tbuckley/cabot-search huggingface dataset:
Reply to Klaus-Peter Dieckmann's Letter to the Editor re: Niels J. van Casteren, Hans Stoop, Gert R. Dohle, Ronald de Wit, J. Wolter Oosterhuis, Leendert H.J. Looijenga. Noninvasive Detection of Testicular Carcinoma In Situ in Semen Using OCT3/4. Eur Urol 2008;54:153–60
Authors: Niels J. van Casteren, Gert R. Dohle, Leendert H.J. Looijenga
Journal: European Urology (2008)
DNA Repair Enzyme Expression and Differential Response to Temozolomide in a Patient With Both Glioblastoma and Metastatic Pancreatic Neuroendocrine Tumor
Authors: Lynn-Kristin Bracht, Patrick Wen, Jeffrey A. Meyerhardt, Matthew H. Kulke, Jason L. Hornick, Mark Redston, Debra Conrad LaFrankie, Peter M. Black, Santosh Kesari, Andrew Norden, Jan Drappatz
Journal: Journal of Clinical Oncology (2008)
Protein Kinase D2 Controls Cardiac Valve Formation in Zebrafish by Regulating Histone Deacetylase 5 Activity
Authors: Steffen Just, Ina M. Berger, Benjamin Meder, Johannes Backs, Andreas Keller, Sabine Marquart, Karen Frese, Eva Patzel, Gerd-Jörg Rauch, Hugo A. Katus, Wolfgang Rottbauer
Journal: Circulation (2011)

The molecular mechanisms that guide heart valve formation are not well understood. However, elucidation of the genetic basis of congenital heart disease is one of the prerequisites for the development of tissue-engineered heart valves.We isolated here a mutation in zebrafish, bungee (bng(jh177)), which selectively perturbs valve formation in the embryonic heart by abrogating endocardial Notch signaling in cardiac cushions. We found by positional cloning that the bng phenotype is caused by a missense mutation (Y849N) in zebrafish protein kinase D2 (pkd2). The bng mutation selectively impairs PKD2 kinase activity and hence Histone deacetylase 5 phosphorylation, nuclear export, and inactivation. As a result, the expression of Histone deacetylase 5 target genes Krüppel-like factor 2a and 4a, transcription factors known to be pivotal for heart valve formation and to act upstream of Notch signaling, is severely downregulated in bungee (bng) mutant embryos. Accordingly, the expression of Notch target genes, such as Hey1, Hey2, and HeyL, is severely decreased in bng mutant embryos. Remarkably, downregulation of Histone deacetylase 5 activity in homozygous bng mutant embryos can rescue the mutant phenotype and reconstitutes notch1b expression in atrioventricular endocardial cells.We demonstrate for the first time that proper heart valve formation critically depends on Protein kinase D2-Histone deacetylase 5-Krüppel-like factor signaling.
The Heimlich Maneuver and the Resuscitation of Near-Drowning Victims-Reply
Authors: Joseph P. Ornato
Journal: JAMA (1986)

In Reply.—  The new standards and guidelines for cardiopulmonary resuscitation and emergency cardiac care 1 restrict the use of the Heimlich maneuver in the management of near-drowning victims to only those circumstances in which the rescuer suspects that foreign (particulate) matter is obstructing the airway. If the victim does not respond appropriately to mouthto-mouth ventilation, the rescuer is permitted to try a Heimlich maneuver on the grounds that a foreign-body obstruction may have been overlooked. The standards specifically state that  attempt to remove water from the breathing passages by any means other than suction may be unnecessary and dangerous because it could eject gastric contents and cause aspiration (p 2929).  The reason for the restriction is that there is inadequate scientific evidence to support the safety or efficacy of the Heimlich maneuver in this setting. Controlled studies have not shown that the Heimlich maneuver is useful in freshwater near-drowning.
Sweet's syndrome induced by granulocyte colony-stimulating factor in a woman with congenital neutropenia
Authors: Marie Aleth Richard, Jean Jacques Grob, Renaud Laurans, Sylvie Hesse, Philippe Brunet, Anne Marie Stoppa, Jean Jacques Bonerandi, Yvon Berland, Dominique Maraninchi
Journal: Journal of the American Academy of Dermatology (1996)
The leukotriene-antagonist ICI-204,219 inhibits the early airway reaction to cumulative bronchial challenge with allergen in atopic asthmatics
Authors: B Dahlen, O Zetterstrom, T Bjorck, SE Dahlen
Journal: European Respiratory Journal (1994)

The hypothesis that cysteinyl-leukotrienes (LTC4, LTD4 and LTE4) are mediators of allergen-induced airway obstruction in asthmatics was tested with the specific receptor antagonist ICI-204,219, in a double-blind, placebo-controlled, randomized, cross-over bronchoprovocation study. On three occasions, cumulative bronchial challenge with specific allergen was performed in 10 males with mild allergic asthma. The first control session established the baseline provocative dose of allergen producing a decrease in forced expiratory volume in one second (FEV1) by 20% (PD20FEV1). The two rechallenges were performed 2 h after oral administration of placebo or 20 mg of ICI-204,219. The allergen dose-response relations were highly reproducible, producing PD20 values at the control session and after placebo treatment which varied by no more than 0.7-1.3 fold (95% confidence interval (95% CI)). After ICI-204,219, the median cumulated allergen dose was 5.5 fold higher, and the group geometric mean PD20 was increased 2.5 times. Furthermore, the recovery time after the immediate bronchoconstriction was shorter (40 vs 60 min). The wheal and flare responses to intradermally injected LTD4 were somewhat inhibited by ICI-204,219, whereas responses to histamine were unaffected. However, the findings suggest that skin testing with LTD4 is unlikely to predict the degree of leukotriene-antagonism in the airways. The findings confirm and extend the indications that cysteinyl-leukotrienes are important mediators of allergen-induced airway obstruction, and that leukotriene-antagonists should be evaluated as a potential new therapy in allergic asthma.
Origins of the First National Medical Convention 1826-1846
Authors: Byron Stookey
Journal: JAMA (1961)

DURING THE TWO DECADES preceding the first National Medical Convention, held in New York in 1846, numerous attempts were made to bring together delegates from the state medical societies and medical institutions in an effort to improve medical education. While these early meetings were unsuccessful in assembling delegates on a national scale, circulars containing copies of the resolutions adopted, urging higher standards of professional training and pleading for a national reform, were sent from time to time to the medical societies and institutions, thus awakening a national interest which contributed eventually to the success of the first national medical convention.  The Medical Society of the State of Vermont sent a circular in December, 1825, and June, 1826, to the medical societies and the medical institutions of New Hampshire, Maine, Massachusetts, Rhode Island, Connecticut, and New York, proposing an increase in the requirements for all candidates for medical licenses and
THE NORMAL FATE OF ERYTHROCYTES
Authors: Peyton Rous, Oswald H. Robertson
Journal: The Journal of Experimental Medicine (1917)

The phagocytosis of red corpuscles, while frequent in the normal dog, rat, and guinea pig, is slight in man, the rhesus monkey, and many rabbits. In cats it is always negligible in amount and frequently absent. Phagocytosis will not suffice as a general explanation of normal blood destruction. When the liver, spleen, and bone marrow of the cat, dog, rabbit, or monkey are slowly perfused with defibrinated blood or Locke"s solution, bodies are given off into the fluid which have the appearance of red corpuscles that have lost their hemoglobin but retained the rest of their cell substance. These bodies possess many of the properties supposedly distinctive of red corpuscles. They are the product of disordered parenchymal cells. By a special method, it has proved possible to search the body, organ by organ, and the circulating blood also, for disintegrating red corpuscles. Shadows of red cells are not present anywhere, nor are hemolyzing red cells found. A hemolytic process, in the ordinary sense of the term, can scarcely play an. important part in normal blood destruction. Instead, it is certain that some red corpuscles, at least, are destroyed in another way; namely, by fragmentation. Normal blood regularly contains small numbers of fragmentation forms-microcytes and poikilocytes-and accumulations of them are regularly present in the spleen, but are found only inconstantly in the other organs. The fragments are in evident process of further subdivision. They occur not only in species in which phagocytosis as a means of cell destruction is negligible (cats), but also in animals in which it is an important process (dogs, some rabbits). The method of study that we have employed is well suited to disclose how the blood is destroyed. The importance of cell fragmentation in this connection is indicated by our failure to find any other means of destruction, save only the phagocytosis already known. Further facts indicating the importance of fragmentation are presented in our second paper, where a general discussion will also be found.
Side-effect of Amitriptyline
Authors: S. Bockner
Journal: BMJ (1965)

MEDITALSOUHALneedle was used and the dorsum of the hand always chosen as the site of injection.With a little care this can be a relatively easy tech- nique.The results were much improved.The local anaesthetic used was prilocaine (Citanest) 0.5% without adrenaline, the aver- age dose being 30 ml. (150 mg.), decreasing to 20 ml.(100 mg.) in thin and frail limbs and increasing to 40 ml.(200 mg.) in fat and more muscular limbs.In one case a total of 60 ml.(300 mg.) had to be injected as the tourniquet accidentally deflated lN minutes after the first 40 ml.had been injected.There were no systemic effects seen in any case.The time of inflation of the tourniquet ranged from 10 minutes to 1 hour 45 minutes.-Iam, etc.,
Nocturnal oesophageal motor activity is dependent on sleep stage.
Authors: F Castiglione, C Emde, D Armstrong, C Schneider, P Bauerfeind, G Stacher, A L Blum
Journal: Gut (1993)

Simultaneous overnight oesophageal pH and manometric and sleep electroencephalographic recordings were performed in eight healthy subjects, aged 20-38 years, to test the hypothesis that the frequency of primary, swallow related contractions decreases progressively with deeper sleep stages whereas the frequency of secondary contractions remains constant throughout the night. During the nocturnal period (2300 to 0700), periods of oesophageal motor quiescence were interspersed by clusters of contractions detected 5 and 15 cm above the lower oesophageal sphincter. Primary contractions decreased in frequency from 1.42/min (median) during arousal periods to 0.22/min during stage 1 sleep, 0.05/min during stages 2 to 4 combined, and 0.03/min during rapid eye movement (REM) sleep. Secondary contractions were also most frequent during arousal periods (0.51/min) and they, too, decreased in frequency during stage 1 (0.35/min) and stages 2 to 4 combined (0.08/min). During REM sleep, however, the frequency of secondary contractions increased (0.50/min) to levels noted during arousal and stage 1 sleep. Compared with primary contractions, secondary contractions had a lower amplitude (51.9 hPa v 76.0 hPa; p = 0.0078) and a shorter duration (3.08 v 4.06 s; p = 0.0078). The results of this study suggest that there is no intrinsic oesophageal motor activity in the absence of a stimulatory input from the central nervous system and that the increased number of secondary contractions during REM sleep may be a result of an REM related increase in autonomic nervous system activity although a temporary decrease of efferent inhibitory influences cannot be ruled out. Nocturnal contraction clusters comprise both primary contractions during arousals and stage 1 sleep and secondary contractions during REM sleep.
A Novel Bone Morphogenetic Protein Signaling in Heterotypic Cell Interactions in Prostate Cancer
Authors: Shangxin Yang, Linda K. Pham, Chun-Peng Liao, Baruch Frenkel, A. Hari Reddi, Pradip Roy-Burman
Journal: Cancer Research (2008)

Abstract We examined the effect of the extracellular bone morphogenetic protein (BMP) 2 and 7, which are up-regulated in the prostate adenocarcinomas of the conditional Pten deletion mouse model, on primary cultures of cancer-associated fibroblasts (CAF) derived from these tumors. In the CAF, we show that BMP2 or BMP7, but not transforming growth factor β-1, can strikingly stimulate secretion of stromal cell–derived factor-1 (SDF-1), also known as CXCL12. The CAF cells express type I and type II BMP receptors as well as the receptor for SDF-1, CXCR4. SDF-1 activation is associated with BMP-induced Smad phosphorylation, and the stimulatory effect is blocked by BMP antagonist, noggin. The findings that BMP treatment can increase SDF-1 pre-mRNA levels in a time-dependent manner and actinomycin D treatment can abolish stimulatory effect of BMP suggest a transcriptional modulation of SDF-1 by BMP signaling. Using a human microvascular endothelial cell line, we show that SDF-1 present in the conditioned medium from the stimulated CAF can significantly induce tube formation, an effect relating to angiogenic function. Furthermore, we found that BMP2 can also protect the CAF from serum starvation–induced apoptosis independent of SDF-1, implying that BMP may induce other factors to sustain the survival of these cells. In short, this report establishes a novel BMP-SDF-1 axis in the prostate tumor along with a new prosurvival effect of BMP that when considered together with our previously described oncogenic properties of BMP indicate a circuitry for heterotypic cell interactions potentially critical in prostate cancer. [Cancer Res 2008;68(1):198–205]
Prevalence of abnormal liver function and response to lifestyle interventions in newly diagnosed type 2 diabetes: preliminary results of a UK randomised controlled study
Authors: R. Parker, N. Guthrie, N. Patel, W. Woltersdorf, R. Andrews, C. Dayan, C. A. McCune
Journal: Gut (2011)

<h3>Introduction</h3> Non-alcoholic fatty liver disease (NAFLD) is increasingly common with a prevalence of between 20% and 34% in Europe and the US. There is a close association between NAFLD and other features of the metabolic syndrome such as insulin resistance, hypertension and obesity. We investigated liver health in patients with diabetes, and the effect of lifestyle interventions on liver health in newly diagnosed type 2 diabetics. <h3>Methods</h3> Patients within 5–8 months of diagnosis of diabetes were identified from four centres in the South West of England. All participants received usual care for patients with diabetes. Patients were randomised to usual care alone (UC), additional dietary advice (D) or additional dietary and exercise advice (D&amp;E). LFTs were measured at baseline and twelve months. <h3>Results</h3> Median age of participants was 61 years, 36% were female. Alcohol intake was modest and did not differ significantly between groups. Modest reductions in BMI and insulin resistance were seen in groups D and D&amp;E: these were not significant. There was no change in blood pressure. At baseline 24 of 424 patients (5.6%) had any abnormality in liver function. At twelve months this was 15 of 212 patients (7.1%). Increased prevalence was seen in all groups except D. Transaminase levels followed the same trend with regard to prevalence at baseline (2.6%) and 12 months (3.7%). AST:ALT ratio (AAR) increased over twelve months with Pearson correlation of 0.92. In patients with abnormal transaminases non-invasive assessment of fibrosis (NAFLD fibrosis score) demonstrated that 20% of patients were at risk of advanced fibrosis at baseline, climbing to 80% at twelve months, without differences between groups. This is 0.5% and 3% of all participants at baseline and twelve months respectively. <h3>Conclusion</h3> In newly diagnosed diabetes abnormalities of liver function persist in the first year of diagnosis regardless of lifestyle intervention. Estimation of fibrosis in a subgroup of patients demonstrated increased prevalence of advanced fibrosis over twelve months. This is consistent with rising AAR over the same period for the whole group. Longer-term follow up of these patients is required, but initial data are similar to cohorts described elsewhere in the literature,1 and reflect a significant risk of liver disease in patients with type 2 diabetes.
Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis
Authors: C J van der Laken, A E Voskuyl, J C Roos, M Stigter van Walsum, E R de Groot, G Wolbink, B A C Dijkmans, L A Aarden
Journal: Annals of the Rheumatic Diseases (2006)

Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of infliximab-anti-infliximab complexes.To investigate the in vivo mechanism of not responding and the role of human anti-chimeric antibodies (HACAs) by using radiolabelled infliximab.Two responding and two non-responding patients with rheumatoid arthritis, infused with radiolabelled infliximab, were investigated by both imaging and serum analysis.Images showed predominant presence of infliximab in blood up to 24 h, with a trend of faster blood clearance and of higher liver/spleen uptake in a non-responding patient. Clinically inflamed joints showed uptake of the drug. The HACA level in the non-responders was high (1641 and 1008 U/ml), but low or not detectable in responders. Sucrose gradients of serum showed antibody complexes in both non-responders. Various sizes of antibody complexes, including very large ones, were observed in a non-responder who developed a serious infusion reaction.Formation of infliximab-anti-infliximab complexes were found in non-responders due to the presence of large amounts of HACA. This finding, supported by both imaging and serum analysis data, may explain failure of infliximab treatment.
High incidence of porokeratosis in renal transplant recipients
Authors: P. HERRANZ, A. PIZARRO, R. DE LUCAS, M.G. ROBAYNA, F.A. RUBIO, A. SANZ, F. CONTRERAS, M. CASADO
Journal: British Journal of Dermatology (1997)

Immunosuppression is a well-documented precipitant of porokeratosis (PK). However, PK is not considered among the most common cutaneous disorders in immunosuppressed patients. We studied prospectively a series of 103 renal transplant patients and found 11 cases (10.68%) of PK. Our series represents the highest incidence of PK in transplant patients reported so far. Our findings suggest that PK in transplant recipients may be more frequent than previously thought.
MHC Haplotype Matching for Unrelated Hematopoietic Cell Transplantation
Authors: Effie W Petersdorf, Mari Malkki, Ted A Gooley, Paul J Martin, Zhen Guo
Journal: PLoS Medicine (2007)

Current criteria for the selection of unrelated donors for hematopoietic cell transplantation (HCT) include matching for the alleles of each human leukocyte antigen (HLA) locus within the major histocompatibility complex (MHC). Graft-versus-host disease (GVHD), however, remains a significant and potentially life-threatening complication even after HLA-identical unrelated HCT. The MHC harbors more than 400 genes, but the total number of transplantation antigens is unknown. Genes that influence transplantation outcome could be identified by using linkage disequilibrium (LD)-mapping approaches, if the extended MHC haplotypes of the unrelated donor and recipient could be defined.We isolated DNA strands extending across 2 million base pairs of the MHC to determine the physical linkage of HLA-A, -B, and -DRB1 alleles in 246 HCT recipients and their HLA-A, -B, -C, -DRB1, -DQB1 allele-matched unrelated donors. MHC haplotype mismatching was associated with a statistically significantly increased risk of severe acute GVHD (odds ratio 4.51; 95% confidence interval [CI], 2.34-8.70, p < 0.0001) and with lower risk of disease recurrence (hazard ratio 0.45; 95% CI, 0.22-0.92, p = 0.03).The MHC harbors genes that encode unidentified transplantation antigens. The three-locus HLA-A, -B, -DRB1 haplotype serves as a proxy for GVHD risk among HLA-identical transplant recipients. The phasing method provides an approach for mapping novel MHC-linked transplantation determinants and a means to decrease GVHD-related morbidity after HCT from unrelated donors.
Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL
Authors: Klaus W Wagner, Elizabeth A Punnoose, Thomas Januario, David A Lawrence, Robert M Pitti, Kate Lancaster, Dori Lee, Melissa von Goetz, Sharon Fong Yee, Klara Totpal, Ling Huw, Viswanatham Katta, Guy Cavet, Sarah G Hymowitz, Lukas Amler, Avi Ashkenazi
Journal: Nature Medicine (2007)
Combined Mometasone Furoate and Formoterol in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD): Phase 3 Efficacy and Safety Study
Authors: D.E. Doherty, E. Kerwin, D.P. Tashkin, C.E. Matiz-Bueno, T. Shekar, S. Banerjee, B. Knorr, H. Staudinger
Journal: Journal of Allergy and Clinical Immunology (2012)

We report findings from a phase 3 trial evaluating the effects of mometasone furoate/formoterol (MF/F), administered via metered-dose inhaler, on pulmonary function in moderate-very severe COPD. This 26-wk, multicenter, randomized, double-blind, placebo (PBO)-controlled trial evaluated MF/F 400/10μg twice daily (BID) and 200/10μg BID in current/ex-smokers (≥10 pack-y) ages ≥40y with moderate−very severe COPD (mean baseline [BL] % predicted FEV1, 38.7%). Subjects received BID treatment with MF/F 400/10μg, MF/F 200/10μg, MF 400μg, F 10μg, or PBO. Lung function was analyzed for mean changes from BL in FEV1 over 0−12hrs (AUC0−12 FEV1) and pre-dose AM FEV1 at endpoint (EP) after 13wks or 26wks of treatment. 1193 subjects received treatment. At 13wks, changes from BL in AUC0−12 FEV1 with MF/F 400/10μg, MF/F 200/10μg, MF 400μg, F 10μg, PBO were 179mL,*†‡ 139mL,*† 53mL, 92mL,* 18mL, respectively (*P≤.004 vs PBO; †P≤.001 vs MF 400μg ‡P≤.001 vs F 10μg). At 26wks, changes from BL in AUC0−12 FEV1 with MF/F 400/10μg, MF/F 200/10μg, MF 400μg, F 10μg, PBO were 152mL,*† 120mL,*‡ 33mL, 63mL,§ 8mL, respectively (*P<.001 vs PBO; †P≤.001 vs MF 400μg, F 10μg; ‡P≤.027 vs MF 400μg, F 10μg; §P=.038 vs PBO). At 26wks, changes from BL in pre-dose AM FEV1 with MF/F 400/10μg, MF/F 200/10μg, MF 400μg, F 10μg, PBO were 92mL,*† 69mL,* 27mL, 10mL, 3mL (*P≤.030 vs PBO, F 10μg; †P=.017 vs MF 400μg). No unexpected AEs were observed; MF/F was generally well tolerated. MF/F treatments significantly improved lung function and were well tolerated in subjects with moderate to very severe COPD.
The Relation between Volume and Outcome in Health Care
Authors: Edward L. Hannan
Journal: New England Journal of Medicine (1999)

Twenty years ago, Luft and colleagues1 showed that hospitals that had higher volumes of specific surgical procedures had significantly lower inpatient mortality rates than did their lower-volume counterparts. Since that time, scores of articles pertaining to the relation between volume and outcome have been published, and studies continue to appear. There is a need to consider how the results of these studies should be incorporated into policies aimed at improving the quality of health care.Most studies focused on surgical procedures rather than on medical conditions, and most used inpatient mortality as the only measure of adverse outcome. Also, most . . .