tbuckley/cabot-search huggingface dataset:
Abstract 17290: Tead1 is Required for Cardiomyocyte Proliferation
Authors: Ruya Liu, Rajaganapathi Jagannathan, Feng Li, Jeongkyung Lee, Vijay K Yechoor, Mousumi Moulik
Journal: Circulation (2018)

Introduction: Mammalian cardiomyocyte (CM) proliferation peaks in the embryonic and neonatal periods. TEAD1, a key transcription factor regulated by the Hippo pathway, is critical for early embryonic CM proliferation. But mid gestation lethality of Tead1 germline deletion precluded the study of its role in CMs at later developmental stages. We recently generated Tead1 floxed (Tead1 F/F ) mice which allows the study of TEAD1 function in CMs at later stages. The objective of this study was to determine requirement of TEAD1 for neonatal CM proliferation. Hypothesis: TEAD1 remains critical for CM proliferation in late embryonic and early neonatal periods through transcriptional regulation of cell cycle promoting genes. Methods and Results: We observed that TEAD1 cardiac expression peaks in the perinatal period. Using Myh6-Cre deletor mice, we knocked out Tead1 in CMs at E10.5 (referred as cKO). cKO pups were born in expected Mendelian frequency, but survived only till day of life (DOL) 9. Systolic dysfunction was evident by ECHO in DOL1 cKO pups and progressed to frank heart failure (HF) by DOL9. Histological exam showed decreased myocardial mass with increased intercellular fibrosis. Ventricles of DOL1 cKO pups demonstrated increased expression of Acta1, Nppa, and Nppb, consistent with HF but showed decreased expression of Myh7, suggesting an impairment in the typical fetal gene program activated in HF. Myocardial immunostaining showed reduction in Ki67 (G1/S/G2/M phase marker) (Fig 1) and PH3-S10 (M phase marker) positive CMs by 82% and 46% respectively in DOL1 cKO hearts, indicating significantly reduced CM proliferation. The expression of essential cell cycle proteins showed a significant decrease in the levels of G1/S regulating proteins, CDK4, CDK6, ppRB S807/811 and S/G2 and G2/M regulating proteins, pWEE1 S642 and Cyclin B1 in cKO hearts (Fig 2). Similar results in ex vivo and in vitro Tead1 knockout models in CMs using neonatal Tead1 F/F CMs and HL1 cells validated the cell autonomous regulation of CM cell cycle by TEAD1. Conclusions: TEAD1 is required for embryonic and neonatal CM proliferation and its loss at mid gestation leads to neonatal HF associated with impaired fetal gene program activation and decreased expression of cell cycle promoting genes.
Behavioral ototoxicology.
Authors: W C Stebbins, M C Rudy
Journal: Environmental Health Perspectives (1978)

Methods for the evaluation in experimental animals of toxic substances that produce hearing impairment are described. In the experiments reported here, animals were trained by positive reinforcement operant conditioning procedures so that their hearing could be examined by behavioral means. When normal hearing was established, aminoglycosidic antibiotics (kanamycin and dihydrostreptomycin) were given daily and hearing tests administered in order that the course of hearing loss could be closely followed. Initial loss of sensitivity to the high frequencies always progressed in time to impairment at the low frequencies, and these changes in hearing were correlated with a loss of receptor cells in the inner ear which started in the basal region of the cochlea and advanced toward the apex. Although such behavioral procedures are moderately expensive to instrument and relatively time-consuming to apply, they are shown to yield valid quantitative measures of hearing. Further, they provide for reliable early detection of the toxic process and a measure of behavioral impairment that can be precisely related to the histopathological changes that occur simultaneously in the inner ear and auditory nerve.
Candida albicans Endocarditis With a Contaminated Aortic Valve Allograft—California, 1996
Journal: JAMA (1997)

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
Abstract 17191: Intraprocedural Dobutamine Use is Independently Associated With Prolonged Length of Stay (LOS) Following Ventricular Tachycardia (VT) Ablation
Authors: Jeffrey D Graham, Michael Rosenberg, Amneet Sandhu, Alexis Tumolo, Wendy Tzou, William Sauer, Ryan Borne, Duy Nguyen
Journal: Circulation (2018)

Introduction: Use of inotropes such as dobutamine remains controversial in the management of heart failure (HF) due to uncertain efficacy and lack of mortality benefit. Furthermore, vasoactive drugs are frequently utilized during VT ablations despite minimal data regarding their effects on outcomes. Vasoactive drugs may impact factors such as long-term VT recurrences and hospital length of stay. Hypothesis: We sought to evaluate the hypothesis that the use of dopamine, dobutamine or phenylephrine have differential effects on outcomes after VT ablations. Methods: A retrospective analysis was completed for all VT ablations from 2013-17 at our institution. Patient characteristics and procedural details were collected for 149 VT ablation cases. Results: The cohort was 81% male, and 67% had cardiomyopathy of which 53% were ischemic with a mean EF of 29% (CI 26.7- 31.4). Average procedure time was 368 minutes (CI 347-388). Vasoactive drugs were used in 87% of patients undergoing VT ablation: phenylephrine (67%), dopamine (40%), dobutamine (37%). The median LOS for all patients was 5 days (mean 7 days, range 1 - 56 days, IQR 2 - 9 days). After adjusting for inducibility, HF and procedural time, the dose of dobutamine, but not dopamine or phenylephrine, was significantly associated with increased length of stay (Fig. 1a). Inducible VT at the end of the procedure also correlated with increased LOS (5.4±0.3 vs 8.6±0.3, p &lt; 0.0001). Procedural time did not associate with increased LOS. Of all covariates, only the number of VTs induced during the procedure was significantly associated with increased VT recurrence (HR 1.22/VT morphology (CI 1.11-1.34, p &lt; 0.001)). Conclusions: Dobutamine, but not phenylephrine or dopamine, was significantly associated with increased length of stay after adjusting for HF, procedural time and inducibility of VT. More research is needed regarding vasoactive drug use in VT ablations and their significance to procedural and post-procedure outcomes.
Use of bone modifying agents for metastatic castrate-resistant prostate cancer.
Authors: Aaron Philip Mitchell, Akriti Mishra Meza, Azeez Farooki, Katherine Panageas, Peter B. Bach, Allison Lipitz-Snyderman, Michael J. Morris
Journal: Journal of Clinical Oncology (2022)

55 Background: Bone modifying agents (BMAs) prevent skeletal related events (SREs) among patients with metastatic, castrate-resistant prostate cancer (mCRPC) involving the bone. The utilization of BMAs among patients with mCRPC and bone metastasis has not been well defined, and the number of patients who may benefit but are undertreated is not known. We conducted this study to measure patterns of BMA among mCRPC patients. Methods: We used linked SEER cancer registry and Medicare claims data. Our cohort included men newly diagnosed with de-novo stage IV prostate adenocarcinoma during 2007-2015, with followup through 2016. We included those age &gt; = 66 at diagnosis, had continuous enrollment in Medicare Parts A and B from 180 days prior to diagnosis through the outcome period and Part D from diagnosis through outcome period, and who received androgen deprivation therapy. We further limited the cohort to those who subsequently received a CRPC-defining therapy (eg., abiraterone, sipuleucel-T, docetaxel if occurring prior to CHAARTED trial results). We grouped the cohort according to those who did vs. did not have evidence of bone metastasis in claims. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of initiating a CRPC-defining therapy. Among patients who received BMAs after initiating CRPC therapy, we further characterized the time at which they first initiated a BMA. Results: Our sample included 1,303 patients, of which 85% had evidence of bone metastasis. Overall, 58% received a BMA within 180 days of initiating a CRPC-defining therapy. 66% of patients with evidence of bone metastasis received BMAs, compared to 16% of those without evidence. Of patients who received BMAs, 38% first received BMAs between 90 days prior to starting CRPC therapy and 180 days after; the remaining 62% were previously receiving BMAs during the castrate-sensitive phase of disease. Among patients with evidence of bone metastasis who initiated CRPC-defining therapy in 2007-2009, 65% received BMAs; this proportion was 69% and 64% for those began CRPC therapy during 2010-2013 and 2014-2016, respectively. Conclusions: Approximately two-thirds of patients with mCRPC and bone metastases received BMAs within 180 days of initiating a CRPC-defining therapy. In most cases BMA therapy was initiated while patients still had castrate-sensitive disease, for which BMAs are indicated only at lower doses for the prevention of osteoporotic fractures. Further work is needed to understand whether real-world dosing is in line with clinical indications, and whether the one-third of patients who did not receive BMA therapy appropriately reflects the proportion of patients with contraindications. Further work is also needed to characterize patient and provider factors associated with appropriate BMA use.
Varicose Veins
Authors: A. D. Wright
Journal: BMJ (1940)

Varicose veins afflict such a huge number of people that here lies a tremendous therapeutic field, and for those who make themselves proficient in this line there are plenty of patients waiting to be treated; and very grateful they will be for the excellent results now to be obtained in this important branch of minor surgery. AetiologyThe aetiological factors most concerned in the develop- ment of varicose veins are:Occupational.-Prolongedstanding, especially in hot rooms, is particularly harmful.It is sometimes said that a chronic ulcer of the leg is a better recommendation for a cook than endless testimonials.Pregnancy.-Here is provided a mechanical and a hormonic cause.The veins of pregnancy regress greatly after delivery, so it is unwise to inject them till well after delivery.It is well to bear in mind that mis- carriages, delivery mishaps, phlegmasias, and even the baby's blemishes will be ascribed to these injections.It is better during pregnancy to rely upon support of the Swollen veins by adhesive strapping or bandages and treat only those which persist after childbirth.0Heredity.-Venouscomplaints tend to run in families and may take the form of varicose veins, thrombophilia, embolism, ulceration, and so on.Phlebitis.-It is probable that even the mildest phlebitis leads to shrivelling of the venous valves, and this starts a spreading venous incompetency.More severe phlebitis will give rise to fibrosis of the muscularis with resulting mural incompetency.Sometimes obstructions in the deep -veins cause dilatation in the superficial venous tree, 'but it is certain that valvular and muscular incompetency are the root of the trouble in almost all post-phlebitic cases.Certain debilitating diseases not actually complicated by phlebitis also seem to lead to the development of varicose veins.Traumna.-An injury to a superficial vein sometimes causes a traumatic thrombosis, and, following on this, valvular or muscular weakness in the injured vein may lead to the development of varicose veins.It is possible also that violent exercise may result in the rupture of a valve in the vein, and vigorous athletes are often given this explanation for their varicose veins in later life.The bursting of the posterior tibial vein (" ruptured plantaris ") is an athletic injury which occasionally leads to varicose veins.Classification Classification of varicose veins is extremely difficuLlt, and yet it is very important from a therapeutic and prognostic point of view.First of all grouping may be made according to the veins affected.
Abstract 129: Effect of Defibrillation Dose and Waveform Characteristics on Defibrillation Success in Pediatric In-Hospital Cardiac Arrest
Authors: Tia T Raymond, Jordan Duval-Arnould, Weilun Quan, Sam Chai, Lyndsay Ryerson, Javier Lasa, Peter Meaney, Robert Berg, Vinay Nadkarni, Dana Niles, Annemarie Silver, Allan de Caen, Dianne Atkins
Journal: Circulation (2018)

Introduction: Amplitude spectral area (AMSA) predicts successful defibrillation (DF) and return of spontaneous circulation (ROSC) in adults but has not been studied during pediatric in-hospital cardiac arrest (IHCA). Hypothesis: We characterized DF dose and AMSA during pediatric IHCA from a pediatric resuscitation quality (pediRES-Q) collaborative and hypothesized that a threshold value of AMSA could predict successful DF. Methods: Children &lt;18 years with witnessed IHCA, ventricular fibrillation (VF) as the initial rhythm, and those who had complete CPR quality metric data captured from the bedside defibrillator (ZOLL R-Series, Chelmsford, MA) were studied. Energy dose, initial AMSA ( i AMSA) and pre-shock AMSA ( p AMSA) [2.5-sec ECG window before defibrillation] for predicting DF success were calculated, together with receiver operator (ROC) curves. Successful DF (sDF) was defined as return of an organized rhythm 5 seconds after DF. Sustained ROSC was defined as &gt;20 minutes without chest compressions. Events with DF due to ventricular tachycardia, inappropriate shocks (i.e. supraventricular tachycardia, conduction block), unavailable AMSA values, and VF events using &lt;1 J/kg for DF were excluded. Results: Between 2015-2018, 34 subjects (median age 7.4 years [1.3,13.1]; median weight 19.4 kgs [8.9, 41.7]) with IHCA due to VF were enrolled. We analyzed 26 shocks in 18 children &lt; 8 years and 25 shocks in 16 children 8 to &lt;18 years. For children &lt; 8 years, the initial DF median dose/kg was 2.5 [2.3,3.3] J/kg with sDF in 14/26 (54%) shocks and sustained ROSC in 10/18 (56%) children. For those 8 to &lt;18 years, initial DF median dose/kg was 3.0 [2.5,3.4] J/kg with sDF in 10/25 (40%) shocks and sustained ROSC in 10/16 (63%). AMSA was significantly higher prior to sDF than in unsuccessful DF ( p AMSA 19.14±8.11 vs.12.0±7.38 mV-Hz, p = 0.0021; i AMSA 19.08±7.38 vs. 11.04±6.57 mV-Hz, p = 0.0053). Area under the ROC curve was 0.765 for p AMSA and 0.796 for i AMSA. Conclusions: We characterized DF dose and AMSA during pediatric IHCA with an initial rhythm of VF and found that sDF was significantly associated with AMSA &gt;19 mV-Hz. Future studies should determine the AMSA threshold that predicts sDF in children due to differences in heart size and cardiac arrest etiology.
Community practice. The cake-bake syndrome and other trials
Authors: F. Mullan
Journal: JAMA (1980)

IN THE fall of 1972,I went to work as a family practitioner in a new community clinic in the barrio of Sante Fe, NM. Although I was a member of the recently established National Health Service Corps (NHSC)<sup>1,2</sup>and, therefore, a federal employee, I was assigned to the community board of<i>La Clinica de la Gente</i>as their physician. My partner (another NHSC physician) and I began to build the practice from the ground up. This included obtaining hospital privileges, joining the local medical society, establishing a medical records system, designing a treatment room, and stocking a small pharmaceutical dispensary. At the same time, we worked with the community board to determine the clinic's fee schedule, hours of operation, patient policies, and hiring policies. The final decisions in these latter areas belonged to the board. While we were generally well received, we were clearly anomalies in the medical community.
Lethal Endotoxin Shock
Authors: J. C. Rosenberg
Journal: JAMA (1966)

Recent studies by Crowel<sup>1</sup>and Smith<sup>1</sup>and Rush et al<sup>2</sup>have drawn attention to the significance of the oxygen deficit incurred during hemorrhagic shock. The results of these investigations support the concept of progressive stagnant hypoxia as the final pathway of irreversible hemorrhagic shock.<sup>3</sup>Endotoxin shock is thought to produce death in a similar fashion, ie, vasoactive substances are released which lead to venous pooling, decreased venous return, decreased cardiac output, and poor tissue perfusion. The latter results in stagnant hypoxia with eventual cellular death. The following experiments were undertaken to quantitate the hypoxia sustained during lethal endotoxin shock by measuring oxygen deficit and lactate production following the administration of<i>Escherichia coli</i>endotoxin. The data reported in this paper were derived from animals that did not develop a pyrogenic response to the endotoxin. If shock was accompanied by fever, oxygen consumption rose, despite progressive deterioration terminating in
Back pain.
Authors: J K Waterlow
Journal: BMJ (1978)

1 in 10 (or greater) chance of diagnosing a brain tumour is not to be missed, then referral of all stroke patients with the appropriate evolution would completely swamp the available CAT scanning resources.Stroke evolution is only one factor determining the attitude of a general physician towards the management of a stroke patient.Considering the scarcity and the costliness of the new diagnostic machinery, information is required concerning the incidence of tumour or subdural haematoma in stroke patients as they present on the general medical ward.
Accidents--speed and the road environment.
Journal: BMJ (1978)

seems to him a silly question, is unlikely to be rewarded with a spontaneous round of applause. Putting yourself acrossIn times of difficulty I have found that platitudes often reveal their deep meaning, and I would be failing in my duty if I did not include some hackneyed advice.Be courteous throughout.Be absolutely honest: it is futile to attempt to put over an insincere impression.Memorise what you have written in your curriculum vitae.Look as if you are interested in that particular job, and don't give the impression that you are there simply because you want promotion.It goes without saying that you will have visited the department before the interview.If you ask a question at the end, it should be about facilities-not about pay or holidays.To the interviewer, the interview is a civilised little chat designed to let the candidate bloom like a rose after rain and reveal all his talents.Interviewees, however, are acutely aware that Darwinian laws apply to pyramidal specialties.They should remember that the interview is not in fact a battle for survival but a courtship ritual: for the unsuccessful suitors there will be other, often more attractive, opportunities, and for the lucky winner the hard work is just beginning.
Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- mice
Authors: Tingting Wang, Yan Dong, Li Yao, Fan Lu, Chenxi Wen, Zhuo Wan, Li Fan, Zhelong Li, Te Bu, Mengying Wei, Xuekang Yang, Yi Zhang
Journal: Bioactive Materials (2022)

Atherosclerosis is characterized by inflammation in the arterial wall, which is known to be exacerbated by diabetes. Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis. In this study, we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout (ApoE-/-) mice, in which increased expression of long-chain acyl-CoA synthetase 1 (Acsl1) in macrophages played an important role. Knockdown of Acsl1 in macrophages (Mφ shAcsl1 ) reprogrammed macrophages to an anti-inflammatory phenotype, especially under hyperglycemic conditions. Injection of Mφ shAcsl1 reprogrammed macrophages into streptozotocin (STZ)-induced diabetic ApoE-/- mice (ApoE-/-+ STZ) alleviated inflammation locally in the plaque, liver and spleen. Consistent with the reduction in inflammation, plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages. Taken together, our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice, possibly by promoting inflammation. Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.
Perforation of the greater gastric curvature by a gastric adenocarcinoma with engulfment of the upper pole of the spleen
Authors: Pierre Mayer, Lucile Héroin, Didier Mutter, Laetitia Oertel, Mathieu Pioche, François Habersetzer, Guillaume Philouze
Journal: Endoscopy (2022)

Perforated gastric cancer is a rare condition [1]. It has an extremely poor prognosis. There are few data in the literature regarding perforated gastric adenocarcinoma involving the spleen [2]. We report here the case of a 66-year-old woman who was admitted to our department with general deterioration, right hypochondrium pain, and anemia of 7.5 g/dl. An abdominal and pelvic computed tomography was performed, revealing a large necrotic mass with irregular contours of the greater curvature of the stomach, measuring 10.3 × 5.7 cm, and multiple coliomesenteric, epiploic, and retroperitoneal (left lateral renal) lymph nodes. Three hypodense irregularly contoured hepatic nodules in segment IV and in the left liver were found as well, highly suspicious of secondary locations given the context. There was also a cystic splenic nodule, suspected of being a metastatic lesion ([Fig. 1]).
The Role of Thrombi in Atherosclerosis
Journal: JAMA (1966)

Experimental and human necropsy observations indicate that a thrombus can and frequently does lead to the intensification and aggrandizement of the human atherosclerotic process. Conversion of a thrombus into atherosclerotic plaque in diseased human arteries was observed in serial sections of six arterial segments, Meyer Friedman, MD, told a symposium on atherosclerotic vascular disease sponsored by the Hahnemann Medical College and Hospital, Philadelphia. Dr. Friedman is director of the Harold Brunn Institute, Mount Zion Hospital and Medical Center, San Francisco. <h3>Subject of Dispute</h3> The role of the thrombus in the pathogenesis of atherosclerosis is, like many other aspects of this disease, a subject of dispute. Broadly speaking, one group, composed primarily of American investigators, considers a thrombotic lesion a late complication of the disease whose origin most likely is due in large part to a chronic lipid disorder. A second school, composed primarily of British investigators, holds that a thrombus,