tbuckley/cabot-search huggingface dataset:
A Molecular Basis for Wolff–Parkinson–White Syndrome
Authors: Craig T. Basson
Journal: New England Journal of Medicine (2001)

Since its initial description1 seven decades ago, the Wolff–Parkinson–White syndrome has attracted cardiologists' attention not only because of its clinical importance but also because of the opportunity it provides to learn about electrical conduction in the heart. Yet, until the report by Gollob and colleagues in this issue of the Journal, 2 the molecular basis of the syndrome remained a mystery. The Wolff–Parkinson–White syndrome affects 1 to 3 persons per 1000.2,3 These persons are born with an abnormal electrical connection, termed an accessory pathway or bypass tract, between the atria and ventricles. Because accessory pathways often have a more rapid . . .
Astrocyte Intermediaries of Septal Cholinergic Modulation in the Hippocampus
Authors: Milan Pabst, Oliver Braganza, Holger Dannenberg, Wen Hu, Leonie Pothmann, Jurij Rosen, Istvan Mody, Karen van Loo, Karl Deisseroth, Albert J. Becker, Susanne Schoch, Heinz Beck
Journal: Neuron (2016)
PTH-125 A national survey of palliative care in end stage liver disease in the UK
Authors: V Vickerstaff, J Low, S Davis, J Bichard, L Greenslade, K Hopkins, A Marshall, D Thorburn, A Langford, L Jones
Journal: Gut (2015)

<h3>Introduction</h3> Liver disease is the third largest cause of premature death in the United Kingdom (UK) and currently accounts for 2% of deaths in England, but there is little strategy to improve care for those dying from it, as well as a lack of research in this area. Understanding of the views of health care professionals (HCP) on how care can be improved for patients dying from cirrhosis is poor. <h3>Aim</h3> To conduct a national survey of primary, secondary and tertiary care providers to explore current attitudes and practices, to identify future training needs, ideas for service improvement and research priorities. <h3>Method</h3> An online questionnaire survey was emailed to a maximum of 6,181 HCPs working in hepatology and gastroenterology (liver), general practice (GP) and specialist palliative care (SPC) across the UK. <h3>Results</h3> 517 HCP responded: 195 from liver, 46 from GPs and 273 from SPC (response rates 4%, 23% and 10% respectively; overall response rate 8%). Nearly all liver and SPC professionals felt that SPC had a role in the care of patients with cirrhosis. Liver professionals tended to refer to SPC whilst patients were in hospital but overall numbers were low, with only 14% (22/161) and 6% (9/61) of liver professionals referring more than 20 patients/year from in-patient and out-patient care respectively. Patients with cirrhosis only made up a median 1% of the SPC workload. All HCPs wanted further training in: managing liver-related symptoms (SPC), symptom control and end of life issues (liver and GP). Open responses were received from 221 participants. Two main research priorities were identified by all three health professional groups: better symptom control (in particular how best to manage recurrent ascites, opioid pharmacology in liver disease and optimal management of pruritus and encephalopathy), and prognostication. <h3>Conclusion</h3> Although all HCPs recognised the important role of SPC in caring for dying patients with cirrhosis, they all needed further training and uptake of skills to improve their confidence. We recommend a focus on improved understanding of the needs of patients with cirrhosis and their families, identification of better ways in communicating with patients at risk of death, smoother links across care boundaries, and enhanced training for all staff groups. <h3>Disclosure of interest</h3> None Declared.
Noshir Hormusjee Wadia
Authors: Jeetha D’Silva
Journal: BMJ (2016)

Pioneer in Indian neurology



Noshir Hormusjee Wadia, one of the founding fathers of neurology in India, was at the vanguard of the development of neurological sciences in the country.

Born in 1925 to a Parsi family of modest means, Wadia eschewed the family’s timber business and became a doctor. In 1950 he graduated from Mumbai’s Grant Medical College and Sir JJ Hospital with a degree in general medicine.

As a graduate student, Wadia was keenly interested in neurology, but the scope for specialisation in the subject did not exist in India at the time. So when he travelled to England to sit the examination for membership of the Royal College of Physicians (MRCP), Wadia was determined to make the most of it. In London he signed up for a three month course on neurology. “My first real flavour of neurology came from the world famous National Hospital for Nervous Diseases in Queen Square,” he wrote in an unpublished memoir. “Neurology is a specialty in which a skilled teacher can demonstrate the nuances of the subject to a whole class of students, and I was overawed by the demonstrations of neurological cases.”

After obtaining his MRCP, Wadia decided to undergo further training in neurology. He joined the department of neurosurgery at Newcastle General Hospital, after which he was appointed regional medical officer at the National Hospital for Nervous Diseases in Maida Vale, London, in 1953. The hospital was then a leading postgraduate training institute in neurology and opened up a whole new world of experiences for the young doctor. It gave him the opportunity to work with some of the finest neurologists in the UK—including Russell Brain. Wadia demonstrated exemplary medical acumen there and was soon appointed registrar to Brain.

After four years in the UK, Wadia returned to India at …
A phase I safety and pharmacokinetic (PK) study of navitoclax (N) in combination with docetaxel (D) in patients (pts) with solid tumors.
Authors: M. Puglisi, L. van Doorn, M. Blanco-Codesido, M. J. De Jonge, K. Moran, J. Yang, T. Busman, C. Franklin, M. Mabry, A. Krivoshik, R. Humerickhouse, L. R. Molife, F. Eskens
Journal: Journal of Clinical Oncology (2011)

2518 Background: N (ABT-263) is a first-in-class orally available Bcl-2 protein inhibitor that in vitro and in vivo potentiates D activity across a variety of solid tumor types. This phase I study was performed to determine the maximum tolerated dose (MTD) and to assess the safety and PK profile of N plus D. Methods: Pts with advanced solid tumors, adequate organ function and ECOG performance status ≤1 were eligible. N at 150 and 200 mg was given PO, QD days (d) 1-3 or d1-5 q21 followed by D 75 mg/ m2 IV on d 1 q21. To compare the PK of either agent alone, N was administered on days 3-5 or 3-7 only in course 2. PK samples were collected for N and D in cycles 1 and 2. Adverse events (AE) were graded by NCI CTCAE V3.0. Results: 15 pts (M/F: 8/7; median age 54 yrs (range 30-71) were treated at 3 dose levels of N: 150 mg and 200mg d1-5 and 200 mg d1-3. DLTs were febrile neutropenia and grade (gr) 4 thrombocytopenia at N 200 mg d1-5 and febrile neutropenia at 200 mg d 1-3. The MTD is set at 150 mg N d1-5 with D 75 mg2 on d1 and at this dose 12 additional pts are currently being enrolled. Other gr 3/4 AEs were neutropenia (43%), fatigue (21%) and thrombocytopenia (14%); frequently occurring grade 1/2 AEs were fatigue (57%), nausea (50%), vomiting (43%), anorexia (36%), constipation (29%), diarrhea (29%), and thrombocytopenia (21%). One pt with NSCLC had a confirmed partial response (PR), one pt with breast cancer had an unconfirmed PR. Five pts showed stable disease; duration of this ranged from 5-18 weeks; 3/5 pts had SD up to 12 weeks, 1/5 pts had SD up to 14 weeks, and 1/5 pts had SD for 18 weeks. Based on limited PK data, there was no apparent PK interaction between N and D (Table). Conclusions: Navitoclax 150 mg for d1-5 can be safely administrated with D 75 mg/m2. This combination is tolerable with no apparent PK interactions. Antitumor activity was observed in 7 pts (2 PR, 5 SD). Cmax/dose (ng/mL/mg)* AUC24/dose (ng*hr/mL/mg)* Navitoclax (150-200 mg, N=7) Navitoclax alone 20.9 ± 10.4 293 ± 174 Navitoclax with D 14.7 ± 11.4 222 ± 166 D (75 mg/m2, N=3) Cmax ( µ g/mL)* AUCinf ( µ g*hr/mL)* D alone 2.6 ± 1.2 2.9 ± 1.2 D with navitoclax 2.3 ± 0.7 2.4 ± 0.7 * Mean +/− SD
NIMG-70DEVELOPMENT OF A POTENTIAL PRE-OPERATIVE RISK STRATIFICATION TOOL OF CEREBELLAR MUTISM SYNDROME IN CHILDREN WITH POSTERIOR FOSSA TUMOUR - A PRELIMINARY RISK SCORING SCHEME
Authors: Robert A. Dineen, Shivaram Avula, Tom Chambers, Manali Dutta, Jo-Fen Liu, Daniele Soria, Philip Quilan, Donald MacArthur, Simon Howarth, Srikrishna Harave, Chan Chang Ong, Conor Mallucci, Ram Kumar, Barry Pizer, David Walker
Journal: Neuro-Oncology (2015)

BACKGROUND: Despite identification of numerous pre-operative cerebellar mutism syndrome (CMS) clinical and radiological predictors, a unifying pre-operative risk stratification model for use during surgical consent is currently lacking. We have previously assembled a cohort of posterior fossa tumour patients and developed a pre-operative risk stratification model using classification algorithms. Our aim is to further develop a preliminary risk-scoring scheme to flag patients at higher risk of post-operative CMS. METHODS: The combined cohort consists of 89 patients from two major treatment centres (age: 2-23yrs, gender 28M,61F, MRI pathology estimate 36 medulloblastoma, 40 pilocytic astrocytoma, 12 ependymoma, 1 non-committal). Post-operative CMS status was ascertained from clinical notes and pre-operative MRI scans, blinded to CMS status, underwent structured evaluation. Multiple logistic regression coefficients for the six predictors selected by decision tree (cerebellar hemisphere invasion, bilateral invasion at middle cerebellar peduncle, dentate nucleus invasion, pathology estimate ependymoma, middle cerebellar peduncle compression and age > 12.4 years) were converted into risk scores. Predicted CMS probability, diagnostic and predictive values were calculated to explore the potential cut-off points. RESULTS: Of the 89 patients, 26 (29%) developed post-operative CMS. Patient's total risk score ranged from -57 to 263, with a greater number being associated with increased risk of CMS. The cut-off with the highest sum of sensitivity and specificity was total score ≥1, with sensitivity 92%, specificity 86%, positive predictive value 73% and negative predictive value 96%. Using cut-off of 0 and 15 allowed separation of the cohort into low (46/89, predicted probability  50%). CONCLUSIONS: A risk stratification model for post-operative CMS could flag patients at increased risk pre-operatively and may influence strategies for surgical treatment of cerebellar tumours. Following future testing and prospective validation, this risk scoring scheme may be utilised during the surgical consenting process.
A novel adjuvanted capsule based strategy for oral vaccination against infectious diarrhoeal pathogens
Authors: Christopher J.H. Davitt, Edel A. McNeela, Stephanie Longet, Joshua Tobias, Vincenzo Aversa, Craig P. McEntee, Monica Rosa, Ivan S. Coulter, Jan Holmgren, Ed C. Lavelle
Journal: Journal of Controlled Release (2016)
Novel Combination Of Lenalidomide-Rituximab Provides An Effective Bridge To Stem Cell Transplantation In Relapsed and/Or Refractory Aggressive B-Cell Non-Hodgkin’s Lymphomas: A Single Center Experience
Authors: Qingqing Cai, Yiming Chen, Dehui Zou, Maria Badillo, Shouhao Zhou, Liang Zhang, Elyse R Lopez, Wenqi Jiang, Hui-qiang Huang, Tongyu Lin, Michael Wang
Journal: Blood (2013)
Health-Related Quality of Life (Hrqol) During Olaparib Maintenance Therapy in Patients with Platinum-Sensitive Relapsed Serous Ovarian Cancer (Psr Soc) and a Brca Mutation (Brcam)
Authors: J.A. Ledermann, P. Harter, C. Gourley, M. Friedlander, I.B. Vergote, G.J.S. Rustin, C. Scott, W. Meier, R. Shapira-Frommer, T. Safra, D.E. Matei, A. Fielding, S. Spencer, B. Bennett, D. Parry, U. Matulonis
Journal: Annals of Oncology (2014)
Cross-Talk in the Female Rat Mammary Gland: Influence of Aryl Hydrocarbon Receptor on Estrogen Receptor Signaling
Authors: Janina Helle, Manuela I. Bader, Annekathrin M. Keiler, Oliver Zierau, Günter Vollmer, Sridar V. Chittur, Martin Tenniswood, Georg Kretzschmar
Journal: Environmental Health Perspectives (2015)

Background:Cross-talk between the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) plays a major role in signaling processes in female reproductive organs.Objectives:We investigated the influence of the AHR ligand 3-methylcholanthrene (3-MC) on ER-mediated signaling in mammary gland tissue of ovariectomized (ovx) rats.Methods:After 14 days of hormonal decline, ovx rats were treated for 3 days with 4 μg/kg 17β-estradiol (E2), 15 mg/kg 8-prenylnaringenin (8-PN), 15 mg/kg 3-MC, or a combination of these compounds (E2 + 3-MC, 8-PN + 3-MC). Whole-mount preparations of the mammary gland were used to count terminal end buds (TEBs). Protein expression studies (immunohistochemistry, immunofluorescence), a cDNA microarray, pathway analyses, and quantitative real-time polymerase chain reaction (qPCR) were performed to evaluate the interaction between AHR- and ER-mediated signaling pathways.Results:E2 treatment increased the number of TEBs and the levels of Ki-67 protein and progesterone receptor (PR); this treatment also changed the expression of 325 genes by more than 1.5-fold. Although 3-MC treatment alone had marginal impact on gene or protein expression, when rats were co-treated with 3-MC and E2, 3-MC strongly inhibited E2-induced TEB development, protein synthesis, and the expression of nearly half of E2-induced genes. This inhibitory effect of 3-MC was partially mirrored when 8-PN was used as an ER ligand. The anti-estrogenicity of ligand-activated AHR was at least partly due to decreased protein levels of ERα in ductal epithelial cells.Conclusion:Our data show transcriptome-wide anti-estrogenic properties of ligand-activated AHR on ER-mediated processes in the mammary gland, thereby contributing an explanation for the chemopreventive and endocrine-disrupting potential of AHR ligands.Citation:Helle J, Bader MI, Keiler AM, Zierau O, Vollmer G, Chittur SV, Tenniswood M, Kretzschmar G. 2016. Cross-talk in the female rat mammary gland: influence of aryl hydrocarbon receptor on estrogen receptor signaling. Environ Health Perspect 124:601–610; http://dx.doi.org/10.1289/ehp.1509680
Case 34-1977
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, John A. Kirkpatrick, David Gang
Journal: New England Journal of Medicine (1977)

Presentation of CaseA 2 1/2 -year-old boy was admitted to the hospital because of respiratory distress.He was born of an uncomplicated first pregnancy of a 22-year-old mother. The presence of Down's syndrome was suspected at birth and later confirmed by chromosomal studies. There was a history of Down's syndrome in a second cousin of the mother. Repeated respiratory-tract infections and breathing difficulty were observed, with wheezing, "rattling respirations" and occasional attacks of respiratory stridor. At the age of five months the child suddenly became unable to inspire while excited, and cyanosis developed; he revived after mouth-to-mouth resuscitation and . . .
CSF corticotropin-releasing hormone in depressed patients and normal control subjects
Authors: A Roy, D Pickar, S Paul, A Doran, G P Chrousos, P W Gold
Journal: American Journal of Psychiatry (1987)

The authors studied CSF corticotropin-releasing hormone (CRH) and plasma cortisol in 22 depressed patients and 18 normal control subjects. CRH levels were similar in the two groups. Depressed patients who were nonsuppressors on the dexamethasone suppression test had significantly higher levels of CRH than suppressors did. The depressed patients' CRH levels were significantly correlated with 4:00 p.m. postdexamethasone plasma cortisol levels. While the inclusion of a depressed patient with an outlier CRH value resulted in the loss of statistical significance for both of these findings, the authors suggest that these results support the hypothesis that hypercortisolism in depressed patients in part reflects a defect at or above the hypothalamus, resulting in hypersecretion of CRH.
Does<i>Pneumocystis carinii</i>Prophylaxis Still Need to Be Lifelong?
Authors: Henry Masur, Jonathan Kaplan
Journal: New England Journal of Medicine (1999)

Before the advent of antiretroviral therapy and prophylaxis against Pneumocystis carinii pneumonia, this type of pneumonia ultimately developed in 60 to 80 percent of adult patients with human immunodeficiency virus (HIV) infection in North America and Western Europe.1 Seventy percent of patients had a second episode of P. carinii pneumonia within 12 months after the first episode.1 The implementation of prophylaxis to prevent an initial episode of pneumonia (primary prophylaxis) or a subsequent episode (secondary prophylaxis) was the first intervention that substantially increased survival and improved the quality of life for patients with HIV infection. It was subsequently recognized that . . .
Heterogeneity Of Patients With Cytogenetically Normal Acute Myeloid Leukemia (CN-AML) and Nucleophosmin-1 (NPM1) Gene Mutation: An Acute Leukemia French Association (ALFA) Study
Authors: Pierre Peterlin, Aline Renneville, Raouf Ben Abdelali, Olivier Nibourel, Xavier Thomas, Cécile Pautas, Stéphane de Botton, Claude Gardin, Emmanuel Raffoux, Jean-Michel Cayuela, Nicolas Boissel, Christine Terré, Karine Celli-Lebras, Sylvie Castaigne, Claude Preudhomme, Hervé Dombret
Journal: Blood (2013)
PTH-185 Mapping the gastric mucosal surface: image mosaicking for capsule endoscopy
Authors: G Holmes, M Hale, ME McAlindon, S Anderson
Journal: Gut (2015)

<h3>Introduction</h3> Upper gastrointestinal (GI) endoscopy is invasive, incurs risks and most findings are not relevant to the symptoms. Yet 1% of the population undergo upper GI endoscopy per annum and the <i>Be Clear on Cancer</i>campaign expects a 52% increase in demand. Several studies suggest that capsule endoscopy (CE) could be used to examine the upper GI tract, but lack of control and difficulties locating landmarks could increase the chance of missed pathology. We aimed to see if it were possible to map the gastric mucosal surface using mosaicking algorithms to stitch together overlapping CE video frames: a technique which could be used to inform clinicians about completeness of examination. <h3>Method</h3> An algorithm for image mosaicking from CE video frames was developed based on the feature selection method SURF (speeded up robust features). This ’blob detection’ method recognises local regions of an image which are distinguishable by properties such as brightness and matches them in overlapping images. SURF is fast to compute, adapts to variations in rotation and scale and therefore is potentially suitable for analysing CE images. In order to establish that there were enough features for image stitching in the CE images we performed a control test: a single CE image from a forward viewing Mirocam Navi (Intromedic, Seoul, South Korea) was divided up into overlapping subsections. Each subsection was separately submitted to a random transformation of scaling, rotation and translation. These images were then given as an input sequence to the algorithm in order to be stitched back together. A further test of the image stitching algorithm was performed using the Capsocam (Capsovision, CA, USA) capsule, which incorporates four 90° side viewing cameras and is therefore advantageous for mapping because of its 360<sup>O</sup>panoramic view. <h3>Results</h3> Using control images from human stomachs we established that there are sufficient features in gastric CE images to allow feature based image mosaicking. This applied to imaging obtained both from both forward viewing and panoramic view devices. Finally, we found that the success of the image mosaicking depended on the movement of the capsule, and whether there were sufficient overlapping features from frame-to-frame for stitching images together. <h3>Conclusion</h3> Our data show that there are sufficient features to stitch together CE video frames confirming the possibility of developing gastric surface mapping using image mosaicking techniques. A degree of control may be necessary in order to achieve a ‘slow sweep’ over the mucosal surface in order to maximise the acquisition of overlapping features. <h3>Disclosure of interest</h3> None Declared.
The role of bone biopsy in the management of patients with renal osteodystrophy.
Authors: H H Malluche, M C Monier-Faugere
Journal: Journal of the American Society of Nephrology (1994)

Renal osteodystrophy is not a uniform disease. Therefore, knowledge of the underlying bone abnormalities is essential in deciding specific therapeutic regimens. To date, however, there is no unequivocal noninvasive means with which to define bone abnormalities accurately. The best tool remains mineralized bone histology requiring bone biopsies. Despite recent technical improvements, this technique is underused because of perceived constraints. This article outlines the procedures necessary for increasing the value of bone biopsies, such as tetracycline labeling, and various biopsy techniques and their potential complications. Bone biopsies provide important information on precisely the type of renal bone disease affecting patients: (1) predominant hyperparathyroid bone disease; (2) low-turnover uremic osteodystrophy, encompassing osteomalacic and adynamic renal bone disease; and (3) mixed uremic osteodystrophy, consisting of mild to moderate hyperparathyroid bone disease and defective mineralization. Also, the degree of the severity of the lesions may be assessed. Finally, the presence and quantity of aluminum deposition in bone can be demonstrated. The determination of aluminum overload is needed before the initiation of any therapeutic regimens because it is well known that potentially serious complications can occur with current treatments such as vitamin D therapies, desferoxamine administration, or parathyroidectomy.
Innovative Self-Regulation Strategies to Reduce Weight Gain in Young Adults
Authors: Rena R. Wing, Deborah F. Tate, Mark A. Espeland, Cora E. Lewis, Jessica Gokee LaRose, Amy A. Gorin, Judy Bahnson, Letitia H. Perdue, Karen E. Hatley, Erica Ferguson, Katelyn R. Garcia, Wei Lang
Journal: JAMA Internal Medicine (2016)

Weight gain occurs commonly in young adults and has adverse effects on health.