case of purely extradural psammomatous meningioma in an adult male affecting the dorsal spine although uncommon meningiomas should be included in the differential diagnosis of extradural intraspinal masses.
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http://dx.doi.org/10.4103/0976-3147.172166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750308PMC
March 2016

Acquired dorsal intraspinal epidermoid cyst in an adult female.

Surg Neurol Int 2016 25;7(Suppl 3):S67-9. Epub 2016 Jan 25.

Department of Pathology, Sir Sunderlal Hospital, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Background: Epidermoid and dermoid cyst comprise <1% of spinal tumors and may be congenital (hamartoma) or acquired (iatrogenic) in origin. Epidermoid cysts within the neuraxis are rare benign neoplasms that are most commonly located in the intracranial region.

Case Description: Here, we report the a case of an acquired intradural extramedullary epidermoid cyst involving the thoracic region in an adult female who had no associated history of an accompanying congenital spinal deformity.

Conclusion: Early diagnosis and immediate surgical intervention reduce patient morbidity. Near complete or subtotal excision of the cyst wall is warranted to prevent inadvertent injury to the spinal cord thus minimizing neurological morbidity.
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http://dx.doi.org/10.4103/2152-7806.174890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743265PMC
February 2016

Functional evaluation of an iridotomy in primary angle closure eyes.

Graefes Arch Clin Exp Ophthalmol 2016 Jun 19;254(6):1141-9. Epub 2016 Feb 19.

Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 110029, India.

Objective: To evaluate the functional efficacy of an iridotomy in primary angle closure (PAC) eyes by measuring IOP responses to provocative tests before and after iridotomy.

Design: Prospective cohort study.

Subjects: 50 consecutive adult patients, 40-60 years of age, having primary angle closure.

Methods: Clinical examination, perimetry, biometry and ultrasound biomicroscopy of the angle were done. A darkroom prone provocative test (DRPPT), a mydriatic test and a Valsalva maneuver were performed before and after the iridotomy.

Main Outcome Measures: IOP change in response to the provocative tests before and after iridotomy, and correlation with baseline parameters.

Results: IOP at baseline and after iridotomy was 14.4 ± 2.7 mmHg and 14.3 ± 2.6 mmHg, respectively (p = 0.)83. There was no significant change on diurnal phasing before and after an iridotomy (p = 0.)11. The mean IOP rise was 5.9 ± 3.7 mmHg on the DRPPT, 4.3 ± 3.5 mmHg on the Mydriatic test and 9.1 ± 4.9 mmHg on the Valsalva maneuver, and was reduced significantly to 3.2 ± 2.1 mmHg, 2.3 ± 1.8 and 6.4 ± 3.5, respectively(p < 0.001 for all tests). The decrease in pupillary block component for all 50 eyes was 46.5 % for the mydriatic test, 45.8 % for the DRPPT and 29.7 % for the Valsalva maneuver. PAC eyes positive on the DRPPT and mydriatic test prior to an iridotomy became negative after laser iridotomy in 75.9 and 84.6 % eyes, respectively, but on the Valsalva maneuver, only 23.8 % became negative. After iridotomy, eyes that continued to be positive on the mydriatic test had a significantly thicker lens (p = 0.02), decreased TCPD (p = 0.014) and narrower trabecular-iris angle (p = 0.048). On the DRPPT, they had a thicker lens (p = 0.03), shorter iris thickness (p = 0.025) and TCPD (p = 0.032), and on the Valsalva maneuver, they had a narrower scleral-ciliary process angle (SCPA; p = 0.019) and shorter TCPD (p = 0.015).

Conclusions: This comprehensive functional evaluation of laser iridotomy in early PAC eyes showed a significant reduction in the pupillary block component of IOP response to provocative testing, possibly decreasing IOP fluctuations over time. An iridotomy does not, however, significantly change mean IOP or diurnal phasing of IOP in PAC eyes. Eyes with a very narrow angle or a thick lens may continue to have angle closure due to other pathomechanisms for angle closure.
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http://dx.doi.org/10.1007/s00417-016-3298-xDOI Listing
June 2016

Nuclear matrix-associated protein SMAR1 regulates alternative splicing via HDAC6-mediated deacetylation of Sam68.

Proc Natl Acad Sci U S A 2015 Jun 15;112(26):E3374-83. Epub 2015 Jun 15.

Chromatin and Disease Biology Laboratory, National Centre for Cell Science, Pune 411007, India;

Pre-mRNA splicing is a complex regulatory nexus modulated by various trans-factors and their posttranslational modifications to create a dynamic transcriptome through alternative splicing. Signal-induced phosphorylation and dephosphorylation of trans-factors are known to regulate alternative splicing. However, the role of other posttranslational modifications, such as deacetylation/acetylation, methylation, and ubiquitination, that could modulate alternative splicing in either a signal-dependent or -independent manner remain enigmatic. Here, we demonstrate that Scaffold/matrix-associated region-binding protein 1 (SMAR1) negatively regulates alternative splicing through histone deacetylase 6 (HDAC6)-mediated deacetylation of RNA-binding protein Sam68 (Src-associated substrate during mitosis of 68 kDa). SMAR1 is enriched in nuclear splicing speckles and associates with the snRNAs that are involved in splice site recognition. ERK-MAPK pathway that regulates alternative splicing facilitates ERK-1/2-mediated phosphorylation of SMAR1 at threonines 345 and 360 and localizes SMAR1 to the cytoplasm, preventing its interaction with Sam68. We showed that endogenously, SMAR1 through HDAC6 maintains Sam68 in a deacetylated state. However, knockdown or ERK-mediated phosphorylation of SMAR1 releases the inhibitory SMAR1-HDAC6-Sam68 complex, facilitating Sam68 acetylation and alternative splicing. Furthermore, loss of heterozygosity at the Chr.16q24.3 locus in breast cancer cells, wherein the human homolog of SMAR1 (BANP) has been mapped, enhances Sam68 acetylation and CD44 variant exon inclusion. In addition, tail-vein injections in mice with human breast cancer MCF-7 cells depleted for SMAR1 showed increased CD44 variant exon inclusion and concomitant metastatic propensity, confirming the functional role of SMAR1 in regulation of alternative splicing. Thus, our results reveal the complex molecular mechanism underlying SMAR1-mediated signal-dependent and -independent regulation of alternative splicing via Sam68 deacetylation.
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http://dx.doi.org/10.1073/pnas.1418603112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491761PMC
June 2015

Pulmonary alveolar microlithiasis: an interesting case report with systematic review of Indian literature.

Front Med 2015 Jun 30;9(2):229-38. Epub 2015 May 30.

Department of Pathology, Pondicherry Institute of Medical Sciences, Pondicherry, 605014, India,

Pulmonary alveolar microlithiasis is a rare disease characterized by intra-alveolar presence of microliths. This study reports an interesting case of pulmonary alveolar microlithiasis and provides a systematic review of cases reported from India. A 23-year-old female presented with a history of cough, wheeze, chest pain, and episodic wheeze for five months. Pulmonary function tests demonstrated an obstructive pattern, and chest Xray showed fine micronodular opacities predominantly involving the middle and lower zones of both lungs. Transbronchial lung biopsy revealed the diagnosis. She responded well to inhaled steroid therapy. A systematic review of literature was performed and identified 73 cases of pulmonary alveolar microlithiasis reported from India. The mean (SD) age of the patients was 28.8 (14.9) years, with an almost equal male:female ratio. Many patients were asymptomatic at presentation. Breathlessness and cough were the most common symptoms, and the disease progressed into respiratory failure associated with cor pulmonale. About one-third of the cases were initially misdiagnosed and treated as pulmonary tuberculosis. Extra-pulmonary manifestations and comorbidities were also evident in our series. This systematic review helps to determine epidemiological and clinical characteristics of pulmonary alveolar microlithiasis. Further research is needed to elucidate the etiopathogenesis, diagnosis, and therapeutic options, which are beneficial in developing and identifying cost-effective treatment for pulmonary alveolar microlithiasis.
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http://dx.doi.org/10.1007/s11684-015-0394-yDOI Listing
June 2015

A KAP1 phosphorylation switch controls MyoD function during skeletal muscle differentiation.

Genes Dev 2015 Mar;29(5):513-25

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;

The transcriptional activator MyoD serves as a master controller of myogenesis. Often in partnership with Mef2 (myocyte enhancer factor 2), MyoD binds to the promoters of hundreds of muscle genes in proliferating myoblasts yet activates these targets only upon receiving cues that launch differentiation. What regulates this off/on switch of MyoD function has been incompletely understood, although it is known to reflect the action of chromatin modifiers. Here, we identify KAP1 (KRAB [Krüppel-like associated box]-associated protein 1)/TRIM28 (tripartite motif protein 28) as a key regulator of MyoD function. In myoblasts, KAP1 is present with MyoD and Mef2 at many muscle genes, where it acts as a scaffold to recruit not only coactivators such as p300 and LSD1 but also corepressors such as G9a and HDAC1 (histone deacetylase 1), with promoter silencing as the net outcome. Upon differentiation, MSK1-mediated phosphorylation of KAP1 releases the corepressors from the scaffold, unleashing transcriptional activation by MyoD/Mef2 and their positive cofactors. Thus, our results reveal KAP1 as a previously unappreciated interpreter of cell signaling, which modulates the ability of MyoD to drive myogenesis.
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http://dx.doi.org/10.1101/gad.254532.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358404PMC
March 2015

An extremely unusual presentation of isolated extrathoracic sarcoidosis of submandibular lymph node in a child.

Lung India 2014 Oct;31(4):413-5

Department of Respiratory Medicine, BPSGMCW, Khanpur Kalan, Sonepat, Haryana, India.

A 12-year-old male child presented with left submandibular lymphadenopathy; excision biopsy revealed noncaseating granuloma with numerous Schaumann bodies in histopathology, suggestive of isolated extrathoracic sarcoidosis, which is an extremely rare entity in the pediatric age group.
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http://dx.doi.org/10.4103/0970-2113.142154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220331PMC
October 2014

Salvaging a solitary necrotic testis in a quadriparetic.

BMJ Case Rep 2014 Nov 6;2014. Epub 2014 Nov 6.

Department of Medicine, People's College of Medical Sciences, Bhopal, Madhya Pradesh, India.

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http://dx.doi.org/10.1136/bcr-2014-205893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225305PMC
November 2014

Forgotten double J stents with a 'Houdini'-like vanishing act.

BMJ Case Rep 2014 May 26;2014. Epub 2014 May 26.

Department of Medicine, People's College of Medical Sciences, Bhopal, Madhya Pradesh, India.

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http://dx.doi.org/10.1136/bcr-2014-205220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039764PMC
May 2014

Signalling mechanisms involved in renal pathological changes during cisplatin-induced nephropathy.

Eur J Clin Pharmacol 2013 Nov 9;69(11):1863-74. Epub 2013 Aug 9.

Cardiovascular Pharmacology Division, Department of Pharmacology, Rajendra Institute of Technology and Sciences, Sirsa, 125 055, India.

Context: Cisplatin, a coordination platinum complex, is used as a potential anti-neoplastic agent, having well recognized DNA-damaging property that triggers cell-cycle arrest and cell death in cancer therapy. Beneficial chemotherapeutic actions of cisplatin can be detrimental for kidneys.

Background: Unbound cisplatin gets accumulated in renal tubular cells, leading to cell injury and death. This liable action of cisplatin on kidneys is mediated by altered intracellular signalling pathways such as mitogen-activated protein kinase (MAPK), extracellular regulated kinase (ERK), or C- Jun N terminal kinase/stress-activated protein kinase (JNK/SAPK). Further, these signalling alterations are responsible for release and activation of tumour necrosis factor (TNF-α), mitochondrial dysfunction, and apoptosis, which ultimately cause the renal pathogenic process. Cisplatin itself enhances the generation of reactive oxygen species (ROS) and activation of nuclear factor-κB (NF-κB), inflammation, and mitochondrial dysfunction, which further leads to renal apoptosis. Cisplatin-induced nephropathy is also mediated through the p53 and protein kinase-Cδ (PKCδ) signalling pathways.

Objective: This review explores these signalling alterations and their possible role in the pathogenesis of cisplatin-induced renal injury.
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http://dx.doi.org/10.1007/s00228-013-1568-7DOI Listing
November 2013

Tissue-specific splicing of a ubiquitously expressed transcription factor is essential for muscle differentiation.

Genes Dev 2013 Jun 30;27(11):1247-59. Epub 2013 May 30.

Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada.

Alternate splicing contributes extensively to cellular complexity by generating protein isoforms with divergent functions. However, the role of alternate isoforms in development remains poorly understood. Mef2 transcription factors are essential transducers of cell signaling that modulate differentiation of many cell types. Among Mef2 family members, Mef2D is unique, as it undergoes tissue-specific splicing to generate a muscle-specific isoform. Since the ubiquitously expressed (Mef2Dα1) and muscle-specific (Mef2Dα2) isoforms of Mef2D are both expressed in muscle, we examined the relative contribution of each Mef2D isoform to differentiation. Using both in vitro and in vivo models, we demonstrate that Mef2D isoforms act antagonistically to modulate differentiation. While chromatin immunoprecipitation (ChIP) sequencing analysis shows that the Mef2D isoforms bind an overlapping set of genes, only Mef2Dα2 activates late muscle transcription. Mechanistically, the differential ability of Mef2D isoforms to activate transcription depends on their susceptibility to phosphorylation by protein kinase A (PKA). Phosphorylation of Mef2Dα1 by PKA provokes its association with corepressors. Conversely, exon switching allows Mef2Dα2 to escape this inhibitory phosphorylation, permitting recruitment of Ash2L for transactivation of muscle genes. Thus, our results reveal a novel mechanism in which a tissue-specific alternate splicing event has evolved that permits a ubiquitously expressed transcription factor to escape inhibitory signaling for temporal regulation of gene expression.
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http://dx.doi.org/10.1101/gad.215400.113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690398PMC
June 2013

Surgery in hydrocephalus of tubercular origin: challenges and management.

Acta Neurochir (Wien) 2013 May 16;155(5):869-73. Epub 2013 Mar 16.

Department Surgery, Era's Lucknow Medical College, Lucknow, India.

Background: Hydrocephalus of tubercular origin is one of the most dreaded and difficult to manage complications of brain tuberculosis. Traditionally, the management has been ventriculoperitoneal shunting, but in recent years emerging interest is in endoscopic ventriculostomy. In this article, we discuss the management protocol of hydrocephalus in various stages of disease.

Methods: A total of 424 cases of tubercular origin hydrocephalus were managed between years 2000 and 2009. Initially the cases were managed by ventriculoperitoneal shunting, which was followed by use of endoscopic third ventriculostomy. Drug-resistant cases were also encountered and managed according to drug sensitivity.

Results: The results provided through evaluation of retrospective data showed a high mortality in cases of hydrocephalus of acute origin if endoscopic third ventriculostomy was performed. The cerebrospinal fluid protein level and neurological status of the patient determined the success or failure of the procedure. For better management, patients were divided into six groups and their management underlined.

Conclusion: The cases of tubercular meningitis with aqueductal stenosis presenting in early stages should be given a trial of endoscopic third ventriculostomy where chronic burnt-out cases or cases with communicating hydrocephalus should be managed by ventriculoperitoneal shunting.
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http://dx.doi.org/10.1007/s00701-013-1658-4DOI Listing
May 2013