tbuckley/cabot-search huggingface dataset:
AMOEBIC ABSCESS OF THE LIVER
Authors: R. J. M. Love
Journal: BMJ (1918)

LIVER, [JUNE 22, 1g98 arrived, according to the officer on duty, " recovered from his slhock and in excellent condition."It seems probable that if this case had been transfused immediately he would never have (leveloped the shock which, untreated, would undoubtedly have meant his death before-he reached the casualtyclearing station. Concltssion.A-lthouglh there has been opportunity to carry out the operation on a very few cases as yet, there is no doubt thlat blood transfusion by the syringe method can be done easily in an A.D.S., and, in the writer's opinion, could be done in an average regimental aid post; and by its use sorne cases of severe primary haemorrhage which would in the natural course of events die in the forward area will live to reach the casualty clearing station.
Effect of Experimental Chronic Renal Insufficiency on Bone Mineral and Collagen Maturation
Authors: J. E. Russell, L. V. Avioli
Journal: Journal of Clinical Investigation (1972)

The effect of chronic renal disease on bone matrix and mineral maturation was evaluated in rats with experimental renal insufficiency of 2-11 wk duration utilizing bromoform-toluene gradient fractionation of bone powder, pulse labeling experiments with 45Ca and proline-3H differential extraction, and X-ray diffraction techniques.
Short Notes on the Treatment of Lupus Vulgaris with "T.R." Tuberculin
Authors: G. G. S. Taylor
Journal: BMJ (1898)

A large variety of preparations of thyroid is employed in the treatment of obesity, myxcedema, and other ailments.Perhaps the tablets of the dried extract are the most popular.But none of the extracted preparations commonly used con- taini all the active ingredients in the same form or proportion as they are found to exist in the gland itself.Last spring I obtained from Mr. E. C. C. Stanford, F.I.C., F.C.S., whose researches on iodine are so well known, a new preparation of the active ingredients-thyroglandin.I have made numerous trials of this substance in a number of cases of obesity, and in one case of myxcedema.CASE I. Obesity.-B.McR., aged 21 married, complained of rapidly increasing gain of flesh, with debility and great shortness of breath on exertion.She was put on I grain of thyroglandin thrice daily for a few days.The dose was then rapidly increased until g grains in the day were being taken.The decrease in weight was as follows: June ist, 12st.41b.; Junle x2th, iIst.io lb. ; July ioth, IISt. 2 lb., August zoth, iost.81b.September 4th, iost.lb. ; September2gth, xost.ilb.Since last date this patient has been taking about i grain daily, and her weight remains fairly stationary.CASE II.Obesity.--R.C, aged 46, married, multipara, consulted me on account of her obesity and dyspncea.She was put on I grain of thyro- glandinithrice daily, and as this dose was well tolerated it was rapidly increased to 9 grains in the day.
Susceptibility of leishmania to oxygen intermediates and killing by normal macrophages
Authors: HW Murray
Journal: The Journal of Experimental Medicine (1981)

This study demonstrates that the promastigote form of virulent Leishmania donovani and Leishmania tropica are both deficient in endogenous enzymatic scavengers of H(2)0(2) (catalase, glutathione peroxidase) and susceptible to low fluxes of H(2)O(2) in a cell-free model. In addition, the killing of promastigotes by H(2)0(2) is markedly enhanced in the presence of a peroxidase and halide. Promastigotes also readily trigger the macrophage oxidative burst including the generation of H(2)0(2), and most intracellular promastigotes are killed within 18 h by unstimulated normal resident cells. Catalase, but not scavengers or quenchers of O(2)(-), OHx, or (1)O(2), protected promastigotes in a cell-free xanthine oxidase microbicidal system, and catalase also partially inhibited the leishmanicidal activity of resident macrophages. Thus, amongst various oxygen intermediates, H(2)0(2) alone appeared to be both necessary and sufficient for promastigote killing. Depriving macrophages of exogenous glucose, which inhibits the generation of oxygen intermediates, achieved effects similar to catalase treatment. These observations directly contrast with the intracellular parasite, T. gondii which is richly endowed with catalase and glutathione peroxidase, highly resistant to H(2)0(2), and requires products of O(2)(-)-H(2)0(2) interaction for effective oxidative killing. Toxoplasmas also fail to trigger the respiratory burst of normal macrophages, and readily multiply within these cells (1-5). Macrophages first activated by in vivo or in vitro immunologic stimuli, however, display an enhanced capacity to generate oxygen intermediates beyond O(2)(-) and H(2)0(2), and are able to kill toxoplasmas or inhibit their intracellular replication (1, 2). These studies illustrate the wide spectrum of susceptibility to oxidative products which appears to exist for virulent intracellular protozoans, and indicate that such differences may be reflected in contrasting fates of parasites within cell-free oxidative environments and the cytoplasm of normal resident macrophages. In addition, these observations also demonstrate that nonactivated phagocytes may display effective microbicidal activity against certain intracellular pathogens utilizing an oxygen-dependent mechanism.
Fatal Food-Induced Anaphylaxis
Authors: J W Yunginger, K G Sweeney, W Q Sturner, L A Giannandrea, J D Teigland, M Bray, P A Benson, J A York, L Biedrzycki, D L Squillace
Journal: JAMA (1988)

Fatal food-induced anaphylaxis is rarely reported. In 16 months, we identified seven such cases involving five males and two females, aged 11 to 43 years. All victims were atopic with multiple prior anaphylactic episodes after ingestion of the incriminated food (peanut, four; pecan, one; crab, one; fish, one). In six cases the allergenic food was ingested away from home. Factors contributing to the severity of individual reactions included denial of symptoms, concomitant intake of alcohol, reliance on oral antihistamines alone to treat symptoms, and adrenal suppression by chronic glucocorticoid therapy for coexisting asthma. In no case was epinephrine administered immediately after onset of symptoms. Premortem or postmortem serum samples were available from six victims; in each case elevated levels of IgE antibodies to the incriminated food were demonstrated. Food-sensitive individuals must self-administer epinephrine promptly at the first sign of systemic reaction. Emergency care providers should be aware of cricothyrotomy as a life-saving procedure.
β <sub>3</sub> Adrenergic Stimulation of the Cardiac Na <sup>+</sup> -K <sup>+</sup> Pump by Reversal of an Inhibitory Oxidative Modification
Authors: Henning Bundgaard, Chia-Chi Liu, Alvaro Garcia, Elisha J. Hamilton, Yifei Huang, Karin K.M. Chia, Stephen N. Hunyor, Gemma A. Figtree, Helge H. Rasmussen
Journal: Circulation (2010)

Background— Inhibition of L-type Ca 2+ current contributes to negative inotropy of β 3 adrenergic receptor (β 3 AR) activation, but effects on other determinants of excitation-contraction coupling are not known. Of these, the Na + -K + pump is of particular interest because of adverse effects attributed to high cardiac myocyte Na + levels and upregulation of the β 3 AR in heart failure. Methods and Results— We voltage clamped rabbit ventricular myocytes and identified electrogenic Na + -K + pump current ( I p ) as the shift in holding current induced by ouabain. The synthetic β 3 AR agonists BRL37344 and CL316,243 and the natural agonist norepinephrine increased I p . Pump stimulation was insensitive to the β 1 /β 2 AR antagonist nadolol and the protein kinase A inhibitor H-89 but sensitive to the β 3 AR antagonist L-748,337. Blockade of nitric oxide synthase abolished pump stimulation and an increase in fluorescence of myocytes loaded with a nitric oxide–sensitive dye. Exposure of myocytes to β 3 AR agonists decreased β 1 Na + -K + pump subunit glutathionylation, an oxidative modification that causes pump inhibition. The in vivo relevance of this was indicated by an increase in myocardial β 1 pump subunit glutathionylation with elimination of β 3 AR–mediated signaling in β 3 AR −/− mice. The in vivo effect of BRL37344 on contractility of the nonfailing and failing heart in sheep was consistent with a beneficial effect of Na + -K + pump stimulation in heart failure. Conclusions— The β 3 AR mediates decreased β 1 subunit glutathionylation and Na + -K + pump stimulation in the heart. Upregulation of the receptor in heart failure may be a beneficial mechanism that facilitates the export of excess Na + .
The Disparate Twins: A Comparative Study of CXCR4 and CXCR7 in SDF-1α–Induced Gene Expression, Invasion and Chemosensitivity of Colon Cancer
Authors: Doreen Heckmann, Patrick Maier, Stephanie Laufs, Li Li, Jonathan P. Sleeman, Marcus J. Trunk, Jörg H. Leupold, Frederik Wenz, W. Jens Zeller, Stefan Fruehauf, Heike Allgayer
Journal: Clinical Cancer Research (2013)

In colorectal cancer, increased expression of the CXC chemokine receptor 4 (CXCR4) has been shown to provoke metastatic disease due to the interaction with its ligand stromal cell-derived factor-1 (SDF-1). Recently, a second SDF-1 receptor, CXCR7, was found to enhance tumor growth in solid tumors. Albeit signaling cascades via SDF-1/CXCR4 have been intensively studied, the significance of the SDF-1/CXCR7-induced intracellular communication triggering malignancy is still only marginally understood.In tumor tissue of 52 patients with colorectal cancer, we observed that expression of CXCR7 and CXCR4 increased with tumor stage and tumor size. Asking whether activation of CXCR4 or CXCR7 might result in a similar expression pattern, we performed microarray expression analyses using lentivirally CXCR4- and/or CXCR7-overexpressing SW480 colon cancer cell lines with and without stimulation by SDF-1α.Gene regulation via SDF-1α/CXCR4 and SDF-1α/CXCR7 was completely different and partly antidromic. Differentially regulated genes were assigned by gene ontology to migration, proliferation, and lipid metabolic processes. Expressions of AKR1C3, AXL, C5, IGFBP7, IL24, RRAS, and TNNC1 were confirmed by quantitative real-time PCR. Using the in silico gene set enrichment analysis, we showed that expressions of miR-217 and miR-218 were increased in CXCR4 and reduced in CXCR7 cells after stimulation with SDF-1α. Functionally, exposure to SDF-1α increased invasiveness of CXCR4 and CXCR7 cells, AXL knockdown hampered invasion. Compared with controls, CXCR4 cells showed increased sensitivity against 5-FU, whereas CXCR7 cells were more chemoresistant.These opposing results for CXCR4- or CXCR7-overexpressing colon carcinoma cells demand an unexpected attention in the clinical application of chemokine receptor antagonists such as plerixafor.
Tumor Heterogeneity and Permeability as Measured on the CT Component of PET/CT Predict Survival in Patients with Non–Small Cell Lung Cancer
Authors: Thida Win, Kenneth A. Miles, Sam M. Janes, Balaji Ganeshan, Manu Shastry, Raymondo Endozo, Marie Meagher, Robert I. Shortman, Simon Wan, Irfan Kayani, Peter J. Ell, Ashley M. Groves
Journal: Clinical Cancer Research (2013)

Abstract Purpose: We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging parameters in patients with non–small cell lung cancer (NSCLC). Experimental Design: The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 ± 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 ± 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUVmax). The mean follow-up periods were 22.6 ± 13.3 months and 28.5± 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan–Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence. Results: Univariate analysis revealed that tumor CT-derived heterogeneity (P &amp;lt; 0.001), PET-derived heterogeneity (P = 0.003), CT-derived permeability (P = 0.002), and stage (P &amp;lt; 0·001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUVmax did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P = 0.021), stage (P = 0.001), and permeability (P &amp;lt; 0.001) were independent survival predictors. These predictors were independent of patient treatment. Conclusions: Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC. Clin Cancer Res; 19(13); 3591–9. ©2013 AACR.
Inherited predisposition to pancreatic cancer
Authors: E EFTHIMIOU
Journal: Gut (2001)

Pancreatic cancer is the fifth leading cause of death from cancer in men and women in Europe and North America. The prognosis has not changed significantly despite improvements in diagnosis and perioperative management. Traditional chemotherapy and radiotherapy regimens have been rather ineffective in providing control of the disease.1 

The only consistent risk factor identified so far is smoking and possibly accounts for a quarter of all cases of pancreatic cancer.2 Diabetes mellitus is another factor associated with an increased risk for the development of pancreatic cancer although it is still unclear if diabetes is a cause or an effect of malignant disease in the organ.3 Surgical resection offers the best chance of prolongation in survival. Unfortunately, in more than 80% of cases, at the time of diagnosis the cancer is either locally advanced or disseminated thus excluding curative resection. Hope for making an appreciable impact on survival has been focused on two areas: early diagnosis of pancreatic precancer and introduction of new therapeutic modalities based on the molecular and genetic abnormalities identified in the disease.4 

Studies have shown an increased risk of pancreatic cancer among relatives of patients with pancreatic cancer (7.8% compared with 0.6% in controls), with no apparent differences in the environmental risk exposures observed in the two groups.5Similar observations were made by Fernandez et al in a study in which 362 histologically confirmed pancreatic cancer cases were compared with 1408 patients admitted to hospital for acute, benign, non-digestive tract disorders. A significant association was noted between a family history of pancreatic cancer and the risk of developing pancreatic cancer (odds ratio 3.0, 95% confidence intervals 1.4–6.6). Even after adjustment for factors such as tobacco consumption, alcohol intake, pancreatitis, and diabetes, the risk of pancreatic cancer remained almost the same in patients …
NATURAL KILLER CELL DEVELOPMENTAL PATHWAYS: A Question of Balance
Authors: James P. Di Santo
Journal: Annual Review of Immunology (2006)

NK cells sit at the crossroads of innate and adaptive immunity and help coordinate tumor immunosurveillance and the immune response against pathogens. Balancing signals to NK cell precursors is crucial for their early development, when transcription factors compete to specify the different lymphocyte subsets. Despite an elaborate schema for NK cell development and differentiation, several major issues remain to be addressed, such as identifying the sites for NK cell maturation and defining the peripheral NK cell niche.
Ethnic Differences in the Vasoconstrictor Activity of Endogenous Endothelin-1 in Hypertensive Patients
Authors: Umberto Campia, Carmine Cardillo, Julio A. Panza
Journal: Circulation (2004)

The pathogenesis of essential hypertension in blacks may differ from that in whites. In particular, black patients usually present with a salt-sensitive, low-renin form, which in animal models is associated with enhanced activity of endothelin-1 (ET-1). This study aimed to assess whether ethnic differences exist in the vascular activity of ET-1 in normotensive and hypertensive blacks and whites.Forearm blood flow (FBF) responses to intraarterial infusion of an ET(A) receptor blocker (BQ-123) were analyzed by plethysmography in 37 normotensive patients and 27 hypertensive patients according to race. BQ-123 did not affect FBF in normotensive subjects (P=0.30), whereas it produced significant vasodilation in hypertensive subjects (P<0.001). In normotensives, FBF response to BQ-123 was similar in white (n =22) and black (n =15) patients (P=0.85). In contrast, in hypertensive patients, the vasodilator effect of ET(A) receptor blockade was significantly higher in blacks (n =13) than in whites (n =14) (P=0.01). To rule out differences in smooth muscle reactivity, the effects of race on FBF responses to exogenous ET-1 were analyzed in the hypertensive subgroups. Endothelin-1 induced a significant vasoconstriction in both white (n =7) and black patients (n =5) (both P<0.001), without differences between them (P=0.46). In 8 black hypertensives, the response to selective ET(A) blockade was not modified by nonselective blockade of ET-1 receptors by co-infusion of BQ-123 and BQ-788 (P=0.66).Hypertensive blacks have enhanced ET(A)-dependent vasoconstrictor tone, probably related to increased production of ET-1. Given the negative vascular effects of ET-1, this abnormality may contribute to the pathogenesis of hypertension and its complications in black patients.
Initial Clinical Experience With the Jarvik 2000 Implantable Axial-Flow Left Ventricular Assist System
Authors: O. H. Frazier, Timothy J. Myers, Igor D. Gregoric, Tehreen Khan, Reynolds Delgado, Mihai Croitoru, Kathy Miller, Robert Jarvik, Stephen Westaby
Journal: Circulation (2002)

Implantable left ventricular assist systems (LVASs) are used for bridging to transplantation, bridging to myocardial improvement, and for permanent circulatory support. Conventional implantable systems have inherent limitations that increase morbidity during support. In contrast, small, efficient, axial-flow pumps, which have been under development for the past decade, have the potential to improve the length and quality of life in patients with severe heart failure. Methods and Results- To assess the safety and clinical utility of the Jarvik 2000, we implanted this device in 10 transplant candidates (mean age 51.3 years) in New York Heart Association (NYHA) class IV. Implantation was achieved through a left thoracotomy during partial cardiopulmonary bypass. The mean support period was 84 days. Within 48 hours postoperatively, the cardiac index increased 43%, pulmonary capillary wedge pressure decreased 52%, systemic vascular resistance decreased significantly, and inotropic support became unnecessary. Eight patients underwent physical rehabilitation and returned to NYHA class I. Their left ventricular dimensions, cardiothoracic ratios, and pressure-volume loop analyses showed good left ventricular unloading. Seven patients underwent transplantation and 3 died during support. No device thrombosis was observed at explantation.The Jarvik 2000 functions as a true assist device by partially unloading the left ventricle, thereby optimizing the patient's hemodynamics. Our preliminary results indicate that this LVAS may safely provide circulatory assistance for heart transplant candidates.
Decline in Rates of Death and Heart Failure in Acute Coronary Syndromes, 1999-2006
Authors: Keith A A Fox, Philippe Gabriel Steg, Kim A Eagle, Shaun G Goodman, Frederick A Anderson, Christopher B Granger, Marcus D Flather, Andrzej Budaj, Ann Quill, Joel M Gore
Journal: JAMA (2007)

ContextRandomized trials provide robust evidence for the impact of pharmacological and interventional treatments in patients with ST-segment elevation and non–ST-segment elevation acute coronary syndromes (NSTE ACS), but whether this translates to changes in clinical practice is unknown.ObjectiveTo determine whether changes in hospital management of patients with ST-segment elevation myocardial infarction (STEMI) and NSTE ACS are associated with improvements in clinical outcome.Design, Setting, and PatientsIn the Global Registry of Acute Coronary Events (GRACE), a multinational cohort study, 44 372 patients with an ACS were enrolled and followed up in 113 hospitals in 14 countries between July 1, 1999, and December 31, 2006.Main Outcome MeasuresTemporal trends in the use of evidence-based pharmacological and interventional therapies; patient outcomes (death, congestive heart failure, pulmonary edema, cardiogenic shock, stroke, myocardial infarction).ResultsUse of pharmacological medications increased over the study period (β-blockers, statins, angiotensin-converting enzyme inhibitors, thienopyridines with or without percutaneous coronary intervention [PCI], glycoprotein IIb/IIIa inhibitors, low-molecular-weight heparin; all P<.001). Pharmacological reperfusion declined in patients with STEMI by −22 percentage points (95% confidence interval [CI], −27 to −17), whereas primary PCI increased by 37 percentage points (95% CI, 33-41). In patients with non-STEMI, rates of PCI increased markedly by 18 percentage points (95% CI, 15-20). Rates of congestive heart failure and pulmonary edema declined in both populations: STEMI, −9 percentage points (95% CI, −12 to −6) and NSTE ACS, −6.9 percentage points (95% CI, −8.4 to −4.7). In patients with STEMI, hospital deaths decreased by 18 percentage points (95% CI, −5.3 to −1.9) and cardiogenic shock by −24 percentage points (95% CI, −4.3 to −0.5). Risk-adjusted hospital deaths declined −0.7 percentage points (95% CI, −1.7 to 0.3) in NSTE ACS patients. Six-month follow-up rates declined among STEMI patients: stroke by −0.8 percentage points (95% CI, −1.7 to 0.1) and myocardial infarction by −2.8 percentage points (95% CI, −6.4 to 0.9). In NSTE ACS, 6-month death declined −1.6 percentage points (95% CI, −3.0 to −0.1) and stroke by 0.7 percentage points (95% CI, −1.4 to 0.1).ConclusionsIn this multinational observational study, improvements in the management of patients with ACS were associated with significant reductions in the rates of new heart failure and mortality and in rates of stroke and mycoardial infarction at 6 months.
Deletion of gene for multidrug resistance in acute myeloid leukaemia with inversion in chromosome 16: prognostic implications
Authors: B.J Kuss, H.J Eyre, S.A Lane, J.K Nancarrow, S.A Whitmore, D.F Callen, R.G Deeley, S.P.C Cole, C.L Willman, K.L Kopecky, C.L Willman, Kj Kopecky, S.R Wolman, C.L Willman, Kj Kopecky, S.R Wolman
Journal: The Lancet (1994)