tbuckley/cabot-search huggingface dataset:
Abstract 306: Proinflammatory Prostaglandin E Impairs Adrenergic Contractility in Animal Hearts
Authors: Yang K Xiang
Journal: Circulation Research (2012)

Introduction: Inflammation is a major risk factor for heart failure; inflammatory prostaglandin E is elevated in myocardium, and has been associated with development of heart failure via cardiac LV remodeling, but the mechanisms remain unclear. Hypothesis: We hypothesize that proinflammatory prostaglandin signaling might affect Left ventricular contractility by directly impairing β-adrenergic (βAR) signaling. Methods and Results: Pretreatment with Prostaglandin E impairs intracellular PKA phosphorylation of substrates in myocardium and cardiac contractile responses under β-adrenergic stimulation. Both prostaglandin E and β-adrenergic agonist isoproterenol induce intracellular cAMP activities in myocytes. However, the cAMP signal under prostaglandin stimulation is confined along the plasma membrane whereas the cAMP signal under isoproterenol stimulation is distributed throughout the cells, including the intracellular sarcoplasmic reticulum (SR), a calcium storage compartment critical for myocyte calcium signaling and contractile response. Interestingly, the prostaglandin E-induced cAMP signal is sufficient for PKA activation, leading phosphorylation and activation of phosphodiesterase 4 on the plasma membrane, a group of enzymes associated with membrane βARs for cAMP degradation. Moreover, pretreatment of prostaglandin E prevents dissociation of phosphodiesterase 4 from βAR induced by isoproterenol, a step necessary for cAMP diffusion from the plasma membrane to the intracellular SR. Together, prostaglandin E induces activation of phosphodiesterase 4 in βAR complex and prevents the cAMP diffusion from the plasma membrane to the SR under isoproterenol stimulation, and inhibits calcium signaling and contractile response in myocytes and animal hearts. Conclusions: This study provides a novel mechanism underlying the phosphodiesterase-mediated signaling crosstalk between two neurohormonal stimulation in myocardium under chronic conditions, and suggests that proinflammatory prostaglandin signaling may impair β-adrenergic contractile in the development of heart failure.
A Pilot Use of Patient-Generated Wound Data to Improve Postdischarge Surgical Site Infection Monitoring
Authors: Heather L. Evans, William B. Lober
Journal: JAMA Surgery (2017)

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 Surgery 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 Surgery journal
Refractory hypokalaemia in an elderly patient
Authors: Subramaniam Nagasayi, Sandra Hui Li Yan, Cleo Chiong
Journal: BMJ (2017)

A 94 year old woman with mild dementia, peripheral vascular disease, and type 2 diabetes mellitus was discharged from hospital after completing antiviral treatment for a lower respiratory tract infection (influenza A3). She was readmitted four days later with secondary pneumonia and bacteraemia (meticillin sensitive Staphylococcus aureus , isolated from blood but not from lung or sputum samples). She was started on intravenous cloxacillin (2 g, every six hours) according to local guidelines. She had no episodes of diarrhoea, vomiting, respiratory muscle weakness, or paralytic ileus. On admission, her temperature was 38°C, blood pressure 141/70 mm Hg, respiratory rate 24 breaths/min, heart rate 114 beats/min, and peripheral capillary oxygen saturation 94%. Chest examination found normal heart sounds and right basal crepitations. Her abdomen was soft and non-tender; and her weight was 43 kg (body mass index 16 kg/m2).

By day five, her respiratory parameters had improved, but she had developed extreme fatigue with refractory hypokalaemia, despite oral and parenteral replacements (table 1⇓). 

View this table:

Table 1 
Serum levels and intravenous potassium replacement





She continued on regular 100 mg aspirin and 20 mg omeprazole once daily and 250 mg tolbutamide twice daily. She was started on 600 mg slow release potassium chloride twice daily in addition to intravenous replacement.

Her haemoglobin level was 134 …
Erratum. Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial. Diabetes Care 2016;39:2026–2035
Authors: Julio Rosenstock, Ronnie Aronson, George Grunberger, Markolf Hanefeld, PierMarco Piatti, Pierre Serusclat, Xi Cheng, Tianyue Zhou, Elisabeth Niemoeller, Elisabeth Souhami, Melanie Davies
Journal: Diabetes Care (2017)
Impact of pre-operative three different regimens on breast-conservation surgery (BCS) and pathological complete response rates (pCR) in locally advanced breast cancer (LABC) in Pakistani patients
Authors: A. G. Alidina, A. Lal, S. Khan
Journal: Journal of Clinical Oncology (2006)

10628 Background: Locally advanced breast cancer accounts for 28% (n 350) of all breast cancer cases (1370 patients) treated at our Aga Khan University Hospital over the last 15 years. This is sharp comparison to the US data (only 3–6% of all cases). Methods: Patients with LABC who received surgery upfront were excluded. One hundred and seventy cases receiving PC were evaluated. Patients receiving TAC (taxotere, Adriamycin and cyclophosphamide)chemotherapy (n 60) were evaluated in a prospective Phase II study (2003- ongoing). These were then compared with FAC/AC or CMF regimens given from1998–2005, the data of which were extracted for Breast Cancer Tumor registry. Women were eligible if they were; histological confirmed invasive infiltrating carcinoma, clinical TNM: T3, T4, N2, N3, M0, as per AJCC (6 th edition), PS 0–1, with adequate renal, liver and hematological functions. Patients were treated with regimens TAC containing T (75 mg/m 2 ), A (50 mg/m 2 ) and C (500 mg/m 2 ) or FAC: F (500 mg/m 2 ), A (50 mg/m 2 ) and C (500 mg/m 2 ) or A (60 mg/m 2 ) C (600 mg/m 2 ) and CMF: C (600 mg/m 2 ), M (40 mg/m 2 ) and F (600 mg/m 2 ) q3wk 2 to 4 cycles. Type of surgery depended upon the response rates and the patients’ desire. Balance to complete a total of 4–6 cycles of chemotherapy was given in the adjuvant setting. Adjuvant hormone therapy was given for receptor positive cases. Results: Demographics, response rates, BCS and toxicities are reported in table. Conclusions: Locally advanced breast cancer is common in this region, owing to lack of screening. Preoperative TAC chemotherapy leads to impressively higher response rates, pathological complete response rates and probability of BCS, than when compared with FAC/AC chemotherapy or CMF chemotherapy, given in the same setting. Where as survival data of patients with TAC is not available, we feel that this will be superior to AC/FAC or CMF, given higher pathological complete response rates. [Table: see text] No significant financial relationships to disclose.
TCTAP A-001 Thirty-day Clinical Outcomes Following Bioresorbable Vascular Scaffold Implantation in Patients Presenting with Acute Coronary Syndromes Versus Stable Coronary Artery Disease: Results from the Italian RAI Registry
Authors: Elisabetta Moscarella, Attilio Varricchio, Alfonso Ielasi, Bernardo Cortese, Maria Carmen De Angelis, Bruno Loi, Giuseppe Tarantini, Francesco Pisano, Alessandro Durante, Michela Facchin, Alessandro Colombo, Luciano Moretti, Gabriele Tumminello, Paolo Calabrò, Donatella Corrado, Giuseppe Steffenino
Journal: Journal of the American College of Cardiology (2017)
Review of Walter Sinnott-Armstrong, ed., <i>Finding Consciousness: The Neuroscience, Ethics and Law of Severe Brain Damage</i>
Authors: Robin Mackenzie
Journal: The American Journal of Bioethics (2017)

M was diagnosed as being in a persistent vegetative state (PVS) after suffering brain damage at 43. Eight years later, after a rediagnosis of a minimally conscious state (MCS), she demonstrated cap...
Risk Factors for Acute Graft-Versus-Host Disease (GvHD) after Related Donor HLA-Matched Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Adult Leukemia: Identification of Modifiable and Non-Modifiable Factors. A CIBMTR Study.
Authors: Theresa Hahn, Philip L. McCarthy, Dan Wang, Mei-Jie Zhang, Mukta Aurora, Steven Pavletic, A. John Barrett, Olle Ringden
Journal: Blood (2007)
CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair
Authors: T.R. Shenoy, G. Boysen, M.Y. Wang, Q.Z. Xu, W. Guo, F.M. Koh, C. Wang, L.Z. Zhang, Y. Wang, V. Gil, S. Aziz, R. Christova, D.N. Rodrigues, M. Crespo, P. Rescigno, N. Tunariu, R. Riisnaes, Z. Zafeiriou, P. Flohr, W. Yuan, E. Knight, A. Swain, M. Ramalho-Santos, D.Y. Xu, J. de Bono, H. Wu
Journal: Annals of Oncology (2017)

Deletion of the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1) is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents a distinct PCa subtype characterized by SPOP mutation and higher genomic instability. However, the role of CHD1 in PCa development in vivo and its clinical utility remain unclear.To study the role of CHD1 in PCa development and its loss in clinical management, we generated a genetically engineered mouse model with prostate-specific deletion of murine Chd1 as well as isogenic CHD1 wild-type and homozygous deleted human benign and PCa lines. We also developed patient-derived organoid cultures and screened patients with metastatic PCa for CHD1 loss.We demonstrate that CHD1 loss sensitizes cells to DNA damage and causes a synthetic lethal response to DNA damaging therapy in vitro, in vivo, ex vivo, in patient-derived organoid cultures and in a patient with metastatic PCa. Mechanistically, CHD1 regulates 53BP1 stability and CHD1 loss leads to decreased error-free homologous recombination (HR) repair, which is compensated by increased error-prone non-homologous end joining (NHEJ) repair for DNA double-strand break (DSB) repair.Our study provides the first in vivo and in patient evidence supporting the role of CHD1 in DSB repair and in response to DNA damaging therapy. We uncover mechanistic insights that CHD1 modulates the choice between HR and NHEJ DSB repair and suggest that CHD1 loss may contribute to the genomic instability seen in this subset of PCas.
Medical Ethics and Torture
Authors: Leonard A. Sagan, Albert Jonsen
Journal: New England Journal of Medicine (1976)

Abstract There is growing evidence of widespread use of torture among political prisoners throughout the world. Medical personnel frequently become involved, sometimes directly, sometimes peripherally as in the examination or treatment of such prisoners. Physicians themselves may become victims of torture when the state attempts to subvert the doctor–patient relation for political purposes. Furthermore, recent studies demonstrate long lasting medical and psychologic effects of torture. For these reasons, physicians have a special opportunity and ethical obligation to resist and oppose torture as well as to support physicians whose lives or professional careers are jeopardized by their refusal to participate in torture. Codes of medical ethics need strengthening to provide clear guidance for the physician who becomes aware of or actively involved in these brutal practices. (N Engl J Med 294:1427–1430, 1976)
Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients
Authors: J. Vidal, L. Muinelo, A. Dalmases, F. Jones, D. Edelstein, M. Iglesias, M. Orrillo, A. Abalo, C. Rodríguez, E. Brozos, Y. Vidal, S. Candamio, F. Vázquez, J. Ruiz, M. Guix, L. Visa, V. Sikri, J. Albanell, B. Bellosillo, R. López, C. Montagut
Journal: Annals of Oncology (2017)

BackgroundRAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice.Patients and methodsRAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated.RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients.ResultsAnalysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment.ConclusionThe high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.
Authors’ reply to Fralick and Kesselheim
Authors: Angela Spelsberg, Ulrich Keil, Christof Prugger
Journal: BMJ (2017)

We agree with Fralick and Kesselheim that “optimally designed post-marketing studies” are urgently needed.1 They recommend applying the new user active comparator design to post-marketing studies. Our finding that data obtained in the numerous ongoing industry funded studies are treated as confidential business information remains a concern.

We found considerable heterogeneity in sponsors’ approach to submitting notifications and summaries of the …
High prevalence of apolipoprotein B dyslipoproteinemias in non-alcoholic fatty liver disease: The lifelines cohort study
Authors: Karlijn J. Nass, Eline H. van den Berg, Klaas Nico Faber, Tim C.M.A. Schreuder, Hans Blokzijl, Robin P.F. Dullaart
Journal: Metabolism (2017)
GPs urged to be cautious when assessing patients’ fitness for endurance sports
Authors: Gareth Iacobucci
Journal: BMJ (2017)

GPs should be careful not to act outside of their competence when asked to declare that their patients are fit to participate in marathons, medical defence experts have said.

The Medical Protection Society (MPS) issued the advice after questions from GPs about whether to sign “fitness to participate” forms for patients before training for marathons or other sporting events when their clinical knowledge may be insufficient to deem the patient fit to take part.

The MPS said …
In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein
Authors: Christoph M. Deeg, Ebrahim Hassan, Pascal Mutz, Lara Rheinemann, Veronika Götz, Linda Magar, Mirjam Schilling, Carsten Kallfass, Cindy Nürnberger, Sébastien Soubies, Georg Kochs, Otto Haller, Martin Schwemmle, Peter Staeheli
Journal: The Journal of Experimental Medicine (2017)

Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses. Here, we describe a new mouse model suitable for such risk assessment, based on the observation that the innate restriction factor MxA represents an effective species barrier that must be overcome by zoonotic viruses. Our mouse lacks functional endogenous Mx genes but instead carries the human MX1 locus as a transgene. Such transgenic mice were largely resistant to highly pathogenic avian H5 and H7 influenza A viruses, but were almost as susceptible to infection with influenza viruses of human origin as nontransgenic littermates. Influenza A viruses that successfully established stable lineages in humans have acquired adaptive mutations which allow partial MxA escape. Accordingly, an engineered avian H7N7 influenza virus carrying a nucleoprotein with signature mutations typically found in human virus isolates was more virulent in transgenic mice than parental virus, demonstrating that a few amino acid changes in the viral target protein can mediate escape from MxA restriction in vivo. Similar mutations probably need to be acquired by emerging influenza A viruses before they can spread in the human population.
Left Ventricular Assist Device as a Bridge to Recovery for Patients With Advanced Heart Failure
Authors: Djordje G. Jakovljevic, Magdi H. Yacoub, Stephan Schueler, Guy A. MacGowan, Lazar Velicki, Petar M. Seferovic, Sandeep Hothi, Bing-Hsiean Tzeng, David A. Brodie, Emma Birks, Lip-Bun Tan
Journal: Journal of the American College of Cardiology (2017)

Left ventricular assist devices (LVADs) have been used as an effective therapeutic option in patients with advanced heart failure, either as a bridge to transplantation, as destination therapy, or in some patients, as a bridge to recovery. This study evaluated whether patients undergoing an LVAD bridge-to-recovery protocol can achieve cardiac and physical functional capacities equivalent to those of healthy controls. Fifty-eight male patients—18 implanted with a continuous-flow LVAD, 16 patients with LVAD explanted (recovered patients), and 24 heart transplant candidates (HTx)—and 97 healthy controls performed a maximal graded cardiopulmonary exercise test with continuous measurements of respiratory gas exchange and noninvasive (rebreathing) hemodynamic data. Cardiac function was represented by peak exercise cardiac power output (mean arterial blood pressure × cardiac output) and functional capacity by peak exercise O2 consumption. All patients demonstrated a significant exertional effort as demonstrated with the mean peak exercise respiratory exchange ratio >1.10. Peak exercise cardiac power output was significantly higher in healthy controls and explanted LVAD patients compared with other patients (healthy 5.35 ± 0.95 W; explanted 3.45 ± 0.72 W; LVAD implanted 2.37 ± 0.68 W; and HTx 1.31 ± 0.31 W; p < 0.05), as was peak O2 consumption (healthy 36.4 ± 10.3 ml/kg/min; explanted 29.8 ± 5.9 ml/kg/min; implanted 20.5 ± 4.3 ml/kg/min; and HTx 12.0 ± 2.2 ml/kg/min; p < 0.05). In the LVAD explanted group, 38% of the patients achieved peak cardiac power output and 69% achieved peak O2 consumption within the ranges of healthy controls. The authors have shown that a substantial number of patients who recovered sufficiently to allow explantation of their LVAD can even achieve cardiac and physical functional capacities nearly equivalent to those of healthy controls.
Prevalence and descriptive epidemiology of atopic dermatitis and its impact on quality of life in Singapore
Authors: S. Cheok, F. Yee, J.Y. Song Ma, R. Leow, M.S.L. Ho, Y.W. Yew, Y.K. Tay, S.A. Rebello, N. Luo, M.J.A. Koh
Journal: British Journal of Dermatology (2017)
Comparative dosimetric study of three-dimensional conformal (3DCRT), intensity modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT) for treatment in pituitary adenomas.
Authors: Subhash Gupta, M. A Laviraj, Haresh Kunhiparambath, Dayanand Sharma, Rajendran M, Pramod Kumar Julka, Goura Kishor Rath
Journal: Journal of Clinical Oncology (2013)

e13043 Background: Radiotherapy is usually delivered after surgery in pituitary adenomas. Usually stereotactic radiotherapy is used in their treatment. The studies evaluating the recent advances like IMRT, VMAT for pituitary adenomas are rare. Present study evaluates 3DCRT, IMRT, and VMAT for the treatment of pituitary adenomas. Methods: Ten patients of pituitary adenomas who were planned for post operative adjuvant radiotherapy were included. Planning CT was done with the patient supine with a customized thermoplastic cast of head on Philips wide bore CT (for 3 mm). The CT images were transferred online to the Pinnacle TPS V.8.0M. Tumor and the critical structures like brain stem and optic nerves were contoured on pinnacle. 3DCRT was planned on pinnacle. The CT images with the contoured structures were sent to Monaco TPS V.3.10.02. IMRT and VMAT were planned on Monaco. Dose: 50 Gy in 25 fractions. PTV indices analyzed: D mean, D2 (dose received by the hottest 2 percent volume), D98 (dose received by 98 percent), homogeneity index HI [(D2-D98)/D50)], and conformity index CI (PTV volume/volume of PTV covered by 95 percent isodose). Dmax and D2 (dose received by hottest 2cc) for the brain stem, right and left optic nerve PRV were evaluated. The average were calculated and compared. Statistical analysis was done by SPSS Version 14. Results: The Table shows that VMAT is better in terms of PTV indices. For the normal structures also VMAT provides the least dose. Conclusions: VMAT is superior to IMRT and both are better than 3DCRT for the radiotherapeutic treatment of pituitary adenoma. [Table: see text]
Functional validation of a genetic locus in the VEGFR-1 tyrosine kinase (TK) domain as a predictive marker for bevacizumab
Authors: Bart Claes, Paul Delmar, Betül Yesilyurt, Joke Reumers, Massimiliano Mazzone, Roland Devlieger, Hans Wildiers, Sanne de Haas, Peter Carmeliet, Eric Van Cutsem, Stefan Scherer, Dieter Lambrechts
Journal: Cancer Research (2012)
Image Gallery: A rare abscess-like presentation of Langerhans cell histiocytosis
Authors: L.J.F. Janssen, P.P.T. Brons, H.W.B. Schreuder, W.A.M. Blokx, E.E. Deurloo, C. van den Bos
Journal: British Journal of Dermatology (2017)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 12‐year‐old boy was evaluated because of local pain in his right arm. Radiological examination was suggestive of a malignancy of the proximal radius (a). A few days after the biopsy a solitary bulla had appeared, surrounded by erythema and subcutaneous induration (b). Immunohistochemistry showed CD1a positivity in most cells (c), confirming the diagnosis of Langerhans cell histiocytosis (LCH). Magnetic resonance imaging showed clear progression of the soft‐tissue extension of the LCH lesions through the skin (d). Subsequently the lesions started to ulcerate (e) and systemic therapy with oral prednisolone was initiated for 3 months. Twelve weeks after cessation of steroids, the skin lesion had healed with scarring, and continuing regeneration of the radius was shown on X‐ray (f). There is a great diversity in the type of skin lesions in children with LCH, but the impressive cutaneous abscess‐like lesion in our patient is uncommon.