tbuckley/cabot-search huggingface dataset:
Pathologic Physiology: Mechanisms of Disease
Authors: Fred W. Whitehouse
Journal: JAMA (1967)

For the most part medical texts either cover a narrow field exhaustively or review a broad subject in less detail, trying to emphasize key points. Sodemans' Pathologic Physiology exemplifies the latter.  That such a book exists today reflects the temerity of its authors and the demand of the medical public, the latter conditioned by salutary experiences with previous editions. In 1967 only a courageous editor supported by a splendid group of contributing authors should attempt to review mechanisms of disease in one volume.  I think the Sodemans have succeeded, for the quality of the text is high and most sections are remarkably current. A few chapters suffer from excessive minutiae. Often a fine line divides a superficial discussion from an encyclopedic one. Authors of such texts as this should not feel compelled to be encyclopedic. Rather, they must present basic pathophysiology lucidly and simply, offering the average reader a solid
Abstract LB-132: Frequent inactivation of the p53/Mieap/BNIP3 mitochondrial quality control pathway in gastric cancer.
Authors: Hitoya Sano, Hiroki Kamino, Yasuyuki Nakamura, Masaki Yoshida, Ryuya Murai, Yuri Saito, Manabu Futamura, Kazuhiro Yoshida, Hirofumi Arakawa
Journal: Cancer Research (2013)

Abstract Recently, we discovered a novel mechanism for mitochondrial quality control (MQC), in which Mieap, a p53-inducible protein, controls MQC by repairing or eliminating unhealthy mitochondria via MALM (Mieap-induced Accumulation of Lysosome-like organelles within Mitochondria) or MIV (Mieap-Induced Vacuole) generation, respectively (1, 2). We also reported that two mitochondrial outer membrane proteins, BNIP3 and NIX, are essential mediators of the MALM (2, 3). To examine the role of Mieap-regulated MQC pathway in tumorigenesis, we analyzed the status of p53, Mieap, BNIP3, and NIX in 50 cases of primary gastric cancer. Of the 50 patients, Mieap and BNIP3 promoter methylation was observed in 2 (4%) and 29 (58%) patients, respectively. A p53 mutation was detected in 2 (10%) of the 20 patients with either Mieap or BNIP3 promoter methylation whereas it was found in 3 (15.8%) of the 19 patients with neither Mieap nor BNIP3 promoter methylation, implying that the p53/Mieap/BNIP3 MQC pathway is inactivated in at least 70% of gastric cancer cases. In a colorectal cancer cell line, hypoxia induced MALM. Knockdown of p53, Mieap, or BNIP3 in the cell line severely inhibited hypoxia-induced MALM, leading to the accumulation of unhealthy mitochondria and increased mitochondrial reactive oxygen species (mtROS) generation. Furthermore, the mtROS dramatically enhanced cancer migration and invasion in hypoxic conditions. These results suggest that the p53/Mieap/BNIP3 MQC pathway plays a tumor-suppressive role in gastric cancer. 1. Miyamoto Y et al. PLoS ONE 6: e16054, 2011 2. Kitamura N et al. PLoS ONE 6: e16060, 2011 3. Nakamura Y et al. PLoS ONE 7: e30767, 2012 Citation Format: Hitoya Sano, Hiroki Kamino, Yasuyuki Nakamura, Masaki Yoshida, Ryuya Murai, Yuri Saito, Manabu Futamura, Kazuhiro Yoshida, Hirofumi Arakawa. Frequent inactivation of the p53/Mieap/BNIP3 mitochondrial quality control pathway in gastric cancer. [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 LB-132. doi:10.1158/1538-7445.AM2013-LB-132
PTU-113 A Regional Audit Of The Management Of Patients With Decompensated Liver Disease
Authors: J Dyson, S McPherson
Journal: Gut (2014)

<h3>Introduction</h3> The recent National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report ‘<i>Measuring the Units</i>’ found that hospitals are missing opportunities to save the lives of people with alcohol-related liver disease (ARLD) by failing to provide early intervention and specialist consultant input.<sup>1</sup> <h3>Methods</h3> We aimed to review the management of patients with decompensated liver disease in the first 24 h after admission to hospital. This was a region-wide audit including all Trusts in the Northern Deanery. An audit proforma was designed and data collected on consecutive admissions over a 3 month period. <h3>Results</h3> 139 patients were included in the study; 69% male, median age 54 years (range 26–86 years). ARLD was the cause of liver disease in 88%. The median MELD score was 19 (range 6–39) and 88% had Child-Pugh Grade B or C disease. The commonest reasons for admission were ascites (28%), GI bleeding (21%), encephalopathy (19%) and jaundice (16%). There was a 9% mortality rate during the admission and average length of stay was 15 days. 82 patients had clinical ascites; 62% had a diagnostic tap within 24 h of admission, 21% waited &gt;24 h and 17% did not have a diagnostic tap. 18% had spontaneous bacterial peritonitis (SBP). Previous alcohol history was only documented in 43% but current daily consumption was documented in 81%. Of patients with documented current alcohol excess, 92% received pabrinex and 94% were started on CIWA. 99% had their renal function checked on admission. 26% had renal impairment; 28% of whom did not have all their nephrotoxins stopped. Hyponatraemia (sodium &lt;125 mmol/L) was present in 9%; 42% of whom did not have diuretics stopped. 27 (19%) patients had known or suspected variceal bleeding. 19% did not receive terlipressin and 30% did not receive vitamin K. 67% of patients had an upper GI endoscopy within 12 h of admission, and 78% within 24 h. Hepatic encephalopathy was present in 32% of patients and lactulose commenced in 98%. 17% of patients were not seen by a consultant (any speciality) within 12 h of admission, 7% were not seen by a gastroenterology or hepatology consultant within 72 h of admission and 39% were not seen within 24 h. <h3>Conclusion</h3> There are clear deficiencies in the acute management of patients with decompensated liver disease across the Northern region in keeping with the findings of the NCEPOD report. The findings of this audit will be shared across the region and we are instituting a ‘care bundle’ to focus on the key management of these patients and guide clinicians to improve patient care. We will re-audit to assess the impact of the ‘care bundle’ on patient care. <h3>Reference</h3> http://www.ncepod.org.uk/2013report1/downloads/Meauring%20the%20Units_summary%20report.pdf <h3>Disclosure of Interest</h3> None Declared.
Candidemia in the Critical Ill: An economic analysis of daily antimicrobial therapy-related costs
Authors: Dominique Vandijck, Stijn Blot, Mieke Depaemelaere, Sandra Oeyen, Kirsten Colpaert, Lieven Annemans, Koenraad Vandewoude, Renaat Peleman, Franky Buyle, Sonia Labeau, Johan Decruyenaere
Journal: Intensive Care Medicine (2007)
THU0474 Association of Il4, IL4R and IL8RB Gene Polymorphisms with the Risk of Developing Rheumatoid Arthritis
Authors: L.M. Canet, R. Cáliz, C.B. Lupiañez, H. Canhão, A. Escudero, I. Filipescu, J. Segura, M.J. Soto-Pino, M.Ά. Ferrer, A. García, L. Romani, E. Pérez-Pampin, A. González-Utrilla, M.Ά. Lόpez-Nevot, E. Collantes, J.E. Fonseca, J. Sainz
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Candidate gene association studies have consistently demonstrated that the dysregulation of the immune responses underlying rheumatoid arthritis (RA) are influenced by single nucleotide polymorphisms (SNPs) in immuno-modulating genes. <h3>Objectives</h3> The aim of this study was to test whether 50 potentially functional SNPs in 17 immuno-modulating genes (<i>IL4, IL4R, IL5, IL8, IL8RA, IL8RB, IL10, IL10RA, IL12A, IL12B, IL13, IL16, IFNG, IFNGR2, CCR5, MIF</i>, and <i>VEGFA</i>) are associated with the risk of RA. <h3>Methods</h3> We genotyped selected SNPs in 1239 RA patients and 1229 controls using KASPar® assays (LGC Genomics). Five percent of samples were included as quality control duplicates. <h3>Results</h3> We found that carriers of the <i>IL4</i><sub>rs2070874T</sub>, <i>IL4</i><sub>rs2243290A</sub>, <i>IL4</i><sub>rs2243250T</sub> and <i>IL4</i><sub>rs2243268C</sub> alleles and the <i>IL8RB</i><sub>rs2230054C/C</sub> and <i>IL8RB</i><sub>rs1126580G/G</sub> genotypes had a significantly increased risk of RA (OR=1.37, 95%CI 1.11-1.71, <i>P</i>=0.004; OR=1.33, 95%CI 1.07-1.65, <i>P</i>=0.009; OR=1.32, 95%CI 1.07-1.63, <i>P</i>=0.01; OR=1.25, 95%CI 1.01-1.56, <i>P</i>=0.04; OR=1.31, 95%CI 1.05-1.63, <i>P</i>=0.01 and OR=1.36, 95%CI 1.10-1.69, <i>P</i>=0.002, respectively) whereas carriers of the <i>IL10</i><sub>rs3024509C/C</sub> genotype showed a significantly decreased risk for the disease (OR=0.26, 95%CI 0.09-0.75, <i>P</i>=0.007). Haplotype analysis also revealed that carriers of the <i>IL4</i><sub>TTCAT</sub> and <i>IL8RB</i><sub>CG</sub> haplotypes had a significantly increased risk of RA (OR=1.28, 95%CI 1.05-1.56, <i>P</i>=0.016 and OR=1.24, 95%CI 1.09-1.41, <i>P</i>=0.001, respectively) whereas carriers of the <i>IL4R</i><sub>GG</sub> haplotype had a decreased risk of developing the disease (OR=0.78, 95%CI 0.63-0-95, <i>P</i>=0.016). Interestingly, the association of the <i>IL4</i><sub>rs2243250</sub> polymorphism was confirmed in a well-powered meta-analysis including 7150 individuals (OR=1.186, 95%CI 1.07-1.31, <i>P</i>=0.0010) although we failed to show a relationship between this promoter variant and the expression levels of <i>IL4</i> mRNA (<i>P</i>=0.51). Finally, SNP-SNP interaction analysis suggested that the <i>IL8RB</i><sub>rs1126580</sub> and <i>IL8RB</i><sub>rs2230054</sub> SNPs also influence on risk of RA through interactions with the <i>CCR5</i><sub>rs2734648</sub> SNP (<i>P</i>=0.028 and 0.026, respectively). <h3>Conclusions</h3> These findings strongly suggest that genetic variants within <i>IL4</i>, <i>IL8RB and</i><i>IL4R</i> genes may play a role in determining the risk for RA. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5176
Infectious Mononucleosis with Intense Jaundice of Long Duration
Authors: Herbert L. Abrams
Journal: New England Journal of Medicine (1948)

JAUNDICE in infectious mononucleosis was first described in 1923 by Downey and McKinlay.1 Since that time, scattered reports of its occurrence have appeared.2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Martin,8 in 1941, described 13 previously reported cases. In 1944 Boger17 found 27 cases, and Spring,14 in the same year, estimated that 35 cases had been recorded. Wechsler21 discovered an additional 25 cases and reported 34 cases of his own from an epidemic of infectious mononucleosis. Thus, at least 100 cases have been described. This figure is in no sense an adequate reflection of the frequency of clinical jaundice in infectious mononucleosis, since undoubtedly many cases remain . . .
A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients
Authors: A.C. Chen, A.J. Martin, R.A. Dalziell, C.A. McKenzie, P.M. Lowe, J.M. Eris, R.A. Scolyer, H.M. Dhillon, J.L. Vardy, V.A. Bielski, G.M. Halliday, D.L. Damian
Journal: British Journal of Dermatology (2016)
AB0767 Biologic treatment patterns in us managed care patients with employer provided health insurance treated for rheumatoid arthritis (ra)
Authors: M. Bonafede, G. J. Joseph, N. Princic, N. A. Shah, D. J. Harrison
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although efficacy of biologics approved for moderate to severe RA is similar in clinical trials, there may be differences in individual patients. As choices for biologic treatment increase, switching, discontinuation, and restarting is common. <h3>Objectives</h3> To explore treatment patterns with etanercept, adalimumab, infliximab, abatacept, certolizumab, golimumab, and rituximab in adult patients with RA. <h3>Methods</h3> The MarketScan Commercial Database was used to identify adults (18-63 years) with RA and ≥1 claim for a biologic of interest between Jan 1, 2008 and Dec 31, 2010 preceded by ≥6-months of enrolment. The first claim meeting these criteria defined the index date and biologic. Patients were grouped based on the first event post index. Patients were “persistent” if they did not have claims for another biologic and continued on their index biologic for 1-year; “switchers” had a claim for another biologic; “restarters” had a 45-day gap after the end of days of supply and a subsequent claim for the index drug. Patients were classified as discontinuing their index biologic if they did not persist for one year. <h3>Results</h3> Of 38,026 patients, 95% indexed on four of the biologics, etanercept (41.6%), adalimumab (27.2%), infliximab (19.2%) and abatacept (6.6%). Of the others, 3.5% received rituximab, 1.2% received golimumab, and 0.6% received certolizumab. Switching rates ranged from 8% for rituximab to 21% for golimumab. Persistence ranged from 38% for rituximab to 67% for infliximab. Restart rates ranged from 7% in infliximab to 16% in etanercept and rituximab. Discontinuation ranged from 15% in infliximab to 38% in rituximab. <h3>Image/graph</h3> <h3>Conclusions</h3> Of the four most frequently prescribed biologics in RA, infliximab users were more likely to be persistent and correspondingly less likely to restart than patients on other agents. Patients starting on subcutaneously (SC) administered agents were most likely to switch to other SC agents, and patients starting in intravenous (IV) agents were more likely to switch to other IV agents. Discontinuation rates were similar across agents. <h3>Disclosure of Interest</h3> M. Bonafede: None Declared, G. Joseph Shareholder of: Amgen Inc., Pfizer Inc., Employee of: Amgen, N. Princic: None Declared, N. Shah Shareholder of: Amgen Inc., Employee of: Amgen, D. Harrison Shareholder of: Amgen Inc., Employee of: Amgen
Massive hemobilia following transpapillary bile duct biopsy treated by using a covered self-expandable metal stent
Authors: Jeong-Yeop Song, Jong Moon, Hyun Choi, Dong Kim, Moon Choi, Tae Lee, Sang-Woo Cha, Young Cho, Sang-Heum Park
Journal: Endoscopy (2014)

Severe hemobilia after a forceps biopsy is very rare [1] [2]. The management of uncontrolled hemobilia after endoscopic procedures includes percutaneous radiologic intervention or surgery [3] [4]. Recently, successful endoscopic hemostasis using covered self-expandable metal stents (CSEMS) for uncontrolled bleeding following sphincterotomy, stent removal, or papillary balloon dilation has been reported [3] [4] [5]. We report a case of massive hemobilia after a transpapillary forceps biopsy of the bile duct and successful endoscopic hemostasis with placement of a CSEMS.
Amine Metabolism after an Overdose of a Monoamine Oxidase Inhibitor
Authors: Eugene T. Baldridge, Leona V. Miller, Bernard J. Haverback, Shannon Brunjes
Journal: New England Journal of Medicine (1962)

SINCE iproniazid was shown to be an effective monoamine oxidase inhibitor by Zeller et al.1 in 1952 there has been extensive use of monoamine oxidase inhibitors, particularly in psychiatric diseases,2 angina pectoris3 and hypertension.4 The usual side effects of monoamine oxidase inhibitors, such as postural hypotension, dizziness and dryness of the mouth, are well known.5 , 6 With excessive doses, marked Central-nervous-system disturbances occur. The management of patients who have ingested an overdose of a monoamine oxidase inhibitor has not been well documented. The purpose of this paper is to report the clinical characteristics of a patient who ingested a large amount . . .
A1.6 Differences of the BCR and TLR9-induced IL-10 production in mouse splenic B cell populations
Authors: K Huber, G Sarmay, D Kovesdi
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Scientific background</h3> A functionally important subset of B cells, known as regulatory B cells (Breg), are specialised to control immune response and immunological diseases such as autoimmunity. Breg cells are best characterised by their inducible production of IL-10 and can appear in different phenotypic forms. Various activation signals, including Toll-like receptors (TLRs), B cell antigen receptor (BCR) or CD40 stimulation can trigger the regulatory transformation of B cells, although it is not clear which of these signals are the most effective and which B cells have the most susceptible phenotype. We have studied the effect of the BCR and TLR9 stimulation on three populations of B cells in mouse spleen (Transitional-2-Marginal Zone Precursors (T2-MZP), Marginal Zone (MZ) and Follicular (FO) B cells) to induce differentiation into Bregs. <h3>Materials and methods</h3> We set up in vitro cultures using sorted B cells from T2-MZP, MZ or FO pools from the spleen of adult mice and stimulated them via the BCR and/or TLR9. The transformation to Breg was monitored by following IL-10 production using gene expression analysis, IL-10-specific ELISA or intracellular IL-10 staining measured by FACS. <h3>Results</h3> Based on our experimental set up, we found that the BCR signal alone was not sufficient to induce IL-10 production, while TLR9 stimulation mediated the regulatory transformation of all B cell types with different extent. Comparing the three populations, we found that B cells from the marginal zone responded more efficiently for TLR9 stimulation. We detected the highest level of secreted IL-10 and the highest number of induced IL-10 positive cells among MZ B cells. The results at protein level were confirmed by gene expression analysis, additionally, at mRNA level a time-dependent synergistic crosstalk through the BCR and TLR9 was observed. <h3>Conclusion</h3> We concluded that MZ B cells were the most inducible B cell population and TLR9 signal alone was efficient to trigger IL-10 production. Using the most sensitive B cell population with the efficient stimulus will help us to study the signalling characteristics of Bregs and their important role in autoimmune diseases. This project was supported by OTKA NK 104846 and by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences.
AB0806 Polymorphisms Analysis of Bone Metabolism Genes in Relation to Bone Mineral Density in Patients with Chronic Periodontitis: Table 1
Authors: T. Lakhdar, R. El jaoudi, A. Ibrahimi, O.K. Ennibi, F. Znat, F. Allali, H. Rkain, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Polymorphisms in Vitamin D receptor (FokI (VDR-F) and BsmI (VDR-B)), Estrogen receptor (Pvu II (ESR1P) and Xba I (ESR1X)), Collagen type1 (SpI (COL1A1) and Calcitonin Receptor (Alu I (CTR)) are thought to be candidate markers for osteoporosis. Based on the fact that osteoporosis and periodontal diseases are bone destructive diseases, we investigated the relationship between polymorphisms in these candidate genes and bone mineral density (BMD) of lumbar spine and femoral neck in patients suffering from chronic periodontitis (CP). <h3>Methods</h3> Lumbar spine and femoral neck BMD of individuals included in this study were diagnosed using the dual X-ray absorptiometry method. Blood was drawn and Genomic DNA was prepared and genotyped using MetaBone Clinical Arrays kit (Genomica, Spain). The genotyping and polymorphisms identification consisted on the simultaneous amplification of five regions of the genome containing the six SNPs of interest. Clinical attachment level (CAL), gingival bleeding index (GI), and probing depth (PD) and Simplified Oral Hygiene Index (OHI-S) were determined in all participants by a single experimented examiner. <h3>Results</h3> Table 1 (below) shows SNPs and variant alleles prevalence of genes associated with metabolic bone disorders in 18 chronic periodontitis patients: Statistical analysis showed that women with CP carrying the genotype VDRF-FOKI (Ff) have a lower lombar BMD (p=0.003) and higher number of teeth loss (p=0.003). However, we were not able, in this preliminary study, to show any association between BMD of lumbar spine L2–L4 and Ward9s BMD in CP patients and polymorphisms in different geotyped genes; Vitamin D receptor BsmI (VDR-B), Estrogen receptor PvuII (ESR1P), Collagen type1 SpI (COL1A1) and Calcitonin Receptor Alui (CTR). Furthermore, no association was found between these polymorphisms and severity parameters of chronic periodontitis. <h3>Conclusions</h3> This preliminary study showed that Lower lombar BMD were observed in patients who carried VDRF-FOKI Ff genotype and lower prevalence of normal variants of VDRB-BSMI, CTR-ALUI and ESR1X-XBAI in the population of chronic periodontitis women. A larger case control study is ongoing in order to get bigger data to complete this report. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5961
PMO-147 Recombinant erythropoetin support is equally effective in the treatment of HCV pre and post transplant
Authors: A Barnabas, D Joshi, K Agarwal
Journal: Gut (2012)

<h3>Introduction</h3> Recombinant EPO is often used in an attempt to improve Hepatitis C virus (HCV) treatment outcomes in complex patient groups. We assessed if its use was as effective in the post-transplant population as in a non-transplant group that also required EPO support. There is currently an absence of clear guidelines in this area and little evidence to support its efficacy overall. <h3>Methods</h3> Between December 2009 and July 2010, 57 patients were prescribed EPO while undergoing HCV treatment. In this group, 13 patients who had undergone liver transplantation were identified. These were matched by HCV, genotype, gender and stage of liver fibrosis with a non-transplant group also treated with EPO. Numbers of patients being re-treated for HCV were similar in transplant and non-transplant groups (6/13 and 7/15 respectively). <h3>Results</h3> 3/15 (19%) in the non-transplant group and 1/13 (7.7%) patients in the transplanted group achieved a sustained virological response to treatment. Discontinuation rates, however, were lower in the non-transplant group (4 vs 8, OR 10.4). The initial Hb was not significantly different between the two groups (mean 12.78 in the transplant group and 13.42 in the non-transplant group, p=0.39). Mean decrement in Hb was similar in transplant and non-transplant groups over the first 8 weeks of treatment (3.07 vs 2.54 g/dl) and the mean time to nadir in haemoglobin was similar in both groups (16 vs 19 weeks). 7/15 (47%) (non-transplant vs 7/13 (54%) transplant patients had a Hb decrement &gt;4 mg/dl on treatment (OR 0.83). Five patients (38%) in the transplant group and 7 (47%) in the non-transplant group required EPO prior to treatment week 8. Median treatment duration was shorter in the transplant group (24 vs 48 weeks). Ribavirin dosages varied widely in both groups and there was significant variation in ribavirin dose reduction strategies. One patient in the non-transplant group developed a deep vein thrombosis and one patient in the transplant group had a CVA while on treatment with EPO. <h3>Conclusion</h3> Anaemia related to hepatitis C treatment both presents and is managed similarly in both transplant and non-transplant difficult-to-treat populations. The risk of thrombotic events with EPO use is significant should be carefully borne in mind when initiating EPO support. <h3>Competing interests</h3> None declared.
Physicians' Aid in Dying
Authors: R I Misbin
Journal: New England Journal of Medicine (1991)

PROPONENTS of Initiative 119 in the state of Washington have gathered more than the 150,000 signatures required to put the initiative on the ballot in November 1991.1 The measure would amend the state's natural-death act to permit "physician aid in dying," defined as "a medical service provided in person by a physician that will end the life of a conscious and mentally competent qualified person in a dignified, painless and humane manner, when requested voluntarily by the patient through a written directive executed at the time the service is desired." Although the wording of the initiative does not give details . . .