tbuckley/cabot-search huggingface dataset:
Regional Fat Deposition as a Factor in FFA Metabolism
Authors: Susanne B. Votruba, Michael D. Jensen
Journal: Annual Review of Nutrition (2007)

Humans have a large variability in body fat distribution, which has tremendous implications for metabolic health. Obese individuals with an upper-body-fat distribution have increased health complications such as dyslipidemia, hypertension, insulin resistance, and type 2 diabetes in comparison with lower-body-obese individuals. Additionally, females have more body fat, a greater proportion of fat in their lower body, and much less visceral fat than do lean males at the same body mass index. The reasons for these differences in body fat distribution have not been clearly identified but could be important. Herein we review what has been learned about regional differences in triglyceride storage capacity and lipolysis as they relate to the causes and consequences of regional fat accumulation. Both sex and site differences in regional fat storage have been described. In contrast, with the exception of variations between men and women in the contribution of visceral adipose tissue to hepatic FFA delivery, most studies have failed to show important sex differences in regional lipolysis in vivo.
An unusual cause of anaemia
Authors: A. P. Wiles, D. J. Lomas, J. Davies, V. Save, E. A. B. Cameron
Journal: Gut (2010)

<h3>Background</h3> The obstructive sleep apnoea syndrome (OSAS) results from a combination of structural and neuromotor factors; however, the relative contributions of these factors have not been studied during the important developmental phase of adolescence. We hypothesised that adenotonsillar volume (ATV), nasopharyngeal airway volume (NPAV), upper airway critical closing pressure (Pcrit) in the hypotonic and activated neuromotor states, upper airway electromyographic response to subatmospheric pressure and the ventilatory response to CO<sub>2</sub> during sleep would be major predictors of OSAS risk. <h3>Methods</h3> 42 obese adolescents with OSAS and 37 weight-matched controls underwent upper airway MRI, measurements of Pcrit, genioglossal electromyography and ventilatory response to CO<sub>2</sub> during wakefulness and sleep. <h3>Results</h3> ATV, NPAV, activated and hypotonic Pcrit, genioglossal electromyography and ventilatory response to CO<sub>2</sub> during sleep were all associated with OSAS risk. Multivariate models adjusted for age, gender, body mass index and race indicated that ATV, NPAV and activated Pcrit each independently affected apnoea risk in adolescents; genioglossal electromyography was independently associated in a reduced sample. There was significant interaction between NPAV and activated Pcrit (p=0.021), with activated Pcrit more strongly associated with OSAS in adolescents with larger NPAVs and NPAV more strongly associated with OSAS in adolescents with more negative activated closing pressure. <h3>Conclusions</h3> OSAS in adolescents is mediated by a combination of anatomic (ATV, NPAV) and neuromotor factors (activated Pcrit). This may have important implications for the management of OSAS in adolescents.
Mortality after admission to hospital with fractured neck of femur: database study
Authors: M. J Goldacre
Journal: BMJ (2002)

The death rate within one year of fractured neck of femur is typically reported as between 20% and 35%. [1]][3] Performance indicators based on mortality after hospital admission for such fractures have been promoted. 4 The only measure of mortality in routine hospital statistics, however, is "in-hospital mortality"-death during the initial admission for the fracture.We analysed inpatient statistics that had been linked to death registration data in the former Oxford NHS health region (population 2.5 million) from 1994 to 1998.
Breast Cancer Angio-histogenesis: Through a Narrow Window
Authors: David L. Page, William D. Dupont
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Breast Cancer Angio-histogenesis: Through a Narrow Window Get access David L. Page, David L. Page Search for other works by this author on: Oxford Academic PubMed Google Scholar William D. Dupont William D. Dupont Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 24, 16 December 1992, Pages 1850–1851, https://doi.org/10.1093/jnci/84.24.1850 Published: 16 December 1992 Article history Received: 10 November 1992 Accepted: 17 November 1992 Published: 16 December 1992
Impact of FcγRIIa-FcγRIIIa Polymorphisms and <i>KRAS</i> Mutations on the Clinical Outcome of Patients With Metastatic Colorectal Cancer Treated With Cetuximab Plus Irinotecan
Authors: Frédéric Bibeau, Evelyne Lopez-Crapez, Frédéric Di Fiore, Simon Thezenas, Marc Ychou, France Blanchard, Aude Lamy, Frédérique Penault-Llorca, Thierry Frébourg, Pierre Michel, Jean-Christophe Sabourin, Florence Boissière-Michot
Journal: Journal of Clinical Oncology (2009)

Purpose The antiepidermal growth factor receptor antibody cetuximab shows activity in irinotecan-refractory metastatic colorectal cancer (mCRC), mainly in wild-type KRAS tumors. Cetuximab may also exert antitumor effects through antibody-dependent cell-mediated cytotoxicity (ADCC) in which antibody Fc portion interacts with Fc receptors (FcγRs) expressed by immune cells. ADCC is influenced by FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms that are clinically relevant in follicular lymphoma and metastatic breast cancer treated with rituximab and trastuzumab, respectively. We investigated the association of FcγR polymorphisms and KRAS mutation with the outcome of irinotecan-refractory mCRC patients treated with cetuximab plus irinotecan. Patients and Methods Tumor and normal tissues from 69 patients were screened for KRAS mutations using a sensitive multiplex assay and genotyped for FcγRIIa and FcγRIIIa polymorphisms by direct sequencing and multiplex allele-specific polymerase chain reaction, respectively. The results were correlated with response and progression-free survival (PFS). Results KRAS mutations were associated with lower response rate (4% v 27% in nonmutated patients; P = .021) and shorter PFS (3.0 v 5.3 months; P = .021). Patients with FcγRIIa-131H/H and/or FcγIIIa-158V/V genotypes had longer PFS than 131R and 158F carriers (5.5 v 3.0 months; P = .005). The difference remained significant for mutated-KRAS patients. By multivariate analysis, KRAS mutation and FcγR combined status were independent risk factors for PFS. Conclusion Combined FcγRIIa/FcγRIIIa polymorphisms are prognostic factors for disease progression in mCRC patients treated with cetuximab plus irinotecan. As these polymorphisms are also clinically relevant in mutated-KRAS mCRC, an important role of ADCC in cetuximab efficacy is presumed.
NHS referrals and children's surgery are suspended at BMI Healthcare's Mount Alvernia Hospital
Authors: A. O'Dowd
Journal: BMJ (2013)

Referrals of all NHS patients and all surgery on children have been suspended at a private hospital in Surrey after an inspection by the main NHS regulator found the hospital to be failing several quality standards.

The BMI Healthcare’s Mount Alvernia Hospital in Guildford, Surrey—an independent acute care hospital—has now replaced its management team after a highly critical inspection by the Care Quality Commission. Care is now back to a good standard, it said.

Inspections carried out in December last year and January this year found medical, surgical, and nursing practices at the hospital were so poor that people were put at “significant risk” that was sometimes “life threatening,” despite staff members themselves raising concerns with …
Corticosteroids and Outcome in Children Undergoing Congenital Heart Surgery
Authors: Sara K. Pasquali, Matthew Hall, Jennifer S. Li, Eric D. Peterson, James Jaggers, Andrew J. Lodge, Bradley S. Marino, Denise M. Goodman, Samir S. Shah
Journal: Circulation (2010)

Children undergoing congenital heart surgery often receive corticosteroids with the aim of reducing the inflammatory response after cardiopulmonary bypass; however, the value of this approach is unclear.
Obstructive Sleep Apnea and Thoracic Aorta Dissection
Authors: Gabriel Sampol, Odile Romero, Armando Salas, José L. Tovar, Patricia Lloberes, Teresa Sagalés, Arturo Evangelista
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Obstructive sleep apnea syndrome (OSAS) is a process that is associated with the development of arterial hypertension, the main risk factor for aortic dissection and during obstructive episodes of the upper airways with marked increases in transmural pressure of the aorta wall. The aim of this work was to study the association between aortic dissection and OSAS. Nineteen consecutive patients with thoracic aorta dissection and 19 hypertensive patients of similar age, sex, and body mass index were studied by clinical questionnaire and polysomnography. Snoring and nonrefreshing sleep were common in both groups. Thirteen patients (68%) from each group showed an apnea-hypopnea index of more than 5 per hour. However, patients with aortic dissection presented a higher apnea-hypopnea index (28 [30.3] versus 11.1 [10.4], p=0.032). Seven patients with dissection presented an apnea-hypopnea index of more than 30 versus 1 patient in the control group (p=0.042). Patients with thoracic aorta dissection presented a high prevalence of previously undiagnosed and frequently severe OSAS. Further studies, including this diagnosis as a prognostic variable in the follow-up of patients with aortic dissection, are required. Our results suggest that in patients with aortic dissection and symptoms consistent with OSAS, a sleep study should be considered in their clinical management.
Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis
Authors: K Adams, P L Shah, L Edmonds, E Lim
Journal: Thorax (2009)

<h3>Background:</h3> Endobronchial ultrasound (EBUS) with transbronchial needle aspiration (TBNA) is becoming widely used for mediastinal lymph node staging in patients with known or suspected lung cancer. While a substantial number of case series have evaluated test performance of this investigation, the small sample sizes limited the ability to accurately evaluate the precision of EBUS-TBNA as a staging modality. A systematic review was performed of published studies evaluating EBUS-TBNA for mediastinal lymph node staging to ascertain the pooled sensitivity and specificity of this investigation. <h3>Methods:</h3> A literature search was constructed and performed by a professional medical librarian to identify the literature from 1960 to February 2008. Pooled specificity and sensitivity was estimated from the extracted data with an exact binomial rendition of the bivariate mixed-effects regression model. <h3>Results:</h3> Of 365 publications, 25 were identified in which EBUS-TBNA was specifically focused on mediastinal node staging. Of these, only 10 had data suitable for extraction and analysis. The overall test performance was excellent with an area under the summary receiver operating characteristics curve of 0.99 (95% CI 0.96 to 1.00); similarly, EBUS-TBNA had excellent pooled specificity of 1.00 (95% CI 0.92 to 1.00) and good pooled sensitivity of 0.88 (95% CI 0.79 to 0.94). <h3>Conclusions:</h3> EBUS-TBNA has excellent overall test performance and specificity for mediastinal lymph node staging in patients with lung cancer. The results compare favourably with published results for computed tomography and positron emission tomography.
Oral ibandronate is as active as intravenous zoledronic acid for reducing bone turnover markers in women with breast cancer and bone metastases
Authors: J.-J. Body, M. Lichinitser, S. Tjulandin, P. Garnero, B. Bergström
Journal: Annals of Oncology (2007)

Background: Phase III study comparing the effect of oral ibandronate and intravenous zoledronic acid on bone markers.Patients and methods: Breast cancer patients with bone metastases received ibandronate 50 mg/day (n = 137) or zoledronic acid 4 mg every 4 weeks (n = 138) for 12 weeks. The primary end point was mean percentage change in serum levels of cross-linked C-terminal telopeptide of type I collagen (S-CTX) at week 12. Urinary CTX (U-CTX), bone alkaline phosphatase (ALP), amino-terminal procollagen propeptide of type I collagen (PINP) and osteocalcin (OC) were also measured and bone pain and safety assessed.Results: Both bisphosphonates significantly reduced S-CTX (mean ibandronate 76% ± 29 (SD) versus mean zoledronic acid 73% ± 47; P < 0.001 for both versus baseline) and U-CTX (ibandronate 78% ± 50 versus zoledronic acid 86% ± 17; P < 0.001). The difference in S-CTX between treatments was 0.6% (confidence interval -1.7% to 3.0%), which was within the prespecified noninferiority margin. Bone ALP, PINP and OC decreased by 26%–47% compared with baseline with both bisphosphonates. Compared with zoledronic acid, ibandronate patients reported fewer adverse events overall (65.0% versus 75.9%), and on days 1–3 (8.0% versus 47.5%), including less pyrexia (overall incidence 0% versus 16.8%) and bone pain (5.8% versus 12.4%).Conclusions: Oral ibandronate was well tolerated and statistically noninferior to zoledronic acid for percentage change in the bone resorption marker, S-CTX.
Common variants in the NLRP3 region contribute to Crohn's disease susceptibility
Authors: Alexandra-Chloé Villani, Mathieu Lemire, Geneviève Fortin, Edouard Louis, Mark S Silverberg, Catherine Collette, Nobuyasu Baba, Cécile Libioulle, Jacques Belaiche, Alain Bitton, Daniel Gaudet, Albert Cohen, Diane Langelier, Paul R Fortin, Joan E Wither, Marika Sarfati, Paul Rutgeerts, John D Rioux, Severine Vermeire, Thomas J Hudson, Denis Franchimont
Journal: Nature Genetics (2008)
Tissue Inhibitor of Metalloproteinase-3 Expression from an Oncolytic Adenovirus Inhibits Matrix Metalloproteinase Activity <i>In vivo</i> without Affecting Antitumor Efficacy in Malignant Glioma
Authors: Martine L.M. Lamfers, Davide Gianni, Ching-Hsuan Tung, Sander Idema, Frederik H.E. Schagen, Jan E. Carette, Paul H.A. Quax, Victor W. Van Beusechem, W. Peter Vandertop, Clemens M.F. Dirven, E. Antonio Chiocca, Winald R. Gerritsen
Journal: Cancer Research (2005)

Abstract Oncolytic adenoviruses exhibiting tumor-selective replication are promising anticancer agents. Insertion and expression of a transgene encoding tissue inhibitor of metalloproteinase-3 (TIMP-3), which has been reported to inhibit angiogenesis and tumor cell infiltration and induce apoptosis, may improve the antitumor activity of these agents. To assess the effects of TIMP-3 gene transfer to glioma cells, a replication-defective adenovirus encoding TIMP-3 (Ad.TIMP-3) was employed. Ad.TIMP-3 infection of a panel of glioma cell cultures decreased the proliferative capacity of these cells and induced morphologic changes characteristic for apoptosis. Next, a conditionally replicating adenovirus encoding TIMP-3 was constructed by inserting the TIMP-3 expression cassette into the E3 region of the adenoviral backbone containing a 24-bp deletion in E1A. This novel oncolytic adenovirus, AdΔ24TIMP-3, showed enhanced oncolytic activity on a panel of primary cell cultures and two glioma cell lines compared with the control oncolytic virus AdΔ24Luc. In vivo inhibition of matrix metalloproteinase (MMP) activity by AdΔ24TIMP-3 was shown in s.c. glioma xenografts. The functional activity of TIMP-3 was imaged noninvasively using a near-IR fluorescent MMP-2–activated probe. Tumoral MMP-2 activity was significantly reduced by 58% in the AdΔ24TIMP-3–treated tumors 24 hours after infection. A study into the therapeutic effects of combined oncolytic and antiproteolytic therapy was done in both a s.c. and an intracranial model for malignant glioma. Treatment of s.c. (U-87MG) or intracranial (U-87δEGFR) tumors with AdΔ24TIMP-3 and AdΔ24Luc both significantly inhibited tumor growth and prolonged survival compared with PBS-treated controls. However, expression of TIMP-3 in the context of AdΔ24 did not significantly affect the antitumor efficacy of this oncolytic agent.
Why are phobias irrational?
Authors: Peter F. Lovibond, David A. T. Siddle, Nigel W. Bond
Journal: Behavioral and Brain Sciences (1995)

Abstract We endorse Davey's view that expectancy processes are intimately involved in fear reactions, but question his model on three grounds. First, the mechanism for generating expectancy bias to both ontogenetic and phylogenetic stimuli is not spelled out. Second, the selective association component is unnecessary. Third, the model fails to provide a clear explanation for the irrationality of phobic reactions.
Olanzapine Treatment of Residual Positive and Negative Symptoms
Authors: Robert W. Buchanan, M. Patricia Ball, Elaine Weiner, Brian Kirkpatrick, James M. Gold, Robert P. McMahon, William T. Carpenter
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Olanzapine has been hypothesized to have superior efficacy in patients with treatment-resistant schizophrenia. The authors examined the comparative efficacy and safety of olanzapine and haloperidol in outpatients with partially responsive schizophrenia. METHOD: Sixty-three outpatients with schizophrenia who met retrospective and prospective criteria for either residual positive or residual negative symptoms entered a 16-week double-blind, parallel-groups comparison of olanzapine and haloperidol. RESULTS: There were no significant differences between the two drugs in their effect on positive or negative symptoms. There were no significant differences between the two treatment groups on measures of social and functional outcome. Olanzapine-treated patients had a significant reduction in extrapyramidal symptoms and subjective measures of stiffness and dry mouth, but the increases in systolic blood pressure and weight in olanzapine-treated patients were significantly greater than they were in haloperidol-treated patients. CONCLUSIONS: Olanzapine has limited differential benefit for either positive or negative symptoms in patients with treatment-resistant schizophrenia. Although olanzapine is associated with fewer extrapyramidal symptoms, other side effects may offset this benefit.
The contradiction unresolved
Authors: Thomas C. Schelling
Journal: Behavioral and Brain Sciences (1996)

Abstract Extreme sensations – thirst, pain – can focus attention on local consequences at the expense of the overall, perhaps for good evolutionary reasons. Maybe the same phenomenon evolves from prolonged use of addictive substances. The matching law explains mistaken choice, not how a person who has confronted personal catastrophe manages to ignore it in making a locally induced choice.
Obesity, Diabetes, and Gut Microbiota
Authors: Giovanni Musso, Roberto Gambino, Maurizio Cassader
Journal: Diabetes Care (2010)

The connection between gut microbiota and energy homeostasis and inflammation and its role in the pathogenesis of obesity-related disorders are increasingly recognized. Animals models of obesity connect an altered microbiota composition to the development of obesity, insulin resistance, and diabetes in the host through several mechanisms: increased energy harvest from the diet, altered fatty acid metabolism and composition in adipose tissue and liver, modulation of gut peptide YY and glucagon-like peptide (GLP)-1 secretion, activation of the lipopolysaccharide toll-like receptor-4 axis, and modulation of intestinal barrier integrity by GLP-2. Instrumental for gut microbiota manipulation is the understanding of mechanisms regulating gut microbiota composition. Several factors shape the gut microflora during infancy: mode of delivery, type of infant feeding, hospitalization, and prematurity. Furthermore, the key importance of antibiotic use and dietary nutrient composition are increasingly recognized. The role of the Western diet in promoting an obesogenic gut microbiota is being confirmation in subjects. Following encouraging results in animals, several short-term randomized controlled trials showed the benefit of prebiotics and probiotics on insulin sensitivity, inflammatory markers, postprandial incretins, and glucose tolerance. Future research is needed to unravel the hormonal, immunomodulatory, and metabolic mechanisms underlying microbe-microbe and microbiota-host interactions and the specific genes that determine the health benefit derived from probiotics. While awaiting further randomized trials assessing long-term safety and benefits on clinical end points, a healthy lifestyle--including breast lactation, appropriate antibiotic use, and the avoidance of excessive dietary fat intake--may ensure a friendly gut microbiota and positively affect prevention and treatment of metabolic disorders.
<i>Very early</i>versus<i>early</i>disease: the evolving definition of the ‘<i>many faces</i>’ of systemic sclerosis
Authors: Marco Matucci-Cerinic, Silvia Bellando-Randone, Gemma Lepri, Cosimo Bruni, Serena Guiducci
Journal: Annals of the Rheumatic Diseases (2012)

Systemic sclerosis (SSc) is a challenge for the rheumatologist as it is easy to diagnose when it is evolved to skin fibrosis with obliterative vasculopathy and organ involvement but its diagnosis remains very difficult in the very early/early phase of the disease because the American College of Rheumatology (ACR) and LeRoy criteria, which are currently those largely used to classify SSc, were shown to be not sensitive enough to reach a very early or an early diagnosis of SSc.1–4 Therefore, the SSc diagnosis may be delayed for several years following the onset of Raynaud's phenomenon (RP) and even after the onset of the first non-RP symptom. This reality implies that the diagnosis, and consequently the therapy, are delayed until skin involvement and/or internal organ involvement are evident5–8 and, in too many cases, already irreversible.6

The fact that organ involvement may be present from the earliest stages of SSc corroborates the necessity of a very early or at least an early diagnosis of SSc to try to identify therapy which might achieve disease remission. Moreover, the rheumatologist is also facing today the problem to position the patient in the SSc evolution from its very early to the early and to the established phase. Previously, several attempts have been made to define the early phase of SSc7 and recently even the concept of very early SSc has been widely accepted and investigated.8 RP, despite its lack of specificity, has been proposed as a pivotal sign in a previous attempt to define criteria for the diagnosis of ‘early’ SSc9 and has been also considered as the main ‘sentinel’ sign10 for the identification of ‘very early …
Re: R. Houston Thompson, Tom Atwell, Grant Schmit, et al. Comparison of Partial Nephrectomy and Percutaneous Ablation for cT1 Renal Masses. Eur Urol 2015;67:252–9
Authors: Homayoun Zargar, Rafael F. Coelho, Jihad H. Kaouk
Journal: European Urology (2014)