tbuckley/cabot-search huggingface dataset:
Daniel Greer Young
Authors: R. Carachi
Journal: BMJ (2014)

Daniel Greer Young (“Dan”) undertook his national service serving in Ghana on a special short service commission, during which time the country celebrated its independence. He returned to Glasgow via the Liverpool School of Tropical Medicine, as an assistant lecturer in the physiology department. His further surgical training was in Glasgow and the Hospital for Sick Children, Great Ormond Street, London, before being appointed a senior lecturer and honorary consultant at the Great Ormond Street and at the Queen Elizabeth Hospital, Hackney.

In 1969 he returned to the University of Glasgow as head of the department of surgical paediatrics. The neonatal surgical unit was established in November 1971, when the hospital moved back to new premises on its original site. This unit was state of the art of its time and has been widely recognised. It was refurbished in 1991 and renamed the “Dan Young Neonatal Surgical Unit” by the chairman of the health board. Over the past 42 years more than 15 000 “surgical” neonates have been cared for in the unit.

Dan developed a fine department of paediatric surgery, was an excellent educator and role model, and trained many younger …
CLINICAL APPLICATIONS OF TC-99m-MICROLITE-LEUKOCYTES.
Authors: Carol S. Marcus, John A. Kuperus, Robert D. Salk, Bi-Ying Chen, Michael G. Stabin, Evelyn E. Watson, Ismael A. Mena, John A. Butler, Phillip L. Henneman, Stanley H. Inkelis, James W. Fain, Timothy W. Lane, Robert J. Rothstein, Samuel E. Wilson
Journal: Clinical Nuclear Medicine (1986)

Marcus, Carol S.; Kuperus, John A.; Salk, Robert D.; Chen, Bi-Ying; Stabin, Michael G.; Watson, Evelyn E.; Mena, Ismael A.; Butler, John A.; Henneman, Phillip L.; Inkelis, Stanley H.; Fain, James W.; Lane, Timothy W.; Rothstein, Robert J.; Wilson, Samuel E. Author Information
Abstract 195: The tumor cell compartment holds the unfavorable prognostic value of miR-21 in gliomas
Authors: Simon K. Hermansen, Rikke H. Dahlrot, Boye S. Nielsen, Steinbjørn Hansen, Bjarne W. Kristensen
Journal: Cancer Research (2012)

Abstract High-grade gliomas are some of the most lethal forms of human cancer and new clinical biomarkers and therapeutic targets are highly needed. MicroRNAs (miRNAs), a group of short noncoding RNAs, hold great potential as new biomarkers and targets as they are commonly deregulated in a variety of diseases including gliomas. MicroRNA-21 (miR-21) is the most consistently over-expressed miRNA in several cancers including gliomas and is therefore very promising as a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in gliomas, paraffin embedded glioma tissue samples from 193 patients with grade I, II, III and IV tumors were analyzed by in situ hybridization (ISH) using LNA-DNA chimeric probes. We found miR-21 expression in tumor cells and tumor-associated blood vessels, whereas no expression was seen in adjacent normal brain parenchyma. Using advanced image analysis we obtained quantitative estimates reflecting the miR-21 expression levels. The miR-21 levels correlated significantly with grade (p = 0.027, rs = 0.161, 95% CI, 0.015 to 0.301) with the highest levels measured in grade IV gliomas. Furthermore, quantitative estimates obtained for the tumor cells alone were significantly associated with poor prognosis in all tumors (p = 0.012) and grade III and IV tumors alone (p = 0.005). This was independent of known clinical parameters (age, grade and sex). In conclusion, we have shown that miR-21 is constricted to tumor cells and tumor blood vessels and that tumor cell miR-21 represent a valuable prognostic biomarker for the disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 195. doi:1538-7445.AM2012-195
CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)—Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)
Authors: M. Schmidt-Hieber, G. Silling, E. Schalk, W. Heinz, J. Panse, O. Penack, M. Christopeit, D. Buchheidt, U. Meyding-Lamadé, S. Hähnel, H.H. Wolf, M. Ruhnke, S. Schwartz, G. Maschmeyer
Journal: Annals of Oncology (2016)

Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell transplantation carry a high risk for CNS infections of up to 15%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying hematological disorder may mimic symptoms of a CNS infection. The prognosis of CNS infections is generally poor in these patients, albeit the introduction of novel substances (e.g. voriconazole) has improved the outcome in distinct patient subgroups. This guideline has been developed by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) with the contribution of a panel of 14 experts certified in internal medicine, hematology/oncology, infectious diseases, intensive care, neurology and neuroradiology. Grades of recommendation and levels of evidence were categorized by using novel criteria, as recently published by the European Society of Clinical Microbiology and Infectious Diseases.
Bending the Cost Curve through Market-Based Incentives
Authors: Joseph R. Antos, Mark V. Pauly, Gail R. Wilensky
Journal: New England Journal of Medicine (2012)

In order to reduce health care spending, the authors suggest two market-based approaches. To reduce federal Medicare spending, they suggest a premium-support model (defined contribution); in the private insurance market, they suggest reducing the tax exemption for employer-sponsored health insurance. Both approaches change the incentives for health care spending.
The impact of midlevel providers on productivity in outpatient oncology clinics at National Comprehensive Cancer Network (NCCN) institutions
Authors: J. M. Hinkel, J. L. Vandergrift, S. J. Perkel, M. B. Waldinger MHSA, W. Levy PA-C, F. M. Stewart
Journal: Journal of Clinical Oncology (2009)

6628 Background: An ASCO workforce study has predicted an oncologist shortage by 2020. Increased reliance on mid-level providers (PA/NPs) has been proposed to ameliorate the physician shortage. However, no methods currently exist to assess the impact of PA/NPs as physician extenders in an oncology setting. Obtaining productivity data is challenging due to variations in PA/NP utilization and billing. NCCN developed a survey to evaluate the use of PA/NPs in cancer centers and to pilot test PA/NP productivity metrics in outpatient oncology clinics. Methods: An online survey instrument was developed in consultation with oncologists, executive administrators, and PA/NP leaders at NCCN institutions. It included questions on work characteristics, allocation of time and labor, and productivity. PA/NP outpatient clinic productivity was measured as the average number of new and follow-up patients seen per half-day clinic (patients per clinic, PPC). A convenience sample was obtained through 15 NCCN institutions that distributed the survey through their own internal PA/NP e-mail lists. Results: A total of 206 PA/NPs completed the survey. A greater proportion of respondents were NPs (54%) than PAs (46%). Most responding PA/NPs listed their primary specialty as medical oncology (MO, 34%), followed by hematologic malignancies/BMT (HM/BMT, 28%) and surgical oncology (SO, 23%). The highest reported productivity was observed for SO specialists (mean = 8.7 PPC, SD = 3.5), followed by MO (mean = 7.6, SD = 4.3), and HM/BMT (mean = 6.1, SD = 2.8). Within the SO and HM/BMT specialties, little difference was observed between NP and PA productivity. Among MO specialists, NPs reported seeing more follow-up patients per clinic (mean = 7.2, SD = 4.3) than PAs (mean = 5.5, SD = 2.7, p = 0.04). In most cases, productivity was unrelated to seniority. However, more experienced HM/BMT NPs were more productive with new patients (r s = 0.46, p = 0.03). Conclusions: Mid-level providers have a measurable impact on productivity in outpatient oncology clinics. Refining productivity metrics for PAs/NPs will help inform workforce projections and staffing decisions for oncology practices/specialists and cancer centers, especially in the face of future physician shortages. No significant financial relationships to disclose.
PWE-149 Minimal Hepatic Encephalopathy Is A Significant Complication In Cirrhotic Patients Admitted To Hospital
Authors: LR Ping, L Mcleman, B Vijayan, A Fraser, A Mukhopadhya
Journal: Gut (2014)

<h3>Introduction</h3> Minimal hepatic encephalopathy (MHE) is a subtle cognitive impairment in patients with cirrhosis or porto-systemic shunts in the absence of abnormalities in standard neurological examination. The diagnosis of MHE has always taken a back seat in the evaluation of patients with cirrhosis primarily due to the fact that it is time consuming and not well validated. However, the prognostic importance of MHE cannot be understated as it has been found to affect motor skills like driving and timely treatment does improve quality of life and progression to overt encephalopathy (OHE). <h3>Objective</h3> To estimate the prevalence of minimal hepatic encephalopathy in a sequential population of cirrhotic patients admitted in the gastroenterology ward at Aberdeen Royal Infirmary. <h3>Methods</h3> 26 patients with a diagnosis of cirrhosis admitted over a 3 week period were included in the study. All patients with overt encephalopathy and sepsis were excluded from the study. The psychometric hepatic encephalopathy score (PHES) was used to assess the patients at the bedside. This comprises of a standardised battery of five paper–pencil psychometric tests: number connexion test A, number connexion test B, the digit symbol test, the line tracing test (time and errors) and the serial dotting test. Minimal hepatic encephalopathy can be diagnosed when the psychometric hepatic encephalopathy score is less than -5. This score can be easily obtained by inputting data in an online tool (http://www.redeh.org/phesapp/datosE.html). <h3>Results</h3> The mean age of the selected cirrhotic patients was 59 ± 2.8 years and 74.1% were male. The commonest aetiology of cirrhosis was alcohol related liver disease (62.9%). 33.3% of patients were Child’s A, 44.4% were Child’s B and 22.3% were Child’s C. The mean MELD score was 16.5 ± 9.2. The median PHES score was 1 (Range -10 to 2). Of the 26 patients evaluated, 7 patients were diagnosed to have MHE (25.9%). The prevalence varied with the Child’s stage, 11.1% in Child’s A, 25% in Child’s B and 60% of Child’s C patients. All patients diagnosed with MHE were commenced on Lactulose. <h3>Conclusion</h3> Hospitalised patients with cirrhosis have a significant prevalence of MHE which is proportional to the stage of the liver disease. Prompt identification and treatment of this cohort will help in preventing them from progressing to overt encephalopathy. <h3>Disclosure of Interest</h3> None Declared.
AB0850-HPR Side effect profile in patients with rheumatoid arthritis on leflunomide with and without loading dose.
Authors: S. Arava, R. R. Uppuluri, F. Fatima, M. Y. Mohiuddin, A. Rani, D. Kumar, S. Challa, S. Jonnada, D. Sri Purna
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Leflunomide (LEF) a pyrimidine synthesis inhibitor is a disease modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). In combination with methotrexate (MTX), it may prove superior to either agent alone. Side effects such as diarrhoea, skin rash, alopecia and hepatitis were observed more in the patients of RA when given leflunomide with loading dose (100mg/d for 3 days). It is considered that the side effects would be lesser when the patients are not given the loading dose of leflunomide. In our study we compared the side effect profile in two cohorts where in one was given loading dose the other did not <h3>Objectives</h3> To evaluate the side effects observed in patients receiving LEF as an add on therapy with or without loading dose in RA <h3>Methods</h3> Three hundred eighty seven patients with active RA without a loading dose of LEF(ARAVA) in combination with MTX were included. The indication to start LEF was suboptimal response to MTX. Hemogram, ESR/CRP and LFT were measured both at entry and monthly for the first six months and every three months thereafter. LEF tolerability was closely monitored and adverse events were noted and followed up. A historic comparison was done with the study conducted at the same centre earlier between October 2001 and December 2003(Firdaus, Rao). <h3>Results</h3> A total of 387 patients of which 332 women (85.7%) and 57 men (14.7%), with a mean age <b>49.7±10.71</b> yrs and drug dosage duration of 6 ± 4.2 yrs were included; 319 (82.4%) patients were seropositive. The side effect profiles were depicted in table -1 <h3>Conclusions</h3> The mild side effects may be same with LEF with or without loading dose but serious adverse events may be more common with loading dose. It looks that depriving the loading dose for the patients may not reduce the side effects which are possibly due to LEF. <h3>References</h3> BykerkV.P. et al Canadian recommendations for the management of RA. J Rheum 2012;39:1559-15982. ErraA. et al Is the recommended dose of LEF the best regimen to treat RA patients? ( L) Rheumatology2003; 42: 1123-1124. MaddisonP. et al LEF in RA: Recommendations through a process of consensus. Rheumatology 2005;44:280-286. Rao URK, Fatima F. LEF as an add on therapy in RA- Adverse events. EULAR 2004 Abstract FRI0120. <h3>Disclosure of Interest</h3> None Declared
Abstract 1463: Pharmacological impact of epithelial-mesenchymal plasticity in the H358 lung tumor model
Authors: Gretchen M. Argast, Peter Mercado, Matthew O'Connor, Iain J. Mulford, Jonathan A. Pachter, David M. Epstein, Stuart Thomson, Julie L.C. Kan
Journal: Cancer Research (2010)

Abstract The phenotypic changes associated with epithelial to mesenchymal transition (EMT) give tumor cells at least two attributes that increase metastatic efficiency. First, mesenchymal cells have lost cell-cell contacts and are more invasive and can therefore escape the primary tumor, whereas epithelial cells remain anchored by cell-cell contacts in the primary tumor. Second, mesenchymal cells in vitro are less sensitive than epithelial cells to agents that inhibit the EGFR pathway. This appears to translate into the clinic, since patients with tumors that express mesenchymal markers do not respond to EGFR targeting therapeutics as well as patients with more epithelial tumors. To determine whether we can control sensitivity to EGFR inhibitors by manipulating a cell's epithelial/mesenchymal status, we examined the role of EMT and its reversibility in tumor cell sensitivity to the EGFR inhibitor erlotinib. We studied in vitro models of EMT driven by Transforming Growth Factor β (TGFβ), Hepatocyte Growth Factor + Oncostatin M (HGF+OSM), Snail or Zeb1 in the H358 non-small cell lung carcinoma model. EMT driven by TGFβ or HGF+OSM caused a significant decrease in sensitivity to erlotinib, while EMT driven by induced expression of Snail or Zeb1 was much less effective, suggesting a change in drug sensitivity requires more input than these canonical EMT transcription factors. Once mesenchymal tumor cells have localized to a metastatic site, it is thought the tumor cells must undergo a mesenchymal to epithelial transition (MET) in order to form a cohesive tumor. We examined the reversibility of EMT in our models and the corresponding erlotinib sensitivity, both by withdrawal of ligand and by pharmacological inhibition of the signaling pathways downstream of the drivers. Using these approaches, we found EMT driven by HGF+OSM was reversible as evidenced by morphology and marker changes, and this reversion correlated with an increase in erlotinib sensitivity, comparable to the parental H358 cells. EMT driven by TGFβ was partially reversed by both ligand withdrawal and pharmacological inhibition of the receptor, and the extent of reversion in erlotinib sensitivity correlated with the extent of marker reversion. These results demonstrate that the extent of reversibility of EMT is dependent on the driver. Furthermore, it may be possible to drive some erlotinib-insensitive tumors back to a more erlotinib-sensitive state with pharmacological agents, thus improving patient response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1463.
Abstract 3762: Second generation PIM inhibitors exhibit improved activity in solid tumor models
Authors: Jason M. Foulks, Yong Xu, Michael Saunders, Xiao-Hui Liu, Benjamin Brenning, Adrianne Clifford, Marcus Wilkes, Bai Luo, Shuping Lai, Shannon Merx, Ashley Chan, Liwen Huang, David Vollmer, Anna Senina, Jihua Liu, Koc-Kan Ho, Michael V. McCullar, Steven B. Kanner
Journal: Cancer Research (2012)

Abstract The proto-oncogene PIM kinase family (PIM-1, -2 and -3) includes constitutively active serine/threonine kinases upregulated in multiple cancer indications, including lymphomas, leukemias, multiple myeloma, prostate and bladder cancers. Overexpression of one or more PIM family members in patient tumors frequently correlates with poor prognosis. The PIM kinases function by inhibiting apoptosis in MYC-driven tumors, and promoting tumor cell survival and proliferation. In the HEK-293T cell line, enhanced PIM kinase substrate BAD phosphorylation (pBAD) was observed following PIM and BAD overexpression. Enhancement of pBAD was inhibited by SGI-1776, a well-described PIM inhibitor, and more effectively by second generation PIM inhibitors exhibiting 4-10 fold improved potency against the PIM kinase family. The current PIM inhibitors display sub-µM activity in pharmacodynamic marker, proliferation and 2D colony formation assays using the UM-UC-3 human bladder cancer cell line. PIM1 and PIM2 overexpression models were established in the human prostate cancer cell line 22RV-1 and the non-tumorigenic mouse NIH-3T3 cell background. Overexpression of PIM kinases led to enhanced cell growth and tumorigenicity in both NIH-3T3 and 22RV-1 cell lines. In vivo xenograft studies using both PIM overexpression models and a clinically relevant solid tumor model facilitated identification of a lead candidate with demonstrated efficacy and favorable toxicity. IND-enabling studies with a lead candidate are underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3762. doi:1538-7445.AM2012-3762
A phase 1 study of weekly high dose sunitinib in patients with advanced solid tumors: Early signs of activity in non-RCC tumor types.
Authors: Maria Rovithi, Johannes Voortman, Anne Marije Luik, Rita Ruijter, Richard de Haas, Richard Honeywell, Mariette Labots, Dennis Poel, Godefridus J. Peters, Arjan W. Griffioen, Henk M.W. Verheul
Journal: Journal of Clinical Oncology (2015)

e13550 Background: Increased exposure to sunitinib is associated with improved outcome. Preclinical data shows promising antitumor activity of intermittent exposure to high sunitinib concentrations. In this phase 1 trial the MTD and tolerability of once weekly oral sunitinib administration were investigated (ClinicalTrials.gov number, NCT02058901). Methods: Key eligibility: patients (pts) with advanced solid malignancies, progressive, refractory to standard treatment, measurable disease and WHO≤ 1. Sunitinib was administered orally once weekly. Starting dose was 200 mg, escalating in increments of 100mg in following cohorts until the maximum tolerated dose (MTD) was reached. Pts continued sunitinib until progression or dose-limiting toxicity (DLT). Antitumor response was evaluated by RECIST 1.1. Sunitinib plasma concentration was determined by LC-MS. Results: In total 20 pts were included, all non-RCC, predominantly CRC (50%). Median age: 59 (43-75) years; previous systemic treatment regimens: median 3 (range 2-8). MTD was set at 300 mg/week, with two DLTs occurring at 400 mg/week: 1 patient with grade (G) 3 bile stasis and 1 patient with G3 fatigue. Most common related AEs were fatigue (79%), nausea (71%), hypoalbuminemia (64%) and anorexia (29%). The majority of AEs were G1-2. Sunitinib PK parameters are summarized in table 1. Minimal accumulation of sunitinib after 42 days of treatment was found. Tumor-response data were available for 13 pts: 9 patients with SD at 8 weeks and of these, 5 pts at 16 wks and 2 pts at 24 wks. All CT scans with SD showed intratumoral necrosis; 4 pts showed >50% decrease in tumor marker. Conclusions: Once weekly administered sunitinib at the MTD of 300mg is feasible with similar tolerability to daily administration. Promising prolonged disease stabilization in this heavily pretreated group of patients was observed. A phase 2 trial in patients with colorectal cancer is in preparation. Clinical trial information: NCT02058901.PK parameters. 200 mg weekly 300 mg weekly 400 mg weekly Average SD Average SD Average SD Cmax, μg/L 167 64 194,3 84,6 226.6 71,3 Tmax, hrs 5,3 1,2 8,3 2,3 6,2 3,0 AUC0-48, mg*hr/L 8,3 7,5 6,4 2,6 7,2 50,0 t1/2, hrs 67,0 11,0 71,3 61,7 65,8 28.4 CL/F, L/hr 16,0 6,7 28,5 26,6 20,9 11.3
Serum Vitamin B<sub>12</sub>Content in Liver Disease
Authors: Thomas D. Stevenson, Marion F. Beard
Journal: New England Journal of Medicine (1959)

THE liver is the principal storage site of vitamin B12 and has an important role in the metabolism of the vitamin. An increased serum content of vitamin B12 found in acute and chronic liver disease has been attributed to the release of the vitamin from the liver owing to hepatic necrosis and to an increased capacity of the serum to bind vitamin B12 as a result of abnormalities in the serum proteins.1 , 2 An increased serum content in acute and chronic myeloid and monocytic leukemia is the result of an increased binding capacity of the serum for vitamin . . .