tbuckley/cabot-search huggingface dataset:
Performance of Comorbidity, Risk Adjustment, and Functional Status Measures in Expenditure Prediction for Patients With Diabetes
Authors: Matthew L. Maciejewski, Chuan-Fen Liu, Stephan D. Fihn
Journal: Diabetes Care (2008)

OBJECTIVE—To compare the ability of generic comorbidity and risk adjustment measures, a diabetes-specific measure, and a self-reported functional status measure to explain variation in health care expenditures for individuals with diabetes. RESEARCH DESIGN AND METHODS—This study included a retrospective cohort of 3,092 diabetic veterans participating in a multisite trial. Two comorbidity measures, four risk adjusters, a functional status measure, a diabetes complication count, and baseline expenditures were constructed from administrative and survey data. Outpatient, inpatient, and total expenditure models were estimated using ordinary least squares regression. Adjusted R2 statistics and predictive ratios were compared across measures to assess overall explanatory power and explanatory power of low- and high-cost subgroups. RESULTS—Administrative data–based risk adjusters performed better than the comorbidity, functional status, and diabetes-specific measures in all expenditure models. The diagnostic cost groups (DCGs) measure had the greatest predictive power overall and for the low- and high-cost subgroups, while the diabetes-specific measure had the lowest predictive power. A model with DCGs and the diabetes-specific measure modestly improved predictive power. CONCLUSIONS—Existing generic measures can be useful for diabetes-specific research and policy applications, but more predictive diabetes-specific measures are needed.
Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors
Authors: Erica T. Warner, Rulla M. Tamimi, Melissa E. Hughes, Rebecca A. Ottesen, Yu-Ning Wong, Stephen B. Edge, Richard L. Theriault, Douglas W. Blayney, Joyce C. Niland, Eric P. Winer, Jane C. Weeks, Ann H. Partridge
Journal: Journal of Clinical Oncology (2015)

To evaluate the relationship between race/ethnicity and breast cancer-specific survival according to subtype and explore mediating factors.Participants were women presenting with stage I to III breast cancer between January 2000 and December 2007 at National Comprehensive Cancer Network centers with survival follow-up through December 2009. Cox proportional hazards regression was used to compare breast cancer-specific survival among Asians (n = 533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n = 14,268), overall and stratified by subtype (luminal A like, luminal B like, human epidermal growth factor receptor 2 type, and triple negative). Model estimates were used to derive mediation proportion and 95% CI for selected risk factors.In multivariable adjusted models, overall, blacks had 21% higher risk of breast cancer-specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For estrogen receptor-positive tumors, black and white survival differences were greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to 5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were 76% and 56% more likely to die as a result of luminal A-like and luminal B-like tumors, respectively. No disparities were observed for triple-negative or human epidermal growth factor receptor 2-type tumors. Asians and Hispanics were less likely to die as a result of breast cancer compared with whites (Asians: HR, 0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For blacks, tumor characteristics and stage at diagnosis were significant disparity mediators. Body mass index was an important mediator for blacks and Asians.Racial disparities in breast cancer survival vary by tumor subtype. Interventions are needed to reduce disparities, particularly in the first 2 years after diagnosis among black women with estrogen receptor-positive tumors.
Quantifying pulmonary perfusion in primary pulmonary hypertension using electron-beam computed tomography
Authors: A.T. Jones, D.M. Hansell, T.W. Evans
Journal: European Respiratory Journal (2004)

Traditionally, a gravitational distribution of pulmonary perfusion has been described in normal subjects. How this may vary in patients with primary pulmonary hypertension (PPH), which is characterised by vascular obstruction due to intimal thickening, smooth muscle cell proliferation and episodes of thrombosis in small and medium sized pulmonary arteries, is unclear. In this study the potential of electron-beam computed tomography in quantifying the distribution of pulmonary perfusion in patients with PPH was investigated. Contrast-enhanced sections were obtained during inspiration in the supine position at baseline and during administration of the vasodilator adenosine in five healthy subjects and five patients with PPH. Under each experimental condition, regions of interest were placed along the nondependent-to-dependent axis and values for relative perfusion derived. In healthy individuals, a marked nondependent-to-dependent gradient in perfusion was observed. By contrast, in PPH, perfusion values were significantly lower and were uniform across the lung section, although the administration of adenosine resulted in increased perfusion in all regions of interest. Electron-beam computed tomography provides physiological and structural information about the pulmonary circulation in subjects with pulmonary vascular disease.
Mitochondrial Sources of H <sub>2</sub> O <sub>2</sub> Generation Play a Key Role in Flow-Mediated Dilation in Human Coronary Resistance Arteries
Authors: Yanping Liu, Hongtao Zhao, Hongwei Li, B. Kalyanaraman, Alfred C. Nicolosi, David D. Gutterman
Journal: Circulation Research (2003)

We previously showed that hydrogen peroxide (H2O2) contributes to flow-induced dilation in human coronary resistance arteries (HCRAs); however, the source of this H2O2 is not known. We hypothesized that the H2O2 is derived from superoxide (O2*-) generated by mitochondrial respiration. HCRAs were dissected from right atrial appendages obtained from patients during cardiac surgery and cannulated with micropipettes. H2O2-derived radicals and O2*- were detected by electron spin resonance (ESR) using BMPO as the spin trap and by histofluorescence using hydroethidine (HE, 5 micromol/L) and dichlorodihydrofluorescein (DCFH, 5 micromol/L). Diameter changes to increases in pressure gradients (20 and 100 cm H2O) were examined in the absence and the presence of rotenone (1 micromol/L), myxothiazol (100 nmol/L), cyanide (1 micromol/L), mitochondrial complex I, III, and IV inhibitors, respectively, and apocynin (3 mmol/L), a NADPH oxidase inhibitor. At a pressure gradient of 100 cm H2O, ubisemiquinone and hydroxyl radicals were detected from effluents of vessels. Including superoxide dismutase and catalase in the perfusate reduced the ESR signals. Relative ethidium and DCFH fluorescence intensities in HCRAs exposed to flow were enhanced (1.45+/-0.15 and 1.57+/-0.12, respectively compared with no-flow) and were inhibited by rotenone (0.87+/-0.17 and 0.95+/-0.07). Videomicroscopic studies showed that rotenone and myxothiazol blocked flow-induced dilation (% max. dilation at 100 cm H2O: rotenone, 74+/-3% versus 3+/-13%; myxothiazol, 67+/-3% versus 28+/-4%; P<0.05). Neither cyanide nor apocynin altered flow-induced dilation. These results suggest that shear stress induced H2O2 formation, and flow-induced dilation is derived from O2*- originating from mitochondrial respiration.
984 COMBINATION OF THE MEDIAN AND VARIABILITY OF LIVER STIFFNESS MEASUREMENTS BY TRANSIENT ELASTOGRAPHY IMPROVES THE ACCURACY OF DIAGNOSING ADVANCED FIBROSIS IN NONALCOHOLIC FATTY LIVER DISEASE
Authors: V.W. Wong, G.L. Wong, A.M. Chim, K. Yiu, A.W. Chan, P.C. Choi, J.J. Sung, H.L Chan
Journal: Journal of Hepatology (2008)
Use of an Insulin Bolus Advisor Improves Glycemic Control in Multiple Daily Insulin Injection (MDI) Therapy Patients With Suboptimal Glycemic Control
Authors: Ralph Ziegler, David A. Cavan, Iain Cranston, Katharine Barnard, Jacqueline Ryder, Claudia Vogel, Christopher G. Parkin, Walter Koehler, Iris Vesper, Bettina Petersen, Matthias A. Schweitzer, Robin S. Wagner
Journal: Diabetes Care (2013)

Use of automated bolus advisors is associated with improved glycemic control in patients treated with insulin pump therapy. We conducted a study to assess the impact of using an insulin bolus advisor embedded in a blood glucose (BG) meter on glycemic control and treatment satisfaction in patients treated with multiple daily insulin injection (MDI) therapy. The study goal was to achieve >0.5% A1C reduction in most patients.This was a 26-week, prospective, randomized, controlled, multinational study that enrolled 218 MDI-treated patients with poorly controlled diabetes (202 with type 1 diabetes, 16 with type 2 diabetes) who were 18 years of age or older. Participants had mean baseline A1C of 8.9% (SD, 1.2 [74 mmol/mol]), mean age of 42.4 years (SD, 14.0), mean BMI of 26.5 kg/m(2) (SD, 4.2), and mean diabetes duration of 17.7 years (SD, 11.1). Control group (CNL) patients used a standard BG meter and manual bolus calculation; intervention group (EXP) patients used the Accu-Chek Aviva Expert meter with an integrated bolus advisor to calculate insulin dosages. Glucose data were downloaded and used for therapy parameter adjustments in both groups.A total of 193 patients (CNL, n = 93; EXP, n = 100) completed the study. Significantly more EXP than CNL patients achieved >0.5% A1C reduction (56.0% vs. 34.4%; P < 0.01). Improvement in treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire scale) was significantly greater in EXP patients (11.4 [SD, 6.0] vs. 9.0 [SD, 6.3]; P < 0.01). Percentage of BG values <50 mg/dL was <2% in both groups during the study.Use of an automated bolus advisor resulted in improved glycemic control and treatment satisfaction without increasing severe hypoglycemia.
Ooplasmic and nuclear transfer to prevent mitochondrial DNA disorders: conceptual and normative issues
Authors: A.L. Bredenoord, G. Pennings, G. de Wert
Journal: Human Reproduction Update (2008)

BACKGROUND; Mitochondrial DNA (mtDNA) disorders are an important cause of human diseases. In view of the limitations of prenatal diagnosis and preimplantation genetic diagnoses, alternatives such as ooplasmic transfer (OT) and nuclear transfer (NT) have been proposed to prevent the transmission of mtDNA mutations. Both OT and NT are radical in the sense that they do not entail genetic selection, but genetic intervention to correct the genetic cause of the disease.After interviews with experts in the field, the relevant literature was searched and analyzed. Bioethical issues were divided into conceptual and normative points.OT is the transfer of normal mitochondria to a carrier's oocyte containing mutant mtDNA. In case of NT, a donated oocyte is enucleated and replaced with the nuclear DNA from a woman carrying a mtDNA mutation. NT can be performed both before and after in vitro fertilization, respectively, with the nucleus of an unfertilized oocyte, with the pronuclei of the zygote, or with the nucleus of a blastomere of an embryo. Conceptual questions regard whether these techniques amount to germ-line modification and human cloning. Normative questions concern, among others, the significance of intervening in the mtDNA, the implications of having 'three genetic parents', the ethics of oocyte donation and the health and safety risks for children conceived as a result of one of these techniques.Further interdisciplinary debate and research is needed to determine whether a clinical application of OT and NT can be morally justified, and if so, under which conditions.
Thrombospondin 1 Promotes Tumor Macrophage Recruitment and Enhances Tumor Cell Cytotoxicity of Differentiated U937 Cells
Authors: Gema Martin-Manso, Susana Galli, Lisa A. Ridnour, Maria Tsokos, David A. Wink, David D. Roberts
Journal: Cancer Research (2008)

Abstract Inhibition of tumor growth by thrombospondin (TSP) 1 is generally attributed to its antiangiogenic activity, but effects on tumor immunity should also be considered. We show that overexpression of TSP1 in melanoma cells increases macrophage recruitment into xenograft tumors grown in nude or beige/nude mice. In vitro, TSP1 acutely induces expression of plasminogen activator inhibitor-1 (PAI-1) by monocytic cells, suggesting that TSP1-induced macrophage recruitment is at least partially mediated by PAI-1. Tumor-associated macrophages (TAM) can either promote or limit tumor progression. The percentage of M1-polarized macrophages expressing inducible nitric oxide synthase is increased in TSP1-expressing tumors. Furthermore, soluble TSP1 stimulates killing of breast carcinoma and melanoma cells by IFN-γ–differentiated U937 cells in vitro via release of reactive oxygen species. TSP1 causes a significant increase in phorbol ester–mediated superoxide generation from differentiated monocytes by interaction with α6β1 integrin through its NH2-terminal region. The NH2-terminal domain of TSP2 also stimulates monocyte superoxide production. Extracellular calcium is required for the TSP1-induced macrophage respiratory burst. Thus, TSP1 may play an important role in antitumor immunity by enhancing recruitment and activation of M1 TAMs, which provides an additional selective pressure for loss of TSP1 and TSP2 expression during tumor progression. [Cancer Res 2008;68(17):7090–10]
Increased Exhaled Cysteinyl-Leukotrienes and 8-Isoprostane in Aspirin-induced Asthma
Authors: Adam Antczak, Paolo Montuschi, Sergei Kharitonov, Pawel Gorski, Peter J. Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The pathogenesis of aspirin-induced asthma (AIA) has not yet been clearly elucidated, although eicosanoid metabolites appear to play an important role. We hypothesized that levels of eicosanoids in exhaled air condensate are abnormal in patients with AIA and that they change in patients receiving steroid therapy. We measured cysteinyl-leukotrienes (cys-LTs), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4), and also 8-isoprostane as a marker of oxidative stress, by enzyme immunoassay in exhaled breath condensate from patients with AIA (17 steroid naive; mean age, 41 ± 23 years; FEV1, 63%pred), 26 patients with aspirin-tolerant asthma (ATA) (11 steroid naive; mean age, 47 ± 18 years; FEV1, 69%pred), and 16 healthy subjects (mean age, 45 ± 17 years; FEV1, 93%pred). Cys-LTs were significantly higher in steroid-naive patients with AIA compared with steroid-naive patients with ATA and healthy subjects (152.3 ± 30.4 and 36.6 ± 7.1 versus 19.4 ± 2.8 pg/ml; p < 0.05 and p < 0.05, respectively). Steroid-naive patients with AIA also had higher levels of 8-isoprostane than normal subjects (131.8 ± 31.0 versus 21.9 ± 4.5 pg/ml; p < 0.05). There were significantly lower levels of both cys-LTs and 8-isoprostanes in steroid-treated patients with AIA. There was no difference in either the PGE2 or LTB4 level between the patient groups. This is the first study to show that cys-LTs and 8-isoprostanes are elevated in expired breath condensate of steroid-naive patients with AIA, and that cys-LTs are decreased in steroid-treated patients. Exhaled PGE2 levels are not reduced, so that it is unlikely that a deficiency of PGE2 is an important mechanism, whereas exhaled LTB4 levels are unchanged, indicating an abnormality beyond 5-lipoxygenase.
Vessel-widening by VEGF
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

A growth factor for blood vessels has also been touted as an inducer of lymph vessel growth. But Wirzenius et al. (page 1431) now find that, although the growth factor spurs the enlargement of existing lymph vessels, it does not induce the sprouting of new ones.






Figure 1

VEGF induces lymph vessel enlargement (top) but not the sprouting of new vessels (bottom).




Lymph vessels are a follow-up act to blood vessels during embryogenesis. Vascular endothelial growth factor (VEGF) induces new blood vessel growth by binding to its receptor VEGFR-2 on vascular endothelial cells. VEGF-C and -D then kick off lymph vessel sprouting by binding to VEGFR-3 on lymphatic endothelial cells. But studies in mice that overexpress VEGF suggest that the two signaling pathways are not completely segregated. The abnormally large lymph vessels in these mice imply that VEGF somehow controls lymph vessel enlargement as well.

The team now finds that VEGFR-2 is also expressed on lymph vessels and induces their widening. But VEGF did not start lymph vessel growth anew: the missing lymph network of mouse embryos lacking VEGF-C and -D was not rescued by VEGF.

Lymphatic enlargement during inflammation helps immune cells accumulate at the site of injury or infection. But lymph vessels that don't later slim down increase the risk of chronic inflammation. Lymph vessel expansion is also dangerous during tumor growth in lymph nodes, as enlarged vessels act as highways for metastasizing tumor cells. Current antitumor strategies that target VEGF prevent blood vessel growth and thus nutrient supply to tumors. This study suggests that anti-VEGF treatment may also prevent tumor metastasis.
DERMATOLOGY AT THE LONDON HOSPITAL
Authors: BRIAN F. RUSSELL
Journal: British Journal of Dermatology (1969)

Journal Article DERMATOLOGY AT THE LONDON HOSPITAL Get access BRIAN F. RUSSELL BRIAN F. RUSSELL Skin Department, The London Hospital London, E.C Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 10, 1 October 1969, Pages 780–793, https://doi.org/10.1111/j.1365-2133.1969.tb15943.x Published: 01 October 1969 Article history Accepted: 18 December 1968 Published: 01 October 1969
Panic Disorder Subtypes: Differential Responses to CO<sub>2</sub> Challenge
Authors: B Biber, T Alkin
Journal: American Journal of Psychiatry (1999)

The purpose of this study was to investigate the possibility of a differential sensitivity to CO2 in patients diagnosed with panic disorder subtypes that were defined by the presence of prominent respiratory symptoms.The authors used a 35% CO2 and 65% O2 mixture as a challenge agent. Fifty-one unmedicated subjects with DSM-III-R panic disorder, who were divided into respiratory (N = 28) and nonrespiratory (N = 23) subtypes by their symptom profiles, underwent a CO2 challenge procedure. Patients in the two groups were compared with regard to physiological and psychological measures, pulmonary function tests, panic rates, and smoking habits.The patients in the respiratory group were significantly more sensitive to CO2 than were the patients in the nonrespiratory group. The respiratory group also had higher scores on the Panic and Agoraphobia Scale and had a longer duration of illness; both of these factors can be indicators of illness severity. In addition, the respiratory group's higher cigarette consumption (mean = 12.46 package-years, SD = 2.49) may have been a contributory factor not only for illness severity but also for the pathogenesis of panic disorder.The CO2 challenge procedure appears to be a good dissection tool in the understanding of different subtypes of panic disorder. Moreover, there may be a more specific association with prominent respiratory symptom subtype and CO2 hypersensitivity.
Interleukin-12: Biological Properties and Clinical Application
Authors: Michele Del Vecchio, Emilio Bajetta, Stefania Canova, Michael T. Lotze, Amy Wesa, Giorgio Parmiani, Andrea Anichini
Journal: Clinical Cancer Research (2007)

Abstract Interleukin-12 (IL-12) is a heterodimeric protein, first recovered from EBV-transformed B cell lines. It is a multifunctional cytokine, the properties of which bridge innate and adaptive immunity, acting as a key regulator of cell-mediated immune responses through the induction of T helper 1 differentiation. By promoting IFN-γ production, proliferation, and cytolytic activity of natural killer and T cells, IL-12 induces cellular immunity. In addition, IL-12 induces an antiangiogenic program mediated by IFN-γ–inducible genes and by lymphocyte-endothelial cell cross-talk. The immunomodulating and antiangiogenic functions of IL-12 have provided the rationale for exploiting this cytokine as an anticancer agent. In contrast with the significant antitumor and antimetastatic activity of IL-12, documented in several preclinical studies, clinical trials with IL-12, used as a single agent, or as a vaccine adjuvant, have shown limited efficacy in most instances. More effective application of this cytokine, and of newly identified IL-12 family members (IL-23 and IL-27), should be evaluated as therapeutic agents with considerable potential in cancer patients.
Successful treatment of resistant giant cell arteritis with etanercept
Authors: A L Tan
Journal: Annals of the Rheumatic Diseases (2003)

Giant cell arteritis (GCA) is a systemic medium to large cell vasculitis that predominantly affects the elderly population.1 Initial high dose corticosteroids are the cornerstone of treatment, which is subsequently tapered.2 However, disease flares are not uncommon and corticosteroid related side effects are frequent.3

The limitations of corticosteroids in the treatment of some cases of GCA have led to the evaluation of other strategies using steroid sparing agents.4–7 In two previous studies patients with resistant GCA were treated with infliximab, a monoclonal chimeric antibody directed against tumour necrosis factor α (TNFα) that binds circulating and membrane bound TNF, with promising results.6,7 The rationale for this approach was that the vasculitic lesions in GCA had prominent macrophage infiltration where excess TNFα production had been demonstrated by immunohistochemistry.8

We report the case of a patient who was treated with the anti-TNFα agent etanercept, which is the fusion protein of the extracellular ligand binding portion of the p75 TNF receptor and the Fc portion of IgG1, on the basis that the GCA could not be controlled and that complications of high dose corticosteroid treatment …
BOMP/EPI intensive alternating chemotherapy for IGCCC poor-prognosis germ-cell tumors: The Spanish Germ-Cell Cancer Group experience (GG)
Authors: J R Germà-Lluch, X Garcia del Muro, J M Tabernero, M Sánchez, J Aparicio, E Alba, A Barnadas
Journal: Annals of Oncology (1999)

Patients with poor-prognosis germ-cell tumors according to the IGCCC have a poor long-term survival. This study evaluates the efficacy and toxicity of the intensive alternating chemotherapy regimen BOMP/EPI in these patients.Patients with IGCCC poor-prognosis germ-cell tumors treated at 13 centres were studied. Treatment consisted of bleomycin 30 mg, vincristine 2 mg, methotrexate 300 mg/m2 and cisplatin 100 mg/m2 (BOMP), alternating after a 14-day interval with etoposide 120 mg/m2 day 1-4, ifosfamide 1.3 g/m2 day 1-4 and cisplatin 25 mg/m2 day 1-4 (EPI). BOMP was administered 21 days after the EPI. Bleomycin was administered weekly per 12 weeks.Thirty-eight patients were treated. The median number of cycles administered was 7 (1-10 cycles). Eighteen patients achieved complete responses with chemotherapy alone (12 had necrosis and 2 mature teratoma at postchemotherapy resection), and four achieved complete responses with chemotherapy and surgical resection of viable cancer. Thus, an overall favorable response was achieved in 22 patients (60%). Four additional patients had marker-negative non-resected residual masses. Eleven patients were considered treatment failures, including one who died early and another who succumbed to granulocytopenic sepsis and renal failure. Hematologic toxicity was the most common, with 26 patients (70%) having grade 4 granulocytopenia. After a median follow-up of 41 months, the actuarial two-year overall survival and progression-free survival were 64% and 58%, respectively.BOMP/EPI is active in poor-prognosis germ-cell tumors according to the IGCCC criteria. The results obtained compare favorably with those expected with conventional chemotherapy, and justify further studies.