tbuckley/cabot-search huggingface dataset:
Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs
Authors: John L. Sapp, George A. Wells, Ratika Parkash, William G. Stevenson, Louis Blier, Jean-Francois Sarrazin, Bernard Thibault, Lena Rivard, Lorne Gula, Peter Leong-Sit, Vidal Essebag, Pablo B. Nery, Stanley K. Tung, Jean-Marc Raymond, Laurence D. Sterns, George D. Veenhuyzen, Jeff S. Healey, Damian Redfearn, Jean-Francois Roux, Anthony S.L. Tang
Journal: New England Journal of Medicine (2016)

Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain.We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock.Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group.In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH ClinicalTrials.gov number, NCT00905853.).
Antipsychotic drug therapy and sexual dysfunction in men
Authors: J E Mitchell, M K Popkin
Journal: American Journal of Psychiatry (1982)

The authors review the literature on male sexual dysfunction associated with antipsychotic drug treatment. Erectile and ejaculatory disturbances have been most frequently reported. Changes in libido have also been reported, but the effects of these drugs on sexual drive have apparently not been systematically studied. Fortunately, most types of sexual dysfunction associated with antipsychotic drugs appear to be medically benign and reversible with drug discontinuation. An exception is priapism, which necessitates prompt urological consultation and may require surgical intervention.
Expiration-Triggered Sinus Arrhythmia Predicts Outcome in Survivors of Acute Myocardial Infarction
Authors: Daniel Sinnecker, Michael Dommasch, Alexander Steger, Anna Berkefeld, Petra Hoppmann, Alexander Müller, Josef Gebhardt, Petra Barthel, Katerina Hnatkova, Katharina M. Huster, Karl-Ludwig Laugwitz, Marek Malik, Georg Schmidt
Journal: Journal of the American College of Cardiology (2016)
Phenomenology and family history of affective disorder in Cushing's disease
Authors: J I Hudson, M S Hudson, G T Griffing, J C Melby, H G Pope
Journal: American Journal of Psychiatry (1987)

Of 16 patients with Cushing's disease, 13 (81%) had lifetime diagnoses of major affective disorder according to DSM-III criteria. However, the rate of familial major affective disorder among these patients was significantly lower than that found among patients with major depression.
Comparison of Efficacy and Safety of 5-Day and 10-Day Schedules of Sgi-110, a Novel Subcutaneous (Sc) Hypomethylating Agent (Hma), in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia (R/R Aml)
Authors: G.J. Roboz, F. Ravandi, P. Kropf, K. Yee, C. O'Connell, E. Griffiths, W. Stock, G. Garcia-Manero, E. Jabbour, N. Daver, N. Pemmaraju, J. Issa, K. Walsh, D. Rizzieri, S. Lunin, S. Naim, Y. Hao, M. Azab, H. Kantarjian
Journal: Annals of Oncology (2014)
The art of instilling confidence
Authors: Dharani Yerrakalva
Journal: BMJ (2016)

I walk up to the GP waiting room to call the next patient. I assert the “power pose”: I drop the pitch of my voice and project the name of the patient. These are things that youthful-looking doctors, whether through small stature, gender, or ethnicity, learn to do to get by. Nobody teaches you this. The sea of patients turn their heads …
Pegamotecan (EZ-246), a novel PEGylated camptothecin conjugate, for treatment of adenocarcinomas of the stomach and gastroesophageal (GE) junction: Preliminary results of a single-agent phase 2 study
Authors: L. C. Scott, T. Evans, J. C. Yao, A. I. Benson, M. Mulcahy, A. Thomas, M. Decatris, S. Falk, M. Rudoltz, J. A. Ajani
Journal: Journal of Clinical Oncology (2004)

4030 Background: The results of a phase 1 study of pegamotecan have been published.1 This phase 2 study was designed to evaluate the activity of pegamotecan in advanced and metastatic adenocarcinomas of the stomach and GE junction. Methods: This multicenter, open-label, single arm study utilized a Fleming 2-stage design. Fifteen subjects were enrolled in the first stage; one response allowed for enrollment of 20 additional subjects. Eligibility criteria included: pathologically confirmed measurable adenocarcinoma of the stomach or GE junction, performance status 0–2, ≤ 1 prior chemotherapy regimens, no prior treatment with a camptothecin analog. Pegamotecan was administered at 7,000 mg/m2 q 3 weeks. The primary endpoint was response rate (RECIST). Secondary endpoints included safety and tolerability, survival, and patient benefit parameters. Results: Preliminary data are available for 15 subjects who received a total of 52 cycles (range 1 – 10). The median age was 62 years (range 36 – 79). Partial responses (PR) were observed in 4 subjects (27%). Two responses were noted after 2 cycles, 1 after 4 cycles, and 1 after 6 cycles. Two of these subjects remained on study for 9 and 10 cycles, respectively. Stable disease (SD) was observed in 6 subjects (40%). Five of these subjects remained on study for 4 cycles, and 1 for 6 cycles. The most common adverse events (AE) were nausea (n=8), anemia (n=6), vomiting (n=5), and fatigue (n=5). Only 1 grade 3 AE (nausea) and 1 grade 4 AE (vomiting) that occurred in the same patient were reported. Two subjects developed grade 2 cystitis, in each of whom dehydration was reported. Another subject who received 10 cycles in whom aggressive hydration was documented did not develop cystitis. Conclusions: Pegamotecan is a promising treatment for adenocarcinoma of the stomach and GE junction. It appears to be well tolerated, with a low incidence of grade 3 and 4 toxicities. Grade 2 cystitis, a known toxicity of camptothecin, was observed in 2 subjects. Data will be updated prior to presentation. 1. Rowinsky EK et al. J Clin Onc 21:148–57, 2003 Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Enzon Pharmaceuticals, Inc. Enzon Pharmaceuticals, Inc.
STEM-06ADULT NEURAL STEM CELLS ARE IRREPLACEABLE
Authors: Terry Burns, Dominic Rodriguez, Sunny Kumar, Matthew Li, Theo Palmer
Journal: Neuro-Oncology (2015)

BACKGROUND: Quiescent tumor-initiating with neural stem cell-like properties are resistant to antiproliferative therapy, enabling tumor recurrence. As such, increasing attention is focused on quiescent tumor stem cells. Quiescent neural stem cells (NSCs) share many features with tumor stem cells and may be ablated by suched targetted therapies, yielding adverse cognitive sequelae. The capacity of the quiescent NSC niche to recover following ablation remains unknown. METHODS: Nestin-creERT2::diphtheria toxin reporter (DTR) mice were induced to express DTR on NSCs with 3 days 150mg/kg i.p. tamoxifen. Ablation and control mice were treated with 100ug/kg diphtheria toxin DT or vehicle, respectively. Proliferative cells were labeled with BrdU prior to sacrifice. For cell replacement experiments, embryonic stem cell (ESC)-derived NSCs were stereotactically implanted into the dentate gyrus and lateral ventricle. RESULTS: Ablation caused 50-80% reduction of quiescent NSCs and BrdU+ within 10 days. NSC loss persisted at least 2 months, and was accompanied by 48% loss of neurogenesis at 2 months (p < 0.01), suggesting inability of the partially vacated neurogenic niche to be repopulated over time by surviving NSCs. ESC-derived NSCs increased proliferation of endogenous NSCs though only modestly impacted the quiescent NSC pool size. Implanted NSCs also differentiated into neurons with appropriate morphology and projections but failed to engraft long term into the quiescent NSC niche. CONCLUSIONS: We demonstrate for the first time that adult NSCs are unable to repopulate the quiescent NSC niche after partial ablation of quiescent NSCs, even though surviving NSCs remain functional and responsive to proliferative stimuli. Primitive ESC-derived NSC also appear unable to engraft into the quiescent vacated niche. These findings suggest that loss of quiescent NSCs irreversibly decreases niche size. Given the importance of neurogenesis for cognition and memory, the potentially irreversible impacts of novel stem cell-targeted antitumor therapies on quiescent NSC pool size should be carefully evaluated.
De novo CD44 expression by proliferating mesangial cells in rat anti-Thy-1 nephritis.
Authors: D J Nikolic-Paterson, Z Jun, G H Tesch, H Y Lan, R Foti, R C Atkins
Journal: Journal of the American Society of Nephrology (1996)

CD44 is the major cell-surface receptor for hyaluronan, and cell-matrix interactions mediated by the CD44/hyaluronan receptor-ligand pair are involved in a variety of cellular functions, including cell migration. The aim of the study presented here was to examine the expression of CD44 and hyaluronan in the mesangial proliferative response in rat anti-Thy-1 nephritis. In normal rat kidney, CD44 is expressed by medullary tubules, some distal tubules and thick ascending limbs of Henle, dendritic-like cells around Bowman's capsule, and some interstitial cells. However, only occasional CD44+ cells were found within the glomerular tuft. In experimental nephritis, there was an early glomerular influx of CD44+ macrophages, which peaked on Day 4 after anti-Thy-1 antibody injection. A striking finding was de novo CD44 expression by mesangial cells. This CD44 expression was restricted to the transient period of mesangial cell proliferation as shown by double-staining with an antibody against the proliferating cell nuclear antigen. Immunohistochemistry staining also demonstrated hyaluronan deposition within segmental areas of proliferating CD44+ cells, suggesting a functional interaction between the CD44/hyaluronan receptor-ligand pair during mesangial cell proliferation. In vitro, rat mesangial cells were shown to express mRNA and protein for the 90-kd isoform of CD44. In addition, hyaluronan-dependent aggregation of CD44+ mesangial cells was specifically inhibited by an anti-CD44 antibody, demonstrating a functional interaction between hyaluronan and the CD44 expressed on the surface of rat mesangial cells. In conclusion, these data suggest that cell-matrix interactions mediated by the CD44/hyaluronan receptor-ligand pair are involved in mesangial cell proliferation in rat anti-Thy-1 nephritis.
In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site
Authors: SJ Hamilton-Dutoit, M Raphael, J Audouin, J Diebold, I Lisse, C Pedersen, E Oksenhendler, L Marelle, G Pallesen
Journal: Blood (1993)
Discontinuing<i>Pneumocystis carinii</i>Prophylaxis
Authors: Pierre-Marie Girard
Journal: New England Journal of Medicine (2001)

Until the widespread adoption of specific prophylaxis in the late 1980s, Pneumocystis carinii pneumonia was among the most common life-threatening opportunistic infections associated with infection with the human immunodeficiency virus (HIV) in industrialized countries. Primary prophylaxis against P. carinii pneumonia is currently recommended for all HIV-infected patients with CD4 cell counts of less than 200 per cubic millimeter and for those receiving cytotoxic chemotherapy. Secondary prophylaxis is recommended for all patients with a history of P. carinii pneumonia.1 The advent of highly active antiretroviral therapy, which can drastically inhibit HIV replication and lead to substantial increases in CD4 cell counts, . . .
Insulin-Like Growth Factor-1 Receptor Deficiency in Macrophages Accelerates Atherosclerosis and Induces an Unstable Plaque Phenotype in Apolipoprotein E–Deficient Mice
Authors: Yusuke Higashi, Sergiy Sukhanov, Shaw-Yung Shai, Svitlana Danchuk, Richard Tang, Patricia Snarski, Zhaohui Li, Patricia Lobelle-Rich, Meifang Wang, Derek Wang, Hong Yu, Ronald Korthuis, Patrice Delafontaine
Journal: Circulation (2016)

We have previously shown that systemic infusion of insulin-like growth factor-1 (IGF-1) exerts anti-inflammatory and antioxidant effects and reduces atherosclerotic burden in apolipoprotein E (Apoe)-deficient mice. Monocytes/macrophages express high levels of IGF-1 receptor (IGF1R) and play a pivotal role in atherogenesis, but the potential effects of IGF-1 on their function are unknown.To determine mechanisms whereby IGF-1 reduces atherosclerosis and to explore the potential involvement of monocytes/macrophages, we created monocyte/macrophage-specific IGF1R knockout (MΦ-IGF1R-KO) mice on an Apoe(-/-) background. We assessed atherosclerotic burden, plaque features of stability, and monocyte recruitment to atherosclerotic lesions. Phenotypic changes of IGF1R-deficient macrophages were investigated in culture. MΦ-IGF1R-KO significantly increased atherosclerotic lesion formation, as assessed by Oil Red O staining of en face aortas and aortic root cross-sections, and changed plaque composition to a less stable phenotype, characterized by increased macrophage and decreased α-smooth muscle actin-positive cell population, fibrous cap thinning, and decreased collagen content. Brachiocephalic artery lesions of MΦ-IGF1R-KO mice had histological features implying plaque vulnerability. Macrophages isolated from MΦ-IGF1R-KO mice showed enhanced proinflammatory responses on stimulation by interferon-γ and oxidized low-density lipoprotein and elevated antioxidant gene expression levels. Moreover, IGF1R-deficient macrophages had decreased expression of ABCA1 and ABCG1 and reduced lipid efflux.Our data indicate that macrophage IGF1R signaling suppresses macrophage and foam cell accumulation in lesions and reduces plaque vulnerability, providing a novel mechanism whereby IGF-1 exerts antiatherogenic effects.
FLT3L and AMD3100 Combination Increases Hematopoietic Stem Cell Mobilization and Leads To Improved Transplantation Outcome
Authors: Shun He, Deng Youcai, Sumithira Vasu, Jianhong Chu, Shunzong Yuan, Jianying Zhang, Zhijin Fan, Craig C Hofmeister, Xiaoming He, Henry March, Steven M. Devine, Jianhua Yu
Journal: Blood (2013)
A synthetic biology-based device prevents liver injury in mice
Authors: Peng Bai, Haifeng Ye, Mingqi Xie, Pratik Saxena, Henryk Zulewski, Ghislaine Charpin-El Hamri, Valentin Djonov, Martin Fussenegger
Journal: Journal of Hepatology (2016)

The liver performs a panoply of complex activities coordinating metabolic, immunologic and detoxification processes. Despite the liver's robustness and unique self-regeneration capacity, viral infection, autoimmune disorders, fatty liver disease, alcohol abuse and drug-induced hepatotoxicity contribute to the increasing prevalence of liver failure. Liver injuries impair the clearance of bile acids from the hepatic portal vein which leads to their spill over into the peripheral circulation where they activate the G-protein-coupled bile acid receptor TGR5 to initiate a variety of hepatoprotective processes.
Serotonin function and depression: neuroendocrine and mood responses to intravenous L-tryptophan in depressed patients and healthy comparison subjects
Authors: L H Price, D S Charney, P L Delgado, G R Heninger
Journal: American Journal of Psychiatry (1991)

This study was designed to compare central serotonergic function in depressed patients and healthy comparison subjects by examining neuroendocrine and mood responses to intravenous L-tryptophan.One hundred twenty-six drug-free patients with DSM-III-R major depression (109 unipolar, 17 bipolar; 68 melancholic, 58 nonmelancholic; 28 psychotic, and 98 nonpsychotic patients) and 58 healthy comparison subjects participated. After an overnight fast, subjects received an intravenous infusion of L-tryptophan, 7 g. Blood was obtained for determination of serum prolactin, serum growth hormone (GH), and plasma tryptophan levels. Visual analogue scales were used to assess mood.Prolactin responses were blunted in nonmelancholic and higher in melancholic and psychotic depressed patients, while GH responses were blunted in combined unipolar, nonmelancholic, and nonpsychotic depressed patients. Controlling for baseline biological, clinical, and demographic factors eliminated the higher prolactin response in the melancholic and psychotic patients, attenuated the blunted GH response in the unipolar patients, and revealed a blunted GH response in the melancholic patients. Patients and comparison subjects differed on five of 13 mood responses, primarily because of baseline differences.These findings are consistent with previous studies demonstrating blunted neuroendocrine responses to intravenous L-tryptophan in depression. Restriction of these findings to specific subtypes of depression may reflect a differential role of serotonergic abnormalities in these subtypes.
Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor
Authors: Veit Rothhammer, Ivan D Mascanfroni, Lukas Bunse, Maisa C Takenaka, Jessica E Kenison, Lior Mayo, Chun-Cheih Chao, Bonny Patel, Raymond Yan, Manon Blain, Jorge I Alvarez, Hania Kébir, Niroshana Anandasabapathy, Guillermo Izquierdo, Steffen Jung, Nikolaus Obholzer, Nathalie Pochet, Clary B Clish, Marco Prinz, Alexandre Prat, Jack Antel, Francisco J Quintana
Journal: Nature Medicine (2016)
Authors’ reply to Large
Authors: James M Bolton, David Gunnell, Gustavo Turecki
Journal: BMJ (2016)

Large brings attention to the observation that inpatients in psychiatric hospitals have a substantially increased risk of suicide.1 2 This point is reflected in our review, where we state: “Although admission to hospital is often intended to provide a safe environment for the suicidal patient, the risk of suicide while an inpatient is high.” In an effort to emphasise this point, we discuss the findings of the Walsh meta-analysis that showed a pooled rate of 147 suicides per 100 000 inpatient years, and then provide a reference for a recent study by Madsen and colleagues that found a strikingly high rate of 860 suicides per 100 000 inpatient years. As Large pointed out we did …
Process Improvement and Adopting the 2015 American Heart Association Resuscitation Guidelines
Authors: Clyde W. Yancy
Journal: JAMA Cardiology (2016)

Bentley J. Bobrow, MD; Daniel W. Spaite, MD; Tyler F. Vadeboncoeur, MD; Chengcheng Hu, PhD; Terry Mullins, MBA; Wayne Tormala, MSW; Christian Dameff, MD; John Gallagher, MD; Gary Smith, MD; Micah Panczyk, MS
Association Between Acute Neuropsychiatric Events and<i>Helicobacter pylori</i>Therapy Containing Clarithromycin
Authors: Angel Y. S. Wong, Ian C. K. Wong, Celine S. L. Chui, Edwin H. M. Lee, W. C. Chang, Eric Y. H. Chen, Wai K. Leung, Esther W. Chan
Journal: JAMA Internal Medicine (2016)

There is a concern that Helicobacter pylori therapy containing clarithromycin might be associated with acute neuropsychiatric events.To examine the association between H pylori therapy containing clarithromycin and acute neuropsychiatric events.A self-controlled case series study was conducted using the Clinical Data Analysis and Reporting System database in Hong Kong to explore any association. The exposure of interest was H pylori therapy containing clarithromycin in the outpatient setting. Study patients, 18 years or older at cohort entry, must have had both exposure to H pylori therapy containing clarithromycin and their first recorded neuropsychiatric events between January 1, 2003, and December 31, 2012. A post hoc nested case-control analysis was also performed in patients receiving H pylori therapy containing clarithromycin.The primary outcome was composite neuropsychiatric events, while secondary outcomes were psychotic events and cognitive impairment. Risk periods in the self-controlled case series analysis were defined as 14-day preexposure period, current use (days 1-14 since prescription start date) and recent use (days 15-30). Age-adjusted incidence rate ratios (IRR) were estimated using the conditional Poisson regression.Of 66 559 patients who had at least 1 outpatient prescription of H pylori therapy containing clarithromycin. Their mean (SD) age at cohort entry was 50.8 (14.8 years); their mean age at first exposure was 55.4 (14.8) years, and 30 910 were male (46.4%). A total of 1824 patients had their first recorded composite neuropsychiatric events during the study period. An increased IRR of 4.12 (35 composite neuropsychiatric events during 72 person-years; 95% CI, 2.94-5.76) during current use was observed but not in recent use (9 events during 82 person-years; IRR, 0.95; 95% CI, 0.49-1.83) and 14-day preexposure period (14 events during 72 person-years; IRR, 1.63; 95% CI, 0.96-2.77) vs baseline (1766 events during 16 665 person-years). Similarly, both the risk of psychotic events and cognitive impairment increased during current use vs baseline, although this subsequently returned to baseline incidence levels during recent use. The crude absolute risks of composite neuropsychiatric events, psychotic events, and cognitive impairment during current use were 0.45, 0.12, and 0.12 per 1000 prescriptions, respectively. The nested case-control analysis also gave similar results to that of the self-controlled case series analysis.This study shows evidence of a short-term increased risk of neuropsychiatric events associated with H pylori therapy containing clarithromycin.
Case 24-1965
Authors: R M GIPSTEIN, J D BOYLE
Journal: New England Journal of Medicine (1965)

Presentation of Case First admission. A sixty-nine-year-old woman was admitted to the hospital because of abdominal swelling. She had been well until nine months previously, when there was the onset of nervousness, nausea, vomiting and marked loss of weight. She had been constipated for many months, and four days before admission abdominal swelling developed. There was no history of pain in the abdomen, jaundice, melena or diarrhea. Physical examination revealed a thin, pigmented woman who appeared chronically ill. A few atelectatic rales were audible at both lung bases. The heart was not enlarged, and there were no murmurs. The abdomen . . .