tbuckley/cabot-search huggingface dataset:
Irradiation Alters Selection for Oncogenic Mutations in Hematopoietic Progenitors
Authors: Andriy Marusyk, Matias Casás-Selves, Curtis J. Henry, Vadym Zaberezhnyy, Jelena Klawitter, Uwe Christians, James DeGregori
Journal: Cancer Research (2009)

Exposure to ionizing radiation and other DNA-damaging carcinogens is strongly associated with induction of malignancies. Prevailing paradigms attribute this association to the induction of oncogenic mutations, as the incidence of oncogenic events is thought to limit initiation and progression of cancers. On the other hand, random mutagenic and genotoxic effects of irradiation are likely to alter progenitor cell populations and the microenvironment, thus altering the selective effects of oncogenic mutations. Using competitive bone marrow transplantation experiments in mice, we show that ionizing irradiation leads to a persistent decline in the numbers and fitness of hematopoietic stem cells, in part resulting from persistent induction of reactive oxygen species. Previous irradiation dramatically alters the selective effects of some oncogenic mutations, substantially inhibiting clonal expansion and leukemogenesis driven by Bcr-Abl or activated N-Ras oncogenes but enhancing the selection for and leukemogenesis driven by the activated Notch1 mutant ICN. Irradiation-dependent selection for ICN expression occurs in a hematopoietic stem cell-enriched pool, which should facilitate the accumulation of additional oncogenic events at a committed T-progenitor stage critical for formation of T-lymphocytic leukemia stem cells. Enhancement of ICN-driven selection and leukemogenesis by previous irradiation is in part non-cell autonomous, as partial restoration of normal hematopoiesis can reverse these effects of irradiation. These studies show that irradiation substantially alters the adaptive landscape in hematopoietic progenitors and suggest that the causal link between irradiation and carcinogenesis might involve increased selection for particular oncogenic mutations.
Routine feedback to GPs who request microbiological tests is effective
Authors: A. P Macgowan, R. Feeney, I. Brown, S. Mcculloch, D. Reeves, A. Lovering
Journal: BMJ (1996)

EDITOR,—Ron A G Winkens and colleagues report a scheme in Maastricht whereby general practitioners are given feedback about tests that they request.1 This provides a good solution to the increasing demands on haematology and chemical pathology laboratories that occur as a result of increasing numbers of requests for tests from the community. The authors give little information, however, on requests for bacteriological, serological, and virological tests. The impact of strategies to manage the demand for tests is poorly studied in microbiology compared with haematology and chemical pathology. …
Neonatal colonization with<i>Staphylococcus aureus</i>is not associated with development of atopic dermatitis
Authors: L. Skov, L.B. Halkjaer, T. Agner, N. Frimodt-Møller, J.O. Jarløv, H. Bisgaard
Journal: British Journal of Dermatology (2009)

Staphylococcus aureus in atopic skin has been associated with exacerbation of eczema. Objectives To investigate a possible association between neonatal colonization with S. aureus and the risk of atopic dermatitis (AD) during the first 3 years of life.The study participants were 356 children born of mothers with asthma from the Copenhagen Prospective Study on Asthma in Childhood. Swabs from the vestibulum nasi and the perineum were cultured at 1 month and 1 year, from acute eczema, and from parents (vestibulum nasi and pharynx). AD development and severity were monitored prospectively.Of the neonates, 5.3% had positive swabs for S. aureus cultured from the vestibulum nasi (51.3%) and/or the perineum (11.3%). Forty-two per cent developed AD, but without association between colonization with S. aureus at 1 month of age and risk of developing AD at 3 years of age. There was a 70% concordance for S. aureus carriage between neonates and parents. At 1 year of age 11.3% children had swabs positive for S. aureus. Fourteen per cent of children tested at the 1-year visit developed AD after the visit but before 3 years of age, but again, there was no association between colonization with S. aureus and the risk of AD. In children seen at acute visits the severity of AD measured by scoring of atopic dermatitis (SCORAD) was significantly higher in children with a positive culture for S. aureus in lesions.Colonization with S. aureus at 1 month of age is not associated with an increased risk of developing AD during the first 3 years of life.
THE INFLUENCE OF RIGHT VENTRICULAR PACING ON RESPONSE TO BIVENTRICULAR PACING: AN ACUTE PRESSURE-VOLUME LOOP STUDY
Authors: Lina Wu, Cornelis P. Allaart, Gerben J. de Roest, Matthijs L. Hendriks, Albert C. van Rossum, Carel C. de Cock
Journal: Journal of the American College of Cardiology (2013)
Central nervous system tumors: what have we learned and where are we heading?
Authors: E. R. Laws
Journal: CA A Cancer Journal for Clinicians (1998)

Molecular biology, laboratory and human studies, and clinical trials have furthered knowledge about the pathogenesis, behavior, and treatment of brain tumors. Technical advances such as functional imaging, computer-guided stereotactic surgical devices, and radiosurgery have improved treatment. The future promises continued progress, with the exploration of areas such as new chemotherapy delivery systems, gene therapy, boron capture therapy, and photodynamic therapy.
776. Evaluation of an Ad5/35-Based Oncolytic Adenovirus Vector Formulated in Icodextrin Delivery Solution in a Model of Ovarian Cancer
Authors: Sudesh Kothari, Shaoheng Ni, Robert Strauss, Andre Lieber
Journal: Molecular Therapy (2006)

Ovarian cancer is the most lethal gynecological cancer, accounting for approximately 14 000 deaths in the United States each year. Recently, gene therapy has become a promising new therapeutic option in the treatment of ovarian cancer, and is currently under intensive clinical investigation utilizing a variety of approaches. Most tumor gene therapy vectors are based on adenovirus type 5. Recent studies, however, have shown that expression of the primary Ad5 receptor, coxsackie-and adenovirus receptor (CAR), is often S300 low on malignant ovarian tumors, thus infection of tumor cells by Ad5 vectors is not efficient. Over the last 5 years we have developed new oncolytic Ad vectors, including chimeric Ad vectors possessing fibers derived from Ad group B serotype 35 (Ad5/35), which use CD46 for uptake into cells. In contrast to the Ad5 receptor, CD46 expression is upregulated in malignant tumors, which enables Ad5/35 vectors to infect malignant tumor cells, including primary ovarian cancer cells, that are refractory to infection with Ad5 vectors. A direct comparison of the oncolytic vector Ad5/35.IR-E1A/TRAIL with an Ad5 vector containing an identical transgene cassette demonstrated the superiority of the Ad5/35 capsid containing vector in infection and lysis of SKOV3-ip1 cells and primary ovarian cancer cells isolated from biopsies. A previous study reported significantly longer persistence of adenovirus in the peritoneal cavity when formulated in icodextrin solution compared to saline and glucose solution. To study the effect of icodextrin on Ad5/35 infection of peritoneal organs, a β-galactosidase expressing Ad5/35 vector was injected into mice with pre-established peritoneal tumors derived from SKOV3-ip1 cells. We found that 15% icodextrin and to a lesser degree 4% icodextrin increased transduction of tumor cells and at the same time decreased transduction of liver or spleen cells. Finally we analyzed the anti-tumor effect of intraperitoneal injection of Ad5/35.IR-E1A/TRAIL in a model with SKOV3-ip1-derived peritoneal tumors. We demonstrated that icodextrin greatly increased the antitumor effect of Ad5/35.IRE1A/TRAIL when compared to PBS formulated vector. Half the mice were tumor-free after injection of the oncolytic vector in 15% icodextrin and the remaining tumors demonstrated large areas of necrosis and fibrosis. (Notably, icodextrin without Ad had no effect on tumor growth.) This study provides a basis for the use of Ad5/35-based oncolytic vectors and icodextrin, in an intraperitoneal setting, for the treatment of ovarian cancer. We acknowledge receipt of support and icodextrin material from CGT Corporation and Innovata PLC (formerly ML laboratories).
Adjuvant Capecitabine, Docetaxel, Cyclophosphamide, and Epirubicin for Early Breast Cancer: Final Analysis of the Randomized FinXX Trial
Authors: Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Riikka Huovinen, Arja Jukkola-Vuorinen, Minna Tanner, Riitta Kokko, Johan Ahlgren, Päivi Auvinen, Outi Paija, Leena Helle, Kenneth Villman, Paul Nyandoto, Greger Nilsson, Marjo Pajunen, Raija Asola, Paula Poikonen, Mika Leinonen, Vesa Kataja, Petri Bono, Henrik Lindman
Journal: Journal of Clinical Oncology (2011)

Capecitabine is an active agent in the treatment of breast cancer. It is not known whether integration of capecitabine into an adjuvant regimen that contains a taxane, an anthracycline, and cyclophosphamide improves outcome in early breast cancer.Women with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive either three cycles of docetaxel and capecitabine (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX; n = 753) or three cycles of docetaxel (T) followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF; n = 747). The primary end point was recurrence-free survival (RFS).During a median follow-up time of 59 months, 214 RFS events occurred (local or distant recurrences or deaths; TX/CEX, n = 96; T/CEF, n = 118). RFS was not significantly different between the groups (hazard ratio [HR], 0.79; 95% CI, 0.60 to 1.04; P = .087; 5-year RFS, 86.6% for TX/CEX v 84.1% for T/CEF). Fifty-six patients assigned to TX/CEX died during the follow-up compared with 75 of patients assigned to T/CEF (HR, 0.73; 95% CI, 0.52 to 1.04; P = .080). In exploratory analyses, TX/CEX improved breast cancer-specific survival (HR, 0.64; 95% CI, 0.44 to 0.95; P = .027) and RFS in women with triple-negative disease and in women who had more than three metastatic axillary lymph nodes at the time of diagnosis. We detected little severe late toxicity.Integration of capecitabine into a regimen that contains docetaxel, epirubicin, and cyclophosphamide did not improve RFS significantly compared with a similar regimen without capecitabine.
EST COMPLICATED BY EPILEPSY
Authors: JORDAN H. LACHMAN, WALTER TUCHMAN
Journal: American Journal of Psychiatry (1964)

A case is presented in which a patient with prominent depression and a background of longstanding but controlled epilepsy underwent EST. Inadvertent interruption of the anticonvulsant medication in the course of hospitalization was followed by postictal phenomena characterized by catatonic-like stupor and coma associated with an abnormal but not sufficiently diagnostic EEG. The stupor cleared gradually upon administration of Mesantoin and barbiturate. This case emphasizes the importance of careful history and the maintenance of appropriate anticonvulsant medication in epileptic patients undergoing shock therapy. Post- or inter-ictal stupor once precipitated presents a state difficult to diagnose with certainty and a challenging management problem.
Research pointers: Association of common genetic variant with susceptibility to invasive pneumococcal disease
Authors: S Roy
Journal: BMJ (2002)

Association of common genetic variant with susceptibility to invasive pneumococcal diseaseHost factors influencing susceptibility to infection with Streptococcus pneumoniae remain incompletely understood, even though it is a major cause of infectious mortality.We report a genetic locus associated with susceptibility to invasive pneumococcal disease.C reactive protein is an acute phase protein that may be important in the early stages of this infection. 1It binds the C polysaccharide of the cell wall of S pneumoniae, activates the classical complement pathway, and in vitro promotes phagocytosis by polymorphonuclear leucocytes. 2 3 In vivo, transgenic mice with human C reactive protein have reduced bacteraemia and longer survival after infection with S pneumoniae than wild type controls. 2Our case-control study compared the frequency of a dinucleotide repeat polymorphism located in an intron of the C reactive protein gene in patients with invasive pneumococcal disease and in healthy controls. 3
A novel in-situ model for continuous observation of transient drug concentration gradients across buccal epithelium at the microscopical level
Authors: A.J. Hoogstraate, C. Cullander, J.F. Nagelkerke, F. Spies, J. Verhoef, A.H.G.J. Schrijvers, H.E. Junginger, H.E. Boddé
Journal: Journal of Controlled Release (1996)
IMPROVED URINE TEST GLASSES AND HOLDER.
Authors: E. G. BALLENGER
Journal: JAMA (1904)

The value of having the urine passed in two or three glasses, with or without washing the anterior urethra, is too well known to need emphasis. The glasses recommended allow the urine to be collected in several portions without being spilled; the importance of this is evident to every physician making many examinations daily, where offices or dispensaries soon have the urinous odor so offensive both to physician and patient. Those who come needing urinary examinations for shreds, pus, etc., frequently do not have micturition well under their control, and when the stream is once started it is stopped with some difficulty and pain, or not at all until the bladder is emptied, and so the two-glass or three-glass test is obtained at the expense of a "broken technic" with the urine spilled. This is obviated by the use of the glasses recommended, which are of a
Late development of pulmonary venous obstruction following Mustard's operation using a dacron baffle.
Authors: D J Driscoll, M R Nihill, T A Vargo, C E Mullins, D G McNamara
Journal: Circulation (1977)

Three patients developed late pulmonary vein obstruction (PVO) following Mustard's operation for transposition of the great arteries. In all three the absence of PVO had been documented by an earlier postoperative cardiac catheterization. At reoperation shrinkage and kinking of the dacron baffle was evident. After Mustard's operation, patients should be observed closely for symptoms and signs of PVO since it can occur insidiously despite previously proven absence of this complication.
Proteomic Analysis Reveals Field-Wide Changes in Protein Expression in the Morphologically Normal Mucosa of Patients with Colorectal Neoplasia
Authors: Abigael C.J. Polley, Francis Mulholland, Carmen Pin, Elizabeth A. Williams, D. Mike Bradburn, Sarah J. Mills, John C. Mathers, Ian T. Johnson
Journal: Cancer Research (2006)

Abstract Models for the pathogenesis of colorectal cancer tend to focus on the localized lesion, with less attention paid to changes in normal-appearing mucosa. Here we used two-dimensional gel electrophoresis and mass spectrometry to define patterns of protein expression in morphologically normal colonic mucosa from 13 healthy subjects, 9 patients with adenomatous polyps, and 9 with cancer. Tumor samples were also compared with the normal mucosa. Systematic gel comparisons identified a total of 839 spots that differed significantly between one or more groups (P &amp;lt; 0.05). Principle component analysis indicated that the first three components accounted for ∼37% of the total variation and provided clear evidence that flat mucosa from healthy subjects differed significantly from that of patients with polyps or cancer. Sixty-one proteins differed significantly between mucosa from healthy subjects and all other tissue types, and 206 differed significantly between healthy mucosa and polyp mucosa. Several of the proteins showing significant underexpression in tumor tissue were cytokeratins and other cytoskeletal components. In contrast, cytokeratins, including several isoforms of cytokeratin 8, were overexpressed in apparently normal mucosa from polyp and cancer patients compared with mucosa from healthy subjects. These findings indicate that protein expression in the apparently normal colonic mucosal field is modified in individuals with neoplastic lesions at sites distant from the lesion. Recognition and further characterization of this field effect at the molecular level may provide protein biomarkers of susceptibility to colorectal cancer and facilitate development of hypotheses for the role of diet and other environmental factors in its causation. (Cancer Res 2006; 66(13): 6553-62)
Reduction of ischemic injury by sublingual nitroglycerin in patients with acute myocardial infarction.
Authors: N A Awan, E A Amsterdam, Z Vera, A N DeMaria, R R Miller, D T Mason
Journal: Circulation (1976)

The effect of sublingual nitroglycerin (NTG) on myocardial ischemic injury was evaluated in eleven patients with acute anterior myocardial infarction. Precordial 35-lead ST-segment maps were obtained in each patient immediately before and 3-10 minutes after 0.4 mg sublingual NTG. The following measurements were made from each ST map: N-ST (number of leads showing ST elevation greater than 1mm), sigmaST (total ST elevation in all leads), ST (average ST-segment elevation in those leads with less than 1mm elevation). Following 0.4 mg sublingual NTG evidence of myocardial ischemic injury as assessed by ST-segment mapping decreased in association with reduction of heart rate X systolic blood pressure product (10.80 X 10(3) to 9.49 X 10(3), P less than 0.001). Group mean values diminished significantly for N-ST (18.1 to 14.4, P less than 0.001), sigma ST (37.9 to 30.1 P less than 0.005) and ST (1.7 to 1.4, P less than 0.001). Evaluation performed by the technique of precordial ST-segment mapping suggests that sublingual nitroglycerin in a commonly employed clinical dose is associated with evidence of reduced ischemic cardiac injury in patients with acute myocardial infarction. This effect appears to be related to reduction of myocardial oxygen demand by the nitrate.
Inflammation stops at Bop
Authors: Amy Maxmen
Journal: The Journal of Experimental Medicine (2009)

Bordetella , the pathogen underlying whooping cough, short-circuits the host immune response by triggering the antiinflammatory cytokine IL-10. Now, [Nagamatsu and colleagues][1] nab the bacterial protein that does the job.

![Figure][2] 

Infection with BopN-deficient Bordetella results in
Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission
Authors: Roland B. Walter, Sarah A. Buckley, John M. Pagel, Brent L. Wood, Barry E. Storer, Brenda M. Sandmaier, Min Fang, Boglarka Gyurkocza, Colleen Delaney, Jerald P. Radich, Elihu H. Estey, Frederick R. Appelbaum
Journal: Blood (2013)
Regulation of eosinophil apoptosis by nitric oxide: Role of c-Jun-N-terminal kinase and signal transducer and activator of transcription 5
Authors: Xianzhi Zhang, None Msc, Eeva Moilanen, Aleksi Lahti, Mari Hämäläinen, Mark A. Giembycz, Peter J. Barnes, Mark A. Lindsay, Hannu Kankaanranta
Journal: Journal of Allergy and Clinical Immunology (2003)
Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study
Authors: WK Hofmann, WJ Kell, P Fenaux, S Castaigne, A Ganser, C Chomienne, R Burnett, C Kowal, D Hoelzer, AK Burnett
Journal: Leukemia (2000)
Later Emotional and Behavioral Problems Associated With Sleep Problems in Toddlers
Authors: Børge Sivertsen, Allison G. Harvey, Ted Reichborn-Kjennerud, Leila Torgersen, Eivind Ystrom, Mari Hysing
Journal: JAMA Pediatrics (2015)

IMPORTANCE Childhood sleep problems have been linked to a range of adverse health outcomes, but there is limited knowledge as to the temporal association between sleep problems and subsequent emotional and behavioral problems in young children.OBJECTIVE To examine whether sleep problems in toddlers aged 18 months are related to both concurrent and subsequent emotional and behavioral problems in preschool children aged 5 years.
RISK FACTORS ASCERTAINED AT PRESENTATION AND MORTALITY AMONG PATIENTS WITH FIRST MYOCARDIAL INFARCTION
Authors: John G. Canto, Catarina I. Kiefe, William J. Rogers, Eric D. Peterson, Paul D. Frederick, William J. French, C. Michael Gibson, Charles V. Pollack, Joseph P. Ornato, Costas G. Lambrew, Robert J. Zalenski, Jan Penney, Alan J. Tiefenbrunn, Philip Greenland
Journal: Journal of the American College of Cardiology (2011)
Cerebral Vasculitis Associated With Cocaine Abuse or Subarachnoid Hemorrhage?
Authors: Karen Weingarten
Journal: JAMA (1988)

To the Editor.  —I read with interest the recent article by Kaye and Fainstat.1I would like to describe a patient who developed white-matter disease apparently related to long-term cocaine abuse. To my knowledge, this hazard of cocaine abuse has not been reported previously.  Report of a Case.  —A 27-year-old man presented with a left-sided seizure. During the past few weeks, he had noticed heaviness and paresthesias in his lower extremities and periods of forgetfulness. His medical history was unremarkable except for occasional intranasal use of cocaine during the past five years. He denied intravenous drug or alcohol abuse and there was no history of cardiac or collagen vascular disease.  Examination disclosed the following values: blood pressure, 110/60 mm Hg; pulse rate, 88 beats per minute; and respirations, 18/min. He was alert, oriented, and without focal neurological findings. Contrast-enhanced computed tomographic scans of the head were normal (Fig 1).
Nitrites and Nitrates in Ischaemic Heart Disease
Authors: G. Sandler
Journal: BMJ (1967)

Amphetamine PrescribingSIR,-Scarcely a day passes without news of another drug haul from a chemist's shop.Thousands of tablets are stolen, and the majority are probably amphetamines.A glance at the Proprietary Drug Lists will show there are at least twenty-two pre- parations containing amphetamine alone or in combination with other drugs.Many are virtually identical and some preparations appear both as central nervous system stimulants and sedatives and tranquillizers.The chemist is obliged to keep a fairly large stock in order to meet all requirements.It is not necessary to reiterate the undesirability of these drugs being self-administered nor the consequent dangers of addiction, of toxic effects, and of antisocial behaviour, and yet the illegal use of amphetamines is increasing and constitutes a serious problem, and the stocks available in the chemists are one important source of supply.How much do we contribute to this prob- lem by continuing to prescribe the drug when its use is unnecessary or outdated ?It is my belief that all these preparations could be scrapped with very little loss to the medical armamentarium.For mild depression there
208 FREE 25(OH) VITAMIN D IS HIGHER IN CIRRHOTICS WITH SYNTHETIC DYSFUNCTION COMPARED WITH INDIVIDUALS WITHOUT LIVER DISEASE DESPITE TOTAL 25(OH)D DEFICIENCY
Authors: J.C. Lai, B. Lizaola, L. Kane, P. Weyland, N.A. Terrault, D. Bikle, J.B. Schwartz
Journal: Journal of Hepatology (2013)
New antiviral and antifungal drugs.
Authors: P G Davey
Journal: BMJ (1990)

was also carried over into the hospices' perception of themselves as essentiallv "technical" if there was a full- time consultant or "non-technical" if there was not.Following the Royal College of Physicians' recogni- tion of palliative medicine as a new specialty it is likely that these differences will increase with the advent of a generation of "accredited hospice consultants," who will displace the "enthusiastic amateurs" of the past.We thank all the respondents to the survey and the nurses at the Leicestershire Hospice for their interest and willing participation, Dr Carol Jagger for statistical help, and Miss K Jeffery for preparing the typescript.