tbuckley/cabot-search huggingface dataset:
The potential role of acid suppression in functional dyspepsia: the BOND, OPERA, PILOT, and ENCORE studies
Authors: N J Talley, K Lauritsen
Journal: Gut (2002)

Dyspepsia is a common condition in the general population but data are lacking on the benefits of effective acid inhibition with proton pump inhibitors in functional dyspepsia. The results of the large, randomised, double blind clinical trials, BOND and OPERA, the Scandinavian PILOT study, and a follow up study, ENCORE, are reviewed. BOND, OPERA, and PILOT aimed to address the question of whether effective acid inhibition with the proton pump inhibitor omeprazole relieves symptoms in patients with functional dyspepsia. ENCORE followed on from this, addressing the consequences of relieving symptoms in patients with functional dyspepsia once they are off therapy.
Cyclosporin A markedly enhances superantigen-induced peripheral T cell deletion and inhibits anergy induction.
Authors: L E Vanier, G J Prud'homme
Journal: The Journal of Experimental Medicine (1992)

Cyclosporin A (CsA) is a well-known immunosuppressive agent that modulates immune tolerance in many ways. CsA can give rise to a state of long-term nonimmunosuppressed transplantation tolerance, but it can also aggravate autoimmune diseases, and provoke specific forms of autoimmunity. These effects, which are often paradoxical, remain largely unexplained. In this study, we investigated the effects of CsA on superantigen (superAg)-reactive peripheral T cells. The intravenous injection of either staphylococcal enterotoxin B (SEB), or Mls-1a cells into Mls-1b recipients, causes long-term in vitro nonresponsiveness (anergy) and partial elimination of the peripheral T cell receptor (TCR) V beta 8+/CD4+ and -V beta 6+/CD4+ T cell subsets, respectively. We report that CsA markedly enhances the peripheral elimination of SEB- and Mls-1a-reactive T cells such that up to 90% of the targeted CD4+/V beta subpopulations are deleted. The degree of deletion depends on the dose and the schedule of CsA administration, and the number of superAg injections. In situations where the extent of deletion is only moderate, we find that the remaining superAg-reactive T cells fail to develop anergy, unlike the T cells of control superAg-immunized mice. Higher doses of CsA are required to enhance T cell deletion (greater than or equal to 25 mg/kg/d, i.p.) than to impair anergy induction (greater than or equal to 6.25 mg/kg/d, i.p.). In view of these results, it appears that the degree of tolerance in CsA/superAg-treated mice depends on the balance between these opposing effects, i.e., enhancement of peripheral elimination versus the abrogation of anergy. The possibility of enhancing or preventing immune tolerance with a drug may have important clinical implications.
Impact of Cardiac Rehabilitation on Mortality and Cardiovascular Events After Percutaneous Coronary Intervention in the Community
Authors: Kashish Goel, Ryan J. Lennon, R. Thomas Tilbury, Ray W. Squires, Randal J. Thomas
Journal: Circulation (2011)

Although numerous studies have reported that cardiac rehabilitation (CR) is associated with reduced mortality after myocardial infarction, less is known about its association with mortality after percutaneous coronary intervention.We performed a retrospective analysis of data from a prospectively collected registry of 2395 consecutive patients who underwent percutaneous coronary intervention in Olmsted County, Minnesota, from 1994 to 2008. The association of CR with all-cause mortality, cardiac mortality, myocardial infarction, or revascularization was assessed with 3 statistical techniques: propensity score--matched analysis (n=1438), propensity score stratification (n=2351), and regression adjustment with propensity score in a 3-month landmark analysis (n=2009). During a median follow-up of 6.3 years, 503 deaths (199 cardiac), 394 myocardial infarctions, and 755 revascularization procedures occurred in the study subjects. Participation in CR, noted in 40% (964 of 2395) of the cohort, was associated with a significant decrease in all-cause mortality by all 3 statistical techniques (hazard ratio, 0.53 to 0.55; P<0.001). A trend toward decreased cardiac mortality was also observed in CR participants; however, no effect was observed for subsequent myocardial infarction or revascularization. The association between CR participation and reduced mortality rates was similar for men and women, for older and younger patients, and for patients undergoing elective or nonelective percutaneous coronary intervention.We found that CR participation after percutaneous coronary intervention was associated with a significant reduction in mortality rates. These findings add support to published clinical practice guidelines, performance measures, and insurance coverage policies that recommend CR for patients after percutaneous coronary intervention.
Does Microalbuminuria Predict Diabetic Nephropathy?
Authors: Han-Henrik Parving, Nish Chaturvedi, GianCarlo Viberti, Carl Erik Mogensen
Journal: Diabetes Care (2002)

Tabaei et al. (1) conclude that “Microalbuminuria may not be as sensitive and specific a predictor of diabetic nephropathy as previously suggested. Other markers of risk for diabetic nephropathy are needed for optimal clinical management.”

This conclusion is based on a 7-year follow-up study of nine (eight women) normotensive type 1 diabetic patients with microalbuminuria and seven middle-aged normotensive type 2 diabetic patients (mainly women) with microalbuminuria. Their conclusions and proposals should be interpreted …
IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis
Authors: Iannis E Adamopoulos, Erika Suzuki, Cheng-Chi Chao, Dan Gorman, Sarvesh Adda, Emanual Maverakis, Konstantinos Zarbalis, Richard Geissler, Agelio Asio, Wendy M Blumenschein, Terrill Mcclanahan, Rene De Waal Malefyt, M Eric Gershwin, Edward P Bowman
Journal: Annals of the Rheumatic Diseases (2014)

Background Psoriatic arthritis (PsA) is a chronic inflammatory disease characterised by clinical features that include bone loss and epidermal hyperplasia. Aberrant cytokine expression has been linked to joint and skin pathology; however, it is unclear which cytokines are critical for disease initiation. Interleukin 17A (IL-17A) participates in many pathological immune responses; however, its role in PsA has not been fully elucidated. Objective To determine the role of IL-17A in epidermal hyperplasia and bone destruction associated with psoriatic arthritis. Design An in vivo gene transfer approach was used to investigate the role of IL-17A in animal models of inflammatory (collagen-induced arthritis) and non-inflammatory (receptor activator of NF-κB ligand (RANKL)-gene transfer) bone loss. Results IL-17A gene transfer induced the expansion of IL-17RA + CD11b + Gr1 low osteoclast precursors and a concomitant elevation of biomarkers indicative of bone resorption. This occurred at a time preceding noticeable joint inflammation, suggesting that IL-17A is critical for the induction of pathological bone resorption through direct activation of osteoclast precursors. Moreover, IL-17A induced a second myeloid population CD11b + Gr1 high neutrophil-like cells, which was associated with cutaneous pathology including epidermal hyperplasia, parakeratosis and Munro's microabscesses formation. Conclusions Collectively, these data support that IL-17A can play a key role in the pathogenesis of inflammation-associated arthritis and/or skin disease, as observed in PsA.
Sarcoplasmic Reticulum Ca <sup>2+</sup> Release Causes Myocyte Depolarization
Authors: Klaus Schlotthauer, Donald M. Bers
Journal: Circulation Research (2000)

Spontaneous sarcoplasmic reticulum (SR) Ca(2+) release causes delayed afterdepolarizations (DADs) via Ca(2+)-induced transient inward currents (I:(ti)). However, no quantitative data exists regarding (1) Ca(2+) dependence of DADs, (2) Ca(2+) required to depolarize the cell to threshold and trigger an action potential (AP), or (3) relative contributions of Ca(2+)-activated currents to DADs. To address these points, we evoked SR Ca(2+) release by rapid application of caffeine in indo 1-AM-loaded rabbit ventricular myocytes and measured caffeine-induced DADs (cDADs) with whole-cell current clamp. The SR Ca(2+) load of the myocyte was varied by different AP frequencies. The cDAD amplitude doubled for every 88+/-8 nmol/L of Delta[Ca(2+)](i) (simple exponential), and the Delta[Ca(2+)](i) threshold of 424+/-58 nmol/L was sufficient to trigger an AP. Blocking Na(+)-Ca(2+) exchange current (I(Na/Ca)) by removal of [Na](o) and [Ca(2+)](o) (or with 5 mmol/L Ni(2+)) reduced cDADs by >90%, for the same Delta[Ca(2+)](i). In contrast, blockade of Ca(2+)-activated Cl(-) current (I(Cl(Ca))) with 50 micromol/L niflumate did not significantly alter cDADs. We conclude that DADs are almost entirely due to I(Na/Ca), not I(Cl(Ca)) or Ca(2+)-activated nonselective cation current. To trigger an AP requires 30 to 40 micromol/L cytosolic Ca(2+) or a [Ca(2+)](i) transient of 424 nmol/L. Current injection, simulating I(ti)s with different time courses, revealed that faster I:(ti)s require less charge for AP triggering. Given that spontaneous SR Ca(2+) release occurs in waves, which are slower than cDADs or fast I(ti)s, the true Delta[Ca(2+)](i) threshold for AP activation may be approximately 3-fold higher in normal myocytes. This provides a safety margin against arrhythmia in normal ventricular myocytes.
Phase I Study Utilizing a Novel Antigen-Presenting Cell–Targeted Vaccine with Toll-like Receptor Stimulation to Induce Immunity to Self-antigens in Cancer Patients
Authors: Michael A. Morse, Robert Chapman, John Powderly, Kimberly Blackwell, Tibor Keler, Jennifer Green, Renee Riggs, Li-Zhen He, Venky Ramakrishna, Laura Vitale, Biwei Zhao, Stephen A. Butler, Amy Hobeika, Takuya Osada, Thomas Davis, Timothy Clay, H. Kim Lyerly
Journal: Clinical Cancer Research (2011)

The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken by immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); however, targeting tumor antigen directly to APC in vivo would be a less complicated strategy. We wished to test whether targeted delivery of an otherwise poorly immunogenic, soluble antigen to APC through their mannose receptors (MR) would induce clinically relevant immunity.Two phase I studies were conducted with CDX-1307, a vaccine composed of human chorionic gonadotropin beta-chain (hCG-β) fused to an MR-specific monoclonal antibody, administered either locally (intradermally) or systemically (intravenously) in patients with advanced epithelial malignancies. An initial dose escalation of single-agent CDX-1307 was followed by additional cohorts of CDX-1307 combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) and the Toll-like receptor (TLR) 3 agonist polyinosinic-polycytidylic acid (poly-ICLC) and TLR7/8 agonist resiquimod to activate the APC.CDX-1307 induced consistent humoral and T-cell responses to hCG-β when coadministered with TLR agonists. Greater immune responses and clinical benefit, including the longest duration of stable disease, were observed with immunization combined with local TLR agonists. Immune responses were induced equally efficiently in patients with elevated and nonelevated levels of serum hCG-β. Antibodies within the serum of vaccinated participants had tumor suppressive function in vitro. Toxicity consisted chiefly of mild injection site reactions.APC targeting and activation induce adaptive immunity against poorly immunogenic self-antigens which has implications for enhancing the efficacy of cancer immunotherapy.
Association Between a Hospital’s Rate of Cardiac Arrest Incidence and Cardiac Arrest Survival
Authors: Lena M. Chen, Brahmajee K. Nallamothu, John A. Spertus, Yan Li, Paul S. Chan
Journal: JAMA Internal Medicine (2013)

IMPORTANCE National efforts to measure hospital performance in treating cardiac arrest have focused on case survival, with the hope of improving survival after cardiac arrest.However, it is plausible that hospitals with high case-survival rates do a poor job of preventing cardiac arrests in the first place.OBJECTIVE To describe the association between inpatient cardiac arrest incidence and survival rates.DESIGN Within a large, national registry, we identified hospitals with at least 50 adult in-hospital cardiac arrest cases between January 1, 2000, and November 30, 2009.We used multivariable hierarchical regression to evaluate the correlation between a hospital's cardiac arrest incidence rate and its case-survival rate after adjusting for patient and hospital characteristics. MAIN OUTCOMES AND MEASURESThe correlation between a hospital's incidence rate and case-survival rate for cardiac arrest. RESULTSOf 102 153 cases at 358 hospitals, the median hospital cardiac arrest incidence rate was 4.02 per 1000 admissions (interquartile range, 2.95-5.65 per 1000 admissions), and the median hospital case-survival rate was 18.8% (interquartile range, 14.5%-22.6%).In crude analyses, hospitals with higher case-survival rates also had lower cardiac arrest incidence (r, -0.16; P = .003).This relationship persisted after adjusting for patient characteristics (r, -0.15; P = .004).After adjusting for potential mediators of this relationship (ie, hospital characteristics), the relationship between incidence and case survival was attenuated (r, -0.07; P = .18).The one modifiable hospital factor that most attenuated this relationship was a hospital's nurse-to-bed ratio (r, -0.12; P = .03).CONCLUSIONS AND RELEVANCE Hospitals with exceptional rates of survival for in-hospital cardiac arrest are also better at preventing cardiac arrests, even after adjusting for patient case mix.This relationship is partially mediated by measured hospital attributes.Performance measures focused on case-survival rates seem an appropriate first step in quality measurement for in-hospital cardiac arrest.
DOES CARDIAC RHYTHM ALONE DETERMINE HUMAN BLOOD PRESSURE VARIATIONS?
Authors: Carl J. Wiggers
Journal: The Journal of Experimental Medicine (1914)

Changes in cardiac rhythm are not the only determinants of blood pressure variations in man. They play a part in the variations of systolic and diastolic pressures, the relative importance of which depends on the degree of arhythmia present and on the depth of respiration which, in itself, causes the systolic and diastolic pressures to decrease during inspiration and increase during expiration. No degree of rate variation can be regarded as a type. The cases range from those in which respiration governs the change of pressures entirely through those where more or less complicated mixtures of heart rate and respiratory influences intermingle to those in which extreme cardiac variations alone determine the pressure changes. The emphatic insistence of Henderson and his collaborators that heart rate changes play a more important part than is commonly recognized in man is true in many cases. That, in certain cases, it is the only determining influence may also be admitted, but they are in the minority. The majority show the intervention of a respiratory influence which controls, at least, the variations of systolic pressure. In the light of these results, the doctrine that, in man, an effective venous pressure exists sufficient during all respiratory phases to insure superimposable beats, must be subjected to further reinvestigation.
SOME EFFECTS OF ARTIFICIAL HEAT ON THE CIRCULATION IN COLD TEMPERATE CLIMATES
Authors: R. F. Fox
Journal: BMJ (1935)

occurred with such a heavy excretion of sugar per se, whether the insulin acted or not.The essential criterion, the unvarying ketosis, showed that no appreciable insulin action took place.The clinical condition and the post-mortem findings indicated no important abnormality, except the cardiac condition.To this, therefore, the failure in insulin action might be ascribed.But the pulse pressure, the absence of oedema, hepatomegaly, and venous congestion, and the high volume of urine showed that a reasonably adequate circulation was being maintained until just before death.We feel, therefore, that the heart condition does not explain the failure of insulin action, and the case seems worth recording.Summary A case of diabetes is recorded which failed to respond to h4undreds of units of insulin a day.
Tumor Growth Rate Provides Useful Information to Evaluate Sorafenib and Everolimus Treatment in Metastatic Renal Cell Carcinoma Patients: An Integrated Analysis of the TARGET and RECORD Phase 3 Trial Data
Authors: Charles Ferté, Serge Koscielny, Laurence Albiges, Laurence Rocher, Jean-Charles Soria, Roberto Iacovelli, Yohann Loriot, Karim Fizazi, Bernard Escudier
Journal: European Urology (2013)
Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40–60 years
Authors: J J Cornelissen, J Versluis, J R Passweg, W L J van Putten, M G Manz, J Maertens, H B Beverloo, P J M Valk, M van Marwijk Kooy, P W Wijermans, M R Schaafsma, B J Biemond, M-C Vekemans, D A Breems, L F Verdonck, M F Fey, M Jongen-Lavrencic, J J W M Janssen, G Huls, J Kuball, T Pabst, C Graux, H C Schouten, A Gratwohl, E Vellenga, G Ossenkoppele, B Löwenberg
Journal: Leukemia (2014)
Cancer Mortality Following Treatment for Adult Hyperthyroidism
Authors: Elaine Ron
Journal: JAMA (1998)

Context.—High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic 131I to the development of cancer, its extensive medical use indicates the need for additional evaluation.Objective.—To evaluate cancer mortality among hyperthyroid patients, particularly after 131I treatment.Design.—A retrospective cohort study.Setting.—Twenty-five clinics in the United States and 1 clinic in England.Patients.—A total of 35,593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91% had Graves disease, 79% were female, and 65% were treated with 131I.Main Outcome Measure.—Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism.Results.—Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86).Conclusions.—Neither hyperthyroidism nor 131I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following 131I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, 131I appears to be a safe therapy for hyperthyroidism.
High-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors.
Authors: R J Motzer, M Mazumdar, D F Bajorin, G J Bosl, P Lyn, V Vlamis
Journal: Journal of Clinical Oncology (1997)

PURPOSE A treatment program that included high-dose carboplatin, etoposide, and cyclophosphamide (CEC) followed by autologous bone marrow transplantation (AuBMT) was investigated as first-line therapy in patients with poor-risk germ cell tumors (GCTs). PATIENTS AND METHODS Previously untreated GCT patients with poor-risk features were treated with etoposide, ifosfamide, and cisplatin (VIP) with or without high-dose CEC plus AuBMT. Patients qualified for a change to high-dose CEC if a prolonged clearance of elevated serum tumor markers was observed after two cycles of the cisplatin-containing regimen. RESULTS Sixteen patients were treated with VIP alone and 14 with VIP and high-dose CEC. Seventeen patients (57%) achieved a complete response. Twenty are alive (67%) and 15 (50%) are free of disease at a median follow-up time of 30 months. For 23 cycles of high-dose CEC, the median time from AuBMT to a granulocyte count &gt; or = 0.5/microL was 11 days (range, 0 to 14) and to a platelet count 50,000/microL, 19 days (range, 14 to 34). The survival of 58 patients treated in two of our center's programs that incorporated high-dose chemotherapy (high-dose carboplatin plus etoposide [CE] and CEC) was compared with our prior experience with conventional-dose cisplatin chemotherapy alone in poor-risk GCT. Patients treated with marker-dependent, early-intervention high-dose chemotherapy experienced longer survival (P = .001). CONCLUSION In this setting, high-dose CEC was well tolerated, cumulative toxicity was lacking, and the recovery of blood counts after AuBMT was rapid. A randomized trial has been initiated to investigate further the role of high-dose CEC in first-line therapy for patients with poor-risk GCT.