tbuckley/cabot-search huggingface dataset:
Gastrointestinal endoscopy in a low budget context: delegating EGD to non-physician clinicians in Malawi can be feasible and safe
Authors: T. Wilhelm, H. Mothes, D. Chiwewe, B. Mwatibu, G. Kähler
Journal: Endoscopy (2011)

Gastrointestinal endoscopy is rarely performed in low-income countries in sub-Saharan Africa. One reason is the lack of available medical doctors and specialists in these countries. At Zomba Central Hospital in Malawi, clinical officers (non-physician clinicians with 4 years of formal training) were trained in upper gastrointestinal endoscopy. Prospectively recorded details of 1732 consecutive esophagogastroduodenoscopies (EGDs) performed between September 2001 and August 2010 were analyzed to evaluate whether upper gastrointestinal endoscopy can be performed safely and accurately by clinical officers. A total of 1059 (61.1 %) EGDs were performed by clinical officers alone and 673 (38.9 %) were carried out with a medical doctor present who performed or assisted in the procedure. Failure and complication rates were similar in both groups (<i>P</i> = 0.105). Endoscopic diagnoses for frequent indications were generally evenly distributed across the two groups. The main difference was a higher proportion of normal findings and a lower proportion of esophagitis in the group with a doctor present, although this was significant only in patients who had presented with epigastric/abdominal pain (<i>P</i> < 0.001). In conclusion, delegating upper gastrointestinal endoscopy to clinical officers can be feasible and safe in a setting with a shortage of medical doctors when adequate training and supervision are provided.
THE EKOSONIC® ENDOVASCULAR SYSTEM PROVIDES IMPROVEMENTS IN THROMBOTIC BURDEN, PULMONARY ARTERIAL PRESSURES AND RIGHT ATRIAL AND VENTRICULAR FUNCTIONS IN PATIENTS WITH ACUTE PULMONARY EMBOLISM AT HIGH OR INTERMEDIATE-HIGH RISK: A SINGLE-CENTER EXPERIENCE
Authors: Cihangir Kaymaz, Selcuk Ozturk, Ozgur Y. Akbal, Nertila Poci, Fatih Yilmaz, Tugba Aktemur, Ruken Bengi Bakal, Necla Kirca, Aykun Hakgor, Nihal Ozdemir
Journal: Journal of the American College of Cardiology (2015)
Optimizing Treatment for Chronic Myeloid Leukemia
Authors: John M. Goldman
Journal: New England Journal of Medicine (1997)

Chronic myeloid leukemia has fascinated hematologists and others for 150 years. It was probably the first form of leukemia to be recognized as an entity in its own right; and the discoveries in this century — first of the Philadelphia chromosome, and more recently of the BCR-ABL fusion gene in leukemic cells from almost all patients with chronic myeloid leukemia — contributed substantially to our understanding of carcinogenesis in general. In the 19th century the treatment of chronic myeloid leukemia, which included solutions of arsenic trioxide and potassium arsenite,1 was ineffective. Radiotherapy, introduced 90 years ago, provided good control of . . .
Abstract 1537: Dual-specificity phosphatase-2 negatively controls chemoresistance in cancer cells
Authors: Lin Shih-Chieh, Tsai Shaw-Jenq
Journal: Cancer Research (2010)

Abstract The limitation of clinical cancer therapy is due to a lot of mechanisms including influence of uptake, metabolism and export of drug from a single cell that contribute to drug resistance at the cellular level. In addition, tumor microenvironment also plays an important role in promoting drug resistance. For example, hypoxia has been reported to induce drug resistance by modulating expression of numerous genes. It has been shown that targeting individual hypoxia-regulated gene decreases drug resistance. However, it is an inefficient and infeasible way to target individual drug resistance-related genes one by one. Here we show that extracellular signal-regulated kinase 1/2 (ERK1/2), a survival pathway, is activated by hypoxia and blocking ERK1/2 pathway attenuates hypoxia-induced drug resistance. Furthermore, we also find that dual-specificity phosphatase-2 (DUSP2), a nuclear phosphatase that controls activity of ERK1/2, is inhibited by hypoxia through transcriptional repression. Inhibition of DUSP2 results in prolonged activation of ERK and increasing cell survival. Overexpression of DUSP2 causes cell apoptosis under normoxia and decreases hypoxia-induced drug resistance while stable knockdown DUSP2 increases drug resistance under normoxia. Moreover, re-expression of DUSP2 under hypoxia blocks tumor growth and enhances drug sensitivity in xenografted mice. Taken together, we identified an important role of DUSP2 involving hypoxia-mediated drug resistance and targeting DUSP2 might provide more specific and efficient way for cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1537.
Aldose Reductase Inhibition Improves Nerve Conduction Velocity in Diabetic Patients
Authors: Roman G. Judzewitsch, Jonathan B. Jaspan, Kenneth S. Polonsky, Clarice R. Weinberg, Jeffrey B. Halter, Eugen Halar, Michael A. Pfeifer, Cynthia Vukadinovic, Lawrence Bernstein, Michael Schneider, Kung-Yee Liang, Kenneth H. Gabbay, Arthur H. Rubenstein, Daniel Porte
Journal: New England Journal of Medicine (1983)

To assess the potential role of polyol-pathway activity in diabetic neuropathy, we measured the effects of sorbinil--a potent inhibitor of the key polyol-pathway enzyme aldose reductase--on nerve conduction velocity in 39 stable diabetics in a randomized, double-blind, cross-over trial. During nine weeks of treatment with sorbinil (250 mg per day), nerve conduction velocity was greater than during a nine-week placebo period for all three nerves tested: the peroneal motor nerve (mean increase [+/- S.E.M.], 0.70 +/- 0.24 m per second, P less than 0.008), the median motor nerve (mean increase, 0.66 +/- 0.27, P less than 0.005), and the median sensory nerve (mean increase, 1.16 +/- 0.50, P less than 0.035). Conduction velocity for all three nerves declined significantly within three weeks after cessation of the drug. These effects of sorbinil were not related to glycemic control, which was constant during the study. Although the effect of sorbinil in improving nerve conduction velocity in diabetics was small, the findings suggest that polyol-pathway activity contributes to slowed nerve conduction in diabetics. The clinical applicability of these observations remains to be determined, but they encourage further exploration of this approach to the treatment or prevention of diabetic neuropathy.
Defective Fc-Receptor Functions Associated with the HLA-B8/DRw3 Haplotype
Authors: Thomas J. Lawley, Russell P. Hall, Anthony S. Fauci, Stephen I. Katz, Max I. Hamburger, Michael M. Frank
Journal: New England Journal of Medicine (1981)

Dermatitis herpetiformis is associated with the HLA-B8/DRw3 haplotype in over 90 per cent of patients, and various percentages have been reported to have circulating immune complexes. Since removal of immune complexes from the circulation is thought to depend on the Fc-receptor function of tissue macrophages, we studied this function by measuring the clearance of IgG-sensitized autologous erythrocytes in 16 patients with dermatitis herpetiformis, in normal controls with the HLA-B8/DRw3 haplotype, and in randomly selected controls. All patients were HLA-B8 positive, and all of 12 patients tested were HLA-DRw3 positive. Erythrocyte clearance was reduced in eight of the 16 patients, but did not correlate with immune-complex levels. Four of eight controls with HLA-B8/DRw3 also had delayed Fc-receptor-mediated clearance as compared with normal controls. In addition, both patients and HLA-B8/DRw3-positive controls had decreased percentages and total numbers of T cells bearing Fc receptors for IgG. These findings indicate a functional Fc-receptor defect associated with the HLA-B8/DRw3 antigens.
A memorable patient: A life saving procedure
Authors: K. Shah
Journal: BMJ (2001)

A 34 year old temple priest from the Maharashtra district of central India was on his way home from a pilgrimage to a temple in northern India. He had been suffering from diarrhoea and vomiting for the past 12 hours. He thought he would cope with it until he arrived home and saw his doctor. But he was wrong. He was fast losing body water and getting colder. I know because I was travelling in the same train, in the same compartment. He was weak and could barely open his eyes. His pulse was weak, thready, and rapid, his extremities were cold and he was perspiring. I told his wife …
THU0032 Involvement of ER stress signals, PERK, IRE1, GRP78 in rankl-induced, C-FOS and NFATC1-mediated osteoclastogenesis
Authors: W.-H. Yoo, E.-G. Lee, M.-S. Sung, M.J. Hong, Y.K. Hong, C.-H. Lee, M.S. Lee
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> ER stress has an important role in the pathogenesis of bone and cartilage destruction in inflammatory conditions, such as RA. However, there were no studies about relations ER stress-specific signals and RANKL-mediated signaling pathways. <h3>Objectives</h3> To investigate the effects of thapsigargin (TG)-induced ER (Endoplasmic Reticulum) stress and chemical chaperone, 4-phenylbutyric acid (PBA) on the RANKL-induced, c-Fos and NFATc1-mediated osteoclastogenesis and its mechanisms. <h3>Methods</h3> Bone marrow cells (BMCs) were obtained from tibia and femur of 5-week-old male imprinting control region (ICR) mice and cultured with M-CSF and RANKL with or without TG, IL-1β, and PBA. mRNA in BMCs transfected with dummy small interfering RNA (SiRNA) or GRP78, PERK and IRE1 SiRNA were profiled using microarray technology. The formation of osteosclasts was evaluated with TRAP staining and resorption pit assay with dentine slice. The expression of ERK 1/2, p-ERK, c-Jun amino-terminal kinase (JNK), p-JNK, p38, p-p38, NF-κB (p65), c-Fos, NFATc1 and ER stress signals, including eIF2α, GRP78, PERK and IRE1 were examined by RT-PCR and immunoblotting. <h3>Results</h3> IL-1β and TG-induced ER stress increased the formation of osteoclasts, which was inhibited by PBA. IL-1β and/or TG-induced osteoclastogenesis was mediated with osteoclast specific signals, including c-Fos, NFATc1 and ER stress associated signaling pathways, PERK, IRE1, GRP78, eIF2α which were downregulated with PBA. Knockdown of the ER stress signals, including PERK, IRE1 and GRP78 by SiRNA inhibited osteoclast-specific signals such as NFATc1 and c-Fos, and thus inhibited IL-1β and/or TG-induced formation of osteoclasts. <h3>Conclusions</h3> ER stress increased the c-Fos and NFATc1-mediated osteoclastogenesis via upregulation of eIF2α, GRP78, PERK and IRE1, and which was inhibited by ER stress inhibitor, PBA. These results suggest that modulation of the mechanisms of ER stress in osteoclast differentiation might be a new therapeutic target to prevent inflammatory and destructive arthritic disease such as RA and diverse osteoporosis. <h3>References</h3> Takayangi H. New immune connections in osteoclast formation. Ann NY Acad Sci 2010;1192:117-123. Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 2010;140:900-17. Yip KH, Zheng MH, Steer JH, Giardina TM, Han R, Lo SZ, Bakker AJ, Cassady AI, Joyce DA, Xu J. Thapsigargin modulates osteoclastogenesis through the regulation of RANKL-induced signaling pathways and reactive oxygen species production. J Bone Miner Res. 2005;20(8):1462-71. <h3>Disclosure of Interest</h3> None Declared
Propofol sedation for colonoscopy with a new ultrathin or a standard endoscope: a prospective randomized controlled study
Authors: U. Töx, B. Schumacher, T. Toermer, G. Terheggen, J. Mertens, B. Holzapfel, W. Lehmacher, T. Goeser, H. Neuhaus
Journal: Endoscopy (2013)

<b>Background and study aims:</b> The majority of colonoscopies in Germany are performed under conscious sedation. Previous studies reported that pediatric colonoscopes reduce the demand for sedative drugs and may improve cecal intubation. The aim of this study was to compare a new ultrathin and a standard colonoscope in terms of propofol demand during colonoscopy. <b>Patients and methods:</b> A total of 203 patients were prospectively randomized to undergo colonoscopy with either a 9.5-mm ultrathin (UTC) colonoscope or a standard colonoscope of variable stiffness. Initially, 40 or 60 mg of propofol were administered according to body weight, followed by bolus injections of 20 mg as deemed necessary. Propofol was administered by a separate physician who was blinded to the endoscope used. Sedation levels were defined according to guidelines; pain and complaints were recorded on a numeric rating scale. <b>Results: </b>Significantly less propofol was required to reach the cecum with the UTC (adjusted mean 94.9 mg [95 % confidence interval (CI) 85.7 – 105.0] vs. 115.3 mg [95 %CI 105.8 – 124.7]; <i>P</i> = 0.003). The level of sedation and pain score were lower with the UTC (sedation level 1 76 % vs. 61 %; <i>P</i> = 0.003; pain score adjusted mean 2.0 [95 %CI 1.7 – 2.4] vs. 2.8 [95 %CI 2.5 – 3.1]; <i>P</i> = 0.001). The rate of ileal and cecal intubation, time to reach the cecum, number of external compressions, withdrawal time, polyp and adenoma detection rate, and patient satisfaction were not different between the two colonoscopes. The time to intubate the ileum was longer with the UTC (1.73 minutes [95 %CI 1.42 – 2.04] vs. 1.22 minutes [95 %CI 0.91 – 1.52]; <i>P</i> = 0.020). <b>Conclusions:</b> Use of a new ultrathin colonoscope was associated with reduced propofol consumption, lower patient sedation levels, and less pain than the standard colonoscope, but ileal intubation time was longer.
Case 11-2002
Authors: Craig T Basson, H Thomas Aretz
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 27-year-old woman was admitted to the hospital because of syncope and two intracardiac masses.The patient had been well until about three years before admission, when she had an episode of numbness in the lower left area of the face, associated with weakness of the right arm and right leg; the numbness lasted 30 to 60 minutes and did not recur. Evaluation at that time included cranial computed tomographic (CT) scanning, which reportedly showed no abnormalities; a cardiac ultrasonographic study was not performed. She was well for the next year. During the two years before admission, . . .
Website of the week: Digital imaging
Authors: D Carnall
Journal: BMJ (1999)

Diagnostic radiologists are enthusiastic proponents of the digital era (see p 168) but most hospitals in Britain still immediately convert the digital information generated by those phosphor screens into film for storage. Chasing, sorting, presenting, and filing x ray films occupies so much medical time that you can’t help yearning for a fast forward button to an era when images are presented in order, weightless, and in the blink of an eye.

Image files are big and need lots of bandwidth, but if you have a fast connection there are a host of resources on the web that let you see the possibilities of retaining and transmitting images in digital form. The BrighamRAD radiology teaching resource of Brigham and Women’s Hospital Department of Radiology (brighamrad.harvard.edu) presents radiographic materials in a searchable database on the web. The material is well presented for learning: you can choose a diagnostic view with no help or a teaching view with arrows. The images have been optimised for transmission over a network, and there are clinical case scenarios that gently chide you if you suggest a non-cost effective investigation strategy.

Academic networks are encouraged to mirror the resource locally if they recommend it to students: one of the best ways of economising on bandwidth is to ensure that frequently used files travel only short distances. In theory, the end user shouldn’t have to think about this, but you might as well have something to occupy your mind as your Progress Bar makes no progress. And while you’re there, check out the business plans for providing radiology opinions all over the globe. (www.partners.org/pw-cgi/dbml.exe?template=/pweb-view/dept/news/article-details.dbml&item_id=6922&dept_id=4)
P246 Lung Transplantation For Patients With Idiopathic Pulmonary Fibrosis And Asymptomatic Coronary Artery Disease
Authors: P. Riddell, K. Redmond, D. Eaton, L. Nolke, S. Javadpour, D. Healy, J. McCarthy, J. Egan
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Lung transplantation significantly improves the survival of patients with advanced idiopathic pulmonary fibrosis (IPF). Concurrent coronary artery disease (CAD) is a relative contraindication to transplantation and can limit access to this therapy. This is particularly relevant as a high prevalence of CAD has been reported in patients with IPF.<sup>1</sup> We sought to determine whether the presence of asymptomatic CAD impacted upon post-transplant survival. <h3>Methods</h3> This retrospective study reviewed all patients who had undergone single lung transplantation for IPF at our centre, between May 2005 to April 2014. We compared post-surgical outcomes for patients with IPF who had an abnormal coronary angiogram (at the time of transplant listing), to those with normal angiography. Kaplan-Meier curves were created to study survival and univarate analysis performed using the Log-Rank score. <h3>Results</h3> In this timeframe, 39 patients underwent lung transplantation for IPF, of which 22 patients (56.4%) had abnormal coronary angiography. Eight of these patients had minor disease, 5 had 10–30% stenosis and 5 had 30–50% stenosis. One patient required coronary artery stenting prior to transplantation, but 3 patients with ≥70% stenosis had no inducible ischaemia on dobutamine stress testing and were managed conservatively. All patients had normal pre-operative left ventricular function. The post-transplant survival of patients with IPF and CAD was 95.7% at 1 year and 70.1% at 5 years. There was no significant difference in survival (p = 0.52) between the cohort with CAD and those with normal pre-operative coronary angiograms. Of note, 1 patient required coronary artery stenting 18 months after transplantation (this patient had 30% LAD stenosis at time of listing). No patients developed chronic arrhythmias, and no patients died as a result of cardiovascular disease. <h3>Conclusion</h3> Although CAD remains a relative contraindication to transplantation, the effects of previous PCI or minor CAD are unknown and may be overstated. This finding is particularly relevant for patients with IPF, who may have an increased prevalence of CAD. <h3>Reference</h3> Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. <i>Am J Respir Crit Care Med</i>. 2006;174(7):810-6
Abstract 2666: Radiation increases permeability and retention of PEG-conjugates in solid tumors.
Authors: Jerry Fong, Daniel J. Ferraro, Jeremy Hunn, Stefan Roberts, Mikhail Y. Berezin, Buck E. Rogers, Dennis E. Hallahan
Journal: Cancer Research (2013)

Abstract Poly-ethylene glycol (PEG), a hydrophobic polymer used to improve the circulation and biocompatibility of biomolecules, accumulates in solid tumors in a size-dependent manner that has been attributed to the enhanced permeability and retention (EPR) effect. Irradiation of cancer disrupts cancer microvasculature, resulting in enhanced EPR effect. In the present study, we found that radiation increases the retention of PEG in solid tumors. The accumulation of PEG in solid tumors was observed with in vivo imaging. Nude mice were prepared with heterotopic unilateral murine and human glioma (GL261, U87) and lung carcinoma (LLC, A549) tumors. A near-infrared (NIR) dye conjugated to PEG was then administered by IV to the mice which were imaged by NIR for seven days. There was increased retention of PEG-dye in tumors that had been irradiated. To further elucidate the mechanism of this increased retention, a similar in vivo imaging experiment was conducted in bilateral heterotopic tumor models (GL261, U87, LLC, A549) for seven days. The irradiated tumors demonstrated increased accumulation of PEG-dye, suggesting that the response to irradiation influenced the accumulation of PEG-dye. To observe the distribution of PEG-dye in the solid tumors, after the in vivo imaging was complete, the tumors were harvested and then sectioned for microscopy and histological staining. PEG-dye was observed in both the necrotic and non-necrotic regions of the tumor. The cancer microvasculature environment differs depending on where the tumor is located; to determine if the increased uptake was limited to only the hind limb, in vivo imaging was conducted in nude mice bearing orthotopic brain (GL261) and lung (LLC) tumors. PEG-dye was also observed to accumulate in these irradiated tumor models. Radiation induced EPR led to cancer specific delivery of PEG conjugates. Collectively, our data suggest that irradiation increases the retention of PEG-dye in solid tumors. This effect appears in more than one tumor type suggesting that the mechanism may arise from an increase in EPR following irradiation of cancer. If so, the concurrent administration of radiation therapy with polymer-conjugated therapeutic complexes may improve targeted drug delivery to cancer. Citation Format: Jerry Fong, Daniel J. Ferraro, Jeremy Hunn, Stefan Roberts, Mikhail Y. Berezin, Buck E. Rogers, Dennis E. Hallahan. Radiation increases permeability and retention of PEG-conjugates in solid tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2666. doi:10.1158/1538-7445.AM2013-2666
How many personnel and how much monitoring are really necessary for nonanesthesiologist administration of propofol for gastrointestinal endoscopy?
Authors: D. Külling, P. Bauerfeind, L. Heuss
Journal: Endoscopy (2011)

We would like to congratulate the European Society of Gastrointestinal Endoscopy (ESGE), the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA), and the European Society of Anesthesiology (ESA) for the joint effort to formulate and endorse a guideline for the nonanesthesiologist administration of propofol (NAAP) for gastrointestinal endoscopy [1]. During the past few years NAAP has become the standard of practice in most gastrointestinal endoscopy units in Switzerland. We read the current European guideline with great interest and were surprised by the recommendations given, and particularly their evidence levels and recommendation grades stated, concerning personnel and monitoring in sections 6.2.1. and 6.2.2., respectively, of the paper.