tbuckley/cabot-search huggingface dataset:
TALEN-mediated functional correction of X-linked chronic granulomatous disease in patient-derived induced pluripotent stem cells
Authors: Anne-Kathrin Dreyer, Dirk Hoffmann, Nico Lachmann, Mania Ackermann, Doris Steinemann, Barbara Timm, Ulrich Siler, Janine Reichenbach, Manuel Grez, Thomas Moritz, Axel Schambach, Toni Cathomen
Journal: Biomaterials (2015)
Neck Pain with Fever
Authors: A R Saha, A M Blackburn
Journal: Journal of the Royal Society of Medicine (1999)

Syrinx was an Arcadian virgin who, when pursued by Pan, turned into a reed, from which Pan made his pipes. She gave her name to the tubular cavitation of the spinal cord. Post-traumatic syrinx is well described in patients with delayed neurological deterioration after spinal cord injury3'4. The period from injury to onset of symptoms is up to 33 years3. Proposed pathophysiological mechanisms include the slosh theory, the suck theory and coalescence of microcysts4. There is probably no benefit in operating on a patient with a small post-traumatic syrinx4. Cord tethering has only occasionally been reported as a late complication of spinal trauma5'6. Repeated abnormal movement at the damaged region and the spinal canal stenosis occurring with age might explain its delayed onset6. Once tethering occurs, it impairs cord function by mechanical distortion or ischaemia5. Detethering has been reported to improve the clinical condition5'6 and in our patient it abolished Lhermitte's sign and the upper limb symptoms.
Abstract 13764: Impact of Endothelial Dysfunction Improvement After Exercise Training on Prognosis in Patients With Recent Myocardial Infarction.
Authors: Margherita Vona, Tiziana Iannino, Serena De Pascalis, Cristina Gallardo, Stephan Cook, Bernard Vermeulen
Journal: Circulation (2010)

Background: In coronary artery disease the endothelial dysfunction is an important predictor of cardiac events. Exercise training (ET) is associated with an improvement of endothelial function (EnF...
Transcriptionally targeted synthetic gene medicines combine anti-cancer activity of therapeutic genes and cationic polymer to achieve long term responses in established solid tumors after systemic adminstration
Authors: Andreas G. Schätzlein, Christine Dufes, Nicol Keith, Alan Bilsland, Ijeoma Uchegbu
Journal: Cancer Research (2006)

4021   Treatment of inaccessible tumors and metastases requires systemic delivery of genes with the help of synthetic or viral vector systems. These nanomedicines have to travel in the blood stream to the tumor, extravasate and traverse the interstitium to reach the cancer cell. A synthetic vector system based on polypropylenimine dendrimer nanocomplexes has the capability to act as a systemic delivery vehicle and mediates efficient transgene expression in tumors after intravenous administration. We have chosen a plasmid expressing the potent cytokine TNFa to explore whether such gene medicines are able to express therapeutically significant amounts of protein. As the TNFa protein is highly toxic on systemic administration we also explored whether such systems when transcriptionally target to the tumor would be able to overcome this toxicity. We found that the systemic tumor necrosis factor alpha (TNFa) gene therapy was efficacious in the experimental treatment of established A431 epidermoid carcinoma, C33a cervix carcinoma and LS174T colorectal adenocarcinoma. Specifically, the systemic injection of dendrimer nanoparticles containing a TNF alpha expression plasmid regulated by telomerase gene promoters (hTR, hTERT) leads to transgene expression, regression of remote xenograft murine tumors, and long term survival of up to 100% of the animals. Interestingly, these dendrimers and to a lesser extend other common polymeric transfection agents also exhibit plasmid-independent anti-tumor activity, ranging from pronounced growth retardation to complete tumor regression. The genetic therapy as well as treatment with dendrimer alone were well tolerated with no apparent signs of toxicity in the animals. The combination of intrinsic dendrimer activity and transcriptionally targeted TNFa when complexed was significantly more potent than either treatment alone or when both were administered in sequence. Futhermore, the synthetic vector has now also been tested in conjunction with other therapeutic genes such as p53 with good success.
Prospective randomized study comparing fourth-week surgery versus eighth- week surgery after neoadjuvant concomitant radiotherapy and infusional 5-FU in T3–4/N0+ rectal cancer: Istanbul R-01 Study
Authors: S. Saglam, D. Bugra, E. Kaytan Saglam, S. Yamaner, O. Asoglu, E. Balik, E. N. Oral, B. Sakar, A. Kizir, Y. Kapran, H. Camlica
Journal: Journal of Clinical Oncology (2009)

4131 Background: Prospective randomized study has been designed to compare the efficacy of fourth week surgery (4WS) versus eighth week surgery (8WS) after concomitant neoadjuvant chemoradiotherapy (NeoadjCTRT) on local recurrence and overall survival (OS) in cT3–4/N0+, mid and distal localized (intraperitoneal) rectal cancers. Pathological regression grades (PRG;Dworak) were evaluated after neoadjCTRT. Methods: During Jan 2002- Nov 2007; 170 pts were randomized to the study in Istanbul University Oncology Institute and Medical Faculty. All rectal cancer pts are T3–4/N0+; distal and mid rectum and received 45 Gy conventionally fractionated RT in 25 daily fractions of 1.8 Gy combined with 225 mg/m 2 /day continous infusion 5-FU. Preoperative staging was performed by endorectal USG and /or MRI and abdominal CT.4cycles FUFA is standard as adjuvant treatment after surgery. Results: 17 pts have been removed (M1, frozen pelvis, refuse surgery, disease progression). Clinical T3N+ was 60.8% before surgery. 76 pts were operated at 4WS and 77 pts at 8WS. Median follow-up was 30 (2–71) months. APR was 31.4%. LAR was 68.6%. Surgical margin positiveness (SMP) and &lt;2mm were detected in 14 pts. R0 resection rate was 90.8%. Median harvested lymph node number were 13. PRG were PRG 0 (1.3%); PRGI in (24.2%); PRGII in (40.5%); PRGIII (17%); PRGIV in (17%). There is no statistical significance between 4WS vs 8WS on pathological regression scores. Local recurrence developed in 8 pts (PRGI:3pts; PRGII:4; PRGrIV:1). There is no statistical difference 4WS v 8WS on local recurrence (5 pts/3). Local recurrence rate was 8.4% in distal rectum (7 pts) and 1.2% in mid rectum (1pts) (p=0.023). SMP and &lt;2mm was statistically significant in local recurrence (p=0.003). 5 years OS were similar in 4WS 75.2% and 8WS 73.9%. Distant metastasis is significant (liver, lung, bone) in distal rectal tumors (p=0,007). SMP or &lt; 2mm is significantly poor in OS (p&lt;0.0001). Conclusions: There is no difference 4WS vs 8WS on local recurrence, OS and PRGs. Important factors for local recurrence and (OS) are having distal rectal tumor and SMP and &lt;2mm. Distal rectal tumors have prone to distant metastases. No significant financial relationships to disclose.
Abstract 14885: CXCL4 Aggravates Mortality and Left Ventricular Dilation Following Myocardial Infarction by Polarizing Macrophages to a Pro-inflammatory M1 Phenotype
Authors: Yonggang Ma, Andriy Yabluchanskiy, Ryan Clark, Presley L Cannon, Elizabeth R Flynn, Yu-Fang Jin, Merry L Lindsey
Journal: Circulation (2014)

CXCL4 deletion attenuates atherosclerosis and mesenteric ischemia/reperfusion injury in mice. CXCL4 roles following myocardial infarction (MI) have not been evaluated. We hypothesized that CXCL4 would exacerbate post-MI wound healing and cardiac dysfunction. Male C57BL/6J mice (n=82) of 3-6 months old were subjected to permanent coronary artery ligation. CXCL4 gene expression significantly increased after MI, peaking at day 5 (p
Abstract 1521: Platelet RNA Content is Increased in Patients with Acute Coronary Syndromes Compared to Patients with stable Coronary Artery Disease and Healthy Individuals
Authors: Erik L Grove, Anne-Mette Hvas, Steen D Kristensen
Journal: Circulation (2007)

Background: Platelets newly released from the bone marrow are characterized by large cell volumes and, contrary to mature platelets, contain RNA, which might reflect an increased capacity of producing proaggregatory proteins. We hypothesized that the fraction of RNA-containing, immature platelets (Immature Platelet Fraction = IPF) is a marker for acute coronary thrombus formation. Methods: Flow cytometric determination of immature platelets was conducted using a RNA fluorescent dye and an automated analyzer (Sysmex XE-2100). Measurements were performed in a total of 426 individuals (365 patients with acute coronary syndromes (ACS), 39 patients with stable coronary artery disease (CAD) and 22 healthy individuals). Results: Geometric mean IPF was 2.5 (CV = 0.37) in the control group, 2.9 (0.43) in patients with stable CAD, 3.0 (0.55) in the non-STEMI/Unstable Angina group and 3.7 (0.56) in patients with STEMI. IPF was significantly increased in STEMI patients compared to all other groups (t-test for log-transformed data: p &lt; 0.004), and the overall difference between groups was significant (ANOVA: p &lt; 0.0001). IPF was increased in active smokers among patients with ACS (3.2 vs 3.6, p=0.02), whereas no relation with age, sex, body mass index or CRP levels was observed. Conclusion: The fraction of RNA-containing platelets is increased in ACS, especially in the acute phase of STEMI. Immature platelets with an increased haemostatic potential may contribute to coronary thrombus formation and may partly explain previous findings of temporary resistance to anti-platelet therapy.
Patients' perceptions of need for primary health care services
Authors: Q. D Sandifer, D. Shickle, S. Vuilo, S. Hopkins
Journal: BMJ (1995)

EDITOR,--Jane L Hopton and Maria Dlugolecka examine the feasibility of using patients' perceptions of need for primary health care services to develop priorities.1 Their study illustrates three important deficiencies in engaging the general public to develop priorities for health care services. Firstly, we wonder how representative the respondents were of the general population. As 64% of the respondents were home owners and 61% car owners, was recruitment principally from the upper social class? Furthermore, it would have been beneficial if …
A case of delayed bleeding after endoscopic submucosal dissection for completely circumferential esophageal cancer
Authors: Hideyuki Chiba, Keiichi Ashikari, Akihiro Takahashi, Toru Goto, Ken Ohata, Nobuyuki Matsuhashi, Atsushi Nakajima
Journal: Endoscopy (2015)

Endoscopic submucosal dissection (ESD) for early esophageal cancer is being performed more frequently. Perforation and stricture are well-known complications of esophageal ESD, but delayed bleeding is very rare. This is the first report of delayed bleeding after esophageal ESD.
Abstract 5463: Dual Channel Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-CT) of Inflammation in Murine Atherosclerotic Plaques
Authors: Matthias Nahrendorf, Peter Waterman, Ralph Weissleder
Journal: Circulation (2008)

Monocyte/macrophages play a key role in the development and progression of atherosclerotic lesions. Here we present a novel hybrid in vivo imaging approach that simultaneously reports on lesion anatomy, phagocytic activity by uptake of fluorescent nanoparticles and extracellular matrix remodeling with a protease-activatable agent, detectable with hybrid FMT-CT imaging. We co-injected 5 aged apoE deficient and 5 wild type mice with 15mg/kg of macrophage-avid nanoparticle (CLIO-680, emission 700nm) and 2nmol of a cathepsin-activatable protease reporter (Prosense-750, emission 780nm). Mice were imaged using a free space dual channel FMT system inside a cartridge that is optically translucent and has multimodal fiducial markers for image fusion incorporated in its frame. While the immobilized mice were anesthetized with isoflurane, the holding device was transferred for ECG-gated high resolution CT (isotropic resolution 50um). During CT acquisition, iodine contrast was delivered at 65ul/min via tail vein. In vivo, we found strong fluorescent signal for uptake of nanoparticles as well as protease activity (p&lt;0.05 WT vs apoE−/− mice), which was mapped to the proximal aorta on CT. Contrast enhanced CT visualized murine aortic plaques. Ex vivo fluorescence reflectance imaging and fluorescence microscopy corroborated in vivo findings and identified macrophages as target cells. FMT-CT imaging of inflammatory atherosclerosis provides quantifiable 3-dimensional maps of macrophage activity and visualizes murine aortic plaques, providing unprecedented insight into disease progression non-invasively.
Abstract 17115: Bayesian Analysis of Risk Stratification Strategies in Non-ST Elevation Acute Coronary Syndromes
Authors: Christopher Lang, Rohit Arora
Journal: Circulation (2011)

Background: Early stratification of patients with acute coronary syndromes is a critical aspect of contemporary cardiology. Risk scores are often used to help identify patients likely to benefit from early interventional strategies, based on expected short term prognosis. Additionally, understanding long term benefit from utilization of risk scores to guide intervention, as well as differential benefit of particular risk scoring strategies can help guide clinical application and management. To investigate this, we compared the PURSUIT, GRACE and TIMI risk scores for NSTEMI, evaluating mortality and non-fatal MI at one year, using Bayesian statistical methods. Methods : Using published retrospective data of 460 patients, Bayesian posterior probabilities were calculated. Risk scoring systems were stratified into high and low risk groups, based on either PURSUIT score of 14, TIMI score of 3, or a GRACE score of 133. Within these groups, early revascularization or conservative management was compared based on mortality or non-fatal MI events at 1 year. Posterior probabilities as well as probabilities of greater than 20% benefit of using a risk scoring system were calculated. Results: Based on the study results, the Bayesian posterior probability for the primary combined endpoint of death and nonfatal MI for the low risk group are 59.3% for PURSUIT, 68.8% for TIMI, and 70.1% for GRACE. The Bayesian posterior probabilities for the high risk group are 73.1% for PURSUIT, 58.6% for TIMI, and 74.0% for GRACE. Probabilities of &gt;20% predictive benefit and sensitivity analysis was calculated, and have similar trends to the posterior probabilities. Conclusions: Bayesian analysis suggests that the using low GRACE and TIMI scores for conservative management have a greater likelihood of clinical benefit than the PURSUIT risk scale. The GRACE and PURSUIT scores have a clinically relevant benefit in predicting patients deemed to be high risk undergoing early revascularization compared to the TIMI score. Overall, the GRACE score was demonstrated to be the most robust scoring system for guiding both interventional and conservative management strategies for 1 year outcomes, and should be applied more widely.
Criteria indicating physiological morbidity were too non-specific
Authors: A. Kelleher, L. Murdoch
Journal: BMJ (1996)

EDITOR,—We were interested to read Joseph Britto and colleagues' paper on the morbidity and severity of illness during interhospital transfer by a specialist paediatric retrieval team.1 It is now generally accepted that critically ill children should be cared for in a specialist paediatric intensive care setting.2 To minimise morbidity and mortality the patients should probably be …
Adenovirus-mediated PEDF expression inhibit s prostate cancer cell growth and results in augmented expression of PAI-2
Authors: Ming Guan, Haowen Jiang, Yuan Lu
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3309 

Pigment epithelium-derived factor(PEDF) is one of the most potent inhibitor of angiogenesis. Loss of PEDF was found in human prostate tumors and associated with the progression toward a metastatic phenotype. To test the therapeutic potential of PEDF, we constructed a replication-defective adenoviral vector capable of efficient transduction and expression of PEDF (Ad-PEDF) in PC-3 prostate carcinoma cells. As controls we used adenoviruses expressing beta-galactosidase (Ad-LacZ). We showed that overexpression of PEDF inhibited proliferation of cells and augmented apoptosis in serum-starved cells, in comparison with Ad-LacZ. Furthermore, Ad-PEDF suppresses anchorage-independent growth cells in soft agar and tumor formation in athymic nude mice associated with decreased microvessel density. Microarray analysis showed that 56 out of 8464 genes were found to be upregulated and downregulated in the PC-3 infected with Ad-PEDF as compared with Ad-LacZ. The differentially expressed genes cover a broad range of functional activities including catalytic activity, protein binding, signal transduction activity and cell invasion. Among them, PAI-2 and DRHC were confirmed to be upregulated with real-time PCR and Western blot, suggesting a possible association with PEDF-induced signaling for cell motility and metastasis. These results can contribute to our understanding of the molecular mechanisms of treatment strategies of PEDF for prostate cancer.
Research and teaching in general practice/primary care
Authors: Denis Pereira Gray
Journal: BMJ (2015)

Campbell and colleagues note that GP academics comprise just 6.5% of all clinical academics.1 General practice is the biggest branch of medicine. It has a variety of clinical challenges that cross the physical-psychological barrier, it best integrates preventive and therapeutic care, and is best able to ameliorate socioeconomic disadvantage. The ratio of 205 full time equivalent GP academics to 32 628 full time equivalent GPs (1:159) is …
Abstract 14990: Sudden Death in Patients with Heart Failure and Preserved Ejection Fraction
Authors: Kyndaron Reinier, Audrey Uy-Evanado, Carmen Teodorescu, Eloi Marijon, Kumar Narayanan, Karen Gunson, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2014)

Introduction: Severely reduced left ventricular ejection fraction (EF) is an established risk factor for sudden cardiac death (SCD), but has limited sensitivity and specificity. We evaluated the contribution of heart failure (HF) with preserved ejection fraction toward risk of SCD in the general population. Hypothesis: We hypothesized that HF would predict risk of SCD, even among patients with preserved EF. Methods: Subjects from an ongoing community-based study of SCD in the northwest US (pop. approx. one million) were included if age ≥18 (2002 - 2012) with clinical history and assessment of EF. Clinical history of heart failure (HF) was determined by physician report. Ejection fraction (EF) was determined from echocardiogram, angiogram, or multigated acquisition scan, and categorized as EF &lt;20%, 20-34%, 35-44%, 45-54%, and ≥55%. Laboratory values of brain natriuretic peptide (BNP) were obtained from routine clinical laboratory testing for a subset of patients. Results: Cases (n=628, mean age 69.9, 65% male) were more likely than controls (n = 580, mean age 66.8, 66% male) to have a history of clinically-recognized HF (58% vs. 24%, p&lt;0.0001) and to have an EF ≤ 35% (27% vs. 12%, p&lt;0.0001). At each EF level above 20%, HF was approximately twice as prevalent in cases compared to controls (Figure, p≤0.002). Median BNP levels were significantly higher for patients with HF vs. those without, across EF categories. Adjusting for age and sex, each category of decreasing EF was associated with an increased risk of SCD (OR 1.4, 95% CI 1.3 - 1.6, p&lt;0.0001), but the association was diminished by adjustment for HF, and for BNP. Odds of SCD were 4-fold higher (p&lt;0.0001) in the presence HF, adjusting for age and sex, across all categories of EF. Conclusions: In this population, the significant role of HF with preserved EF in SCD was confirmed by BNP level trends. Improvements in SCD prevention will require focused investigation of high risk SCD markers in patients with heart failure and preserved EF.
Abstract 18812: Clinical and Cardiac Features in Patients Showing Out-of-Hospital Cardiac Arrest After Subarachnoid Hemorrhage
Authors: Wataru Mitsuma, Masahiro Ito, Makoto Kodama, Makoto Tomita, Hiroshi Endoh, Aizawa Yoshifusa
Journal: Circulation (2010)

Background: Subarachnoid hemorrhage (SAH) has been known as one of the etiologies of out-of-hospital cardiac arrest (OHCA). However, the detailed clinical features of these patients remain unknown....
Cryoballoon Ablation of Pulmonary Veins for Paroxysmal Atrial Fibrillation
Authors: Douglas L. Packer, Robert C. Kowal, Kevin R. Wheelan, James M. Irwin, Jean Champagne, Peter G. Guerra, Marc Dubuc, Vivek Reddy, Linda Nelson, Richard G. Holcomb, John W. Lehmann, Jeremy N. Ruskin
Journal: Journal of the American College of Cardiology (2013)
Second-Generation Drug-Eluting Stent Implantation Followed by 6- Versus 12-Month Dual Antiplatelet Therapy
Authors: Antonio Colombo, Alaide Chieffo, Arian Frasheri, Roberto Garbo, Monica Masotti-Centol, Neus Salvatella, Juan Francisco Oteo Dominguez, Luigi Steffanon, Giuseppe Tarantini, Patrizia Presbitero, Alberto Menozzi, Edoardo Pucci, Josepa Mauri, Bruno Mario Cesana, Gennaro Giustino, Gennaro Sardella
Journal: Journal of the American College of Cardiology (2014)
Use of palliative chemotherapy and targeted agents in elderly patients with metastatic colorectal cancer (mCRC).
Authors: Matthew Chan, Daniel John Renouf, Caroline Speers, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2012)

6018 Background: Elderly patients are increasingly diagnosed with advanced cancers, but they are consistently underrepresented in clinical trials, which may lead to undertreatment. Our aims were to 1) evaluate the impact of advanced age on patterns of first-line chemotherapy and bevacizumab use in mCRC, 2) examine the reasons for treatment choices and 3) compare adverse events and treatment discontinuations in elderly vs young patients. Methods: A random sample of mCRC patients diagnosed from 2006 to 2007 and referred to any 1 of 5 regional cancer centers in British Columbia, Canada was reviewed. Summary statistics were used to describe treatment patterns between the elderly (&gt;/=70 years) and young (&lt;70 years). Cox regression was used to determine the effect of systemic therapy on overall survival, controlling for age and confounders. Results: We identified 800 patients: 43% elderly and 57% young; 56% men; and 26 / 36 / 38% ECOG 0 / 1 / 2+, respectively. Fewer elderly patients were given chemotherapy (52% vs 79%, p&lt;0.001). Among those treated, most common first-line palliative regimens for elderly vs young included: capecitabine (50 vs 15%), FOLFIRI (26 vs 38%), and FOLFOX (15 vs 37%) (all p&lt;0.001). Those aged &gt;/=70 were also less likely to receive bevacizumab in their regimens (22 vs 50%, p&lt;0.001). The most frequent reasons for no systemic therapy were similar between age groups: patient choice (31 vs 28%), poor ECOG (16 vs 17%), and significant co-morbidity (11 vs 13%). Risk of chemotherapy (p=0.30) and bevacizumab (p=0.39) adverse events were comparable between elderly and young as were rates of early chemotherapy (p=0.07) and bevacizumab (p=0.79) discontinuation. Receipt of systemic therapy +/- bevacizumab was associated with improved survival from mCRC (HR for death 0.50, 95% CI 0.31-0.62, p&lt;0.001), regardless of advanced age (p interaction for age and treatment = 0.33). Conclusions: Elderly patients with mCRC are more likely to receive no chemotherapy, capecitabine monotherapy, or a regimen without bevacizumab. However, in carefully selected elderly patients, adverse events, treatment discontinuations, and overall survival benefit from treatment appear similar to those observed for younger patients.