tbuckley/cabot-search huggingface dataset:
Abstract 3863: Deletion Of Integrin Alpha7 Leads To Altered Cardiac Conduction And Sudden Death Associated With Connexin43 Downregulation
Authors: Raja Nadif, Michael Emerson, Ulrike Mayer, Ludwig Neyses, Elizabeth Cartwright
Journal: Circulation (2008)

Effective propagation of the electrical impulse throughout the myocardium is highly dependent on cell-to-cell and cell-to-extracellular matrix interactions. Increasing evidence indicates that dysregulation of cellular adhesion is a critical determinant in the genesis of arrhythmia. Null mutations in the integrin α7 gene, an essential mediator of cellular adhesion in cardiac and skeletal muscles, have been linked to myopathy in humans, however, the in vivo role of the integrin α7 subunit in the heart is undefined. The mouse model of integrin α7 deletion dies prematurely at one year of age. We therefore analysed the cardiac phenotype in integrin α7 deficient mice (α7 −/− ) to determine whether their premature death was associated with altered cardiac conduction. One year old integrin α7 −/− mice exhibited altered cardiac conduction characterised by spontaneous atrial fibrillation and prolonged QTc duration (α7 −/− : 25.7±0.74ms, α7 +/+ : 19.5±0.61ms; n=6; p&lt;0.001, QTc=QT/(RR/100) 1/2 ). The abnormal cardiac conduction was associated with downregulation of connexin43. However, no significant changes were observed in the expression of ion chanels that have been linked to long QT syndrome or atrial fibrillation (kv1.1, kv1.5, kcne1, kcnq1, erg1, Cav1.2 and Cav1.3). In addition, α7 −/− mice displayed increased susceptibility to drug-induced arrhythmias: treatment with ouabain (2mg/kg BW) in combination with isoprenaline (2.5mg/kg BW) induced atrial fibrillation and ventricular tachycardia and eventually death in 6 month-old integrin α7 −/− mice, but not in α7 +/+ mice. Interestingly, α7 −/− also displayed concentric ventricular hypertrophy with increased septal wall thickness and reduced left ventricular end-diastolic diameter starting from 6 months of age. These structural changes were accompanied by an increase in myocyte size and increased ERK1/2 phosphorylation. In conclusion, deletion of the integrin α7 gene in mice leads to ventricular hypertrophy and to abnormal cardiac conduction. The integrin α7 deficient mice have a marked propensity to lethal arrhythmias through alterations in gap junctions but not ion channels. The integrin α7 knockout model provides new insight into the link between the extracellular matrix and cardiac conduction.
Doctors and managers
Authors: H. Mascie-Taylor
Journal: BMJ (2003)

Editor—Whether this cry is that of a beleaguered health service manager or a consultant who feels that his or her powers have been eroded a little more, the lack of understanding between managers and doctors is manifest.1-1 Why is this so?

The degrees of certainty and agreement in medicine are often perceived to be greater than they are. Although evidence based medicine informs us that treating hypertension is a good thing, that same evidence will remind us that it is impossible for a doctor to discern whether the patient sat in front of them will be the 1 in 500 people to benefit from the antihypertensive drug on offer. By the time patients have pondered the side effects and remembered something that they were told in the pub it is almost a matter of chance whether they will take the drug—and there are many more barriers to prescribing bendrofluazide.1-2 Yet, patients with hypertension would benefit from the input of a manager to support the interaction between patient and healthcare system, without which the system will fail.

We argue that the reason these tensions exist lies in the opposing world views held by both groups: clinicians see their work as an art to be expressed in the unique care afforded to each patient, and as such intrinsically immune to the homogenisation of management. But managers' world view consists of precisely that—the broad thrusts of commissioning, audit, and risk management.

Both are right. There is depth and mystery in much of medicine, but to stop there would be inadequate. Sense is needed to cope, assure, and improve. Managers need to understand that the process of dividing into manageable parts has real dangers—a loss of meaning. Doctors meanwhile need to understand that through such division, their complex art can be more easily understood. World views can be different and still be complementary.

We commend the notion of professional permeability. Let ideas spread by osmosis between the groups by seeking out the other's perspective. What about doctors and managers sharing a community of practice?

No—they wouldn't understand.
Complete Remission of Metastatic Neuroendocrine Paragastric Carcinoma After “Neoadjuvant” Peptide Receptor Radionuclide Therapy and Surgery
Authors: Matthias C. Schmidt, Klara Uhrhan, Thomas Fischer, Stephan Schmitz, Birgid Markiefka, Alexander Drzezga, Dirk Stippel
Journal: Clinical Nuclear Medicine (2015)

A 48-year-old man presenting with upper abdominal pain was diagnosed with neuroendocrine tumor after biopsy of a paragastric mass with multiple liver metastases. (68)Ga-DOTATATE PET/CT showed intense uptake in the paragastric tumor and in multiple liver metastases not allowing primary surgery. Two cycles with cumulative 14.6 GBq (177)Lu-DOTATATE were given resulting in a considerable improvement. Subsequent surgery resulted in a complete remission as demonstrated by (68)Ga-DOTATATE PET/CT. Usually, peptide receptor radionuclide (PRRT) therapy is considered a palliative treatment. Few patients demonstrate a very favorable response allowing resection of the primary tumor after downstaging metastatic disease burden.
Adjuncts to Cancer Surgery
Authors: Steven G. Economou
Journal: Annals of Internal Medicine (1992)

This book offers an explanation for the host of adjunctive protocols currently in use for diagnosing, treating and monitoring the cancer patient. The principles on which a test or manoeuvre are based are explained, as are the indications and contra-indications for its use. Clinically relevant discussions of the use of monoclonal antibodies, newer imaging techniques and endoscopy highlight the coverage of diagnostic adjuncts. Palliative measures for controlling intractable pain, immunotherapy and psychological support are among the therapeutic adjunctive methods presented.
A novel method for endoscopic placement of a capsule endoscope with use of a transparent hood and real-time viewer
Authors: Yuji Ino, Tomonori Yano, Hirotsugu Sakamoto, Yoshikazu Hayashi, Hiroyuki Osawa, Alan Lefor, Hironori Yamamoto
Journal: Endoscopy (2015)

Capsule endoscopy relies on an intact swallowing mechanism and unimpeded passage of the capsule through the pylorus [1]. A new method for endoscopic placement of the capsule is described.
Evaluation of Apoptotic Molecular Markers in Myelodysplastic Syndrome Patients
Authors: Emília Cortesão, Ana Cristina Gonçalves, Maria Isabel Sousa, Carlos Moucho, Luís Rito, Emília Magalhães, Ana Isabel Espadana, Maria Amélia Pereira, Adriana Teixeira, José Nascimento Costa, Ana Bela Sarmento
Journal: Blood (2008)
Abstract 499: Ionic Remodeling and Sinoatrial Node Dysfunction Associated with Atrial Tachycardia: A Possible Molecular Basis for Tachy-Brady Syndrome
Authors: Yung-Hsin Yeh, Chang Gung, Brett Burstein, Xiao Yan Qi, Masao Sakabe, Denis Chartier, Zhiguo Wang, Stanley Nattel
Journal: Circulation (2007)
Economic burden of metastatic melanoma in a commercially insured U.S. population.
Authors: S. Ray, O. Tunceli, A. Ganguli, S. Kamat, T. Gu, J. Singer, Y. Luo, Y. Xu
Journal: Journal of Clinical Oncology (2010)

e19000 Background: The economic burden of metastatic melanoma is sparsely studied. This study estimates healthcare utilization and costs of metastatic melanoma patients in a US managed care population. Methods: The HealthCore Integrated Research Database containing claims data from a large geographically diverse commercially insured population was used to identify patients age ≥ 18 yrs with ≥ 6 months pre- and ≥ 1 month post-index enrollment between 1/1/2004–5/31/2009. Patients with ≥ 2 melanoma claims (ICD- 9-CM 172.xx, V10.82) and no other malignant tumors were grouped into 2 exclusive cohorts: metastatic melanoma (MM) and non-metastatic melanoma (non- MM) cohorts. The MM cohort comprised patients with ≥ 1 claim for diagnosis of metastasis (ICD-9-CM 196.x-198.x) or systemic chemotherapy. The non- MM cohort comprised the remaining patients (no claims for diagnosis of metastasis or chemotherapy). First diagnosis date of melanoma or MM was the index date for each patient in the respective groups. Each cohort was matched 1:1 with patients with no claims for any cancer (NC) by age, gender, insurance type and region to form two matched case-control groups. Per-patient-per-month (PPPM) healthcare utilization and costs were estimated for each group after adjusting for baseline differences between cases and controls using multivariate regression. Results: The study included 697 MM, 17,756 non-MM (mean age 56.1 and 54.4 yrs respectively) and their matched NC controls. For MM patients vs. NC controls, PPPM utilization was 2-7 times higher for inpatient (0.07 vs. 0.01), out-patient (2.42 vs. 0.64), and office visits (1.05 vs. 0.41), all with p < 0.0001, but similar for emergency room (ER) visits (0.10 vs. 0.07, p = 0.51). For non-MM vs. NC, utilization was similar for ER (0.06 vs. 0.07, p = 0.86) and inpatient visits (0.0103 vs. 0.0105, p = 0.98), and marginally higher for outpatient (1.08 vs. 0.59, p < 0.0001) and office (0.65 vs. 0.40, p < 0.0001) visits. The PPPM total cost was 7.5 times higher for MM vs. NC ($3,118 vs. $415, p < 0.0001) and 1.7 times higher for non-MM vs. NC ($562 vs. $340, p < 0.0001). Conclusions: The cost burden from resource utilization increases substantially with metastasis of melanoma. Effective treatments are needed to reduce this burden. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories
Pathologie und Klinik der Nierenerkrankungen (Nephrosen, Nephritiden und Schrumpfnieren).
Authors: Fritz Munk
Journal: JAMA (1926)

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
Gene expression subtype and p53 mutational status are correlated among neoadjuvantly treated breast cancers in UNC LCCC9819 and I-SPY1 (CALGB 150007/ACRIN 6657)
Authors: L. A. Carey, D. Oh, L. Sawyer, S. Edmiston, D. Tolbert, D. Moore, M. Buxton, L. Esserman, C. Perou, K. Conway
Journal: Journal of Clinical Oncology (2006)

10048 Background: LCCC9819 and I-SPY1 are designed to examine multiple potential predictive markers and assays simultaneously in biopsies from neoadjuvantly treated patients. Both p53 mutation status and molecular ‘intrinsic‘ subtype have been associated with chemosensitivity. In this preliminary analysis, we present the p53 mutation spectra by molecular subtype from patients enrolled in the combined LCCC 9819 and I-SPY1 datasets. Methods: Patients received neoadjuvant anthracycline-based chemotherapy with pre-therapy biopsies. p53 mutation analysis was performed by p53 GeneChip assay for point mutations/1 bp deletions followed by SSCP if GeneChip-negative. Abnormal GeneChip or SSCP were confirmed by sequencing. DNA microarrays used Agilent human microarrays and a common reference strategy approach. Results: 51 patients were treated on LCCC9819 and have available molecular analyses; 87 from I-SPY1. 111 patients have completed p53 mutation analysis, revealing a high proportion (42%) with abnormal p53. Of these, several were in known hotspots, including R175H (4 mutations), R248L (1), R273H (3), and R273C (2). Most were missense mutations (81%), however, there were 8 (17%) null and 1 (2%) silent mutations. Most (91%) mutations were in the DNA binding domain. Molecular subtypes are known on 111 tumors: 22% Luminal A, 22% Luminal B, 3% Normal-like, 23% HER2+/ER−, 27% Basal-like, and 3% unclassified. Among those with both assays complete, we found that p53 mutations differed by subtype (Table). Conclusions: P53 mutations are common in these independent neoadjuvant datasets, and differ in frequency between molecular subtypes, which may have implications for predictive factor identification. Future analyses will include aCGH, cell cycle protein analysis, proteomics, and clinical data including response to chemotherapy. (supported by UNC Breast SPORE-CA58223, NIH M01RR00046, DAMD 17–02–1-0521). [Table: see text] No significant financial relationships to disclose.
Focused psychiatric curriculum selection: student, psychiatrist, and nonpsychiatrist physician expectations
Authors: W Johnson, J Snibbe, K Hoffman, L Evans
Journal: American Journal of Psychiatry (1977)

The authors obtained curriculum needs analysis data from second-year medical students and compared these with data obtained from nonpsychiatrist physicians and psychiatrists. All groups felt that interviewing skills, the doctor-patient relationship, managing the dying patient, and evaluation of suicidal patients were important topics. All gave psychological testing, behavior modification, mental retardation, and psychoanalytic theory the lowest teaching priority. The students gave a higher rating to all topics than did the other groups. The authors suggest that this kind of analysis can facilitate curriculum selection and implementation.
The Psychosocial Transplant Evaluation Rating Scale (TERS) Prospectively Predicts Inferior Overall Survival Outcome for High Risk Scoring Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Dawn Speckhart, Scott R. Solomon, Xu Zhang, Lawrence E. Morris, Asad Bashey, H. Kent Holland
Journal: Blood (2014)
SOUND ADVICE FOR TUNNEL TRAVELLERS: AVOID TUNNEL TRAVEL AFTER RECENT EAR SURGERY
Authors: D W Proops
Journal: BMJ (1994)

This article briefly summarises the guidelines recently issued to doctors by Eurotunnel. These guidelines focus on the effects upon the ears of travelling in the Channel Tunnel. Rapid changes in ambient pressure occur when entering the tunnel at speed, or when two trains pass each other. This increase in pressure deflects the intact tympanic membrane medially. Most people can equalise the relative pressures each side of the tympanic membrane by swallowing, or by some other such manoeuvre such as yawning. However, the rapid change of pressure experienced on a train may not give time for these natural measures to work. The article discusses the chances that otic barotrauma may occur.
Randomized Trial Comparing Axillary Clearance Versus No Axillary Clearance in Older Patients With Breast Cancer: First Results of International Breast Cancer Study Group Trial 10-93
Authors: Carl-Magnus Rudenstam, David Zahrieh, John F Forbes, Diana Crivellari, Stig B Holmberg, Piercarlo Rey, David Dent, Ian Campbell, Jürg Bernhard, Karen N Price, Monica Castiglione-Gertsch, Aron Goldhirsch, Richard D Gelber, Alan S Coates
Journal: Journal of Clinical Oncology (2005)

Purpose Axillary clearance in early breast cancer aims to improve locoregional control and provide staging information but is associated with undesirable morbidity. We therefore investigated whether avoiding axillary surgery in older women would result in improved quality of life (QL) with similar disease-free survival (DFS) and overall survival (OS). Patients and Methods Between 1993 and 2002, women ≥ 60 years old with clinically node-negative operable breast cancer in whom adjuvant tamoxifen was considered indicated regardless of pathologic nodal status were randomly assigned to primary surgery plus axillary clearance (Sx + Ax) followed by tamoxifen (Tam) versus Sx without Ax followed by Tam for 5 consecutive years. The primary end point was QL reported by the patient and by physician assessment. Results A total of 473 patients (234 to Sx + Ax, 239 to Sx) were randomly assigned. The median age was 74 years; 80% had estrogen receptor–positive disease. In both the patients' subjective assessment of their QL and the physicians' perception of the patients' QL, the largest adverse QL effects of Ax were observed from baseline to the first postoperative assessment, but the differences tended to disappear in 6 to 12 months. At a median follow-up of 6.6 years, results for Sx + Ax and Sx yielded similar DFS (6-year DFS, 67% v 66%; hazard ratio [HR] Sx + Ax/Sx, 1.06; 95% CI, 0.79 to 1.42; P = .69) and OS (6-year OS, 75% v 73%; HR Sx + Ax/Sx, 1.05; 95% CI, 0.76 to 1.46; P = .77). Conclusion Avoiding axillary clearance for women ≥ 60 years old who have clinically node-negative disease and receive Tam for endocrine-responsive disease yields similar efficacy with better early QL.
Abstract 022: Atrial Fibrillation and Cognitive Decline: The Cardiovascular Health Study
Authors: Evan L Thacker, Barbara McKnight, Bruce M Psaty, W. T Longstreth, Colleen M Sitlani, Alice M Arnold, Annette L Fitzpatrick, Sascha Dublin, Rebecca F Gottesman, Susan R Heckbert
Journal: Circulation (2012)

Objective. We sought to determine whether atrial fibrillation (AF) was associated with cognitive decline in the absence of stroke. Methods. We included Cardiovascular Health Study participants aged 65+ who did not have AF or prior stroke at baseline and had at least one Modified Mini-Mental State Examination (3MSE) during the study. AF was identified by hospital discharge diagnoses and annual study ECGs. The 3MSE (score range 0–100) was administered annually up to nine times from 1990/91 to 1998/99. Mixed effects linear regression was used to characterize the relationship of cognitive decline with AF and age, adjusted for birth year, sex, race, education, smoking, alcohol use, diabetes, hypertension, systolic blood pressure, coronary heart disease, and heart failure. Interaction terms for AF and age variables with incident clinical stroke were used to allow estimation of cognitive decline in the absence of stroke. Results. Analyses included 5,199 participants with a mean of 6.7 3MSE scores. During follow-up 11% of participants (554 of 5,199) had AF identified. Panel A of the Figure shows mean 3MSE score trajectories for participants without AF (solid line) and after AF was identified at ages 70, 75, 80, and 85 (dashed lines). Panel B shows the trajectory for participants without AF set to zero (solid horizontal line) and differences in mean trajectories after AF was identified relative to participants without AF (dashed lines). Gray shading shows 95% CIs. Having newly-identified AF was not associated with a difference in 3MSE score relative to participants of the same age without AF. However, after AF was identified, 3MSE scores declined 2.3 points faster per five years, relative to participants without AF. For example, after AF was identified at age 80, mean 3MSE score declined 9.1 points by age 85, versus 6.8 points for participants without AF. Conclusions. In older adults without clinical stroke, the average rate of cognitive decline was greater after AF was identified.
Relative Importance of History of Heart Failure Hospitalization and N-Terminal Pro–B-Type Natriuretic Peptide Level as Predictors of Outcomes in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Søren L. Kristensen, Pardeep S. Jhund, Lars Køber, Robert S. McKelvie, Michael R. Zile, Inder S. Anand, Michel Komajda, John G.F. Cleland, Peter E. Carson, John J.V. McMurray
Journal: JACC Heart Failure (2015)
Deletion of 9p21 in urine specimens collected from patients with a history of hematuria and bladder cancer
Authors: K. Crewell, J. Qian, D. Weber, M. Medina, D. Hossain, D. G. Bostwick
Journal: Journal of Clinical Oncology (2009)

11038 Background: Fluorescence in situ hybridization (FISH) of voided urine sediment is a sensitive and specific test for the detection of urothelial carcinoma. Common bladder cancer FISH testing consists of 4 DNA probes to chromosomes 3, 7, and 17 and band 9p21. The pattern of enumeration anomalies for these 4 DNA probes are not well documented. We sought to determine the incidence of chromosomal anomalies detected by these 4 probes in urine specimens. Methods: Urine samples from a total of 13,284 patients with a history of hematuria and/or bladder cancer were included for study. FISH was performed in each case using fluorescence-labeled probes to the pericentromeric regions of chromosomes 3, 7, and 17 and band 9p21; cytology was also performed in all cases. Follow-up bladder biopsy information was collected from 280 cases. Results: In total, 91.6% (12163/13284) of urine samples were sufficient for FISH analysis. The overall FISH positive rate was 5.7% (691/12163), and the most frequent patterns of chromosomal anomalies were gains of chromosomes 3 and 7 (56.5%), 7 and 17 (51.6%), and 3 and 17 (36.9%). Deletion of 9p21 was observed in only 12% of cases, and was never observed as the only chromosomal anomaly. The mean number of positive cells in FISH-positive cases was 8.8 (range 4–22). Among 280 cases with matching bladder biopsies, 178 (63.6%) had urothelial carcinoma. FISH was more sensitive than cytology for the detection of urothelial carcinoma (77.4% vs. 53.5%, respectively) (p= 0.03), but there was no significant difference in specificity (68% vs. 71.6%, respectively) (p&gt; 0.05). Conclusions: Gains of chromosomes 3 and 7 by FISH were the most common enumeration anomalies in urine specimens, while deletion of 9p21 only was rare and never seen isolation. FISH was significantly more sensitive than cytology for the detection of urothelial carcinoma with equivalent specificity. No significant financial relationships to disclose.
Radon and smoking status
Authors: R.J. Roscoe
Journal: JAMA (1989)

The authors of two letters to the editor regarding an article entitled, Lung cancer mortality among non-smoking uranium miners exposed to radon daughters, disagree with the risk analysis regarding nonsmokers and the conclusions drawn by the original authors. In a reply letter, the authors comment on each point raised in the letters, and reaffirm their original conclusion that the common exposure for all miners was radon daughters, which is the most likely explanation for the high observed lung cancer risk.