tbuckley/cabot-search huggingface dataset:
Evaluating the prognostic significance of <i>JAK2</i> in distant breast cancer recurrence.
Authors: Carl Anthony Blau, Christopher P. Miller, Amanda N. Kortum, Jason D. Thorpe, Michel Schummer, Kathy O'Briant, Catherine M. Coy, J David Beatty, Nicole D. Urban
Journal: Journal of Clinical Oncology (2013)

e22178 Background: Estrogen, progesterone, and epidermal growth factor receptor ligands stimulate growth in a subset of breast cancers, however recent studies suggest roles for additional factors such as interleukins-6 and 8, prolactin, and erythropoietin. These and other growth factors act upon ligand-specific receptors to activate janus kinase 2 (JAK2), and JAK2 inhibitors are under investigation as a novel targeted therapy. We tested whether erythropoietin receptor (EPOR) or JAK2 mRNA levels are associated with distant breast cancer recurrence. Methods: We used quantitative RT-PCR to measure mRNA levels of JAK2, EPOR and a series of control genes using archival tumors from 112 women who experienced distant breast cancer recurrence (cases) and 112 tumors from women who did not (controls). Cases and controls were matched for tumor size, lymphovascular invasion, nodal status, extra-nodal extension, and ER/PR/HER2. Recurrence risks were evaluated using logistic regression. Associations between mRNA levels (via microarray data) and recurrence-free survival were validated in an independent cohort from the Netherlands Cancer Institute (n=295) using Cox proportional hazards regression. Results: Increasing JAK2 mRNA levels strongly correlated with a reduced risk of distant recurrence in our case control study (univariate p=0.0004, multivariate p=0.003), and with improved recurrence-free survival in the validation cohort (univariate p=0.0009; multivariate p=0.003). Remarkably, in the validation cohort, the ranking of the prognostic significance of JAK2 (top 3.5% of ~25,000 genes) was comparable to the known strong prognostic indicator of recurrence, ESR1 (top 1.3%). Similarly although less prominently, increasing EPORmRNA levels were significantly associated with reduced distant recurrence in our case control study (continuous model: univariate p=0.01, multivariate p=0.05) and with improved recurrence free survival in the validation cohort in univariate (p=0.03) but not multivariate analysis (p=0.35). Conclusions: JAK2 mRNA levels in breast tumors correlate with a reduced risk of recurrence. Understanding the mechanistic basis for this association is important for the rational application of JAK2 inhibitors.
Abstract 694: More Extensive Left Ventricular Hypertrophy in Transthyretin-Type Cardiac Amyloidosis as Compared to Primary Light-Chain Cardiac Amyloidosis
Authors: Evan Appelbaum, Caitlin Harrigan, Warren J Manning, Frederick L Ruberg, Michael Gibson, Martha Skinner, Kenneth J Tripp, Jeff Packman, Donna Grogan
Journal: Circulation (2008)

Background : Cardiac amyloidosis is generally described as a disease with left ventricular (LV) wall thickening, but data supporting LV morphologic differences between types of amyloidosis are lacking. We sought to examine LV morphologic differences between patients with light chain (AL) and transthyretin (TTR)-type amyloidosis with cardiac involvement using volumetric cardiovascular magnetic resonance (CMR). Methods : Patients with proven AL (n =21) and TTR amyloidosis (n =14) underwent cine CMR using standard methods. Volumetric LV mass, LV volumes, and LV mass/volume ratio were measured by an independent core lab blinded to all patient data, using a contiguous short-axis stack of images covering the left ventricle. Results : Both groups demonstrated a male predominance (TTR 86%, AL 67%) with patients in the TTR group older than AL group (74±8yr vs 61 ± 12yr p=0.002). There were no differences in the degree of heart failure symptoms in the TTR and AL groups: NHYA Class I: 4 vs 5; Class II/III: 9 vs 15; Class IV: 0 vs 1, respectively (p=0.68). The maximum anteroseptal thickness was greater in the TTR group (17.9 ± 3.6mm vs. 14.1 ± 3.3mm; p&lt;0.001). Left ventricular end-diastolic mass was also greater in TTR compared to AL amyloid (236 ± 63g vs. 186 ± 61 g; p=0.02) with no significant difference in LV end-diastolic volume (TTR: 154 ± 32 ml vs. 155 ± 45 ml; p=0.89). The LV mass to volume ratio for TTR amyloidosis was significantly greater than the AL group (1.58 ± 0.5 vs. 1.24 ± 0.4; p=0.02). Conclusions : These data demonstrate that LV morphology differs between TTR and AL cardiac amyloidosis, with increased wall thickness and mass in TTR despite similar baseline symptoms and clinical characteristics. Given the reported more aggressive course of AL vs. TTR cardiac amyloidosis, the clinical significance of these findings needs to be further evaluated.
Sodium amylobarbitone in the differential diagnosis of confusion
Authors: N G Ward, D B Rowlett, P Burke
Journal: American Journal of Psychiatry (1978)

The authors describe the use of intravenous sodium amylobarbitone to differentiate between functional and organic confusion. Four psychiatric patients with functional confusion developed a clear sensorium on this drug. Since previous studies have demonstrated that organic confusion is increased by sodium amylobarbitone, the authors conclude that the drug can be an aid in the differential diagnosis of confusion. They discuss possible applications.
PTH-203 Clinical benefits of pump infusion pressure monitoring in patients on home parenteral nutrition
Authors: M Small, M Kallis, A Tsoukalis, JC Cascailh, SM Gabe
Journal: Gut (2015)

<h3>Introduction</h3> The role of monitoring intravenous pump infusion pressures in the early diagnosis or treatment of catheter related problems has not been fully realised. Previous industry collaboration resulted in the development of a system to monitor infusion pressures.<sup>1 </sup>This follow on study aimed to identify the normal range of infusion pressures in patients on home parenteral nutrition and if these could aid in the diagnosis and treatment of catheter related problems. <h3>Method</h3> 26 patients consented to have their infusion pressures monitored. Infusion pressures were recorded on the Micrel PN+ pump and exported anonymously using GPRS technology to a secure Micrelcare™ server. Any patient receiving home parenteral nutrition (not just those using the Micrel PN+) experiencing a partial or total occlusions had infusion pressures measured pre and post intervention to restore patency to their catheter. <h3>Results</h3> 5484 infusions were recorded from 26 patients over 410 days. The average infusion pressure was 0.28 ± 0.09 (range 0.01–0.85) bar and did not increase with infusion rate (r = 0.3). 20(77%) patients had open ended devices, 4(15%) valved devices and 2(8%) had implanted ports. There was no difference in the pressure readings between devices p = 0.91. There were 69 readings above the Upper Confidence Interval of 0.56 bar from 6 patients. 60 (87%) were from 1 patient with a valved port who reported multiple downstream occlusions. These alarms stopped after changing to a longer length Huber™ needle, but high readings were still recorded. Comparison with the readings from a non valved port revealed those from the valved port were significantly higher p &lt; 0.0001. 1 patient with clinically confirmed thrombosis had a pressure spike of 0.67 bar 5 days before presenting with symptoms. Pressures in the preceding 6 months were within normal limits (≤0.56 bar). 6 patients (all not on regular monitoring via the Micrel PN+) had a partial or total occlusion. Mean pre intervention pressure was 0.31 ± 0.048 bar, post intervention it was 0.2 bar ±0.055, p = 0.007. <h3>Conclusion</h3> This study describes the normal range of infusion pressures in patients on home parenteral nutrition and how these can be used in the diagnosis and treatment of catheter related problems such as occlusion or thrombosis. Sudden spikes in infusion pressure may be indicative of an upcoming complication, however the extent to which these can be used to accurately predict specific complications such as thrombosis requires further analysis. <h3>Disclosure of interest</h3> M. Small: None Declared, M. Kallis Paid Instructor for: Micrel Medical Devices, A. Tsoukalis Employee of: Micrel Medical Devices, J. Cascailh Employee of: Micrel Medical Devices, S. Gabe: None Declared. <h3>Reference</h3> Gabe, <i>et al.</i><i>Clin Nutr. </i>2013;32(Suppl 1):S15
New York University medical cadavers found in mass grave
Authors: Owen Dyer
Journal: BMJ (2016)

Bodies donated to New York University’s medical school have been found in unmarked mass graves on Hart Island, where New York City buries the dead it considers unclaimed and indigent. The donors, while living, had signed forms assuring them that their remains would be either returned to their families or cremated once the school had finished using them.

The number of donors to end up on Hart Island is likely to remain a mystery. A New York Times analysis of data held on 62 000 burials by the nonprofit Hart Island Project found hundreds of bodies that had been buried one to three years after their death. Most of these were believed to be medical cadavers. But there have been …
Freedom of inquiry and subjects' rights: historical perspective
Authors: D F Musto
Journal: American Journal of Psychiatry (1977)

The author presents an historical overview of the various attitudes toward animal and human experimentation. He cites advocates (Bacon, Welch) and opponents (Johnson, Shaw) and traces the debate from the Graeco-Roman era, through the rise of the scientific establishment, to the present. Controversy over the fundamental rights of individual research subjects versus a future-oriented freedom of inquiry has been and continues to be a dilemma for clinicians and research scientists.
P2-126: The role of pax transcription factors in lung carcinogenesis: relationship to c-Met receptor tyrosine kinase
Authors: Rajani Kanteti, Vidya Nallasura, Cindy Wang, Rabia Hasan, Sivakumar Loganathan, Ramasamy Jagadeeswaran, Aliya Husain, Deborah Lang, Ravi Salgia
Journal: Journal of Thoracic Oncology (2007)
Comparison of the ACTH suppression test and dexamethasone suppression test in depressed patients
Authors: K Demisch, L Demisch, H J Bochnik, F Schulz
Journal: American Journal of Psychiatry (1983)

Fourteen depressed patients were given the dexamethasone and ACTH suppression tests. The results of 71% agreed, suggesting that in a subgroup of depressed patients dexamethasone resistance reflects a central rather than peripheral dysfunction of the hypothalamic-pituitary-adrenal axis.
Bromocriptine
Authors: Jan Koch-Weser, David Parkes
Journal: New England Journal of Medicine (1979)

BROMOCRIPTINE (2-bromo-alpha-ergocryptine, Parlodel) (Fig. 1), an ergot derivative with dopamine receptor agonist actions that lowers prolactin levels in the blood,1 2 3 4 5 was developed by Flückiger as a compound with powerful action on prolactin but with little toxicity to the vascular system or uterus.6 , 7 The FDA-approved package insert gives as the only indication "the short-term treatment of amenorrhea/galactorrhea associated with hyperprolactinemia due to varied etiologies, excluding demonstrable pituitary tumors." The drug is considered "not indicated in the management of infertility" because "safe use has not been demonstrated in pregnancy." This review will discuss bromocriptine from the broader, British perspective.Mechanism of Action . . .
AB1007 Determination of Free Carnitine and Acyl-Carnitine Status of Patients with Juvenile Idiopathic Arthritis
Authors: E. Kıykım, A.-C. Aktuglu-Zeybek, K. Barut, T. Zubarioglu, M.S. Cansever, A. Aydin, O. Kasapcopur
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is not a single disease; it9s group of all arthritis with unknown etiology, starting before 16 years of age and lasting at least 6 weeks long. JIA is the most common rheumatic disease in childhood. Carnitine is an important molecule in cellular energy metabolism. Secondary carnitine deficiency can be detected in chronic diseases by either renal loss or increased demand. <h3>Objectives</h3> We hypothesized that secondary carnitine deficiency may be seen to increased demand in JIA patients. In the present study our aim is to determine free carnitine and acyl-carnitine levels of Turkish JIA patients. <h3>Methods</h3> 114 patients with a diagnosis of juvenile idiopathic arthritis and a healthy 50 individuals served as control group, were included to the study. A fasting blood sample was taken for free carnitine and acyl-carnitine esters with tandem mass spectrometry from children in both groups. <h3>Results</h3> Screening of acyl-carnitine profile revealed free carnitine, C14, C16, C16-OH, C18 and C18:2-OH carnitine levels were higher (p&lt;0,0001, p&lt;0,0001, p&lt;0,0001, p&lt;0,0001 and p=0,004 respectively), while C6 carnitine levels were lower (p&lt;0,0001) in JIA patients than the control group. Free carnitine levels were significantly higher (48.05±13.36 μmol/L) in patients under anti-inflammatory drug therapy than those who did not receive any treatment (43.18±7.96 μmol/L) (p=0,004). <h3>Conclusions</h3> In the present study we were not able to define secondary carnitine deficiency in JIA patients, therefore routine carnitine supplementation is not recommended in all patients with JIA. <h3>References</h3> Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007 Mar 3; 369(9563):767-78. Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad. Sci.2004; 1033:42–51. <h3>Disclosure of Interest</h3> None declared
Another possible food-borne outbreak of hepatitis A in the Netherlands indicated by two closely related molecular sequences, July to October 2011
Authors: N Fournet, D Baas, W van Pelt, C Swaan, H J Ober, L Isken, J Cremer, I Friesema, H Vennema, I Boxman, M Koopmans, L Verhoef
Journal: Eurosurveillance (2012)

In November 2011, a cluster of initially five cases of hepatitis A infection with closely related strains was identified in the Netherlands. England reported possibly related cases. Strains with identical sequences had been involved in previous outbreaks linked to semi-dried tomatoes. Investigation of the Dutch cluster suggested a link with ready-to-eat salads including those containing semi-dried tomatoes. Despite trace-back, a source was not identified. Vigilance is needed, and rapid sharing of data may help source-tracing.
Progressions of a Reticulum-Cell Sarcoma of the Mouse &lt;italic&gt;In Vivo&lt;/italic&gt; and &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: Clyde J. Dawe, Michael Potter, Joseph Leighton
Journal: JNCI Journal of the National Cancer Institute (1958)

A histiocytic neoplasm, induced by methylcholanthrene in a DBA/2 mouse and adapted to ascites form, has been observed in serial mouse transfer and in continuous culture for 2 years. In vivo, the neoplasm showed a minor amount of morphologic progression toward a less well-differentiated histiocytic form. In vitro, morphologic progression was marked by the appearance of cells with single or multiple giant nuclei. Ascites tumors resulting from inoculation of cultures into mice 11 months after explantation showed greater morphologic change than the tumors carried continuously in mice during the same period. Changes consisted in increased pleomorphism, the occurrence of numerous giant cells, and the loss of distinctive histiocytic features. Ascites tumors derived from cultures at 11 months showed a nearly pure hypotetraploid population, compared with a predominantly hyperdiploid population in the serially mouse-passed line at comparable time. Mitoses in cells in culture after 24 months showed chromosome numbers predominantly in the near-diploid range. Metacentric chromosomes were found both in long-term cultures and in ascites tumors derived from cultures, but not in the serially mouse-passed line. In continuous mouse passage the ascites tumor showed at the 15th and 69th transfers nearly equal virulence. After 8 and 11 months in continuous culture, the ascites tumors derived from these cultures showed a marked decrease of virulence. After 11 months or more in culture, inoculums of 106 culture cells into mice rarely resulted in tumor production. Mechanisms of origin of the observed changes of latent period, virulence, and tumor-producing ability are discussed.
Case 31-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Mary Ellen B. Wohl, Eugene J. Mark
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 12 1/2-week-old boy was admitted to the hospital because of tachypnea and bilateral rales.The child was born of a full-term pregnancy; the second trimester was complicated by streptococcal pharyngitis, which was treated with ampicillin, and a urinary tract infection, for which trimethoprim–sulfamethoxazole was administered; the mother had recurrent epistaxes, and her hemoglobin level at the time of delivery was approximately 9 g per 100 ml. A cesarean section was performed because of cephalopelvic disproportion. The boy's birth weight was 5.1 kg. Apgar scores were 10 at one and five minutes; rapid respirations were noted shortly . . .
Targeting the ASCT2 glutamine uptake and metabolism pathway in triple-negative breast cancer
Authors: M. van Geldermalsen, Q. Wang, C.G. Bailey, Y. Feng, R. Nagarajah, A. Marshall, A. Thoeng, S. O'Toole, J.E.J. Rasko, J. Holst
Journal: Annals of Oncology (2015)
Medication for Attention Deficit–Hyperactivity Disorder and Criminality
Authors: David Cohen
Journal: New England Journal of Medicine (2013)

Background-Attention deficit hyperactivity disorder (ADHD) is a common disorder that is associated with criminal behavior.Pharmacological treatment is available for ADHD and may reduce the risk of criminality Methods-We gathered information on all individuals with a diagnosis of ADHD (N=25,656), their pharmacological treatment, and subsequent criminal convictions in Sweden during 2006 to 2009 using Swedish national registers.We used stratified Cox regression analyses to compare the rate of criminality while on ADHD medication, compared with the rate for the same individual while off medication.Results-Compared to non-medication periods, the criminality rate while on medication was significantly decreased by 32% (stratified Cox Regression hazard ratio: 0.68; 95 % confidence interval: 0.63-0.73)for men and 41% (hazard ratio: 0.59; 95 % confidence interval: 0.50-0.70)for women.The rate reduction remained between 17-46% in sensitivity analyses among males, including different exposures (e.g., type of treatment -stimulant and non-stimulant) and outcomes (e.g., type of crime -less severe, violent, and substance-related conviction).Conclusions-We found statistically significant associations between ADHD medication and criminality in within-individual comparisons, with lower rates of criminality observed during periods on treatment.These findings raise the possibility that medication treatment reduces the risk of criminality among patients with ADHD.About 5% of all children in the Western world fulfill diagnostic criteria for ADHD 1 and a large proportion of these are treated pharmacologically 2 .ADHD is associated with criminality 3,4 and externalizing disorders 5 .Beneficial short-term effects of ADHD medication on symptoms of ADHD and associated conduct problems have been demonstrated in numerous randomized controlled studies with children 6-8 and adults [9][10][11] .ADHD symptoms are largely persistent from childhood into adulthood 12 , but one prominent feature of ADHD-treatment is that medication discontinuation is common 13,14 , especially in adolescence and early adulthood 15 .The importance of treatment discontinuation for criminality and other longer-term outcomes is largely unknown.
AZT: A Biochemical Response Modifier of Methotrexate and 5-Fluorouracil Cytotoxicity in Human Ovarian and Pancreatic Carcinoma Cells
Authors: G Weber, M Nagai, N Prajda, H Nakamura, T Szekeres, E Olah
Journal: Cancer Communications (1991)

In ovarian and pancreatic carcinoma cell lines, the activity of the salvage enzyme, thymidine kinase (EC 2.7.1.21), was 2- to 13-fold higher than that of the key enzyme of thymidylate de novo biosynthesis, thymidylate synthase (dTMP synthase, EC 2.1.1.45). AZT (3'-azido-3'-deoxythymidine, zidovudine) competitively inhibited thymidine kinase activity in extracts of human ovarian and pancreatic carcinoma cells, with Dixon plots yielding Ki = 1.1 microM in both cell lines. AZT (20 microM) yielded synergistic cytotoxicity with methotrexate (0.4 microM) in human pancreatic carcinoma cells in clonogenic assay and also with methotrexate (0.02 microM) in human ovarian carcinoma cells, as measured by cell counts. Thymidine (10 microM) and hypoxanthine (100 microM) reversed these inhibitions. AZT (20 or 40 microM) also provided synergistic cytotoxicity with 5-fluorouracil (0.5 and 1.0 microM) in human pancreatic carcinoma cells in clonogenic assay. These studies suggest a new role for AZT, which, as an inhibitor of thymidine salvage, should be useful as a biochemical response modifier to provide a synergistic clinical anticancer impact on de novo biosynthesis of thymidylates in conjunction with methotrexate or 5-fluorouracil.
Recommendations of the ESGE Workshop on Ethics in Teaching and Learning Endoscopy
Authors: A. Axon, L. Aabakken, P. Malfertheiner, I. Danielides, S. Ladas, J. Hochberger, C. Williams, D. Campbell, M. Zakaria
Journal: Endoscopy (2003)

The ethical implications of teaching and training in gastrointestinal endoscopy can be derived from the basic principle of Hippocrates: ”to help or at least not to harm”. The goal of ethical teaching can be summarized as follows:
SP0150 Genetics of Vasculitis: Lessons Learned from Genome-Wide Association Studies
Authors: J. Martin
Journal: Annals of the Rheumatic Diseases (2015)

In the past years there has been a dramatic increase in genomic discoveries involving complex, non-Mendelian diseases, as a result of genome-wide association (GWA) studies. Typically, GWAs analyze millions of single-nucleotide polymorphism (SNP) covering most of the genome and have significantly advanced our understanding of the genetic aspects of different vasculitis. Thus, recent GWAS have identified genetic association of ERAP1, CCR1-CCR3, STAT4, KLRC4, GIMAP4, and TNFAIP3 with Behcet9s disease; BLK and CD40 with Kawasaki disease; SERPINA1 and SEMA6A with antineutrophil cytoplasmic antibody associated vasculitides or IL12B and FCGR2A/FCGR2A in Takayasu arteritis. In addition, these studies has allowed a more precise role of HLA region in vasculitis, through the identification of amino acid position of HLA-B and HLA-DR molecules implicated in the risk of Behcet9s disease an giant cell arteritis. Further genetic (NGS) and functional studies are needed in order to better understand the pathophysiological consequences of the genetic variants associated with vasculitidies. <h3>Disclosure of Interest</h3> None declared
Countertransference: a neglected subject in clinical supervision
Authors: M K Goin, F Kline
Journal: American Journal of Psychiatry (1976)

As an acknowledged aspect of psychotherapy, countertransference would be an anticipated subject for discussion in clinical supervision. However, the authors' review of videotapes of 24 supervisors working with second-year residents revealed that 12 made no comments on the subject, 8 approached the subject directly, and 4 approached it indirectly. The authors discuss the reasons for this avoidance of countertransference issues and note that discussion of countertransference does not necessarily change supervision into therapy.