Publications by authors named "Gaurav Tyagi"

41 Publications

Xanthogranulomatous Colloid Cyst in a 13-Year-Old Boy: A Case Report and Surgical Implications.

Pediatr Neurosurg 2022 5;57(3):202-206. Epub 2022 Apr 5.

Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India.

Introduction: Colloid cysts are relatively uncommon lesions in the pediatric population. The xanthogranulomatous (XG) variant is very rare with less than 30 reported cases.

Case Report: In this report, the patient was a 13-year-old boy who presented with transient episodes of headache with blurring of vision. His MRI brain showed a T2 hyperintense well-defined cystic lesion, with an eccentrically located T2 hypointense partially enhancing nodule, at the foramen of Monro. He underwent middle frontal gyrus transcortical, transchoroidal gross total excision of the cyst. The histopathology of the lesion revealed an XG colloid cyst. The patient recovered well from the procedure and was relieved of the symptoms.

Conclusion: XG colloid cyst may present with altered radiological features compared to the normal variant. This can pose a diagnostic dilemma, and it is important to differentiate it from a craniopharyngioma or a parasitic cyst, as in our case. When considered preoperatively, surgeons should be conscious to review their surgical strategies. Stereotactic aspiration of the XG cyst should be avoided as contents are thicker and heterogeneous than the usual. The spillage of cyst contents should be prevented. Also, the XG cysts are likely to have a poor cyst-fornix or -choroid plexus interface due to inflammation limiting complete resection.
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http://dx.doi.org/10.1159/000524480DOI Listing
June 2022

Sella Bugged! Abscess Inside a Craniopharyngioma: Case Report with Literature Review.

Pediatr Neurosurg 2022 9;57(3):191-195. Epub 2022 Mar 9.

Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India.

Introduction: Abscess within a craniopharyngioma (CPG) is extremely rare and only 8 such cases have been reported in literature. Most patients present with hypopituitarism and visual disturbances. We report the first ever case of a CPG with abscess in a pediatric patient.

Case Report: A 10-year-old girl presented with visual deterioration and bitemporal hemianopia. Her CT and MRI brain suggested of a sellar-suprasellar CPG. Due to ill-developed sino-nasal anatomy, a transcranial approach was made for the lesion. The lesion was well capsulated, thick walled, and appeared inflamed. Upon incising the wall, thick yellowish pus was drained out in a controlled manner. This was followed by a partial resection of the CPG wall and eccentric, adhered, calcified residue was left behind with an Ommaya drain. The abscess culture grew Enterococcus species and histopathology revealed adamantinomatous CPG. Patient underwent culture sensitive antibiotics course followed by radiation for the residue. She was doing well at 1-year follow-up with clinical and radiological improvement.

Conclusion: This is the first report of a pediatric case with secondary abscess in CPG. Operative management of such a case includes controlled drainage of pus without dissemination into the surrounding arachnoid space. The tumor and abscess have to be addressed as separate surgical entities; infection control and wherever complete resection is not feasible, partial safe resection followed by radiotherapy is a viable option.
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http://dx.doi.org/10.1159/000523977DOI Listing
June 2022

Corrigendum to "Bleomycin induced lung fibrosis increases work of breathing in the mouse" [Pulm. Pharmacol.Therapeut. 25 (2012) 281-285].

Pulm Pharmacol Ther 2022 Jun 3;73-74:102122. Epub 2022 Mar 3.

Hoffmann-La Roche, pRED, Pharma Research & Early Development, DTA Inflammation, 340 Kingsland Street, Nutley, NJ, 07110, USA.

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http://dx.doi.org/10.1016/j.pupt.2022.102122DOI Listing
June 2022

Surgical management of simultaneous supra- and infratentorial hemorrhages in a pediatric patient with multiple cavernomas.

J Cerebrovasc Endovasc Neurosurg 2022 Feb 28. Epub 2022 Feb 28.

Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India.

Multiple intracranial cavernomas are rare and occur mostly in familial cases. Clinical presentation with simultaneous rupture of two or more lesions has only been reported in four cases to date. A 15-year-old boy presented with simultaneous right frontal and superior vermian hematomas with hydrocephalus. The patient underwent a ventriculoperitoneal shunt, and his magnetic resonance imaging (MRI) revealed multiple cavernomas with bleed in the above-mentioned locations. The patient underwent a midline suboccipital craniotomy and excision of the cavernoma. The supratentorial lesions were left in situ in lieu of small size, no history of seizures, mass effect, or other neurological deficits. The patient recovered well from surgery with significant improvement in truncal ataxia. He remained asymptomatic for supratentorial lesions at follow-up. Cavernomas should be considered as differential diagnoses in cases of multiple intraparenchymal hemorrhages, especially in pediatric patients. The surgical management should be rationalized based on the lesion location, the eloquence of the surrounding parenchyma, mass effect, and the risks of re-rupture. Due to the rarity of multiple simultaneous hemorrhages, the management of multiple cavernomas remains controversial. The patient's relatives can be screened with MRI to rule out the familial form of the disease. Strict clinical and radiological follow-up is a must in such patients.
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http://dx.doi.org/10.7461/jcen.2022.E2021.08.001DOI Listing
February 2022

Shunt Implants - Past, Present and Future.

Neurol India 2021 Nov-Dec;69(Supplement):S463-S470

Department of Neurosurgery, NIMHANS, Bengaluru, Karnataka, India.

Background: The treatment of hydrocephalus has evolved over centuries from being an enigma to the use of complex bioprosthetics. Major developments have taken place in the past few decades in shunt hardware and technology, with the use of complex flow regulating valves and biomaterials such as medical-grade silicone having revolutionized the management of hydrocephalus.

Objective: To discuss the evolution of shunts over the decades and how they will evolve in the future.

Material And Methods: In this article, we mention an overview of the evolution of shunt technology and hardware from the prehistoric, pre-shunt era to the modern shunt and a brief insight into the future of hydrocephalus treatment. We review the history, development, and pioneers in shunt development and discuss the various types and parts of a shunt system.

Conclusions: Shunts have been developed from the works of Galen and Hippocrates to the latest technologies using in vivo flow biosensors, computational analysis of flow dynamics, and use of artificial intelligence. This has led to an individualized and appropriate management that can be provided to even the most complex cases of hydrocephalus.
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http://dx.doi.org/10.4103/0028-3886.332263DOI Listing
February 2022

Large Parenchymal Perianeurysmal Cyst: A Case Report.

J Neurosci Rural Pract 2021 Oct 7;12(4):800-803. Epub 2021 Sep 7.

Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India.

Parenchymal perianeurysmal cysts are rare. We report a case of 50-year-old woman who presented with persistent headaches and episodes of vomiting for the last 2 months. Magnetic resonance imaging of the brain showed a well-defined solitary cystic lesion with a mural nodule measuring 5.4 × 5.2 × 4.6 cm in the right basifrontal region. The mural nodule was cortically based. It was hypointense on T2-weighted fluid-attenuated inversion recovery and showed intense contrast enhancement with few nonenhancing areas-no evidence of diffusion restriction. The cyst wall was nonenhancing, and magnetic resonance angiogram was unremarkable. Differential diagnoses included intra-axial gliomas such as ganglioglioma and pleomorphic xanthoastrocytoma. Right pterional craniotomy and a transcortical approach were made. Subtotal excision of cyst and clipping of right middle cerebral artery bifurcation thrombosed aneurysm were done. After 6 months of follow-up, patient is stable without any deficits. A parenchymal perianeurysmal cyst is a rare entity; it is crucial to be considered a differential diagnosis in any cystic lesion with the mural nodule.
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http://dx.doi.org/10.1055/s-0041-1735243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559064PMC
October 2021

Toe-First Technique for End to Side Microvascular Anastomosis.

World Neurosurg 2021 10 27;154:73-77. Epub 2021 Jul 27.

Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address:

Background: The use of the classic 2-ends anchoring technique is common in end-to side (ES) microvascular anastomosis. The literature on the toe-first (TF) technique is limited. In the current study we present the successful outcomes with the TF technique in ES anastomoses in rat femoral vessels model.

Methods: ES microvascular anastomosis with the tf technique was performed in the femoral vessels of 10 Sprague Dawley rats. Two-throw reef knot interrupted sutures were used in all cases. Individual parameters during the procedure were recorded for analysis. The immediate and delayed (cut open technique after 2 weeks) patencies were confirmed. An illustrative case showing the use of this technique in superficial temporal artery to middle cerebral artery bypass in a pediatric moyamoya disease case is included.

Results: The average suturing time was 40.14 ± 5.30 minutes, the procedures were completed with an average of 14.57 ± 1.90 sutures. The average time per suture was 2.78 ± 0.43 minutes. The immediate patency was 100% (10 of 10 cases). Two rats died of unknown cause in the observation period. The delayed patency was 100% in the remaining 8 cases (average observation: 29.6 days).

Conclusions: The TF interrupted suture technique of ES microvascular anastomosis with 2-throw reef knots is feasible with excellent immediate and delayed patency rates. The distinct advantages of the TF are the continuous visualization of the recipient lumen during anastomoses, avoiding back-wall bites, and the ability to correct any discrepancy in the recipient-donor lumens during the procedure.
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http://dx.doi.org/10.1016/j.wneu.2021.07.091DOI Listing
October 2021

Management of a Persistent Oblique Occipital Sinus with Staged Ligation in a Case of Medulloblastoma: A Case Report.

Pediatr Neurosurg 2021 15;56(5):460-464. Epub 2021 Jul 15.

National Institute of Mental Health and Neurosciences, Bangalore, India.

Introduction: A patent persistent occipital sinus (OS) can be seen in 10% of adults. The presence of such a dominant draining OS can present as a challenge for posterior fossa surgeries. Occlusion or division of the sinus can cause venous hypertension, causing a cerebellar bulge or increased intra-op bleeding.

Case Report: A 3-and-a-half-year-old female child presented with a vermian medulloblastoma with hydrocephalus. MR venography (MRV) revealed a large patent OS draining from the torcula to the right sigmoid sinus. She underwent a left Frazier's point VP shunt followed by a midline suboccipital craniotomy for the lesion. The OS was divided during a "Y"-shaped durotomy. Following the sinus ligation, there was a significant cerebellar bulge and excessive bleeding from the lesion. We released cisternal CSF and punctured the tumor cysts to allow the brain bulge to settle. Hemostasis was secured, and surgery was deferred, an augmented duroplasty was done, and bone flap was removed to allow for intracranial pressure decompression. The patient was electively ventilated for 24 h and weaned off gradually. A repeat MRV at 7 days showed the reorganization of the venous outflow at the torcula. Reexploration with tumor resection was done on post-op day 10. The patient recovered well from the surgery and was referred for adjuvant therapy.

Conclusion: Surgeons should carefully analyze venous anatomy before posterior fossa surgeries. The persistent dominant OS, when present, should be taken care of while planning the durotomy. A hypoplastic but persistent transverse sinus allowed us to ligate and divide the OS. By doing a staged division of the sinus, reorganization of the venous outflow from the torcula can be allowed to occur, and the lesion can be resected.
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http://dx.doi.org/10.1159/000517214DOI Listing
October 2021

Anterior Odontoid Screw Fixation for C2 Fractures: Surgical Nuances, Complications, and Factors Affecting Fracture Union.

World Neurosurg 2021 08 28;152:e279-e288. Epub 2021 May 28.

Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address:

Objective: Type II odontoid fractures are the commonest C2 fractures. The management of dens fractures remains controversial with various radiological and fracture morphological factors affecting the approach and outcomes.

Methods: All cases of anterior odontoid screw fixation between 2010 and 2020 were retrospectively analyzed. Patients' clinical, radiological (type of fracture, orientation, displacement, and diastasis), operative (single vs. double screw) and follow-up records were documented. The postoperative imaging findings were classified into grades I (excellent), II (good), and III (poor) based on the anatomical alignment with the screw. Follow-up cervical computed tomography was reviewed for fracture union.

Results: A total of 49 patients with a mean age of 37.3 ± 13.8 years were included in the study. The average time from injury to surgery was 23.1 ± 22.2 days. The bicortical screw purchase and superoposterior odontoid tip breach significantly affected the postoperative alignment (P = 0.035 each). Fracture union was noted in 41 (83.7%) patients. The horizontal fracture displacement ≥2.5 mm (P = 0.02) and poor postoperative fracture alignment (P < 0.001) resulted in worse fracture union rates. Transient dysphagia was the commonest complication (n = 12), whereas screw breakout (n = 2) and pullout (n = 2) were other hardware-related complications. One patient underwent re-exploration for screw readjustment and 2 underwent posterior instrumentation.

Conclusions: Anterior odontoid screw fixation is technically straightforward, less morbid, and preserves biomechanical cervical mobility, when compared with the posterior instrumentation. With careful patient selection, meticulous surgical planning, and intraoperative image-guided screw insertion, good fracture union outcomes can be obtained. In the current study, we were able to achieve stable fracture union in 83.7% patients.
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http://dx.doi.org/10.1016/j.wneu.2021.05.077DOI Listing
August 2021

Management of Neurosurgical Cases in a Tertiary Care Referral Hospital During the COVID-19 Pandemic: Lessons from a Middle-Income Country.

World Neurosurg 2021 04 29;148:e197-e208. Epub 2020 Dec 29.

Department of Neurosurgery, National Institute of Mental Health and Neurosciences Bengaluru, Karnataka, India. Electronic address:

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has been at its peak for the past 8 months and has affected more than 215 countries around the world. India is now the second most-affected nation with more than 48,000,000 cases and 79,000 deaths. Despite this, and the fact that it is a lower-middle-income nation, the number of deaths is almost one third that of the United States and one half that of Brazil. However, there has been no experience published from non-COVID-19-designated hospitals, where the aim is to manage noninfected cases with neurosurgical ailments while keeping the number of infected cases to a minimum.

Methods: We analyzed the number of neurosurgical cases (nontrauma) done in the past 5 months (March-July 2020) in our institute, which is the largest neurosurgical center by volume in southern India, and compared the same to the concurrent 5 months in 2019 and 5 months preceding the pandemic. We also reviewed the total number of cases infected with COVID-19 managed during this time.

Results: We operated a total of 630 cases (nontrauma) in these 5 months and had 9 COVID-19 infected cases operated during this time. There was a 57% (P = 0.002) reduction in the number of cases operated as compared with the same 5 months in the preceding year. We employed a dual strategy of rapid antigen testing and surgery for cases needing emergency intervention and reverse transcriptase-polymerase chain reaction test for elective cases. The hospital was divided into 3 zones (red, orange, and green) depending on infectivity level with minimal interaction. Separate teams were designated for each zone, and thus we were able to effectively manage even infected cases despite the absence of pulmonology/medical specialists.

Conclusions: We present a patient management protocol for non-COVID-19-designated hospitals in high-volume centers with the constraints of a lower-middle-income nation and demonstrate its effectiveness. Strict zoning targeted testing and effective triage can help in management during the pandemic.
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http://dx.doi.org/10.1016/j.wneu.2020.12.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832520PMC
April 2021

End-to-Side Microvascular Anastomosis on Rat Femoral Vessels Using Only 2-Throw Knot Interrupted Sututres - Evaluation of Feasibility and Patency Rates on Rat Femoral Vessels Model.

World Neurosurg 2021 04 5;148:e145-e150. Epub 2021 Jan 5.

National Institute of Mental Health and Neurosciences, Bangalore, India.

Background: The use of a 3-throw knot for anastomosis by microvascular neurosurgeons is the usual standard. There is an inherent belief that the third throw adds extra security to the knot; however, the third throw can make the knot heavy and unbalanced and can exert undue extra pressure on the opposing walls of the small-caliber intracranial vessels. This study evaluated the feasibility and efficiency of 2-throw reef knot interrupted sutures for an end-to-side microvascular anastomosis.

Methods: A prospective observational study of end-to-side anastomosis using a femoral artery-to-vein model was performed in 30 Sprague-Dawley rats. All anastomoses were done using 2-throw reef knot interrupted sutures. Ten procedures each were done by the heel-first, toe-first, and classic 2-ends techniques. Individual parameters were recorded for analysis. The delayed patency was confirmed by reexploration after a mean duration of 19.82 ± 8.12 days.

Results: The overall patency rates were 100% in the immediate period and 96.43% (27 of 28) in the delayed period. The average clamping time, average suturing time, and the average time per suture were 65.48 ± 16.93 minutes, 40.94 ± 11.22 minutes, and 3.18 ± 1.10 minutes, respectively. Two rats died in the postoperative period.

Conclusions: The end-to-side microvascular anastomosis with 2-throw reef knots is feasible, with excellent immediate and delayed patency rates.
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http://dx.doi.org/10.1016/j.wneu.2020.12.078DOI Listing
April 2021

Chronic Periodontitis is Associated With Cerebral Atherosclerosis -A Nationwide Study.

Cureus 2020 Nov 7;12(11):e11373. Epub 2020 Nov 7.

Neurology, Palmetto Health-University of South Carolina School of Medicine, Columbia, USA.

Introduction Chronic periodontitis and atherosclerosis share common risk factors and produce the same inflammatory markers. Many studies found a high prevalence of chronic periodontitis in patients with atherosclerosis but there is no strong evidence to support a specific association of chronic periodontitis with cerebral atherosclerosis. We aimed to study the concurrent prevalence and association of chronic periodontitis with cerebral atherosclerosis and cerebrovascular diseases among the US population. Methods We performed a cross-sectional analysis of a Nationwide Inpatient Sample with adult hospitalizations to identify the primary diagnosis of cerebrovascular diseases [acute ischemic stroke (AIS), hemorrhagic stroke (HS), and transient ischemic attack (TIA)] with concurrent cerebral atherosclerosis and chronic periodontitis. Multivariate survey logistic regression models were fitted to evaluate the linkage of chronic periodontitis with cerebral atherosclerosis and cerebrovascular diseases. Results Of total 56,499,788 hospitalizations, 0.01% had chronic periodontitis. Prevalence of chronic periodontitis was higher in 50-64 years (36.18% vs. 23.91%), males (59.19% vs. 41.06% in females), Afro-Americans (25.93% vs. 15.21%), and 0-25th percentile median-household-income-category (38.31% vs. 30.15%) compared to non-chronic periodontitis. There was significantly higher prevalence of cerebral atherosclerosis (0.71% vs. 0.41%; p<0.0001) with weak evidence of high prevalence of cerebrovascular diseases (AIS:2.21% vs. 1.97%; p=0.1563; HS:0.57% vs. 0.46%; p=0.1560) among chronic periodontitis compared to non-chronic periodontitis. In regression analysis, odds of having cerebral atherosclerosis were 2.48-folds higher in patients with chronic periodontitis compared to that without-chronic periodontitis, and cerebral atherosclerosis patients were associated with higher odds of TIA (aOR:2.40; p<0.0001), AIS (aOR:3.35; p<0.0001), and HS (aOR:1.51; p<0.0001) compared to without-cerebral atherosclerosis. No significant relationship between chronic periodontitis and cerebrovascular diseases was observed. Conclusion Although chronic periodontitis may not directly increase the risk of cerebrovascular diseases, it increases the burden of cerebrovascular diseases by evidently increasing the risk of cerebral atherosclerosis. Early identification of chronic periodontitis and atherosclerotic risk factors may help to mitigate the risk of cerebrovascular diseases.
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http://dx.doi.org/10.7759/cureus.11373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721345PMC
November 2020

Radiation Shielding Concrete with alternate constituents: An approach to address multiple hazards.

J Hazard Mater 2021 02 7;404(Pt B):124201. Epub 2020 Oct 7.

Department of Civil Engineering, Birla Institute of Technology and Science (BITS) Pilani, Pilani Campus, 333031, India. Electronic address:

Radiation Shielding Concrete (RSC) is a superior alternative to many conventional and modern shields against gamma and neutron radiation hazards. The present work is the first comprehensive review on utilization of alternate materials, emphasizing hazardous industrial byproducts, as constituents of RSC. Such usage enhances the performance, sustainability, and affordability of RSC. Added advantages are the immobilization of wastes and the conservation of natural resources for RSC. The review analyses incorporation of ferrous and non-ferrous slags, mines wastes, plastics, red mud, cathode ray tube's glass, metallic wastes, fly ash, silica fume, and miscellaneous residues. Besides, utilization of fibers, nanoparticles, and calcined clay is investigated. The influence on shielding efficiency is adjudged by scrutinizing changes in parameters such as half-value layer and linear attenuation coefficients. Similarly, variations in mechanical and durability properties are investigated and compared. The underlying responsible factors related to the physical, chemical and morphological characteristics of materials and their consequences on RSC's behavior are correlated. In association with alternatives, the advantages, disadvantages, and possible treatment methods are discussed. The country-wise, material-specific, and progressive research trends are revealed to facilitate future work in this upcoming field. Finally, conclusions are drawn with exposition of current bottlenecks and scope of future research.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124201DOI Listing
February 2021

Trapped fourth ventricle-treatment options and the role of open posterior fenestration in the surgical management.

Acta Neurochir (Wien) 2020 10 26;162(10):2441-2449. Epub 2020 Apr 26.

Department of Neurosurgery, II Floor, Faculty Block, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru, India.

Background: Trapped fourth ventricle (TFV) is a rare and difficult to treat condition. Most patients have a past inciting event (infection, IVH, trauma) and history of prior CSF diversion. The symptoms are due to the mass effect on brainstem and cerebellum. Rarely, TFV can also be associated with syrinx formation due to a dissociated craniospinal CSF flow near the fourth ventricle outlets. We present our experience and outcomes of open posterior fenestration in 11 cases, along with an overview of the surgical management of TFV.

Methods: Between 2011 and 2018, 11 patients of TFV were operated by the posterior approach fenestration of the fourth ventricle outlets and arachnoid dissection. The clinical and radiological findings of the patients were retrieved from the hospital database. The surgical technique is described in detail. The patients' neurological status and imaging findings in the follow-up were recorded and compared.

Results: The average age of the patients was 23.55 years. The most common presenting symptoms were headache (9/11) and gait imbalance (7), with TB meningitis being the commonest etiology. Ten patients had a history of prior CSF diversion with two presenting with shunt malfunction. Mean follow-up duration was 33.33 months. The improvement in neurological status was observed in 9/11 patients, 2 remained status quo. On follow-up imaging, 8/11 (72.72%) patients had a decrease in the size of TFV while syrinx improved in 3/5 (60%).

Conclusion: Multiple surgical approaches have been described for TFV. Endoscopic fourth ventriculostomy with aqueductoplasty is gaining popularity in the past two decades. However, an open posterior fenestration of the midline fourth ventricle outlet (magendieplasty) along with sharp arachnoid dissection (adhesiolysis) along the cerebello-medullary cisterns and paracervical gutters is relatively simple and provides physiological fourth ventricular CSF outflow. This is especially useful in TFV with syrinx as the craniospinal CSF circulation is established.
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http://dx.doi.org/10.1007/s00701-020-04352-3DOI Listing
October 2020

Persistent Trigeminal Artery: Neuroanatomic and Clinical Relevance.

World Neurosurg 2020 Feb 15;134:e214-e223. Epub 2019 Oct 15.

Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India.

Introduction: Persistent trigeminal artery (PTA) is the most common remnant of primitive circulation communicating the developing carotid and vertebrobasilar junction. Although discovered incidentally, an altered hemodynamic may lead to an increased association of aneurysms, vascular malformations, and stroke. Neurosurgeons should be aware of the presence and significance of PTA when interpreting imaging and planning interventions.

Methods: We retrospectively reviewed all magnetic resonance angiography and cerebral digital subtraction angiography performed between 2012 and 2017 for the presence of PTA. The radiologic and anatomic details were noted and analyzed along with the clinical profiles. We categorized the radiologic findings with respect to the available classification systems. A review of the available literature was done comparing our results.

Results: We found 33 cases of incidentally detected PTA. The average age of the patients was 45.42 years. The lateral surface of the proximal cavernous internal carotid artery was the most common origin (n = 23). Only 3 cases had a medial/transsellar course. Most cases were Saltzman/Weon type I (19/33). Intracranial aneurysms were associated with 6 patients (18.18%). Trigeminal neuralgia (TN) was a presenting feature in 5 patients. None had a direct neurovascular conflict at the root entry zone.

Conclusions: Our study is one of the largest to describe the incidence of PTA. We emphasized the importance of PTA to the neurosurgeons; increased association of aneurysms, as a route for intervention in occlusive disease of the posterior fossa; risk of injury and bleeding during transsphenoidal surgery; and the association with TN. However, we found that only PTA variants are likely to be associated with TN because of their cisternal course causing NV conflict.
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http://dx.doi.org/10.1016/j.wneu.2019.10.025DOI Listing
February 2020

Expression of mycolic acid in response to stress and association with differential clinical manifestations of tuberculosis.

Int J Mycobacteriol 2019 Jul-Sep;8(3):237-243

Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.

Background: Extrapulmonary tuberculosis (EPTB), accounting for 10%-20% of all cases of tuberculosis (TB), is known to be determined by host immunity. However, the contribution of bacterial factors to the development of EPTB has not been studied extensively. Mycolic acids are predominant lipids constituting the cell wall of Mycobacterium tuberculosis, and keto-mycolic acid is involved in the synthesis of foamy macrophages that facilitate persistence of mycobacteria. Hence, the present study was performed to gain an insight into variable expression of mycolic acids in clinical isolates of M. tuberculosis under stress.

Methods: Pansusceptible clinical isolates of M. tuberculosis from patients with lymph node TB (LNTB) (n = 10) and pulmonary TB (PTB) (n = 10) were subjected to sodium dodecyl sulfate (SDS) stress, and the expression of mycolic acid and its biosynthetic genes was compared. Any bias arising due to the genotype of the clinical isolates was ruled out by performing single-nucleotide polymorphism cluster grouping (SCG), wherein no significant difference was observed between the SCG of LNTB or PTB isolates.

Results: The expression of α-mycolic acid during the exposure to SDS was high in 7/10 (70%) LNTB and 6/10 (60%) PTB isolates. Methoxy mycolic acid showed an increased expression in 7/10 (70%) LNTB isolates and 4/10 (40%) PTB isolates. Increased expression of keto-mycolic acid on exposure with SDS was observed in 8/10 (80%) M. tuberculosis LNTB and 3/10 (30%) PTB isolates. Similarly, the mycolic acid synthesis gene, fas, was upregulated more in LNTB isolates than PTB isolates in vitro and ex vivo. SCG 3a was the most common SCG observed in 40% (8/20) of the isolates, followed by SCG 3b in 30% (6/20) of the isolates. There was no significant difference between the SCG of LNTB or PTB isolates.

Conclusion: The higher expression of keto-mycolic acid in LNTB as against PTB isolates may indicate better survival in LNTB isolates in the presence of stress.
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http://dx.doi.org/10.4103/ijmy.ijmy_69_19DOI Listing
January 2020

Gene Expression in Intracranial Aneurysms-Comparison Analysis of Aneurysmal Walls and Extracranial Arteries with Real-Time Polymerase Chain Reaction and Immunohistochemistry.

World Neurosurg 2019 Oct 13;130:e117-e126. Epub 2019 Jun 13.

Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.

Background: This study was aimed at evaluating the gene expression levels of 4 genes in the intracranial aneurysm wall and comparing them with extracranial arteries. The analysis was done using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Also, a correlation of the differential genetic expression was done with various patient clinical and radiologic factors.

Methods: The quantitative assessment of ribonucleic acid levels was done with RT-PCR and was validated with IHC. The genes studied were collagen 1A2 (COL1A2), tissue inhibitor of metalloproteinase 4 (TIMP4), cathepsin B (CTSB), and alpha-1 antitrypsin (α-1 AT). The analysis was done on 24 aneurysm sacs and superficial temporal/occipital artery samples from patients undergoing surgical clipping.

Results: The mean fold change of COL1A2 in the aneurysm sample was 8.89, that of TIMP4 was 10.16, that of CTSB was 1.02, and that of α-1 AT was 1.46 when compared with normal control vessel on PCR. On semiquantitative IHC, COL1A2 was 94.44%, α-1 AT was 77.8% overexpressed, CTSB was positive in 50%, and the expression of TIMP4 was 94.4% underexpressed in aneurysmal walls. There was no statistically significant correlation between patient profile and gene expression.

Conclusions: On RT-PCR and IHC analysis, COL1A2 and α-1 AT were overexpressed, CTSB was marginally overexpressed, and TIMP4 had equivocal expression in the aneurysmal sac when compared with the normal extracranial vessel. This is the first study of its kind in the Indian population with the largest sample size on live human patients.
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http://dx.doi.org/10.1016/j.wneu.2019.06.002DOI Listing
October 2019

Multiple Remote Sequential Supratentorial Epidural Hematomas-An Unusual and Rare Complication After Posterior Fossa Surgery.

World Neurosurg 2019 Aug 6;128:83-90. Epub 2019 May 6.

Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India.

Background: Postoperative hemorrhage is a serious complication of intracranial surgery. Epidural hematomas (EDHs) are one of the common forms of bleeding after surgery, with ≤12% of patients requiring re-exploration. However, distant or remote site EDHs have been rare, in particular, those in a supratentorial location after infratentorial surgery.

Case Description: We report an unusual complication of surgery for fourth ventricular outlet obstruction. A young male patient developed multiple sequential supratentorial EDHs after posterior fossa surgery. He required 2 re-explorations after the primary surgery for evacuation of the EDHs within 24 hours. In the available data, we found only 28 such reported cases previously. Only 2 additional cases have been reported to have sequential EDHs after surgery. Various theories have been postulated, ranging from sudden intracranial pressure decompression, pin site hematoma, and shunt site bleeding due to dural stripping. None has been proven to definitively explain the complication.

Conclusions: We wished to highlight this unusual complication of posterior fossa surgery, with an emphasis on rapid computed tomography scanning of the brain for patients in the early postoperative period with any neurological deterioration. Early radiological detection and timely intervention can be lifesaving.
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http://dx.doi.org/10.1016/j.wneu.2019.04.228DOI Listing
August 2019

Lack of association of novel mutation Asp397Gly in aftB gene with ethambutol resistance in clinical isolates of Mycobacterium tuberculosis.

Tuberculosis (Edinb) 2019 03 25;115:49-55. Epub 2019 Jan 25.

Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India. Electronic address:

To discover additional genotypic indicators for ethambutol (EMB) resistant M. tuberculosis, we studied polymorphisms in arabinofuranosyl transferase encoding genes aftA (Rv3792), aftB (Rv3805) and aftC (Rv2673) in 38 EMB resistant and 34 EMB susceptible isolates from India and a repository established by the World Health Organization (WHO) Special Programme for Research and Training in Tropical Disease (TDR) by DNA sequencing. The results were correlated with the minimum inhibitory concentration (MIC) of EMB and mutations in embB (Rv3795). The most common non-synonymous polymorphism identified in aftB was Asp397Gly in 12/38 (31.6%) EMB resistant and 3/34 (8.8%) EMB susceptible isolates. Interestingly, 10/12 (83.3%) EMB resistant isolates with aftB Asp397Gly mutation also carried embB306, embB402 or embB497 mutations. Association of Asp397Gly polymorphism with EMB resistance was statistically significant (p 0.0216). However, overexpression of the mutant aftB in M. tuberculosis H37Rv did not exhibit any change in the MIC. Whole genome sequencing of a panel of Indian isolates and SNP cluster grouping (SCG) of TDR strains revealed an association between aftB mutation Asp397Gly and Beijing genotype or SCG2, a cluster group representing the Beijing genotype. To conclude, though aftBAsp397Gly mutation is not associated with EMB resistance, this mutation may be a phylogenetic marker for the Beijing clade.
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http://dx.doi.org/10.1016/j.tube.2019.01.004DOI Listing
March 2019

Duplication of Ventral Dura as a Cause of Ventral Herniation of Spinal Cord-A Report of Two Cases and Review of the Literature.

World Neurosurg 2019 Jun 6;126:346-353. Epub 2019 Mar 6.

Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India.

Background: Idiopathic spinal cord herniation (ISCH) is a treatable spinal disease. It is rare and often misdiagnosed, causing a delay in management. The etiology is multifactorial, with one of the causes being duplication of the ventral dura. The spinal cord herniates within this defect and becomes strangulated, causing neurological deficits. We report the duplication of a ventral spinal cord as an important cause of ISCH in our review.

Case Description: We present 2 cases of ISCH with duplication of the dura, including their relevant clinical and imaging features. The patients underwent surgical reduction of the herniated spinal cord with enlargement of the defect and placement of a dural substitute ventral to the cord. We have also reported the outcomes of the 2 patients, with an emphasis on the factors predictive of poor outcomes (i.e., long-standing symptoms, a delay in intervention, poor neurological status at presentation, and a thinned out atrophic spinal cord found during surgery). We also reviewed the available data for duplication of the dura with ISCH.

Conclusions: Very few asymptomatic patients can be treated conservatively. The surgical outcomes have been favorable for symptomatic patients. Proper exposure, gentle manipulation while reducing the herniated spinal cord, enlargement of the defect, and the use of intraoperative monitoring will help limit the postoperative deficits. Duplication of the ventral dura is an important cause of ISCH. It prevents the formation of an anterior pseudomeningocele after surgery. Owing to the rarity of the disease and the lack of follow-up data with recurrence rates, it has not been possible to form clear guidelines for management.
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http://dx.doi.org/10.1016/j.wneu.2019.02.143DOI Listing
June 2019

Methyl-accepting chemotaxis like Rv3499c (Mce4A) protein in Mycobacterium tuberculosis H37Rv mediates cholesterol-dependent survival.

Tuberculosis (Edinb) 2018 03 31;109:52-60. Epub 2018 Jan 31.

Department of Microbiology, V. P. Chest Institute, University of Delhi, Chatra Marg, Delhi, 110007, India. Electronic address:

Cholesterol, an essential cellular component in macrophages, is exploited for entry and long-term survival of Mycobacterium inside the host. Cholesterol-deficient macrophages can restrict the cholesterol-dependent entry of Mycobacterium. Rv3499c protein in Mycobacterium has high binding affinity for cholesterol. Rv3499c gene is a part of mce4 operon which is reported to act as cholesterol transport system in mycobacteria. Earlier we reported Rv3499c protein to localise on cell wall and facilitate entry of Mycobacterium inside macrophages. Here we performed fold recognition and multiple sequence alignment to find similarity with methyl-accepting chemotaxis protein (MCP). MCP allows detection of level of nutrient in the medium, which in this case is cholesterol. We showed Rv3499c protein expression is important for host cholesterol utilization by Mycobacterium for its survival. Infected female balb/c mice presented increased CFU of Rv3499c overexpressing M. tuberculosis H37Rv marked with early disease conditions and increased lung pathology. Thus, findings suggest specific domain of MCP of Rv3499c help in regulation of downstream PDIM synthesis pathways for ligand utilization by M. tuberculosis H37Rv.
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http://dx.doi.org/10.1016/j.tube.2018.01.004DOI Listing
March 2018

Role of Vitamins B, C, and D in the fight against tuberculosis.

Int J Mycobacteriol 2017 Oct-Dec;6(4):328-332

Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, New Delhi, India.

Worldwide, tuberculosis (TB) is still a serious and significant health concern, more so with the emergence of multidrug-resistant-TB. The inability of mankind to control this infection stems from the fact that the vaccines and drugs that were once effective against TB are no longer efficacious. This has led to a search for new antituberculous agents and adjuvant therapy. Vitamins are being revisited for their role in pathogenicity as well as for their antimycobacterial properties. Vitamins such as biotin and thiamin are essential for Mycobacterium tuberculosis and are required for establishment of infection. On the other hand, vitamins such as Vitamin C and Vitamin D have been shown to possess antimycobacterial properties. To combat M. tuberculosis, innovative strategies need to be devised, keeping in mind the efficacy of the agent to be used. Vitamins can prove to be useful agents capable of modifying the life cycle and biology of M. tuberculosis. We present here a brief overview of the available knowledge on thiamin, biotin, Vitamin C, and Vitamin D, keeping TB treatment and control in perspective.
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http://dx.doi.org/10.4103/ijmy.ijmy_80_17DOI Listing
September 2018

PDIM and SL1 accumulation in Mycobacterium tuberculosis is associated with mce4A expression.

Gene 2018 Feb 6;642:178-187. Epub 2017 Oct 6.

Department of Microbiology, V. P. Chest Institute, University of Delhi, Chatra Marg, Delhi, India. Electronic address:

Lipid metabolism forms the heart and soul of Mycobacterium tuberculosis life cycle. Starting from macrophage invasion at cholesterol rich micro-domains to a sustainable survival for infection by utilizing cholesterol, Mycobacterium displays the nexus of metabolic pathways around host derived lipids. mce4 operon acts as cholesterol import system in M. tuberculosis and here we demonstrate role of mce4A gene of this operon in cholesterol catabolism. Here M. tuberculosis H37Rv overexpressing Rv3499c (mce4A) recombinant was used as a model to decipher the metabolic flux during intake and utilization of host lipids by mycobacteria. We analysed the impact of mce4A expression on carbon shift initiated during cholesterol utilization necessary for long term survival of mycobacterium. Through transcriptional analysis, upregulation in methylcitrate cycle (MCC) and methylmalonyl pathway (MMP) genes was observed in Rv3499c overexpressing recombinants of M. tuberculosis H37Rv. Up-regulation of methylmalonyl pathway associated enzyme encoding genes increased accumulation of virulence associated mycobacterial lipids phthiocerol dimycocerates (PDIM) and sulfolipid (SL1). We demonstrate that MCC and MMP associated enzyme encoding genes are upregulated upon mce4A overexpression and lead to enhanced accumulation of PDIM and SL1 which are responsible for pathogenicity of M. tuberculosis.
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http://dx.doi.org/10.1016/j.gene.2017.09.062DOI Listing
February 2018

Hypersensitivity Reactions to Obinutuzumab in Cynomolgus Monkeys and Relevance to Humans.

Toxicol Pathol 2017 07;45(5):676-686

4 Pharmaceutical Sciences, Roche Innovation Center New York, New York, New York, USA.

Obinutuzumab (GA101, Gazyva™, Gazyvaro®, F. Hoffmann-La Roche AG, Basel, Switzerland) is a humanized, glycoengineered type II antibody targeted against CD20. The preclinical safety evaluation required to support clinical development and marketing authorization of obinutuzumab included repeat-dose toxicity studies in cynomolgus monkeys for up to 6-month dosing with a 9-month recovery period. Results from those studies showed decreases in circulating B cells and corresponding B-cell depletion in lymphoid tissues, consistent with the desired pharmacology of obinutuzumab. Hypersensitivity reactions were noted at all doses in the 6-month study and were attributed to the foreign recognition of the drug construct in cynomolgus monkeys. Findings in monkeys were classified as acute hypersensitivity reactions that were evident immediately after dosing, such as excessive salivation, erythema, pruritus, irregular respiration, or ataxia, or chronic hypersensitivity reactions characterized by glomerulonephritis, arteritis/periarteritis, and inflammation in several tissues including serosal/adventitial inflammation. Immune complex deposits were demonstrated in tissues by immunohistochemistry, immunofluorescence, and electron microscopy. Some of, but not all, the animals that developed these reactions had detectable antidrug antibodies or circulating immune complexes accompanied by loss of drug exposure and pharmacodynamic effect. On the basis of clinical evidence to date, hypersensitivity reactions following obinutuzumab are rare, further supporting the general view that incidence and manifestation of immunogenicity in nonclinical species are generally not predictive for humans.
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http://dx.doi.org/10.1177/0192623317723539DOI Listing
July 2017

High-Output Cardiac Failure Due to Hereditary Hemorrhagic Telangiectasia: A Case of an Extra-Cardiac Left to Right Shunt.

Int J Angiol 2017 Jun 2;26(2):125-129. Epub 2016 Jun 2.

Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California.

High-output cardiac failure is a rare complication of hereditary hemorrhagic telangiectasia and can potentially be mistaken for other entities. We present a case of high-output cardiac failure because of large hepatic arteriovenous malformations, review the literature regarding the cardiac manifestations of the disease, and discuss the possible differential diagnoses.
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http://dx.doi.org/10.1055/s-0035-1568878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446252PMC
June 2017

Survival in Patients with Degenerative Mitral Stenosis: Results from a Large Retrospective Cohort Study.

J Am Soc Echocardiogr 2016 05 28;29(5):461-9. Epub 2016 Feb 28.

Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California. Electronic address:

Background: Severe mitral annular calcification causing degenerative mitral stenosis (DMS) is increasingly encountered in patients undergoing mitral and aortic valve interventions. However, its clinical profile and natural history and the factors affecting survival remain poorly characterized. The goal of this study was to characterize the factors affecting survival in patients with DMS.

Methods: An institutional echocardiographic database was searched for patients with DMS, defined as severe mitral annular calcification without commissural fusion and a mean transmitral diastolic gradient of ≥2 mm Hg. This resulted in a cohort of 1,004 patients. Survival was analyzed as a function of clinical, pharmacologic, and echocardiographic variables.

Results: The patient characteristics were as follows: mean age, 73 ± 14 years; 73% women; coronary artery disease in 49%; and diabetes mellitus in 50%. The 1- and 5-year survival rates were 78% and 47%, respectively, and were slightly worse with higher DMS grades (P = .02). Risk factors for higher mortality included greater age (P < .0001), atrial fibrillation (P = .0009), renal insufficiency (P = .004), mitral regurgitation (P < .0001), tricuspid regurgitation (P < .0001), elevated right atrial pressure (P < .0001), concomitant aortic stenosis (P = .02), and low serum albumin level (P < .0001). Adjusted for propensity scores, use of renin-angiotensin system blockers (P = .02) or statins (P = .04) was associated with better survival, and use of digoxin was associated with higher mortality (P = .007).

Conclusions: Prognosis in patients with DMS is poor, being worse in the aged and those with renal insufficiency, atrial fibrillation, and other concomitant valvular lesions. Renin-angiotensin system blockers and statins may confer a survival benefit, and digoxin use may be associated with higher mortality in these patients.
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http://dx.doi.org/10.1016/j.echo.2015.12.012DOI Listing
May 2016

Progression of degenerative mitral stenosis: insights from a cohort of 254 patients.

J Heart Valve Dis 2014 Nov;23(6):707-12

Background And Aim Of The Study: Degenerative mitral stenosis (DMS) is an increasingly common echocardiographic finding, yet the clinical and biological behavior and rate of progression of the condition are unknown.

Methods: A total of 254 patients was identified from the authors' echocardiographic database with DMS, defined as severe mitral annular calcification with extension into the mitral leaflets resulting in transmitral flow acceleration with a mean diastolic gradient of >2 mmHg in the absence of commissural fusion. Each patient required paired echocardiograms to have been recorded at least three months apart. Clinical, biochemical and pharmacological data were collected from each patient and related to the annualized rate of increase in mean diastolic mitral gradient and stenosis severity on a scale of 0 to 3.

Results: The characteristics of the patients were as follows: mean age 71 +/- 15 years; female gender 73%; and left ventricular ejection fraction 66 +/- 13%. Diabetes was present in 50% of patients, renal insufficiency in 40%, and coronary artery disease in 50%. Over a follow up period of 2.6 +/- 2.2 years, the mean gradient was increased by 0.8 +/- 2.4 mmHg (range: 0-15 mmHg) per year, while the stenosis grade was increased by 0.18 +/- 0.5 (range: 0-3) per year. The rate of progression was faster in patients with lesser degrees of stenosis (p = 0.01) and low serum albumen levels (p = 0.04), and slower in those receiving beta-blockers (p = 0.01). Milder stenosis, diabetes mellitus and lack of beta-blocker use were independent predictors of faster DMS progression.

Conclusion: DMS progression is highly variable, but generally slow; its progression is accelerated in the presence of diabetes mellitus, but is retarded by beta-blocker use. DMS may be an active biological process offering potentially modifiable targets for intervention.
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November 2014

Volvulus of ileal S-pouch: A rare complication of ileal pouch anal anastomoses.

Int J Surg Case Rep 2014 23;5(10):717-9. Epub 2014 Aug 23.

Department of General Surgery, S.M.S. Medical College, JLN Marg, Jaipur 302004, Rajasthan, India. Electronic address:

Introduction: Ileal pouch anal anastomosis (IPAA) after total proctocolectomy is a frequently performed surgery for medically refractory ulcerative colitis (UC). Volvulus of the ileal pouch as a complication of IPAA is extremely rare. We present a case of volvulus of S-type ileal pouch.

Presentation Of Case: A 28 year old male, with history of total proctocolectomy with IPAA for severe UC in 2009 presented with signs of bowel obstruction. Emergency laparotomy was done and a volvulus of the S-type ileal pouch was derotated and pouchpexy done.

Discussion: The IPAA has a wide spectrum of complications, with obstruction of proximal small bowel occurring frequently. Volvulus of the ileal pouch is extremely rare with only 3 reported cases. Early diagnosis and intervention is important to salvage the pouch. Computed tomography (CT) may aid the diagnosis in stable patients.

Conclusion: The diagnosis of ileal pouch volvulus although rare, should be kept in mind when dealing with patients complaining of recurrent obstruction following IPAA.
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http://dx.doi.org/10.1016/j.ijscr.2014.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189055PMC
October 2014

Revisiting a protocol for extraction of mycobacterial lipids.

Int J Mycobacteriol 2014 Sep 7;3(3):168-72. Epub 2014 Aug 7.

Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India. Electronic address:

Determination of lipid content of any biological sample is essential for various kinds of studies related to pathogenicity and drug development. Thus, reliable methods for the quantitative extraction of lipids are of critical importance. The mycobacterial cell wall is largely composed of lipids. Commonly used methods to extract lipids, such as the Bligh and Dyer method or the Folch method, yield a low amount of lipids when applied to mycobacterial cells. This study presents an efficient modification of Chandramauli's method, a less known method developed at this institute earlier that is able to yield a considerably higher concentration of mycobacterial lipids.
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http://dx.doi.org/10.1016/j.ijmyco.2014.07.008DOI Listing
September 2014

Huge trichobezoar causing obstructive jaundice.

BMJ Case Rep 2014 Feb 27;2014. Epub 2014 Feb 27.

Department of General Surgery, Sawai Man Singh Hospital, Jaipur, Rajasthan, India.

Trichobezoars are composed of hair or hair-like fibres that are commonly observed in the gastrointestinal tract of children and young women with psychiatric illnesses. Presentation of trichobezoars can be diverse. We report a case of a 29-year-old woman who presented with obstructive jaundice and a large upper abdominal lump. She was diagnosed with post-traumatic stress disorder on psychiatric evaluation. She underwent exploratory laparotomy and a large trichobezoar was removed. Her postoperative course was uneventful and she was referred to the psychiatric department for further management.
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http://dx.doi.org/10.1136/bcr-2013-201667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939418PMC
February 2014
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