tbuckley/cabot-search huggingface dataset:
The new NHS information technology strategy
Authors: J. C Wyatt
Journal: BMJ (2001)

As a general practitioner piloting 21st century electronic links across the healthcare system, you get a thrill each time you send a prescription direct to the pharmacist. Then you find that, because pharmacists now telephone holders of uncashed prescriptions, your drugs bill is up by 20%. Equally, some of your patients send thoughtful emails, but you need nearly two hours a week to respond properly.1 You can use the new technology to collect and analyse data about your clinical practice, and the quality of the data is definitely improving. But managing information is becoming an end in itself, and you have to devote ever more time to it. You feel you are busier than ever.2 In such ways does technology change the practice of medicine.

The events in this scenario, and more, are likely to happen when the new NHS information technology strategy,3 published in February, is implemented. On balance, the arrival of networks to communicate clinical information with anyone in the NHS, is welcome. After a very slow …
Chronic myeloid leukemia CD34+ cells have elevated levels of phosphatidylinositol 3,4,5 trisphosphate (PtdIns(3,4,5)P3) and lack a PtdIns(3,4,5)P3 response to cytokines and chemotactic factors; effects reversed by imatinib
Authors: H G Hamzah, A Pierce, W A Stewart, C Peter Downes, A Gray, A Irvine, E Spooncer, A D Whetton
Journal: Leukemia (2005)
Response and progression in recurrent malignant glioma
Authors: K. R. Hess, E. T. Wong, K. A. Jaeckle, A. P. Kyritsis, V. A. Levin, M. D. Prados, W. K. A. Yung
Journal: Neuro-Oncology (1999)

In this article we report the results of a study of the relationship between response and progression in 375 patients with recurrent glioma enrolled in phase II chemotherapy trials. We reviewed the records of patients from 8 consecutive phase II trials, including 225 patients with recurrent glioblastoma multiforme and 150 with recurrent anaplastic astrocytoma. Median age was 45 years (range, 15–82) and median Karnofsky performance score was 80 (range, 60–100). Forty-one patients (11%) had more than two prior resections and/or more than two prior chemotherapy regimens. Best response was complete (n = 1) or partial (n = 33) in 34 patients (9%). Median time to response was 14 weeks, and median response duration was 44 weeks. Simon-Makuch estimates for 52-week progression-free survival for patients progression-free at 13 weeks were 48% for response and 28% for nonresponse. When response was treated as a time-dependent covariate in a Cox proportional hazards regression analysis, response was associated with significantly lower failure rates (hazard ratio 0.5; 95% confidence interval 0.3–0.8; P = 0.0016). This study showed that response in recurrent glioma is associated with a significant reduction in progression rates.
Effects of insulin and glucose on renal phosphate reabsorption
Authors: M Allon
Journal: Journal of the American Society of Nephrology (1992)

Both insulin deficiency and glycosuria are known to inhibit the tubular reabsorption of phosphate. This inhibition has previously been evaluated either in the fasted state or on a normal phosphate diet. The goal of this study was to evaluate how dietary phosphate depletion affected the relative effects of insulin deficiency and glycosuria on the tubular reabsorption of phosphate. Rats were maintained on either a low- (0.03%) or normal (0.8%) phosphate diet. After 5 days, one half of the animals in each group received streptozotocin to induce short-term insulin deficiency, whereas the other half received vehicle alone. Two days later, sodium-dependent phosphate uptake by renal brush border membrane vesicles (BBMV) was evaluated in each of the four experimental groups. The effect of glucose on phosphate uptake was determined by the addition of varying concentrations of glucose (between 0 and 32 mmol/L) to the extravesicular transport fluid. BBMV phosphate uptake was about threefold higher in the nondiabetic rats fed a low-phosphate diet as compared with the nondiabetic animals maintained on a normal phosphate diet. In rats maintained on a low-phosphate diet, streptozotocin treatment prevented the increase in BBMV phosphate transport; in contrast, in animals fed a normal phosphate diet, streptozotocin treatment had no effect on BBMV phosphate transport. Extravesicular glucose significantly inhibited phosphate transport in a dose-related manner, regardless of dietary phosphate or insulin status. Because fasting mimics the catabolic state associated with insulin deficiency, BBMV phosphate transport was also measured in rats fasted for 48 h after the administration of streptozotocin or vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
Impact of Cultural and Linguistic Factors on Symptom Reporting by Patients With Cancer
Authors: Xin Shelley Wang, Charles S Cleeland, Tito R Mendoza, Young Ho Yun, Ying Wang, Toru Okuyama, Valen E Johnson
Journal: JNCI Journal of the National Cancer Institute (2010)

BackgroundPatient reporting of the severity and impact of symptoms is an essential component of cancer symptom management and cancer treatment clinical trials. In multinational clinical trials, cultural and linguistic variations in patient-reported outcomes instruments could confound the interpretation of study results.
Lyn Kinase Mediates Cell Motility and Tumor Growth in EGFRvIII-Expressing Head and Neck Cancer
Authors: Sarah E. Wheeler, Elena M. Morariu, Joseph S. Bednash, Charlton G. Otte, Raja R. Seethala, Simion I. Chiosea, Jennifer R. Grandis
Journal: Clinical Cancer Research (2012)

EGF receptor variant III (EGFRvIII) has been detected in several cancers in which tumors expressing this truncated growth factor receptor show more aggressive behavior. The molecular mechanisms that contribute to EGFRvIII-mediated tumor progression that are amenable to targeted therapy are incompletely understood. The present study aimed to better define the role of Src family kinases (SFKs) in EGFRvIII-mediated cell motility and tumor growth of head and neck squamous cell carcinomas (HNSCC).HNSCC models expressing EGFRvIII were treated with dasatinib, a pharmacologic inhibitor of SFKs.SFK inhibition significantly decreased cell proliferation, migration, and invasion of EGFRvIII-expressing HNSCC cells. Administration of dasatinib to mice bearing EGFRvIII-expressing HNSCC xenografts resulted in a significant reduction of tumor volume compared with controls. Immunoprecipitation with anti-c-Src, Lyn, Fyn, and Yes antibodies followed by immunoblotting for phosphorylation of the SFK activation site (Y416) showed specific activation of Lyn kinase in EGFRvIII-expressing HNSCC cell lines and human HNSCC tumor specimens. Selective inhibition of Lyn using siRNA decreased cell migration and invasion of EGFRvIII-expressing HNSCCs compared with vector control cells.These findings show that Lyn mediates tumor progression of EGFRvIII-expressing HNSCCs in which strategies to inhibit SFK may represent an effective therapeutic strategy.
Intracellular Mg2+ and magnesium depletion in isolated renal thick ascending limb cells.
Authors: L J Dai, G A Quamme
Journal: Journal of Clinical Investigation (1991)

Magnesium reabsorption and regulation within the kidney occur principally within the cortical thick ascending limb (cTAL) cells of the loop of Henle. Fluorometry with the dye, mag-fura-2, was used to characterize intracellular Mg2+ concentration ([Mg2+]i) in single cTAL cells. Primary cell cultures were prepared from porcine kidneys using a double antibody technique (goat anti-human Tamm-Horsfall and rabbit anti-goat IgG antibodies). Basal [Mg2+]i was 0.52 +/- 0.02 mM, which was approximately 2% of the total cellular Mg. Cells cultured (16 h) in high magnesium media (5 mM) maintained basal [Mg2+]i, 0.48 +/- 0.02, in the normal range. However, cells cultured in nominally magnesium-free media possessed [Mg2+]i, 0.27 +/- 0.01 mM, which was associated with a significant increase in net Mg transport, (control, 0.19 +/- 0.03 and low Mg, 0.35 +/- 0.01 nmol.mg-1 protein.min-1) as assessed by 28Mg uptake. Mg(2+)-depleted cells were subsequently placed in high Mg solution (5 mM) and the Mg2+ refill rate was assessed by fluorescence. [Mg2+]i returned to normal basal levels, 0.53 +/- 0.03 mM, with a refill rate of 257 +/- 37 nM/s. Mg2+ entry was not changed by 5.0 mM Ca2+ or 2 mM Sr2+, Cd2+, Co2+, nor Ba2+ but was inhibited by Mn2+ approximately La3+ approximately Gd3+ approximately Zn2+ approximately Be2+ at 2 mM. Intracellular Ca2+ and 45Ca uptake was not altered by Mg depletion or Mg2+ refill, indicating that the entry is relatively specific to Mg2+. Mg2+ uptake was inhibited by nifedipine (117 +/- 20 nM/s), verapamil (165 +/- 34 nM/s), and diltiazem (194 +/- 19 nM/s) but enhanced by the dihydropyridine analogue, Bay K 8644 (366 +/- 71 nM/s). These antagonists and agonists were reversible with removal and [Mg2+]i subsequently returned to normal basal levels. Mg2+ entry rate was concentration and voltage dependent and maximally stimulated after 4 h in magnesium-free media. Cellular magnesium depletion results in increases in a Mg2+ refill rate which is dependent, in part, on de novo protein synthesis. These data provide evidence for novel Mg2+ entry pathways in cTAL cells which are specific for Mg2+ and highly regulated. These entry pathways are likely involved with renal Mg2+ homeostasis.
Optimization of Natural Killer T Cell–Mediated Immunotherapy in Cancer Using Cell-Based and Nanovector Vaccines
Authors: C. Faveeuw, F. Trottein
Journal: Cancer Research (2014)

α-Galactosylceramide (α-GalCer) represents a new class of immune stimulators and vaccine adjuvants that activate type I natural killer T (NKT) cells to swiftly release cytokines and to exert helper functions for acquired immune responses. This unique property prompted clinicians to exploit the antitumor potential of NKT cells. Here, we review the effects of α-GalCer in (pre)clinics and discuss current and future strategies that aim to optimize NKT cell-mediated antitumor therapy, with a particular focus on cell-based and nanovector vaccines.
Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial
Authors: M. Matucci-Cerinic, C. P. Denton, D. E. Furst, M. D. Mayes, V. M. Hsu, P. Carpentier, F. M. Wigley, C. M. Black, B. J. Fessler, P. A. Merkel, J. E. Pope, N. J. Sweiss, M. K. Doyle, B. Hellmich, T. A. Medsger, A. Morganti, F. Kramer, J. H. Korn, J. R. Seibold
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> Ischaemic digital ulcers (DUs) are common in patients with systemic sclerosis (SSc) and are a cause of disease-related morbidity. In an earlier trial, treatment with bosentan, an oral endothelin receptor antagonist, reduced the occurrence of new DUs by 48%. The present study (RAPIDS-2, for 'RAndomized, double-blind, Placebo-controlled study with bosentan on healing and prevention of Ischemic Digital ulcers in patients with systemic Sclerosis') was conducted to more fully evaluate the effects of bosentan treatment on DUs associated with SSc. <h3>Methods</h3> This double-blind, placebo-controlled trial conducted at 41 centres in Europe and North America randomised 188 patients with SSc with at least 1 active DU ('cardinal ulcer') to bosentan 62.5 mg twice daily for 4 weeks and 125 mg twice daily thereafter for 20 weeks (n=98) or matching placebo (n=90; total 24 weeks). The two primary end points were the number of new DUs and the time to healing of the cardinal ulcer. Secondary end points included pain, disability and safety. <h3>Results</h3> Over 24 weeks, bosentan treatment was associated with a 30% reduction in the number of new DUs compared with placebo (mean±standard error: 1.9±0.2 vs 2.7±0.3 new ulcers; p=0.04). This effect was greater in patients who entered the trial with more DUs. There was no difference between treatments in healing rate of the cardinal ulcer or secondary end points of pain and disability. Peripheral oedema and elevated aminotransferases were associated with bosentan treatment. <h3>Conclusions</h3> Bosentan treatment reduced the occurrence of new DUs in patients with SSc but had no effect on DU healing. Bosentan was well tolerated and may be a useful adjunct in the management of patients with SSc with recurrent DUs.
Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.
Authors: A Hänninen, S Jalkanen, M Salmi, S Toikkanen, G Nikolakaros, O Simell
Journal: Journal of Clinical Investigation (1992)

Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.
Aldosterone-Stimulated SGK1 Activity Mediates Profibrotic Signaling in the Mesangium
Authors: Yoshio Terada, Hitoshi Kuwana, Takahiko Kobayashi, Tomokazu Okado, Noriko Suzuki, Takanobu Yoshimoto, Yukio Hirata, Sei Sasaki
Journal: Journal of the American Society of Nephrology (2008)

Several recent reports support the hypothesis that aldosterone contributes to the progression of renal injury. Mineralocorticoids increase the expression of serum- and glucocorticoid-inducible protein kinase 1 (SGK1), which is upregulated in several fibrotic diseases. It was hypothesized that SGK1 may mediate the effects of aldosterone on glomerular fibrosis and inflammation. In primary cultures of rat mesangial cells, aldosterone stimulated the expression, phosphorylation, and kinase activity of SGK1, as well as SGK1-dependent NF-kappaB activity. Furthermore, aldosterone augmented the promoter activity and protein expression of intercellular adhesion molecule-1 (ICAM-1), which modulates the inflammatory response, and the profibrotic cytokine connective tissue growth factor (CTGF) in an SGK1- and NF-kappaB-dependent manner. Similar to the in vitro results, uninephrectomized rats that were treated with aldosterone demonstrated increased glomerular expression of SGK1, ICAM-1, and CTGF proteins than untreated rats; these changes were accompanied by hypertension, glomerulosclerosis, and inflammation. In conclusion, these findings suggest that aldosterone stimulates ICAM-1 and CTGF transcription via the activation of SGK1 and NF-kappaB, effects that may contribute to the progression of aldosterone-induced mesangial fibrosis and inflammation.
Integrated care: a new model for COPD management?
Authors: T. A. R. Seemungal, J. A. Wedzicha
Journal: European Respiratory Journal (2006)

Total healthcare expenditure in countries of the Organisation for Economic Co-operation and Development has risen from an average of 5% of gross domestic product in 1970 to ∼10% in 2002 1. In 2002, pharmaceutical expenditure ranged from 10% of the total healthcare expenditure in Sweden to 21% in France 1, and a major portion of this expenditure arose through hospital care. Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases worldwide 2 and a common cause of hospitalisation. An analysis of the economic cost of COPD in the UK shows that 54% accrues from hospitalisation; a further 32% is equally divided between scheduled care and drug treatment 3. The Study of Risk Factors of COPD Exacerbation (EFRAM Study) showed that among a wide range of potential risk factors, only previous admissions, lower forced expiratory volume in one second, and the under-prescription of oxygen are independently associated with a higher risk of admission for a COPD exacerbation 4. Under-prescription of home oxygen is easily modifiable once hypoxia has been diagnosed, but hospital admission rates for COPD remain a challenge for pulmonologists and chest therapists alike. In the current issue of the European Respiratory Journal , there is a new and interesting attempt at management of the severe COPD patient. Casas et al. 5 advance a model that may have great potential for the cross-cultural modification of hospitalisation rates for COPD. Previous studies have shown that self-management of COPD within the community can reduce hospitalisation 6 and exacerbation severity 6, 7. The economic efficacy of these models is unknown, but since hospitalisation contributes the greatest proportion of costs for COPD, models targeting patients at risk for hospitalisation may be expected to have the widest appeal to chest physicians and healthcare providers …
Cc Chemokine Receptor (Ccr)3/Eotaxin Is Followed by Ccr4/Monocyte-Derived Chemokine in Mediating Pulmonary T Helper Lymphocyte Type 2 Recruitment after Serial Antigen Challenge in Vivo
Authors: Clare M. Lloyd, Tracy Delaney, Trang Nguyen, Jane Tian, Carlos Martinez-A, Anthony J. Coyle, Jose-Carlos Gutierrez-Ramos
Journal: The Journal of Experimental Medicine (2000)

Isolated peripheral blood CD4 cells from allergic individuals express CC chemokine receptor (CCR)3 and CCR4 after expansion in vitro. In addition, human T helper type 2 (Th2) cells polarized in vitro selectively express CCR3 and CCR4 at certain stages of activation/differentiation and respond preferentially to the ligands eotaxin and monocyte-derived chemokine (MDC). However, controversy arises when the in vivo significance of this distinct expression is discussed. To address the functional role of CCR3/eotaxin and CCR4/MDC during the in vivo recruitment of Th2 cells, we have transferred effector Th cells into naive mice to induce allergic airway disease. Tracking of these cells after repeated antigen challenge has established that both CCR3/eotaxin and CCR4/MDC axes contribute to the recruitment of Th2 cells to the lung, demonstrating the in vivo relevance of the expression of these receptors on Th2 cells. We have shown that involvement of the CCR3/eotaxin pathway is confined to early stages of the response in vivo, whereas repeated antigen stimulation results in the predominant use of the CCR4/MDC pathway. We propose that effector Th2 cells respond to both CCR3/eotaxin and CCR4/MDC pathways initially, but that a progressive increase in CCR4-positive cells results in the predominance of the CCR4/MDC axis in the long-term recruitment of Th2 cells in vivo.
Screening for Type 2 Diabetes and Impaired Glucose Metabolism
Authors: Stephen Colagiuri, Zafirul Hussain, Paul Zimmet, Adrian Cameron, Jonathan Shaw
Journal: Diabetes Care (2004)

OBJECTIVE—To assess the Australian protocol for identifying undiagnosed type 2 diabetes and impaired glucose metabolism. RESEARCH DESIGN AND METHODS—The Australian screening protocol recommends a stepped approach to detecting undiagnosed type 2 diabetes based on assessment of risk status, measurement of fasting plasma glucose (FPG) in individuals at risk, and further testing according to FPG. The performance of and variations to this protocol were assessed in a population-based sample of 10,508 Australians. RESULTS—The protocol had a sensitivity of 79.9%, specificity of 79.9%, and a positive predictive value (PPV) of 13.7% for detecting undiagnosed type 2 diabetes and sensitivity of 51.9% and specificity of 86.7% for detecting impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). To achieve these diagnostic rates, 20.7% of the Australian adult population would require an oral glucose tolerance test (OGTT). Increasing the FPG cut point to 6.1 mmol/l (110 mg/dl) or using HbA1c instead of FPG to determine the need for an OGTT in people with risk factors reduced sensitivity, increased specificity and PPV, and reduced the proportion requiring an OGTT. However, each of these protocol variations substantially reduced the detection of IGT or IFG. CONCLUSIONS—The Australian screening protocol identified one new case of diabetes for every 32 people screened, with 4 of 10 people screened requiring FPG measurement and 1 in 5 requiring an OGTT. In addition, 1 in 11 people screened had IGT or IFG. Including HbA1c measurement substantially reduced both the number requiring an OGTT and the detection of IGT or IFG.
Bioimpedance monitoring of rehydration in cholera
Authors: J.J. McDonald, B. Chanduvi, G. Velarde, L. Carrillo, V. Torre, J. Watanabe, J. Villarreal, A. Ramirez-Ramos, R. Mantle, F. Diaz, R.H. Gilman
Journal: The Lancet (1993)

Measurement of bioimpedance (BI) is a simple non-invasive technique that relies on the different conductivity of tissues to define body composition and can be easily adapted to automated monitoring. We assessed the accuracy of Bl in monitoring rehydration and acute fluid fluxes in 35 Peruvian cholera patients. Patients were monitored throughout the acute phase of diarrhoea and followed up at 3 and 10 days. Bl was compared with other objective measures of dehydration including packed cell volume, serum protein, and calculated fluid balance.Bl rapidly detected inadequate treatment and acute fluid flux, correlating highly with intravascular hydration as measured by serum protein and packed cell volume. Bl values during dehydration were significantly raised compared with 10-day convalescent values and age-matched controls (p<0·05). We also encountered an unexpected difference in the bioelectrical response to dehydration and rehydration between sexes. We conclude that Bl has uses in monitoring dehydrated patients, in oral rehydration trials, and in physiological studies.