tbuckley/cabot-search huggingface dataset:
Cancer Risks After Endometrial Cancer in Mismatch Repair Mutation Carriers
Authors: Patrick M. Lynch
Journal: JNCI Journal of the National Cancer Institute (2013)

11%, 9%, and 11%, respectively, and the relative risks compared with the general population were significantly increased for each. Strengths of the study include the substantial patient population, of relatively unbiased source, the comprehensive approach to genetic diagnosis and cohort follow-up, and the experience of the investigators. The data on cancer incidence after endometrial cancer diagnosis are helpful but require attention to the details of surveillance, not all of which were available. Frequency of colonoscopy or other screening was based on questionnaires. Interventions to communicate HNPCC/LS screening guidelines or to otherwise foster cancer surveillance were not identified and were presumably heterogeneous. For these reasons, it is worth considering the aftermath of endometrial cancer diagnosis in the setting of HNPCC/LS. Unsurprisingly, a protective role for colonoscopy screening was seen. A linear reduction in freedom from colorectal cancer was found with increased interval of surveillance, from 44% in those having annual exam to 13% in those with exams at 4- to 5- year intervals. However, colorectal cancer did occur despite even annual surveillance. This phenomenon has been seen in more formal screening studies, underscoring the limitations of colonoscopy generally in assuring protection against colorectal cancer (9). More specifically, the subtlety of early lesions and their rapid growth to become interval cancer was very likely a factor, although unproven by the limited numbers. Consistent with other data, colorectal cancer risk was lower in MSH6 mutation carriers (standardized incidence ratios of 4.46 vs 38.7 and 58.5 for MLH1 and MSH2 mutation carriers, respectively). Despite this, no changes in screening guidelines have yet been recommended for MSH6 mutation carriers. Colorectal cancer risk could not be assessed for PMS2 mutation carriers because data were not collected for them. This group has been considered to be at lower risk of colorectal cancer (10). No data were available regarding screening for other at-risk organs. The modest increased risk of breast cancer was thought to have perhaps been an artifact of increased screening, but no actual screening data were brought to bear on this. Again, no enhancement of breast cancer screening has yet been recommended in HNPCC/LS.
Cluster analysis in the COPDGene study identifies subtypes of smokers with distinct patterns of airway disease and emphysema
Authors: Peter J Castaldi, Jennifer Dy, James Ross, Yale Chang, George R Washko, Douglas Curran-Everett, Andre Williams, David A Lynch, Barry J Make, James D Crapo, Russ P Bowler, Elizabeth A Regan, John E Hokanson, Greg L Kinney, Meilan K Han, Xavier Soler, Joseph W Ramsdell, R Graham Barr, Marilyn Foreman, Edwin van Beek, Richard Casaburi, Gerald J Criner, Sharon M Lutz, Steven I Rennard, Stephanie Santorico, Frank C Sciurba, Dawn L DeMeo, Craig P Hersh, Edwin K Silverman, Michael H Cho
Journal: Thorax (2014)

<h3>Background</h3> There is notable heterogeneity in the clinical presentation of patients with COPD. To characterise this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from the COPDGene study. <h3>Methods</h3> We applied a clustering method, k-means, to data from 10 192 smokers in the COPDGene study. After splitting the sample into a training and validation set, we evaluated three sets of input features across a range of <i>k</i> (user-specified number of clusters). Stable solutions were tested for association with four COPD-related measures and five genetic variants previously associated with COPD at genome-wide significance. The results were confirmed in the validation set. <h3>Findings</h3> We identified four clusters that can be characterised as (1) relatively resistant smokers (ie, no/mild obstruction and minimal emphysema despite heavy smoking), (2) mild upper zone emphysema-predominant, (3) airway disease-predominant and (4) severe emphysema. All clusters are strongly associated with COPD-related clinical characteristics, including exacerbations and dyspnoea (p&lt;0.001). We found strong genetic associations between the mild upper zone emphysema group and rs1980057 near <i>HHIP</i>, and between the severe emphysema group and rs8034191 in the chromosome 15q region (p&lt;0.001). All significant associations were replicated at p&lt;0.05 in the validation sample (12/12 associations with clinical measures and 2/2 genetic associations). <h3>Interpretation</h3> Cluster analysis identifies four subgroups of smokers that show robust associations with clinical characteristics of COPD and known COPD-associated genetic variants.
Reconstituting Vascular Microenvironment of Neural Stem Cell Niche in Three‐Dimensional Extracellular Matrix
Authors: Yoojin Shin, Kisuk Yang, Sewoon Han, Hyun‐Ji Park, Yun Seok Heo, Seung‐Woo Cho, Seok Chung
Journal: Advanced Healthcare Materials (2014)

Neural stem cells (NSCs) reside in a vascular microenvironment termed the “NSC niche.” Blood vessels in the NSC niche play an important role in maintaining an appropriate balance between NSC self‐renewal and differentiation that serves to maintain homeostasis. Understanding the role of brain vessels in the NSC niche will facilitate basic research in neurogenesis and vasculogenesis as well as aid the development of potential therapies for degenerative disorders. Here, an in vitro‐reconstituted NSC‐vascular niche consisting of a 3D brain vasculature and extracellular matrix (ECM) microenvironment that allows NSCs to adopt physiologically relevant phenotypes through the combined effects of ECM components, chemical gradients, and signaling effectors from the brain vasculature is described. The reconstituted niche can provide precise spatiotemporal control of the NSC niche, regulating self‐renewal, proliferation and colony formation of NSCs, and suppressing neuronal generation but promoting NSC differentiation into astrocytes and oligodendrocytes. It is proved that Notch effectors regulate both the astrocyte differentiation and NSC self‐renewal, but the astrocyte differentiation is more active in NSCs in close proximity to brain vasculature. A potential role of the other vascular microenvironmental factor of pigment epithelium‐derived factor from brain vasculature in the regulation of NSC self‐renewal is also proved.
PD04-06: A Randomised Controlled Trial of Quality of Life and Fatigue after Support Group Intervention in Primary Breast Cancer Patients.
Authors: H Granstam Björneklett, C Lindemalm, M-L Ojutkangas, A Berglund, H Letocha, P Strang, L Bergkvist
Journal: Cancer Research (2011)

Abstract Background: When diagnosed with breast cancer, most women's lives change as well as their perspectives on and appreciation of life. The aim of the present study was to evaluate whether psychosocial support intervention could influence health- related quality of life and fatigue during the first year after diagnosis. Material and Methods: Of 382 patients with newly diagnosed breast cancer, 191 + 191 patients were randomized to an intervention group or to a routine control group respectively. The intervention group received support intervention that lasted one week on a residential basis, followed by four days of follow-up two months later. The support intervention included informative-educational parts, relaxation training, mental visualisation and nonverbal communication. Health-related quality of life was measured using the EORTC-QLQ 30 and QLQ-BR23 questionnaires and fatigue with the Norwegian version of the Fatigue scale at baseline, 2, 6 and 12 months after intervention. Result: There were a time-dependant improvement in both functional and symptom scales between baseline and 12 months as measured by the EORTC QLQ 30 and BR 23 questionnaires and there was a decrease in fatigue between baseline and after 2 months with further improvement up to 12 months in both groups but there were no differences between the intervention and control groups at any point in time. Conclusion: Health related Quality of Life improves and symptoms of fatigue decreases over time, but we could not see any additional effect from the rehabilitation program in this setting. Key words: Support intervention, breast cancer, health- related quality of life, fatigue, EORTC-QLQ 30 and BR 23, the Norwegian version of the fatigue scale. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-06.
IN VITRO SYNTHESIS AND SECRETION OF LYSOZYME BY MONONUCLEAR PHAGOCYTES
Authors: Salmon Gordon, Jean Todd, Z. A. Cohn
Journal: The Journal of Experimental Medicine (1974)

Pure cultures of three types of mononuclear phagocytes-mouse peritoneal macrophages, unstimulated or after thioglycollate stimulation, and human monocytes-synthesize and secrete large amounts of lysozyme in vitro. The macrophage lysozyme is indistinguishable from authentic lysozyme in its ability to lyse M. lysodeikticus, inhibition by specific antisera, a similar size of 14,000 and cationic charge. Lysozyme secretion in culture is characterized by a large net increase in total lysozyme, 4-20-fold in 3 h, 75-95% of which is in the medium, and its continued extracellular accumulation over at least 2 wk in culture. Lysozyme is the major (14)C-labeled protein secreted into the medium by both unstimulated and thioglycollate-stimulated macrophages and the 0.75-1 microg produced per 1 x 10(6) cells/day represents 0.5-2.5% of the total cell protein. Lysozyme is a cell-specific marker for mononuclear phagocytes and the PMN, which contains preformed enzyme, since it is absent in lymphoid cells and a variety of fibroblast and epithelioid cell lines. Lysozyme production is also a useful measure of mononuclear phagocyte cell number. The rate of lysozyme production and secretion is remarkably constant for all cell types under a variety of culture conditions. Production by the mouse macrophage increases threefold on the 2nd day in culture and then remains linear with time. Production is optimal at a relatively low serum concentration, but can be maintained, in the absence of serum, in lactalbumin hydrolysate or, at a reduced level in basal media. The production and secretion of lysozyme are independent of the production of macrophage acid hydrolases. Net increase and secretion of lysozyme occur under conditions where acid hydrolases like N-acetyl beta-glucosaminidase, beta-glucuronidase, beta-galactosidase, and cathepsin D are neither accumulated nor secreted. Massive phagocytosis of latex particles has no effect on lysozyme production and secretion. Lysozyme production can be rapidly inhibited by treatment with cycloheximide (0.4 microg/ml) whereas inhibition of its production by colchicine (10(-6) M) occurs only after a lag period of more than 8 h, and is probably due to a secondary effect. These results show that mouse macrophages provide a simple in vitro system to measure lysozyme secretion and its control. These studies also indicate the possible importance of mononuclear phagocytes in the secretion of a variety of biologically active products and in the modification of their environment.
A Proposal for Structured Reporting of Randomized Controlled Trials
Authors: Erik Andrew, Aslam Anis, Tom Chalmers, Mildred Cho, Mike Clarke, David Felson, Peter Gøtzsche, Richard Greene, Alejandro Jadad, Wayne Jonas, Terry Klassen, Paul Knipschild, Andreas Laupacis, Curtis L. Meinert, David Moher, Graham Nichol, Andy Oxman, Stuart Pocock, Joan Reisch, David Sackett, Kenneth Schulz, Judy Snider, Peter Tugwell, Jon Tyson, Wikke Walop, Sharon Walsh, George Wells
Journal: JAMA (1994)

A RANDOMIZED controlled trial (RCT) is the most reliable method of assessing the efficacy of health care interventions.<sup>1,2</sup>Reports of RCTs should provide readers with adequate information about what went on in the design, execution, analysis, and interpretation of the trial. Such reports will help readers judge the validity of the trial. There have been several investigations evaluating how RCTs are reported. In an early study, Mahon and Daniel<sup>3</sup>reviewed 203 reports of drug trials published between 1956 and 1960 in the<i>Canadian Medical Association Journal</i>. Only 11 reports (5.4%) fulfilled their criteria of a valid report. In a review of 45 trials published during 1985 in three leading general medical journals, Pocock and colleagues<sup>4</sup>reported that a statement about sample size was only mentioned in five (11.1%) of the reports, that only six (13.3%) made use of confidence intervals, and that the statistical analyses tended to
Apple polyphenol extracts prevent damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo
Authors: G Graziani
Journal: Gut (2005)

Fresh fruit and vegetables exert multiple biological effects on the gastrointestinal mucosa.To assess whether apple extracts counteract oxidative or indomethacin induced damage to gastric epithelial cells in vitro and to rat gastric mucosa in vivo.Apple extracts were obtained from freeze dried apple flesh of the "Annurca" variety. Cell damage was induced by incubating MKN 28 cells with xanthine-xanthine oxidase or indomethacin and quantitated by MTT. In vivo gastric damage was induced by indomethacin 35 mg/kg. Intracellular antioxidant activity was determined using the (2,2'-azinobis (3-ethylbenzothiazolin-6-sulfonate) method. Malondialdehyde intracellular concentration, an index of lipid peroxidation, was determined by high pressure liquid chromatography with fluorometric detection.(1) Apple extracts decreased xanthine-xanthine oxidase or indomethacin induced injury to gastric epithelial cells by 50%; (2) catechin or chlorogenic acid (the main phenolic components of apple extracts) were equally effective as apple extracts in preventing oxidative injury to gastric cells; and (3) apple extracts (i) caused a fourfold increase in intracellular antioxidant activity, (ii) prevented its decrease induced by xanthine-xanthine oxidase, (iii) counteracted xanthine-xanthine oxidase induced lipid peroxidation, and (iv) decreased indomethacin injury to the rat gastric mucosa by 40%.Apple extracts prevent exogenous damage to human gastric epithelial cells in vitro and to the rat gastric mucosa in vivo. This effect seems to be associated with the antioxidant activity of apple phenolic compounds. A diet rich in apple antioxidants might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species.
Nontraumatic rhabdomyolysis: an unusual complication of diabetic hyperosmolar nonketotic (HONK) state
Authors: K K Gangopadhyay
Journal: Journal of the Royal Society of Medicine (2006)

Rhabdomyolysis is an uncommon but underestimated complication of HONK. 1 We present the case of a patient presenting with HONK complicated by rhabdomyolysis. CASE HISTORYA 75-year-old man of Asian origin was admitted with a 2day history of being generally unwell.He noted progressive polyuria, polydipsia for about 2 months prior to admission.There was no history of trauma, seizures, muscle pain, chest pain, drug or alcohol abuse.He had no past medical history including no known diabetes mellitus.He was a non-smoker and did not drink alcohol.On admission his blood pressure was 150/90, pulse rate 110/minute regular, temperature 368C.Physical examination was only remarkable for dehydration.Laboratory investigations on admission revealed venous plasma glucose 42 mmol/L; sodium 152 mmol/L; potassium 4.4 mmol/ L; urea 13.4 mmol/L; creatine 147 mmol/L; arterial blood gas ph 7.36, HCO 3 23.9 mmol/L; serum osmolality 362 mOsm/kg; serum creatine kinase 6309 iu/L with CKMB fraction of 0.9%; troponin I 50.1 ng/L; albumin 50 g/L; bilirubin 12 mmol/L; alanine transferase 60 iu/L; alkaline phosphatase 127 iu/L; serum amylase 75 iu/L; haemoglobin 16.8 g/L; leucocytes 17610 9 platelets 267610 9 ; C-reactive protein 8 mg/L; erythrocyte sedimentation rate 16 mm in the first hour; urine dipstix revealed 4+ glucose; the chest X-ray and electrocardiograph were unremarkable.The patient was treated with rehydration and continuous insulin infusion for 48 h.The creatine kinase rose from 6309 iu/L on admission to a peak level of 11 275 iu/L on day 2 before reducing to 3292 iu/L on day 3.By day 3 his sodium had normalized to 137 mmol/L and creatine to 74 mmol/L.Blood and urine cultures were negative.The patient was feeling much better by day 2 when he was put on a twice-daily insulin regime.Due to important commitments at home the patient had to be discharged on day 3.
Association of Age at Diagnosis and Genetic Mutations in Patients With Neuroblastoma
Authors: Nai-Kong V. Cheung
Journal: JAMA (2012)

Neuroblastoma is diagnosed over a wide age range from birth through young adulthood, and older age at diagnosis is associated with a decline in survivability.To identify genetic mutations that are associated with age at diagnosis in patients with metastatic neuroblastoma.Whole genome sequencing was performed on DNA from diagnostic tumors and their matched germlines from 40 patients with metastatic neuroblastoma obtained between 1987 and 2009. Age groups at diagnosis included infants (0-<18 months), children (18 months-<12 years), and adolescents and young adults (≥12 years). To confirm the findings from this discovery cohort, validation testing using tumors from an additional 64 patients obtained between 1985 and 2009 also was performed. Formalin-fixed, paraffin-embedded tumor tissue was used for immunohistochemistry and fluorescence in situ hybridization. Telomere lengths were analyzed using whole genome sequencing data, quantitative polymerase chain reaction, and fluorescent in situ hybridization.Somatic recurrent mutations in tumors from patients with neuroblastoma correlated with the age at diagnosis and telomere length.In the discovery cohort (n = 40), mutations in the ATRX gene were identified in 100% (95% CI, 50%-100%) of tumors from patients in the adolescent and young adult group (5 of 5), in 17% (95% CI, 7%-36%) of tumors from children (5 of 29), and 0% (95% CI, 0%-40%) of tumors from infants (0 of 6). In the validation cohort (n = 64), mutations in the ATRX gene were identified in 33% (95% CI, 17%-54%) of tumors from patients in the adolescent and young adult group (9 of 27), in 16% (95% CI, 6%-35%) of tumors from children (4 of 25), and in 0% (95% CI, 0%-24%) of tumors from infants (0 of 12). In both cohorts (N = 104), mutations in the ATRX gene were identified in 44% (95% CI, 28%-62%) of tumors from patients in the adolescent and young adult group (14 of 32), in 17% (95% CI, 9%-29%) of tumors from children (9 of 54), and in 0% (95% CI, 0%-17%) of tumors from infants (0 of 18). ATRX mutations were associated with an absence of the ATRX protein in the nucleus and with long telomeres.ATRX mutations were associated with age at diagnosis in children and young adults with stage 4 neuroblastoma.clinicaltrials.gov Identifier: NCT00588068.
Studies on Digitalis XIV: Influence of Cardiac Norepinephrine Stores on the Response of Isolated Heart Muscle to Digitalis
Authors: JAMES F. SPANN, EDMUND H. SONNENBLICK, THEODORE COOPER, CHARLES A. CHIDSEY, VALLEE L. WILLMAN, EUGENE BRAUNWALD
Journal: Circulation Research (1966)

On the basis of studies on cardiac tissue removed from animals treated with antiadrenergic drugs, a number of investigators have suggested that the positive inotropic response to digitalis requires norepinephrine in the cardiac muscle. In the present study the action of strophanthidin was studied in isolated papillary muscles obtained from normal cat hearts, from chronic, totally cardiac-denervated, norepinephrine-depleted hearts, and from reserpine-treated, norepinephrine-depleted cats. Complete force-velocity and length-tension curves were recorded. Following the addition of strophanthidin (1.0µg/ml) to the bath, maximum isometric tension rose by averages of 2.17 ± 0.32 g/mm 2 in the normal muscles and 2.65 ± 0.50 g/mm 2 in the muscles from the denervated cats, but increased significantly less ( P &lt; 0.05) in the muscles from the reserpine-treated animals (1.09 ± 0.36 g/mm 2 ). In addition to these changes in isometric tension, strophanthidin increased the maximum velocity of contraction (V max ) to a comparable extent in normal and denervated muscles, with a smaller elevation of V max in reserpine-treated muscles. Strophanthidin reduced the absolute refractory period to an equal extent in all three groups of muscles. From a comparison of the inotropic responses of the muscles from normal and cardiac-denervated cats it is concluded that cardiac norepinephrine stores and neural integrity are not essential for the positive inotropic effect of strophanthidin or for its effects on the duration of the absolute refractory period. However, it appears that prior reserpine treatment may interfere with the inotropic response to digitalis by a mechanism other than norepinephrine depletion.
Hepatic abscess mimicking hepatocellular carcinoma in a patient with alcoholic liver disease
Authors: Jin Woong Kim, Sang Soo Shin, Suk Hee Heo, Hyo Soon Lim, Young Hoe Hur, Jo Heon Kim
Journal: Clinical and Molecular Hepatology (2013)

Hepatic abscesses are known to present with various imaging findings according to the degree of maturation and internal contents.1 Hepatic abscess rarely mimics hepatic neoplasm such as HCC. As evidenced by our case, if there are no clinical and laboratory findings suggestive of hepatic abscess, hepatic abscess that presents with imaging findings, such as early arterial enhancement and delayed washout, mosaic pattern of enhancement, and well-defined tumoral capsule with delayed enhancement could be hardly differentiated from HCC.
Accidents in the home among children under 5: ethnic differences or social disadvantage?
Authors: R. Alwash, M. McCarthy
Journal: BMJ (1988)

Accidents in the home to children under 5 in a multiracial population with a high level of social disadvantage were studied by interviewing at home the parents of 402 children attending the accident department of a west London hospital during one year. The parents9 country of birth, whether they were employed, and their housing conditions were recorded using the definitions of the 1981 census. Four ethnic groups (British (183 children), Asian (127), Caribbean (61), and other (31)) were identified. Though attendance rates based on the populations of electoral wards at the census and standardised for distance from the hospital showed no significant differences among the ethnic groups, there was a strong gradient by social class and strong associations with unemployment of the mother (although not of the father), overcrowding, and tenure of housing. Social disadvantage seems to be more important than ethnicity as a determinant of accidents to children in the home.
Aluminium in Bone from Patients with Renal Failure
Authors: V. Parsons, C. Davies, C. Goode, C. Ogg, J. Siddiqui
Journal: BMJ (1971)

Some samples of bone from patients with renal failure contained more aluminium than others, and the concentration tended to be highest in patients who had been uraemic or on dialysis longest. The significance of the association of raised concentrations of aluminium in bone with renal failure is discussed.