tbuckley/cabot-search huggingface dataset:
Combined therapy with PPARα agonist and l-carnitine rescues lipotoxic cardiomyopathy due to systemic carnitine deficiency
Authors: T ASAI, K OKUMURA, R TAKAHASHI, H MATSUI, Y NUMAGUCHI, H MURAKAMI, R MURAKAMI, T MUROHARA
Journal: Cardiovascular Research (2006)

Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily and are key regulators of fatty acid oxidation (FAO) in the heart. Systemic carnitine deficiency (SCD) causes disorders of FAO and induces hypertrophic cardiomyopathy with lipid accumulation. We hypothesized that activation of PPARalpha by fenofibrate, a PPARalpha agonist, in addition to conventional L-carnitine supplementation may exert beneficial effects on the lipotoxic cardiomyopathy in juvenile visceral steatosis (JVS) mouse, a murine model of SCD.Both wild-type (WT) and JVS mice were fed a normal chow, 0.2% fenofibrate containing chow (FE), a 0.1% L-carnitine containing chow (CA) or a 0.1% L-carnitine + 0.2% fenofibrate containing chow (CA + FE) from 4 weeks of age. Four to 8 animals per group were used for each experiment and 9 to 11 animals per group were used for survival analysis.At 8 weeks of age, JVS mice exhibited marked ventricular hypertrophy, which was more attenuated by CA + FE than by CA or FE alone. CA + FE markedly reduced the high plasma and myocardial triglyceride levels and increased the low myocardial ATP content to control levels in JVS mice. In JVS mice, myocardial 1,2-diacylglycerol (DAG) was significantly increased and showed a distinct fatty acid composition with elevation of 18:1(n-7,9) and 18:2(n-6) fatty acids compared with that in WT mice. CA + FE significantly altered the fatty acid composition of DAG and inhibited the membrane translocation of cardiac protein kinase C beta2 in JVS mice. Furthermore, CA + FE prevented the progressive left ventricular dysfunction and dramatically improved the survival rate in JVS mice (survival rate at 400 days after birth: 89 vs. 0%, P < 0.0001).PPARalpha activation, in addition to l-carnitine supplementation, may rescue the detrimental lipotoxic cardiomyopathy in SCD by improving cardiac energy and lipid metabolism as well as systemic lipid metabolism.
Prospective 10-year evaluation of hypobetalipoproteinemia in a cohort of 772 firefighters and cross-sectional evaluation of hypocholesterolemia in 1,479 men in the National Health and Nutrition Examination Survey I
Authors: Charles J. Glueck, William Kelley, Arun Gupta, Robert N. Fontaine, Ping Wang, Peter S. Gartside
Journal: Metabolism (1997)
Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints.
Authors: M W Lark, E K Bayne, J Flanagan, C F Harper, L A Hoerrner, N I Hutchinson, I I Singer, S A Donatelli, J R Weidner, H R Williams, R A Mumford, L S Lohmander
Journal: Journal of Clinical Investigation (1997)

To examine the activity of matrix metalloproteinases (MMPs) and aggrecanase in control and diseased human articular cartilage, metabolic fragments of aggrecan were detected with monospecific antipeptide antibodies. The distribution and quantity of MMP-generated aggrecan G1 fragments terminating in VDIPEN341 were compared with the distribution of aggrecanase-generated G1 fragments terminating in NITEGE373. Both types of G1 fragments were isolated from osteoarthritic cartilage. The sizes were consistent with a single enzymatic cleavage in the interglobular domain region, with no further proteolytic processing of these fragments. Both neoepitopes were also detected by immunohistochemistry in articular cartilage from patients undergoing joint replacement for osteoarthritis (OA), rheumatoid arthritis (RA), and in cartilage from adults with no known joint disease. In control specimens, the staining intensity for both G1 fragments increased with age, with little staining in cartilage from 22-wk-old fetal samples. There was also an increase with age in the extracted amount of MMP-generated neoepitope in relation to both aggrecan and collagen content, confirming the immunohistochemical results. After the age of 20-30 yr this relationship remained at a steady state. The staining for the MMP-generated epitope was most marked in control cartilage exhibiting histological signs of damage, whereas intense staining for the aggrecanase-generated fragment was often noted in adult cartilage lacking overt histological damage. Intense staining for both neoepitopes appeared in the more severely fibrillated, superficial region of the tissue. Intense immunostaining for both VDIPEN- and NITEGE- neoepitopes was also detected in joint cartilage from patients with OA or RA. Cartilage in these specimens was significantly more degraded and high levels of staining for both epitopes was always seen in areas with extensive cartilage damage. The levels of extracted VDIPEN neoepitope relative to collagen or aggrecan in both OA and RA samples were similar to those seen in age-matched control specimens. Immunostaining for both types of aggrecan fragments was seen surrounding the cells but also further removed in the interterritorial matrix. In some regions of the tissue, both neoepitopes were found while in others only one was detected. Thus, generation and/or turnover of these specific catabolic aggrecan fragments is not necessarily coordinated. Our results are consistent with the presence in both normal and arthritic joint cartilage of proteolytic activity against aggrecan based on both classical MMPs and "aggrecanase."
Update in Perioperative Medicine
Authors: Paul Casner
Journal: Annals of Internal Medicine (2004)

Letters21 September 2004Update in Perioperative MedicinePaul Casner, MD, PhDPaul Casner, MD, PhDFrom Texas Tech University Health Sciences Center, El Paso, TX 79905.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-6-200409210-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In the 2004 Update in perioperative medicine (1), Smetana and colleagues reviewed the latest revision of the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for perioperative cardiovascular evaluation before noncardiac surgery, which essentially confirm the earlier version. The ACC/AHA guidelines recommend using functional capacity based on the Duke Activity Status Index. These guidelines are at odds with those issued in an American College of Physicians (ACP) position paper, which stated that functional assessment “has not been shown to add to clinical risk index evaluation in the operative setting” (2). The ACP did not include functional assessment ...References1. Smetana GW, Cohn SL, Lawrence VA. Update in perioperative medicine. Ann Intern Med. 2004;140:452-61. [PMID: 15023711] LinkGoogle Scholar2. Guidelines for assessing and managing the perioperative risk from coronary artery disease associated with major noncardiac surgery. American College of Physicians. Ann Intern Med. 1997;127:309-12. [PMID: 9265433] LinkGoogle Scholar3. Palda VA, Detsky AS. Perioperative assessment and management of risk from coronary artery disease. Ann Intern Med. 1997;127:313-28. [PMID: 9265434] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Paul Casner, MD, PhDAffiliations: From Texas Tech University Health Sciences Center, El Paso, TX 79905. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoGuidelines for Assessing and Managing the Perioperative Risk from Coronary Artery Disease Associated with Major Noncardiac SurgeryPerioperative Assessment and Management of Risk from Coronary Artery Disease Valerie A. Palda and Allan S. Detsky Update in Perioperative Medicine Gerald W. Smetana , Steven L. Cohn , and Valerie A. Lawrence Update in Perioperative Medicine Stephen A. Hilty Update in Perioperative Medicine Gerald W. Smetana , Steven L. Cohn , and Valerie A. Lawrence Metrics 21 September 2004Volume 141, Issue 6Page: 486KeywordsAlgorithmsCardiac surgeryCardiology and cardiovascular diseasesThoracic surgery ePublished: 21 September 2004 Issue Published: 21 September 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Current Therapy for Infrarenal Aortic Aneurysms
Authors: Calvin B. Ernst
Journal: New England Journal of Medicine (1997)

In 1951 the treatment of abdominal aortic aneurysms was revolutionized when Dubost et al. successfully replaced such an aneurysm with a homograft.1 Before that seminal operation, the treatment of abdominal aortic aneurysms was ineffective because there was no treatment that could prevent the lethal rupture of these aneurysms. The goal of surgical treatment was to prevent rupture, with acceptable rates of operative morbidity and mortality. Over the ensuing 46 years, surgical therapy has been refined so that aortic reconstruction has become a safe and frequently performed procedure, with approximately 46,000 repairs carried out in 1992 in the United States.2 Such . . .
Magnetic compression for treatment of large oesophageal diverticula: a new endoscopic approach for a risky surgical disease?
Authors: Simon Bouchard, Vincent Huberty, Daniel Blero, Jacques Devière
Journal: Gut (2015)

### Message

Magnetic compression resulting in serosa-to-serosa apposition followed by pressure necrosis has been shown to be able to create solid anastomostic connections and has been reported in conditions such as oesophageal atresia, benign biliary strictures and malignant gastric outlet obstruction. This first series evaluated this technique for the management of large intrathoracic oesophageal diverticula by creating a communication between the bottom of the diverticulum and the distal oesophagus followed, in a second endoscopy session, by the transection of the proximal septum. Four patients underwent this procedure without complications and with excellent clinical outcome, suggesting that this might be a very promising endoscopic approach avoiding surgery in these difficult cases (figure 1).



Figure 1 
(A) Fluoroscopic view of a gastroscope advanced to the level of a large lower oesophageal diverticulum. (B) Endoscopic view after placement of two magnets, with one magnet at the base of the diverticulum and the other at the opposite side of the septum, in the oesophagus. (C) Ten days following their endoscopic placement, the magnets have joined together, have migrated into the diverticulum and have been removed. The magnet-induced anastomosis between the diverticulum and the oesophagus is clearly visualised. (D) A control gastroscopy is performed 24 h after completion of the …
Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2–harboring clones as main relapse-driving force in childhood ALL
Authors: Maria Morak, Andishe Attarbaschi, Susanna Fischer, Christine Nassimbeni, Reinhard Grausenburger, Stephan Bastelberger, Stefanie Krentz, Gunnar Cario, David Kasper, Klaus Schmitt, Lisa J. Russell, Ulrike Pötschger, Martin Stanulla, Conny Eckert, Georg Mann, Oskar A. Haas, Renate Panzer-Grümayer
Journal: Blood (2012)
What's in a Name When Efficacy Isn't Efficacious?
Authors: Jack L. Lesher
Journal: JAMA (1992)

<h3>To the Editor.</h3> —This letter relates to the article by Kreiss et al<sup>1</sup>published in<i>JAMA</i>. I am concerned that the title is somewhat confusing, as it seems to suggest that the nonoxynol 9 may indeed be effective in preventing human immunodeficiency virus (HIV) acquisition. If I understand the article correctly, this is in fact not the case, and the authors state that they were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women. I wonder if a title such as "Failure of Nonoxynol 9 Contraceptive Sponge Use..." or "Lack of Efficacy of Nonoxynol 9 Contraceptive Sponge Use..." would have been more appropriate. My fear is that busy clinicians may glance at a title and try to extract information from that, and in this case would come up with misleading information. I showed the title to my wife,
Inpatient Management: Variations in some Aspects of Practice in Scotland
Authors: M. A. Heasman, V. Carstairs
Journal: BMJ (1971)

Data for four aspects of inpatient management-namely, variations in length of stay, the time patients spend in hospital before or after operation, and the proportion of patients operated on in surgical units-show considerable variations in certain aspects of practice by Scottish consultants. It is suggested that there may be simple explanations for some of the observed variations. The differences could be due to great variation in the constraints encountered by the consultants in their work, or to wide differences of opinion about the optimum treatment for specific diagnoses.
Abstract P5-13-03: Factors associated with prophylactic mastectomy among BRCA-positive patients with no personal history of breast cancer
Authors: N Elsayegh, A Gutierrez-Barrera, G Baum, K Muse, M Jackson, A Woodson, P Jessica, H Kuerer, J Litton, B Arun
Journal: Cancer Research (2013)

Abstract Background: The rate of prophylactic mastectomy (PM) has recently increased1. A deleterious mutation in the BRCA1 or BRCA 2 genes is among the major reasons why patients pursue PM 2, 3. Women with BRCA1 or BRCA2 gene mutations have up to an 87% risk to develop an invasive breast cancer (BC), and up to 45% risk for ovarian cancer (OC)2, 3. Most studies evaluating predictors of PM in BRCA mutation carriers are performed among women with breast cancer; however, accurate predictors for PM among unaffected BRCA mutation carriers are less defined. In a single institution study we aimed to evaluate predictors of PM among BRCA carriers with no personal history of breast cancer. Method: One hundred seventy seven women with no personal history of BC, who tested positive for a BRCA1 or BRCA 2 germline mutation, were included in the study. Patients’ characteristics were obtained from a prospectively maintained research database under an IRB approved protocol at UT MD Anderson Cancer Center. Univariate analyses using chi-square and logistic regression analysis were used to determine predictive factors associated with PM. The patient characteristics examined included age, martial and educational status, bilateral salphingo-oophorectomy (BSO), family history of 1st and 2nd degree relatives with breast (BC) and ovarian cancer (OC), race, and BRCA genetic test result. Results: Out of the 177 BRCA1 and BRCA 2 positive patients, 51 (29%) elected for PM. The average age for the cohort was 44 years (range 23-91). The majority were Caucasian (81%), and married (72%) with a college degree (64%). One hundred sixty-four (92%) patients had 1st and 2nd degree relatives with BC, 93 (53%) had 1st and 2nd degree relatives with OC, and 85 (48%) had undergone BSO. A logistic regression model was run to identify factors associated with undergoing PM, including family history of OC, family history of BC, BSO and age. Patients with a family history of OC were 2.5 times more likely than those without to have had a PM (p = 0.0125), and patients who had a BSO were 0.137 times less likely to have had a PM (p &amp;lt;.0001). Only 12 patients did not have a family history of BC and none of those patients had a PM, so an Odds Ratio could not be calculated. However, it was determined through the Fisher's exact test that patients with a family history of BC were more likely to undergo a PM (p = 0.0198). Conclusion: The rate of PM in our cohort was slightly lower than expected. Factors associated with PM included a family history of BC and OC. Interestingly, having had a BSO was associated with lower likelihood of undergoing PM (menopausal status will be further evaluated); possibly due to the knowledge that BSO reduces breast cancer risk. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-03.
High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia
Authors: Wing Leung, Dario Campana, Jie Yang, Deqing Pei, Elaine Coustan-Smith, Kwan Gan, Jeffrey E. Rubnitz, John T. Sandlund, Raul C. Ribeiro, Ashok Srinivasan, Christine Hartford, Brandon M. Triplett, Mari Dallas, Asha Pillai, Rupert Handgretinger, Joseph H. Laver, Ching-Hon Pui
Journal: Blood (2011)
Report of the American Society of Echocardiography Committee on Nomenclature and Standards in Two-dimensional Echocardiography.
Authors: W L Henry, A DeMaria, R Gramiak, D L King, J A Kisslo, R L Popp, D J Sahn, N B Schiller, A Tajik, L E Teichholz, A E Weyman
Journal: Circulation (1980)
Home blood sampling for plasma glucose assay in control of diabetes.
Authors: S Howe-Davies, R R Holman, M Phillips, R C Turner
Journal: BMJ (1978)

Estimation of plasma glucose in home blood samples is needed to improve diabetic control. Sufficiently precise measurements on capillary blood were obtained by (a) storing Reflotest glucose-oxidase strips in a desiccant container before reading and (b) collecting blood samples into a simple vacuum bottle containing potassium fluoride (assay of sodium content indicating volume of plasma collected). The precision of the methods (+/- 1 SD) was +/-0.35 mmol/1 (+/-6.3 mg/100 ml). Clinical reliability was assessed by measuring the basal plasma glucose concentration at home on different mornings in patients with maturity-onset diabetes, the day-to-day variation (+/- 1 SD) being +/-0.73 and +/-0.92 mmol/1 (+/-13.2 and +/-16.6 mg/100 ml) respectively. The mean basal plasma glucose concentration in all 84 patients with maturity-onset diabetes from three general practices was 8 mmol/1 (144 mg/100 ml), 44 of the values exceeding 6 mmol/1 (108 mg/100 ml). Improving control by monitoring the basal plasma glucose concentration in maturity-onset diabetes might help to prevent diabetic complications.
Young Children's Probability of Dying Before and After Their Mother's Death: A Rural South African Population-Based Surveillance Study
Authors: Samuel J. Clark, Kathleen Kahn, Brian Houle, Adriane Arteche, Mark A. Collinson, Stephen M. Tollman, Alan Stein
Journal: PLoS Medicine (2013)

Brian Houle and colleagues examine the temporal relationship between mother and child death by using 15 years of data (1994–2008) from household surveys conducted in the Agincourt sub-district of South Africa.
Polycystic Kidney Disease and Hyperuricemia
Authors: Manuel Martinez-Maldonado
Journal: Annals of Internal Medicine (1974)

Comments1 January 1974Polycystic Kidney Disease and HyperuricemiaMANUEL MARTINEZ-MALDONADO, M.D., F.A.C.P.MANUEL MARTINEZ-MALDONADO, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-1-116_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Newcombe's letter (Ann Intern Med70:605, 1973) relating his experience with the high prevalence of gouty arthritis in patients with polycystic kidney disease was of definite interest to us because it corroborates our 1965 report (1) of this association. We called attention to a family, of which we examined and studied 19 members of 3 generations, with polycystic kidney disease definitely diagnosed in 3 males and one female; 2 of the males had clear-cut acute gouty arthritis with hyperuricemia, and the other had hyperuricemia alone. One of the patients who had gouty arthritis had renal insufficiency....Reference1. RIVERAMARTINEZ-MALDONADORAMIREZ DE ARELLANO JMG: Association of hyperuricemia and polycystic kidney disease. Bol Asoc Med PR 57(5) :251-262, 1965 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byClinical Aspects of Gout and Associated Disease StatesPolycystic renal diseaseAutosomal Dominant Polycystic Kidney Disease—More Than a Renal DiseaseGout secondary to chronic renal disease: studies on urate metabolism.Abnormal Urate Excretion Associated with Renal and Systemic Disorders, Drugs, and Toxins 1 January 1974Volume 80, Issue 1Page: 116-116KeywordsArthritisPolycystic kidney disease Issue Published: 1 January 1974 PDF downloadLoading ...
Presidential commission urges revamp of US mental health system
Authors: D. Josefson
Journal: BMJ (2003)

A drastic reorganisation of the mental healthcare system in the United States is needed, says the New Freedom Commission of Mental Health, a panel of 22 experts on mental health and social services.

The commission was founded in April 2002 by a presidential directive, in a bid to eliminate inequality among US citizens with disabilities. President Bush asked the commission to identify problems in US mental healthcare and disability programmes and to suggest potential solutions.

The commission drew on research, expert testimony, and input from over 2300 users, …
Abstract 4663: KRAS, BRAF, and EGFR mutational analysis in ovarian, colon, and lung cancers by highly multiplex PCR/barcoded-magnetic-bead (BMB) suspension-array assays
Authors: Jason Lei, Julia Hsu, Peggy Jen, Daniel Huang, Andre Chung, Lloyd Kao, Miller Chang, Chiou-Chung Yuan, Wei-Hwa Lee, Chi-Tai Yeh, Dean Tsao
Journal: Cancer Research (2014)

Abstract Anti-epithelial growth factor receptor (EGFR) monoclonal antibodies and small molecule EGFR inhibitors have been used for treating metastatic colorectal cancer (mCRC) and non-small cell lung cancer (NSCLC), respectively. However, since a relatively large proportion of the mCRC and NSCLC patients carry the activating KRAS/BRAF mutations that can render these EGFR-targeted therapies ineffective, the KRAS/BRAF mutation testing is now required for such prescription. In contrast, epithelial ovarian cancer (EOC) thus far has been treated by surgery, radiotherapy, and/or chemotherapy depending on the tumor stages. However, it has been shown that a high percentage of tumors of the mucinous, endometrioid, low-grade serous, and other types of EOC patients also contain KRAS or BRAF somatic mutations, suggesting that drugs targeting the mediators of the EGFR pathway may have implications on treating EOC of certain types. The conventional analysis of the KRAS, BRAF, and EGFR mutations has been done by multiple reactions with one mutation target per reaction, thus requiring a large amount of precious patient sample for complete testing. Here we present three highly multiplex molecular diagnostic assays, utilizing amplification by allele-specific PCR and automatic detection by a platform designed around the barcoded-magnetic-bead (BMB) suspension-array technology, for detection of 12 KRAS (in codons 12 and 13), six BRAF (in codon 600), and 21 EGFR (in exons 18-21) mutations in mCRC, NSCLC, and EOC patient samples. The results indicate that, albeit all the reaction components are in single wells, these highly multiplex PCR/BMB assays, by comparing with the sequencing results, not only are sensitive and specific but also can conserve precious tissue specimens, save operating time and labor, reduce turnaround time, and increase assay throughput. Citation Format: Jason Lei, Julia Hsu, Peggy Jen, Daniel Huang, Andre Chung, Lloyd Kao, Miller Chang, Chiou-Chung Yuan, Wei-Hwa Lee, Chi-Tai Yeh, Dean Tsao. KRAS, BRAF, and EGFR mutational analysis in ovarian, colon, and lung cancers by highly multiplex PCR/barcoded-magnetic-bead (BMB) suspension-array assays. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4663. doi:10.1158/1538-7445.AM2014-4663