tbuckley/cabot-search huggingface dataset:
02.12 Il-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro
Authors: Marie-Astrid Boutet, Aurélie Najm, Géraldine Bart, Sophie Touchais, Valérie Trichet, Pierre Layrolle, Cem Gabay, Gaby Palmer, Frédéric Blanchard, Benoit Le Goff
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> IL-38 is a newly characterised cytokine that belongs to the IL-1 family and is expressed in the rheumatoid arthritis (RA) synovial tissue but its exact function and mechanism of action are still misunderstood. Here, we analysed for the first time the effect of IL-38 overexpression in the joints of mice with arthritis and in human macrophages and synovial fibroblasts <i>in vitro</i>. <h3>Materials and methods</h3> Articular injections of an adeno-associated virus (AAV2/8) encoding IL-38 were performed in Collagen-Induced Arthritis (CIA), K/BxN Serum Transfer-Induced Arthritis (STIA) and Antigen-Induced Arthritis (AIA) in mice. The effect of IL-38 overexpression was evaluated through clinical scores, histology, immunohistochemistry, microCT and RT-qPCR analysis. <i>In vitro</i>, THP-1 monocytes/macrophages were transduced with a lentiviral vector to overexpress IL-38. Effect of conditioned media from these transduced THP-1 cells was also tested on primary culture: M1 macrophages and fibroblast-like synoviocytes from RA patients (RA-FLS). <h3>Results</h3> Clinical inflammatory scores were significantly decreased after AAV IL-38 injection in joints of mice with CIA and STIA, but not AIA. This decrease was accompanied by reduced macrophage infiltration and a decreased expression of Th17 signature cytokines (IL-17, IL-23, IL-22, CCL20, CXCL1). However, IL-38 overexpression had no effect on cartilage or bone destruction. <i>In vitro</i>, THP-1 macrophages expressed significantly less IL-6 and IL-23 after IL-38 overexpression. Conditioned media from these cells, containing released IL-38, was also able to exert an anti-inflammatory effect on human primary M1 macrophages and RA-FLS by reducing their IL-6 expression. <h3>Conclusion</h3> This study shows for the first time that IL-38 overexpression attenuates the severity of experimental arthritis in two mice arthritis models. IL-38 may exert its anti-inflammatory effects by decreasing the production of pro-inflammatory cytokines by macrophages and synovial fibroblasts. This effect can lead to the development of novel treatment strategies in arthritis.
Surgical quality and the impact of liver resection on outcome in the New EPOC study.
Authors: Sian Alexandra Pugh, John A. Bridgewater, O James Garden, David Cunningham, Tim Maughan, Tom Maishman, Mike Radford, Amy Whitehead, Jane Mellor, Gareth Griffith, John Neil Primrose
Journal: Journal of Clinical Oncology (2018)

3559 Background: The New EPOC study demonstrated a shorter overall survival (OS) with the addition of cetuximab to chemotherapy for operable colorectal liver metastasis. The combination of a liver resection with EGFR inhibition is unique to this study. Consequently this analysis explores both surgical quality and the impact of volume of liver resected on outcome. Methods: Data is presented for 257/271 patients (early study withdrawals excluded). Details of surgery were completed by the operating or lead surgeon in 19 UK specialist centres. The report of no residual tumour in the pathological specimen was queried in each case. Volume of liver resected was estimated and patients divided into tertiles (tertile 1: ≤20.5%, tertile 2 20.6-50.0%, tertile 3: > 50.0%) to investigate association with OS. Results: Operations were performed on 221/257 patients (113 chemo alone CT, 108 chemo and cetuximab CTX) of which 207 (108 CT, 99 CTX) underwent a resection. A further 15 had surgery that included ablation (5 CT, 10 CTX). 159 had major resections (88 CT, 71 CTX) and the median estimated volume of total liver volume resected was the same in both groups (CT 30.6% IQR 17.4-63.4, CTX 28.1% 17.0-63.4). Those with a small volume (tertile 1, ≤20.5%) of liver resected appeared to have a shorter OS with cetuximab (median OS for CT: not reached, CTX: 55.3 months, HR: 2.45 (95% CI: 1.14-5.24), p = 0.021). By contrast those with a larger volume of liver resected (tertiles 2 & 3) had similar outcomes irrespective of the use of cetuximab (median OS for CT: 81.0 months, CTX: 79.0 months, HR: 1.18 (95% CI: 0.72-1.95), p = 0.509). Examination of the pathological specimen revealed no residual tumour (complete pathological response) in 17 patients (10 CT, 7 CTX) of whom 5 subsequenly died (3 CT, 2 CTX). Other surgical data, including the number of R1 resections (13 CT, 19 CTX), was similar between the study arms. Conclusions: These exploratory analyses suggest the technical aspects of surgery are similar between the treatment groups and that those patients having smaller volume resections may be disadvantaged by the addition of cetuximab. Clinical trial information: 2006-003121-82.
&lt;TITLE&gt;Tossing and turning with insomnia&lt;/TITLE&gt;
Authors: Mi Hwang, Richard Glass, Jeff Molter
Journal: JAMA (1999)

public service of JAMA and the AMA.The information and recommendations appearing on this page are appropriate in most instances; but they are not a substitute for medical diagnosis.For specific information concerning your personal medical condition, JAMA and AMA suggest that you consult your physician.
Practice of Surgery: Current Review
Authors: Alan Marty
Journal: JAMA (1975)

Collating 1,246 references, this collection of 19 review articles emphasizes subject selectivity and textual clarity. As before, important advances in areas of current surgical interest are emphasized. New operative procedures such as the interposition mesocaval shunt for portal vein decompression, intraoperative autotransfusion for acute trauma patients, and arterial reconstruction below the knee in highly selected cases are all well described. Similarly, as the need grows for surgeons in community hospitals to obtain and send more cadaver kidneys to transplant centers, an excellent chapter meticulously details the best methods of renal preservation and operative procurement technique. Fresh thinking about old problems is also included: eg, how to improve America's emergency medical service "nonsystem" or how the pathophysiology and management of colon obstructions differ from those of smallbowel obstructions. Learning is enhanced by mixing empiric observations with common sense. Thus, the higher incidence of sigmoid volvulus in males rather than females becomes
Arthritis in Children with Meningitis Caused by Hemophilus Influenzae
Journal: JAMA (1963)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Amylin compared with calcitonin gene-related peptide: structure, biology, and relevance to metabolic disease
Authors: G. J. Cooper
Journal: Endocrine Reviews (1994)

Journal Article Amylin Compared with Calcitonin Gene-Related Peptide: Structure, Biology, and Relevance to Metabolic Disease Get access Garth J. S. Cooper Garth J. S. Cooper 1Biochemistry and Molecular Biology Group, School of Biological Sciences, and Department of Medicine, School of Medicine, University of Auckland Private Bag 92019, Auckland, New Zealand *Address requests for reprints to: Garth J. S. Cooper, School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. Search for other works by this author on: Oxford Academic Google Scholar Endocrine Reviews, Volume 15, Issue 2, 1 April 1994, Pages 163–201, https://doi.org/10.1210/edrv-15-2-163 Published: 01 April 1994
Low-Molecular-Weight Heparin for Pulmonary Embolism
Authors: John W. Eikelboom, Andrew McQuillan, Daniel J. Quinlan
Journal: Annals of Internal Medicine (2004)

Letters7 September 2004Low-Molecular-Weight Heparin for Pulmonary EmbolismJohn W. Eikelboom, MBBS, Andrew McQuillan, MBBS, and Daniel J. Quinlan, MBBSJohn W. Eikelboom, MBBSFrom Royal Perth Hospital, Perth WA 6001, Australia, and King's College Hospital, London SE5 9RS, United Kingdom.Search for more papers by this author, Andrew McQuillan, MBBSFrom Royal Perth Hospital, Perth WA 6001, Australia, and King's College Hospital, London SE5 9RS, United Kingdom.Search for more papers by this author, and Daniel J. Quinlan, MBBSFrom Royal Perth Hospital, Perth WA 6001, Australia, and King's College Hospital, London SE5 9RS, United Kingdom.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-5-200409070-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:In the Discussion section of our paper, we stated that the number of outcome events was modest and that our meta-analysis therefore lacked statistical power to reliably detect clinically worthwhile differences in treatment effect between LMWH and unfractionated heparin. However, the pooled data presented in our paper reflect the totality of the currently available randomized evidence, and it is extremely unlikely that there will be further randomized trials comparing LMWH and unfractionated heparin for the initial treatment of pulmonary embolism. Therefore, our data are probably the best evidence that we will ever have concerning this question.It is ... Author, Article, and Disclosure InformationAffiliations: From Royal Perth Hospital, Perth WA 6001, Australia, and King's College Hospital, London SE5 9RS, United Kingdom. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoLow-Molecular-Weight Heparin Compared with Intravenous Unfractionated Heparin for Treatment of Pulmonary Embolism Daniel J. Quinlan , Andrew McQuillan , and John W. Eikelboom Low-Molecular-Weight Heparin for Pulmonary Embolism Anita Karne and Nirav R. Shah Metrics 7 September 2004Volume 141, Issue 5Page: 407-408KeywordsConfidence intervalsHeparinLow molecular weight heparinPulmonary embolismRandomized trialsResearch designStatistical dataStatistical methods ePublished: 7 September 2004 Issue Published: 7 September 2004 CopyrightCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Bone disease in primary biliary cirrhosis: Does ursodeoxycholic acid make a difference?
Authors: Keith D. Lindor, Christine H. Janes, Jeffrey S. Crippin, Roberta A. Jorgensen, Rolland E. Dickson
Journal: Hepatology (1995)

Ursodeoxycholic acid (UDCA) has been proposed as beneficial therapy for patients with primary biliary cirrhosis (PBC). The effects of UDCA on metabolic bone disease, a major source of morbidity in patients with PBC, are essentially unknown. Preliminary information suggests that UDCA may improve biochemical indices of bone disease, although information about the effects of bone disease, although information about the effects of UDCA on bone density is lacking. In this study, we describe the effects of UDCA on lumbar spine bone mineral densities over a 3-year period during which patients were enrolled in a randomized, double-blind, therapeutic trial of UDCA for the treatment of PBC. Lumbar spine dual-photon densitometry was measured at entry and annually. Eighty-eight patients, 50 in the UDCA group and 38 in the placebo group, had serial measurements available for up to 3 years. There was no statistical difference between the two treatment groups at entry with respect to histologist stage, total bilirubin, age, use of calcium supplement, vitamin D levels, or estrogen. After 3 years of treatment, there was no significant difference in the lumbar spine bone desnitometry measurements between the UDCA-treated and placebo groups. We conclude that, after 3 years of treatment, UDCA is not associated with statistically significant differences in the rate of bone loss from the lumbar spine in patients when compared with placebo despite beneficial effects of treatment on the underlying liver disease. Further efforts to define effective treatments for the bone disease need to be pursued. (Hepatology 1995;21:389-392.)
Identification of the Slynar Gene (AY070435) and Related Brain Expressed Sequences as a Candidate Gene for Susceptibility to Affective Disorders Through Allelic and Haplotypic Association With Bipolar Disorder on Chromosome 12q24
Authors: Gursharan Kalsi
Journal: American Journal of Psychiatry (2006)

Objective: Three linkage studies of bipolar disorder have implicated chromosome 12q24.3, with significant lod scores of over 3.00. Several other linkage studies have found lod scores between 2.00 and 3.00. In order to identify which gene on this chromosome is responsible, the authors carried out tests of allelic association with bipolar disorder in order to fine map an affective disorder susceptibility gene. Method: DNA samples from 681 bipolar disorder patients and 570 comparison subjects from Denmark and the United Kingdom were genotyped with markers close to the region at which the authors had found maximum linkage in previous studies. Results: Single marker allelic association was found with four markers in the Danish cohort. Seven markers in exactly the same region were then found to show significant allelic association in the U.K. cohort. Tests of haplotypic association were also significant, confirming the single marker allelic associations. Conclusions: These positive fine mapping results validate earlier linkage studies and implicate a 278-kilobase region of chromosome 12 that contributes to the etiology of bipolar disorder. Several brain transcripts are transcribed from sequences in the region. The main candidate gene has no known function but is found in human brain cDNA and is homologous to a Macaque brain cDNA. Sequencing of expressed sequences and control regions in the area should identify etiological base pair changes that increase susceptibility to bipolar disorder.
Pediatrics.
Journal: JAMA (1933)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A first-in-human phase I study of sEphB4-HSA (sEphB4) with expansion in hepatocellular (HCC) and cholangiocarcinoma (CCA).
Authors: Jacob Stephen Thomas, Heinz-Josef Lenz, Syma Iqbal, Afsaneh Barzi, Vinay Duddalwar, Sarah Cole, Rabia Rehman, Xiomara Menendez, Valery Krasnoperov, Ren Liu, Qingru Feng, Parkash S. Gill, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2018)

e16136 Background: EphrinB4, a receptor kinase, is associated with stage and survival in epithelial cancers. sEphB4 is a fusion protein of soluble EphB4 and albumin. sEphB4 binds to EphrinB2, a protein expressed in tumor cells and vessels, and blocks bidirectional signaling. sEphB4 downregulates the PI3K/AKT/mTOR pathway, inhibits angiogenesis, and promotes recruitment of cytotoxic T cells and NK cells. MTD was not reached during dose escalation. The RP2D was 10 mg/Kg weekly. Here we report the results of the expansion cohorts in HCC and CCA. Methods: The study evaluated the safety, PK, PD and efficacy of sEphB4 in pts with advanced solid tumors in a 3+3 design with expansion at the RP2D in 7 solid tumors including HCC and CCA. Pts received sEphB4 10 mg/kg IV weekly in 28-day cycles. Eligibility included ECOG 0-1, Child-Pugh score ≤ 7, platelets > 50,000, AST/ALT ≤ 3xULN, serum bilirubin ≤ 1.5mg/dL and no uncontrolled hypertension. Results: 29 pts were treated: 17 HCC and 12 biliary cancers (8 CCA and 4 gallbladder). Median age was 63(25-77). ECOG PS was 1 in 76%. Median prior regimens were 1 (0-6) for HCC and 2 (1-3) for biliary cancers. 2 HCC pts had prior liver transplantation, 9 had prior anti PD-1 therapy and 2 had Child-Pugh score of B7. Median number of cycles was 4 (1-21) in HCC and 2 (1-17) in CCA. No grade 4 treatment-related adverse events (TRAE). Grade 3 TRAE were hypertension (41%) and fatigue, headache, neutropenia all in 1 pt each. Disease progression was the most common reason for treatment discontinuation. Median PFS in months was 5.0 (1.9-7.8) in HCC and 3.0 (1.6-9.2) in CCA. Median OS in months was 11.9 (5.6-27.1) in HCC and 12.0 (3.0-28.2) in CCA. Disease control rate was 70% in HCC and 42% in CCA including 1 PR in HCC. 8 out of 9 pts with 2-3+ EphrinB2 by IHC had disease control ≥ 4 months. 1 out of 7 pts with negative EphrinB2 had disease control ≥ 4 months. Conclusions: sEphB4 has a manageable safety profile with preliminary evidence of anti-tumor activity in pretreated pts with HCC and biliary cancers. Several trials combining sEphB4-HSA with cytotoxic chemotherapy or immunotherapy are ongoing. Clinical trial information: NCT01642342.
Current therapy for hypercholesterolemia
Authors: C. B. Blum
Journal: JAMA (1989)

THE EVIDENCE is now in that lowering cholesterol levels reduces the risk of coronary heart disease (CHD). A century of animal data as well as morphological, genetic, and metabolic studies in man point to a strong association between serum cholesterol levels and coronary artery disease. Prospective epidemiologic studies show a graded relationship between serum cholesterol and coronary risk extending to cholesterol levels below 4.14 mmol/L (&lt;160 mg/dL), ie, well into the desirable range for serum cholesterol.<sup>1</sup>Clinical trials performed in man provide the final validation of the cholesterol-atherogenesis connection. In the Lipid Research Clinics Coronary Primary Prevention Trial, over a 7-year period a 12.5% decrease in low-density lipoprotein (LDL) cholesterol levels was associated with a 19% decrease in the incidence of myocardial infarction and CHD death.<sup>2,3</sup>In addition, treatment was associated with a significant reduction in the development of angina, a positive exercise test, and the need for
Surgical management of complex partial seizures
Authors: S Uematsu
Journal: JAMA (1990)

<h3>CASE PRESENTATION</h3> Jocelyn Jenkins, MD A 23-YEAR-OLD, left-handed white woman with a history of uncontrollable complex partial seizures was admitted to The Johns Hopkins Epilepsy Center for further evaluation and management. The patient was the product of a normal, spontaneous vaginal delivery and achieved normal early milestones. At age 18 months, after receiving smallpox vaccine, she experienced two febrile seizures. The second seizure was associated with transient right hemiparesis. She was treated with phenobarbital and was asymptomatic until about age 6 years, when she developed complex partial seizures that were refractory to high doses of many medications, both alone and in combinations. Some of the medications used were phenytoin sodium, phenobarbital, valproic acid, carbamazepine, and ethosuximide. A computed tomographic scan of the brain was normal. A magnetic resonance imaging (MRI) T<sub>2</sub>-weighted image showed an area of hyperintensity along the left periventricular white matter on both horizontal and coronal
Capecitabine (X) chemoradiation (CRT) in the preoperative treatment of patients (pts) with rectal adenocarcinomas: A phase II GERCOR trial
Authors: O. Dupuis, B. Vié, G. Lledo, C. Hennequin, M. Noirclerc, M. Bennamoun, J. M. Pavlovitch, J. H. Jacob
Journal: Journal of Clinical Oncology (2004)

3538 Background: X CRT is attractive since the active metabolite, 5-FU, is a potent radiosensitizer. There is a strong preclinical rationale based on higher TP levels in tumor, which are further upregulated with radiation, TP being the final metabolising enzyme of X to 5-FU. X has potential to enhance the results of rectal cancer CRT. A phase I study recommended X 825 mg/m2 twice daily with pelvic RT. Methods: We conducted a multicenter, phase II trial to evaluate the efficacy of pre-operative X CRT in pts with adenocarcinoma of the lower or middle third of the rectum, suitable for curative surgery, T3-T4 or N+. Pts had no inflammatory bowel disease, adequate biological parameters, written informed consent. RT delivered 45 Gy in 25 fractions over 5 weeks. X was taken 7 days/week, 825 mg/m2 morning and evening, throughout RT. Surgery was 5 to 7 weeks after the end of RT. The primary endpoint was complete histological response rate; secondary endpoints were downstaging and tolerability. Results: From July 2002 to June 2003, 51 pts were included, 17 women and 34 men, median age 62 years [35–78], with median KPS (Karnofsky) 90% [80–100]. Sixty three percent of tumors involved the lower third of the rectum, 45% were fixed.. Initial endoscopic US/MRI classification was T2, T3, T4 in 4, 45 and 1 cases respectively, 1 pt was T3 on CT evaluation. Median delivered dose was 45 Gy [39,6–45 Gy] in 32 to 44 days. RT was temporarily interrupted in 3 pts (2 G3, 1 G2 skin reaction + G2 diarrhoea in 1) and X stopped before the end of RT in 2 pts (2 G2 hand-foot syndrome + G3 diarrhoea in 1). Adverse events were mostly gastrointestinal (10 pts G2, 3 pts G3 diarrhoea) and cutaneous (8 pts G2 and 2 pts G3 local skin reaction); 3 pts experienced G2 hand-foot syndrome. Fifty pts had surgery (29 conservative), 1 refused. Histopathology revealed 24% complete responses (95% CI 12–36%), 12% persistence of only minimal tumor cell foci and 23% additional T downstaging. Resection margins were tumor free in 100%. Conclusions: X CRT is well tolerated and efficacy supports further exploration, as a single agent and as part of new therapeutic strategies with chemo- and biological therapies. No significant financial relationships to disclose.