tbuckley/cabot-search huggingface dataset:
Prof. Om Prakash Sharma, 1936–2012
Authors: Marjolein Drent, Ulrich Costabel, Robert P. Baughman
Journal: European Respiratory Journal (2012)

A gentle giant of learning and inspiration peacefully passed away on August 19, 2012 at home in Los Angeles, at the age of 76 years.Om's academic accomplishments speak for themselves.But they don't convey the gleam that was always in his eye, nor his infectious smile.He only had positive things to say and was always encouraging.He was a great man, whose profound learning, humility and gentle approach to others will be a lifelong source of inspiration to those who knew him.The entire sarcoidosis community is mourning the passing of a true friend and academic teacher.For those of us lucky enough to know him, his passing is very sad news.For those of you who had not met him, you have missed a great opportunity.Om always spoke with a calm reassurance, yet he was very passionate about many things.Many of us have our favourite Om stories, but they mostly centre around how he encouraged us.Om Sharma was truly a great clinician and teacher, who not only added new knowledge to the mysteries of sarcoidosis, but kept news of this disease important for patients and physicians outside the field.His persona embodied the best qualities of a mentor, and of a wonderful and generous friend.Beside his professional merits we would like to stress Om Sharma's outstanding commitment towards his patients.
Does cartilage volume or thickness distinguish knees with and without mild radiographic osteoarthritis? The Framingham Study
Authors: S Reichenbach, M Yang, F Eckstein, J Niu, D J Hunter, C E McLennan, A Guermazi, F Roemer, M Hudelmaier, P Aliabadi, D T Felson
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: To examine whether the quantity of cartilage or semiquantitative scores actually differ in knees with mild radiographic osteoarthritis compared with knees without osteoarthritis. Methods: Framingham Osteoarthritis Study participants had knee tibiofemoral magnetic resonance imaging-based measurements of cartilage. Using three-dimensional FLASH-water excitation sequences, cartilage volume, thickness and subregional cartilage thickness were measured and cartilage scored semiquantitatively (using the whole-organ magnetic resonance imaging score; WORMS). Using weight-bearing radiographs, mild osteoarthritis was defined as Kellgren/Lawrence (K/L) grade 2 and non-osteoarthritis as K/L grade 0. Differences between osteoarthritis and non-osteoarthritis knees in median cartilage measurements were tested using the Wilcoxon rank sum test. Results: Among 948 participants (one knee each), neither cartilage volume nor regional thickness were different in mild versus non-osteoarthritis knees. In mild osteoarthritis, cartilage erosions in focal areas were missed when cartilage was quantified over large regions such as the medial tibia. For some but not all subregions of cartilage, especially among men, cartilage thickness was lower (p&lt;0.05) in mild osteoarthritis than non-osteoarthritis knees. Because semiquantitative scores captured focal erosions, median WORMS scores were higher in mild osteoarthritis than non-osteoarthritis (all p&lt;0.05). In moderate/severe osteoarthritis (K/L grades 3 or 4), osteoarthritis knees had much lower cartilage thickness and higher WORMS scores than knees without osteoarthritis. Conclusions: In mild osteoarthritis, the focal loss of cartilage is missed by quantitative measures of cartilage volume or thickness over broad areas. Regional cartilage volume and thickness (eg, medial tibia) are not different in mild osteoarthritis versus non-osteoarthritis. Subregional thickness may be decreased in mild osteoarthritis. Semiquantitative scoring that assesses focal cartilage damage differentiates mild osteoarthritis from non-osteoarthritis.
Primary thyroid marginal zone B-cell lymphoma in a patient with psoriatic arthritis treated with etanercept
Authors: Hyunju Jin, Hyun-Ho Cho, Won-Jeong Kim, Je-Ho Mun, Margaret Song, Hoon-Soo Kim, Hyun-Chang Ko, Moon-Bum Kim, Byung-Soo Kim
Journal: Journal of the American Academy of Dermatology (2014)
Prevalence of KIT Expression in Human Tumors
Authors: Philip Th. Went, Stephan Dirnhofer, Marcel Bundi, Martina Mirlacher, Peter Schraml, Sara Mangialaio, Sasa Dimitrijevic, Juha Kononen, Alessandro Lugli, Ronald Simon, Guido Sauter
Journal: Journal of Clinical Oncology (2004)

KIT is a target for imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Gastrointestinal stromal tumors (GISTs) express KIT and respond favorably to imatinib therapy. To determine other tumors in which such a molecular targeted therapy might be indicated, we investigated KIT expression in different human tumor types. Because recent studies in GISTs suggest that KIT-activating mutations predict response to imatinib therapy, we also sequenced a subset of positive tumors.More than 3,000 tumors from more than 120 different tumor categories were analyzed by immunohistochemistry in a tissue microarray format. Seven commercially available anti-KIT antibodies were initially evaluated. The antibody A4502 (DAKO) was selected for analysis because of a high frequency of positivity in GIST and low staining background in other tissues. To determine the frequency of KIT mutations in various tumor types, the exons 2, 8, 9, 11, 13, and 17 (where mutations previously were reported) were sequenced in 36 tumors with strong KIT expression.KIT positivity was detected in 28 of 28 GISTs (100%), 42 of 50 seminomas (84%), 34 of 52 adenoid-cystic carcinomas (65%), 14 of 39 malignant melanomas (35%), and eight of 47 large-cell carcinomas of the lung (17%), as well as in 47 additional tumor types. KIT mutations were found in six of 12 analyzed GISTs, but only in one of 24 other tumors.The results suggest that KIT expression occurs infrequently in most tumor types and that, with the exception of GISTs, KIT gene mutations are rare in immunohistochemically KIT-positive tumors.
Reinfection tuberculosis: two cases in the family of a patient with drug-resistant disease.
Authors: P Ormerod, C Skinner
Journal: Thorax (1980)

A 42-year-old housewife died of drug-resistant pulmonary tuberculosis. Two sons had earlier completed a course of treatment for drug-sensitive disease. Six months after her death both sons developed sputum-positive tuberculosis with a drug resistance pattern identical to that of their mother during her last year of life, and including resistance to drugs which neither son had received. In both cases immunocompetence to tuberculin was shown so that reinfection arose purely as a result of heavy exposure.
Quality assessment: is the truth in the outcome?
Authors: C. K. van der Ent
Journal: European Respiratory Journal (2007)

Healthcare workers and medical centres are increasingly requested to report data about their results of medical treatment. Governments call hospitals to account for their results in order to plan new healthcare structures, and to support new regulations in medical systems. Insurance companies are highly interested in the results of medical treatments to enable cost-effectiveness of care and benchmarking between different providers. Centres with the “best care” for the “lowest price” are popular in the financial departments of healthcare agencies. Newspapers and magazines regularly fill their columns with comparisons of hospital performances regarding patient safety and satisfaction. And last, but not least, patients themselves want to know and have the right to know whether their medical centre and their doctor deliver good quality of care.

Several systems have been developed to evaluate quality of care, sometimes with far-reaching consequences. In the UK, general practitioners' remuneration is now directly linked to the scores attained in the Quality and Outcomes Framework 1. The success of such an approach depends, in part, on designing a robust and clinically meaningful set of indicators. Outcome measures regarding the results of treatment are often attractive at first glance, but their interpretation can be complicated. Patients can be pleased to know that their doctor has the highest lung function results for chronic obstructive pulmonary disease or asthma patients in the country, but in most cases they …
Audit of a new appointments system in a hospital outpatient clinic.
Authors: M Jennings
Journal: BMJ (1991)

OBJECTIVE--To assess the effect of a new appointments system on patients9 waiting time. DESIGN--Replacement of an existing system of regularly spaced appointments at 10 minute intervals with one in which the doctor arranged appointments according to his perception of individual patients9 requirements, from December 1988 to June 1989. SETTING--One general medical outpatient clinic. PATIENTS--All (181) [corrected] patients under regular review with fixed appointment times during six months; those arriving for blood testing before the start of the clinic and those requiring ambulance transport were excluded. MAIN OUTCOME MEASURES--Mean waiting time (mean of difference between appointment time and start of consultation), maximum waiting time, number of patients, and total duration of clinics. RESULTS--Mean waiting time was reduced by about 30 minutes (from 39.6 to 9.5 mins) over the six months. There was no change in the number of patients attending (mean 15.8 v 15.4) or the duration of the clinics (mean 187 v 160 mins). CONCLUSION--Efficiency was improved by simple adjustment to the appointments system used in the hospital outpatient clinic.
Influences of systemic diseases on periodontitis in children and adolescents
Authors: Joerg Meyle, José R. Gonzáles
Journal: Periodontology 2000 (2001)

Systemic diseases affecting the host response as primary immunodeficiencies or secondary defects caused by lack of nutrients or changes in the local tissues are very often accompanied by early-onset prepubertal periodontitis. Local treatment in combination with systemic antibiotics may in milder forms improve the situation, but in many cases the success is questionable and premature loss of teeth occurs. Since the genetic basis of many of the diseases has been identified, future developments permit the correction of at least some of these defects by gene therapy.
Large-Scale Network Dysfunction in Major Depressive Disorder
Authors: Roselinde H. Kaiser, Jessica R. Andrews-Hanna, Tor D. Wager, Diego A. Pizzagalli
Journal: JAMA Psychiatry (2015)

Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive.To investigate network dysfunction in MDD through a meta-analysis of rsFC studies.Seed-based voxelwise rsFC studies comparing individuals with MDD with healthy controls (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web of Science, and EMBASE) and authors contacted for additional data.Twenty-seven seed-based voxel-wise rsFC data sets from 25 publications (556 individuals with MDD and 518 healthy controls) were included in the meta-analysis.Coordinates of seed regions of interest and between-group effects were extracted. Seeds were categorized into seed-networks by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive or reduced negative connectivity) or hypoconnectivity (increased negative or reduced positive connectivity) with each seed-network.Major depressive disorder was characterized by hypoconnectivity within the frontoparietal network, a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network involved in attending to the external environment. Major depressive disorder was also associated with hyperconnectivity within the default network, a network believed to support internally oriented and self-referential thought, and hyperconnectivity between frontoparietal control systems and regions of the default network. Finally, the MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions.Reduced connectivity within frontoparietal control systems and imbalanced connectivity between control systems and networks involved in internal or external attention may reflect depressive biases toward internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression.
Benefit From Exemestane As Extended Adjuvant Therapy After 5 Years of Adjuvant Tamoxifen: Intention-to-Treat Analysis of the National Surgical Adjuvant Breast and Bowel Project B-33 Trial
Authors: Eleftherios P. Mamounas, Jong-Hyeon Jeong, D. Lawrence Wickerham, Roy E. Smith, Patricia A. Ganz, Stephanie R. Land, Andrea Eisen, Louis Fehrenbacher, William B. Farrar, James N. Atkins, Eduardo R. Pajon, Victor G. Vogel, Joan F. Kroener, Laura F. Hutchins, André Robidoux, James L. Hoehn, James N. Ingle, Charles E. Geyer, Joseph P. Costantino, Norman Wolmark
Journal: Journal of Clinical Oncology (2008)

Patients with early-stage, hormone receptor-positive breast cancer have considerable residual risk for recurrence after completing 5 years of adjuvant tamoxifen. In May 2001, the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated accrual to a randomized, placebo-controlled, double-blind clinical trial to evaluate the steroidal aromatase inhibitor exemestane as extended adjuvant therapy in this setting.Postmenopausal patients with clinical T(1-3)N(1)M(0) breast cancer who were disease free after 5 years of tamoxifen were randomly assigned to 5 years of exemestane (25 mg/d orally) or 5 years of placebo. Our primary aim was to test whether exemestane prolongs disease-free survival (DFS). In October 2003, results of National Cancer Institute of Canada (NCIC) MA.17 showing benefit from adjuvant letrozole in this setting necessitated termination of accrual to B-33, unblinding, and offering of exemestane to patients in the placebo group.At the time of unblinding, 1,598 patients had been randomly assigned; 72% in the exemestane group continued on exemestane and 44% in the placebo group elected to receive exemestane. With 30 months of median follow-up, original exemestane assignment resulted in a borderline statistically significant improvement in 4-year DFS (91% v 89%; relative risk [RR] = 0.68; P = .07) and in a statistically significant improvement in 4-year relapse-free survival (RFS; 96% v 94%; RR = 0.44; P = .004). Toxicity, assessed up to time of unblinding, was acceptable for the adjuvant setting.Despite premature closure and crossover to exemestane by a substantial proportion of patients, original exemestane assignment resulted in non-statistically significant improvement in DFS and in statistically significant improvement in RFS.
Severe endobronchial obstruction in a girl with relapsing polychondritis: treatment with Nd YAG laser and endobronchial silicon stent
Authors: O Sacco, B Fregonese, M Oddone, A Verna, E Tassara, C Mereu, GA Rossi
Journal: European Respiratory Journal (1997)

Relapsing polychondritis (RP) is an uncommon disorder of unknown aetiology characterized by inflammation and destruction of the cartilaginous structures of many organs, including the tracheobronchial tree. When untreated, there is a high mortality rate, usually from respiratory obstructive complications. An 8 year old white girl, with a previous diagnosis of RP, was referred to our department for evaluation of worsening dyspnoea. Bronchoscopy showed localized inflammatory and fibrotic alterations of the mucosa, leading to severe obstruction of the left mainstem bronchus at its origin. The condition was successfully treated by endoscopic neodymium yttrium aluminium garnet (Nd YAG) laser. Re-evaluation of the patient, 7 months later, demonstrated bronchial stenosis and malacia requiring mechanical dilatation and positioning of an endobronchial silicon stent, which was well-tolerated by the patient.
Expression of Constitutive and Inducible Nitric Oxide Synthases in the Vascular Wall of Young and Aging Rats
Authors: María R. Cernadas, Lourdes Sánchez de Miguel, Margarita García-Durán, Fernando González-Fernández, Inmaculada Millás, Mercedes Montón, José Rodrigo, Luis Rico, Patricia Fernández, Trinidad de Frutos, Juan A. Rodríguez-Feo, José Guerra, Carlos Caramelo, Santos Casado, Antonio López-Farré
Journal: Circulation Research (1998)

Abstract —Two NO synthase (NOS) isoforms have been described in vessels, an endothelial constitutive NOS (eNOS) and an inducible NOS (iNOS). The purpose of the present study was to examine the endothelium-dependent and endothelium-independent hypotensive response in aging rats, analyzing the ability of their vessels to produce NO. The studies were performed in 2 groups of euvolemic, conscious, male Wistar rats: aging rats (n=20, 18 months old) and young rats (n=20, 5 months old). The hypotensive responses to acetylcholine, bradykinin, and sodium nitroprusside were determined. Furthermore, the expression of the NOS isoforms by Western blot and the eNOS and iNOS activities, defined as Ca 2+ -dependent and Ca 2+ -independent conversion of [ 14 C] l -arginine into [ 14 C] l -citrulline, respectively, were also determined. In the aging rats, we found an impaired hypotensive response to acetylcholine and bradykinin (2 NO- and endothelium-dependent hypotensive agents) that was accompanied by a preserved hypotensive response to sodium nitroprusside. Aging rats also demonstrated an enhanced sensitivity response to the pressor effect of the l -arginine antagonist l - N ω -nitro- l -arginine and a reduced vasoconstrictor response to angiotensin II. The inhibition of NO synthesis normalized the pressor effect of angiotensin II in the aging animals. Nitrite plus nitrate plasma levels were increased in aging rats. Furthermore, cGMP content was also higher in the aging vessels. In the aging aortas, the expression of both eNOS and iNOS isoforms was enhanced. However, in aging rats, the activity of the eNOS isoform was markedly reduced, a finding that was accompanied by the presence of iNOS activity. The vessel wall of aging rats showed an enhanced expression of eNOS and iNOS isoforms. However, eNOS activity was reduced in the aging animals. These findings could explain the impaired endothelium-dependent hypotensive response associated with aging.
John Forbes Munro
Authors: J. C. J. Munro
Journal: BMJ (2014)

John Forbes Munro’s medical education was delayed because of the demands of national service. He joined the Royal Army Medical Corps and trained as a physiotherapist. By the time he had completed his service he had lost his faith, but acquired an empathy and passionate commitment for the health and welfare for those less privileged than himself. Moreover, after working for two years in a strictly hierarchical environment, he had developed a tendency to challenge those whom he believed abused their authority. He left the military with a disregard for uniforms—which later translated to the clinician’s traditional smart dark suit and tie. Despite the fact that he came to the Edinburgh medical school with no scientific secondary education, he graduated with honours.

In 1969 John applied for a consultant physician post at the Eastern General and Edenhall hospitals—run-down neglected institutions that were of little interest to the Edinburgh medical establishment or the rapidly expanding medical school. He set about building a patient centred medical unit team that was to become a major force in Edinburgh. He promoted the concept that the patients’ management should always be seen in the context of their families and set aside one evening a week to talk to patients’ relatives. He insisted that teaching should be a major function of the unit as he believed it had a …
Expression of cGMP-Dependent Protein Kinase I and Phosphorylation of Its Substrate, Vasodilator-Stimulated Phosphoprotein, in Human Endothelial Cells of Different Origin
Authors: Richard Draijer, Arie B. Vaandrager, Christine Nolte, Hugo R. de Jonge, Ulrich Walter, Victor W.M. van Hinsbergh
Journal: Circulation Research (1995)

Abstract Previous studies demonstrated that the thrombin-induced permeability of endothelial cell monolayers is reduced by the elevation of cGMP. In the present study, the presence of cGMP-dependent protein kinase (cGMP-PK) immunoreactivity and activity in various types of human endothelial cells (ECs) and the role of cGMP-PK in the reduction of thrombin-induced endothelial permeability was investigated. cGMP-PK type I was demonstrated in freshly isolated ECs from human aorta and iliac artery as well as in cultured ECs from human aorta, iliac vein, and foreskin microvessels. Addition of the selective cGMP-PK activator 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP) to these ECs caused phosphorylation of the vasodilator-stimulated phosphoprotein (VASP), an established cGMP-PK substrate, which is localized at cell-cell contact sites of confluent ECs. cGMP-PK type I expression decreased during serial passage of ECs, which correlated with a diminished ability of 8-pCPT-cGMP to induce VASP phosphorylation. Preincubation of aorta and microvascular EC monolayers with 8-pCPT-cGMP caused a 50% reduction of the thrombin-stimulated permeability, as determined by measuring the peroxidase passage through EC monolayers on porous filters. Furthermore, the thrombin-induced rise in cytoplasmic [Ca 2+ ] i was strongly attenuated by the cGMP-PK activator in fura 2-loaded aorta ECs. In contrast, cGMP-PK could not be demonstrated in freshly isolated and cultured human umbilical vein ECs. Incubation of umbilical vein ECs with 8-pCPT-cGMP did not cause VASP phosphorylation and had no effect on the thrombin-induced increases in cytoplasmic Ca 2+ and endothelial permeability. These data indicate that cGMP-PK type I is expressed in various types of human macrovascular and microvascular ECs but is absent or expressed in very low amounts in umbilical vein ECs. cGMP-PK type I expression in ECs may be important in the regulation of endothelial permeability and the release of factors involved in vasoregulation and hemostasis.
Expression of survivin and bax/bcl-2 in peroxisome proliferator activated receptor-γ ligands induces apoptosis on human myeloid leukemia cells in vitro
Authors: J.J. Liu, R.W. Huang, D.J. Lin, J. Peng, X.Y. Wu, Q. Lin, X.L. Pan, Y.Q. Song, M.H. Zhang, M. Hou, F. Chen
Journal: Annals of Oncology (2005)
Medical implications of ultra marathon running: observations on a six day track race.
Authors: M. A. Hutson
Journal: British Journal of Sports Medicine (1984)

Medical records were kept of the injuries and illnesses sustained by competitors in a six day running race held in Nottingham in August 1982. The overall rate of injuries sufficiently severe to affect running performance was 60 per cent. These injuries are itemised and discussed with particular reference to the problems raised by this ultra distance race.