tbuckley/cabot-search huggingface dataset:
Provide GPs with spirometry, not spirometers
Authors: P. Enright
Journal: Thorax (2008)

Investigators from Tasmania, an island state of Australia (famous for its marsupial devils), have demonstrated, in this issue of Thorax ,1 that both the quantity and quality of spirometry tests provided by nurses visiting general practitioner (GP) offices were much better than when GPs were given a spirometer and taught when and how to use it (see page 408) . The visiting (peripatetic or itinerant) nurses tested 59% of the target group of ever smokers over the age of 35 years, compared with only 8% tested by the GPs with their own spirometer. Quality goals for spirometry were met by 76% of the tests done by the nurses but only by 44% of the tests done by the GPs.

In this issue of Thorax , a study is described in which investigators from Poland2 offered spirometry testing by visiting nurses to all 2250 adult patients over the age of 39 years in the practice of a single GP (see page 402) . Over 87% of the target group responded by scheduling a visit to the office for spirometry testing. Post-bronchodilator (post-BD) spirometry was done for those with airway obstruction pre-BD. Quality goals for spirometry were met for 92% of the tests. Post-BD airway obstruction, consistent with chronic obstructive pulmonary disease (COPD), was detected in 9% of …
Phase II Presurgical Feasibility Study of Bevacizumab in Untreated Patients With Metastatic Renal Cell Carcinoma
Authors: Eric Jonasch, Christopher G. Wood, Surena F. Matin, Shi-Ming Tu, Lance C. Pagliaro, Paul G. Corn, Ana Aparicio, Pheroze Tamboli, Randall E. Millikan, Xuemei Wang, John C. Araujo, Wadih Arap, Nizar Tannir
Journal: Journal of Clinical Oncology (2009)

Purpose To assess safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC), and to explore the hypothesis that pretreatment of patients with antiangiogenic therapy will select patients who benefit most from cytoreductive nephrectomy. Patients and Methods Patients with newly diagnosed, clear cell mRCC whose primary tumors were considered resectable were enrolled. In this single-arm, phase II trial, patients received bevacizumab plus erlotinib (first patients, n = 23) or bevacizumab alone (n = 27 patients) for 8 weeks followed by restaging. If patients demonstrated progressive disease and had declining performance statuses after 8 weeks, nephrectomy procedures were deferred. Postoperatively, patients continued on the study drug or drugs if disease stabilization or regression had occurred. Results Between March 2005 and March 2008, 52 patients were enrolled on study, and 50 were included in the analysis. By Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk, features. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI, 5.5 to 15.6 months). Median overall survival was 25.4 months (95% CI, 11.4 months to not estimable). Two perioperative deaths occurred; neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients and treatment delay for two others. Conclusion Presurgical treatment with bevacizumab therapy yields clinical outcomes comparable to post-surgical treatment with antiangiogenic therapy in patients with mRCC, but it may result in wound-healing delays. Prospective, randomized trials to test the use of presurgical therapy as a method to select appropriate patients for cytoreductive nephrectomy are warranted.
Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders
Authors: Sarah E. Soden, Carol J. Saunders, Laurel K. Willig, Emily G. Farrow, Laurie D. Smith, Josh E. Petrikin, Jean-Baptiste LePichon, Neil A. Miller, Isabelle Thiffault, Darrell L. Dinwiddie, Greyson Twist, Aaron Noll, Bryce A. Heese, Lee Zellmer, Andrea M. Atherton, Ahmed T. Abdelmoity, Nicole Safina, Sarah S. Nyp, Britton Zuccarelli, Ingrid A. Larson, Ann Modrcin, Suzanne Herd, Mitchell Creed, Zhaohui Ye, Xuan Yuan, Robert A. Brodsky, Stephen F. Kingsmore
Journal: Science Translational Medicine (2014)

Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown. One hundred families with 119 children affected by NDD received diagnostic WGS and/or WES of parent-child trios, wherein the sequencing approach was guided by acuity of illness. Forty-five percent received molecular diagnoses. An accelerated sequencing modality, rapid WGS, yielded diagnoses in 73% of families with acutely ill children (11 of 15). Forty percent of families with children with nonacute NDD, followed in ambulatory care clinics (34 of 85), received diagnoses: 33 by WES and 1 by staged WES then WGS. The cost of prior negative tests in the nonacute patients was $19,100 per family, suggesting sequencing to be cost-effective at up to $7640 per family. A change in clinical care or impression of the pathophysiology was reported in 49% of newly diagnosed families. If WES or WGS had been performed at symptom onset, genomic diagnoses may have been made 77 months earlier than occurred in this study. It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients.
Effects of D-4F on Vasodilation and Vessel Wall Thickness in Hypercholesterolemic LDL Receptor–Null and LDL Receptor/Apolipoprotein A-I Double-Knockout Mice on Western Diet
Authors: Jingsong Ou, Jingli Wang, Hao Xu, Zhijun Ou, Mary G. Sorci-Thomas, Deron W. Jones, Paul Signorino, John C. Densmore, Sushma Kaul, Keith T. Oldham, Kirkwood A. Pritchard
Journal: Circulation Research (2005)

Previously we showed L-4F, a novel apolipoprotein A-I (apoA-I) mimetic, improved vasodilation in 2 dissimilar models of vascular disease: hypercholesterolemic LDL receptor-null (Ldlr(-/-)) mice and transgenic sickle cell disease mice. Here we determine the mechanisms by which D-4F improves vasodilation and arterial wall thickness in hypercholesterolemic Ldlr(-/-) mice and Ldlr(-/-)/apoA-I null (apoA-I(-/-)), double-knockout mice. Ldlr(-/-) and Ldlr(-/-)/apoA-I(-/-) mice were fed Western diet (WD) with and without D-4F. Oral D-4F restored endothelium- and endothelial NO synthase (eNOS)-dependent vasodilation in direct relationship to duration of treatments and reduced wall thickness in as little as 2 weeks in vessels with preexisting disease in Ldlr(-/-) mice. D-4F had no effect on total or HDL cholesterol concentrations but reduced proinflammatory HDL levels. D-4F had no effect on plasma myeloperoxidase concentrations but reduced myeloperoxidase association with apoA-I as well as 3-nitrotyrosine in apoA-I. D-4F increased endothelium- and eNOS-dependent vasodilation in Ldlr(-/-)/apoA-I(-/-) mice but did not reduce wall thickness as it had in Ldlr(-/-) mice. Vascular endothelial cells were treated with 22(R)-hydroxycholesterol with and without L-4F. 22(R)-Hydroxycholesterol decreased NO (*NO) and increased superoxide anion (O2*-) production and increased ATP-binding cassette transporter-1 and collagen expression. L-4F restored *NO and O2*- balance, had little effect on ATP-binding cassette transporter-1 expression, but reduced collagen expression. These data demonstrate that although D-4F restores vascular endothelial cell and eNOS function to increase vasodilation, HDL containing apoA-I, or at least some critical concentration of the antiatherogenic lipoprotein, is required for D-4F to decrease vessel wall thickness.
Respiratory Symptoms in the First 7 Years of Life and Birth Weight at Term
Authors: Daan Caudri, Alet Wijga, Ulrike Gehring, Henriette A. Smit, Bert Brunekreef, Marjan Kerkhof, Maarten Hoekstra, Jorrit Gerritsen, Johan C. de Jongste
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The relation between birth weight and respiratory symptoms and asthma in children remains unclear. Previous studies focused on a relation at separate ages. A longitudinal analysis may lead to a better understanding.To estimate the effect of birth weight on the development and course of respiratory symptoms and asthma in the first 7 years of life.In a prospective birth cohort study, 3,628 children with a gestational age 37 weeks or more were monitored for 7 years. Parental questionnaires were used to assess respiratory health yearly. Associations of birth weight with respiratory symptoms (wheezing, coughing, respiratory infections) and doctor's diagnosis of asthma were assessed in a repeated-event analysis.Lower birth weight was associated with more respiratory symptoms (odds ratio [OR] per kg decrease in birth weight, 1.21; 95% confidence interval [CI], 1.09-1.34). The effect of birth weight increased from age 1 to 5, but decreased thereafter and was no longer significant at the age of 7. The effect of birth weight on respiratory symptoms was significantly greater among children exposed to tobacco smoke in their home than among nonexposed children (OR at 5 yr: 1.21 [95% CI, 1.02-1.44] and 1.52 [95% CI, 1.23-1.87], respectively). Birth weight and a doctor's diagnosis of asthma were not related (OR, 1.06; 95% CI, 0.82-1.37).A lower birth weight in children born at term is associated with a transiently increased risk of respiratory symptoms. This effect is enhanced by environmental tobacco smoke exposure.
Imaging Bone and Soft Tissue Tumors with the Proliferation Marker [18F]Fluorodeoxythymidine
Authors: Andreas K. Buck, Ken Herrmann, Christian Meyer zum Büschenfelde, Malik E. Juweid, Mark Bischoff, Gerhard Glatting, Gregor Weirich, Peter Möller, Hans-Jürgen Wester, Klemens Scheidhauer, Tobias Dechow, Christian Peschel, Markus Schwaiger, Sven N. Reske
Journal: Clinical Cancer Research (2008)

We have determined the ability of positron emission tomography (PET) with the thymidine analogue 3'-deoxy-3'[18F]fluorothymidine (FLT) to detect manifestation sites of bone and soft tissue tumors, to assess tumor grading, and to differentiate malignant from benign tumors.In this prospective bicenter trial, FLT-PET was done in 22 patients with established or suspected soft or bone tissue lesions. Routine diagnostic procedures included incisional biopsy, magnetic resonance imaging, and/or contrast-enhanced spiral computed tomography in all patients and [18F]fluorodeoxyglucose (FDG)-PET in 15 patients. Forty-five to 60 minutes after i.v. injection of 350 to 425 MBq FLT, emission and transmission scanning was done. Tracer uptake in the tumor was evaluated semiquantitatively by calculation of mean and maximum standardized uptake values (FLT-SUV) and compared with respective values of FDG. Results were correlated to histopathology and tumor grading.FLT-PET detected all malignant bone or soft tissue tumors (17 of 17). Mean FLT-SUV in benign lesions was 0.7 (range, 0.3-1.3), and 1.3 in low-grade sarcoma (grade 1; range, 1.0-1.6), 4.1 (range, 2.2-6.0; P = 0.002) and 6.1 (range, 2.5-8.3; P = 0.001) in grade 2 and grade 3 tumors, respectively. FLT but not FDG uptake correlated significantly with tumor grading (r = 0.71 versus r = 0.01), and a cutoff value of 2.0 for FLT-SUV discriminated between low- and high-grade tumors.In this clinical study, the proliferation marker FLT was suitable for imaging malignant bone or soft tissue tumors. FLT but not FDG uptake correlated significantly with the tumor grade, suggesting FLT as superior PET tracer for noninvasive grading of sarcomas.
Which laboratory variable is related with time trial performance time in the Tour de France?
Authors: A Lucia, J Hoyos, M Pérez, A Santalla, C P Earnest, J L Chicharro
Journal: British Journal of Sports Medicine (2004)

To investigate the relationship between several physiological variables that can be easily obtained during cycle ergometer gradual testing (for example, peak power output (W(peak)), Vo(2max), or ventilatory threshold (VT)) and actual (>50 km) time trials (TT) time performance during the Tour de France.We collected data in professional cyclists from the first TT of the 1998 Tour de France (TT1, 58 km distance; n = 6 cyclists) and the first (TT2, 56.5 km; n = 5) and second TT of the 1999 Tour de France (TT3, 57 km; n = 5).A negative relationship was found between power output (W) at VT (VT(Watt)) and TT final time (s) in TT1 (r = -0.864; p = 0.026; standard error of estimate (SEE) of 73 s; and 95% confidence limits (95% CL) -0.98; -0.18), TT2 (r = -0.77; p = 0.27; SEE of 139 s; and 95% CL -0.98; 0.35), and TT3 (r = -0.923; p = 0.025; SEE of 94 s; and 95% CL -1.00; -0.22).Actual performance in long TT during the Tour de France (>50 km distance, performed after at least 1-2 weeks of continuous competition), in which some cumulative fatigue inevitably occurs, is related, at least in part, to the power output that elicits the VT. No other routine physiological variable (for example, Vo(2max) or W(peak)) is related to performance in this type of event.
Genetic characterization of fas-associated phosphatase-1 as a putative tumor suppressor gene on chromosome 4q21.3 in hepatocellular carcinoma.
Authors: Shiou-Hwei Yeh, Dai-Chen Wu, Ching-Yi Tsai, Ti-Jung Kuo, Wei-Che Yu, Yuan-Shau Chang, Chi-Ling Chen, Ching-Fang Chang, Ding-Shinn Chen, Pei-Jer Chen
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: Allelic loss at chromosome 4q21-23 occurs frequently in human hepatocellular carcinoma, and the putative tumor suppressor gene (TSG) has not yet been identified. We studied the Fas-associated phosphatase-1 (FAP-1) gene as a potential candidate TSG in this region. EXPERIMENTAL DESIGN: The expression level of FAP-1 RNA in hepatocellular carcinomas was evaluated by RNase protection and quantitative PCR. Sodium bisulfite modification and subsequent single-strand conformational polymorphism and sequence analyses were used to assay the methylation of CpGs at FAP-1 promoter. Direct sequencing of the FAP-1 coding region was conducted for detecting the genetic mutations. Two common single nucleotide polymorphisms of FAP-1 were selected for evaluating their association with the hepatocellular carcinoma trait in sporadic and familial hepatocellular carcinomas. Moreover, the functional effect of FAP-1 on cellular proliferation has been evaluated by small interfering RNA approach. RESULTS: Around 50% of hepatocellular carcinomas showed significantly decreased expression of FAP-1 compared with the corresponding nontumorous liver tissues. In most cases, the RNA level was well correlated with the methylation status of promoter CpGs, suggesting that the promoter methylation may contribute to the down-regulation. Several genetic mutations of FAP-1 have been identified in hepatocellular carcinomas. The G/G genotype of FAP-1 cSNP6304 was significantly associated with the increased risk of multiplex familial hepatocellular carcinomas (odds ratio, 2.44; 95% confidence interval, 1.19-5.01). Finally, knockdown expression of FAP-1 was shown to enhance the cellular proliferation in PLC5 cells. CONCLUSIONS: FAP-1 could be inactivated during hepatocarcinogenesis, mainly attributed by allelic loss and promoter methylation. The genetic mutations and polymorphisms may also confront with the higher hepatocellular carcinoma risk. These results first suggested FAP-1 as a putative TSG in hepatocarcinogenesis.
Effects of a comprehensive self-management programme in patients with chronic obstructive pulmonary disease
Authors: E. Monninkhof, P. van der Valk, J. van der Palen, C. van Herwaarden, G. Zielhuis
Journal: European Respiratory Journal (2003)

The aim of this study was to assess the effects of a comprehensive self-management intervention on health-related quality of life (HRQoL), symptoms and walking distance in patients with stable moderately severe chronic obstructive pulmonary disease (COPD). This study was part of the overall COPD study of the Dept of Pulmonary Medicine, Enschede, which consisted of an inhaled corticosteroid (ICS) trial and a self-management trial. After the ICS trial, all patients were randomised again to a self-management and a control group. The self-management intervention consisted of a skill-oriented patient education programme and a near-home fitness programme, on top of usual care. The control group received usual care by the treating chest physician. HRQoL was measured by the St George's Respiratory Questionnaire (SGRQ) and walking distance by the 6-min walking test. Patients recorded their symptoms in diaries and graded their health status from 1-10 in a weekly report. Altogether, 248 COPD patients were randomly allocated to either an intervention (127) or control (121) group. No differences in the SGRQ scores within and between both groups were observed over 1 yr. Similarly, no differences in symptom scores and 6-min walking distance were found within and between groups. The intervention group reported more exacerbations than the control group. The majority (69%) of the exacerbations in the intervention group were self-treated at home. This study failed to show positive effects of a self-management programme among moderately severe chronic obstructive pulmonary disease patients.
Crystal Formation in Inflammation
Authors: Bernardo S. Franklin, Matthew S. Mangan, Eicke Latz
Journal: Annual Review of Immunology (2016)

The formation and accumulation of crystalline material in tissues is a hallmark of many metabolic and inflammatory conditions. The discovery that the phase transition of physiologically soluble substances to their crystalline forms can be detected by the immune system and activate innate immune pathways has revolutionized our understanding of how crystals cause inflammation. It is now appreciated that crystals are part of the pathogenesis of numerous diseases, including gout, silicosis, asbestosis, and atherosclerosis. In this review we discuss current knowledge of the complex mechanisms of crystal formation in diseased tissues and their interplay with the nutrients, metabolites, and immune cells that account for crystal-induced inflammation.
Collectrin Is Involved in the Development of Salt-Sensitive Hypertension by Facilitating the Membrane Trafficking of Apical Membrane Proteins via Interaction With Soluble <i>N</i> -Ethylmaleiamide-Sensitive Factor Attachment Protein Receptor Complex
Authors: Akihiro Yasuhara, Jun Wada, Sandra M. Malakauskas, Yanling Zhang, Jun Eguchi, Atsuko Nakatsuka, Kazutoshi Murakami, Motoko Kanzaki, Sanae Teshigawara, Kazuya Yamagata, Thu H. Le, Hirofumi Makino
Journal: Circulation (2008)

Collectrin, a homologue of angiotensin converting enzyme 2, is expressed in pancreatic beta cells and renal proximal tubular and collecting duct cells under the control of hepatocyte nuclear factors-1alpha and -1beta. Because collectrin interacts with the soluble N-ethylmaleiamide-sensitive factor attachment protein receptor (SNARE) complexes, we investigated whether collectrin is involved in sodium handling in hypertension by vesicle trafficking of apical membrane proteins. Collectrin physically interacts with the SNARE complex: snapin, synaptosomal-associated protein 23 kDa, syntaxin-4, and vesicle-associated membrane protein-2 in mIMCD-3 cells. siRNA knockdown of collectrin resulted in a reduction in membrane-associated aquaporin-2, alpha-epithelial Na+ channel, and H+-ATPase. Collectrin and SNARE proteins were abundantly expressed in collecting ducts of Wistar-Kyoto rats. Wistar-Kyoto rats and spontaneously hypertensive rats 7 weeks of age were subjected to normal-salt (1% NaCl) and high-salt (8% NaCl) chow for 10 weeks. High-salt chow prominently elevated blood pressure, oral intake, and urinary excretion of NaCl and water in both groups. Although urinary excretion of aldosterone was significantly suppressed in both groups, collectrin expression was upregulated and associated with the maintenance of aquaporin-2, alpha-epithelial Na+ channel, and H+-ATPase in membrane fractions. Collectrin promoter activities and mRNA and protein expressions were upregulated and ubiquitinated collectrin was reduced by high NaCl (175 to 225 mmol/L) and not altered by 1 micromol/L aldosterone in mIMCD-3 cells. Upregulation of collectrin by high NaCl independent of aldosterone functionally links to the trafficking of apical membrane proteins via the SNARE complex, and collectrin may be responsible for the sodium retention in salt-sensitive hypertension.
Hand eczema - prognosis and consequences: a 7-year follow-up study
Authors: A.H. Petersen, J.D. Johansen, M. Hald
Journal: British Journal of Dermatology (2014)

Hand eczema is recognized as a long-lasting disease with personal and societal repercussions. Long-term studies are required to generate information on factors contributing to a poor outcome.The aims of this 7-year follow-up study were to evaluate the clinical course of patients with hand eczema, the occupational consequences and to identify risk factors associated with a poor prognosis.In all, 536 patients with hand eczema participated and were examined by a dermatologist. The clinical severity was assessed at baseline and 7 years later using a self-administrated photographic guide. Additional information was obtained from a questionnaire.Based on the photographic guide, 73% experienced a clinical improvement. Notably, 20% had moderate to very severe hand eczema at follow-up. Severe hand eczema or frequent eruptions at baseline and eczema in other body locations during the follow-up period were risk factors of a poor prognosis. The same factors, as well as being a woman, were associated with occupational consequences and low health-related quality of life. Of those with persistent hand eczema only 40% had visited a dermatologist during the follow-up period and 7% had oral treatment.The disease had improved 7 years later; nevertheless, many patients continued to have considerable symptoms. Patients with a greater risk of a poor outcome are characterized by frequent eruptions, severe hand eczema and more widespread eczema. It should be questioned if more aggressive therapy and closer medical follow-up would be beneficial.
Cisplatin, vinblastine, and bleomycin in inoperable non-small cell lung cancer.
Authors: R Stuart-Harris, R M Fox, D Raghavan, A S Coates, D Hedley, J A Levi, R L Woods, M H Tattersall
Journal: Thorax (1985)

Forty two patients with inoperable non-small cell lung cancer were entered into a phase II study of the combination chemotherapy regimen PVB (cisplatin 60 mg/m2 by intravenous infusion over two hours on day 1, vinblastine 4 mg/m2 by intravenous bolus on days 1 and 2, and bleomycin 15 mg intramuscularly on days 1, 8, and 15), repeated at three weekly intervals. Twelve of 40 evaluable patients (30%) achieved partial responses; there were no complete responses. The median duration of response was 16 weeks (range greater than 8-73 weeks). The median survival of responding patients calculated from entry to the study until death (40 weeks) was superior to that of patients failing to respond (15 weeks). Treatment was accompanied by signs of moderate toxicity, particularly myelosuppression, nausea and vomiting, alopecia, and neuropathy. One patient died from a neutropenic infection. PVB is a moderately toxic regimen for non-small cell lung cancer and appears similar in efficacy and toxicity to high dose cisplatin and vindesine.