tbuckley/cabot-search huggingface dataset:
Catecholamine-producing cells in the synovial tissue during arthritis: modulation of sympathetic neurotransmitters as new therapeutic target
Authors: S. Capellino, M. Cosentino, C. Wolff, M. Schmidt, J. Grifka, R. H. Straub
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> The proinflammatory and anti-inflammatory role of the sympathetic nervous system in early and late inflammation is an unresolved paradox. A drastic loss of sympathetic nerve fibres in the synovial tissue of patients with rheumatoid arthritis (RA) has previously been demonstrated. The presence of tyrosine hydroxylase (TH)-positive cells in RA and osteoarthritis (OA) has been determined, but the role of these cells in inflammation is still unclear. <h3>Objective</h3> To characterise TH-positive cells in inflamed RA and OA synovial tissue and to study their role in inflammation. <h3>Methods</h3> Synovial samples were obtained from 32 patients with OA and 19 patients with RA and from 10 control patients. Synovial tissue samples were used for immunofluorescence staining. Synovial cells were isolated by tissue digestion and immediately used for cell culture. For in vivo experiments, collagen type-II arthritis in DBA/1J mice was induced. <h3>Results</h3> TH+ cells were present only in inflamed tissue and not in controls. Catecholamine-storing vesicles and vesicular monoamine transporter 2 (VMAT2) were identified in the synovial tissue. Experimental increase of cytoplasmic catecholamines by VMAT2 blockade strongly reduced tumour necrosis factor (TNF) independently of canonical extracellular β-adrenergic signalling. In addition, VMAT2 blockade increased cyclic AMP (cAMP) and cAMP responsive element binding protein, responsible for TNF inhibition. In vivo, appearance of VMAT2 positive cells was confirmed. VMAT2 blockade ameliorated inflammation also in vivo. <h3>Conclusions</h3> This study demonstrates that local catecholamine-producing cells start to replace sympathetic nerve fibres around the onset of disease, and modulation of locally produced catecholamines has strong anti-inflammatory effects in vivo and in vitro.
Physicians Accessing the Internet, the PAI Project
Authors: Bonnie I. Chi-Lum
Journal: JAMA (1996)

Some of us have been expecting physicians to move en masse to use that wonderful beast of burden—the computer—for several decades.<sup>1</sup>But, with each new wave of exciting hardware, glitzy software, and mass promotion, physicians en masse have instead shunned routine personal use of computers in their education and practice. Of course, for decades physicians' offices and hospitals have used computers for scheduling and billing, their libraries for MEDLINE searches, their clinical laboratories for reporting laboratory results, and their imaging centers for advanced diagnosis with great success. And a number of physicians— mostly at large centers or as part of specialized professional groups like the American Medical Informatics Association— indeed are pushing the edge of the envelope when it comes to computer applications. Yet, personal direct computer use for medical purposes by hundreds of thousands of US physicians has lagged badly behind the capability of the systems and technology.
A medical icon
Authors: T. Dalrymple
Journal: BMJ (2011)

Several doctors have been diplomats but few have been both diplomats and Orthodox monks. This was the trajectory of the Russian Konstantin Leontiev (1831-91); he was also a novelist, dramatist, literary critic, belletrist, philosopher, and theologian. He knew both Turgenev and Tolstoy and wrote critically of the latter.

He was a somewhat reluctant medical student. He described his anatomical studies at Moscow University with clear distaste: “The sprawling bodies on the slabs of strangled old men, drunkards frozen stiff in the streets, murdered wantons, whose corpses the students tore to pieces, laughing and blaspheming in all sorts of ways.”

He regarded his fellow students as a bad …
The role of dipeptidyl peptidase-4 inhibitors
Authors: D. Lasserson, J. Mant
Journal: BMJ (2012)

Will be clearer once ongoing trials are complete 

Type 2 diabetes is a progressive disease and greater treatment intensity is needed over time to control increasingly abnormal glucose concentrations.1 In the linked article (doi:10.1136/bmj.e1369), Karagiannis and colleagues present a systematic review and meta-analysis of the risks and benefits associated with one of the relatively new classes of oral hypoglycaemic drugs, the dipeptidyl peptidase-4 (DPP-4) inhibitors.2

DPP-4 inhibitors reduce the breakdown of the glucose responsive incretin hormones, mainly glucagon-like peptide 1 (GLP-1); they have multiple physiological effects that together normalise glucose homeostasis without increasing body weight.3 Because GLP-1 is released in response to raised rather than normal glucose concentrations, DPP-4 inhibitors may be less likely to cause hypoglycaemia than other oral hypoglycaemic agents.3 Increased GLP-1 activity is associated with favourable changes in cardiovascular risk parameters of weight, lipids, blood pressure, and ventricular function, but no trials of DPP-4 inhibitors that are powered to detect differences in cardiovascular events have been reported.4

Karagiannis and colleagues examined two potential roles of DPP-4 inhibitors in type 2 diabetes: as monotherapy (compared with metformin) and …
Abstract 482: The HER-2 erbB receptor is vital for growth of breast cancer cells in bone
Authors: Scott J. Dawsey, Kathleen M. Woods Ignatoski, Kathleen C. Day
Journal: Cancer Research (2010)

Abstract HER-2 is a receptor tyrosine kinase that has been shown to be over expressed in 30% of human primary breast cancers (BrCa). Our animal model data and human bone met data, which we present here, indicates that HER-2 up-regulation is required for breast cancer cells to grow in and remodel bone. However, most bone metastases from BrCa will arise from a primary diagnosis of ER positive/HER-2 negative disease. We found that MCF-7 cells, an ER positive/HER-2 negative breast cancer model, formed tumors in bone that had up-regulated HER-2 protein expression. In order to directly test whether or not HER-2 expression has an affect on bone metastasis, we engineered a knock down of the HER-2 receptor in MCF-7 cells by utilizing a lentivirus plasmid containing the shRNA to the HER-2 receptor. Both the shRNA HER-2 knock-down and the vector-only control expressed the Green Fluorescence Protein (GFP) and puromycin resistance for plasmid selection. Our engineered MCF-7 control cells (shVector alone) or the HER-2 knock-down (shHER-2) were injected into the tibia of SCID mice. We found that both the vector-only and HER-2 knock-down cells grew tumors in mouse tibia. Anti-HER-2 immunohistochemical (IHC) analysis showed that the HER-2 protein was re-expressed in the knock down cells in tumors formed in tibiae. Additionally, we found that in eight patients with breast cancer bone metastasis, 100% of these cases contained a significant expression of HER-2 positive cells by IHC. As confirmation of our mouse studies, we found that all of the human bone biopsies obtained from ER positive/HER-2 negative disease were up-regulated for HER-2 in the bone microenvironment. Concomitant with our human data, MCF-7 cells required exogenous estrogen to form tumors in mammary fat pads and did not require exogenous estrogen to form tumors in bone. Therefore, we believe that BrCa cells can change, up-regulate protein expression of HER-2, and become estrogen independent in the bone microenvironment. It may be that these women could benefit from intervention with agents against HER-2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 482.
Two cases of refractory warm autoimmune hemolytic anemia treated with rituximab
Authors: S. Ramanathan, J. Koutts, M.S. Hertzberg
Journal: American Journal of Hematology (2005)

Autoimmune hemolytic anemia is thought to be mediated via auto-antibodies produced by lymphoid B cells. This may be an idiopathic process or secondary to an underlying infection or lymphoproliferative disorder. Conventional treatment comprises immunosuppression with corticosteroids and, in some cases, splenectomy. A proportion of patients require lifelong immunosuppression to maintain disease remission. Monoclonal antibody rituximab has gained widespread acceptance in the management of B-cell malignancies. Additionally, it has been used to treat disorders associated with auto-antibody production, such as cold hemagglutinin disease, immune thrombocytopenia, and Evans syndrome. Its use in the treatment of patients with autoimmune hemolytic anemia in the setting of allogeneic bone marrow transplantation as well as in patients with an underlying lymphoproliferative disease has also been reported. We report herein the successful use of rituximab in the treatment of two patients with idiopathic refractory warm autoimmune hemolytic anemia, who are still in remission at 15 and 9 months following treatment. Am. J. Hematol. 78:123–126, 2005. © 2005 Wiley-Liss,Inc.
Setting a strategy for health.
Authors: A. Smith
Journal: BMJ (1992)

The artificial limb and appliance centres were criticised in a report published in 1987 to the Department of Health by a committee chaired by Lord McColl.The committee suggested that the service could be improved Useful addresses: by raising the technical standards of amputation; by setting up specialistThe Royal Association For Disability and multidisciplinary hospital teams that would work in close cooperation with Rehabilitation (RADAR), 25 Mortimer Street, the medical staff at the centres and take an active part in rehabilitation; by London Wl 8AB, tel: 071-637 5400giving more responsibility to prosthetists and encouraging them to be British Limbless Ex-Servicemen's responsible for continuing care; and, finally, by restructuring of Association (BLESMA), 185-187 High Road, management.Some changes have already been implemented -such as the Frankland Moore House, Chadwell Heath, integration of the service into health regions with integrated budgets.Essex RM6 6NA, tel: 081-590-1124 Prosthetists may now tender for provision and service contracts, thus National Association for Limbless Disabled allowing them to become independent of the major suppliers of artificial (NALD), 31, The Mall, Ealing, London, W5 limbs.2PX,
Lymphomas 1, Including Hodgkin's Disease
Authors: Joseph M. Baron
Journal: JAMA (1982)

The first volume on lymphomas in the larger series of monographs in<i>Cancer Treatment and Research</i>provides an in-depth, multiauthored review of "Pathology" (Tindle), "Clinical Features" (Stein), "Radiographic Staging" (Hamlin), "Radiation Therapy" (Zagars and Rubin), and "Chemotherapy" (Glick). Juxtaposition of detailed material in these closely interacting specialty areas in the single volume emphasizes the importance of each aspect in achieving optimal current management of patients with lymphoma. The extensive written text is amply illustrated with photomicrographs and reproductions of x-ray films, ultrasonograms, and computed tomograms. Tabular summaries help in the presentation of extensive material cited from the literature. The single subject index for the complete volume makes for easy access to the text material. The comprehensive coverage of previous literature, extensive bibliographic citations, and careful objective coverage of newer aspects and areas of controversy make this volume an excellent reference for practicing clinical specialists, as well as a particularly helpful
Abstract 900: Associations between orotate phosphoribosyl transferase polymorphism and survival in patients with colorectal cancer treated with 5-FU-based adjuvant chemotherapy: A thirteen year follow-up study
Authors: Ching-Yu Lai, Shih-Ni Chang, Fung-Chang Sung, Ling-Ling Hsieh, Reiping Tang, Chih-Ching Yeh
Journal: Cancer Research (2010)

Abstract Introduction: 5-Fluorouracil (5-FU) is one of the first line anti-cancer drugs used in the chemotherapy for colorectal cancer (CRC) in older to raise survival rate. Orotate phosphoribosyl transferase (OPRT) plays an important role to regulate the 5-FU activity. This study examined the association between OPRT polymorphism and overall survival of CRC patients treated with 5-FU-based chemotherapy. Method: A total of 532 patients diagnosed with CRC and received 5-FU-based chemotherapy after surgery between 1995 January and 2001 December was included in the present study. We genotyped the OPRT G638C (Gly213Ala) polymorphism using the polymerase chain reaction combined with the restriction fragment length polymorphism analysis (PCR-RFLP). Survival analyses on OPRT polymorphism were displayed with Kaplan-Meier curves and performed with log-rank test. The association between OPRT genotypes and survival was analyzed using Cox proportional hazard models. Results: There were no significantly genetic effects on overall survival, even the adjustment for age, gender, or tumor stage in the Cox proportional hazard models. However, the Kaplan-Meier curves showed that stage II and III CRC patients with OPRT G/G genotype had a significantly poor survival (log-rank p = 0.02). Compared to the OPRT G/G genotype, the OPRT G/C + C/C genotype was significantly associated with better overall survival (Hazard ratio (HR) = 0.64, 95% CI = 0.43 − 0.96). Conclusion: Our findings suggest that the OPRT polymorphism may modify drugs activity to serve a prognostic predictor for CRC patients who receive 5-FU-based chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 900.
Curcumin Maintenance Therapy for Ulcerative Colitis: Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial
Authors: Hiroyuki Hanai, Takayuki Iida, Ken Takeuchi, Fumitoshi Watanabe, Yasuhiko Maruyama, Akira Andoh, Tomoyuki Tsujikawa, Yosihihide Fujiyama, Keiichi Mitsuyama, Michio Sata, Masami Yamada, Yasushi Iwaoka, Kazunari Kanke, Hideyuki Hiraishi, Kazuhisa Hirayama, Hajime Arai, Shigehito Yoshii, Masato Uchijima, Toshi Nagata, Yukio Koide
Journal: Clinical Gastroenterology and Hepatology (2006)
Health Care Quality Varies Widely Across the States
Authors: Mike Mitka
Journal: JAMA (2007)

ment to recognize the behaviors as inappropriate or unacceptable. Or they may lack the language skills to report feelings of distress. In producing the manual, Fletcher enlisted experts in intellectual disability and psychiatric conditions, and 3 to 6 authors wrote each chapter. The DM-ID text includes a description of each disorder, a summary of the DSM-IV diagnostic criteria, a review of the literature, and an evaluation of the strength of evidence supporting the literature conclusions. It discusses the etiology and pathogenesis of the disorders and provides adaptations of the diagnostic criteria for individuals with intellectual disability. The manual also covers special issues such as behavioral traits of genetic conditions.
PATHOGENESIS OF BRONCHITIS, IN INFANTS AND CHILDREN.Read in the Section on Diseases of Children at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: W. S. CHRISTOPHER
Journal: JAMA (1893)

The doctrine that bronchitis is the result of exposure to cold and moisture, is so generally accepted, that it is rather uncommon to lay stress upon the other factors which lead to it. And yet a consideration of the subject leads to the belief that these other factors are perhaps the more important and the more frequent causes. Your attention is therefore invited to a general consideration of the etiologic factors leading to bronchitis in infante and childhood. Many of the exanthemata have bronchitis as a concurrent symptom. Especially is this true of measles and rötheln. Influenza and whooping cough must also be included in the list of acute infectious diseases which present this condition. It is customary to speak of the bronchitis accompanying these diseases as a specific bronchitis. The qualifying title is very proper, but the bronchitis does not differ in any way from the same condition induced by
Hyperglucagonemia of Renal Failure
Authors: Gordon L. Bilbrey, Gerald R. Faloona, Martin G. White, James P. Knochel, Julio Borroto
Journal: Journal of Clinical Investigation (1974)

Elevation of plasma glucagon concentration has been observed in starvation and illnesses associated with increased catabolism such as diabetes mellitus and severe infections. Thus, we examined plasma glucose, immunoreactive insulin (IRI, microunits per milliliter) and glucagon (IRG, picograms per milliliter) responses to a beef meal (1 g/kg body wt) and intravenous glucose (1.5 g/min for 45 min) in patients with chronic renal failure (CRF).
Precautions With Supplemented Fasting
Authors: Victor Vertes
Journal: JAMA (1977)

To the Editor. —  Supplemented Fasting as a Large-Scale Outpatient Program (p 2151), reviews our results with 519 massively obese patients treated up to March 1976. Since that time, our total patient experience has enlarged to approximately 1,300.  Four instances of sudden death have now been seen in this enlarged series, three since acceptance of our manuscript. One was judged to be accidental, but three occurred in patients, aged 39 to 51 years and 115.3 to 144.6 kg in weight, who were found dead at home. Prior to institution of supplemented fasting, these three patients all evidenced cardiac disease (likely of coronary etiology) as well as one or more of the following risk factors: hypertension, hypertriglyceridemia, or diabetes.  Sudden death is a well-known hazard of coronary disease, and its frequency is reported to increase directly with body weight. 1 Its occasional occurrence in a large aggregation of obese persons, many
Southall plans new career as expert witness in child protection cases
Authors: C. Dyer
Journal: BMJ (2010)

David Southall, the paediatrician who was restored to the United Kingdom’s medical register last week, is about to relaunch himself as an expert witness in child abuse cases. Ten years after he last worked in child protection, but still a leading expert on fabricated or induced illness, he wants to help plug the gap left by doctors who are shunning the work for fear of career suicide.

After 24 inquiries into his work over the past 12 years by the General Medical Council, his employers, a government commissioned review, police, the attorney general, and even the fraud squad and the Charity Commission, the former professor of paediatrics still sees it as his mission to stop children being harmed.

Whether the way will now be clear for him to take up his shattered career again hinges on an imminent decision by the GMC. Dr Southall won his appeal against the council’s decision last year to strike him off the register but only on the basis that the fitness to practise panel gave inadequate reasons ( BMJ 2010;340:c2448, 4 May, doi:10.1136/bmj.c2448).

The Court of Appeal sent the case back to the GMC last week for rehearing by a new panel. But Lord Justice Leveson, who delivered judgment on behalf of all three judges, said that he was “far from convinced that the public interest would be served” by a rehearing of the factual allegation that Dr Southall had accused Mandy Morris, during an interview with her 12 years ago, of killing her child.

Dr Southall maintains, backed up by a social worker who was present, that he never made the accusation but merely outlined a range of scenarios.

It seems likely that the GMC, whose fitness to practise panel took him to task for “deep seated attitudinal problems” in the Mandy …
Bortezomib for Myeloma — Much Ado about Something
Authors: Angela Dispenzieri
Journal: New England Journal of Medicine (2005)

Multiple myeloma is a neoplastic plasma-cell dyscrasia that will cause more than 11,000 deaths in 2005 in the United States alone.1 The usefulness of the many therapies for multiple myeloma is limited, and virtually all patients eventually die from the disease. When thalidomide was shown to be effective against relapsed myeloma in 1999,2 more than 30 years had elapsed since a clinical response to any single agent had been reported in at least 25 percent of treated patients.35 By the early 2000s, it had become clear that another two agents — lenolidomide6 and bortezomib7 — had activity against malignant . . .
CD25+ CD4+ T Cells, Expanded with Dendritic Cells Presenting a Single Autoantigenic Peptide, Suppress Autoimmune Diabetes
Authors: Kristin V. Tarbell, Sayuri Yamazaki, Kara Olson, Priscilla Toy, Ralph M. Steinman
Journal: The Journal of Experimental Medicine (2004)

In the nonobese diabetic (NOD) mouse model of type 1 diabetes, the immune system recognizes many autoantigens expressed in pancreatic islet beta cells. To silence autoimmunity, we used dendritic cells (DCs) from NOD mice to expand CD25+ CD4+ suppressor T cells from BDC2.5 mice, which are specific for a single islet autoantigen. The expanded T cells were more suppressive in vitro than their freshly isolated counterparts, indicating that DCs from autoimmune mice can increase the number and function of antigen-specific, CD25+ CD4+ regulatory T cells. Importantly, only 5,000 expanded CD25+ CD4+ BDC2.5 T cells could block autoimmunity caused by diabetogenic T cells in NOD mice, whereas 10(5) polyclonal, CD25+ CD4+ T cells from NOD mice were inactive. When islets were examined in treated mice, insulitis development was blocked at early (3 wk) but not later (11 wk) time points. The expanded CD25+ CD4+ BDC2.5 T cells were effective even if administered 14 d after the diabetogenic T cells. Our data indicate that DCs can generate CD25+ CD4+ T cells that suppress autoimmune disease in vivo. This might be harnessed as a new avenue for immunotherapy, especially because CD25+ CD4+ regulatory cells responsive to a single autoantigen can inhibit diabetes mediated by reactivity to multiple antigens.
Endogenous opioid peptides in the pathogenesis of ascites
Authors: Jens H. Henriksen
Journal: Hepatology (1989)

Methionine enkephalin and catecholamines were measured in carefully collected plasma samples from 25 patients with cirrhosis and ascites, and 25 with cirrhosis without ascites, 15 disease and 15 healthy controls. Methionine enkephalin was invariably raised in the ascites group, the median value being 4.6-6.9 times that of the other three groups. Similarly, in the ascites group, median noradrenaline was increased 2.5-4.2 and median adrenaline 1.8-2.5 times that of the other groups. Plasma methionine enkephalin is considerably raised in patients with cirrhotic ascites and has actions which could enable it to be an initiating factor of ascites formation.
Quality Measures and the Individual Physician
Authors: Danielle Ofri
Journal: New England Journal of Medicine (2010)

additional costs associated with increased monitoring and reporting of industry relationships.These proposed changes in federal policy would represent a step toward creating a more organized, efficient, and effective system related to academic-industry relationships.Like all policy changes, however, they would be neither perfect nor easily implemented.Research relationships with industry should be allowed and even encouraged, but we must ensure that they are consistently disclosed and properly managed by institutions according to empirically based guidance.