tbuckley/cabot-search huggingface dataset:
Dose-related patterns of glucocorticoid-induced side effects
Authors: D Huscher, K Thiele, E Gromnica-Ihle, G Hein, W Demary, R Dreher, A Zink, F Buttgereit
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To identify patterns of self-reported health problems relating to dose and duration of glucocorticoid intake in unselected patients with rheumatoid arthritis from routine practice. <h3>Methods:</h3> Data from 1066 patients were analysed. The clinical status and drug treatment were reported by the physician, health problems during the past 6 months by the patient using a comprehensive list of symptoms. Patients with ongoing glucocorticoid treatment for more than 6 months and current doses of less than 5, 5–7.5 and over 7.5 mg/day prednisone equivalent were compared with a group without any glucocorticoid treatment for at least 12 months. <h3>Results:</h3> The frequency of self-reported health problems was lowest in the group without glucocorticoid exposition and increased with dosage. Two distinct dose-related patterns of adverse events were observed. A "linear" rising with increasing dose was found for cushingoid phenotype, ecchymosis, leg oedema, mycosis, parchment-like skin, shortness of breath and sleep disturbance. A "threshold pattern" describing an elevated frequency of events beyond a certain threshold value was observed at dosages of over 7.5 mg/day for glaucoma, depression/listlessness and increase in blood pressure. Dosages of 5 mg/day or more were associated with epistaxis and weight gain. A very low threshold was seen for eye cataract (&lt;5 mg/day). <h3>Conclusion:</h3> The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit–risk ratio.
Prognostic Implication of Anemia on In-Hospital Outcomes After Percutaneous Coronary Intervention
Authors: Ronald S. McKechnie, Dean Smith, Cecelia Montoye, Eva Kline-Rogers, Michael J. O’Donnell, Anthony C. DeFranco, William L. Meengs, Richard McNamara, John G. McGinnity, Kirit Patel, David Share, Arthur Riba, Sanjaya Khanal, Mauro Moscucci
Journal: Circulation (2004)

Background— Although prior studies have shown a relationship between anemia and in-hospital mortality after coronary artery bypass grafting and acute myocardial infarction (MI), the prognostic implication of anemia in patients undergoing percutaneous coronary intervention (PCI) is unknown. Therefore, we evaluated the relationship between anemia and outcomes of PCI. Methods and Results— Clinical and outcome data on 48 851 consecutive PCIs were prospectively collected. Patients were classified as anemic using the World Health Organization definition (&lt;12.0 g/dL in women and &lt;13.0 g/dL in men). A total of 6471 men (21.7%) and 4659 women (30.4%) were anemic. Anemic men and women were older and had a higher percentage of comorbidities compared with their nonanemic cohorts ( P &lt;0.0001 for all comparisons). When compared with nonanemic patients, anemic patients had higher in-hospital mortality (3.0% versus 0.8% in men; 2.4% versus 1.5% in women; P ≤0.0001) and postprocedural MI (2.0% versus 1.6% in men; 2.4% versus 1.6% in women; P ≤0.02) and a higher combined major cardiovascular events end point, including death, MI, and cerebrovascular event (5.0% versus 2.6% in men; 5.1% versus 3.5% in women; P &lt;0.0001). After adjustment for comorbidities, anemia was associated with a higher risk of in-hospital mortality (odds ratio [OR], 2.29; 95% CI, 1.79 to 2.92; P &lt;0.0001) and MI (OR, 1.34; 95% CI, 1.05 to 1.72; P =0.02) and major cardiovascular events (OR, 1.2; 95% CI, 1.05 to 1.34). Significant gender interactions were observed for death in men and for MI in women. Conclusions— Preprocedural anemia is associated with increased adverse in-hospital outcomes after PCI. Whether optimization of hemoglobin before PCI is of clinical benefit will need to be determined in a randomized clinical trial.
Lithium's Antisuicidal Efficacy: Elucidation of Neurobiological Targets Using Endophenotype Strategies
Authors: Colleen E. Kovacsics, Irving I. Gottesman, Todd D. Gould
Journal: The Annual Review of Pharmacology and Toxicology (2008)

Lithium used as a drug treatment for major mental disorders such as bipolar disorder and depression is effective in reducing the risk of both attempted and completed suicide. However, the mechanisms underlying lithium's antisuicidal actions are not yet known, limiting the development of novel lithium-mimetic compounds that may help reduce suicide risk with fewer undesirable side effects. Suicide is a complex behavior, complicated to study in humans, and impossible to fully reproduce in animal models. The endophenotype approach, by which quantitative measures of neurobiological function are used to assess and subclassify psychiatric illness, may present a path to new discoveries. Aggression and impulsivity are candidate endophenotypes strongly associated with suicide; we review the evidence supporting aggression and impulsivity as suicide endophenotypes, as well as the effects of lithium on these constructs in both humans and rodents. Examining the mechanisms that contribute to lithium's antiaggressive and antiimpulsive effects may assist in understanding how lithium acts to reduce the risk of suicide and in elucidating the neurobiological underpinnings of suicidal behavior.
BLOOD PLASMA PROTEIN PRODUCTION AS INFLUENCED BY VARIOUS DEGREES OF HYPOPROTEINEMIA AND BY AMINO ACIDS
Authors: S. C. Madden, A. P. Turner, A. P. Rowe, G. H. Whipple
Journal: The Journal of Experimental Medicine (1941)

When blood plasma proteins are depleted by bleeding with return of the washed red blood cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal but their resistance to infection is distinctly below normal. Introduction of variables into this standardized existence gives information relative to plasma protein production. Plasma protein production under these conditions with a plasma protein concentration of 3.5 to 4.2 gm. per cent is relatively constant. As the plasma protein concentration rises the plasma protein removed falls rapidly (Table 1). At 4.6 gm. per cent the protein removed is less than 50 per cent of the amount removed at a plasma protein level of 4.0 gm. per cent. Cystine appears to be an important amino acid for plasma protein formation. This shows in Table 2 and is supported by data coming from published experiments. These experiments related to the factors which control plasma protein production bear on the problems of shock, hemorrhage, and protein wastage and their treatment by plasma injections which hold the attention of surgeons and physiologists at the moment. Again we would emphasize the fluidity of body protein including plasma protein-an ebb and flow between protein depots and plasma protein-a "dynamic equilibrium" of body protein. A discussion of the passage of large protein molecules through cell borders is submitted.
Intracoronary Delivery of Hematopoietic Bone Marrow Stem Cells and Luminal Loss of the Infarct-Related Artery in Patients With Recent Myocardial Infarction
Authors: Samer Mansour, Marc Vanderheyden, Bernard De Bruyne, Bart Vandekerckhove, Leen Delrue, Inge Van Haute, Guy Heyndrickx, Stephane Carlier, Gaston Rodriguez-Granillo, William Wijns, Jozef Bartunek
Journal: Journal of the American College of Cardiology (2006)
Two-years of a community maintenance follow-up program in patients with COPD
Authors: Fabricio Zambom, Pilar Cebollero, María Hernández, Esteban Gorostiaga, Javier Ibañez, Javier Hueto, José Cascante, Milagros Antón
Journal: European Respiratory Journal (2012)

Introduction: Benefits of short-term outpatient rehabilitation programs (RP) have been showed in patients with COPD that decline gradually over one year after discharge. Moreover, the capacity of maintenance follow-up programs to preserve the benefits of pulmonary rehabilitation programs is controversial.

Therefore, the objective of this study was to examine the efficacy of a two year, supervised, community maintenance follow-up program to maintain the benefits of an initial 12-week outpatient RP.

Methods: Eight patients (moderate to severe) COPD men (GOLD), dyspnea 2-3 (MMRC) were included. All patients performed a two years, supervised, community maintenance program (CMP)(twice a week) following a 12-week outpatient rehabilitation program (twice a week). Maximal dynamic resistance (1RM) of the upper limb (chest press and dorsal) and lower limb (leg press and leg extension), and peak power output at 70% of 1RM in leg press were measured. Analysis of variance with repeated measures was used for statistical analysis.

Results: Initial data from the RP were used as a baseline for all outcomes. 1RM in leg press increased (P <0.001) by 20% in RP and 22% in CMP from baseline. 1RM in chest press increased (P <0.001) by 32% in RP and 45% in CMP. 1RM in knee extension and dorsal increased (P <0.001) by 36 and 35% in RP and 38 and 35% in CMP, respectively. Power output of the lower limb at 70% of 1RM increased by 33% in RP and 30% in CMP (from 555 ± 108 to 738 ± 312 to 720 ± 258 w, P <0.05) from baseline.

Conclusions: A low volume, supervised, CMP is able to maintain and improve the benefits of a short-term RP in COPD patients.

Supported by Ministry of education of Spain and Health Department of Navarre.
Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-β signaling from tumor suppression to oncogenesis in early chronic hepatitis B
Authors: Miki Murata, Koichi Matsuzaki, Katsunori Yoshida, Go Sekimoto, Yoshiya Tahashi, Shigeo Mori, Yoshiko Uemura, Noriko Sakaida, Junichi Fujisawa, Toshihito Seki, Kazuki Kobayashi, Koutaro Yokote, Kazuhiko Koike, Kazuichi Okazaki
Journal: Hepatology (2008)

Hepatitis B virus X (HBx) protein is suspected to participate in oncogenesis during chronic hepatitis B progression. Transforming growth factor beta (TGF-beta) signaling involves both tumor suppression and oncogenesis. TGF-beta activates TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Reversible shifting of Smad3-mediated signaling between tumor suppression and oncogenesis in HBx-expressing hepatocytes indicated that TbetaRI-dependent pSmad3C transmitted a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promoted cell growth. We used immunostaining, immunoblotting, and in vitro kinase assay to compare pSmad3L- and pSmad3C-mediated signaling in biopsy specimens representing chronic hepatitis, cirrhosis, or hepatocellular carcinoma (HCC) from 90 patients chronically infected with hepatitis B virus (HBV) with signaling in liver specimens from HBx transgenic mice. In proportion to plasma HBV DNA levels, early chronic hepatitis B specimens showed prominence of pSmad3L in hepatocytic nuclei. HBx-activated JNK/pSmad3L/c-Myc oncogenic pathway was enhanced, while the TbetaRI/pSmad3C/p21(WAF1) tumor-suppressive pathway was impaired as human and mouse HBx-associated hepatocarcinogenesis progressed. Of 28 patients with chronic hepatitis B who showed strong oncogenic pSmad3L signaling, six developed HCC within 12 years; only one of 32 patients showing little pSmad3L developed HCC. In contrast, seven of 30 patients with little Smad3C phosphorylation developed HCC, while no patient who retained hepatocytic tumor-suppressive pSmad3C developed HCC within 12 years.HBx shifts hepatocytic TGF-beta signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway in early carcinogenic process. Hepatocytic pSmad3L and pSmad3C assessment in HBV-infected liver specimens should prove clinically useful for predicting risk of HCC.
Emergency hospital admissions via accident and emergency departments in England: time trend, conceptual framework and policy implications
Authors: Thomas E Cowling, Michael A Soljak, Derek Bell, Azeem Majeed
Journal: Journal of the Royal Society of Medicine (2014)

The urgent and emergency care services in England’s National Health Service (NHS) are currently the subject of a national review. The existing system, which is experiencing increases in demand, has been described as unaffordable, unsustainable and fragmented.1 In August 2013, the Prime Minister’s Office and Department of Health announced that an additional £500 million would be made available to relieve pressures on accident and emergency (A&E) departments.2 Since then, the National Audit Office and Public Accounts Committee have both published reports on emergency admissions to hospital, focusing on the management of demand and the value gained from public expenditure.3,4 In this article, we briefly review the current roles of A&E departments in England and then describe how the proportion of emergency hospital admissions that occurred via A&E departments increased from 2001–2002 to 2010–2011. We present a conceptual framework for helping to explain this trend and discuss the potential implications for national policy.
A System of Practical Surgery.
Journal: JAMA (1904)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Fluoroquinolone Therapy for the Prevention of Multidrug-Resistant Tuberculosis in Contacts. A Cost-Effectiveness Analysis
Authors: Gregory J. Fox, Olivia Oxlade, Dick Menzies
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Fluoroquinolone (FQN) therapy of latent tuberculosis infection among contacts of individuals with multidrug-resistant tuberculosis (MDR-TB) is controversial.To determine the potential benefits, risks (including acquired FQN resistance), and cost-effectiveness of FQN therapy to prevent TB in contacts of individuals with MDR-TB.We used decision analysis to estimate costs and outcomes associated with no therapy compared with a 6-month course of daily FQN therapy to treat latent TB infection in contacts of individuals with MDR-TB. Outcomes modeled were the incidence of MDR-TB, MDR-TB with FQN resistance, TB-related death, quality-adjusted life years, and health system costs.FQN preventive therapy resulted in health system savings, lower incidence of MDR-TB, and lower mortality than no treatment. We found the incidence of MDR-TB with acquired FQN resistance would also be lower with FQN therapy of infected contacts.In our model, FQN preventive therapy resulted in substantial health system savings and in reduced mortality, incidence of MDR-TB, and incidence of acquired FQN-resistant disease as well as improved quality of life. FQN therapy remained cost saving with improved outcomes even if the effectiveness of therapy in preventing MDR-TB was as low as 10%.
Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes.
Authors: M B Goldring, J R Birkhead, L F Suen, R Yamin, S Mizuno, J Glowacki, J L Arbiser, J F Apperley
Journal: Journal of Clinical Investigation (1994)

Immortalized human chondrocytes were established by transfection of primary cultures of juvenile costal chondro- cytes with vectors encoding simian virus 40 large T antigen and selection in suspension culture over agarose.Stable cell lines were generated that exhibited chondrocyte morphology, continuous proliferative capacity (> 80 passages) in monolayer culture in serum-containing medium, and ex- pression of mRNAs encoding chondrocyte-specific collagens II, IX, and XI and proteoglycans in an insulin-containing serum substitute.They did not express type X collagen or versican mRNA.These cells synthesized and secreted extra- cellular matrix molecules that were reactive with mono- clonal antibodies against type II collagen, large proteoglycan (PG-H, aggrecan), and chondroitin-4-and chondroitin-6sulfate. Interleukin-1,8 (IL-1p) decreased the levels of type II collagen mRNA and increased the levels of mRNAs for collagenase, stromelysin, and immediate early genes (egr-1, c-fos, c-jun, and jun-B).These cell lines also expressed reporter gene constructs containing regulatory sequences (-577/+3,428 bp) of the type II collagen gene (COL2A1) in transient transfection experiments, and IL-1p8 suppressed this expression by 50-80%.These results show that immor- talized human chondrocytes displaying cartilage-specific modulation by IL-1,3 can be used as a model for studying normal and pathological repair mechanisms.(
Phase I Clinical Trial of the Chimeric Anti-Mesothelin Monoclonal Antibody MORAb-009 in Patients with Mesothelin-Expressing Cancers
Authors: Raffit Hassan, Steven J. Cohen, Martin Phillips, Ira Pastan, Elad Sharon, Ronan J. Kelly, Charles Schweizer, Susan Weil, Daniel Laheru
Journal: Clinical Cancer Research (2010)

MORAb-009 is a chimeric monoclonal antibody that targets mesothelin, a tumor differentiation antigen overexpressed in pancreatic cancer, ovarian cancer, mesothelioma, and other malignancies. We conducted a phase I clinical trial of MORAb-009 in patients with advanced mesothelin-expressing cancers to determine its safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD).Cohorts consisting of 3 to 6 subjects each received MORAb-009 intravenously on days 1, 8, 15, and 22 at progressively increasing doses ranging from 12.5 to 400 mg/m(2). Disease evaluation with computed tomography occurred on day 35. Subjects with responding or stable disease could receive additional cycles of MORAb-009.A total of 24 subjects were treated including 13 mesothelioma, 7 pancreatic cancer, and 4 ovarian cancer patients. The median number of MORAb-009 infusions was 4 (range 1-24 infusions). At the 400 mg/m(2) dose level, 2 subjects experienced DLT (grade 4 transaminitis and a grade 3 serum sickness). Thus, although there were other contributing causes of these adverse events, 200 mg/m(2) was considered the MTD. Other adverse events at least possibly related to MORAb-009 included 7 drug hypersensitivity events (all grade 1 or 2) and a thromboembolic event (grade 4). Eleven subjects had stable disease. There was a dose-dependent increase in serum MORAb-009 concentration.MORAb-009 is well tolerated and the MTD when administered weekly is conservatively set at 200 mg/m(2). In this group of previously treated patients, 11 subjects had stable disease. Phase II studies of MORAb-009 in different mesothelin-expressing cancers are ongoing.
Personality and Risk of Physical Illness
Authors: Timothy W. Smith, Justin MacKenzie
Journal: Annual Review of Clinical Psychology (2006)

Several personality characteristics have been linked in multiple well-designed prospective studies to subsequent physical health outcomes, such as longevity and the development and course of cardiovascular disease. The evidence is strongest for negative affectivity/neuroticism, anger/hostility and related traits, and optimism. Models of mechanisms underlying these associations have emphasized physiological effects of stress, exposure to stressors, and health behavior. Preliminary evidence supports the viability of some mechanisms, but formal mediational tests are lacking. In addition to addressing limitations and inconsistencies in this literature, future research should address developmental aspects of these psychosocial risk factors, contextual moderators of their health effects, and intervention applications in the prevention and management of disease. In these efforts, greater incorporation of concepts and methods in the structural, social-cognitive, and interpersonal perspectives in the field of personality are needed.
Assessment of intraparenchymal lung collateral ventilation
Authors: Marco Anile, Daniele Diso, Federico Venuta
Journal: Thorax (2012)

We read with interest the paper of Marshall et al entitled ‘Direct visualisation of collateral ventilation in COPD with hyperpolarised gas MRI’.1 Collateral ventilation (CV) is defined as ‘the ventilation of alveolar structures through passages that bypass the normal airway’.2 This happens through the intra-alveolar pores of Kohn, the bronchioloalveolar communications of Lambert and the intrabronchiolar pathways of Martin. These pathways exist in normal lungs, but CV is ineffective since flow resistance is 50 times greater than through the normal airway. In emphysematous lungs, the alveolar wall destruction enlarges the accessory pathways and the presence of airway obstruction increases expiratory resistance; this allows gas to move freely from one …
Long-Term Amiodarone Administration Remodels Expression of Ion Channel Transcripts in the Mouse Heart
Authors: Sabrina Le Bouter, Aziza El Harchi, Céline Marionneau, Chloé Bellocq, Arnaud Chambellan, Toon van Veen, Christophe Boixel, Bruno Gavillet, Hugues Abriel, Khai Le Quang, Jean-Christophe Chevalier, Gilles Lande, Jean J. Léger, Flavien Charpentier, Denis Escande, Sophie Demolombe
Journal: Circulation (2004)

The basis for the unique effectiveness of long-term amiodarone treatment on cardiac arrhythmias is incompletely understood. The present study investigated the pharmacogenomic profile of amiodarone on genes encoding ion-channel subunits.Adult male mice were treated for 6 weeks with vehicle or oral amiodarone at 30, 90, or 180 mg x kg(-1) x d(-1). Plasma and myocardial levels of amiodarone and N-desethylamiodarone increased dose-dependently, reaching therapeutic ranges observed in human. Plasma triiodothyronine levels decreased, whereas reverse triiodothyronine levels increased in amiodarone-treated animals. In ECG recordings, amiodarone dose-dependently prolonged the RR, PR, QRS, and corrected QT intervals. Specific microarrays containing probes for the complete ion-channel repertoire (IonChips) and real-time reverse transcription-polymerase chain reaction experiments demonstrated that amiodarone induced a dose-dependent remodeling in multiple ion-channel subunits. Genes encoding Na+ (SCN4A, SCN5A, SCN1B), connexin (GJA1), Ca2+ (CaCNA1C), and K+ channels (KCNA5, KCNB1, KCND2) were downregulated. In patch-clamp experiments, lower expression of K+ and Na+ channel genes was associated with decreased I(to,f), I(K,slow), and I(Na) currents. Inversely, other K+ channel alpha- and beta-subunits, such as KCNA4, KCNK1, KCNAB1, and KCNE3, were upregulated.Long-term amiodarone treatment induces a dose-dependent remodeling of ion-channel expression that is correlated with the cardiac electrophysiologic effects of the drug. This profile cannot be attributed solely to the amiodarone-induced cardiac hypothyroidism syndrome. Thus, in addition to the direct effect of the drug on membrane proteins, part of the therapeutic action of long-term amiodarone treatment is likely related to its effect on ion-channel transcripts.