tbuckley/cabot-search huggingface dataset:
Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia
Authors: A Breier, R W Buchanan, B Kirkpatrick, O R Davis, D Irish, A Summerfelt, W T Carpenter
Journal: American Journal of Psychiatry (1994)

Clozapine is an atypical neuroleptic with superior efficacy in severely ill, treatment-resistant inpatients with schizophrenia. To determine if clozapine's differential efficacy generalizes to less ill, outpatients populations, the authors examined the effects of clozapine on positive and negative symptoms in outpatients with schizophrenia.Outpatients with schizophrenia who had histories of partial response to conventional neuroleptics and who had not responded to a prospective 6-week trial of fluphenazine participated in a 10-week, double-blind, parallel-groups comparison of clozapine and haloperidol. Thirteen men and six women were given clozapine, and 15 men and five women were given haloperidol. Clinical response rates were determined and effects on primary versus secondary negative symptoms were addressed. Doses of clozapine and haloperidol at the end of the 10-week trial were 410.5 mg/day (SD = 45.8) and 24.8 mg/day (SD = 5.5), respectively.Clozapine was superior to haloperidol for treating positive symptoms. In addition, eight of the patients given clozapine and only one of the patients given haloperidol fulfilled clinical responder criteria. Clozapine was also superior to haloperidol for treating negative symptoms, although these effects were relatively minor. Negative symptoms were significantly affected in the subgroup of patients with nondeficit schizophrenia but not in the subgroup with deficit schizophrenia. Overall, clozapine was well tolerated.Clozapine has superior efficacy for treating positive symptoms in partially responsive outpatients with chronic schizophrenia, suggesting that it has utility for a broad spectrum of patients with schizophrenia beyond the most severely ill.
PSRO: advantages, risks, and potential pitfalls
Authors: R Dorsey, F Sullivan
Journal: American Journal of Psychiatry (1975)

The authors propose that active physician participation in current review methodologies, including PSRO, can lessen the potential for such problems as the development of unrealistic standards, emphasis on review and record keeping as ends rather than means, and ineffectuality of the systems themselves. Potential advantages of PSRO are seen in areas of quality assessment and improvement, economy, and enhancement of the continuing learning processess of physicians. The authors suggest that physicians should resist pressures toward separation of reviewing authority from clinical competence.
Endothelial Function In Tanzanian Children With Sickle Cell Disease: Baseline Results From The Vascular Function Intervention Trial (VFIT)
Authors: Sharon E. Cox, Julie Makani, Elizabeth Ellins, Gurishaeli Walter, Selemani Mtunguja, Fenella J. Kirkham, Charles RJ Newton, Andrew M. Prentice, Julian P. Halcox
Journal: Blood (2013)
PWE-283 A single centre’s 10 year experience of tems excision of scar
Authors: AE Williams, K Mohammed, J Simson, B Levy
Journal: Gut (2015)

<h3>Introduction</h3> An increased volume of colonoscopy has resulted in more polyps being detected, some of which contain early cancer. In the rectum, such polyps are often removed endoscopically and then found to have cancer with involved margins, posing a management dilemma. Transanal endomucosal MicroSurgery (TEMS) offers a method for scar resection to detect residual cancer whilst avoiding major surgery. The aims of this study were to determine the frequency of such cases, what proportion of them had residual cancer in the scar and if they did not, what proportion later recurred. <h3>Method</h3> Our TEMS database was scrutinised for all ‘TEMS Excision of Scar’ cases. To confirm survival a case notes review was performed and all patients contacted by telephone. For deceased patients the general practice was contacted for cause of death. The data was analysed using SPSS. <h3>Results</h3> 18 procedures were performed between January 2004 and January 2015. Twelve were male with a mean age of 72. Three patients were found to have residual cancer in their scar and were recommended further treatment. Of the 15 patients with no residual cancer there was one recurrence at 4 years (6.7%). This patient died one week following major resection. Seven times as many procedures were performed in 2014 compared to 2004. <h3>Conclusion</h3> TEMS excision of scar appears to be a good discriminator for selecting patients who would benefit from conservative treatment following endoscopic polypectomy with cancer found at the diathermy edge. More cases and longer follow up is required to ensure TEMS excision of scar is a safe option for the future as the frequency of this clinical situation increases. <h3>Disclosure of interest</h3> None Declared.
The Neoplastic Transformation as a Biological Fractionation of Related Enzyme Systems
Authors: Jesse P. Greenstein, Paul J. Fodor, Florence M. Leuthardt
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article The Neoplastic Transformation as a Biological Fractionation of Related Enzyme Systems Get access Jesse P. Greenstein, Jesse P. Greenstein Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul J. Fodor, Paul J. Fodor Search for other works by this author on: Oxford Academic PubMed Google Scholar Florence M. Leuthardt Florence M. Leuthardt National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 2, October 1949, Pages 271–278, https://doi.org/10.1093/jnci/10.2.271 Published: 01 October 1949 Article history Received: 02 August 1949 Published: 01 October 1949
Using ToxCast™ Data to Reconstruct Dynamic Cell State Trajectories and Estimate Toxicological Points of Departure
Authors: Imran Shah, R. Woodrow Setzer, John Jack, Keith A. Houck, Richard S. Judson, Thomas B. Knudsen, Jie Liu, Matthew T. Martin, David M. Reif, Ann M. Richard, Russell S. Thomas, Kevin M. Crofton, David J. Dix, Robert J. Kavlock
Journal: Environmental Health Perspectives (2015)

High-content imaging (HCI) allows simultaneous measurement of multiple cellular phenotypic changes and is an important tool for evaluating the biological activity of chemicals.Our goal was to analyze dynamic cellular changes using HCI to identify the "tipping point" at which the cells did not show recovery towards a normal phenotypic state.HCI was used to evaluate the effects of 967 chemicals (in concentrations ranging from 0.4 to 200 μM) on HepG2 cells over a 72-hr exposure period. The HCI end points included p53, c-Jun, histone H2A.x, α-tubulin, histone H3, alpha tubulin, mitochondrial membrane potential, mitochondrial mass, cell cycle arrest, nuclear size, and cell number. A computational model was developed to interpret HCI responses as cell-state trajectories.Analysis of cell-state trajectories showed that 336 chemicals produced tipping points and that HepG2 cells were resilient to the effects of 334 chemicals up to the highest concentration (200 μM) and duration (72 hr) tested. Tipping points were identified as concentration-dependent transitions in system recovery, and the corresponding critical concentrations were generally between 5 and 15 times (25th and 75th percentiles, respectively) lower than the concentration that produced any significant effect on HepG2 cells. The remaining 297 chemicals require more data before they can be placed in either of these categories.These findings show the utility of HCI data for reconstructing cell state trajectories and provide insight into the adaptation and resilience of in vitro cellular systems based on tipping points. Cellular tipping points could be used to define a point of departure for risk-based prioritization of environmental chemicals.Shah I, Setzer RW, Jack J, Houck KA, Judson RS, Knudsen TB, Liu J, Martin MT, Reif DM, Richard AM, Thomas RS, Crofton KM, Dix DJ, Kavlock RJ. 2016. Using ToxCast™ data to reconstruct dynamic cell state trajectories and estimate toxicological points of departure. Environ Health Perspect 124:910-919; http://dx.doi.org/10.1289/ehp.1409029.
Generalized Anxiety Disorder
Authors: Janet M. Torpy, Alison E. Burke, Robert M. Golub
Journal: JAMA (2011)

Generalized Anxiety Disorder Everyone worries and has fears in appropriate situations.In some circumstances, fear can be lifesaving, and the body' s response to fear is called the fight-or-flight reaction.When anxiety (worry, fear, apprehension, or unease) happens over otherwise common things or events, is difficult for the individual to control, is excessive, and lasts at least 6 months, this is called generalized anxiety disorder.Along with the other types of anxiety disorders (obsessive-compulsive disorder, panic disorder, social anxiety disorder, posttraumatic stress disorder, and phobias), generalized anxiety disorder is fairly common.Unlike the separate episodes of severe panic anxiety that occur in panic disorder, the level of anxiety fluctuates gradually in persons who have generalized anxiety disorder.Anxiety disorders affect more than 40 million adults in the United States alone, about 18% of the population.Worldwide, approximately 20% of persons who receive primary health care have anxiety disorders or depression.
Multidisciplinary approach in patients with stage IV colorectal cancer with liver metastasis (LCRC): A multidisciplinary group experience from Rimini “Infermi” city Hospital
Authors: L. Veneroni, E. Tamburini, B. Rudnas, E. Cavagna, G.M. Palini, F. Paratore, M. Roversi, G. Donati, A. Venturi, M. Valli, E. Giampalma, A.R. Lombardi, M. Fantini, G. Francioni, D. Tassinari
Journal: Annals of Oncology (2015)
Point prevalence study of antibiotic use in a paediatric hospital in Italy
Authors: M L Ciofi Degli Atti, M Raponi, A  E Tozzi, G Ciliento, J Ceradini, T Langiano
Journal: Eurosurveillance (2008)

A survey aimed to describe the prevalence of antibiotic use in hospitalised children was conducted in June 2007, in Bambino Gesù Children's Hospital in Rome which has the highest annual number of inpatients among paediatric hospitals in Italy. Data were collected by reviewing medical charts of all patients hospitalised for >48 hours. A total of 412 hospitalised children were evaluated; their median age was 42.3 months, and 55.6% were males. Antibiotics were prescribed to 181 of the 412 patients (43.9%). The prevalence was lowest (37.7%) in medical wards, higher (51.1%) in intensive care units and highest (52.2%) in surgical wards. Of the patients treated with antibiotics in surgical wards, 71% received the treatment as prophylaxis. The most frequently prescribed antibiotics were ceftazidime and the combination of amoxicillin and clavulanic acid. The observed prevalence of antibiotic use was within the range recently reported from other paediatric hospitals in Europe; however, it is advisable to collect data from all over the country in order to identify priority areas and design interventions. These results also highlight the need to implement guidelines for surgical prophylaxis in children, and to further investigate reasons for prescription of parenteral antibiotic therapy in paediatric hospitals.
Whole-body diffusion-weighted MRI: a new gold standard for assessing disease burden in patients with multiple myeloma?
Authors: C Pawlyn, L Fowkes, S Otero, J R Jones, K D Boyd, F E Davies, G J Morgan, D J Collins, B Sharma, A Riddell, M F Kaiser, C Messiou
Journal: Leukemia (2015)

Whole-body diffusion-weighted MRI: a new gold standard for assessing disease burden in patients with multiple myeloma?
<i>MSH2</i> Dysregulation Is Triggered by Proinflammatory Cytokine Stimulation and Is Associated with Liver Cancer Development
Authors: Yuji Eso, Atsushi Takai, Tomonori Matsumoto, Tadashi Inuzuka, Takahiro Horie, Koh Ono, Shinji Uemoto, Kyeryoung Lee, Winfried Edelmann, Tsutomu Chiba, Hiroyuki Marusawa
Journal: Cancer Research (2016)

Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here, we demonstrated that TNFα stimulation induced transcriptional downregulation of MSH2, a member of the mismatch repair family, via NF-κB-dependent miR-21 expression in hepatocytes. Liver cancers developed in ALB-MSH2(-) (/) (-)AID(+), ALB-MSH2(-) (/) (-), and ALB-AID(+) mice, in which MSH2 is deficient and/or activation-induced cytidine deaminase (AICDA) is expressed in cells with albumin-producing hepatocytes. The mutation signatures in the tumors developed in these models, especially ALB-MSH2(-) (/) (-)AID(+) mice, closely resembled those of human hepatocellular carcinoma. Our findings demonstrated that inflammation-mediated dysregulation of MSH2 may be a mechanism of genetic alterations during hepatocarcinogenesis. Cancer Res; 76(15); 4383-93. ©2016 AACR.
Placental Pathology Associated with Household Air Pollution in a Cohort of Pregnant Women from Dar es Salaam, Tanzania
Authors: Blair J. Wylie, Emmanuel Matechi, Yahya Kishashu, Wafaie Fawzi, Zul Premji, Brent A. Coull, Russ Hauser, Majid Ezzati, Drucilla J. Roberts
Journal: Environmental Health Perspectives (2016)

Smoke from the burning of biomass fuels has been linked with adverse pregnancy outcomes such as low birth weight, stillbirth, and prematurity.To identify potential underlying mechanisms of adverse perinatal outcomes, we explored the association of placental pathology with household air pollution in pregnant women from urban/periurban Tanzania who cook predominantly with charcoal.Between 2011 and 2013, we measured personal exposures to fine particulate matter (PM2.5) and carbon monoxide (CO) over 72 hr among a cohort of Tanzanian pregnant women. Placentas were collected after delivery for examination. Placental pathologies of inflammatory, hypoxic, ischemic/hypertensive, infectious and thrombotic etiologies were diagnosed, blinded to exposure levels. Using multiple logistic regression, we explored the association of PM2.5 and CO exposure with placental pathology.One hundred sixteen women had personal air exposure measurements and placental histopathology available for analysis. PM2.5 and CO exposures were moderate [geometric means (GSD) were 40.5 μg/m3 (17.3) and 2.21 ppm (1.47) respectively]; 88.6% of PM2.5 measurements exceeded World Health Organization air quality guidelines. We observed an increase in the odds (per 1-unit increase in exposure on the ln-scale) of fetal thrombotic vasculopathy (FTV) both with increasing PM2.5 [adjusted odds ratio (aOR) = 5.5; 95% CI: 1.1, 26.8] and CO measurements (aOR = 2.5; 95% CI: 1.0, 6.4) in adjusted models only. FTV also was more common among pregnancies complicated by stillbirth or low birth weight.Fetal thrombosis may contribute to the adverse outcomes associated with household air pollution from cook stoves during pregnancy. Larger studies are necessary for confirmation. Citation: Wylie BJ, Matechi E, Kishashu Y, Fawzi W, Premji Z, Coull BA, Hauser R, Ezzati M, Roberts D. 2017. Placental pathology associated with household air pollution in a cohort of pregnant women from Dar es Salaam, Tanzania. Environ Health Perspect 125:134-140; http://dx.doi.org/10.1289/EHP256.
The successful professional woman: on being married to one
Authors: T Nadelson, L Eisenberg
Journal: American Journal of Psychiatry (1977)

Feminity and professionalism traditionally have been regarded as incompatible. From their own experience and that of colleagues and patients, the authors argue that female personhood is enriched by professional committment. In consequence, the woman with a career becomes a more stimulating spouse and parent. Problems of role differentiation and of time allocation stress the dual-career marriage, but coping with those stresses enhances personal growth and leads to a more rewarding marital relationship. The authors consider themselves the most fortunate of men.
FRI0318 Serum URIC Acid as an Independent Risk Factor on Progression of Chronic Kidney Disease in Gout Patients with URIC Acid Lowering Agent
Authors: E.-J. Park, E.Y. Hee, S. Lee, J. Hwang, E.-J. Kwon, J. Kim, E.-M. Koh
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Hyperuricemia is particularly common in patients with chronic kidney disease (CKD). Its role, however, as a risk factor for renal outcomes of CKD is debated and those data in gout patients with CKD are rare. <h3>Objectives</h3> This aim of study was to evaluate long-term effect of serum uric acid (SUA) level on progression of CKD in gout patients with uric acid lowering treatment. <h3>Methods</h3> All patients who had a first visit for gout with CKD at Samsung Medical Center between 1995 and 2003, and follow-up until December 2012 or expired during follow-up period were included and retrospective analyzed. CKD was defined as an estimated glomerular filtration rate GFR) of &lt;60 mL/min/1.73m<sup>2</sup> via the Modification of Diet in Renal Disease Study equation more than 3 months according to the Kidney Disease Outcome Quality Initiative CKD classification. All serum creatinine and matched SUA taken during follow-up period were analyzed by using mixed effect model to determine the effect of SUA level on renal outcome. <h3>Results</h3> One-hundred eleven gout patients with CKD were observed. The mean age of the patients at diagnosis of gout was 51.3 and mean follow-up duration was 13 years. Baseline estimated GFR and serum creatinine were 47.7 mL/min/1.73m<sup>2</sup> and 1.62 mg/dL, respectively. Eight (7.2%) patients revealed CKD stage 4 and the rest of patients (92.8%) were CKD stage 3. Maintaining the SUA below 6 mg/dL showed protective effect on serum creatinine and estimated GFR compared with maintaining SUA more than 6 mg/dL (<i>p</i> &lt;0.0001 and <i>p</i> =0.02, respectively). The elevation of SUA as a continuous variable was also related to poor renal outcome in gout patients with CKD (<i>p</i> &lt;0.0001). This effect of SUA on progression of CKD was not changed after adjusting for duration of gout and age at baseline, time-dependent hypertension, diabetes mellitus, hyperlipidemia, obesity, intrinsic renal diseases, and obstructive renal diseases. In particular, for every 1 mg/dL increase of the SUA, serum creatinine revealed to be increased by 0.019 mg/dL in group with SUA more than 6 mg/dL. Hypertension, diabetes mellitus and intrinsic renal disease were independent risk factors for progression of CKD in gout patients (<i>p</i> &lt;0.0001, <i>p</i> &lt;0.0001 and <i>p</i> =0.014, respectively). <h3>Conclusions</h3> Our long term follow-up data demonstrated the SUA level was independent risk factor for progression of CKD in gout patients with uric acid lowering treatment. Maintaining of SUA level below 6 mg/dL would be essential to protect renal function in gout patients with CKD. <h3>Disclosure of Interest</h3> None declared
233TiP A randomized phase II trial of neoadjuvant chemotherapy compared with chemoradiotherapy in locally advanced gastroesophageal and gastric adenocarcinoma
Authors: J. Jin, X. Wang, D.B. Zhao, Y. Chi, H. Zhao, L. Yang, A.P. Zhou, L.M. Jiang, Y. Tang, H. Ren, N. Li, W.Y. Liu, Y.X. Li
Journal: Annals of Oncology (2015)
Chemotherapy Pharmacodynamics and Neuroimaging and Neurocognitive Outcomes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia
Authors: Kevin R. Krull, Yin Ting Cheung, Wei Liu, Slim Fellah, Wilburn E. Reddick, Tara M. Brinkman, Cara Kimberg, Robert Ogg, Deokumar Srivastava, Ching-Hon Pui, Leslie L. Robison, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2016)

To examine associations among methotrexate pharmacodynamics, neuroimaging, and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy-only protocol.This longitudinal study linked pharmacokinetic assays collected during therapy to neurocognitive and brain imaging outcomes during long-term follow-up. A total of 218 (72.2%) of 302 eligible long-term survivors were recruited for outcome studies when they were more than 5 years post-diagnosis and older than 8 years of age. At long-term follow-up, survivors were an average of 13.8 years old and 7.7 years from diagnosis, and 51% were male. Neurocognitive testing, functional magnetic resonance imaging (MRI) during an executive function task, and structural MRI with diffusion tensor imaging were conducted. Generalized linear models were developed to identify predictors, and models were adjusted for age at diagnosis, sex, and parent education.Intelligence was within normal limits (mean, 98; standard deviation, 14) compared with population expectations (mean, 100; standard deviation, 15), though measures of executive function, processing speed, and memory were less than population means (all P < .02 after correction for false discovery rates). Higher plasma concentration of methotrexate was associated with a poorer executive function score (P < .02). Higher plasma methotrexate was also associated with higher functional MRI activity, with thicker cortices in dorsolateral prefrontal brain regions, and with white matter microstructure in the frontostriatal tact. Neurocognitive impairment was associated with these imaging findings as well. Associations did not change after adjustment for age or dose of leucovorin rescue.Survivors of childhood acute lymphoblastic leukemia treated on contemporary chemotherapy-only protocols demonstrate executive dysfunction. A higher plasma concentration of methotrexate was associated with executive dysfunction as well as with a thicker cortex and higher activity in frontal brain regions, regions often associated with executive function.