tbuckley/cabot-search huggingface dataset:
Water Drinking Acutely Improves Orthostatic Tolerance in Healthy Subjects
Authors: Christoph Schroeder, Victoria E. Bush, Lucy J. Norcliffe, Friedrich C. Luft, Jens Tank, Jens Jordan, Roger Hainsworth
Journal: Circulation (2002)

Background— Orthostatic symptoms and syncope are common, even in apparently healthy subjects. In patients with severe autonomic dysfunction, water drinking elicits an acute pressor response and improves orthostatic hypotension. We tested the hypothesis that water drinking also improves orthostatic tolerance in healthy subjects. Methods and Results— In a randomized, controlled, crossover fashion, 13 healthy subjects (9 men, 4 women, 31±2 years) ingested 500 mL and 50 mL of mineral water 15 minutes before head-up tilt on two separate days. Finger blood pressure, brachial blood pressure, heart rate, thoracic impedance, and blood flow velocity in the brachial artery and the middle cerebral artery were measured. Orthostatic tolerance was determined as the time to presyncope during a combined protocol of 20 minutes of 60° head-up tilt alone, followed by additional increasing steps of lower body negative pressure (−20, −40, and −60 mm Hg for 10 minutes each or until presyncope). Drinking 500 mL of water improved orthostatic tolerance by 5±1 minute (range, −1 to +11 minutes, P &lt;0.001). After drinking 500 mL of water, supine mean blood pressure increased slightly ( P &lt;0.01) as the result of increased peripheral resistance ( P &lt;0.01). It also blunted both the increase in heart rate and the decrease in stroke volume with head-up tilt. Cerebral blood flow regulation improved after water drinking. Conclusions— Water drinking elicits an acute hemodynamic response and changes in cerebrovascular regulation in healthy subjects. These effects are associated with a marked improvement in orthostatic tolerance.
Some Effects of Calcium on the Activation of Human Factor VIII/Von Willebrand Factor Protein by Thrombin
Authors: Mary Ellen Switzer, Patrick A. McKee
Journal: Journal of Clinical Investigation (1977)

When Factor VIII/von Willebrand factor (FVIII/vWF) protein is rechromatographed on 4% agarose in 0.25 M CaCl(2), the protein and vWF activity appear in the void volume, but most of the FVIII procoagulant activity elutes later. Recent evidence suggests that the delayed FVIII procoagulant activity is a proteolytically modified form of FVIII/vWF protein that filters anomalously from agarose in 0.25 M CaCl(2). To test whether or not thrombin is the protease involved, the effect of 0.25 M CaCl(2) on FVIII/vWF and its reaction with thrombin was examined. About 30% of the FVIII procoagulant activity was lost immediately when solutions of FVIII/vWF protein were made 0.25 M in CaCl(2). When FVIII in 0.15 M NaCl was activated with 0.04 U thrombin/ml and then made 0.25 M in CaCl(2), the procoagulant activity of a broad range of FVIII/vWF protein concentrations remained activated for at least 6 h. But, in 0.25 M CaCl(2), the increase in FVIII procoagulant activity in response to thrombin was much more gradual and once activated, the procoagulant activity was stabilized by 0.25 M CaCl(2). When thrombin-activated FVIII/vWF protein was filtered on 4% agarose in 0.15 M NaCl, there was considerable inactivation of FVIII procoagulant activity; however, the procoagulant activity that did remain eluted in the void volume. In contrast, when thrombin-activated FVIII/vWF protein was filtered in 0.25 M CaCl(2), the FVIII procoagulant activity eluted well after the void volume and remained activated for 6 h. The procoagulant peak isolated by filtering nonthrombin-activated FVIII/vWF protein on agarose in 0.25 M CaCl(2) was compared to that isolated from thrombin-activated FVIII/vWF protein. Both procoagulant activity peak proteins had about the same specific vWF activity as the corresponding void volume protein. Before reduction, the sodium dodecyl sulfate gel patterns for the two procoagulant activity peak proteins were the same. After reduction, the gel pattern for the nonthrombin-activated procoagulant activity peak protein contained bands of 195,000, 148,000-120,000, 79,000, 61,000, 51,000, and 18,000 daltons whereas the pattern for the reduced thrombin-activated procoagulant activity peak protein always lacked the higher molecular weight bands, but consistently showed the four lower molecular weight bands to be well resolved. Taken together, these results imply that thrombin generates the FVIII procoagulant activity that is stabilized by 0.25 M CaCl(2) and elutes aberrantly from 4% agarose in that solvent.
Upper limb fractures in rugby in Huddersfield 1986-1990.
Authors: K S Eyres, A Abdel-Salam, J Cleary
Journal: British Journal of Sports Medicine (1991)

Most injuries sustained by rugby players affect the soft tissues, and fracture is relatively uncommon. Whereas the lower limb is most affected in footballers, the upper limb tends to be injured in rugby players. Thirty consecutive fractures and ten dislocations affecting the upper limb, sustained by 35 rugby players, are reported.
Smoking and tuberculosis: a chance or causal association?
Authors: G H Bothamley
Journal: Thorax (2005)

Possible explanations for the association between smoking and tuberculosis

In 1956 Doll and Hill1 wrote that “ the relationship between smoking and mortality from pulmonary tuberculosis is distinct, but with a disease so influenced by social factors more precise data are needed to justify a direct cause and effect hypothesis ”.

The essential risk factors for human tuberculosis are (1) the tubercle bacillus, (2) a susceptible host, and (3) an environment which allows the tubercle bacilli to survive transit from one host to the next. All other risk factors are subsumed under these headings. If smoking is a risk factor for tuberculosis, then it must act by increasing the susceptibility of the human host or the probability of transmission by encouraging infectious individuals to cough (this requires smoking to be a social as much as an individual pursuit). If the association between smoking and tuberculosis is more apparent than real, then smoking may be a pointer to other risk factors. These include social class—itself a marker for overcrowding, poor ventilation and rooms with no natural light as well as poor nutrition—general ill health and, increasingly, HIV infection with prostitution and intravenous drug use.

Tuberculous infection and tuberculosis as a disease are entirely different states. The former is commonly characterised by tuberculin reactivity (despite the known problem of exposure to non-tuberculous mycobacteria and the cross reactivity of the mixture of antigens2). Approximately one third of the world’s population may be infected with the tubercle bacillus, but only eight million (0.4%) develop tuberculosis each year.

Studies conflict as to whether smoking affects delayed hypersensitivity to tuberculin. Kuemmerer and Comstock3 noted that …
Diffuse Eruption of Necrotic Papules and Nodules
Authors: Patrick A. Armstrong, Jason S. Reichenberg, Dayna G. Diven, Alde Carlo P. Gavino
Journal: JAMA Dermatology (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Adverse Prognostic Impact of Abnormal Lesions Detected by Genome-Wide Single Nucleotide Polymorphism Array–Based Karyotyping Analysis in Acute Myeloid Leukemia With Normal Karyotype
Authors: Jun Ho Yi, Jungwon Huh, Hee-Jin Kim, Sun-Hee Kim, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Sang Kyun Sohn, Joon Ho Moon, Sung Hyun Kim, Kyoung Ha Kim, Jong Ho Won, Yeung Chul Mun, Hawk Kim, Jinny Park, Chul Won Jung, Dong Hwan Kim
Journal: Journal of Clinical Oncology (2011)

This study attempted to analyze the prognostic role of single nucleotide polymorphism array (SNP-A) -based karyotying in 133 patients with acute myeloid leukemia with normal karyotype (AML-NK), which presents with diverse clinical outcomes, thus requiring further stratification of patient subgroups according to their prognoses.A total of 133 patients with AML-NK confirmed by metaphase cytogenetics (MC) and fluorescent in situ hybridization analysis were included in this study. Analysis by Genome-Wide Human SNP 6.0 Array was performed by using DNAs derived from marrow samples at diagnosis.Forty-three patients (32.3%) had at least one abnormal SNP lesion that was not detected by MC. One hundred thirteen abnormal SNP lesions included 55 losses, 23 gains, and 35 copy-neutral losses of heterozygosity. Multivariate analyses showed that detection of abnormal SNP lesions by SNP-A karyotyping results in an unfavorable prognostic value for overall survival (hazard ratio [HR], 2.69; 95% CI, 1.50 to 4.82; P = .001); other significant prognostic factors included secondary AML (HR, 5.55; 95% CI, 1.80 to 17.14; P = .003), presence of the FLT3 mutation (HR, 3.17; 95% CI, 1.71 to 5.87; P < .001), and age (HR, 1.03; 95% CI, 1.01 to 1.05; P = .020).Our data demonstrated that abnormal SNP lesions detected by SNP-A karyotyping might indicate an adverse prognosis in patients with AML-NK, thus requiring a more sophisticated treatment strategy for improvement of treatment outcomes.
Hedgehog pathway activity in the LADY prostate tumor model
Authors: Jerry Gipp, Guangyu Gu, Curtis Crylen, Susan Kasper, Wade Bushman
Journal: Molecular Cancer (2007)

Robust Hedgehog (Hh) signaling has been implicated as a common feature of human prostate cancer and an important stimulus of tumor growth. The role of Hh signaling has been studied in several xenograft tumor models, however, the role of Hh in tumor development in a transgenic prostate cancer model has never been examined.We analyzed expression of Hh pathway components and conserved Hh target genes along with progenitor cell markers and selected markers of epithelial differentiation during tumor development in the LADY transgenic mouse model. Tumor development was associated with a selective increase in Ihh expression. In contrast Shh expression was decreased. Expression of the Hh target Patched (Ptc) was significantly decreased while Gli1 expression was not significantly altered. A survey of other relevant genes revealed significant increases in expression of Notch-1 and Nestin together with decreased expression of HNF3a/FoxA1, NPDC-1 and probasin.Our study shows no evidence for a generalized increase in Hh signaling during tumor development in the LADY mouse. It does reveal a selective increase in Ihh expression that is associated with increased expression of progenitor cell markers and decreased expression of terminal differentiation markers. These data suggest that Ihh expression may be a feature of a progenitor cell population that is involved in tumor development.
Nitric Oxide–Releasing Drugs
Authors: Claudio Napoli, Louis J. Ignarro
Journal: The Annual Review of Pharmacology and Toxicology (2003)

Pharmacological compounds that release nitric oxide (NO) have been useful tools for evaluating the broad role of NO in physiology and therapeutics. NO deficiency has been implicated in the genesis and evolution of several disease states. Both medical needs and commercial opportunities have fostered attempts to modulate NO in the human body for therapeutic gain. Strategies for NO modulation encompass antiinflammatory, sexual dysfunction, and cardiovascular indications. Apart from newly developed drugs, several commonly used cardiovascular drugs exert their beneficial action, at least in part, by modulating the NO pathway. This review discusses the fundamental pharmacological properties and mechanisms of action of NO-releasing drugs. Some of these compounds may enter in the clinical arena providing important therapeutic benefits in human diseases.
Through a Glass Darkly
Authors: Mark D. Stegall, Robert S. Gaston, Fernando G. Cosio, Arthur Matas
Journal: Journal of the American Society of Nephrology (2014)

A common lament is that long-term kidney transplant outcomes remain the same despite improvements in early graft survival. To be fair, progress has been made-in both our understanding of chronic injury and modestly, graft survival. However, we are still a long way from actually solving this important and difficult problem. In this review, we outline recent data supporting the existence of several causes of renal allograft loss, the incidences of which peak at different time points after transplantation. On the basis of this broadened concept of chronic renal allograft injury, we examine the challenges of clinical trial design in long-term studies, including the use of surrogate end points and biomarkers. Finally, we suggest a path forward that, ultimately, may improve long-term renal allograft survival.
Phenotypic Analysis of Prostate-Infiltrating Lymphocytes Reveals TH17 and Treg Skewing
Authors: Karen Sandell Sfanos, Tullia C. Bruno, Charles H. Maris, Lauren Xu, Christopher J. Thoburn, Angelo M. DeMarzo, Alan K. Meeker, William B. Isaacs, Charles G. Drake
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Pathologic examination of prostate glands removed from patients with prostate cancer commonly reveals infiltrating CD4+ and CD8+ T cells. Little is known about the phenotype of these cells, despite accumulating evidence suggesting a potential role for chronic inflammation in the etiology of prostate cancer. Experimental Design: We developed a technique that samples the majority of the peripheral prostate through serial needle aspirates. CD4+ prostate-infiltrating lymphocytes (PIL) were isolated using magnetic beads and analyzed for subset skewing using both flow cytometry and quantitative reverse transcription-PCR. The transcriptional profile of fluorescence-activated cell sorted prostate-infiltrating regulatory T cells (CD4+, CD25+, GITR+) was compared with naïve, peripheral blood T cells using microarray analysis. Results: CD4+ PIL showed a paucity of TH2 (interleukin-4–secreting) cells, a surprising finding given the generally accepted association of these cells with chronic, smoldering inflammation. Instead, CD4+ PIL seemed to be skewed towards a regulatory Treg phenotype (FoxP3+) as well as towards the TH17 phenotype (interleukin-17+). We also found that a preponderance of TH17-mediated inflammation was associated with a lower pathologic Gleason score. These protein level data were reflected at the message level, as analyzed by quantitative reverse transcription-PCR. Microarray analysis of pooled prostate-infiltrating Treg revealed expected Treg-associated transcripts (FoxP3, CTLA-4, GITR, LAG-3) as well as a number of unique cell surface markers that may serve as additional Treg markers. Conclusion: Taken together, these data suggest that TH17 and/or Treg CD4+ T cells (rather than TH2 T cells) may be involved in the development or progression of prostate cancer.
T-Cell–Depleted Reduced-Intensity Conditioning Transplantation for Lymphoma: Do Donor Lymphocyte Infusions Really Matter?
Authors: Koen van Besien, Vaishalee Kenkre, Andrew S. Artz
Journal: Journal of Clinical Oncology (2011)

We congratulate Thomson et al 1 on another excellent contribution to the transplantation literature with the demonstration that T-cell-depleted transplantation can lead to prolonged survival in patients who have experienced multiple relapses of follicular lymphoma.The authors report a high response rate using donor lymphocyte infusions (DLI) with or without chemotherapy in patients who have experienced relapse after allogeneic transplantation.Using a similar regimen, we have observed frequent durable remissions and conversion to full donor chimerism after treatment with rituximab or nucleoside analogs even without DLI. 2 Thus, we concur with the high response rate for relapse, although the value of DLI versus other therapeutic modalities and the need for full donor chimerism for sustained remission requires additional study.A number of questions arise, however, regarding the authors' recommendation to use DLI to prevent relapse in patients with mixed chimerism.In our experience with the use of similar conditioning regimens, mixed chimerism is quite common and varies in degree. 3e and others have failed to find a relationship between the degree of mixed chimerism and risk for disease recurrence. 3,4The authors state, "In the group given DLIs for MC [mixed chimerism] alone at 6 months, this effect was maintained, with patients converting to full donor status having a significant reduction in RR [relapse risk] compared with patients who exhibited persistent MC."Statistical modeling of a variable that changes with time can be complicated.Additional details about the analysis would be useful, such as the degree and cellular compartment of mixed chimerism that prompted treatment, the chimerism time point(s) analyzed to predict relapse risk, and whether adjustments were made for time elapsed.We are unsure how patients with mixed donor chimerism after DLI can be combined in an analysis with patients who have mixed chimerism and never underwent DLI.If one does not use a single time point, the analysis would tend to show a benefit of DLI, given that those who remain alive without disease may receive additional DLI infusions to convert to full chimerism.In other words, lack of relapse may predict for full donor chimerism.Even if post-DLI mixed chimerism predicts for relapse, one does not know a priori who will achieve full donor chimerism with DLI; thus, such a result does not inform the decision to proceed with DLI.We advocate that prospective study of the risks and benefits of prophylactic DLI after alemtuzumab conditioning be undertaken.Until prospective studies are performed, the excellent results of salvage therapy with or without DLI at the time of relapse support salvage therapy rather than prophylactic DLI.
Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
Authors: Denise Harold, Richard Abraham, Paul Hollingworth, Rebecca Sims, Amy Gerrish, Marian L Hamshere, Jaspreet Singh Pahwa, Valentina Moskvina, Kimberley Dowzell, Amy Williams, Nicola Jones, Charlene Thomas, Alexandra Stretton, Angharad R Morgan, Simon Lovestone, John Powell, Petroula Proitsi, Michelle K Lupton, Carol Brayne, David C Rubinsztein, Michael Gill, Brian Lawlor, Aoibhinn Lynch, Kevin Morgan, Kristelle S Brown, Peter A Passmore, David Craig, Bernadette McGuinness, Stephen Todd, Clive Holmes, David Mann, A David Smith, Seth Love, Patrick G Kehoe, John Hardy, Simon Mead, Nick Fox, Martin Rossor, John Collinge, Wolfgang Maier, Frank Jessen, Britta Schürmann, Reinhard Heun, Hendrik van den Bussche, Isabella Heuser, Johannes Kornhuber, Jens Wiltfang, Martin Dichgans, Lutz Frölich, Harald Hampel, Michael Hüll, Dan Rujescu, Alison M Goate, John S K Kauwe, Carlos Cruchaga, Petra Nowotny, John C Morris, Kevin Mayo, Kristel Sleegers, Karolien Bettens, Sebastiaan Engelborghs, Peter P De Deyn, Christine Van Broeckhoven, Gill Livingston, Nicholas J Bass, Hugh Gurling, Andrew McQuillin, Rhian Gwilliam, Panagiotis Deloukas, Ammar Al-Chalabi, Christopher E Shaw, Magda Tsolaki, Andrew B Singleton, Rita Guerreiro, Thomas W Mühleisen, Markus M Nöthen, Susanne Moebus, Karl-Heinz Jöckel, Norman Klopp, H-Erich Wichmann, Minerva M Carrasquillo, V Shane Pankratz, Steven G Younkin, Peter A Holmans, Michael O'Donovan, Michael J Owen, Julie Williams
Journal: Nature Genetics (2009)
Erythromycin to prevent exacerbations of bronchiectasis
Authors: Shea McNeill
Journal: Thorax (2013)

Erythromycin to prevent exacerbations of bronchiectasisThe purpose of this study was to evaluate whether low-dose erythromycin would reduce pulmonary exacerbations in patients with non-cystic fibrosis (CF) brocnchiectasis with a history of frequent exacerbations.In comparison to previously published work using azithromycin prophylaxis, a prolonged period of 12 months was used for evaluation and there were attempts to more precisely quantify the bacterial resistance associated with prolonged macrolide use.In this randomised, double-blind, placebo-controlled trial, 679 patients were screened with 117 randomised after the exclusion criteria were applied.A total of 107 completed the study.Reasons for exclusion included no high-resolution CT confirmed bronchiectasis and insufficient pre-trial exacerbations.Fifty-nine individuals were randomised to the erythromycin group (oral erythromycin ethylsuccinate 400 mg twice daily) and 58 to the placebo group.There was a significant reduction in 'protocol defined pulmonary exacerbations' in the erythromycin group.In the pre-specified subgroup of patients with baseline Pseudomonas aeruginosa airway infection, again there was significant improvement.There was an increase in the proportion of macrolide-resistant oropharyngeal streptococci in the erythromycin group.Long-term, low-dose erythromycin appears effective in reducing pulmonary exacerbations in non-CF bronchiectasis.There is evidence that it may also protect against lung function decline and contribute to a reduction in sputum production.Of concern is the significant increase in macrolide oropharyngeal streptococci resistance.For this reason, it may be advisable for a larger, multicentre population study of longer duration to be carried out prior to any widespread application in clinical practice.A study comparing erythromycin, azithromycin and placebo using similar outcome measures would be of interest.
C-Reactive Protein and Insulin Resistance in Subjects With Thalassemia Minor and a Family History of Diabetes
Authors: Peter C.Y. Tong, Maggie C.Y. Ng, Chung S. Ho, Wing Y. So, June K.Y. Li, Chris W.K. Lam, Clive S. Cockram, Juliana C.N. Chan
Journal: Diabetes Care (2002)

received honoraria from Probiodrug, which synthesizes inhibitors of DP IV