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1.  Removal of self expandable metallic airway stent: A rare case report 
Covered self expandable metallic airway stents (SEMS) have been used for benign tracheal stenosis, post intubation tracheal stenosis, tracheal burn or trauma, tracheo-broncho-malacia, and extrinsic compression of trachea. Their placement is considered to be permanent, with open surgery the only way to remove the stent, though there are few cases reports of their removal with the bronchoscope, but the complications after their removal are very high. In our patient, one and a half years after placement of SEMS, she developed cough with dyspnoea, video bronchoscopy showed stenosis above the level of stent with granulation tissue inside the stent, stent fracture in lower part and stent migration to right main bronchus, thus she had all conceivable complications of stent placement. The stent was removed with the help of rigid bronchoscope under general anaesthesia. She was discharged the following day. The case is being reported because it was unique in having all the possible complications of stent placement, and rare as we could take out the stent in Toto. Thirdly, the stent could be removed without any complication.
PMCID: PMC3644838  PMID: 23661920
Granulation tissue inside the stent; stenosis above the stent; stent fracture; stent migration
2.  Mother with daughters 
PMCID: PMC3519031  PMID: 23243359
3.  Potato swelling of sternum 
PMCID: PMC3775205  PMID: 24049260
4.  Tracheo-esophageal fistula: Successful palliation after failed esophageal stent 
The incidence of tracheo-esophageal (TO) fistula is on the rise, especially after palliative management for esophageal malignancies. We report a case of cancer of esophagus who after chemotherapy and radiotherapy developed TO fistula. Placement of an esophageal stent helped him in taking food orally, but his cough and dyspnoea continued to worsen. Fibreoptic bronchoscopy demonstrated a severely compressed trachea secondary to protrusion of esophageal stent which responded very well to an Ultraflex-covered tracheal stent and the patient achieved relief from cough and dyspnoea.
PMCID: PMC3424874  PMID: 22919174
Fibreoptic bronchoscopy; tracheo-esophageal fistula; Ultraflex stent
5.  Glue therapy in hemoptysis: A new technique 
Hemoptysis is defined as the spitting of blood derived from the lungs or bronchial tubes as a result of pulmonary or bronchial hemorrhage. There is a large chunk of patients with hemoptysis who do not respond to conservative treatment including use of cough suppressants, antibiotics, vitamin C, hemostatics, and anxiolytics. The advanced management of such a situation is bronchial artery embolization (BAE) or open thoracic surgery, which is often not possible. We have attempted a cheap, effective, and safe alternative in the form of intrabronchial instillation of glue (n-butyl cyanoacrylate) under vision with the help of a therapeutic video bronchoscope (OLYMPUS T-180). The glue is instilled through a polyethylene catheter placed through the working channel of the video bronchoscope.
PMCID: PMC3424875  PMID: 22919175
Hemoptysis; video bronchoscopy; glue therapy; n-butyl cyanoacrylate (glue)
6.  Genitourinary histoplasmosis in post-renal transplant patient: Diagnostic dilemma 
Genitourinary histoplasmosis is very rare and to our knowledge only four cases of epididymal histoplasmosis and nine cases of prostatic histoplasmosis have been reported in literature. We hereby report a case of a middle-aged male, who presented three years after renal transplant, with complaints of fever, pain, and swelling in the scrotum. Imaging disclosed an enlarged right epididymis with prostatic and retrotrigonal abscess, suggesting tuberculosis infection. However, histopathology of the epididymal biopsy revealed histoplasmosis, and the drained pus on culture confirmed infection with Histoplasma capsulatum.
PMCID: PMC3507415  PMID: 23204674
Epididymis; histoplasmosis; prostate
7.  Bronchoscopic management of bronchopleural fistula with intrabronchial instillation of glue (N-butyl cyanoacrylate) 
Bronchopleural fistula (BPF) is a communication between the pleural space and bronchial tree.
Materials and Methods:
A series of 9 cases are reported where BPF was identified and managed with intrabronchial instillation of glue (N-butyl-cyanoacrylate) through a video bronchoscope.
Out of 9 patients the BPF was successfully sealed in 8 cases (88.88%). In 1 patient of postpneumonectomy, the fistula was big, that is >8 mm who had a recurrence after the procedure. In one case of pyopneumothorax the leak reduced slowly and it took us 14 days to remove the intercostal drainage tube. Rest of the patients had a favorable outcome. No complications were observed in a follow-up of 6 months.
In our opinion, it is a cost-effective, viable, and safe alternative compared with costly, time-consuming, and high-risk surgical procedures.
PMCID: PMC3276025  PMID: 22345907
Bronchopleural fistula; intercostal drainage tube; N-butyl cyanoacrylate glue; video bronchoscopy
9.  Controlling hemoptysis: An alternative approach 
Hemoptysis is a very common symptom in the practice of pulmonary physicians of India. We present a case of uncontrolled hemoptysis managed with bronchial artery embolization. Bronchial artery embolization is an effective treatment for patients with hemoptysis. Serious complications are rare, but may occur if the arterial supply to other structures is compromised.
PMCID: PMC2893435  PMID: 20616945
Bronchial artery embolization; bronchogenic carcinoma; fiber optic bronchoscopy; hemoptysis
10.  Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration 
Cell  2013;153(2):376-388.
In vertebrates, activation of innate immunity is an early response to injury, implicating it in the regenerative process. However, the mechanisms by which innate signals might regulate stem cell functionality are unknown. Here we demonstrate that type 2 innate immunity is required for regeneration of skeletal muscle after injury. Muscle damage results in rapid recruitment of eosinophils, which secrete IL-4 to activate the regenerative actions of muscle resident fibro/adipocyte progenitors (FAPs). In FAPs, IL-4/IL-13 signaling serves as a key switch to control their fate and functions. Activation of IL-4/IL-13 signaling promotes proliferation of FAPs to support myogenesis, while inhibiting their differentiation into adipocytes. Surprisingly, type 2 cytokine signaling is also required in FAPs, but not myeloid cells, for rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues.
PMCID: PMC3663598  PMID: 23582327
11.  Type 2 innate lymphoid cells control eosinophil homeostasis 
Nature  2013;502(7470):245-248.
Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80 years ago,1 and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins, mediate eosinophil development and survival,2 and tissue recruitment,3 respectively, the processes underlying the basal regulation of these signals remain unknown. Here, we show that serum IL-5 is maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive,4 ILC2 co-express IL-5 and IL-13, which is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide (VIP) also stimulates ILC2 through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.
PMCID: PMC3795960  PMID: 24037376
12.  Surface modification of a polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) nanocomposite polymer as a stent coating for enhanced capture of endothelial progenitor cells 
Biointerphases  2013;8(1):22.
An unmet need exists for the development of next-generation multifunctional nanocomposite materials for biomedical applications, particularly in the field of cardiovascular regenerative biology. Herein, we describe the preparation and characterization of a novel polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) nanocomposite polymer with covalently attached anti-CD34 antibodies to enhance capture of circulating endothelial progenitor cells (EPC). This material may be used as a new coating for bare metal stents used after balloon angioplasty to improve re-endothelialization. Biophysical characterization techniques were used to assess POSS-PCU and its subsequent functionalization with anti-CD34 antibodies. Results indicated successful covalent attachment of anti-CD34 antibodies on the surface of POSS-PCU leading to an increased propensity for EPC capture, whilst maintaining in vitro biocompatibility and hemocompatibility. POSS-PCU has already been used in 3 first-in-man studies, as a bypass graft, lacrimal duct and a bioartificial trachea. We therefore postulate that its superior biocompatibility and unique biophysical properties would render it an ideal candidate for coating medical devices, with stents as a prime example. Taken together, anti-CD34 functionalized POSS-PCU could form the basis of a nano-inspired polymer platform for the next generation stent coatings.
PMCID: PMC3979469  PMID: 24706135
POSS-PCU; Stent coatings; Anti-CD34 antibody; Endothelialization; Endothelial progenitor cell capture; Nanotechnology; Regenerative medicine; Biomaterials
13.  Spatial behavior and seizure-induced changes in c-fos mRNA expression in young and old rats 
Neurobiology of aging  2012;34(4):1184-1198.
The subcellular processes of gene induction and expression in the hippocampus are likely to underlie some of the known age-related impairments in spatial learning and memory. It is well established that immediate-early genes are rapidly and transiently induced in response to neuronal activity and this expression is required for stabilization of durable memories. To examine whether age-related memory impairment might be caused, in part, by differences in the level of cellular activation or subcellular processing, c-fos expression in CA1 pyramidal and dentate gyrus granule cells in the dorsal hippocampus of young and old rats was determined using fluorescence in situ hybridization and reverse transcription polymerase chain reaction. No significant age differences were found in the numbers of pyramidal or granule cells that show c-fos expression; however, c-fos mRNA transcripts were altered in these 2 cell types in aged animals. These findings suggest that though the networks of cells that participate in behavior or seizure-induced activity are largely maintained in aged rats, their RNA transcript levels are altered. This might, in part, contribute to cognitive deficits frequently observed with advancing age.
PMCID: PMC3665155  PMID: 23158763
Aging; Immediate early-genes; Transcription; Learning and memory; Synaptic plasticity; Seizures
14.  Why do obstetric patients go to the ICU? A 3-year-study 
Pregnant women are at risk to develop complications due to illness related to pregnancy or due to aggravation of pre-existing disease. These patients also require critical care and ICU admissions in some cases. To determine the current spectrum of diseases in an obstetric population resulting in admission to the intensive care unit (ICU) at a tertiary care hospital.
A retrospective case series study and analysis of data from obstetric patients admitted for critical care management.
0.26% of the total obstetric patients admitted to the hospital required ICU admissions. 46% of patients were admitted to ICU for ventilator support. Pre-eclampsia and obstetrical hemorrhage were the common diagnosis for these patients.
Critically ill obstetric patients require a team approach of the obstetrician, anesthesiologist and intensive care specialist for the optimal care of these patients.
PMCID: PMC3862664  PMID: 24600086
Critical care in obstetrics; Eclampsia; ICU admissions; Maternal mortality; Obstetrical hemorrhage
15.  Is HAPO the exclusive diagnosis of pulmonary oedema at HA? 
PMCID: PMC3862917  PMID: 24600104
16.  Whole-cell inactivated Leptospirosis vaccine 
Leptospirosis is an infectious disease of worldwide distribution that is caused by pathogenic spirochete bacteria of the genus Leptospira. It is transmitted by the urine of an infected animal and contagious in a moist environment. Epidemiological studies indicate that infection is commonly associated with certain occupational workers such as farmers, sewage workers, veterinarians, and animal handlers. The annual incidence is estimated at 0.1–1 per 100,000 in temperate climates to 10–100 per 100,000 in the humid tropics. A disease incidence of more than 100 per 100,000 is encountered during outbreaks and in high-exposure risk groups. The 11 countries in South-East Asia (SEA) together have a population of more than 1.7 billion and a work force of about 770 million with more than 450 million people engaged in agriculture. Because of the large number of serovars and infection sources and the wide differences in conditions of transmission, the control of leptospirosis is complicated and will depend on local conditions. The available leptospirosis vaccines are mono- or polyvalent cellular suspensions. These cells are inactivated by chemical agents like formaldehyde and phenol, or by physical agents like heat. The vaccine confers protection for not longer than about one year, while there are cases that need revaccination six months later during epidemic periods.
PMCID: PMC3903893  PMID: 23295984
bacteria; incidence; outbreak; prevention; vaccine
17.  MAVS Protein Is Attenuated by Rotavirus Nonstructural Protein 1 
PLoS ONE  2014;9(3):e92126.
Rotavirus is the single, most important agent of infantile gastroenteritis in many animal species, including humans. In developing countries, rotavirus infection attributes approximately 500,000 deaths annually. Like other viruses it establishes an intimate and complex interaction with the host cell to counteract the antiviral responses elicited by the cell. Among various pattern recognition receptors (PAMPs) of the host, the cytosolic RNA helicases interact with viral RNA to activate the Mitochondrial Antiviral Signaling protein (MAVS), which regulates cellular interferon response. With an aim to identify the role of different PAMPs in rotavirus infected cell, MAVS was found to degrade in a time dependent and strain independent manner. Rotavirus non-structural protein 1 (NSP1) which is a known IFN antagonist, interacted with MAVS and degraded it in a strain independent manner, resulting in a complete loss of RNA sensing machinery in the infected cell. To best of our knowledge, this is the first report on NSP1 functionality where a signaling protein is targeted unanimously in all strains. In addition NSP1 inhibited the formation of detergent resistant MAVS aggregates, thereby averting the antiviral signaling cascade. The present study highlights the multifunctional role of rotavirus NSP1 and reinforces the fact that the virus orchestrates the cellular antiviral response to its own benefit by various back up strategies.
PMCID: PMC3958477  PMID: 24643253
18.  Towards a Comprehensive Catalog of Zebrafish Behavior 1.0 and Beyond 
Zebrafish  2013;10(1):70-86.
Zebrafish (Danio rerio) are rapidly gaining popularity in translational neuroscience and behavioral research. Physiological similarity to mammals, ease of genetic manipulations, sensitivity to pharmacological and genetic factors, robust behavior, low cost, and potential for high-throughput screening contribute to the growing utility of zebrafish models in this field. Understanding zebrafish behavioral phenotypes provides important insights into neural pathways, physiological biomarkers, and genetic underpinnings of normal and pathological brain function. Novel zebrafish paradigms continue to appear with an encouraging pace, thus necessitating a consistent terminology and improved understanding of the behavioral repertoire. What can zebrafish ‘do’, and how does their altered brain function translate into behavioral actions? To help address these questions, we have developed a detailed catalog of zebrafish behaviors (Zebrafish Behavior Catalog, ZBC) that covers both larval and adult models. Representing a beginning of creating a more comprehensive ethogram of zebrafish behavior, this effort will improve interpretation of published findings, foster cross-species behavioral modeling, and encourage new groups to apply zebrafish neurobehavioral paradigms in their research. In addition, this glossary creates a framework for developing a zebrafish neurobehavioral ontology, ultimately to become part of a unified animal neurobehavioral ontology, which collectively will contribute to better integration of biological data within and across species.
PMCID: PMC3629777  PMID: 23590400
19.  Discordant diagnosis of malaria in a family of child refugees from Sierra Leone 
The clinical presentation and diagnosis of malaria involving a family with seven children who arrived in Canada as refugees is reported. Discrepancies in front-line testing using microscopy and rapid diagnostic tests compared with confirmatory testing using real-time polymerase chain reaction in this cluster of symptomatic and asymptomatic patients were identified.
PMCID: PMC3630033  PMID: 24421796
Diagnosis; Malaria; Refugees
20.  Immune aspects of the breast tumor microenvironment 
Breast cancer management  2013;2(3):231-244.
The immune response in the tumor microenvironment is complex, consisting of cells from both the adaptive and innate immune systems. The phenotype and function of these cells are dictated by cytokines present in the microenvironment, as well as by the interactions of these cells with the tumor cells and each other. Technological advances have allowed investigators to better identify the specific immune cells present and immune-related gene signatures overexpressed in the tumor microenvironment. Increased knowledge of tumor immunology has allowed us to better understand how these cells and the developing tumor interact. Together, these advances have prompted the conduct of numerous studies investigating the prognostic and predictive significance of immune infiltrates.
PMCID: PMC3917569  PMID: 24516507
21.  Weekly nab-Rapamycin in Patients with Advanced Nonhematologic Malignancies: Final Results of a Phase 1 Trial 
This dose-finding phase 1 study investigated the maximum tolerated dose (MTD) and safety of weekly nab-rapamycin in patients with untreatable advanced nonhematologic malignancies.
Experimental Design
nab-Rapamycin was administered weekly for 3 weeks followed by 1 week of rest, with a starting dose of 45mg/m2. Additional doses were 56.25, 100, 150, and 125 mg/m2.
Of 27 enrolled patients, 26 were treated. Two dose-limiting toxicities (DLTs) occurred at 150mg/m2 (grade 3 AST elevation and grade 4 thrombocytopenia), and 2 DLTs occurred at 125mg/m2 (grade 3 suicidal ideation and grade 3 hypophosphatemia). Thus, the MTD was declared at 100mg/m2. Most treatment-related adverse events (TRAEs) were grade 1/2, including thrombocytopenia (58%), hypokalemia (23%), mucositis (38%), fatigue (27%), rash (23%), diarrhea (23%), nausea (19%), anemia (19%), hypophosphatemia (19%), neutropenia (15%), and hypertriglyceridemia (15%). Only 1 grade 3 nonhematologic TRAE (dyspnea) and 1 grade 3 hematologic event (anemia) occurred at the MTD. One patient with kidney cancer had a partial response. The longest clinical benefits were observed in 2 patients: 1 patient with mesothelioma (SD: 365 days) and 1 patient with neuroendocrine tumor (SD: 238 days). The Cmax and AUC increased with dose between 45–150mg/m2, except for a relatively low AUC at 125 mg/m2. nab-Rapamycin significantly inhibited mTOR targets S6K and 4EBP1.
The clinical dose of single agent nab-rapamycin was established at 100 mg/m2, which was well tolerated with preliminary evidence of response and SD, and produced a fairly dose proportional pharmacokinetic profile in patients with unresectable advanced nonhematologic malignancies.
PMCID: PMC3935482  PMID: 24089446
22.  Severity of Hepatitis C Virus (Genotype-3) Infection Positively Correlates with Circulating MicroRNA-122 in Patients Sera 
Disease Markers  2014;2014:435476.
Introduction. Hepatitis C virus (genotype-3) causes acute and chronic hepatitis infection predomination in India. The infectious phase of the virus requires various host factors for its survival and subsequent viral particle production. Small RNA molecules like microRNA-122 (miR-122) are one such factor mostly present in the liver and play a supportive role in viral replication. Objective. In this study, diagnostic potential of miR-122 is evaluated in the sera of chronic hepatitis C patients. Methods. miRNAs were isolated from the sera samples of patients as well as controls and miR-122 expression was quantified by real-time PCR. Results. A significant augmentation was observed in the level of circulating miR-122 (median level, 0.66 versus 0.29, P = 0.001) in patients compared to controls with ROC value of 0.929 ± 0.034 (P < 0.001). Interestingly, miR-122 level also depicted a significant positive correlation with serum ALT (r = 0.53), AST (r = 0.44), and viral load (r = 0.52). Conclusion. The study thus unveiled the role of miR-122 as a plausible diagnostic biomarker during HCV genotype-3 infection in India.
PMCID: PMC3948614
23.  Larvicidal Activity of Cassia occidentalis (Linn.) against the Larvae of Bancroftian Filariasis Vector Mosquito Culex quinquefasciatus 
Background & Objectives. The plan of this work was to study the larvicidal activity of Cassia occidentalis (Linn.) against the larvae of Culex quinquefasciatus. These larvae are the most significant vectors. They transmit the parasites and pathogens which cause a deadly disease like filariasis, dengue, yellow fever, malaria, Japanese encephalitis, chikungunya, and so forth, which are considered harmful towards the population in tropic and subtropical regions. Methods. The preliminary laboratory trail was undertaken to determine the efficacy of petroleum ether and N-butanol extract of dried whole plant of Cassia occidentalis (Linn.) belonging to the family Caesalpiniaceae at various concentrations against the late third instar larvae of Culex quinquefasciatus by following the WHO guidelines. Results. The results suggest that 100% mortality effect of petroleum ether and N-butanol extract of Cassia occidentalis (Linn.) was observed at 200 and 300 ppm (parts per million). The results obviously showed use of plants in insect control as an alternative method for minimizing the noxious effect of some pesticide compounds on the environment. Thus the extract of Cassia occidentalis (Linn.) is claimed as more selective and biodegradable agent. Conclusion. This study justified that plant Cassia occidentalis (Linn.) has a realistic mortality result for larvae of filarial vector. This is safe to individual and communities against mosquitoes. It is a natural weapon for mosquito control.
PMCID: PMC3943188
24.  Rapamycin-induced modulation of HIV gene transcription attenuates progression of HIVAN 
HIV-associated nephropathy (HIVAN) is the manifestation of HIV genes expression by kidney cells in the presence of specific host factors. Recently, rapamycin (sirolimus) has been demonstrated to modulate the progression of HIVAN. We hypothesized that rapamycin would modulate the progression of HIVAN by attenuating HIV genes expression. To test our hypothesis, three weeks old Tg26 mice (n=6) were administered either vehicle or rapamycin (5 mg/kg/day, intraperitoneally) for eight weeks. At the end of experimental period, kidneys were harvested. In in vitro studies, human podocytes were transduced with either HIV-1 (NL4-3) or empty vector (EV), followed by treatment with either vehicle or rapamycin. Total RNA and proteins were extracted from renal tissues/ cellular lysates and HIV gene transcription/translation was measured by real time PCR and Western blotting studies. Renal histological slides were graded for glomerular sclerosis and tubular dilatation with microcyst formation. Rapamycin attenuated both glomerular and tubular lesions in Tg26 mice. Rapamycin decreased transcription of HIV genes both in renal tissues as well as in HIV-1 transduced podocytes. Our data strongly indicate that HIV-1 long terminal repeat-mediated transcriptional activity was targeted by rapamycin. Rapamycin enhanced podocyte NF-kB and CREB activities but then it decreased AP-1 binding activity. Since expression of HIV genes by kidney cells has been demonstrated to be the key factor in the development HIVAN, it appears that rapamycin-induced altered transcription of HIV genes might have partly contributed to its disease modulating effects.
PMCID: PMC3535680  PMID: 23010541
25.  Clinico-Microbiological Profile of Chronic Pulmonary Aspergillosis from a Tertiary Care Centre in Southern India 
Background: Pulmonary aspergillosis is commonly seen in immunocompromised individuals. A significant rise has been seen in these cases in the past decade, owing to growing number of patients with impaired immune status.
Aim: This study includes the detailed clinical and microbiological profiles of all the culture positive cases of pulmonary aspergillosis, detected in three years, from Jan 2008–Dec 2010, at our tertiary care centre.
Methods: A hospital based observational and retrospective study was conducted to study the clinico-microbiological characteristics of patients with pulmonary aspergillosis. Respiratory specimens which showed repeated isolation of Aspergillus were included in the study. Demographic details, clinical findings and predisposing factors were noted down for all the patients. Treatment of patients with antifungal agents and their responses to treatment were also documented.
Results: There were 22 patients with male to female ratio of 1.2:1 and mean age of 52.5 years. The most common underlying lung disease was presence of bronchial asthma in 27.3% (6/22) cases. Many patients (40.9%; 9/22) were on steroid treatment. Cough with expectoration was the most common symptom observed in 72.7% (16/22) cases. Microbiologically, microscopy showed positivity for the presence of gram positive, acutely branched, fungal hyphae, suggestive of Aspergillus, in all the cases. Aspergillus fumigatus was the predominant species that was isolated in 40.9% (9/22) cases. All the diagnosed patients were given either oral itraconazole or intravenous amphotericin B. A clinical improvement was observed in 72.5% (16/22) cases, but 27.3% (6/22) patients died.
Conclusion: Pulmonary aspergillosis presents with non-specific clinical and radiological findings. An early suspicion and diagnosis is essential, especially in patients with underlying lung disease, to prevent dissemination and invasion.
PMCID: PMC3919323  PMID: 24551620
Aspergillus; Pulmonary aspergillosis,; Chronic obstructive pulmonary disease

Results 1-25 (423)