tbuckley/cabot-search huggingface dataset:
Initial Insight on the Determinants of Podocyte Polarity
Authors: Lawrence B. Holzman, Puneet Garg
Journal: Journal of the American Society of Nephrology (2009)

Glomerular disease manifest by proteinuria is associated with changes in the architecture of podocyte foot processes and the structure of podocyte intercellular junctions. For this reason, there is great interest in defining the cellular mechanisms that determine and maintain normal podocyte morphology in health, that results in changes in podocyte morphology in disease, and might affect recovery of normal podocyte structure after disease. Much research in this area has focused on protein complexes localized to the podocyte intercellular junction.

This work has been propelled by identification of several genes that encode proteins targeted to the intercellular junction, which when mutated in human congenital disease result either in failure of podocyte development or in an inability of the podocyte to maintain its normal architecture. Among these disease genes is Nphs1 , which encodes Nephrin, a transmembrane protein of the cell adhesion family targeted to the intercellular junction of the mature podocyte foot process.1 With structurally similar Neph1 protein, Nephrin-Neph1 forms a complex in the plane of the cell membrane that recruits proteins of the actin polymerization complex regulating foot process actin cytoskeletal dynamics.2–4 In doing so, these proteins coordinate foot process intercellular junction formation and maintenance with development and homeostasis of podocyte morphology. Given the complexity of these cellular processes, our knowledge of the precise mechanisms by which nephrin operates remain rudimentary.

Polarity, or the asymmetric distribution of cellular constituents, is a fundamental property of polarized cells that defines cellular architecture and tissue organization essential for cellular function.5 Renal tubular epithelial cells are polarized along the apical-basal axis that extends from the tubular basement membrane to the apical luminal surface. In this example, epithelial polarity is defined by the asymmetric distribution …
ABC of the upper gastrointestinal tract: Oesophagus: Atypical chest pain and motility disorders
Authors: J. Bennett
Journal: BMJ (2001)

Chest pain has been a diagnostic problem for centuries. Heberden's superb clinical description of angina pectoris (and other chest pains) still stands, but today's doctors may be no better at diagnosing cardiac pain accurately than their predecessors 60 years ago. Even when a doctor is sure that the pain is non-cardiac, the more inquiring patient often wants a more specific label.

Much of the interest in this subject has arisen from the extensive investigation of patients concerned that their symptoms could be cardiac in origin. Given the associated and inevitable selection bias, there is little objective evidence on which to base practice, but the oesophagus is undoubtedly one of the organs that can generate problematic chest pain.

This article describes the oesophageal disorders responsible, and ways to diagnose them. Psychological factors are often important in patients with chest pain, so that common sense, understanding a patient and his or her problem, and good communication are usually more important than diagnostic tests and powerful drugs.

Oesophageal pain has many patterns: it is often described as burning, sometimes as gripping, and it can also be pressing, boring, or stabbing. Usually in the anterior chest, it tends to be felt mainly in the throat or epigastrium and sometimes radiates to the neck, back, or upper arms—all of which may equally apply to cardiac pain. The commonest patterns of cardiac and oesophageal pains are quite different and well recognised, but perhaps 20% of each are much harder to feel confident about.



Frequency of pain experienced in different anatomical sites by patients with cardiac pain and oesophageal pain



Discomfort or pain from the oesophagus may arise from irritant stimuli to the mucosa or from mechanical effects on …
Heart Rate Is a Marker of Amiodarone Mortality Reduction in Severe Heart Failure
Authors: Daniel R. Nul, Hernán C. Doval, Hugo O. Grancelli, Sergio D. Varini, Saul Soifer, Sergio V. Perrone, Noemí Prieto, Omar Scapin
Journal: Journal of the American College of Cardiology (1997)
FRI0136 Duration between Symptom Onset and Spondyloarthritis Diagnosis – Changes over A Decade
Authors: S. Löfvendahl, I.F. Petersson, E. Haglund, A. Bremander, L. Jacobsson, A. Jöud
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The delay of diagnosis after symptom onset for various subgroups of spondyloarthritis (SpA) is considerable. Increasing focus on this over the last decades may have decreased this delay (1-2). <h3>Objectives</h3> To study the duration between symptom onset and date of diagnosis of SpA and its subgroups: ankylosing spondylitis (AS), psoriatic arthritis (PsA), and unspecified spondyloarthritis (USpA). A special focus was to study the change over the past decade. <h3>Methods</h3> The Swedish SpAScania cohort (N=5,771, = all patients diagnosed with SpA between 2003 and 2007 in primary or secondary care in the Skåne region, total n=1.3 million 2013) was used. We analyzed patients (n=952) identified as having AS (n=173), PsA (n=579) or USpA (n=200) by a rheumatologist or internist at least one time or by any other physician twice during 2003 to 2007 responding to a postal survey in 2009 and 2011. The survey included questions on years for start of symptoms and diagnosis. All patients included had a self-reported diagnosis of SpA between 1997 and 2007 in the survey 2009. The information from 2009 was used to calculate the duration between symptom onset and date of diagnosis and the response from the 2011 survey to investigate the reliability of these answers (647 patients responded to the survey in both 2009 and 2011 and were hence eligible for reliability analysis). The mean duration (years) was calculated (95% CI), both unadjusted and adjusted for sex, age and year of diagnosis. <h3>Results</h3> The overall mean duration between symptom onset and date of a SpA diagnosis was 6.8 years (95% CI: 6.3-7.3), without any obvious secular change up through 2007. The mean duration for AS was 9.0 (95% CI: 7.8-10.3), for PsA 6.0 (5.4-6.6) and USpA 7.2 (95% CI: 6.1-8.3). There was an overall good consistency between the self-assessed year of symptom start, measured in 2009 and in 2011 (ρ=0.58). However, there was a variation between subgroups, consistency being higher in AS (ρ =0.84) and lower in PsA (ρ =0.53). <h3>Conclusions</h3> The duration between symptom onset and diagnosis was longest for AS and shortest for PsA with USpA in between. Up to 2007 there was no significant trend for any decrease in such delay for any of the subgroups. <h3>References</h3> Sorensen J, Hetland ML. Duration of symptoms before diagnosis in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Ann Rheum Dis 2013;72(Suppl3):80. Salvadorini G, Bandinelli F, DelleSedie A, Riente L, Candelieri A, Generini S. Ankylosing spondylitis: how diagnostic and therapeutic delay have changed over the last six decades. Clin Exp Rheumatol. 2012 Jul-Aug;30(4):561-5. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3102
Increased bone metabolism in rheumatoid arthritis as measured by the whole-body retention of 99Tcm methylene diphosphonate.
Authors: C Rajapakse, R Thompson, D M Grennan, B M Winston, P Patel, P M Nuttall, J Murphy, J B Weiss
Journal: Annals of the Rheumatic Diseases (1983)

Bone metabolism in 21 patients with rheumatoid disease was investigated by measurement of the 24-hour whole body retention (WBR) of 99Tcm methylene diphosphonate (MDP) in parallel with clinical, radiological, and biochemical measurements (urinary excretion of hydroxyproline) of disease activity. Corticosteroid-treated patients of those with other forms of metabolic bone disease were excluded from the study. WBR was increased in the rheumatoid patients as compared with 21 age- and sex-matched controls (p less than 0.05), and there was a significant correlation in the rheumatoid group between WBR and urinary excretion of hydroxyproline (p less than 0.01) and between urinary excretion of hydroxyproline and an articular index (p less than 0.05) and global index (p less than 0.01) of disease activity. The increased WBR of the rheumatoid patients was not explicable by factors such as immobilisation, and the results are interpreted as reflecting an overall increase in bone metabolism which may occur in rheumatoid arthritis as part of the disease process.
Sarcomere length-resting tension relation in single frog atrial cardiac cells.
Authors: M Tarr, J W Trank, P Leiffer, N Shepherd
Journal: Circulation Research (1979)

It generally has been thought that the relatively high resting tension characteristic of cardiac tissue resides in structures (collagen, elastin) external to the individual cardiac cells, but the evidence to support this conclusion has been indirect, since the resting tension of intact single cardiac cells has not been determined previously. The purpose of the present investigation was to determine the resting tension (stress)-sarcomere length relationships of single intact frog atrial cells. For tension determinations, a single cell was attached between two poly-L-lysine coated glass beams; one beam served as a compliant calibrated cantilevered force beam, and length changes were imposed on the cell by movement of the other beam. Coventional bright-field light microscope techniques were used to view the cell, the sarcomere pattern within the cell, and the position of the force beam. The resting tension of the intact cell increased from a value of about 10 nN at a sarcomere length of 2.35 microns to a value of about 130 nN at a sarcomere length of 3.45 microns. Lagrangian and Eulerian resting stress-sarcomere length relationships were computed from the resting tension-sarcomere length relationships. The Lagrangian stress increased from a value of about 0.6 mN/mm2 at a sarcomere length of 2.35 microns to a value of about 7 mN/mm2 at a sarcomere length of 3.45 microns. These values of stress are about 8- to 30-fold less than those previously reported for intact frog atrial tissue and indicate that the resting tension of intact frog atrial preparations resides primarily in structures external to the individual cardiac cell.
Genome‐wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles
Authors: Laura Mosca, Pellegrino Musto, Katia Todoerti, Marzia Barbieri, Luca Agnelli, Sonia Fabris, Giacomo Tuana, Marta Lionetti, Eleonora Bonaparte, Silvia Maria Sirchia, Vitina Grieco, Gabriella Bianchino, Fiorella D'Auria, Teodora Statuto, Carmela Mazzoccoli, Luciana De Luca, Maria Teresa Petrucci, Fortunato Morabito, Massimo Offidani, Francesco Di Raimondo, Antonietta Falcone, Tommaso Caravita, Paola Omedè, Mario Boccadoro, Antonio Palumbo, Antonino Neri
Journal: American Journal of Hematology (2012)

Primary plasma cell leukemia (pPCL) is a rare, yet aggressive form of de novo plasma cell tumor, distinct from secondary PCL (sPCL) which represents a leukemic transformation of pre-existing multiple myeloma (MM). Herein, we performed a comprehensive molecular analysis of a prospective series of pPCLs by means of FISH, single nucleotide polymorphism (SNP) array and gene expression profiling (GEP). IGH@ translocations were identified in 87% of pPCL cases, with prevalence of t(11;14) (40%) and t(14;16) (30.5%), whereas the most frequent numerical alterations involved 1p (38%), 1q (48%), 6q (29%), 8p (42%), 13q (74%), 14q (71%), 16q (53%), and 17p (35%). We identified a minimal biallelic deletion (1.5 Mb) in 8p21.2 encompassing the PPP2R2A gene, belonging to a family of putative tumor suppressors and found to be significantly down-regulated in deleted cases. Mutations of TP53 were identified in four cases, all but one associated with a monoallelic deletion of the gene, whereas activating mutations of the BRAF oncogene occurred in one case and were absent in N- and K-RAS. To evaluate the influence of allelic imbalances in transcriptional expression we performed an integrated genomic analysis with GEP data, showing a significant dosage effect of genes involved in transcription, translation, methyltransferase activity, apoptosis as well as Wnt and NF-kB signaling pathways. Overall, we provide a compendium of genomic alterations in a prospective series of pPCLs which may contribute to improve our understanding of the pathogenesis of this aggressive form of plasma cell dyscrasia and the mechanisms of tumor progression in MM.
P14.03 * MEDULLOBLASTOMA IN MOROCCO: A RETROSPECTIVE REVIEW
Authors: H. Hami, A. Ayoujil, F. Habib, A. Soulaymani, A. Mokhtari, A. Quyou
Journal: Neuro-Oncology (2014)

INTRODUCTION: Medulloblastoma is the most common malignant brain tumor in children. The aim of this study is to describe the epidemiological characteristics of medulloblastoma in Morocco. METHODS: This is a descriptive retrospective study of cases diagnosed and treated for medulloblastoma between 1994 and 2004 at Al Azhar Oncology Center in Rabat. RESULTS: There were 23 cases diagnosed with medulloblastoma at Al Azhar Oncology Center, accounting for 7.8% of all brain tumors reported during the study period. Medulloblastomas were more common among males than females, with a male-female ratio of 1.3. The average age at diagnosis was 18.6 ± 4.1 years (range 2-67 years). Nearly two-thirds of the patients (65.2%) were under the age of 15 years and 86.7% of all pediatric medulloblastomas were diagnosed in children under the age of 10. Among the cases for whom the outcome was known, three children under the age of 6 years died during the study period. CONCLUSIONS: The most recent estimates of medulloblastoma incidence and mortality in the world reveal sharp differences between developed and developing countries possibly related to missed opportunities for early diagnosis and incomplete reporting of medulloblastoma in Africa.
Vertebral Body Hemangioma Showing Increased Uptake of Tc-99m MDP and Decreased Tc-99m Labeled Red Blood Cells
Authors: R. K. HALKAR, M. M. MOTAWY, H. G. HEBBAR, M. S. JAHAN
Journal: Clinical Nuclear Medicine (1994)

A 40-year-old woman who previously had surgery for liposarcoma of the small intestine complained of lowback ache. Roentgenography and computed tomography of the lumbar vertebrae demonstrated classical findings of hemangioma of the L5 vertebra. Tc-99m MDP planar Images showed a hot area in the region of the L5 vertebra, and tomographic images confirmed the Increased tracer concentration in the body of the L5 vertebra. Tc-99m labeled red blood cell blood pool images after a 2-hour delay did not reveal increased tracer concentration in the region of L5. Review of the old x-ray and clinical follow up confirmed the lesion to be a hemangioma. Review of the literature includes two reports of radlonuclide Imaging of hemangloma; one calvarial hemangioma showed no abnormal increased uptake of Tc-99m MDP, and a vertebral hemangioma showed decreased Tc-99m MDP uptake. Compared with these, the present case is a variant.
Seeing the message
Authors: Chetan Suresh Modi
Journal: BMJ (2006)

All NHS patients attending hospital have their religion diligently documented in a box somewhere in the case notes, but we tend to forget that sometimes our patients' beliefs are more important for them than anything we might be able to offer.

I recall clerking an anxious patient admitted for coronary artery bypass grafting and being surprised that he was in deep discussion with the hospital priest. I settled down to …
Transdermal Nicotine for Ulcerative Colitis
Authors: Mario Guslandi
Journal: Annals of Internal Medicine (1997)

Letters15 September 1997Transdermal Nicotine for Ulcerative ColitisMario Guslandi, MD and Alberto Tittobello, MDMario Guslandi, MDUniversity of Milan; Milan, ItalySearch for more papers by this author and Alberto Tittobello, MDUniversity of Milan; Milan, ItalySearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-6-199709150-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with great interest the paper by Sandborn and colleagues [1] on transdermal nicotine for ulcerative colitis. In agreement with their data, we also reported that transdermal nicotine, when added to mesalamine, induces clinical alleviation of mild to moderate ulcerative colitis [2]. In fact, nicotine patches allowed most patients with a history of poor tolerance to corticosteroids to avoid prednisone therapy [2]. Although if administered alone, transdermal nicotine seems less effective than oral steroids in active disease [3] and no better than placebo as maintenance treatment [4], we also observed that patients who responded to nicotine ...References1. Sandborn WJ, Tremaine W, Offord KP, Lawson GM, Petersen BT, Batts KP, et al. Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1997; 126:364-71. Google Scholar2. Guslandi M, Tittobello A. Pilot trial of nicotine patches as an alternative to corticosteroids in ulcerative colitis. J Gastroenterol. 1996; 31:627-9. Google Scholar3. Thomas GA, Rhodes J, Ragunath K, Mani V, Williams GT, Newcombe RG, et al. Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis. Eur J Gastroenterol Hepatol. 1996; 8:769-76. Google Scholar4. Thomas GA, Rhodes J, Mani V, Williams GT, Newcombe RG, Russell MA, et al. Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med. 1995; 332:988-92. Google Scholar Author, Article, and Disclosure InformationAuthors: Mario Guslandi, MD; Alberto Tittobello, MDAffiliations: University of Milan; Milan, Italy PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySmoking in inflammatory bowel disease: Impact on disease course and insights into the aetiology of its effectMetabolism and biochemical effects of nicotine for primary care providersTransdermal nicotine for induction of remission in ulcerative colitis 15 September 1997Volume 127, Issue 6Page: 492KeywordsColitisCorticosteroid therapyNicotineResearch designSteroidsUlcerative colitis ePublished: 15 August 2000 Issue Published: 15 September 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Maximal suppression of renin-angiotensin system in nonproliferative glomerulonephritis
Authors: Carmela Iodice, Mario M. Balletta, Roberto Minutolo, Paolo Giannattasio, Stefano Tuccillo, Vincenzo Bellizzi, Maurizio D'Amora, Giorgio Rinaldi, Giuseppe Signoriello, Giuseppe Conte, Luca De Nicola
Journal: Kidney International (2003)
Below-Knee Elastic Compression Stockings To Prevent the Post-Thrombotic Syndrome
Authors: Paolo Prandoni, Anthonie W.A. Lensing, Martin H. Prins, Michela Frulla, Antonio Marchiori, Enrico Bernardi, Daniela Tormene, Laura Mosena, Antonio Pagnan, Antonio Girolami
Journal: Annals of Internal Medicine (2004)

Because only limited evidence suggests that elastic stockings prevent the post-thrombotic syndrome in patients with symptomatic deep venous thrombosis (DVT), these stockings are not widely used.To evaluate the efficacy of compression elastic stockings for prevention of the post-thrombotic syndrome in patients with proximal DVT.Randomized, controlled clinical trial.University hospital.180 consecutive patients with a first episode of symptomatic proximal DVT who received conventional anticoagulant treatment.Before discharge, patients were randomly assigned to wear or not wear below-knee compression elastic stockings (30 to 40 mm Hg at the ankle) for 2 years. Follow-up was performed for up to 5 years.The presence and severity of the post-thrombotic syndrome were scored by using a standardized scale.Post-thrombotic sequelae developed in 44 of 90 controls (severe in 10) and in 23 of 90 patients wearing elastic stockings (severe in 3). All but 1 event developed in the first 2 years. The cumulative incidence of the post-thrombotic syndrome in the control group versus the elastic stockings group was 40.0% (95% CI, 29.9% to 50.1%) versus 21.1% (CI, 12.7% to 29.5%) after 6 months, 46.7% (CI, 36.4% to 57.0%) versus 22.2% (CI, 13.8% to 30.7%) after 1 year, and 49.1% (CI, 38.7% to 59.4%) versus 24.5% (CI, 15.6% to 33.4%) after 2 years. After adjustment for baseline characteristics, the hazard ratio for the post-thrombotic syndrome in the elastic stockings group compared with controls was 0.49 (CI, 0.29 to 0.84; P = 0.011).This study lacked a double-blind design.Post-thrombotic sequelae develop in almost half of patients with proximal DVT. Below-knee compression elastic stockings reduce this rate by approximately 50%.
P13.03 * HYPOFRACTIONATED STEREOTACTIC RADIOTHERAPY (HSR) IN RECURRENT HIGH GRADE GLIOMA: A SAFE AND EFFECTIVE APPROACH
Authors: A. Ascolese, F. Pessina, P. Navarria, S. Tomatis, P. Mancosu, E. Clerici, L. Bello, F. Lobefalo, M. Grimaldi, M. Scorsetti
Journal: Neuro-Oncology (2014)

PURPOSE: Tumor control and survival in patients with high grade glioma (HGG) are limited. Local recurrence occurs usually in primary site within 1-3 years from initial treatment. Treatment at recurrence are not standardized and various therapeutic approach can be used. Hypofractionated Stereotactic Radiotherapy (HSR) has been shown as a feasible and effective treatment for recurrent high grade glioma previously treated with conventional radiotherapy. HSRS allows a precise delivery of radiation with optimal sparing of normal and functional brain in eloquent areas. In addition, hypofractionation of delivery dose could get a potential radiobiological advantage on tumor cells. The aim of this study is to evaluate safety and efficacy of salvage HSRS in recurrent high grade glioma patients. End points of the analyses are toxicity, rate of local control and patient's survival. MATERIALS AND METHODS: Adult patients with Karnosky Performance Status (KPS) ≥70 and a disease free interval higher than 1 year were included. Gadolinium- MRI and C11METPET were performed before and every 3 months thereafter. The Median dose delivered on the PTV was 25 Gy (range 25-50 Gy) in 5 fractions (range 5-10). Volumetric Modulated Arc therapy (VMAT) by Rapid Arc (RA) technique was used. Response and toxicity were evaluated using RANO criteria and CTCAE 3.0 respectively. RESULTS: Between January 2006 and December 2013, 25 patients (15 males and 10 females) were treated; the median age was 41 years (range 26-75 years). Sixteen of them had Glioblastoma, 5 Anaplastic Oligoastrocytoma and 4 Anaplastic Astrocytoma. At recurrence, before HSR 9 patients underwent partial surgical resection and 5 received a second line chemotherapy . Median time between the first RT treatment and HSRS re- irradiation was 18 months (range 12-77 months). The Median follow up was 11.1 months (1.3-19.2 months). No G3-G4 toxicity was observed. Response in according to RANO criteria was recorded in 14 patients (56%). Median survival was 11.5 months (range 1.3-19.2 months). PFS at 1 year was 30% and OS at 1 and 2 years were 40% and 20%. At the last follow up 12 patients were alive and 13 died. CONCLUSION: HSR re-irradiation is a feasible, safe and effective therapeutic option for patients with recurrent HGG. VMAT RA technique improves target coverage while minimizing higher dose to normal tissue with remarkable radiological and clinical response and negligible toxicity.