tbuckley/cabot-search huggingface dataset:
Bone turnover in early rheumatoid arthritis. 1. Biochemical and kinetic indexes.
Authors: P N Sambrook, B M Ansell, S Foster, J M Gumpel, R Hesp, J Reeve, J M Zanelli
Journal: Annals of the Rheumatic Diseases (1985)

Biochemical, hormonal, and kinetic indexes of bone turnover were measured in 17 ambulant female patients with rheumatoid arthritis (RA) of recent onset (mean disease duration 14.2 months) and 19 controls. Mean serum osteocalcin concentration and 85Sr accretion rates were reduced and mean urinary hydroxyproline-creatinine ratios were increased in RA, but these differences were not significant compared with control values. Mean total body potassium (TBK), an index of skeletal muscle mass, was significantly reduced in RA, and the ratio of observed to predicted TBK correlated with indexes of bone formation. No abnormality of skeletal metabolism could be shown in early RA, but reduced rates of bone formation associated with diminished muscle mass may influence the development of osteopenia later in the disease.
Relation between socioeconomic status and tumour stage in patients with breast, colorectal, ovarian, and lung cancer: results from four national, population based studies
Authors: D H Brewster, C S Thomson, D J Hole, R J Black, P L Stroner, C R Gillis
Journal: BMJ (2001)

Although there is evidence that patients with cancer from deprived communities in Scotland might present with more advanced disease, 1-3 this finding has not been replicated in every study. 4 Using data from four population based audits, we investigated whether there is any relation between socioeconomic status and tumour stage at presentation in patients with breast, colorectal, ovarian, and lung cancer.
Pulmonary actinomycosis appearing as a "ball-in-hole" on chest radiography and bronchoscopy.
Authors: M. J. Hsieh, W. B. Shieh, K. S. Chen, T. J. Yu, H. P. Kuo, Y. H. Tsai
Journal: Thorax (1996)

A 40 year old diabetic man with pulmonary actinomycosis was admitted to hospital with recurrent haemoptysis. The chest radiograph showed an air meniscus in the left upper lobe, a rare presentation of pulmonary actinomycosis. Bronchoscopic examination revealed a mass in a cavity which has never been reported previously. He underwent lobectomy and the surgical specimen revealed sulphur granules, the typical pathological finding of actinomycosis, without evidence of fungal or mycobacterial infection.
Dutch and British doctors lead in information technology while Canada and the US slow to adopt it, study shows
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

Doctors in the Netherlands and the United Kingdom are leaders in using health information technology. Doctors in the United States and Canada lag behind, according to a study of seven nations by the Commonwealth Fund, a non-profit making organisation that works to advance health systems.

The study covered doctors’ use of health information technology in Australia, Canada, Germany, the Netherlands, New Zealand, the United Kingdom, and the United States ( Health Policy 2008 Nov 26, doi:10.1016/j.healthpol.2008.10.002).

Nearly all doctors in the Netherlands (98%), and most in New Zealand (92%), …
Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP1-interactor, showing reduced expression in early Alzheimer's disease
Authors: Yuji Kajiwara, Sonia Franciosi, Nagahide Takahashi, Lisa Krug, James Schmeidler, Kevin Taddei, Vahram Haroutunian, Ulrik Fried, Michelle Ehrlich, Ralph N Martins, Samuel Gandy, Joseph D Buxbaum
Journal: Molecular Neurodegeneration (2010)

Abstract Background The low-density lipoprotein receptor related protein 1 (LRP1) has been implicated in Alzheimer's disease (AD) but its signalling has not been fully evaluated. There is good evidence that the cytoplasmic domain of LRP1 is involved in protein-protein interactions, important in the cell biology of LRP1. Results We carried out three yeast two-hybrid screens to identify proteins that interact with the cytoplasmic domain of LRP1. The screens included both conventional screens as well as a novel, split-ubiquitin-based screen in which an LRP1 construct was expressed and screened as a transmembrane protein. The split-ubiquitin screen was validated in a screen using full-length amyloid protein precursor (APP), which successfully identified FE65 and FE65L2, as well as novel interactors (Rab3a, Napg, and ubiquitin b). Using both a conventional screen as well as the split-ubiquitin screen, we identified NYGGF4 as a novel LRP1 interactor. The interaction between LRP1 and NYGGF4 was validated using two-hybrid assays, coprecipitation and colocalization in mammalian cells. Mutation analysis demonstrated a specific interaction of NYGGF4 with an NPXY motif that required an intact tyrosine residue. Interestingly, while we confirmed that other LRP1 interactors we identified, including JIP1B and EB-1, were also able to bind to APP, NYGGF4 was unique in that it showed specific binding with LRP1. Expression of NYGGF4 decreased significantly in patients with AD as compared to age-matched controls, and showed decreasing expression with AD disease progression. Examination of Nyggf4 expression in mice with different alleles of the human APOE4 gene showed significant differences in Nyggf4 expression. Conclusions These results implicate NYGGF4 as a novel and specific interactor of LRP1. Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered early in disease. Genetic and functional studies have implicated both LRP1 and NYGGF4 in obesity and cardiovascular disease and the physical association of these proteins may reflect a common mechanism. This is particularly interesting in light of the dual role of ApoE in both cardiovascular risk and AD. The results support further studies on the functional relationship between NYGGF4 and LRP1.
Impaired pancreatic polypeptide release in chronic pancreatitis with steatorrhoea.
Authors: T E Adrian, H S Besterman, C N Mallinson, C Garalotis, S R Bloom
Journal: Gut (1979)

Pancreatic polypeptide (PP) is a newly discovered hormonal peptide localised in a distinct endocrine cell type in the pancreas. PP circulates in plasma and in normal subjects levels rise substantially on the ingestion of food (mean rise 138 pmol/l). In 10 patients with chronic pancreatitis with exocrine deficiency the PP response to a test breakfast was greatly reduced (mean rise 20 pmol/l, P less than 0.001). PP response to the meal was normal in 10 patients with active coeliac disease and 12 patients with acute tropical sprue with steatorrhoea.
The Coriell personalized medicine collaborative pharmacogenomics appraisal, evidence scoring and interpretation system
Authors: Neda Gharani, Margaret A Keller, Catharine B Stack, Laura M Hodges, Tara J Schmidlen, Daniel E Lynch, Erynn S Gordon, Michael F Christman
Journal: Genome Medicine (2013)

Implementation of pharmacogenomics (PGx) in clinical care can lead to improved drug efficacy and reduced adverse drug reactions. However, there has been a lag in adoption of PGx tests in clinical practice. This is due in part to a paucity of rigorous systems for translating published clinical and scientific data into standardized diagnostic tests with clear therapeutic recommendations. Here we describe the Pharmacogenomics Appraisal, Evidence Scoring and Interpretation System (PhAESIS), developed as part of the Coriell Personalized Medicine Collaborative research study, and its application to seven commonly prescribed drugs.
Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints
Authors: S Uderhardt, D Diarra, J Katzenbeisser, J-P David, J Zwerina, W Richards, G Kronke, G Schett
Journal: Annals of the Rheumatic Diseases (2009)

Objective To study whether Dickkopf (DKK)-1, an inhibitor of wingless (Wnt) signalling, is involved in the fusion of sacroiliac joints. Methods Mice transgenic for tumour necrosis factor (TNFtg mice), which develop bilateral sacroiliitis, were treated with vehicle, anti-TNF antibody or anti-DKK1 antibody. Sacroiliac joints were analysed for histological signs of inflammation, bone erosion, osteoclast formation and ankylosis. Moreover, expression of collagen type X, β-catenin and DKK-1 was assessed by immunohistochemistry. Results There were no signs of spontaneous ankylosis of the sacroiliac joints in TNFtg mice. TNF blockade effectively reduced inflammation, bone erosion and osteoclast numbers in the sacroiliac joints, but did not lead to ankylosis. Blockade of DKK1 had no effect on inflammatory signs of sacroiliitis, but significantly reduced bone erosions and osteoclast counts. Moreover, DKK1 blockade promoted expression of collagen type X, the formation of hypertrophic chondrocytes and ankylosis of sacroiliac joints. Conclusion DKK1 influences inflammatory remodelling of sacroiliac joints by prevention of joint ankylosis. This may indicate an important role of the Wnt signalling pathway in the structural bone changes of axial joint disease. Although this model does not reflect the entire spectrum of ankylosing spondylitis in humans, it helps to explain the pathophysiological processes of sacroiliac joint ankylosis, which is a hallmark of the spondyloarthritides.
Myocardial Injury and Long-term Mortality Following Moderate to Severe Carbon Monoxide Poisoning
Authors: Christopher R. Henry, Daniel Satran, Bruce Lindgren, Cheryl Adkinson, Caren I. Nicholson, Timothy D. Henry
Journal: JAMA (2006)

Carbon monoxide (CO) poisoning is a common cause of toxicological morbidity and mortality. Myocardial injury is a frequent consequence of moderate to severe CO poisoning. While the in-hospital mortality for these patients is low, the long-term outcome of myocardial injury in this setting is unknown.To determine the association between myocardial injury and long-term mortality in patients following moderate to severe CO poisoning.Prospective cohort study of 230 consecutive adult patients treated for moderate to severe CO poisoning with hyperbaric oxygen and admitted to the Hennepin County Medical Center, a regional center for treatment of CO poisoning, between January 1, 1994, and January 1, 2002. Follow-up was through November 11, 2005.All-cause mortality.Myocardial injury (cardiac troponin I level > or =0.7 ng/mL or creatine kinase-MB level > or =5.0 ng/mL and/or diagnostic electrocardiogram changes) occurred in 85 (37%) of 230 patients. At a median follow-up of 7.6 years (range: in-hospital only to 11.8 years), there were 54 deaths (24%). Twelve of those deaths (5%) occurred in the hospital as a result of a combination of burn injury and anoxic brain injury (n = 8) or cardiac arrest and anoxic brain injury (n = 4). Among the 85 patients who sustained myocardial injury from CO poisoning, 32 (38%) eventually died compared with 22 (15%) of 145 patients who did not sustain myocardial injury (adjusted hazard ratio, 2.1; 95% confidence interval, 1.2-3.7; P = .009).Myocardial injury occurs frequently in patients hospitalized for moderate to severe CO poisoning and is a significant predictor of mortality.
Mechanisms of Neural Patterning and Specification in the Development Cerebellum
Authors: M E Hatten, N Heintz
Journal: Annual Review of Neuroscience (1995)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Utility of Incorporating Genetic Variants for the Early Detection of Prostate Cancer
Authors: Robert K. Nam, William W. Zhang, John Trachtenberg, Arun Seth, Laurence H. Klotz, Aleksandra Stanimirovic, Sanoj Punnen, Vasundara Venkateswaran, Ants Toi, D. Andrew Loblaw, Linda Sugar, Katherine A. Siminovitch, Steven A. Narod
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Several single nucleotide polymorphisms (SNP) have been associated with the risk of prostate cancer. The clinical utility of using SNPs in the early detection of prostate cancer has not been evaluated. Experimental Design: We examined a panel of 25 SNPs from candidate genes and chromosomal regions in 3,004 unselected men who were screened for prostate cancer using serum prostate-specific antigen (PSA) and digital rectal examination. All underwent a prostate biopsy. We evaluated the ability of these SNPs to help predict the presence of prostate cancer at biopsy. Results: Of the 3,004 patients, 1,389 (46.2%) were found to have prostate cancer. Fifteen of the 25 SNPs studied were significantly associated with prostate cancer (P = 0.02-7 × 10−8). We selected a combination of 4 SNPs with the best predictive value for further study. After adjusting for other predictive factors, the odds ratio for patients with all four of the variant genotypes compared with men with no variant genotype was 5.1 (95% confidence interval, 1.6-16.5; P = 0.006). When incorporated into a nomogram, genotype status contributed more significantly than PSA, family history, ethnicity, urinary symptoms, and digital rectal examination (area under the curve = 0.74). The positive predictive value of the PSA test ranged from 42% to 94% depending on the number of variant genotypes carried (P = 1 × 10−15). Conclusions: SNP genotyping can be used in a clinical setting for the early detection of prostate cancer in a nomogram approach and by improving the positive predictive value of the PSA test.
Uncinate Fasciculus Findings in Schizophrenia: A Magnetic Resonance Diffusion Tensor Imaging Study
Authors: Marek Kubicki, Carl-Fredrik Westin, Stephan E. Maier, Melissa Frumin, Paul G. Nestor, Dean F. Salisbury, Ron Kikinis, Ferenc A. Jolesz, Robert W. McCarley, Martha E. Shenton
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. METHOD: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. RESULTS: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. CONCLUSIONS: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.
Mitoxantrone and Cytarabine Induction, High-Dose Cytarabine, and Etoposide Intensification for Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia: Children’s Cancer Group Study 2951
Authors: Robert J. Wells, Mary T. Adams, Todd A. Alonzo, Robert J. Arceci, Jonathan Buckley, Allen B. Buxton, Kathryn Dusenbery, Alan Gamis, Margaret Masterson, Terry Vik, Phyllis Warkentin, James A. Whitlock
Journal: Journal of Clinical Oncology (2003)

To evaluate the response rate, survival, and toxicity of mitoxantrone and cytarabine induction, high-dose cytarabine and etoposide intensification, and further consolidation/maintenance therapies, including bone marrow transplantation, in children with relapsed, refractory, or secondary acute myeloid leukemia (AML). To evaluate response to 2-chlorodeoxyadenosine (2-CDA) and etoposide (VP-16) in patients who did not respond to mitoxantrone and cytarabine.Patients with relapsed/refractory AML (n = 101) and secondary AML (n = 13) were entered.Mitoxantrone and cytarabine induction achieved a remission rate of 76% for relapsed/refractory patients and 77% for patients with secondary AML, with a 3% induction mortality rate. Cytarabine and etoposide intensification exceeded the acceptable toxic death rate of 10%. The response rate of 2-CDA/VP-16 was 8%. Two-year overall survival was estimated at 24% and was better than historical control data. Patients with secondary AML had similar outcomes to relapsed or refractory patients. Initial remission longer than 1 year was the most important prognostic factor for patients with primary AML (2-year survival rate, 75%), whereas for patients with primary AML, with less than 12 months of initial remission, survival was 13% and was similar to that of refractory patients (6%).Mitoxantrone and cytarabine induction is effective with reasonable toxicity in patients with relapsed/refractory or secondary AML. The cytarabine and etoposide intensification regimen should be abandoned because of toxicity. Patients with relapsed AML with initial remissions longer than 1 year have a relatively good prognosis.
Oxidative stress and lung permeability during chlorine-induced acute lung injury in mice
Authors: Linda Elfsmark, Lina Ågren, Christine Akfur, Barbro Ekstrand-Hammarström, Anders Bucht
Journal: European Respiratory Journal (2013)

Clinical diagnosis and prognosis of respiratory injury after accidental inhalation of chlorine is complicated by unknown exposure levels of the individuals, delayed symptoms and a wide range in pathological out-come. Here we used a murine model for chlorine-induced lung injury to evaluate if indicators of oxidative stress and lung permeability can be used as biomarkers of acute lung injury.  Mice was exposed to 200 ppm Cl2 during 15 min by nose-only inhalation. Bronchoalveolar lavage fluid (BALF) and serum was sampled from 2 h up to 14 days post exposure and analysed with ELISA regarding oxidation of phospholipids (8-isoprostane PGF2α), albumin, surfactant protein D (SP-D) and Clara cell specific protein 16 (CC16). The dose-response of the markers was also determined in mice exposed to 25, 50, 100 and 200 ppm Cl2 and their specificity was evaluated in another murine model for chemical-induced lung injury (mustard gas analogue).  Exposure to Cl2 caused a dose-dependent increase of 8-isoprostane PGF2α in BALF and the highest concentration of Cl2 significantly increased (p  We conclude that 8-isoprostan PGF2α represents a promising local biomarker for chlorine-induced lung injury that potentially could be used as a diagnostic tool.
Respiratory mechanics studied by multiple linear regression in unsedated ventilated patients
Authors: R Peslin, JF da Silva, F Chabot, C Duvivier
Journal: European Respiratory Journal (1992)

Respiratory mechanics during artificial ventilation are commonly studied with methods which require a specific respiratory pattern. An alternative is to analyse the relationship between tracheal pressure (P) and flow (V') by multiple linear regression (MLR) using a suitable model. The value of this approach was evaluated in 12 unsedated patients, mechanically-ventilated for acute respiratory failure, and most with a history of chronic obstructive or restrictive respiratory disease. After correction for the non-linear resistance of the endotracheal tube, the data were analysed with the linear first order model: P = P0 + E.V + R.V' where E and R are total respiratory elastance and resistance, and P0 is the static recoil pressure at end-expiration. After exclusion of the cycles which clearly exhibited muscular activity, a good fit was observed in 25 out of 36 records (relative root-mean-square error less than 10%); the values of E and R were reproducible within cycles, and consistent with the patient's condition and the ventilatory mode. The intrinsic positive end-expiratory pressure (PEEPi), as derived from P0 and the applied PEEP, averaged 1.1 +/- 1.0 hPa. Using more sophisticated models, allowing for mechanical non-homogeneity or non-linearity of R or E, rarely improved the fit and often provided unrealistic data. In several subjects the discrepancy between the data and the first order model was consistent with expiratory flow limitation, which may severely impair the analysis. We conclude that, except in the case of expiratory flow limitation, the method is useful for routine clinical use and better implemented with the simple linear model.
Is nicotine replacement therapy for smoking cessation effective in the "real world"? Findings from a prospective multinational cohort study
Authors: R. West, X. Zhou
Journal: Thorax (2007)

<h3>Background:</h3> Increasing smoking cessation rates is an important goal in preventing lung cancer and chronic obstructive pulmonary disease. Nicotine replacement therapy (NRT) has been found in clinical trials to improve the chances of success at stopping, but recent cross-sectional survey data have raised doubts as to whether it is effective when used by smokers making quit attempts unsupervised outside clinical trials. Because of biases inherent in cross-sectional surveys, this issue can only be adequately addressed using longitudinal studies. This paper reports the first study of its kind to examine the issue. <h3>Methods:</h3> The ATTEMPT cohort is a multinational cohort study with data collection by the internet which recruited smokers of ⩾5 cigarettes per day aged 35–65 years who were intending to stop smoking within the next 3 months. Phase 1 began in spring 2003 and involved 2009 smokers from the USA, UK, Canada and France. Phase 2 involved 3645 smokers and included the same countries plus Spain. Follow-up assessments were carried out every 3 months. 492 smokers who made a quit attempt without formal behavioural support or bupropion in the first 3-month follow-up period were identified from phase 1, 357 of whom were followed up for a further 6 months. The phase 2 sample involved 906 smokers making quit attempts, 732 of whom were followed up. At baseline, demographic characteristics, smoking history and nicotine dependence were assessed. Smokers who made quit attempts were questioned on methods used to aid them. The main outcome measure was self-report of complete abstinence throughout both the 3-month periods following the quit date. <h3>Results:</h3> 35.6% of smokers followed up in phase 1 and 29.6% of those followed up in phase 2 used NRT. The odds ratios comparing abstinence for 6 months in those using and those not using NRT, adjusting for nicotine dependence, were 3.0 (95% CI 1.2 to 7.5) for the phase 1 sample and 2.1 (95% CI 1.0 to 4.1) for the phase 2 sample. The difference in success rates between those using NRT and those not using it, adjusted for the Fagerstrom test for nicotine dependence (FTND) score, was 6% in the phase 1 sample and 3.7% in the phase 2 sample. The improved odds of success were not explicable in terms of motivation to use some form of aid to cessation or differential loss to follow-up. <h3>Conclusion:</h3> NRT use by smokers making self-initiated quit attempts without formal behavioural support is associated with improved long-term abstinence rates.