tbuckley/cabot-search huggingface dataset:
Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients.
Authors: S De Marchi, E Falleti, R Giacomello, G Stel, E Cecchin, G Sepiacci, N Bortolotti, F Zanello, F Gonano, E Bartoli
Journal: Journal of the American Society of Nephrology (1996)

Vascular access dysfunction is an important cause of morbidity for dialysis patients and a major contributor to hemodialysis cost. Thrombosis is a leading cause of vascular access failure, and usually results from stenotic lesions in the venous outflow system. This study was designed to explore the impact of serum levels of various risk factors for thrombosis and accelerated fibrointimal hyperplasia on progressive stenosis, and the subsequent thrombosis of hemodialysis fistula. A cross-sectional and 2-yr prospective pilot study was performed in 30 nondiabetic hemodialysis patients with primary arteriovenous fistula. Venous dialysis pressure, urea recirculation, color Doppler sonography, and angiography were used to monitor vascular access patency. Eleven patients (37%) developed a progressive stenosis in the venous circuit, which was complicated by thrombosis in three patients. Compared with the patients without fistula dysfunction, these patients had higher serum levels of monocyte chemoattractant protein-1 and interleukin-6, two cytokines that regulate the proliferation of vascular smooth muscle cells, which is the key mechanism in the pathogenesis of fistula stenosis. In addition, they had hyperinsulinemia, hyperlipidemia, and increased plasma levels of two hemostasis-derived risk factors for thrombosis: plasminogen activator inhibitor type 1 and factor VII. Monocyte chemoattractant protein-1, interleukin-6, plasminogen activator inhibitor type 1, factor VII, triglycerides, and the ratios for cholesterol/HDL-cholesterol, apolipoprotein (apo) A-I/ apo C-III, apo A-I/apo B, and glucose/insulin were independent predictors of fistula dysfunction. This study demonstrates the influece of cytokines, hemostasis-derived vascular risk factor, hyperinsullnemia, and abnormallties of lipids and apolipoproteins on primary fistula survival. The assessment of these factors might be useful for the identification of the patients at risk of fistula stenosis and thrombosis.
Immunoglobulin lambda light chain genes in rheumatoid arthritis.
Authors: D Sidebottom, D M Grennan, P A Sanders, A Read
Journal: Annals of the Rheumatic Diseases (1987)

Restriction fragment length polymorphisms (RFLPs) obtained by hybridisation of an immunoglobulin lambda constant region probe to Eco RI digests of genomic deoxyribonucleic acid (DNA) obtained from rheumatoid arthritis (RA) and control subjects have been compared. Polymorphic bands of 8, 13, 18, and 23 kb (kilobases) were shown. The 8/8 genotype and 8 kb allele were increased and the 8/18 genotype and 18 kb allele decreased in the RA group. This effect was independent of HLA and Gm. These findings suggest that genes linked to the loci for the immunoglobulin lambda constant region may influence susceptibility to RA.
Peroxisome Proliferator-Activated Receptor γ Coactivator 1 Coactivators, Energy Homeostasis, and Metabolism
Authors: Christoph Handschin, Bruce M. Spiegelman
Journal: Endocrine Reviews (2006)

Many biological programs are regulated at the transcriptional level. This is generally achieved by the concerted actions of several transcription factors. Recent findings have shown that, in many cases, transcriptional coactivators coordinate the overall regulation of the biological programs. One of the best-studied examples of coactivator control of metabolic pathways is the peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) family. These proteins are strong activators of mitochondrial function and are thus dominant regulators of oxidative metabolism in a variety of tissues. The PGC-1 coactivators themselves are subject to powerful regulation at the transcriptional and posttranslational levels. Recent studies have elucidated the function of the PGC-1 coactivators in different tissues and have highlighted the implications of PGC-1 dysregulation in diseases such as diabetes, obesity, cardiomyopathy, or neurodegeneration.
Atrial Reentrant Tachycardia After Surgery for Congenital Heart Disease
Authors: Thomas Paul, Britta Windhagen-Mahnert, Thomas Kriebel, Harald Bertram, Renate Kaulitz, Thomas Korte, Michael Niehaus, Jürgen Tebbenjohanns
Journal: Circulation (2001)

The purpose of the present study was to determine the role of a novel, noncontact mapping system for assessing a variety of atrial reentrant tachycardias (ART) in patients after the surgical correction of congenital heart disease.In 14 patients, an electrophysiological study using the Ensite 3000 system was performed to assess ARTs resistant to medical treatment. Sixteen different forms of ART were inducible in the 14 patients studied. The reentrant circuit of all ARTs could be characterized and localized with respect to anatomic landmarks such as atriotomy scars, intraatrial patches/baffles, and cardiac structures. In 15 of the 16 ARTs (in 13 of the 14 patients), a target area of the reentrant circuit for radiofrequency current application (ie, an area of conduction between 2 anatomical obstacles such as surgical barriers and cardiac structures of electrical isolation) could be localized within the systemic venous atrium. Nine patients exhibited macroreentry, and 4 showed microreentry. In 12 patients, ART could be terminated by creating linear radiofrequency current lesions (75 degrees C, 180 to 390 s). Completeness of linear lesions after radiofrequency current delivery was proven by analyzing color-coded isopotential maps of atrial activation while applying atrial pacing techniques. The mean duration of the procedures was 286 minutes (range, 130 to 435 minutes); fluoroscopy time ranged from 7 to 33.8 minutes (mean, 17.4 minutes).In patients with ART after the surgical correction of congenital heart disease, the use of the noncontact mapping system allows for characterization of the tachycardia and guidance for effective radiofrequency current delivery.
Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial
Authors: Simon Nadel, Brahm Goldstein, Mark D Williams, Heidi Dalton, Mark Peters, William L Macias, Shamel A Abd-Allah, Howard Levy, Robinette Angle, Dazhe Wang, David P Sundin, Brett Giroir
Journal: The Lancet (2007)
Localization of cholinergic innervation in guinea pig heart by immunohistochemistry for high-affinity choline transporters
Authors: D Hoover
Journal: Cardiovascular Research (2004)

Previous studies have used acetylcholinesterase (AChE) histochemistry to identify cholinergic nerves in the heart, but this enzyme is not a selective marker for cholinergic neurons. This study maps cholinergic innervation of guinea pig heart using a new antibody to the human high-affinity choline transporter (CHT), which is present only in cholinergic nerves.Immunohistochemistry was used to localize CHTs in frozen and paraffin sections of heart and whole mount preparations of atrial ganglionated nerve plexus. AChE-positive nerve fibers were identified in sections from separate hearts for comparison.Control experiments established that the antibody to human CHT selectively labeled cholinergic neurons in the guinea pig. CHT-immunoreactive nerve fibers and AChE-positive nerves were very abundant in the sinus and AV nodes, bundle of His, and bundle branches. Both markers also delineated a distinct nerve tract in the posterior wall of the right atrium. AChE-positive nerve fibers were more abundant than CHT-immunoreactive nerves in working atrial and ventricular myocardium. CHT-immunoreactive nerves were rarely observed in left ventricular free wall. Both markers were associated with numerous parasympathetic ganglia that were distributed along the posterior atrial walls and within the interatrial septum, including the region of the AV node.Comparison of labeling patterns for CHT and AChE suggests that AChE histochemistry overestimates the density of cholinergic innervation in the heart. The distribution of CHT-immunoreactive nerve fibers and parasympathetic ganglia in the guinea pig heart suggests that heart rate, conduction velocity, and automaticity are precisely regulated by cholinergic innervation. In contrast, the paucity of CHT-immunoreactive nerve fibers in left ventricular myocardium implies that vagal efferent input has little or no direct influence on ventricular contractile function in the guinea pig.
Bronchoalveolar Lavage and Lung Biopsy in Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: A Systematic Review and Meta-Analysis
Authors: DeepakBabu Chellapandian, Thomas Lehrnbecher, Bob Phillips, Brian T. Fisher, Theoklis E. Zaoutis, William J. Steinbach, Joseph Beyene, Lillian Sung
Journal: Journal of Clinical Oncology (2015)

Purpose The objective of this study was to describe the diagnostic yield and complication rate of bronchoalveolar lavage (BAL) and lung biopsy in the evaluation of pulmonary lesions in patients with cancer and recipients of hematopoietic stem-cell transplantation (HSCT). Methods We conducted a systematic literature review and performed electronic searches of Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were recipients of HSCT, and if they underwent BAL or lung biopsy for the evaluation of pulmonary lesions. Only English language publications were included. Results In all, 14,148 studies were screened; 72 studies of BAL and 31 of lung biopsy were included. The proportion of procedures leading to any diagnosis was similar by procedure type (0.53 v 0.54; P = .94) but an infectious diagnosis was more common with BAL compared with lung biopsy (0.49 v 0.34; P &lt; .001). Lung biopsy more commonly led to a noninfectious diagnosis (0.43 v 0.07; P &lt; .001) and was more likely to change how the patient was managed (0.48 v 0.31; P = .002) compared with BAL. However, complications were more common with lung biopsy (0.15 v 0.08; P = .006), and procedure-related mortality was four-fold higher for lung biopsy (0.0078) compared with BAL (0.0018). Conclusion BAL may be the preferred diagnostic modality for the evaluation of potentially infectious pulmonary lesions because of lower complication and mortality rates; thus, choice of procedure depends on clinical suspicion of infection. Guidelines to promote consistency in the approach to the evaluation of lung infiltrates may improve clinical care of patients.
Nanobody-Based Targeting of the Macrophage Mannose Receptor for Effective<i>In Vivo</i>Imaging of Tumor-Associated Macrophages
Authors: Kiavash Movahedi, Steve Schoonooghe, Damya Laoui, Isabelle Houbracken, Wim Waelput, Karine Breckpot, Luc Bouwens, Tony Lahoutte, Patrick De Baetselier, Geert Raes, Nick Devoogdt, Jo A. Van Ginderachter
Journal: Cancer Research (2012)

Tumor-associated macrophages (TAM) are an important component of the tumor stroma and exert several tumor-promoting activities. Strongly pro-angiogenic TAMs that reside in hypoxic tumor areas highly express macrophage mannose receptor (MMR, CD206). In this study, we targeted MMR+ TAMs using nanobodies, which are single-domain antigen-binding fragments derived from Camelidae heavy-chain antibodies. MMR-specific nanobodies stained TAMs in lung and breast tumor single-cell suspensions in vitro, and intravenous injection of 99mTc-labeled anti-MMR nanobodies successfully targeted tumor in vivo. Retention of the nanobody was receptor-specific and absent in MMR-deficient mice. Importantly, co-injection of excess unlabeled, bivalent anti-MMR nanobodies reduced nanobody accumulation in extratumoral organs to background levels, without compromising tumor uptake. Within tumors, the 99mTc-labeled nanobodies specifically labeled MMR+ TAMs, as CCR2-deficient mice that contain fewer TAMs showed significantly reduced tumor uptake. Further, anti-MMR nanobodies accumulated in hypoxic regions, thus targeting pro-angiogenic MMR+ TAMs. Taken together, our findings provide preclinical proof of concept that anti-MMR nanobodies can be used to selectively target and image TAM subpopulations in vivo.
Vascular Endothelial Growth Factor and Semaphorin Induce Neuropilin-1 Endocytosis via Separate Pathways
Authors: Anna Salikhova, Ling Wang, Anthony A. Lanahan, Miaoliang Liu, Michael Simons, William P. J. Leenders, Debabrata Mukhopadhyay, Arie Horowitz
Journal: Circulation Research (2008)

The neuropilin (Nrp)1 receptor is essential for both nervous and vascular system development. Nrp1 is unusually versatile, because it transmits both chemoattractive and repulsive signals in response to vascular endothelial growth factor (VEGF)-A and class 3 semaphorins, respectively. Both Nrp1 and VEGF receptor 2 undergo ligand-dependent endocytosis. We sought to establish the endocytic pathway of Nrp1 and to determine whether uptake is required for its signaling. Whereas Nrp1 underwent clathrin-dependent endocytosis in response to VEGFA 165 treatment, semaphorin 3C (sema3C) induced lipid raft–dependent endocytosis. The myosin VI PDZ (postsynaptic density 95, Disk large, Zona occludens-1) adaptor protein synectin was essential for Nrp1 trafficking. Sema3C failed to inhibit migration of synectin −/− endothelial cells, mirroring the lower migratory response of these cells to VEGFA 165 . These results show that the endocytic pathway of Nrp1 is determined by its ligand and that the trafficking of Nrp1 is essential for its signaling.
Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement
Authors: Jack Cuzick, Florian Otto, John A Baron, Powel H Brown, John Burn, Peter Greenwald, Janusz Jankowski, Carlo La Vecchia, Frank Meyskens, Hans Jörg Senn, Michael Thun
Journal: The Lancet Oncology (2009)
ABC of nutrition. Some principles.
Authors: A S Truswell
Journal: BMJ (1985)

10 000 years ago.There has not been enough time for our species to evolve any new mechanisms required by the recent food supply but presumably our bodies have evolved well adapted for doing what hunter-gatherers did and eating what they ate.We have information from archaeological records and from studies of the few fast disappearing groups of contemporary hunter-gatherers.* Experiments ofnature and travellers' tales-From peoples who eat different foods from us, under stable conditions or during a disaster, we can form hypotheses about the physiological effects ofdifferent food patterns that we could not easily persuade our fellow countrymen to adopt.We have, for example, learnt about the physiological role of very long chain polyunsaturated fatty acids from the Eskimos, and about deficiency diseases from nutritional experiences ofprisoners of war.* Epidemiological studies range in the power of their design.Associations Hunter-gatherers in general were lean, ate more plant and correlations ofdisease characteristics and dietary variables do not prove than animal foods though they did eat meat or seafoods.They ate a variety of foods, had a high fibre intake, but cause and effect, but prospective studies, especially if repeated i different took no salt or alcohol and concentrated sugar only rarely groups, give valuable information on the relation between usual diets and (as wild honey).chronic diseases.
Association of Metabolic Dysregulation With Volumetric Brain Magnetic Resonance Imaging and Cognitive Markers of Subclinical Brain Aging in Middle-Aged Adults
Authors: Zaldy S. Tan, Alexa S. Beiser, Caroline S. Fox, Rhoda Au, Jayandra J. Himali, Stephanie Debette, Charles DeCarli, Ramachandran S. Vasan, Philip A. Wolf, Sudha Seshadri
Journal: Diabetes Care (2011)

OBJECTIVE Diabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer’s disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults. RESEARCH DESIGN AND METHODS Framingham Offspring participants who underwent volumetric MRI and detailed cognitive testing and were free of clinical stroke and dementia during examination 7 (1998–2001) constituted our study sample (n = 2,439; 1,311 women; age 61 ± 9 years). We related diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, and glycohemoglobin levels to cross-sectional MRI measures of total cerebral brain volume (TCBV) and hippocampal volume and to verbal and visuospatial memory and executive function. We serially adjusted for age, sex, and education alone (model A), additionally for other vascular risk factors (model B), and finally, with the inclusion of apolipoprotein E-ε4, plasma homocysteine, C-reactive protein, and interleukin-6 (model C). RESULTS We observed an inverse association between all indices of metabolic dysfunction and TCBV in all models (P &amp;lt; 0.030). The observed difference in TCBV between participants with and without diabetes was equivalent to approximately 6 years of chronologic aging. Diabetes and elevated glycohemoglobin, HOMA-IR, and fasting insulin were related to poorer executive function scores (P &amp;lt; 0.038), whereas only HOMA-IR and fasting insulin were inversely related to visuospatial memory (P &amp;lt; 0.007). CONCLUSIONS Metabolic dysregulation, especially insulin resistance, was associated with lower brain volumes and executive function in a large, relatively healthy, middle-aged, community-based cohort.
Death by Design
Authors: W. Robb MacLellan, Michael D. Schneider
Journal: Circulation Research (1997)

Programmed cell death (apoptosis) is recognized, increasingly, as a contributing cause of cardiac myocyte loss with ischemia/reperfusion injury, myocardial infarction, and long-standing heart failure. Although the exact mechanisms initiating apoptosis in these in vivo settings remain unproven, insights into the molecular circuitry controlling apoptosis more widely suggest the potential to protect mammalian ventricular muscle from apoptosis through one or more of these pathways, by pharmacological means or, conceivably, gene transfer.
Gemcitabine and ISIS-2503 for Patients With Locally Advanced or Metastatic Pancreatic Adenocarcinoma: A North Central Cancer Treatment Group Phase II Trial
Authors: Steven R. Alberts, Mark Schroeder, Charles Erlichman, Preston D. Steen, Nathan R. Foster, Dennis F. Moore, Kendrith M. Rowland, Suresh Nair, Loren K. Tschetter, Tom R. Fitch
Journal: Journal of Clinical Oncology (2004)

Purpose Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study. Methods Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m 2 intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks. Results Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism. Conclusion This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.
Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation.
Authors: L Brochard, A Rauss, S Benito, G Conti, J Mancebo, N Rekik, A Gasparetto, F Lemaire
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation, but their respective effects on the outcome of weaning from mechanical ventilation are not known. We conducted a randomized trial in three intensive care units in mechanically ventilated patients who met standard weaning criteria. Those who could not sustain 2 h of spontaneous breathing were randomly assigned to be weaned with T-piece trials, with synchronized intermittent mandatory ventilation (SIMV), or with pressure support ventilation (PSV). Specific criteria for performing tracheal extubation were defined for each modality. The number of patients who could not be separated from the ventilator at 21 d (i.e., who failed to wean) was compared between the groups. Patients in whom tracheal intubation was required in a 48-h period following extubation were also classified as failures. Among 456 mechanically ventilated patients who met weaning criteria, 109 entered into the study (35 with T piece, 43 with SIMV, and 31 with PSV). The three groups were comparable in terms of etiology of disease or characteristics at entry in the study. When all causes for weaning failure were considered, a lower number of failures was found with PSV than with the other two modes, with the difference just reaching the level of significance (23% for PSV, 43% for T piece, 42% for SIMV; p = 0.05). After excluding patients whose weaning was terminated for complications unrelated to the weaning process, the difference became highly significant (8% for PSV versus 33% and 39%, p < 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)