tbuckley/cabot-search huggingface dataset:
Unusual treatment of patent foramen ovale after pneumonectomy
Authors: W. N. Welvaart, A. Becker, J. T. Marcus, A. Vonk-Noordegraaf, J. W. A. Oosterhuis, M. A. Paul
Journal: European Respiratory Journal (2010)

AML) (fig.1d).The patient was referred to oncology where he was treated for the blast crisis of AML.A repeat BAL fluid analysis after 14 days of treatment for PCP was negative for P. jirovecii.HIV-positive patients with a CD4 count ,200 mL -1 are considered at risk for PCP [1].HIV-negative patients with PCP are predominantly those on immunosuppression or chemotherapy for an underlying disease process [2].Irrespective of the underlying cause, the predisposition to PCP in the ''at risk'' patients is primarily due to a decrease in their cell-mediated immunity [3].Additionally, in patients on glucocorticoids for .12weeks, suppression of lung surfactant may be an additional factor [4].Though haematological malignancies constitute 30% of all the malignancies associated with PCP, the median time from cancer diagnosis to the first episode of PCP is usually 2 yrs [2].Moreover, PCP as the sole presenting feature of an underlying occult haematological malignancy has not been reported previously.On presentation, our patient had no evidence of leukaemia.In retrospect, PCP was thus the first clinical manifestation of his occult malignancy.Though the blast crisis manifested 3 weeks after the first signs and symptoms of PCP, a bone marrow analysis would have revealed AML even on presentation.This would in turn explain the decreased immunity and, therefore, his predisposition to PCP.The infiltrates on CT scan of the chest could not be attributed to leukaemia because the WBC count was normal at that time.Serum LDH generally ranges from 361 IU?L -1 to 1,217 IU?L -1 in patients with PCP [5].The higher than expected LDH served as an additional clue towards an underlying haematological malignancy in our patient.In conclusion, PCP can thus be the sole atypical presentation of leukaemia.Since the transformation time from occult to overt leukaemia can be variable (weeks to months), bone marrow analysis should be considered in HIV-negative patients with no identifiable risk factors for PCP on presentation.
Correlation of oxygenation with vascular permeability-surface area but not with lung water in humans with acute respiratory failure and pulmonary edema.
Authors: K L Brigham, K Kariman, T R Harris, J R Snapper, G R Bernard, S L Young
Journal: Journal of Clinical Investigation (1983)

We used a single-pass multiple tracer technique to measure cardiac output, extravascular lung water (EVLW) and lung vascular [14C]urea permeability-surface area (PSu) in 14 patients with acute respiratory failure and pulmonary edema. All patients had increased EVLW, but EVLW in the 10 surviving patients (0.26 +/- 0.06 SE ml/ml total lung capacity [TLC]) was not significantly different from that in the five patients who died (0.22 +/- 0.05). EVLW did not correlate with intravascular pressures or with alveolar-arterial oxygen pressure difference (A-aDO2). PSu was lower in surviving patients (0.50 +/- 0.16 SE ml/s X liter TLC) than in patients who died (3.44 +/- 0.36; P less than 0.05) and also lower than in previously reported data in patients with normal PSu. PSu correlated significantly with A-aDO2. Serial studies showed that PSu returned from a low value toward normal in a patient who survived but remained high in a patient who died. We conclude that the amount of edema in the lungs measured by indicator methods was not the principal determinant of either the magnitude of oxygenation defect or survival in the patients studied. We interpret the low PSu in surviving patients as decreased surface area and infer that the ability of the lung circulation to reduce perfusion of damaged and edematous areas was important in preserving oxygenation. A high PSu, presumably reflecting perfusion of areas with increased permeability, was a sign of especially poor prognosis. Multiple tracer techniques for measuring lung vascular PSu may help to define the pathogenesis and to evaluate therapies of acute lung injury in humans. Such measurements may be a more useful clinical tool than measurements of lung water in patients with acute respiratory failure and pulmonary edema.
An Address on the Therapeutics of the Uric Acid Diathesis
Authors: I. B. Yeo
Journal: BMJ (1888)

to King's College Hospital.(Coni4cuded from page 19.) 1N the next place, we must pass on to consider the more important medicinal agents which have been proposed for the treatment of this diathesis and its various morbid manifestations, and, first of all:Colchicum.-I would ask you to consider the use and value of col-This drug has been much discredited of late years, and if one the results of this discussion is to remove that discredit, it will, in my opinion, have done practical medicine a real service, the drg may have frequently been misused, I do not doubt;
Obstructive Sleep Apnea in Patients with Abdominal Aortic Aneurysms
Authors: Rebecca H. Mason, Gion Ruegg, Jeremy Perkins, Maxine Hardinge, Beatrice Amann-Vesti, Oliver Senn, John R. Stradling, Malcolm Kohler
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Abdominal aortic aneurysms (AAA) are associated with life-threatening complications. The likelihood that an AAA will rupture is influenced by the aneurysm diameter and its expansion rate; reasons for rapid expansion are largely unknown.Objectives: To determine the prevalence of obstructive sleep apnea (OSA) in patients with AAA, and investigate a possible association between OSA and rate of AAA expansion.Methods: A total of 127 patients (11 females), included in an AAA surveillance program, agreed to participate and underwent a sleep study. Annual AAA expansion was determined retrospectively from available ultrasound measurements. OSA was characterized using both oxygen desaturation index (ODI) and apnea–hypopnea index (AHI). Univariate and multivariate analysis was performed to assess the effect of OSA severity on AAA expansion.Measurements and Main Results: Mean age was 67.9 (SD, 6) years. Median interval between the first and last AAA measurements was 18 (range, 2–113) months. An ODI or AHI of greater than 10 was found in 40.5% and 41.5% of the patients, respectively. Patients with an ODI greater than 30 (n = 12) had a significantly faster median yearly AAA expansion rate (2.9; quartiles 2/5.7 mm/y) than patients with an ODI 0–5 (n = 47; 1.2; quartiles 0/3.1 mm/y) or 6–15 (n = 43; 1.3; quartiles 0/2.7 mm/y) (P < 0.05). In multivariate regression analysis, controlling for cardiovascular risk factors and medications, ODI greater than 30 remained an independent risk factor for AAA expansion.Conclusions: In patients with AAA, OSA is highly prevalent. Severe OSA may be a causal factor for faster AAA expansion, but this needs to be proved in a randomized controlled intervention trial.
Radical Sunni doctor convicted of violent assault in demonstration is struck off medical register
Authors: C. Dyer
Journal: BMJ (2014)

A British doctor who fled the United Kingdom after being charged with a violent assault during a pro-Sunni demonstration has been struck off the medical register in his absence, five months after his case led to the first successful prosecution of Islamic sectarian violence in Britain.

Mirza Tariq Ali, 39, who qualified in Pakistan in 1998, worked locum shifts as a general surgery registrar in several hospitals around London. He became a supporter of the radical Sunni preacher Anjem Choudary and joined a march organised by supporters of Choudary through central London in May 2013.

An internet circular advertising the “March …
Hibernation in Noncontracting Mammalian Cardiomyocytes
Authors: Tammy M. Casey, Peter G. Arthur
Journal: Circulation (2000)

Background —The aim of the present study was to establish whether isolated neonatal mammalian cardiomyocytes were capable of downregulating energy-using processes other than contraction while maintaining metabolic stability when oxygen availability was reduced. Methods and Results —Metabolic response of cardiomyocytes was investigated under moderate (5 to 6 μmol/L) and severe (2 to 3 μmol/L) forms of hypoxia. Cells exposed to oxygen concentrations of 5 to 6 μmol/L exhibited rates of oxygen consumption, which were decreased to 64% of normoxic rates. Rates of cellular energy usage were decreased because this reduced rate of oxygen consumption was not associated with either decreased intracellular ATP and phosphocreatine concentrations or a compensatory switch to glycolysis. When cells were exposed to oxygen concentrations of 2 to 3 μmol/L, rates of oxygen consumption decreased to 9% of normoxic rates. This decreased rate of oxygen consumption was associated with energetic stress, because a significant switch to glycolysis occurred and intracellular phosphocreatine concentrations were decreased by 40%. Rates of cellular energy usage were further decreased as indicated by stable intracellular ATP concentrations. Conclusions —Our results suggest that isolated cardiomyocytes are capable of downregulating energy-consuming processes other than contraction when oxygen supply is decreased. Regions of myocardial tissue are also capable of downregulating metabolic activity during ischemia by shutting down contractile activity (myocardial hibernation). We suggest that metabolic downregulation associated with myocardial hibernation may not be exclusively due to reduced rates of contractile activity. Other energy-using processes (eg, protein synthesis, mRNA synthesis, ion channel activity, and proton leak) may also be shut down.
Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes
Authors: Aimee M. Powelka, Asha Seth, Joseph V. Virbasius, Evangelos Kiskinis, Sarah M. Nicoloro, Adilson L. Guilherme, Xiaoqing Tang, Juerg R. Straubhaar, Andrew D. Cherniack, Malcolm G. Parker, Michael P. Czech
Journal: Journal of Clinical Investigation (2005)

Using an siRNA-based screen, we identified the transcriptional corepressor RIP140 as a negative regulator of insulin-responsive hexose uptake and oxidative metabolism in 3T3-L1 adipocytes. Affymetrix GeneChip profiling revealed that RIP140 depletion upregulates the expression of clusters of genes in the pathways of glucose uptake, glycolysis, TCA cycle, fatty acid oxidation, mitochondrial biogenesis, and oxidative phosphorylation in these cells. Conversely, we show that reexpression of RIP140 in mouse embryonic fibroblasts derived from RIP140-null mice downregulates expression of many of these same genes. Consistent with these microarray data, RIP140 gene silencing in cultured adipocytes increased both conversion of [14C]glucose to CO2 and mitochondrial oxygen consumption. RIP140-null mice, previously reported to resist weight gain on a high-fat diet, are shown here to display enhanced glucose tolerance and enhanced responsiveness to insulin compared with matched wild-type mice upon high-fat feeding. Mechanistically, RIP140 was found to require the nuclear receptor ERRα to regulate hexose uptake and mitochondrial proteins SDHB and CoxVb, although it likely acts through other nuclear receptors as well. We conclude that RIP140 is a major suppressor of adipocyte oxidative metabolism and mitochondrial biogenesis, as well as a negative regulator of whole-body glucose tolerance and energy expenditure in mice.
L-BLP25: A Peptide Vaccine Strategy in Non–Small Cell Lung Cancer
Authors: Randeep Sangha, Charles Butts
Journal: Clinical Cancer Research (2007)

Abstract MUC1 is a mucinous glycoprotein which is overexpressed and under or aberrantly glycosylated in many human malignancies. MUC1 is associated with cellular transformation and can confer resistance to genotoxic agents. L-BLP25 is a peptide vaccine strategy that targets the exposed core peptide of MUC1. In preclinical studies, L-BLP25 induced a cellular immune response characterized by T-cell proliferation in response to MUC1 and production of IFN-γ. Phase I and II trials have established the dose and schedule of the vaccine as well as its excellent safety profile. A randomized phase II trial of maintenance L-BLP25 versus best supportive care in patients with stage IIIB/IV non–small cell lung cancer who experienced clinical benefit from initial therapy has been reported. Updated survival analysis of this trial continues to show a strong survival trend in favor of L-BLP25 (median survival, 30.6 versus 13.3 months) in a subgroup of patients with locoregional stage IIIB disease. These promising results will be tested in a phase III trial of L-BLP25 versus placebo in patients with stage III non–small cell lung cancer after response to primary chemoradiotherapy.
Factors in Successful Narcotics Renunciation
Authors: BARBARA BESS, SAMUEL JANUS, ALFRED RIFKIN
Journal: American Journal of Psychiatry (1972)

The authors studied 17 former narcotic addicts in order to determine what factors enabled them to successfully renounce drug use. Among their most important findings were that most of these ex-addicts had grown up in intact families, with fathers who provided suitable models for work roles; that antisoical behavior was not prominent before addiction; and that, in most cases, traumatic events coincided with both the beginning and the end of drug use.
Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions
Authors: Brian J P Huntly, Francois Guilhot, Alistair G Reid, George Vassiliou, Evelin Hennig, Christina Franke, Jennie Byrne, Andre Brizard, Dietger Niederwieser, Julie Freeman-Edward, Gavin Cuthbert, Nick Bown, Richard E Clark, Elizabeth P Nacheva, Anthony R Green, Michael W N Deininger
Journal: Blood (2003)
Reform of General Practice
Authors: R. E. Heap, C. Gunn, A. F. Wright, J. A. Beattie, L. Sheldon, R. A. P. Whitelaw, K. McCreath, G. K. M. Hall, E. Kilmurray, G. J. K. Turner, J. A. Murray, H. Riddle, W. V. Bayne, J. L. Swanston, R. K. W. Sharp
Journal: BMJ (1964)
Fertility of Female Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Daniel M. Green, Toana Kawashima, Marilyn Stovall, Wendy Leisenring, Charles A. Sklar, Ann C. Mertens, Sarah S. Donaldson, Julianne Byrne, Leslie L. Robison
Journal: Journal of Clinical Oncology (2009)

This study was undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on fertility.We reviewed the fertility of female participants in the Childhood Cancer Survivor Study (CCSS), which consisted of 5-year survivors, and a cohort of randomly selected siblings who responded to a questionnaire. Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered; the cumulative dose of drug administered for several drugs of interest; and the doses, volumes, and dates of administration of all radiation therapy.There were 5,149 female CCSS participants, and there were 1,441 female siblings of CCSS participants who were age 15 to 44 years. The relative risk (RR) for survivors of ever being pregnant was 0.81 (95% CI, 0.73 to 0.90; P < .001) compared with female siblings. In multivariate models among survivors only, those who received a hypothalamic/pituitary radiation dose > or = 30 Gy (RR, 0.61; 95% CI, 0.44 to 0.83) or an ovarian/uterine radiation dose greater than 5 Gy were less likely to have ever been pregnant (RR, 0.56 for 5 to 10 Gy; 95% CI, 0.37 to 0.85; RR, 0.18 for > 10 Gy; 95% CI, 0.13 to 0.26). Those with a summed alkylating agent dose (AAD) score of three or four or who were treated with lomustine or cyclophosphamide were less likely to have ever been pregnant.This large study demonstrated that fertility is decreased among female CCSS participants. The risk factors identified may be utilized for pretreatment counseling of patients and their parents.
Liver Fat Is Increased in Type 2 Diabetic Patients and Underestimated by Serum Alanine Aminotransferase Compared With Equally Obese Nondiabetic Subjects
Authors: Anna Kotronen, Leena Juurinen, Antti Hakkarainen, Jukka Westerbacka, Anja Cornér, Robert Bergholm, Hannele Yki-Järvinen
Journal: Diabetes Care (2007)

The purpose of this study was to determine whether type 2 diabetic patients have more liver fat than age-, sex-, and BMI-matched nondiabetic subjects and whether liver enzymes (serum alanine aminotransferase [S-ALT] and serum aspartate aminotransferase) are similarly related to liver fat in type 2 diabetic patients and normal subjects.Seventy type 2 diabetic patients and 70 nondiabetic subjects matched for BMI, age, and sex were studied. Liver fat ((1)H-magnetic resonance spectroscopy), body composition (magnetic resonance imaging), and biochemical markers of insulin resistance were measured.The type 2 diabetic patients had, on average, 80% more liver fat and 16% more intra-abdominal fat than the nondiabetic subjects. The difference in liver fat between the two groups remained statistically significant when adjusted for intra-abdominal fat (P < 0.05). At any given BMI or waist circumference, the type 2 diabetic patients had more liver fat than the nondiabetic subjects. The difference in liver fat between the groups rose as a function of BMI and waist circumference. Fasting serum insulin (r = 0.55, P < 0.0001), fasting plasma glucose (r = 0.29, P = 0.0006), A1C (r = 0.34, P < 0.0001), fasting serum triglycerides (r = 0.36, P < 0.0001), and fasting serum HDL cholesterol (r = -0.31, P = 0.0002) correlated with liver fat similarly in both groups. The slopes of the relationships between S-ALT and liver fat were significantly different (P = 0.004). Liver fat content did not differ between the groups at low S-ALT concentrations (10-20 units/l) but was 70-200% higher in type 2 diabetic patients compared with control subjects at S-ALT concentrations of 50-200 units/l.Type 2 diabetic patients have 80% more liver fat than age-, weight-, and sex-matched nondiabetic subjects. S-ALT underestimates liver fat in type 2 diabetic patients.
Enhancement of Antitumor Immunity in Lung Cancer by Targeting Myeloid-Derived Suppressor Cell Pathways
Authors: Anandi Sawant, Cara C. Schafer, Tong Huan Jin, Jaroslaw Zmijewski, Hubert M. Tse, Justin Roth, Zhihuan Sun, Gene P. Siegal, Victor J. Thannickal, Stefan C. Grant, Selvarangan Ponnazhagan, Jessy S. Deshane
Journal: Cancer Research (2013)

Abstract Chemoresistance due to heterogeneity of the tumor microenvironment (TME) hampers the long-term efficacy of first-line therapies for lung cancer. Current combination therapies for lung cancer provide only modest improvement in survival, implicating necessity for novel approaches that suppress malignant growth and stimulate long-term antitumor immunity. Oxidative stress in the TME promotes immunosuppression by tumor-infiltrating myeloid-derived suppressor cells (MDSC), which inhibit host protective antitumor immunity. Using a murine model of lung cancer, we demonstrate that a combination treatment with gemcitabine and a superoxide dismutase mimetic targets immunosuppressive MDSC in the TME and enhances the quantity and quality of both effector and memory CD8+ T-cell responses. At the effector cell function level, the unique combination therapy targeting MDSC and redox signaling greatly enhanced cytolytic CD8+ T-cell response and further decreased regulatory T cell infiltration. For long-term antitumor effects, this therapy altered the metabolism of memory cells with self-renewing phenotype and provided a preferential advantage for survival of memory subsets with long-term efficacy and persistence. Adoptive transfer of memory cells from this combination therapy prolonged survival of tumor-bearing recipients. Furthermore, the adoptively transferred memory cells responded to tumor rechallenge exerting long-term persistence. This approach offers a new paradigm to inhibit immunosuppression by direct targeting of MDSC function, to generate effector and persistent memory cells for tumor eradication, and to prevent lung cancer relapse. Cancer Res; 73(22); 6609–20. ©2013 AACR.
Disruption of LDL receptor gene in transgenic SREBP-1a mice unmasks hyperlipidemia resulting from production of lipid-rich VLDL
Authors: Jay D. Horton, Hitoshi Shimano, Robert L. Hamilton, Michael S. Brown, Joseph L. Goldstein
Journal: Journal of Clinical Investigation (1999)

Transgenic mice that overexpress the nuclear form of sterol regulatory element binding protein-1a (SREBP-1a) in liver (TgBP-1a mice) were shown previously to overproduce cholesterol and fatty acids and to accumulate massive amounts of cholesterol and triglycerides in hepatocytes. Despite the hepatic overproduction of lipids, the plasma levels of cholesterol (∼45 mg/dl) and triglycerides (∼55 mg/dl) were not elevated, perhaps owing to degradation of lipid-enriched particles by low-density lipoprotein (LDL) receptors. To test this hypothesis, in the current studies we bred TgBP-1a mice with LDL receptor knockout mice. As reported previously, LDLR–/– mice manifested a moderate elevation in plasma cholesterol (∼215 mg/dl) and triglycerides (∼155 mg/dl). In contrast, the doubly mutant TgBP-1a;LDLR–/– mice exhibited marked increases in plasma cholesterol (∼1,050 mg/dl) and triglycerides (∼900 mg/dl). These lipids were contained predominantly within large very-low-density lipoprotein (VLDL) particles that were relatively enriched in cholesterol and apolipoprotein E. Freshly isolated hepatocytes from TgBP-1a and TgBP-1a;LDLR–/– mice overproduced cholesterol and fatty acids and secreted increased amounts of these lipids into the medium. Electron micrographs of livers from TgBP-1a mice showed large amounts of enlarged lipoproteins within the secretory pathway. We conclude that the TgBP-1a mice produce large lipid-rich lipoproteins, but these particles do not accumulate in plasma because they are degraded through the action of LDL receptors.
Osler, Flexner, apprenticeship and 'the new medical education'
Authors: T. Dornan
Journal: Journal of the Royal Society of Medicine (2005)

These are bewildering times for doctors who teach medical students. The UK General Medical Council (GMC) has reminded them they have a duty to teach,1 yet stirred up such radical change that their task is unrecognizably different from what they themselves experienced as students.2,3 This essay draws on biographies of two people who changed the face of medical education in the 20th century to trace the origins of this bewilderment and suggest a direction for the 21st century.4,5 Most of today's doctors just associate the name of William Osler with nodes they were taught about but never see. In Michael Bliss's biography, he comes to life as a master clinician, apprentice-master, and humanist role model. I first became aware of Abraham Flexner as the author of a century-old report that got medical education into the mess it is in today. Wrong. He was a visionary educationalist who raised standards of medicine round the world by wedding it with biomedical science. After vignettes of these two men, I describe what the GMC has recommended and read between the lines of its recommendations. To finish, I suggest the wheel has come full circle. Apprenticeship, central to Osler and Flexner's educational visions, needs to be revitalized.