tbuckley/cabot-search huggingface dataset:
Laser Doppler measurement of rectal mucosal blood flow
Authors: A V Emmanuel, M A Kamm
Journal: Gut (1999)

Gut mucosal blood flow measurement is used to study a variety of disorders and possibly extrinsic neural function.To determine optimal measurement criteria and validate this technique as a measure of level of activity of extrinsic autonomic gut innervation.In 26 healthy volunteers a laser Doppler mucosal probe was applied 10 cm from the anus. Response to inhaled salbutamol 200 microgram and ipratropium 40 microgram, intravenous metoprolol 2.5 mg, and direct sacral nerve electrostimulation (in nine incontinent patients) was also studied.The coefficient of variation for subjects studied under identical conditions on two, three, and four days was 0.06, 0.05, and 0.06, respectively. Mean mucosal blood flow increased after a standard meal. Blood flow decreased for 15 minutes after smoking and returned to baseline at 30 minutes. Fasted measurements at 0900, 1200, 1600, and 2200 were similar. There was a negative correlation between blood flow and body size but not age. Follicular phase mucosal flow was less and more reproducible than luteal. Mucosal blood flow was highest in men and lowest in postmenopausal women. Inhaled salbutamol did not change blood flow; ipratropium significantly reduced, and metoprolol and sacral nerve stimulation increased flow.Measurement of gut mucosal blood flow by laser Doppler flowmetry is highly reproducible. Eating, smoking, body size, sex, ovulatory status, and menstrual phase influence blood flow. Changes in mucosal blood flow induced by autonomically active drugs and nerve stimulation confirm the role of the mucosal microcirculation as a measure of extrinsic nerve activity.
Blood Pressure and Mortality in U.S. Veterans With Chronic Kidney Disease
Authors: Csaba P. Kovesdy, Anthony J. Bleyer, Miklos Z. Molnar, Jennie Z. Ma, John J. Sim, William C. Cushman, L. Darryl Quarles, Kamyar Kalantar-Zadeh
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: The ideal blood pressure (BP) to decrease mortality rates in patients with non–dialysis-dependent chronic kidney disease (CKD) is unclear. Objective: To assess the association of BP (defined as the combination of systolic BP [SBP] and diastolic BP [DBP] at the individual level) with death in patients with CKD. Design: Historical cohort between 2005 and 2012. Setting: All U.S. Department of Veterans Affairs health care facilities. Patients: 651 749 U.S. veterans with CKD. Measurements: All possible combinations of SBP and DBP were examined in 96 categories from lowest (<80/<40 mm Hg) to highest (>210/>120 mm Hg), in 10–mm Hg increments. Associations with all-cause mortality were examined in time-dependent Cox models with adjustment for relevant confounders. Results: Patients with SBP of 130 to 159 mm Hg combined with DBP of 70 to 89 mm Hg had the lowest adjusted mortality rates, and those in whom both SBP and DBP were concomitantly very high or very low had the highest mortality rates. Patients with moderately elevated SBP combined with DBP no less than 70 mm Hg had consistently lower mortality rates than did patients with ideal SBP combined with DBP less than 70 mm Hg. Results were consistent in subgroups of patients with normal and elevated urinary microalbumin–creatinine ratios. Limitation: Mostly male patients, inability to establish causality, and large number of patients missing proteinuria measurement. Conclusion: The optimal BP in patients with CKD seems to be 130 to 159/70 to 89 mm Hg. It may not be advantageous to achieve ideal SBP at the expense of lower-than-ideal DBP in adults with CKD. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and U.S. Department of Veterans Affairs.
Expression of Inducible Nitric Oxide Synthase After Endothelial Denudation of the Rat Carotid Artery
Authors: Fernando González-Fernández, Antonio López-Farré, Juan A. Rodríguez-Feo, Jerónimo Farré, José Guerra, Jose Fortes, Inmaculada Millás, Margarita García-Durán, Luis Rico, Pedro Mata, Lourdes Sánchez de Miguel, Santos Casado
Journal: Circulation Research (1998)

Abstract —There is functional evidence suggesting that endothelial denudation stimulates inducible nitric oxide synthase (iNOS) activity in the vascular wall. In vitro studies have shown that iNOS expression in smooth muscle cells is reduced by endothelial cells. In the present study we have analyzed the time course of iNOS protein expression in the arterial wall after in vivo deendothelialization. Endothelial denudation was performed in the left carotid artery of Wistar rats, and the right carotid artery was used as control. Whereas iNOS protein was weakly expressed 6, 24, and 48 hours after endothelial denudation, a marked iNOS expression was found 7, 14, and 30 days after vascular damage. Because platelet adhesion and aggregation occur early after endothelial damage, we studied the role of activated platelets in the negative modulation of iNOS protein expression during the first 2 days after endothelial denudation. Early after in vivo endothelial injury, platelet-depleted rats showed a marked iNOS protein expression in the vascular wall. Similar results were obtained by blocking the platelet glycoprotein (GP) IIb/IIIa. Although iNOS protein is present in the arterial wall several days after endothelial denudation, early after arterial wall injury iNOS protein is weakly expressed. Platelets play a crucial role in preventing iNOS protein expression early after endothelial damage, an effect that can be avoided with GP IIb/IIIa blockers. Although iNOS protein was weakly expressed in vivo in the rat carotid artery wall 6, 24, and 48 hours after balloon endothelial denudation, a marked iNOS expression was found 7, 14, and 30 days after arterial damage. iNOS expression could be increased early after endothelial injury by removing circulating platelets and by an antibody against the GP IIb/IIIa. In conclusion, platelets prevent iNOS protein expression early after endothelial balloon damage, an effect that can be avoided with GP IIb/IIIa blocking agents.
Prevention of Respiratory Diseases
Journal: Thorax (1994)

<b>Objective.</b> To assess the impact of a continuing education course that focused on the development of management competencies on pharmacists working in Brazil’s public health system. <b>Methods.</b> A specialization blended in-service course (360 hours) entitled Pharmaceutical Service and Access to Medicine Management was offered to pharmacists working within the Brazilian public health system. Data on course outcomes were collected through individual interviews with pharmacists who worked in the Brazilian public health system, as well as from focus groups and records of researchers’ observations. The analysis was based on models of learning and training evaluation theory. <b>Results.</b> The findings showed proximal outcomes on students’ knowledge, skills, and attitudes; behavioral changes; and programmatic outcomes in the organization and management of health services, promoting the recognition and integration of the “pharmaceutical services division” – a dedicated sector within the health departments in municipalities and states. The inputs (course content, structure, and in-service hands-on activities) were directly linked to the outcomes reported by participants and helped them to overcome some of the barriers to using knowledge and skills in the workplace. <b>Conclusion.</b> A well-structured course including leaning activities to intervene in the workplace had a positive impact on pharmacists’ behavior and contributed to the capacity building of the organizations in which they operate.
Acute exposure to biomass smoke causes oxygen desaturation in adult women
Authors: O. P. Kurmi, S. Gaihre, S. Semple, J. G. Ayres
Journal: Thorax (2010)

<h3>Introduction</h3> Falls and fall-related injuries are a serious cause of morbidity and cost to society. Environmental hazards are implicated as a major contributor to falls among older people. A recent Cochrane review found an environmental assessment, undertaken by an occupational therapist, to be an effective approach to reducing falls. However, none of the trials included a cost-effectiveness evaluation in the UK setting. This protocol describes a large multicentre trial investigating the clinical and cost-effectiveness of environmental assessment and modification within the home with the aim of preventing falls in older people. <h3>Methods and analysis</h3> A two-arm, modified cohort randomised controlled trial, conducted within England, with 1299 community-dwelling participants aged 65 years and above, who are at an increased risk of falls. Participants will be randomised 2:1 to receive either usual care or home assessment and modification. The primary outcome is rate of falls (falls/person/time) over 12 months assessed by monthly patient self-report falls calendars. Secondary self-reported outcome measures include: the proportion of single and multiple fallers, time to first fall over a 12-month period, quality of life (EuroQoL EQ-5D-5L) and health service utilisation at 4, 8 and 12 months. A nested qualitative study will examine the feasibility of providing the intervention and explore barriers, facilitators, workload implications and readiness to employ these interventions into routine practice. An economic evaluation will assess value for money in terms of cost per fall averted. <h3>Ethics and dissemination</h3> This study protocol (including the original application and subsequent amendments) received a favourable ethical opinion from National Health Service West of Scotland REC 3. The trial results will be published in peer-reviewed journals and at conference presentations. A summary of the findings will be sent to participants. <h3>Trial registration number</h3> ISRCTN22202133; Pre-results.
A BAC clone fingerprinting approach to the detection of human genome rearrangements
Authors: Martin Krzywinski, Ian Bosdet, Carrie Mathewson, Natasja Wye, Jay Brebner, Readman Chiu, Richard Corbett, Matthew Field, Darlene Lee, Trevor Pugh, Stas Volik, Asim Siddiqui, Steven Jones, Jacquie Schein, Collin Collins, Marco Marra
Journal: Genome biology (2007)

We present a method, called fingerprint profiling (FPP), that uses restriction digest fingerprints of bacterial artificial chromosome clones to detect and classify rearrangements in the human genome. The approach uses alignment of experimental fingerprint patterns to in silico digests of the sequence assembly and is capable of detecting micro-deletions (1-5 kb) and balanced rearrangements. Our method has compelling potential for use as a whole-genome method for the identification and characterization of human genome rearrangements.
Sports injuries: diagnosis and management, 3rd edn
Authors: B Sawyer
Journal: British Journal of Sports Medicine (2006)

Authored by Christopher Norris, Published by Elsevier, 2004, £42.50, hardcover, pp 465. ISBN 0750652233

The physiotherapy student is clearly the target of this text book, which is packed with information and ably illustrated.

The preface outlines aspects of the third edition that have been updated, amended, and increased to enhance its practical feel, while also improving the reader’s access to information.

I was impressed with the clear, concise illustrations. The practical therapy sections were simple to visualise thanks to an excellent group of photographs demonstrating the specific techniques. Simple captions clarified any outstanding questions.

I also found that the highlighted …
Medical Treatment of Inflammatory Bowel Disease
Authors: F Shanahan, S Targan
Journal: Annual Review of Medicine (1992)

Advances in the drug treatment of inflammatory bowel disease include the development of site-specific delivery systems for 5-aminosalicylate (5-ASA), topically active corticosteroids with minimal systemic bioavailability, and a variety of antagonists to specific inflammatory mediators. These novel therapeutic approaches have emerged from pharmaceutical improvements on traditional drugs and also from an improved understanding of the mucosal immune system and the pathogenesis of inflammatory bowel disease.
A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population
Authors: Alex B. Haynes, Thomas G. Weiser, William R. Berry, Stuart R. Lipsitz, Abdel-Hadi S. Breizat, E. Patchen Dellinger, Teodoro Herbosa, Sudhir Joseph, Pascience L. Kibatala, Marie Carmela M. Lapitan, Alan F. Merry, Krishna Moorthy, Richard K. Reznick, Bryce Taylor, Atul A. Gawande
Journal: New England Journal of Medicine (2009)

Surgery has become an integral part of global health care, with an estimated 234 million operations performed yearly. Surgical complications are common and often preventable. We hypothesized that a program to implement a 19-item surgical safety checklist designed to improve team communication and consistency of care would reduce complications and deaths associated with surgery.Between October 2007 and September 2008, eight hospitals in eight cities (Toronto, Canada; New Delhi, India; Amman, Jordan; Auckland, New Zealand; Manila, Philippines; Ifakara, Tanzania; London, England; and Seattle, WA) representing a variety of economic circumstances and diverse populations of patients participated in the World Health Organization's Safe Surgery Saves Lives program. We prospectively collected data on clinical processes and outcomes from 3733 consecutively enrolled patients 16 years of age or older who were undergoing noncardiac surgery. We subsequently collected data on 3955 consecutively enrolled patients after the introduction of the Surgical Safety Checklist. The primary end point was the rate of complications, including death, during hospitalization within the first 30 days after the operation.The rate of death was 1.5% before the checklist was introduced and declined to 0.8% afterward (P=0.003). Inpatient complications occurred in 11.0% of patients at baseline and in 7.0% after introduction of the checklist (P<0.001).Implementation of the checklist was associated with concomitant reductions in the rates of death and complications among patients at least 16 years of age who were undergoing noncardiac surgery in a diverse group of hospitals.
Cost Minimization Study of Image-Guided Core Biopsy Versus Surgical Excisional Biopsy for Women With Abnormal Mammograms
Authors: Robert M. Golub, Charles L. Bennett, Tammy Stinson, Luz Venta, Monica Morrow
Journal: Journal of Clinical Oncology (2004)

To describe the clinical and economic consequences of image-guided core biopsy versus surgical excisional biopsy of mammographically identified breast lesions.Clinical and economic data were collected for 1121 patients undergoing core biopsies and 501 patients undergoing surgical biopsies between 1996 and 1998. Lesions were classified according to mammographic degree of suspicion and type of radiographic abnormality. Costs were measured from the societal perspective. A decision analytic model was constructed, with probabilistic sensitivity analysis.Lesions diagnosed via core versus surgical biopsy were less likely to be masses (39% v 55%), less likely to be classified as high cancer suspicion (17% v 26%), and less likely to be treated with a single procedure (74% v 81%; P <.001 for each). Cancers diagnosed by a surgical biopsy were less likely to have had a single operative procedure (33% v 84%) and were associated with higher total costs whether mastectomy (US dollars 2775 v US dollars 1849) or lumpectomy (US dollars 2112 v US dollars 1365) was used. Sensitivity analysis showed core biopsy optimal in 95.4% of trials. Core biopsy was favored for low-suspicion lesions, calcifications, and masses, and overall for patients who underwent lumpectomy alone.Image-guided core biopsy can be cost-saving compared with surgical biopsy, particularly when the mammographic abnormality is classified as low suspicion or consists of calcifications or masses. Moving to a policy in which core biopsy is the preferred approach in these settings has the potential to result in significant cost savings.
Cryptogenic organising pneumonia
Authors: J. A. Kastelik, M. Greenstone, D. V. McGivern, A. H. Morice
Journal: European Respiratory Journal (2006)

To the Editors: 

We have read with interest the paper by Cordier 1 describing the current understanding of the pathogenesis, aetiology, diagnosis and treatment of cryptogenic organising pneumonia (COP). The author acknowledged that corticosteroids remain the standard treatment of COP, usually resulting in rapid clinical, and slower radiological, improvements. Although the response to corticosteroids is generally good, a proportion of patients can experience early or late relapses. In addition, some patients may be unable to tolerate corticosteroids, or the disease may continue to deteriorate, despite therapy with corticosteroids. Therefore, there is a need for alternative therapies to treat this condition. Cordier 1 only …
Defects in secretion, aggregation, and thrombus formation in platelets from mice lacking Akt2
Authors: Donna Woulfe, Hong Jiang, Alicia Morgans, Robert Monks, Morris Birnbaum, Lawrence F. Brass
Journal: Journal of Clinical Investigation (2004)

Prior studies have shown that PI3Ks play a necessary but incompletely defined role in platelet activation. One potential effector for PI3K is the serine/threonine kinase, Akt, whose contribution to platelet activation was explored here. Two isoforms of Akt were detected in mouse platelets, with expression of Akt2 being greater than Akt1. Deletion of the gene encoding Akt2 impaired platelet aggregation, fibrinogen binding, and granule secretion, especially in response to low concentrations of agonists that activate the Gq-coupled receptors for thrombin and thromboxane A2. Loss of Akt2 also impaired arterial thrombus formation and stability in vivo, despite having little effect on platelet responses to collagen and ADP. In contrast, reducing Akt1 expression had no effect except when Akt2 was also deleted. Activation of Akt by thrombin was abolished by deletion of Gαq but was relatively unaffected by deletion of Gαi2, which abolished Akt activation by ADP. From these results we conclude that Akt2 is a necessary component of PI3K-dependent signaling downstream of Gq-coupled receptors, promoting thrombus growth and stability in part by supporting secretion. The contribution of Akt1 is less evident except in the setting in which Akt2 is absent.
Antidepressant induced cholestasis: hepatocellular redistribution of multidrug resistant protein (MRP2)
Authors: P Milkiewicz
Journal: Gut (2003)

We report two cases of antidepressant induced cholestasis.We describe the first reported case of acute cholestasis due to citalopram (selective serotonin reuptake inhibitor) occurring in a patient who also experienced obstetric cholestasis in association with each of three pregnancies; in a second patient cholestasis developed due to dothiepin (tricyclic antidepressant), and six years later due to paroxetine. In both cases liver biopsies showed features of a "pure" cholestasis with total resolution within 1-6 months after withdrawal of the causative drug. Immunostaining for the canalicular transporter, multidrug resistant protein 2 (MRP2), responsible for biliary secretion of several organic anions including bilirubin glucuronides, showed sustained expression in both biopsies as well as relocalisation with appearance of strong staining of the basolateral membrane of the hepatocyte. This finding has also not been reported previously.We postulate that intracellular redistribution of MRP2 may reflect an adaptive compensatory mechanism which helps in the elimination of the drug or its cholestatic metabolites from the hepatocyte back to the sinusoidal space and subsequent excretion in urine. Changes seen in these two patients differ from findings previously reported in rats where downregulation of mrp2 occurs in response to experimentally induced cholestasis. We speculate that the rat is more advanced than humans in its ability to downregulate canalicular transporter expression as protection against progressive intrahepatic cholestasis.
Visceral and Subcutaneous Adipose Tissue Volumes Are Cross-Sectionally Related to Markers of Inflammation and Oxidative Stress
Authors: Karla M. Pou, Joseph M. Massaro, Udo Hoffmann, Ramachandran S. Vasan, Pal Maurovich-Horvat, Martin G. Larson, John F. Keaney, James B. Meigs, Izabella Lipinska, Sekar Kathiresan, Joanne M. Murabito, Christopher J. O’Donnell, Emelia J. Benjamin, Caroline S. Fox
Journal: Circulation (2007)

Background— Excess adiposity is associated with greater systemic inflammation. Whether visceral adiposity is more proinflammatory than subcutaneous abdominal adiposity is unclear. Methods and Results— We examined the relations of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), assessed by multidetector computerized tomography, to circulating inflammatory and oxidative stress biomarkers in 1250 Framingham Heart Study participants (52% women; age 60±9 years). Biomarkers were examined in relation to increments of SAT and VAT after adjustment for age, sex, smoking, physical activity, menopause, hormone replacement therapy, alcohol, and aspirin use; additional models included body mass index and waist circumference. SAT and VAT were positively and similarly (with respect to strength of association) related to C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, P-selectin, and tumor necrosis factor receptor-2 (multivariable model R 2 0.06 to 0.28 [SAT] and 0.07 to 0.29 [VAT]). However, compared with SAT, VAT was more highly associated with urinary isoprostanes and monocyte chemoattractant protein-1 (SAT versus VAT comparison: isoprostanes, R 2 0.07 versus 0.10, P =0.002; monocyte chemoattractant protein-1, R 2 0.07 versus 0.08, P =0.04). When body mass index and waist circumference were added to the models, VAT remained significantly associated with only C-reactive protein ( P =0.0003 for women; P =0.006 for men), interleukin-6 ( P =0.01), isoprostanes ( P =0.0002), and monocyte chemoattractant protein-1 ( P =0.008); SAT only remained associated with fibrinogen ( P =0.01). Conclusions— The present cross-sectional data support an association between both SAT and VAT with inflammation and oxidative stress. The data suggest that the contribution of visceral fat to inflammation may not be completely accounted for by clinical measures of obesity (body mass index and waist circumference).
Retroviral gene therapy with an immunoglobulin-antigen fusion construct protects from experimental autoimmune uveitis
Authors: Rajeev K. Agarwal, Yubin Kang, Elias Zambidis, David W. Scott, Chi-Chao Chan, Rachel R. Caspi
Journal: Journal of Clinical Investigation (2000)

Immunoglobulins can serve as tolerogenic carriers for antigens, and B cells can function as tolerogenic antigen-presenting cells. We used this principle to design a strategy for gene therapy of experimental autoimmune uveitis, a cell-mediated autoimmune disease model for human uveitis induced with the uveitogenic interphotoreceptor retinoid-binding protein (IRBP). A retroviral vector was constructed containing a major uveitogenic IRBP epitope in frame with mouse IgG1 heavy chain. This construct was used to transduce peripheral B cells, which were infused into syngeneic recipients. A single infusion of transduced cells, 10 days before uveitogenic challenge, protected mice from clinical disease induced with the epitope or with the native IRBP protein. Protected mice had reduced antigen-specific responses, but showed no evidence for a classic Th1/Th2 response shift or for generalized anergy. Protection was not transferable, arguing against a mechanism dependent on regulatory cells. Importantly, the treatment was protective when initiated 7 days after uveitogenic immunization or concurrently with adoptive transfer of primed uveitogenic T cells. We suggest that this form of gene therapy can induce epitope-specific protection not only in naive, but also in already primed recipients, thus providing a protocol for treatment of established autoimmunity.