tbuckley/cabot-search huggingface dataset:
Hyperkalemic Neuromyopathy in Addison's Disease
Authors: Richard H. Pollen, Robert H. Williams
Journal: New England Journal of Medicine (1960)

ALTHOUGH a deficiency of adrenocortical hormones is commonly associated with potassium retention, clinical manifestations of hyperkalemia in untreated Addison's disease are quite rare.1 However, a Landry type of rapidly ascending muscular weakness that leads to flaccid quadriplegia but tends to preserve cerebration and cranial-nerve function is occasionally observed with the high serum potassium levels accompanying renal insufficiency.2 3 4 These patients die from the neuromyocardial effect of excess potassium ion.Although it is recognized that the administration of potassium salts to patients with Addison's disease5 , 6 and even to normal subjects7 may induce profound muscle weakness, cramps and vivid olfactory and cutaneous paresthesias, . . .
P1-12-06: The Role of MAPK and PI3K/AKT/mTOR Signaling in Innate Lapatinib Resistance.
Authors: M McDermott, N O'Brien, K McDonald, J Crown, N O'Donovan, D Slamon
Journal: Cancer Research (2011)

Abstract Background: Lapatinib is a tyrosine kinase inhibitor which blocks downstream MAPK and P13K/AKT/mTOR proliferation and survival signaling pathways in HER2 positive breast cancer cell lines, tumor xenografts and HER2 positive breast cancer patients. However, pre-clinical and clinical studies have shown that not all HER2 positive patients respond to lapatinib and thus innate resistance to lapatinib exists. The identification of biomarkers of lapatinib response is therefore critical and would enable individual therapeutic decisions to be based on tumor biology rather than basic histopathology data alone. The aim of this study was to examine the role of MAPK and PI3K/AKT/mTOR signaling in a panel of lapatinib sensitive and resistant HER2−amplified breast cancer cell lines to identify pharmacodynamic markers of response to lapatinib treatment. Methods: Dose response curves were generated to determine sensitivity to lapatinib in a panel of 17 HER2−amplified breast cancer cell lines. Total and phosphorylated levels of HER2, HER3, EGFR, AKT, ERK, S6K and eEF2 were determined following 24 hours lapatinib treatment in each of the cell lines. Results: Twelve of the cell lines were sensitive to lapatinib with IC50g &amp;lt; 1 μM while 5 of the cell lines were innately resistant to lapatinib with IC50g &amp;gt; 1 μM. Levels of pHER2 and pHER3 were decreased in response to lapatinib in all cell lines independent of sensitivity to lapatinib. This suggests that inhibition of HER2/HER3 activation is not indicative of response to lapatinib treatment. There was also no correlation between the levels of HER2, HER3, and EGFR and sensitivity to lapatinib in the cell line panel. In lapatinib sensitive cell lines, lapatinib decreased PI3K (pAKT), mTOR (pS6K) and MAPK (pERK) signaling and increased peEF2 levels. In contrast the levels of pAKT, pS6K, peEF2 and pERK were maintained following lapatinib treatment in lapatinib resistant cells. The continued activation of these proteins in the presence of lapatinib suggests a possible feedback mechanism that warrants further investigation. These data confirm that maintained signaling through either the P13K/AKT/mTOR pathway or the MAPK pathways in the presence of lapatinib can be an early pharmacodynamic biomarker of response. Conclusions: Maintenance of pAKT, pS6K, peEF2 and pERK levels, in response to lapatinib treatment correlates with lapatinib resistance. These data suggest that alterations in the P13K/AKT/mTOR and MAPK pathways play an important role in innate lapatinib resistance and pharmacologically targeting these pathways is a rational therapeutic approach for overcoming innate lapatinib resistance. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-06.
P10.02 * UTERINE CARCINOSARCOMA WITH PARANEOPLASTIC CEREBELLAR DEGENERATION: CASE ANALYSIS WITH LITERATURE REVIEW
Authors: K. R. Kaufman, T. T. Sensiba, P. J. Struck
Journal: Neuro-Oncology (2014)

INTRODUCTION: Paraneoplastic neurologic syndromes (PNS), a heterogeneous group of oncologic immune-mediated neurologic disorders, often antedate cancer diagnosis. PNS recognition results in early cancer screening/treatment. Paraneoplastic cerebellar degeneration (PCD) is an aggressive/debilitating/fatal PNS characterized by pancerebellar symptoms – progressive ataxia/dysarthria/nystagmus/vertigo. PCD is predominantly associated with breast/gynecologic cancers. Though 12 onconeural antibodies are implicated in PCD, anti-Yo antibody is the most common/specific antibody seen in PCD. We present the first case of anti-Yo PCD associated with uterine carcinosarcoma. METHOD: Case analysis. CASE: 78yo female presented with month-long history of ataxia/gait instability/falls and abrupt onset diplopia/nausea/vomiting without fever/syncope/headache /dysarthria. Past medical history was significant for right breast T1 N0 invasive ductal carcinoma s/p partial mastectomy and adjuvant whole breast radiation that occurred 1 year prior to presentation. Neurologic exam revealed intact language/comprehension, left sixth cranial nerve palsy, truncal/limb ataxia, bilateral horizontal nystagmus, and symmetric 3+ deep tendon reflexes without focal deficits or dystonia noted. Routine blood work was unremarkable. Brain MRI with/without contrast noted no evidence of metastatic disease/demyelinating process/hemorrhage/infarction. She declined CSF studies. Within two months, she developed dysarthria/dysphagia and was unable to stand without assistance due to progressive ataxia. PNS laboratory evaluation yielded high titer of anti-Yo antibody (1/245,760) with positive Western blot assay as the only onconeural antibody. Chest/abdomen/pelvis CT scan demonstrated multiple soft tissue lesions in the omentum with bilateral sub-centimeter pulmonary nodules. Tumor marker analysis noted elevated CA-125/CA-27.29/CA-15.3. CT guided biopsy of omental lesions revealed poorly differentiated carcinosarcoma. Immunohistochemistry confirmed malignant stage IV uterine carcinosarcoma. Chemotherapy with IVIG was initiated. Though tumor burden size decreased, PCD progressed (bedbound, increased anti-Yo antibody titers). Rapid neurologic decline required hospice 8 months after PCD diagnosis associated with uterine carcinosarcoma. She died 1 month later. CONCLUSIONS: This case confirms anti-Yo PCD association with uterine carcinosarcoma. PCD requires early cancer screening/treatment and aggressive multi-modal immunotherapy interventions. Clinicians should have a low threshold for PCD. Double primary cancers must be considered. Prospective trials addressing anti-Yo PCD therapeutic interventions, illness progression, associated cancer, double primary, and survival are indicated. Clinicians require further education regarding PCD and other PNS.
Melanotic Schwannoma Mimicking Myositis Ossificans
Authors: O Konez, P K Vyas, M Goyal
Journal: Clinical Nuclear Medicine (2000)

Pelvic radiographs of a 20-year-old woman showed a bony mass lesion lateral to the left iliac bone. CT and Tc-99m MDP whole-body scanning were also performed for further assessment. All studies strongly suggested a diagnosis of myositis ossificans; however, a pathologic diagnosis of melanotic schwannoma was made after the mass was excised. Cases of melanotic schwannoma have been reported in different anatomic locations, some of which were reported to be a component of the Carney complex. Further diagnostic work-up in this patient revealed no other signs of this complex.
AB1079 Total Knee Replacement from the Patient's Perspective. A Qualitative Study
Authors: E. Nuñez, P. Isla, M.C. Olivé, A. Pascual, A. Saulό, S. Sastre, L. Lozano, J.M. Segur, M. Nuñez
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Total knee replacement (TKR) is effective in relieving pain and improving function in patients with severe osteoarthritis (OA) However, studies report that 14-30% of patients are dissatisfied with the result and do not achieve the expected benefits, especially in function. <h3>Objectives</h3> To examine the factors influencing decision-making before TKR. <h3>Methods</h3> We made a phenomenological study of the determinants that lead patients to accept, delay or reject TKR (this study is part of a larger study). Demographic and clinical data were collected and pain intensity measured by the WOMAC scale. Focus groups were conducted and the results transcribed and analysed using the 4-stage analysis of qualitative data according to Ritchie, Spencer and O9Connor (2003). <h3>Results</h3> 12 patients (9 female, mean age 71.58 + 6.02 years, BMI 37.43 + 5.32, mean comorbidities 6.73 + 2.19 and mean WOMAC pain 14.9 + 8.89, function 15.77 + 8.6, total 15. 71 + 8. 22) were included: 6 had received, 4 were waiting for and 2 had rejected TKR. Focus groups identified widespread pain (pain intensity functional limitations), causal beliefs and perceptions (OA a natural process associated with age, obesity, physical work, sport) mood (importance of optimism), professional-user relationship (communication, experience of OA) expectations (need for surgery conditioned by pain, lost function, surgical risks), and social support (promotion of healthy habits and adherence conditioned by family and social support) as factors influencing attitudes to undergoing TKR. <h3>Conclusions</h3> The process of deciding to undergo TKR is complex and influenced by multiple factors. TKR improves a small proportion of an aging painful body. Our results suggest the need of care before and after TKR, psychosocial support and preventive and educational programmes. <h3>References</h3> Ritchie J, Spencer L, O9Connor W. Carrying out qualitative analysis. In Ritchie J. and Lewis J. (eds.) guide for social science students and researchers Oaks; New Delhi. Qualitative research practice: A. Sage: London; Thousand; 2003 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4508
AB0129 8-oxoguanine DNA glycosylase (OGG1) regulates the cellular function and survival of chondrocytes in response to catabolic stresses in osteoarthritis
Authors: K. Yudoh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is well known that chondrocytes produce excess amounts of reactive oxygen species (ROS) as well as proinflammatory cytokines and chemokines in response to mechanical and chemical stresses. An oxidized form of guanine, 8-oxo-7,8-dihydroxyguanine (8-oxoguanine) is a major causative lesion for mutagenesis by ROS, since it can form a stable base pair with adenine as well as with cytosine during DNA replication.8-oxoguanine DNA glycosylase (Ogg1) repairs the 8-oxoguanine, one of the most abundant DNA adducts caused by oxygen free radicals. <h3>Objectives</h3> This study identified mitochondrial Ogg1 as a pathogenic mechanism in response to catabolic factors in osteoarthritis (OA). <h3>Methods</h3> 8-oxoguanine and Ogg1 expressions were investigated in human OA cartilage and rat OA cartilage by immunohistologic analysis. We studied whether OA-related catabolic factors influence expression of Ogg1 or 8-oxoguanine in OA chondrocytes and analyzed the relationship among cellular function, apoptosis and Ogg1 or 8oxoguanine expression in human chondrocytes. <h3>Results</h3> We observed the increased level of 8-oxoguanineand the decreased level of Ogg1 in OA chondrocytes in comparison with normal chondrocytes in OA rats as well as in patients with OA. We found that Ogg1 silencing using siRNA reduced chondrocyte activity and augments apoptosis in chondrocytes. <h3>Conclusions</h3> The accumulation of an oxidized form of guanine, 8-oxoguanine, and down-regulation of its repair enzyme Ogg1 in OA chondrocytes may be involved in the pathogenesis of OA. Our study suggests that Ogg1 prevents catabolic stress-mediated chondrocyte dysfunction and apoptosis that might affect the maintenance of articular cartilage. <h3>Disclosure of Interest</h3> None Declared
Correlation Between PET/CT Parameters and KRAS Expression in Colorectal Cancer
Authors: Shang-Wen Chen, Hua-Che Chiang, William Tzu-Liang Chen, Te-Chun Hsieh, Kuo-Yang Yen, Shu-Fen Chiang, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2014)

Purpose The objective of this study was to correlate the association between mutated KRAS and wild-type colorectal cancer (CRC) by using various 18F-FDG PET–related parameters. Methods One hundred twenty-one CRC patients who had undergone preoperative PET/CT were included in this study. Several PET/CT-related parameters, including SUVmax and various thresholds of metabolic tumor volume, total lesion glycolysis, and PET/CT-based tumor width, were measured. Tumor- and PET/CT-related parameters were correlated with genomic expression between KRAS mutant and wild-type groups, using a Mann-Whitney U test and logistic regression analysis. Results Colorectal cancer tumors with a mutated KRAS exhibited higher SUVmax and an increased accumulation of FDG among several threshold methods. Multivariate analysis showed that SUVmax and using a 40% threshold level for maximal uptake of TW (TW40%) were the 2 predictors of KRAS mutations. The odds ratio was 1.23 for SUVmax (P = 0.02; 95% confidence interval, 1.01–1.52) and 1.15 for TW40% (P = 0.02; 95% confidence interval, 1.02–1.30). The accuracy of SUVmax for predicting mutated KRAS was higher in patients with colon or sigmoid colon cancers, whereas it was TW40% in those with rectal cancers. Conclusions SUVmax and TW40% were associated in CRC with KRAS mutations. PET/CT parameters can supplement genomic analysis to determine KRAS expression in CRC.
PTU-102 Alcoholic Liver Disease in working Age Men Constitutes the Main Burden of Large Volume Paracentesis (LVP) in Devon and Significant Cost Savings are Possible
Authors: E Wesley, B Conduit, J Christie, U Thalheimer
Journal: Gut (2013)

<h3>Introduction</h3> The burden of liver disease is steadily rising in the UK, partly secondary to alcohol misuse. Ascites requiring LVP is one of the major complications leading to hospital admission in patients with cirrhosis. Clear guidelines<sup>1</sup> exist regarding correct replacement of albumin and these also state that routine use of blood products to correct coagulopathy is not necessary. However, these are not always consistently applied. Our aim was to assess the demographic data of patients with cirrhosis undergoing LVP at our centre along with the use of albumin replacement and blood products. <h3>Methods</h3> We identified patients who had undergone LVP at our hospital during a 12 month period from October 2010 by reviewing the admission book of our department and by reviewing a list of all the ascitic fluid samples sent to our microbiology department. Case notes for these patients were reviewed and data were collected on patient demographics, aetiology of cirrhosis, use of blood products and human albumin solution (HAS) and volume of ascites drained. <h3>Results</h3> 56 LVP were performed on 28 patients. 24 were male, age range 30 – 84 years (median 59 years). Alcohol was either the only or a contributory cause of cirrhosis in 25 (89%) of patients. None had hepatitis B or C virus infection. 5 patients received fresh frozen plasma (14 units in total) and 1 received octaplex® prior to LVP. The total cost was £1024. 8 patients had less than 5L ascites drained and received a total of 19 units of 20% HAS. 16 patients received more than 8g albumin per litre of ascites drained (a total of 31 unnecessary units). The total cost of this was £1400. The potential cost saving per procedure was £49.47. However data on albumin administration was unavailable for 7 patients and this could be an underestimate. <h3>Conclusion</h3> Alcohol is the predominant cause of cirrhosis requiring LVP in our population and working age men constitute the largest proportion. Significant cost savings can be made by avoiding unnecessary blood products and by avoiding excessive use of albumin or administering other fluids when less than 5 litres of ascites are drained. Trusts should ensure relevant protocols are in place. <h3>Disclosure of Interest</h3> None Declared <h3>Reference</h3> EASL clinical practise guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. <i>Journal of hepatology</i> 2010; 53(3):397–417.
US Youth Soccer Concussion Policy
Authors: Y. Tony Yang, Christine M. Baugh
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 5507: Mechanistic study of a new 4-(3, 5-dimethoxyphenyl)-N-(7-fluoro-3-methoxyquinoxalin-2-yl)piperazine-1-carboxamide compound (RX-5902).
Authors: Young Bok Lee, Deog Joong Kim, Gina Chun Kost, Julie Frank, Chang-Ho Ahn, Zhi-Ren Liu
Journal: Cancer Research (2013)

Abstract In our previous study, we showed that a novel compound 1-(3,5-dimethoxyphenyl)-4-[(6-fluoro-2-methoxyquinoxalin-3-yl)aminocarbonyl] piperazine induces apoptosis of cancer cells by downregulation of Bcl-2 protein levels and causing G2/M cell cycle arrest. We observed also a synergistic effect in growth inhibition when combined with known anticancer agents in cancer cells and potent anti-growth activity in drug-resistant cancer cells as well as anti-proliferation of cancer cells at IC50 values of low nanomolar concentrations. Oral administration of the compound led to inhibition of tumor growth and enhanced survival in several tumor xenograft models. Our recent studies indicated that the compound interacts with p68 RNA helicase (also known as DDX5), a member of the DEAD box family of RNA helicases. p68 has been demonstrated to play a vital role in cell proliferation and tumor/cancer progression. Our studies showed that the compound did not exert its anti-cancer effects by inhibition of RNA unwinding by p68. Instead, the compound completely abrogated the β-catenin stimulated ATPase activity of p68 with an IC50 of 61 nM. More extensive studies are ongoing to validate and further characterize our interesting discovery. Citation Format: Young Bok Lee, Deog Joong Kim, Gina Chun Kost, Julie Frank, Chang-Ho Ahn, Zhi-Ren Liu. Mechanistic study of a new 4-(3, 5-dimethoxyphenyl)-N-(7-fluoro-3-methoxyquinoxalin-2-yl)piperazine-1-carboxamide compound (RX-5902). [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 5507. doi:10.1158/1538-7445.AM2013-5507
IN-HOSPITAL MORTALITY AMONG PATIENTS RECEIVING AN IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR IN THE UNITED STATES: 2000 TO 2012
Authors: Ra'Ad Tashman, Elena Dolmatova, Kasra Moazzami, Monali Patel, Victor Mazza, Marc Klapholz, Alfonso Waller
Journal: Journal of the American College of Cardiology (2016)
Feasibility and safety of endoscopic transumbilical thoracic surgical lung biopsy: A survival study in a canine model
Authors: WH Chen, Y Chu, CJ Yeh, CY Liu, HC Yuan, PJ Ko, YH Liu
Journal: Endoscopy (2012)

Background: Post-thoracotomy discomfort is an unavoidable complication following thoracoscopic surgery. Transumbilical laparoscopy allows the patient to undergo various surgical procedures associated with abdominal diseases and prevents post-thoracotomy discomfort by avoiding the creation of an incision through the chest wall. The aim of this study was to evaluate the feasibility and safety of transumbilical thoracic exploration and surgical lung biopsy in a canine survival model.
Hepatic Copper Overload and Features of Indian Childhood Cirrhosis in an American Sibship
Authors: Jay H. Lefkowitch, Christine L. Honig, Mary E. King, Jack W. C. Hagstrom
Journal: New England Journal of Medicine (1982)

We studied the clinical histories of four white American siblings who died at 4 1/2 to six years of age of an unknown form of cirrhosis, in an effort to identify the etiologic factors in this familial syndrome. The family history disclosed no Indian heritage or parental consanguinity. The children were born and raised in New Jersey. Each had been well until progressive lethargy, abdominal swelling, jaundice, and fever developed four to seven months before death. The liver histopathology in each case closely resembled that of Indian childhood cirrhosis and included severe panlobular liver-cell swelling with Mallory body formation, prominent pericellular fibrosis, "micro-micronodular" cirrhosis, and marked deposits of copper and copper-binding protein. Hepatic copper levels were as high as 2083 μg per gram of tissue (normal, <50 μg). A number of features distinguish this syndrome from Wilson's disease and familial cholestatic disorders of childhood. A genetically determined disturbance in copper metabolism appears to be the most likely cause. (N Engl J Med. 1982;307:271–7.)