tbuckley/cabot-search huggingface dataset:
Out of hours care
Authors: A Z Kadri
Journal: BMJ (1995)

Working as a general practitioner in the NHS for the past 10 years I too have often used the analogy of the juggler: all the balls are not equal-more harm is caused if we drop some balls than if we drop others.I together with many of my colleagues have become demoralised and exhausted juggling with so many balls.Every so often someone throws yet another ball our way.We are finding that it is less and less enjoyable to juggle-what is more, we are dropping more and more balls and too many are getting damaged.In my metaphor the balls represent medical condition-treatment pairs.An imagined contract with our patients might go like this: would you allow us to drop breast reconstruction after mas- tectomy so that we can guarantee that we will always be able to treat triple vessel coronary disease within three months?By advocating explicit rationing, I am suggesting that we health workers drop some of the balls so that it becomes a joy to juggle again.The consequence of this is that the balls which really matter will stay in the air.
Abstract 20353: Serum and Glucocorticoid-Regulated Kinase 1 (SGK1) Activation Predisposes to Lethal Reperfusion Ventricular Arrhythmias while Inhibition Is Protective in a Mouse Model of Ischemia-Reperfusion
Authors: Saumya Das, Chun Yang Xiao, Katherine Hessler, Ashley Knight, Evan L Graham, Anthony Rosenzweig
Journal: Circulation (2010)

Background: Transgenic (TG) mice with cardiac-specific expression of constitutively-active SGK1 (SGK1-CA) have cardiac dysfunction, ventricular arrhythmias (VA), and increased persistent Na current INaL. Expression of dominant negative SGK1 (SGK1-DN) in the heart protects against progression to heart failure following pressure-overload. We tested the hypothesis that SGK1 activation may be deleterious, while inhibition may be beneficial in a mouse model of ischemia/reperfusion (I/R). Methods: TG mice and age-matched wild-type (WT) littermates were subjected to 30 min. ischemia and either 24 hour (acute I/R) or 4 weeks reperfusion (chronic I/R). Heart rhythm was monitored acutely and by implanted recorders for 24 hours following I/R. Harvested hearts were analyzed for infarct size, area at risk and TUNEL positive cells. Results: SGK1-CA TG mice subjected to I/R had an increase in mortality (8/10) compared with WT (7/29) or SGK1-DN mice (2/16), p =0.006. There was a trend towards increased PVCs in the SGK-CA...
Gender differences in personality disorders
Authors: M Golomb, M Fava, M Abraham, J F Rosenbaum
Journal: American Journal of Psychiatry (1995)

The aim of this study was to assess gender differences in personality disorders. Since heterogeneity of axis I diagnoses could introduce variability in the assessment of axis II diagnoses, the authors studied a group of patients with a primary diagnosis of major depression.A total of 316 patients were evaluated with the Personality Diagnostic Questionnaire--Revised, a self-rating measure, or the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II), a clinician-rated instrument, or both. Axis II disorders were assessed with the Personality Diagnostic Questionnaire--Revised for 288 patients with major depression. The SCID-II was administered to 117 subjects, with an additional 95 subjects receiving the SCID-II for cluster B diagnoses only.The mean 17-item Hamilton Depression Rating Scale scores for 108 men (mean age = 39.28 years) and 208 women (mean age = 39.11) were 19.0 (SD = 3.8) and 19.6 (SD = 6.9), respectively. Men were significantly more likely than women to meet criteria for narcissistic, antisocial, and obsessive-compulsive personality disorders as measured by the Personality Diagnostic Questionnaire--Revised and for narcissistic and obsessive-compulsive personality disorders as measured by the SCID-II.These findings are consistent with those of previous studies showing a greater prevalence of antisocial and narcissistic personality disorders in men. In contrast with other investigations, however, neither the Personality Diagnostic Questionnaire--Revised nor the SCID-II revealed a higher prevalence of any personality disorder in women.
Abstract 17689: Imaging Mitochondrial Function of Mesenchymal Stem Cells Transplanted to the Myocardium
Authors: Federico Franchi, Karen M Peterson, Ramasamy Paulmurugan, Amir Lerman, Martin G Rodriguez-Porcel
Journal: Circulation (2014)

Introduction: Stem cells have poor survival after transplantation, what can limit the use of these therapies. Mitochondrial dysfunction has been recognized as a limiting event that can lead to cell death. Here, we hypothesized that the mitochondrial function of progenitor cells can be monitored in vivo using reporter gene-based molecular imaging. A better understanding of the biology of transplanted stem cells in the ischemic myocardium can lead to optimization of cell therapies. Methods: Using RT-PCR we identified the antioxidant NAD(P)H:Quinone oxidoreductase (NQO1) enzyme as a marker of mitochondrial dysfunction in mouse Mesenchymal Stem Cells (MSCs) that were treated with a mitochondrial stressor, diethyl maleate (DEM). We then constructed a luciferase reporter gene driven by the NQO1 promoter. After in vitro validation, MSCs were transplanted into a mouse model of ischemia/reperfusion (IR, n=4) and mitochondrial function was monitored by bioluminescence imaging. Results: MSCs treated with DEM had an increase in NQO1 reporter gene signal that inversely correlated with the amount of the mitochondrial by-product adenosine tri-phosphate (ATP, r = -0.9643, p = 0.0028; Fig 1A). Mitochondrial dysfunction was preserved by the use of a mitochondria-targeted antioxidant Mito-Tempo (MT), correcting ATP and NQO1 luciferase signal. In vivo studies showed that MSCs yielded higher Firefly luciferase activity in IR mice compared to sham and this signal was normalized when cells were pre-treated with MT (Fig 1B). Data was confirmed by ex vivo measurement of Firefly luciferase activity, which was 4.9-fold higher in the IR group than in shams, after correction for cell number (Fig 1C). Conclusions: We have developed a novel imaging strategy that allows noninvasive assessment of the mitochondrial status of transplanted stem cells in the ischemic myocardium. Knowing when transplanted cells “suffer’ from mitochondrial dysfunction may allow optimization of these therapies.
The Belgian cord blood banking project: Hematological results and practical issues
Authors: Y. Beguin, Bénédicte Brichard, Christiane Vermylen, Guy Cornu, C Debruyn, Marc De Bruyère, D Hemptinne, A Delforge, Véronique Deneys, G. Fillet, I Joris, Philippe Lefèvre, M Massy, JM Paulus, N Raymakers, Jp. Schaaps, D. Sondag, Vancauwenberge, P Strijckmans
Journal: Blood (1995)
Long-term results of treatment of bone sarcomas in a developing country. Indian perspective of last 3 decades
Authors: A. Chandra
Journal: Journal of Clinical Oncology (2005)

9067 Objectives: Treatment outcomes of patients with two most common primary malignant bone sarcomas (Osteosarcoma and Ewings’ Sarcoma) has changed over last three decades. Few studies have been reported less developed countries. We report here our experience in last 3 decades from a Regional Cancer centre, Cancer Institute (WIA), Chennai, India. Patients and Methods: 897 patients registered from January 1970 to December 1999, 499 were evaluable for survival analysis. 328 were non-metastatic Osteogenic sarcoma and 171 were non-metastatic Ewings sarcoma Event free survival (EFS) rates and 95% confidence intervals (CI) by Kaplan Meier analysis. Prognostic factors were identified by Log-rank statistics, Cox and Logistic regression. Prior to 1985 we had limited access to chemotherapy drugs and radical resection was the treatment offered. After 1985 patients had neo-adjuvant chemotherapy and limb sparing local treatment of primary tumour. Results: On December 2004, 5 years EFS of Osteogenic sarcoma treated during 1970–1985 (n=70) was 0.32 (95% CI 0.26–0.42) which improved to 64% during the latter time period (n=198) which was statistically significant. EFS of Ewings sarcoma 5 years after diagnosis was 0.063 and improved to 0.53 (p< 0.05). Metastatic tumour, large volume disease, chemotherapy response non-compliance to therapy were adverse prognostic factors. Conclusion: Limited resources, multiple constraints and among other difficult factors we had improvement in our supportive care, surgical techniques, radiation therapy. Oncology in a developing country is challenging No significant financial relationships to disclose.
First human case of Usutu virus neuroinvasive infection, Italy, August-September 2009
Authors: M Pecorari, G Longo, W Gennari, A Grottola, A MT Sabbatini, S Tagliazucchi, G Savini, F Monaco, M L Simone, R Lelli, F Rumpianesi
Journal: Eurosurveillance (2009)

We report the first worldwide case of Usutu virus (USUV) neuroinvasive infection in a patient with diffuse large B cell lymphoma who presented with fever and neurological symptoms and was diagnosed with meningoencephalitits. The cerebrospinal fluid was positive for USUV, and USUV was also demonstrated in serum and plasma samples by RT-PCR and sequencing. Partial sequences of the premembrane and NS5 regions of the viral genome were similar to the USUV Vienna and Budapest isolates.
Abstract 2616: RFX1-dependent activation of SHP-1 inhibits STAT3 signaling in hepatocellular carcinoma cells
Authors: Jung-Chen Su
Journal: Cancer Research (2014)

Abstract Obatoclax is under clinical trial currently. Previously, we have demonstrated that SC-2001, an obatoclax analogue, has potent anti-tumor effect in HCC cells through the SHP-1/p-STAT3 cascade. However, the molecular mechanism by which SC-2001 activates SHP-1 is still elusive. Regulatory factor X (RFX) 1 is a transcription factor that has been linked to negative regulation of tumor progression. Nevertheless, its biological function in HCC cells is far from clear. In this study, by modulating its expression, we demonstrated that RFX1 is important in regulating SHP-1 in HCC cells. Ectopic expression of RFX1 can lead to activation of SHP-1 and inhibition of colony forming in HCC cells. Importantly, in a xenograft mouse model, RFX-1 overexpression obviously inhibited the growth rate of HCC tumors, indicating its tumor suppressor role. In addition, we found that SC-2001-induced apoptosis effect is regulated by RFX1. We showed that SC-2001 enhanced RFX1 nuclear translocation and binded to SHP-1 promoter to activate SHP-1 transcription. Moreover, knockdown of RFX1 reversed the anti-tumor effect of SC-2001 in vivo. Most important, we proved that SC-2001 displayed more potent anti-tumor effect than sorafenib, a clinically approved drug for HCC, in in vitro and in vivo assays. Furthermore, combination treatment of SC-2001 and sorafenib showed synergistic effect in HCC cells. Collectively, our study confirmed that RFX1 acts as a tumor suppressor in HCC and might be a new target for HCC therapy. The findings of this study also provide a new lead compound for target therapy via the activation of the RFX1/SHP-1 pathway. (Supported by NSC-102-2325-B-010-007) Citation Format: Jung-Chen Su. RFX1-dependent activation of SHP-1 inhibits STAT3 signaling in hepatocellular carcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2616. doi:10.1158/1538-7445.AM2014-2616
Respiratory function in elderly with 'senile' or 'juvenile' pulmonary phenotype: Results from the KORA-Age study
Authors: Holger Schulz, Jürgen Behr, Rudolf M. Huber, Dennis Nowak, Joachim Heinrich, Annette Peters, Rudolf A. Jörres, Stefan Karrasch
Journal: European Respiratory Journal (2012)

Background:  Lung function, typically assessed by spirometry, is a strong predictor for overall morbidity and mortality. To improve our mechanistic understanding we examined whether poor spirometric lung function is associated with general respiratory limitations in elderly subjects with apparently healthy lungs.   Methods:  Spirometry was performed in a random population sample from the region of Augsburg, Germany (n=935, aged 65-90y). From subjects free of lung disease (COPD, Asthma) two subgroups with either poor (9senile9; n=87) or favourable (9juvenile9; n=82) lung function were selected from the lower and upper 10% of the FEV1%pred distribution. TLC, DLCO, peak inspiratory pressure at RV (Pimax), the decrease in airway pressure at 0.1s (P01), and 6MWD were determined.   Results:  P01 and P01/MV were not affected by age, while spirometric values, DLCO/VA and Pimax showed an age dependent decline. 9Senile9 phenotype subjects had 10% lower DLCO (p   Discussion:  Elderly subjects with poor spirometry, while being free from overt lung disease, also suffer from age related limitations in gas exchange capacity, reduced muscle strength, and increased workload during breathing. This limited respiratory capacity may contribute to reduced physical fitness and morbidity.   Supported by German Federal Ministry of Education and Research (BMBF FKZ 01ET0713) as part of the 9Health in old age9 program .
Abstract P438: Staying Active improves Insulin Resistance independent of the Metabolic Syndrome and Obesity
Authors: Ebenezer T Oni, Wasim Muzaik, Michael J Blaha, Arthur S Agatston, Roger S Blumenthal, Raquel D Conceiçao, Romeu S Meneghelo, Carvalho A J, Raul D Santos, Khurram Nasir
Journal: Circulation (2014)

Background: The progression of cardio-metabolic disease is believed to be driven by increasing Insulin resistance (IR). While increased physical activity (PA) is often encouraged among individuals with metabolic syndrome to improve their IR, there is limited information on its impact among individuals without metabolic syndrome (MS) or obesity. We aimed to ascertain the effect of PA on IR across a spectrum of metabolic conditions. Methods: We evaluated 5,795 healthy Brazilian subjects (43±10 years, 79% males) without clinical coronary heart disease between November 2008 and July 2010. We defined IR using Triglyceride: High Density Lipoprotein-Cholesterol ratio (TG: HDL) &gt; 3.0. PA was assessed using the International Physical Activity Questionnaire (IPAQ) scale and MS was classified with the IDF criteria. Obesity was defined as having a BMI ≥ 30. Results: The prevalence of IR was 39% (n=2,233), 1,316 (23%) were obese and 1,161 (20%) had metabolic syndrome. IR was significantly higher among individuals with the metabolic syndrome (84%) vs. individuals with no metabolic syndrome (27%), p&lt;0.001. Overall 1,308 (23%) were sedentary, 2,008 (35%) minimally active and 2,473(42%) very active. There were significant reduction in IR prevalence with increasing physical activity (sed: 48%, minimally active: 43%, active= 31%, p&lt;0.001). As shown in table below, after adjusting for confounding variables, higher activity levels was 20-56% less likely associated with IR. The benefits appeared to extend to individuals with and without MS or Obesity. Conclusions: PA presents a dose response association with insulin resistance independent of the MS or Obesity. Staying active has tremendous benefits in reducing insulin resistance across populations regardless of their metabolic profile.
Prospective evaluation of 2-[18F]-2-deoxy-D-glucose positron emission tomography in staging of regional lymph nodes in patients with cutaneous malignant melanoma.
Authors: D J Macfarlane, V Sondak, T Johnson, R L Wahl
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess prospectively the accuracy of 2-[l8F]-2-deoxy-D-glucose positron emission tomography (FDG-PET) for predicting regional node involvement in cutaneous malignant melanoma (CMM). PATIENTS AND METHODS Twenty-three patients with CMM (primary lesions &gt; 1.5 mm thick) scheduled for lymph node dissection (LND) were preoperatively studied with FDG-PET. Thirteen patients underwent therapeutic LND of 14 node basins, while nine patients had elective LND of 10 node basins. Medical problems precluded surgery in one patient. Two observers unaware of the clinical node status-apart from whether a recent surgical scar was present-read attenuation-corrected reconstructed transverse images acquired between 50 and 60 minutes after injection. Intensity of FDG uptake was scored as 0 to 3 + on a semiquantitative four-point scale: 0, no uptake; 1 +, faint; 2 +, moderate; and 3 +, intense uptake. A node group was considered positive on FDG-PET if it contained at least one focus of FDG uptake of &gt; or = 2+ intensity. Histopathologic examination of the 24 dissected node groups served as a reference. RESULTS Considering regional node basins, PET imaging demonstrated 11 true-positive (TP), 10 true-negative (TN), two false-negative (FN), and one false-positive (FP) result, for an overall accuracy of 88%. Histopathologic from one FN case showed seven malignant cells in a marginal node sinus. The FP was due to reactive changes postbiopsy. In one patient, clinically involved lymph nodes were correctly categorized TN by PET. At least four additional 2 + foci seen outside the dissected regions on PET may represent metastases and are being monitored. CONCLUSION FDG-PET accurately predicted regional node status in 88% of CMM cases. The failure to detect micrometastatic disease may be due to the limitations of the imaging equipment and technique used here.
Abstract 15758: Peak Oxygen Consumption Does Not Depend on Aortic Valve Opening During Exercise in Patients with a Continuous Flow Left Ventricular Assist Device
Authors: Jose Gonzalez-Costello, Lindsay K Murray, Sofia Shames, Agnes Koczo, Nir Uriel, Daniel B Sims, Paolo C Colombo, Hiroo Takayama, Yoshifumi Naka, Linda D Gillam, Ulrich P Jorde
Journal: Circulation (2011)

Introduction: Patients with heart failure and a continuous flow left ventricular assist device (LVAD) have an increased incidence of aortic insufficiency. Closing the aortic valve (AV) at the time ...
Tau pathogenesis is promoted by Aβ1-42 but not Aβ1-40
Authors: Xiaoyan Hu, Xiaoling Li, Mingrui Zhao, Andrew Gottesdiener, Wenjie Luo, Steven Paul
Journal: Molecular Neurodegeneration (2014)

The relationship between the pathogenic amyloid β-peptide species Aβ1–42 and tau pathology has been well studied and suggests that Aβ1–42 can accelerate tau pathology in vitro and in vivo. The manners if any in which Aβ1–40 interacts with tau remains poorly understood. In order to answer this question, we used cell-based system, transgenic fly and transgenic mice as models to study the interaction between Aβ1–42 and Aβ1–40. In our established cellular model, live cell imaging (using confocal microscopy) combined with biochemical data showed that exposure to Aβ1–42 induced cleavage, phosphorylation and aggregation of wild-type/full length tau while exposure to Aβ1–40 didn't. Functional studies with Aβ1–40 were carried out in tau-GFP transgenic flies and showed that Aβ1–42, as previously reported, disrupted cytoskeletal structure while Aβ1–40 had no effect at same dose. To further explore how Aβ1–40 affects tau pathology in vivo, P301S mice (tau transgenic mice) were injected intracerebrally with either Aβ1–42 or Aβ1–40. We found that treatment with Aβ1–42 induced tau phosphorylation, cleavage and aggregation of tau in P301S mice. By contrast, Aβ1–40 injection didn't alter total tau, phospho-tau (recognized by PHF-1) or cleavage of tau, but interestingly, phosphorylation at Ser262 was shown to be significantly decreased after direct inject of Aβ1–40 into the entorhinal cortex of P301S mice. These results demonstrate that Aβ1–40 plays different role in tau pathogenesis compared to Aβ1–42. Aβ1–40 may have a protective role in tau pathogenesis by reducing phosphorylation at Ser262, which has been shown to be neurotoxic.
Human podocytes rapidly utilize glucose by both GLUT1 and GLUT4 in response to insulin; with significant differences in glucose transporter levels occurring in diabetic nephropathy
Authors: R J M Coward, G I Welsh, G D Holman, D Kerjaschki, J M Tavare, P W Mathieson, M A Saleem
Journal: Journal of the American Society of Nephrology (2003)
Lesson of the week: Treatment resistant epilepsy or convulsive syncope?
Authors: A. Zaidi, P. Clough, B. Scheepers, A. Fitzpatrick
Journal: BMJ (1998)

The diagnosis of epilepsy is complicated by various conditions that can mimic an epileptic seizure, and cardiovascular conditions causing syncope may account for many cases of so called secondary seizures.1 Convulsive syncope—that is, cerebral anoxic seizure activity secondary to transient global impairment of blood flow—can be difficult to differentiate from epilepsy. The differentiation is, however, important because syncope can be treated effectively, especially when it is due to a bradycardia.1 In addition, long term anticonvulsant treatment is expensive and can cause serious morbidity.2 We present the cases of three patients thought to have treatment resistant epilepsy who were subsequently found to have a cardiac condition.

### Case 1

A 32 year old woman was referred to the epilepsy clinic in January 1995 with a four year history of recurrent blackouts. She described episodes in which she became weak and had to lie on the floor followed by loss of consciousness lasting for about 1 minute with clenching of her fist and sometimes jerking, especially of the legs, but no incontinence or tongue biting. She normally recovered quickly, although she was tired afterwards. The episodes occurred up to four times a week. In 1991, a 72 hour electroencephalogram had given normal results, but a trace taken after sleep deprivation showed some left sided slow wave changes. She was started on phenytoin for presumed epilepsy. She subsequently tried several anticonvulsant drugs including lamotrigine, sodium valproate, clobazam, vigabatrin, carbamazepine, and gabapentin with no significant improvement apart from a short period when clobazam was introduced. Her condition had deteriorated with gabapentin.

At referral …
Follow-up of Asbestos-exposed Individuals Using Mesothelioma Serum Biomarkers
Authors: K. Hollevoet, J. Van Cleemput, J. Thimpont, P. De Vuyst, L. Bosquée, Kristiaan Nackaerts, Y. Kishi, Catherine Legrand, J. R. Delanghe, J. P. van Meerbeeck
Journal: Journal of Thoracic Oncology (2010)
Risk language and dialects
Authors: D M Campbell, P. Barclay, S. Costigan, M. Davies, J. Murty
Journal: BMJ (1998)

Editor—Calman and Royston remind health professionals of their obligation to communicate risk in a language and dialect with which individuals or groups are comfortable.1 It is not only in clinical medicine that appropriate communication of risk is essential. The environmental health literature is littered with examples of failed dialogue. 

Communities often create risk dichotomies, demanding absolute safety and being unable to perceive any grey areas between safe and dangerous. On occasion this may be correct—for example, should we evacuate or not? Environmental standards tend to dichotomise. If the standard is 15 ppb, people may deduce that 14 ppb is safe and 16 ppb dangerous. Expressing risk in relative rather than absolute terms, as shown by Calman and Royston, avoids making an environmental standard into a watershed figure with all results above the standard perceived as dangerous and everything below the standard as safe. Risk numbers should be expressed in ranges, such as 1-9 ppb as low risk, 10-19 as moderate risk, etc. 

Several elements of risk can be used to describe risk to communities. Among these are concentrations (for example, g/l); exposures (how much is likely to be inhaled?); probabilities (how likely is it to happen?); quantities (how much effluent was released?); and risk levels (expected deaths per year). All of these outline different aspects of risk, but practitioners often confuse elements when attempting to put risks into context. Saying that a risk is like a drop in a swimming pool may be misleading: a small concentration of a hazardous chemical could be associated with a substantial risk. It also may not answer the question the public is asking. Questions about risk require answers about risk. Calman and Royston’s model is a useful contribution to the task.