tbuckley/cabot-search huggingface dataset:
Audit of survival on long-term oxygen therapy
Authors: Catherine Billings, Alan Bullock, Ruth Darwin, Christine Wrench, Rod Lawson
Journal: European Respiratory Journal (2013)

Aims:  UK survival data for patients prescribed long-term oxygen therapy (LTOT) is sparse. We aimed to assess: adherence to BTS 2006 guidelines (1) for the assessment of LTOT; and equability of survival benefit of LTOT throughout the Sheffield area and to compare the survival rate for Sheffield patients with the gold standard studies;   Methods:  Patients prescribed LTOT >15 h/day between 2005-2011 were identified from our database. Date of prescription, demographics, assessment, smoking status, post code, and date of death were used for Kaplan-Meier survival curves.   Results:  41% had an initial oxygen assessment. Survival compared well with the randomised controlled trials of LTOT.  No significant difference in survival was noted for gender, smoking status or deprivation. Median survival of COPD patients was 3 times that of interstitial lung disease. Initial assessment of patients for LTOT was below the recommended standard. but the Oxygen Service has now expanded and a full assessment of all patients on LTOT in Sheffield will be carried out in the next 18 months.   Conclusions:  Survival of Sheffield patients on LTOTwas amongst the best reported(2) and survival benefit appears equitable across city. A re-audit is planned for 2 years time.   References  1 . British Thoracic Society (2006). Clinical component for the home oxygen service in England and Wales  2 . Ringbaek TJ. (2006). Dan Med Bull. 53: 310-315.
European and North American populations should be screened for coeliac disease
Authors: P J Kumar
Journal: Gut (2003)

<h3>ABSTRACT</h3> Social structure can have profound evolutionary and ecological implications for animal populations. Structure can arise and be maintained via social preferences or be indirectly shaped by habitat structure. Understanding how social structure emerges is important for understanding the potential links between social structure and evolutionary and ecological processes. Here, we study a large community of wild birds fitted with uniquely-coded passive integrated transponder (PIT) tags and recorded on a grid of automated feeders fitted with radio frequency identification (RFID) antennae. We show that both large-scale and fine-scale network communities are consistent across years in this population, despite high generational turn-over. Studying the process that generates community structure, here the movement of individual birds across the woodland, suggests an important role of habitat geometry in shaping population-level social community structure. Our study highlights how relatively simple factors can produce apparent emergent social structure at the population scale, which has widespread implications for understanding eco-evolutionary dynamics.
Efficacy of TNFα blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis
Authors: Johanna Callhoff, Joachim Sieper, Anja Weiß, Angela Zink, Joachim Listing
Journal: Annals of the Rheumatic Diseases (2014)

Objectives This meta-analysis investigates the efficacy of tumour necrosis factor α (TNFα) blockers versus placebo for the treatment of ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). Methods A systematic literature search was conducted independently by two reviewers. Double-blind randomised controlled trials (RCTs) investigating the efficacy of adalimumab, certolizumab, etanercept, golimumab or infliximab in approved dosages in comparison with placebo were included. The use of concomitant non-steroidal antirheumatic drugs was allowed. The outcome parameters were improvement in disease activity and function measured by the Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI) and ASAS40 response. The effect sizes of the changes in BASDAI/BASFI between TNFα blocker and placebo comparator groups were calculated. Mixed effect models were applied separately for RCTs with AS and nr-axSpA patients and differences between those groups were evaluated in a joint model. Results 20 studies with data from 3096 patients were included in the analysis: 15 studies with AS patients, four with nr-axSpA patients and one with both. For AS patients, TNFα blockers showed better efficacy than placebo for BASDAI (effect size 1.00), BASFI (effect size 0.67) and ASAS40 response (OR 4.7). For nr-axSpA patients, the differences were smaller (effect sizes 0.73, 0.57; OR 3.6). However, after adjustment for the year of publication as a proxy for disease severity, no differences in the effect sizes between the AS and nr-axSpA trials were observed. Conclusions Compared with placebo, TNFα blockers improve disease activity and functional capacity clinically meaningful for both AS and nr-axSpA patients.
A histopathological study of 643 cutaneous horns
Authors: R.C.H. YU, D.W. PRYCE, A.W. MACFARLANE, T.W. STEWART
Journal: British Journal of Dermatology (1991)

A retrospective study of 643 cutaneous horns examined in our department between 1970 and 1989 revealed that 38.9% were derived from malignant or premalignant epidermal lesions, and 61.1% from benign lesions. Four main features were associated with premalignant or malignant histopathological change at the base of a cutaneous horn (base pathology). These were: (i) age--the mean age of the patients whose cutaneous horns showed premalignant or malignant base pathology was 8.9 years greater than the mean age of the patients where base pathology was benign (P less than 0.0005); (ii) sex--males were more likely to develop a cutaneous horn with (pre)malignant base pathology (P less than 0.001); (iii) site--over 70% of all (pre)malignant lesions were found on the nose, pinnae, backs of hands, scalp, forearms and the face; a cutaneous horn found at these sites was 2.1 times more likely to have derived from a (pre)malignant base than from any other part of the body (P less than 0.0001); (iv) geometry of the lesion--lesions with a wide base or a low height-to-base ratio were significantly more likely to show (pre)malignant base pathology. Of those solar keratoses giving rise to cutaneous horns, 8.9% also showed histological evidence of change to squamous cell carcinoma (SCC); this figure was not significantly different from the 6.2% of solar keratoses without horns that showed SCC change during the same period (1970-89).
Membrane distribution and adsorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes.
Authors: D T Fearon, I Kaneko, G G Thomson
Journal: The Journal of Experimental Medicine (1981)

C3b receptors on human polymorphonuclear leukocytes (PMN) were nonrandomly distributed in small clusters on the plasma membranes of these cells when assessed by indirect immunofluorescence at 0 degree C using monospecific rabbit Fab' or F(ab')2 anti-C3b receptor and tetramethylrhodamine isothiocyanate (TRITC)-conjugated goat IgG anti-F(ab')2. When PMN were incubated with the bivalent anti-C3b receptor at 37 rather than at 0 degree C, almost no immunofluorescence was observed, which indicates that the C3b receptor-F(ab')2 complexes had been rendered inaccessible to TRITC-IgG anti-F(ab')2. Endocytosis of the anti-C3b receptor ligand was quantitated by measuring the binding 131I-IgG anti-F(ab')2 by PMN that had previously taken up 125I-F(ab')2 anti-C3b receptor at 0 and at 37 degree C, respectively. There was a constant 2: 1 molar ratio of anti-F(ab')2 to anti-C3b receptor with PMN that had been incubated with the first antibody at 0 degree C. In contrast, when increments of F(ab')2 anti-C3b receptor were taken up by the cells at 37 degree C, there was a dose-related decline in this molar ratio to a minimum of 0.2 molecules of anti-F(ab')2 anti-F(ab')2 bound per molecule of PMN-associated anti-C3b receptor. 125I-F(ab')2 anti-C3b receptor taken up by PMN at 37 degree C was also inaccessible to release by proteolytic treatment of the cells with pronase. The rate of endocytosis of 125I-F(ab')2 anti-C3b receptor was rapid as the PMN-bound antibody fragment became inaccessible to 131I-IgG anti-F(ab')2 within 10 min during incubation of the cells at 37 degree C. In contrast to these findings, 125I-Fab' anti-C3b receptor that was taken up by PMN at 37 degree C remained accessible to both 131I-IgG anti-F(ab')2 and to proteolytic release by pronase, which suggests that monovalent interaction of ligand with C3b receptors was not sufficient for induction of endocytosis. The requirement for multivalency was also demonstrated using the C3b-OR, the normal ligand for the C3b receptor. 125I-C3b-OR was specifically bound by PMN but remained on the cell receptor. 125I-C3b-OR was specifically bound by PMN but remained on the cell surface, as determined by its accessibility to pronase, unless it was cross-linked with F(ab')2 anti-C3. Although C3b receptors on PMN do not mediate internalization of adsorptive pinocytosis of soluble ligand indicates their potential for the clearance of C3b-bearing immune complexes without recruitment of other cell surface receptors.
Large meals and large arteries: Is resistin the link?
Authors: J HERRMANN
Journal: Cardiovascular Research (2005)

See article by Jung et al. [11] (pages 76–85) in this issue.  “To lengthen thy Life, lessen thy Meals.” 

Benjamin Franklin, Poor Richard's Almanack, 1733 

The burden of chronic diseases is on the rise on all continents, and the predictions for its detrimental effects on the individual and society resemble the warnings of a hurricane approaching land [1]. Most of the storm settles on complications of cardiovascular disease, the risk of which is increased by a factor of two to three even by the clustering of “prestages” of traditional cardiovascular factors, referred to as the “metabolic syndrome” and related to insulin resistance ever since Reaven's seminal work in 1987 [2]. Five different major sets of criteria are currently in place for the diagnosis of the metabolic syndrome, with the entire concept being very critically appraised by representatives of American and European diabetes societies, yet again endorsed by the American Heart Association, and with a worldwide definition by the International Diabetes Federation appearing on the horizon [3,4]. The most apparent underlying risk factor for the metabolic syndrome is truncal or visceral obesity and hence waist circumference or waist-to-hip ratio are better clinical parameters than body mass index [3]. Hence, as society is “supersizing” so is the risk of cardiovascular diseases and the call to the cardiovascular practice and research community.

Once considered to serve no other purpose than to store energy, adipose tissue has been increasingly recognized as an active endocrine organ, capable of synthesizing and secreting so-called adipokines. One of the 21st century editions of these substances is resistin, a 12.5-kDa, 114-amino acid polypeptide, rich in cysteine residues, that can form dimers and hexamers in the new family of resistin-like molecules [5,6]. The name “resistin” is derived from its discovery in the search for a … 

*Tel.: +1 507 255 5890; fax: +1 507 255 1824. Email address: herrmann.joerg{at}mayo.edu
Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes
Authors: Valérie Abadie, Edgar Badell, Patrice Douillard, Danielle Ensergueix, Pieter J. M. Leenen, Myriam Tanguy, Laurence Fiette, Sem Saeland, Brigitte Gicquel, Nathalie Winter
Journal: Blood (2005)
Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair
Authors: Lao H Saal, Sofia K Gruvberger-Saal, Camilla Persson, Kristina Lövgren, Mervi Jumppanen, Johan Staaf, Göran Jönsson, Maira M Pires, Matthew Maurer, Karolina Holm, Susan Koujak, Shivakumar Subramaniyam, Johan Vallon-Christersson, Håkan Olsson, Tao Su, Lorenzo Memeo, Thomas Ludwig, Stephen P Ethier, Morten Krogh, Matthias Szabolcs, Vundavalli VVS Murty, Jorma Isola, Hanina Hibshoosh, Ramon Parsons, Åke Borg
Journal: Nature Genetics (2007)
Cost analysis of video-assisted thoracic surgery<i>versus</i>thoracotomy: critical review
Authors: P. Van Schil
Journal: European Respiratory Journal (2003)

Cost containment has become an important issue in thoracic surgery. Applying the principles of evidence-based medicine a literature search was performed to determine whether video-assisted thoracic surgery (VATS) has an advantage over thoracotomy concerning total cost. Only eight studies specifically looked at cost; all but one were retrospective. Lung biopsy by VATS yielded higher operating room costs compared with limited thoracotomy. The cost of VATS wedge resection of lung nodules was competitive with open techniques. In a prospective study regarding the treatment of pneumothorax by VATS, no advantages were demonstrated compared with axillary minithoracotomy. In two retrospective studies the total economic cost of VATS was lower but not all relevant factors were considered. Lung volume reduction surgery by VATS had a lower total inpatient cost compared with sternotomy but no specific details were provided. Finally, VATS treatment of lung cancer yielded conflicting results regarding total hospital charges. From these studies it is clear that video-assisted thoracic surgery has a higher initial cost. Whether this is offset by a more rapid discharge remains to be proven. There is a definite need for high-quality prospective randomised studies.
Correcting for sequence biases in present/absent calls
Authors: Eugene F Schuster, Eric Blanc, Linda Partridge, Janet M Thornton
Journal: Genome biology (2007)

Abstract The probe sequence of short oligonucleotides in Affymetrix microarray experiments can have a significant influence on present/absent calls of probesets with absent target transcripts. Probesets enriched for central Ts and depleted of central As in the perfect-match probes tend to be falsely classified as having present transcripts. Correction of non-specific binding for both perfect-match and mismatch probes using probe-sequence models can partially remove the probe-sequence bias and result in better performance of the MAS 5.0 algorithm.
BCL-2 GENE FAMILY IN THE NERVOUS SYSTEM
Authors: D. E. Merry, S. J. Korsmeyer
Journal: Annual Review of Neuroscience (1997)

▪ Abstract A growing family of genes that share homology with the bcl-2 proto-oncogene is involved in the regulation of cell death. Many of these proteins show widespread expression and are expressed in the nervous system in developing and adult organisms. A physiologic role for Bcl-2 and Bcl-x in neuron survival has been shown. In addition, these proteins have been shown to protect neurons from a wide array of toxic insults. In this review, we discuss the Bcl-2 family of proteins with regard to their structure and interactions. We then discuss the role of apoptotic cell death in the development of the nervous system and as a response to neuronal injury. Lastly, we discuss the evidence for a role for these cell death regulators in neuronal death decisions.
Subcellular Distribution of Cyclic Adenosine 3', 5'-Monophosphate-Binding Protein and Estrogen Receptors in Control Pituitaries and Estrogen-Induced Pituitary Tumors
Authors: G. Piroli, L. S. Weisenberg, C. Grillo, A. F. De Nicola
Journal: JNCI Journal of the National Cancer Institute (1990)

Binding of cyclic adenosine 3',5'-monophosphate (cAMP) and steroid receptors was studied in cytoplasmic and nuclear fractions of pituitaries from castrated rats, in rats subjected to acute (60 min) or short-term (4 days) estradiol (E2) treatment, and in diethylstilbestrol-induced pituitary tumors (DES-T). E2 receptors were primarily in nuclear extracts in all animals that were given estrogens, whereas cytosolic receptors were low to absent. Contrarily, castrated rats showed high quantities of cytoplasmic receptor but little in nuclear sites. The progestin receptor was induced only in 4-day E2-treated rats and in DES-T. cAMP binding was stimulated in cytosol from 4-day E2-treated rats and in DES-T, but a significant reduction in binding was also noted in nuclear extracts from DES-T. Scatchard analysis for the cytosolic cAMP-binding activity demonstrated a two-component system, and the increased cAMP binding obtained in DES-T seemed to be caused by an increase in the low-affinity, high-capacity binder [regulatory type II (RII) subunit of protein kinase]. Suggestion of the preferential estrogenic induction of RII was also obtained by DEAE-cellulose chromatography, which provided separation of RI and RII subunits. The results suggest that sustained estrogenization leads to induction of cytosolic cAMP-binding protein and increased levels of nuclear E2 receptor. In DES-T, this effect resulted in an inverse subcellular distribution of both binding proteins, which may be related to abnormal growth of the pituitary, as has been postulated for hormone-dependent mammary tumors.
Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis
Authors: F. Z. Bischoff
Journal: Human Reproduction Update (2002)

Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50–75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95–100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.
Plasma, Tumor, and Tissue Disposition of STEALTH Liposomal CKD-602 (S-CKD602) and Nonliposomal CKD-602 in Mice Bearing A375 Human Melanoma Xenografts
Authors: William C. Zamboni, Sandra Strychor, Erin Joseph, Dustin R. Walsh, Beth A. Zamboni, Robert A. Parise, Margaret E. Tonda, Ning Y. Yu, Charles Engbers, Julie L. Eiseman
Journal: Clinical Cancer Research (2007)

Abstract Purpose: S-CKD602 is a STEALTH liposomal formulation of CKD-602, a camptothecin analogue. The cytotoxicity of camptothecin analogues is related to the duration of exposure in the tumor. STEALTH liposomal formulations contain lipid conjugated to methoxypolyethylene glycol and have been designed to prolong drug circulation time, increase tumor delivery, and improve the therapeutic index. For STEALTH liposomal formulations of anticancer agents to achieve antitumor effects, the active drug must be released into the tumor extracellular fluid (ECF). Experimental Design: S-CKD602 at 1 mg/kg or nonliposomal CKD-602 at 30 mg/kg was administered once via tail vein to mice bearing A375 human melanoma xenografts. Mice (n = 3 per time point) were euthanized at 0.083 to 24 h, 48 h, and 72 h after S-CKD02 and from 0.083 to 24 h after nonliposomal CKD-602. Plasma samples were processed to measure encapsulated, released, and sum total (encapsulated plus released) CKD-602, and tumor and tissue samples were processed to measure sum total CKD-602. Microdialysis samples of tumor ECF were obtained from 0 to 2 h, 4 to 7 h, and 20 to 24 h after nonliposomal CKD-602 and from 0 to 2 h, 24 to 27 h, 48 to 51 h, and 72 to 75 h after S-CKD602. A liquid chromatography-mass spectrometry assay was used to measure the total (sum of lactone and hydroxyl acid) CKD-602. The area under the concentration-versus-time curves (AUC) from 0 to infinity and time &amp;gt;1 ng/mL in tumor were estimated. Results: For S-CKD602, the CKD-602 sum total AUC in plasma and tumor and the CKD-602 AUC in tumor ECF were 201,929, 13,194, and 187 ng/mL h, respectively. For S-CKD602, 82% of CKD-602 remains encapsulated in plasma. For nonliposomal CKD-602, the CKD-602 AUC in plasma and tumor and the CKD-602 AUC in tumor ECF were 9,117, 11,661, and 639 ng/mL·h, respectively. The duration of time the CKD-602 concentration was &amp;gt;1 ng/mL in tumor ECF after S-CKD602 and nonliposomal CKD-602 was &amp;gt;72 and ∼20 h, respectively. For S-CKD602, the CKD-602 sum total exposure was 1.3-fold higher in fat as compared with muscle. The ratio of CKD-602 sum total exposure in fat to muscle was 3.8-fold higher after administration of S-CKD602 compared with nonliposomal CKD-602. Conclusion: S-CKD602 provides pharmacokinetic advantages in plasma, tumor, and tumor ECF compared with nonliposomal CKD-602 at 1/30th of the dose, which is consistent with the improved antitumor efficacy of S-CKD602 in preclinical studies. The distribution of S-CKD602 is greater in fat compared with muscle whereas the distribution of nonliposomal CKD-602 is greater in muscle compared with fat. These results suggest that the body composition of a patient may affect the disposition of S-CKD602 and released CKD-602.
Disappearance of a biliary cyst
Authors: Jean Frédéric Blanc, Charles Balabaud, Jean Saric, Paulette Bioulac-Sage
Journal: Journal of Hepatology (2004)

A 72 year old woman was seen at the hospital clinic (09/02) for a fever resistant to Cefuroxime. Her blood cell count was elevated (104,000 WBC/mm3—77% PMN). Liver blood tests were normal except for a three fold rise in GGT. The known simple liver cyst (asterisk) in the left lobe (CT Scan 02/02, panel 1) had enlarged (45 mm), with a thickened irregular contour and an heterogeneous content (CT Scan 09/02, panel 2). The serological diagnosis for echinococcus was negative. A left hepatectomy was performed one month later. On sectioning, there was no cyst but a tumor-like lesion (15 mm). Microscopically, the lesion was an inflammatory pseudotumor (panel 3), with many positive α SMA and KP1 positive cells (arrows, panel 4). The wall of the cyst (arrow) was easily identified among inflammatory cells (panel 3 low and high magnification, lower and upper part respectively). It is possible to reconstruct the events which occurred in the last few months. The silent single biliary cyst became infected and transformed spontaneously or under treatment (Cefpodoxime and Metronidazole were administered after the failure of Cefuroxime) into an inflammatory pseudo tumor. It is likely that the patient would have been cured without surgery. Infection of single biliary cysts is rare [1Shoji F. Kitamura M. Shirabe K. Kai H. Akiyoshi T. Sigimachi K. Infected hepatic cyst in a patient with multiple hepatic cysts: report of a case diagnosed by change of ultrasonographic findings.Eur J Gastroenterol Hepatol. 2000; 12: 703-705Crossref PubMed Scopus (15) Google Scholar]. Inflammatory pseudo tumor as a consequence of an infected biliary cyst has, to our knowledge, never been reported. It could represent an intermediate stage towards the reported disappearance of biliary cyst [2Hoshida H. Onda M. Tajiri T. Mamada Y. Taniai N. Uchida E. et al.Spontaneous disappearance of a hepatic cyst.J Nippon Med Sch. 2001; 68: 58-60Crossref PubMed Scopus (12) Google Scholar].