tbuckley/cabot-search huggingface dataset:
Comparison of Dopamine and Norepinephrine in the Treatment of Shock
Authors: Daniel De Backer, Patrick Biston, Jacques Devriendt, Christian Madl, Didier Chochrad, Cesar Aldecoa, Alexandre Brasseur, Pierre Defrance, Philippe Gottignies, Jean-Louis Vincent
Journal: New England Journal of Medicine (2010)

Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other.In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events.The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses).Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)
Prurigo pigmentosa associated with ketosis
Authors: K. Murao, Y. Urano, N. Uchida, S. Arase
Journal: British Journal of Dermatology (1996)

Journal Article Prurigo pigmentosa associated with ketosis Get access K. Murao, K. Murao Department of Dermatology, School of Medicine, University of Tokushima, Tokushima 770, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Urano, Y. Urano Department of Dermatology, School of Medicine, University of Tokushima, Tokushima 770, Japan Search for other works by this author on: Oxford Academic Google Scholar N. Uchida, N. Uchida Department of Dermatology, School of Medicine, University of Tokushima, Tokushima 770, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Arase S. Arase Department of Dermatology, School of Medicine, University of Tokushima, Tokushima 770, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 2, 1 February 1996, Pages 379–381, https://doi.org/10.1111/j.1365-2133.1996.tb07643.x Published: 01 February 1996
Medroxyprogesterone for Acromegaly
Authors: Richard L. Atkinson
Journal: JAMA (1973)

To the Editor.—  In a case report of hyperosmolar nonketotic coma in an acromegalic patient (222:814, 1972), Paul Milloy dismisses the possibility that medroxyprogesterone acetate may have been a causative factor in the disorder. Our experience in a series of six acromegalic patients 1 treated for up to six months with medroxyprogesterone showed a deterioration in glucose tolerance in five of the six patients. Glucose tolerance gradually improved after therapy with medroxyprogesterone was stopped. Jackson and Ormston 2 had similar results in some of the acromegalics in their series, and Spellacy et al 3 and Gershberg et al 4 noted deterioration of glucose tolerance in nonacromegalics receiving medroxyprogesterone.  Since Milloy's patient was the first acromegalic with hyperosmolar nonketotic coma ever described, and since her condition was subsequently controlled with diet alone, it may be reasonable to assume the medroxyprogesterone had a role in the development of the syndrome.  Our data
Patterns of myoglobin release after reperfusion of injured myocardium.
Authors: A K Ellis, T Little, A R Zaki Masud, F J Klocke
Journal: Circulation (1985)

Myoglobin is an intracardiac protein that is released into the blood after myocardial injury and is then cleared rapidly by the kidneys. This study was undertaken to determine whether successful reperfusion of damaged myocardium could be assessed by examination of blood myoglobin concentration-time patterns. After release of a 2 hr occlusion of the mid left anterior descending coronary artery in 11 dogs that had been instrumented over the long term, immunoreactive arterial plasma concentration of myoglobin, [Mb], rose rapidly to a peak within 25 +/- 2(SEM) min (range 20 to 40). Individual peaks were three to 165 times the myoglobin levels immediately before release of the occlusion. Myoglobin was cleared rapidly from plasma, falling to one-half its peak level 38 +/- 3 min after the peak. Similarly well-defined peaks in [Mb] were evident in plasma from the great cardiac vein (GCV), with a mean time to peak of 16 +/- 2 min and a magnitude of two to 177 times prerelease values. In contrast, arterial and GCV creatine kinase activity-time curves showed less defined peaks and they occurred later and with more variability (60 to 330 min after reperfusion). In nine patients with acute infarction, successful coronary artery reopening was also accompanied by a sharp four- to sixteenfold rise in plasma [Mb] within 1 to 2 hr. Elevations in plasma creatine kinase were slower and more prolonged, peaking at 2 to 18 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of Relapsed Central Nervous System Lymphoma with High-Dose Methotrexate
Authors: Scott R. Plotkin, Rebecca A. Betensky, Fred H. Hochberg, Stuart A. Grossman, Glenn J. Lesser, L. Burt Nabors, Brian Chon, Tracy T. Batchelor
Journal: Clinical Cancer Research (2004)

Over the past decade, high-dose methotrexate has emerged as the single most effective agent in the initial treatment of primary nervous system lymphoma. However, the majority of patients who respond initially to treatment relapse. The optimal management of these patients has not been determined. We performed a multicenter, retrospective study of high-dose methotrexate in patients with relapsed central nervous system lymphoma.Patients with relapsed disease were eligible if they achieved a complete response to initial treatment with methotrexate-based chemotherapy or received methotrexate after gross total resection or interstitial radiation. All of the patients were retreated with a regimen containing high-dose methotrexate (>/=3 g/m(2)).Twenty-two patients with a median age of 58 years were included in the study. Overall response rates were 91% to first salvage (20 of 22 patients) and 100% to second salvage (4 of 4 patients). Median survival was 61.9 months after first relapse (95% confidence interval, 42.1- infinity ) and 91.9 months overall (95% confidence interval, 47.2- infinity ). Toxicity was primarily hematologic with 10 episodes of grade 3 or 4 toxicity during 566 cycles of chemotherapy.These results indicate that high-dose methotrexate remains effective for relapsed central nervous system lymphoma in patients who initially respond to methotrexate and raise the possibility of deferring more toxic salvage regimens in this select group of patients.
Malignant Histiocytosis
Authors: HENRY S. KINGDON
Journal: Annals of Internal Medicine (1970)

Two patients manifested the typical clinical and pathological features of malignant histiocytosis. Objective remissions of 3 months and 2 months, respectively, were induced by combination chemotherapy with vincristine and prednisone. The patients eventually died from complications of this rapidly progressive and uniformly fatal illness without significant prolongation of survival time. Combined chemotherapy may be useful for induction of remission in this disorder, and suitable maintenance programs should be developed.
Detection of Circulating Tumor Cells in Early-Stage Breast Cancer Metastasis to Axillary Lymph Nodes
Authors: Taku Nakagawa, Steve R. Martinez, Yasufumi Goto, Kazuo Koyanagi, Minoru Kitago, Tatsushi Shingai, David A. Elashoff, Xing Ye, Frederick R. Singer, Armando E. Giuliano, Dave S.B. Hoon
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Clinical and pathologic prognostic factors do not always accurately predict disease outcome. Patients with early-stage breast cancer may harbor clinically significant but undetected systemic disease. We hypothesized that a multimarker quantitative real-time reverse transcription-PCR (qRT) assay could detect circulating tumor cells (CTC) in patients with early-stage breast cancer and correlate with sentinel lymph node (SLN) and non-SLN metastasis status. Experimental Design: Blood samples from 90 women with the American Joint Committee on Cancer stages I to III breast cancer and 39 age-matched normal healthy volunteers were assessed by qRT for mRNA expression of three markers: stanniocalcin-1 (STC-1), N-acetylgalactosaminyltransferase (GalNacT), and melanoma antigen gene family-A3 (MAGE-A3). CTC biomarker detection was correlated with overall axillary LN (ALN), SLN, and non-SLN histopathology status. Results: CTCs were detected in 39 of 90 (43%) patients, but not in normal volunteers. At least one CTC biomarker was detected in 10 of 35 (29%) stage I patients, 19 of 42 (45%) stage II patients, and 10 of 13 (77%) stage III patients. In multivariate analysis, only lymphovascular invasion and ≥2 CTC biomarkers detected significantly correlated with ALN metastasis [odds ratio (OR), 12.42; 95% confidence interval (95% CI), 3.52-43.77, P &amp;lt; 0.0001; and OR, 3.88; 95% CI, 1.69-8.89, P = 0.001, respectively]. The number of CTC biomarkers detected similarly correlated with SLN and non-SLN metastasis status (P = 0.0004). At least one CTC biomarker was detected in 10 of 11 (91%) patients with non-SLN metastases. Conclusion: The detection of CTCs offers a novel means to assess the presence of systemic disease spreading relative to SLN and ALN histopathology status.
Angiotensin II Activates the Smad Pathway in Vascular Smooth Muscle Cells by a Transforming Growth Factor-β–Independent Mechanism
Authors: Juan Rodríguez-Vita, Elsa Sánchez-López, Vanesa Esteban, Mónica Rupérez, Jesús Egido, Marta Ruiz-Ortega
Journal: Circulation (2005)

Background— Angiotensin II (Ang II) participates in vascular fibrosis. Transforming growth factor-β (TGF-β) is considered the most important fibrotic factor, and Smad proteins are essential components of the TGF-β signaling system. Our aim was to investigate whether Ang II activates the Smad pathway in vascular cells and its potential role in fibrosis, evaluating connective tissue growth factor (CTGF) and extracellular matrix (ECM) proteins. Methods and Results— Systemic infusion of Ang II into Wistar rats increased aortic Smad2, phosphorylated-Smad2, and Smad4 expression, associated with CTGF upregulation. In growth-arrested vascular smooth muscle cells, Ang II treatment for 20 minutes caused Smad2 phosphorylation, nuclear translocation of phosphorylated-Smad2 and Smad4, and increased Smad DNA-binding activity. Ang II also caused Smad overexpression and Smad-dependent gene transcription. The AT 1 antagonist losartan diminished Ang II-induced Smad activation. The blockade of endogenous TGF-β did not modify the activation of Smad caused by Ang II. The p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 diminished Ang II-induced Smad2 phosphorylation. These data show that Ang II activates the Smad pathway via AT 1 receptors and MAPK activation independently of TGF-β. Transient transfection with Smad7, which interferes with receptor-mediated activation of Smad2, diminished Ang II-induced CTGF promoter activation, gene and protein expression, and fibronectin and type-1 procollagen overexpression, showing that Smad activation is involved in Ang II-induced fibrosis. Conclusions— Our results show that Ang II activates the Smad signaling system in vascular cells in vivo and in vitro. Smad proteins are involved in Ang II-induced CTGF and ECM overexpression independently of TGF-β. This novel finding suggests that Smad activation could be involved in the profibrogenic effects of Ang II in vascular diseases.
Flavone-8-Acetic Acid (Flavonoid) Profoundly Reduces Platelet-Dependent Thrombosis and Vasoconstriction After Deep Arterial Injury In Vivo
Authors: Jozef S. Mruk, Mark W. I. Webster, Magda Heras, Joel M. Reid, Diane E. Grill, James H. Chesebro
Journal: Circulation (2000)

Flavone-8-acetic acid (FAA; [Flavonoid]), an adjuvant antitumor drug, inhibits ristocetin-induced aggregation of human platelets. The effect of FAA on platelet-dependent thrombosis was studied in vivo in the porcine carotid artery after deep arterial injury by balloon angioplasty.(111)In-labeled autologous platelet and (125)I-labeled porcine fibrin(ogen) deposition, and the incidence of macroscopic mural thrombosis onto deeply injured artery (tunica media) were compared in 20 pigs (40+/-1 kg [mean+/-SEM], body surface area=1.0+/-0.1 m(2)), randomized to FAA bolus (n=10) of 5.5g/m(2), followed by an infusion at 0.14g. m(-2). min(-1) or placebo (n=10). Vasoconstriction was measured immediately beyond the dilated segment using quantitative angiography. Platelet deposition (x10(6)/cm(2) of carotid artery) was reduced over 12-fold in pigs treated with FAA (13+/-3 versus 164+/-51, P=0.001) compared with placebo. Fibrin(ogen) deposition (x10(12) molecules/cm(2) of carotid artery) did not significantly differ in FAA-treated pigs versus placebo (40+/-8 versus 140+/-69, P=0.08). Large mural thrombi were present in 100% of placebo-treated pigs versus very small thrombi in 40% of FAA-treated pigs (P=0.005). Vasoconstriction was reduced from 46+/-6% in the placebo group to 15+/-3% in the FAA group (P<0.001). Plasma level of FAA before angioplasty was 515+/-23 microgram/mL. The activated partial thromboplastin time was unchanged. The bleeding time was >2SD above the normal mean in 4 of 5 treated pigs (increased from 157+/-29 to 522+/-123 s).FAA markedly reduced platelet deposition, mural thrombi, and injury-induced vasoconstriction after deep arterial injury, suggesting that a major inhibition of platelet glycoprotein Ibalpha may be beneficial therapy.
EFFECTS OF INTRADERMAL GAMMA-INTERFERON IN CUTANEOUS LEISHMANIASIS
Authors: G. Harms, A.K. Chéhadé, P. Racz, M. Douba, R.D. Naiff, H. Feldmeier, K. Zwingenberger, S. Talhari, A. Mouakeh, L. Näkel, P.G. Kremsner, U. Bienzle
Journal: The Lancet (1989)
Specific Clinical and Biological Features Characterize Inflammatory Bowel Disease–Associated Colorectal Cancers Showing Microsatellite Instability
Authors: Magali Svrcek, Jamila El-Bchiri, Alexandra Chalastanis, Emilie Capel, Sylvie Dumont, Olivier Buhard, Carla Oliveira, Raquel Seruca, Céline Bossard, Jean-François Mosnier, Françoise Berger, Emmanuelle Leteurtre, Anne Lavergne-Slove, Marie-Pierre Chenard, Richard Hamelin, Jacques Cosnes, Laurent Beaugerie, Emmanuel Tiret, Alex Duval, Jean-François Fléjou
Journal: Journal of Clinical Oncology (2007)

Microsatellite instability (MSI) due to mismatch repair (MMR) deficiency has been reported to occur at variable frequencies in inflammatory bowel disease-associated intestinal neoplasias (IBD-Ns). We investigated a large series of IBD-N for associations between MSI and several biologic and clinical parameters related to tumors, patients, and their treatment.A total of 277 IBD-Ns in 205 patients were screened for MSI. Biologic and clinical variables of patients with high levels of DNA microsatellite instability high (MSI-H) were collected and compared with those associated with 33 MSI-H non-IBD colorectal cancers (CRCs).A total of 27 IBD-Ns from 17 patients were found to be MSI-H. Compared with sporadic MSI-H CRCs, patients presented with a younger age at diagnosis, and there was no female predominance and no right-sided predominance. Unlike sporadic MSI-H CRCs, MSI-H IBD-Ns presented with heterogeneous mismatch repair defects involving MLH1, MSH2, MSH6, or PMS2, and a low frequency of MLH1 promoter methylation. They exhibited frequent BRAF mutations and frameshift mutations in genes containing coding repeat sequences.The mechanisms underlying MMR deficiency in MSI-H IBD-Ns are different from those in sporadic MSI-H tumors and seem to be more related to those observed in hereditary MSI-H tumors. However, BRAF mutations were observed in MSI-H IBD-Ns, similar to sporadic MSI-H tumors, but unlike hereditary MSI-H tumors. Finally, the mutational events in target genes for instability are the same in MSI-H IBD-N tumors as in non-IBD sporadic and hereditary colorectal MSI-H cancers, indicating a colon-related repertoire of target gene alterations.
Thymic Stromal Lymphopoietin (TSLP) Expression in Chronic Rhinosinusitis
Authors: A. Kato, A. Peters, R. Chandra, M.R. Comeau, E.A. Rickel, A.L. Budelsky, L. Suh, K.E. Harris, D. Conley, L.C. Grammer
Journal: Journal of Allergy and Clinical Immunology (2009)
Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK
Authors: J Gribbin, R B Hubbard, I Le Jeune, C J P Smith, J West, L J Tata
Journal: Thorax (2006)

Idiopathic pulmonary fibrosis (IPF) and sarcoidosis are common diagnoses in patients attending chest clinics, but little is known about the epidemiology of these diseases. We used data from a general practice database to provide information on the current incidence of IPF and sarcoidosis in the UK.Data were extracted for all patients with a diagnosis of IPF or sarcoidosis between 1991 and 2003. The whole population of the database was used to calculate disease incidence stratified by age, sex, region, and time period. Poisson regression was used to compare the incidence between populations and Cox regression was used to compare survival between populations.920 cases of IPF (mean age 71 years, 62% male) and 1019 cases of sarcoidosis (mean age 47 years, 47% male) were identified. The overall incidence rate per 100 000 person-years was 4.6 for IPF and 5.0 for sarcoidosis. The incidence of IPF increased progressively between 1991 and 2003 (p<0.00001), and was highest in Northern England and Scotland (p<0.0001). The survival of patients with IPF was stable over time. In contrast, the incidence of sarcoidosis was highest in London, West Midlands and Northern Ireland and remained stable over time.The incidence of IPF has more than doubled between 1990 and 2003; this is not due to the ageing of the UK population or an increased ascertainment of milder cases. The incidence of sarcoidosis has not changed during this time period. Our findings suggest that more than 4000 new cases of IPF and 3000 new cases of sarcoidosis are currently diagnosed each year in the UK.
Ectopic lymphoid neogenesis in psoriatic arthritis
Authors: J. D Canete, B. Santiago, T. Cantaert, R. Sanmarti, A. Palacin, R. Celis, E. Graell, B. Gil-Torregrosa, D. Baeten, J. L Pablos
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium, where it is thought to drive local antigen-dependent B cell development and autoantibody production. This process involves the expression of specific homing chemokines and the development of high endothelial venules (HEV). <b>Objective:</b> To investigate whether these mechanisms occur in psoriatic arthritis (PsA) synovium, where autoantibodies have not been described and the organisation and function of B cells is not clear, and to analyse their clinical correlates. <b>Methods:</b> Arthroscopic synovial biopsy specimens from patients with PsA before and after tumour necrosis factor α blockade were characterised by immunohistochemical analysis for T/B cell segregation, peripheral lymph node addressin (PNAd)-positive HEV, and the expression of CXCL13, CCL21 and CXCL12 chemokines in relation to the size of lymphoid aggregates. <b>Results:</b> Lymphoid aggregates of variable sizes were observed in 25 of 27 PsA synovial tissues. T/B cell segregation was often observed, and was correlated with the size of lymphoid aggregates. A close relationship between the presence of large and highly organised aggregates, the development of PNAd+ HEV, and the expression of CXCL13 and CCL21 was found. Large organised aggregates with all LN features were found in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern or severity of the disease. The synovial LN pattern remained stable over time in persistent synovitis, but a complete response to treatment was associated with a regression of the LN features. <b>Conclusions:</b> LN occurs frequently in inflamed PsA synovial tissues. Highly organised follicles display the characteristic features of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the microanatomical bases for germinal centre formation are present in PsA. The regression of LN on effective treatment indicates that the pathogenic and clinical relevance of these structures in PsA merits further investigation.
Value of magnetic resonance angiography for the detection of intracranial aneurysms in autosomal dominant polycystic kidney disease.
Authors: J Huston, V E Torres, P P Sulivan, K P Offord, D O Wiebers
Journal: Journal of the American Society of Nephrology (1993)

The association of intracranial aneurysms with autosomal dominant polycystic kidney disease (ADPKD), the 30-day mortality rate exceeding 50% for aneurysmal rupture, the effectiveness of surgical repair of unruptured aneurysms with a low surgical risk, and the development of noninvasive imaging techniques for their detection have led physicians to consider the value of screening patients with ADPKD for unruptured intracranial aneurysms. The sensitivity and specificity of high-resolution computed tomography and magnetic resonance imaging for the diagnosis of small intracranial aneurysms have been disappointing. To determine the value of magnetic resonance angiography (MRA), 85 patients with ADPKD without symptoms related to an intracranial aneurysm and 2 patients with ADPKD presenting with a subarachnoid hemorrhage or a suspected aneurysmal leak were studied. MRA was performed with the Multisequence Vascular Package (GE Medical Systems) with use of three-dimensional time-of-flight and three-dimensional phase-contrast techniques, and postprocessing maximum intensity projection images were generated to eliminate the problem of overlapping vessels. Asymptomatic intracranial aneurysms were detected in 6 (22%) of 27 patients with and 3 (5%) of 56 patients without a family history of intracranial aneurysm or subarachnoid hemorrhage (P = 0.02, information missing in 2 patients) and in the 2 patients who presented with a symptomatic aneurysm. A stepwise logistic regression analysis indicated that a family history of intracranial aneurysm or subarachnoid hemorrhage was independently associated with the presence of intracranial aneurysms. All of the aneurysms were < or = 6.5 mm in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)