bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Factors and Survival in Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy
Authors: Crvenkova Simonida 
Published: January 2015

BACKGROUND: According to the literature, performance status, stage-tumor dimension and nodal status, weight loss, were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer.AIM: To evaluate the treatment results and the prognostic variables in our patients treated with sequential and concurrent chemoradiotherapy.MATERIAL AND METHODS: In the study 85 patients were randomly assigned to one of the two treatment arms. In the sequential arm, 45 patients had previously received sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy (RT). In the second concurrent group, 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT, followed by two cycles of consolidation chemotherapy of carboplatine and etoposide. We described all phases of the conformal three dimensional (3-D) RT.RESULTS: From October 2005 to March 2008, 93 patients were enrolled. Eight patients were not eligible, seven had stage IV and one patient had pleural effusion. They were all initially considered to have stage IIIB disease. Â The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm. The differences were statistically significant (log-rank test p=0.0039). The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group. The differences were statistically significant (log-rank test p=0.0023). We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method: - age, p<0.05; - performant status, p<0.001; - weight loss, p<0.001; tumor dimension, p<0.05; and - nodal involvement, p<0.05.CONCLUSION: In our study, the dose-limiting toxicity, esophagitis was reduced by performing conformal radiotherapy. Conformal thoracic radiotherapy and new radiotherapy technics, such as respiratory gated radiotherapy, allow dose escalating and may probably improve survival and local control in lung cancer patients.
Granzymes Regulate Proinflammatory Cytokine Responses
Authors: Wensink Annette C. , Hack C. Erik , Bovenschen Niels 
Published: January 2015

Abstract
Granzymes (Grs) are serine proteases mainly produced by cytotoxic lymphocytes and are traditionally considered to cause apoptosis in tumor cells and virally infected cells. However, the cytotoxicity of several Grs is currently being debated, and additional, predominantly extracellular, functions of Grs in inflammation are emerging. Extracellular soluble Grs are elevated in the circulation of patients with autoimmune diseases and infections. Additionally, Grs are expressed by several types of immune cells other than cytotoxic lymphocytes. Recent research has revealed novel immunomodulatory functions of Grs. In this review, we provide a comprehensive overview on the role of Grs in inflammation, highlighting their role in cytokine induction and processing.
Transoesophageal echocardiography: What a neuroanaesthesiologist should know?
Authors: Choudhury Minati 
Published: January 2015

AbstractTransoesophageal echocardiography (TEE) is a semi invasive imaging modality rapidly gained credence and popularity in the cardiothoracic centers worldwide by mid 1990s. It has also been found to be useful in some noncardiac surgical procedures, in particular in the management of neurosurgical patients and haemodynamically unstable patients in intensive care units (ICUs). The principal goal of basic transoesophageal echocardiographic examination encompass a broad range of anatomic imaging including the diagnosis of air embolism, causes of haemodynamic instability, ventricular size and function, volume status, and complications from invasive procedures, as well as the clinical impact or etiology of pulmonary dysfunction in ICU. TEE is relatively cheap and semi-invasive, but it should not be used as a stand-alone device but as a tool which provides data in addition to the data acquired from other forms of monitoring. The establishment of TEE in perioperative neuro anaesthetic care though recent, may result in a significant change in the role of the anaesthetsiologist who, using TEE can provide new information which may change the course and the outcome of surgical procedures.
Stem-cell therapy for neurologic diseases
Authors: Sharma Shilpa , Gupta Devendra 
Published: January 2015

AbstractWith the advent of research on stem cell therapy for various diseases, an important need was felt in the field of neurological diseases. While congenital lesion may not be amenable to stem cell therapy completely, there is a scope of partial improvement in the lesions and halt in further progression. Neuro degenerative lesions like Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis have shown improvement with stem cell therapy. This article reviews the available literature and summarizes the current evidence in the various neurologic diseases amenable to stem cell therapy, the plausible mechanism of action, ethical concerns with insights into the future of stem cell therapy.
Mannitol versus hypertonic saline for intra-operative brain relaxation during aneurysm surgery
Authors: Sharma Shalini , Grover Vinod , Mathew Preethy 
Published: January 2015

Abstract
Background: The study was designed to compare the effects of equiosmolar and equivolemic 3% hypertonic saline (HTS) and 20% mannitol (M) on brain relaxation during aneurysm surgery. Materials and Methods: A prospective, randomised, double-blind study was undertaken in patients scheduled for surgical clipping of intracranial aneurysms presenting with Fisher grade I, II or III. The patients received either 300 mL of 3% hypertonic saline (HTS group) or 300 mL of 20% mannitol infusion (M group) during a period of 15 minutes at the start of scalp incision. The PaCO2 was maintained at 3.4-4.7 kilo Pascal, arterial blood pressure was maintained within ± 20% of baseline and central venous pressure was maintained at 5-10 cm of water. The haemodynamics, arterial blood gases and serum sodium concentration were compared. Surgeons assessed the condition of the brain as bulging, firm, satisfactorily relaxed and perfectly relaxed. An anaesthesiologist also assessed intra-operative brain relaxation. Results: The brain relaxation achieved with hypertonic saline was as good as that with mannitol. Urine output with mannitol was higher than with hypertonic saline (P < 0.04). Hypertonic saline caused an increase in serum sodium over one hour (P < 0.001) but resolved in 24 hours. Conclusions: The brain relaxation was equal in both the groups as assessed by the anaesthesiologist as well as the surgeon while the transient rise in serum sodium in hypertonic saline group returned to normal within 24 hours.
Monitoring the depth of anaesthesia using the new modified entropy sensors during supratentorial craniotomy: Our experience
Authors: Sharma Richa , Manninen Pirjo , Venkatraghavan Lashmikumar 
Published: January 2015

Abstract
Background: Monitoring the depth of anaesthesia can be a challenge in patients undergoing supratentorial craniotomy because the conventional sensors for both bispectral index and entropy monitors lose their contact with a brain after scalp elevation. The new sensors for the entropy monitor are more flexible and can be placed in different locations. The purpose of this study was to determine the feasibility on the use of new GE entropy sensors in monitoring depth of anaesthesia in patients undergoing supratentorial craniotomy. Materials and Methods: We retrospectively reviewed the data from 20 consecutive patients undergoing supratentorial craniotomy who had the monitoring of the depth of anaesthesia using modified entropy sensors. Prior to the induction of anaesthesia, the new GE entropy sensor (P/N M1038681) was applied in a modified fashion. We measured the state entropy (SE) and response entropy (RE) at 12 perioperative time points. Entropy values were compared with the clinical indices of depth of anaesthesia. Results: Data from 20 consecutive patients (orbitozygomatic craniotomy [10] and bifrontal craniotomy [10]) were analysed. Monitoring was possible in all the patients. The changes in entropy values correlated with clinical indices of depth of anaesthesia. However, some patients showed variations in absolute values (RE and SE) during the intraoperative period without any changes in the level of anaesthetic depth. Conclusions: Monitoring the depth of anaesthesia is feasible with the use of new entropy sensors in patients undergoing supratentorial craniotomy. In contrast to standard sensors, the new sensors offer flexibility with the placement.
Comparison of oral intubation using flexible fibreoptic bronchoscope with or without rigid cervical collar: A clinical study
Authors: Gill Nitesh , Purohit Shobha , Godara Mukesh 
Published: January 2015

Abstract
Background: Device like fibreoptic bronchoscope is gold standard for difficult intubation situations. It can be performed by both orotracheal and nasotracheal route. But, through nasal route there are more chances of nasal bleeding and pressure necrosis while through oral route there is only one problem, which is clearing of upper airway for bronchoscope. Manoeuvres like jaw thrust and chin lift are very useful in clearing upper airway for bronchoscope. The aim of this study was to compare ease of oral intubation using flexible fibreoptic bronchoscope with or without rigid cervical collar, in terms of need of manoeuvres: Jaw thrust and Chin lift. Materials and Methods: 25 patients in age range 20-50 years, of ASA ? - II, and of either sex undergoing elective surgery under general anaesthesia were randomly allocated into each group. There were two groups: Group A (Rigid Cervical Collar) and group B (Without Collar). Intubating condition was assessed in between these groups with need of manoeuvres like jaw thrust and chin lift. Quantitative data i.e. age, weight, thyromental distance and sternomental distance were presented as mean value and standard deviation. Intergroup comparison of quantitative data was done by t-test and probability was considered to be significant if less than <0.05. Categorical data i.e. sex, ASA grade, Mallampati grade and need of manoeuvres were presented as number and were compared among groups using Chi-square test. P < 0.05 was considered statistically significant. Results: There was significant (P < 0.05) difference between group A and group B in terms of use of manoeuvres for ease of intubation and clearing upper airway. In group B, need of jaw thrust and chin lift for clearing airway is significantly (P < 0.05) higher than collar group. Conclusion: We concluded that as far as the oral intubation with flexible fibreoptic bronchoscope is concerned, rigid cervical collar is very useful tool for making intubation easier.
Perioperative pentoxifylline therapy attenuates early postoperative neuro-cognitive decline in patients undergoing coronary artery bypass grafting surgery using cardiopulmonary bypass
Authors: Das Sambhunath , Kailash Suparna , Mehta Manu , Bisoi Akshya 
Published: January 2015

Abstract
Background: Postoperative cognitive decline (POCD) after coronary artery bypass grafting (CABG) is a common problem. Studies show that pentoxifylline administration reduces inflammation induced by cardiopulmonary bypass and brain injury after ischaemia. Hence the perioperative use of pentoxifylline in attenuating POCD was evaluated in the study. Materials and Methods: Eighty patients were divided randomly into two groups from 106 patients scheduled for CABG surgery. The study group was administered pentoxifylline 400 mg twice daily orally from day of admission to 7th day after surgery, whereas the control group patients received placebo. Neurocognitive assessment was assessed by an independent clinical psychologist one day after admission to hospital and again on 7th postoperative day. The data was analyzed and a P < 0.05 was considered significant results. Results: Pentoxifylline-treated group showed no statistically significant difference in animal naming test scores (10.3 ± 2.2 versus 9.4 ± 2.5, P = 0.07), digit symbol substitution test (26.1 ± 7.47 vs 22.2 ± 6.07, P = 0.09) and 8 subtests of Post Graduate Institute-memory scale. The control group had significant POCD as detected by animal naming test (10.5 ± 3.7 versus 8.6 ± 3.9, P = 0.008), digit symbol substitution test (20.2 ± 8.2 versus 14.7 ± 8.9, P = 0.008) and five subtests of memory scale (P = 0.01, 0.04, 0.003, 0.005 and 0.02). The incidence of POCD was 50% in placebo-treated group compared to 22.5% in pentoxifylline group. Conclusions: The perioperative use of pentoxifylline attenuates the early postoperative neurocognitive decline after CABG using cardiopulmonary bypass.
Profound hypertension with dexmedetomidine during insertion of deep brain stimulator
Authors: Tedder Allison , Rakhman Evgeny , Manninen Pirjo , Venkatraghavan Lashmikumar 
Published: January 2015

AbstractDexmedetomidine is now frequently used in the anaesthetic management of patients undergoing deep brain stimulator insertion for movement disorders. We present two patients with Parkinson’s disease and dystonia who developed marked increase in blood pressure and level of sedation during the infusion of a loading dose of dexmedetomidine (1 mcg/kg over 10 min). Both patients required treatment of their blood pressure. The first patient also had a computed tomography of the brain to rule out an intracranial event. The patients recovered from these untoward events in approximately 30 min. The possible explanations for both the hypertension and oversedation were underestimation of the severity of the patients’ underlying disease process and a relative overdose of the loading dose of dexmedetomidine.
Management of a patient undergoing sitting position craniotomy for acoustic neuroma with co-existing interstitial lung disease
Authors: Suvarna Deepa , Baliarsing Lipika , Gujjar Pinakin , Agarwal Rashmi 
Published: January 2015

AbstractA 38-year-old woman with acoustic neuroma associated with occupational interstitial lung disease (ILD) was successfully managed for sitting position craniotomy using carefully titrated desflurane-based anaesthesia. The anaesthetic challenges included maintenance an adequate depth of anaesthesia, reducing perioperative airway events and ensuring smooth recovery. While dealing with ILD patient in sitting position, careful risk assessment is important because it will help us predict the course of the perioperative events. Balanced general anaesthesia using desflurane fulfilled the requirement of good depth and smooth recovery in this patient. Though there are reports of maintenance of anaesthesia with other inhalational agents, there are scanty reports of using desflurane in these cases.
Practical Applications in Immunohistochemistry: Evaluation of Diffuse Large B-Cell Lymphoma and Related Large B-Cell Lymphomas
Authors: O'Malley Dennis P. , Auerbach Aaron , Weiss Lawrence M. 
Published: January 2015

Context
Diffuse large B-cell lymphoma is the most commonly diagnosed subtype of lymphoma worldwide. The current World Health Organization (WHO) classification includes several subtypes, based on a combination of clinical, immunohistochemical, and genetic differences. Immunohistochemical staining is essential in evaluating diffuse large B-cell lymphoma and many related large B-cell lymphomas and aggressive B-cell lymphomas.

Objective
To address different immunohistochemical features used for identification, subclassification, prognosis and in some cases, therapy, of diffuse large B-cell lymphoma and related lymphomas.

Data Sources
The information outlined in this review article is based on our experiences with routine cases, on the current WHO classification of hematopoietic and lymphoid tumors, and on a review of English-language articles published throughout 2014.

Conclusions
Features and diagnostic criteria of diffuse large B-cell lymphoma, aggressive variants of B-cell lymphomas, including Burkitt lymphoma and “double-hit” lymphomas, are discussed. Identification of cell of origin (germinal center type versus activated B-cell type) is discussed at length. Finally, practical approaches for diagnosis are discussed.
Role of mantle flow in Nubia‐Somalia plate divergence
Authors: Stamps D. S. , Iaffaldano G. , Calais E. 
Published: December 2014

AbstractPresent‐day continental extension along the East African Rift System (EARS) has often been attributed to diverging sublithospheric mantle flow associated with the African Superplume. This implies a degree of viscous coupling between mantle and lithosphere that remains poorly constrained. Recent advances in estimating present‐day opening rates along the EARS from geodesy offer an opportunity to address this issue with geodynamic modeling of the mantle‐lithosphere system. Here we use numerical models of the global mantle‐plates coupled system to test the role of present‐day mantle flow in Nubia‐Somalia plate divergence across the EARS. The scenario yielding the best fit to geodetic observations is one where torques associated with gradients of gravitational potential energy stored in the African highlands are resisted by weak continental faults and mantle basal drag. These results suggest that shear tractions from diverging mantle flow play a minor role in present‐day Nubia‐Somalia divergence.
Dealing with the complex drug–drug interactions: Towards mechanistic models
Authors: Varma Manthena V. , Pang K. Sandy , Isoherranen Nina , Zhao Ping 
Published: December 2014

AbstractUnmanageable severe adverse events caused by drug‐drug interactions (DDIs), leading to market withdrawals or restrictions in the clinical usage, are increasingly avoided with the improvement in our ability to predict such DDIs quantitatively early in drug development. However, significant challenges arise in the evaluation and/or prediction of complex DDIs caused by inhibitor drugs and/or metabolites that affect not one but multiple pathways of drug clearance. This review summarizes the discussion topics at the 2013 AAPS symposium on “Dealing with the complex drug‐drug interactions: towards mechanistic models”. Physiologically based pharmacokinetic (PBPK) models, in combination with the established in vitro‐to‐in vivo extrapolations of intestinal and hepatic disposition, have been successfully applied to predict clinical pharmacokinetics and DDIs, especially for drugs with CYP‐mediated metabolism, and to explain transporter‐mediated and complex DDIs. Although continuous developments are being made towards improved mechanistic prediction of the transporter‐enzyme interplay in the hepatic and intestinal disposition and characterizing the metabolites contribution to DDIs, the prediction of DDIs involving them remains difficult. Regulatory guidelines also recommended use of PBPK modeling for the quantitative prediction and evaluation of DDIs involving multiple perpetrators and metabolites. Such mechanistic modeling approaches culminate to the consensus that modeling is helpful in predicting DDIs or quantitatively rationalizing the clinical findings in complex situations. Furthermore, they provide basis for the prediction and/or understanding the pharmacokinetics in populations like patients with renal impairment, pediatrics, or various ethnic groups where the conduct of clinical studies might not be feasible in early drug development stages and yet some guidance on management of dosage is necessary. Copyright © 2014 John Wiley & Sons, Ltd.
Modeling of the pharmacokinetic/pharmacodynamic interaction between irbesartan and hydrochlorothiazide in normotensive subjects
Authors: Hedaya Mohsen A. , Helmy Sally A. 
Published: December 2014

AbstractPurposeTo investigate the pharmacokinetic/pharmacodynamic (PK/PD) interaction between irbesartan (IRB) and hydrochlorothiazide (HCT) in normotensive subjects.MethodsA three‐way crossover study was used. Serial drug concentrations and drug effects, including systolic and diastolic blood pressure and heart rate were monitored after administration of irbesartan and hydrochlorothiazide alone and in combination. The data were fitted to a PK/PD model and the parameters for irbesartan and hydrochlorothiazide when administered alone and in combination were compared.ResultsThe plasma profiles for irbesartan and hydrochlorothiazide followed the two‐compartment model after a single dose. The PK parameters of irbesartan were not affected by hydrochlorothiazide; however irbesartan decreased the hydrochlorothiazide AUC by 25% and increased its clearance by 25%. There were no significant changes in heart rate after each drug alone or in combination. Irbesartan plus hydrochlorothiazide had a greater blood pressure lowering effect compared with irbesartan alone, despite the unchanged irbesartan PK. The relationship between irbesartan plasma concentration and its effects plotted in chronological order showed anticlockwise hysteresis. The PD parameter estimates for the effect of irbesartan on systolic blood pressure, when administered with hydrochlorothiazide were significantly different from those when irbesartan was administered alone. This was manifested by a 25% increase in Emax, and a 40% decrease in EC50, suggesting a synergistic blood pressure lowering effect for the combination. While parameter estimates for the effect of irbesartan on diastolic blood pressure were changed by hydrochlorothiazide, the differences were only significant for EC50.ConclusionA limited potential for clinically significant interactions between irbesartan and hydrochlorothiazide at the given doses were observed; therefore, no dosage adjustments were recommended for either drug when used together. (ClinicalTrials.gov Identifier NCT01858610) Copyright © 2014 John Wiley & Sons, Ltd.
One‐way trip: Influenza virus' adaptation to gallinaceous poultry may limit its pandemic potential
Authors: Long Jason S. , Benfield Camilla T. , Barclay Wendy S. 
Published: December 2014

SummaryWe hypothesise that some influenza virus adaptations to poultry may explain why the barrier for human‐to‐human transmission is not easily overcome once the virus has crossed from wild birds to chickens. Since the cluster of human infections with H5N1 influenza in Hong Kong in 1997, chickens have been recognized as the major source of avian influenza virus infection in humans. Although often severe, these infections have been limited in their subsequent human‐to‐human transmission, and the feared H5N1 pandemic has not yet occurred. Here we examine virus adaptations selected for during replication in chickens and other gallinaceous poultry. These include altered receptor binding and increased pH of fusion of the haemagglutinin as well as stalk deletions of the neuraminidase protein. This knowledge could aid the delivery of vaccines and increase our ability to prioritize research efforts on those viruses from the diverse array of avian influenza viruses that have greatest human pandemic potential.Also watch the Video Abstract.