tbuckley/cabot-search huggingface dataset:
Soluble CD40 Ligand in Pulmonary Arterial Hypertension
Authors: Jan K. Damås, Kari Otterdal, Arne Yndestad, Halfdan Aass, Nils O. Solum, Stig S. Frøland, Svein Simonsen, Pål Aukrust, Arne K. Andreassen
Journal: Circulation (2004)

Inflammatory processes seem to be involved in pulmonary arterial hypertension (PAH). CD40 ligand (L) may promote inflammation and thrombus formation, and we hypothesized that CD40L could be involved in the pathogenesis of PAH.Several significant findings were revealed when examining the possible role of CD40L in PAH. (1) Patients with primary (n=13) and secondary (n=11) PAH but not those with chronic thromboembolic pulmonary hypertension (n=8) had increased plasma levels of soluble (s) CD40L compared with control subjects (n=8). (2) PAH patients using warfarin had markedly lower sCD40L levels than those without such therapy. (3) sCD40L levels were higher in arterial (femoral artery) compared with mixed venous blood (pulmonary artery), suggesting enhanced release or reduced clearance in the pulmonary vasculature. (4) Platelets from PAH patients showed enhanced spontaneous and SFLLRN-stimulated release of sCD40L compared with control subjects. (5) In vitro, recombinant sCD40L induced monocyte chemoattractant protein (MCP)-1 and interleukin-8 gene expression in endothelial cells, and plasma levels of these chemokines were raised in all PAH groups, significantly correlated to sCD40L and hemodynamic parameters. (6) Although prostacyclin therapy (3 months) showed clinical benefit, this therapy had no effect on sCD40L and increased MCP-1 levels in PAH patients, and prostacyclin enhanced MCP-1 in CD40L-stimulated endothelial cells.Our findings suggest a role for CD40L in the pathogenesis of PAH, possibly operating through an interaction between platelets and endothelial cells involving chemokine-related mechanisms.
Microsomal Epoxide Hydrolase, Endotoxin, and Lung Function Decline in Cotton Textile Workers
Authors: Jingqing Hang, Wei Zhou, Xiaorong Wang, Hongxi Zhang, Bixiong Sun, Helian Dai, Li Su, David C. Christiani
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Occupational exposure to endotoxin in organic dust may induce lung function decline. Microsomal epoxide hydrolase (mEH) detoxifies reactive oxygen species generated by endotoxin exposure, and polymorphisms of the mEH gene are associated with altered enzyme activity. We investigated the associations between mEH polymorphisms, endotoxin exposure, and lung function decline in a 20-year prospective study of 265 workers exposed to endotoxin and 234 control subjects. mEH Tyr113His and His139Arg polymorphisms were genotyped by the 5' nuclease assay, and data were analyzed using multivariate linear regression models, adjusting for important covariates. Overall, the annual decline rate of FEV1 was 29.47 ml during the 20-year follow-up. Endotoxin exposure was associated with faster lung function decline among genotypes associated with slower enzyme activity: estimates (SE) of annual FEV1 decline rates for endotoxin exposure were -2.33 (2.07), -2.81 (1.66), and -6.73 (2.83) ml for Tyr/Tyr, Tyr/His, and His/His genotype groups, respectively, for the Tyr113His polymorphism; and -1.82 (2.58) and -4.27 (1.33) ml for Arg/Arg + His/Arg and His/His genotypes, respectively, for the His139Arg polymorphism. We conclude that mEH polymorphisms modify the association between occupational endotoxin exposure and longitudinal lung function decline.
Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists
Authors: R. M. D. Smyth, J. J. Kirkham, A. Jacoby, D. G. Altman, C. Gamble, P. R. Williamson
Journal: BMJ (2011)

To provide information on the frequency and reasons for outcome reporting bias in clinical trials.Trial protocols were compared with subsequent publication(s) to identify any discrepancies in the outcomes reported, and telephone interviews were conducted with the respective trialists to investigate more extensively the reporting of the research and the issue of unreported outcomes.Chief investigators, or lead or coauthors of trials, were identified from two sources: trials published since 2002 covered in Cochrane systematic reviews where at least one trial analysed was suspected of being at risk of outcome reporting bias (issue 4, 2006; issue 1, 2007, and issue 2, 2007 of the Cochrane library); and a random sample of trial reports indexed on PubMed between August 2007 and July 2008.Australia, Canada, Germany, the Netherlands, New Zealand, the United Kingdom, and the United States.Frequency of incomplete outcome reporting-signified by outcomes that were specified in a trial's protocol but not fully reported in subsequent publications-and trialists' reasons for incomplete reporting of outcomes.268 trials were identified for inclusion (183 from the cohort of Cochrane systematic reviews and 85 from PubMed). Initially, 161 respective investigators responded to our requests for interview, 130 (81%) of whom agreed to be interviewed. However, failure to achieve subsequent contact, obtain a copy of the study protocol, or both meant that final interviews were conducted with 59 (37%) of the 161 trialists. Sixteen trial investigators failed to report analysed outcomes at the time of the primary publication, 17 trialists collected outcome data that were subsequently not analysed, and five trialists did not measure a prespecified outcome over the course of the trial. In almost all trials in which prespecified outcomes had been analysed but not reported (15/16, 94%), this under-reporting resulted in bias. In nearly a quarter of trials in which prespecified outcomes had been measured but not analysed (4/17, 24%), the "direction" of the main findings influenced the investigators' decision not to analyse the remaining data collected. In 14 (67%) of the 21 randomly selected PubMed trials, there was at least one unreported efficacy or harm outcome. More than a quarter (6/21, 29%) of these trials were found to have displayed outcome reporting bias.The prevalence of incomplete outcome reporting is high. Trialists seemed generally unaware of the implications for the evidence base of not reporting all outcomes and protocol changes. A general lack of consensus regarding the choice of outcomes in particular clinical settings was evident and affects trial design, conduct, analysis, and reporting.
The identification of CFHR5 nephropathy
Authors: Daniel P Gale
Journal: Journal of the Royal Society of Medicine (2011)

In 2006 I was working as a registrar in renal medicine at Hammersmith Hospital. One of my colleagues, Patrick Maxwell, was interested in investigating families in which multiple individuals had unexplained renal disease. He felt that hunting for the genes underlying their conditions was worthwhile, feasible and would make an excellent project for a clinical researcher: recent technical advances in genetics – principally the ability to genotype large numbers of markers across the genome relatively easily – have made linkage studies more widely accessible to researchers, so with Patrick Maxwell's help and supervision I embarked on the study of one such family.
Characterizing Mucous Cell Remodeling in Cystic Fibrosis
Authors: Steven R. Hays, John V. Fahy
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Relatively few studies have characterized mucous cells or mucins in detail in cystic fibrosis (CF), and the relationship between mucous cell abnormalities and neutrophilic inflammation is uncertain.To characterize mucous cell phenotypes and mucin profiles in CF and to determine if neutrophils accumulate around goblet cells in the epithelium and gland acini in the submucosa.Bronchial biopsies were collected from 7 subjects with CF and 15 control subjects, and the morphology of mucous cells was measured. Immunostains for gel-forming mucins and neutrophil elastase were quantified.Goblet cell size was increased in CF (p = 0.004), but the number of goblet cells was normal. The volume of submucosal glands was fourfold higher than normal (p = 0.031), but the proportion of mucous and serous cells in CF glands was normal. The patterns of expression of gel-forming mucins in epithelial and submucosal compartments in CF were similar to normal. Although neutrophil elastase immunostaining was intense in the epithelium in CF, neutrophils were largely absent around gland acini in the submucosa.The most prominent pathologic feature in the CF airway is an increase in submucosal gland volume, but serous cell transdifferentiation to mucous cells does not occur, nor are gland acini inflamed with neutrophils. The mechanism for increased submucosal gland volume in CF deserves further study.
The doctor as romantic hero. A study of idealization
Authors: E. Wilbank
Journal: JAMA (1972)

"The physician can abolish pain, relieve his fellow mortals from sickness. He is indisputably usefullest of all men." With these words, Thomas Carlyle characterized more than his own personal feelings. The physician in the 19th century held a place of high esteem in the eyes of the nonmedical world. This exalted position, based in part on his relation to power over life and death, transcended the usual social strata connected with money, possessions, politics, or family ties. Although the 19th century is supposedly the beginning of the scientific age, the dominant flourish of romanticism is nowhere more apparent than the superhuman role accorded the physician in literature. In this period, readers of fiction supported a literature largely of escape. Volumes of humor, or sentimental novels by authors such as Mary Jane Holmes and Edward P. Roe, were best sellers. The public wanted to read about life in its ideal form:
Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor.
Authors: K Matsushima, K Morishita, T Yoshimura, S Lavu, Y Kobayashi, W Lew, E Appella, H F Kung, E J Leonard, J J Oppenheim
Journal: The Journal of Experimental Medicine (1988)

The cDNA coding for human monocyte-derived neutrophil-specific chemotactic factor (MDNCF) was cloned from LPS-stimulated human monocyte mRNA. The cDNA sequence codes for a polypeptide consisting of 99 amino acids, including a putative signal sequence. Comparison of the deduced amino acid sequence with the NH2-terminal amino acid sequence of natural MDNCF shows that the mature functional protein comprises 72 amino acids, beginning with serine at residue 28. The deduced amino acid sequence shows striking similarity to several platelet-derived factors, a v-src-induced protein, a growth-regulated gene product (gro), and an IFN-gamma inducible protein. The availability of the MDNCF cDNA enabled us to use it as a probe to identify inducers of MDNCF mRNA expression in human PBMC. MDNCF mRNA was increased greater than 10-fold within 1 h after stimulation with LPS, IL-1, or TNF, but not by IFN-gamma, IFN-alpha, or IL-2. Furthermore, we also determined that LPS, IL-1, and TNF stimulated the mononuclear cells to produce biologically active MDNCF. This observation may account for the in vivo capacity of IL-1 and TNF to induce netrophil infiltrates.
Viburnum Prunifolium in Abortion
Authors: A. D. L. Napier
Journal: BMJ (1886)

every half-hour.She suffered no pain at all; was uite cheerful and sensible, though very weak; was not sick at all a ter the o eration but became gradually exhausted, and died thlirty hours after the opera- tion.There was no sign of peritonitis.I was not permitted to make a post maorkm examination.It may be objected that this is, in cases of cancer, at best merely a palliative operation.In this respect, I may say that it is equally valuable with gastrostomy and colotomy, and other operations for the relief of obstruction from the same cause ; and these we have no hesita- tion in performing.If it can be undertaken earlier in the disease, I believe its results will be favourable.I also think that it ought to be done in less time than I took over it; and in this case, I slould not consider it such a dangerous operation.WhetheT the jei'unuim should be approximated to the stomach by causing it to form a hernia through the great omentum, as in my case, or, as in Mr. Barker's case, by Causing it to encircle the transverse colon (as, from his description, I gather it did), and so reach the anterior surface of the stomach, I am unable to say.I think that this operation will, in future, be found a valuable addi- tion to surgery; and I believe that Professor Billroth has proposed that it should take the place of pylorectomy.
Markers of Increased Risk of Intracerebral Hemorrhage After Intravenous Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke in Clinical Practice
Authors: David Tanne, Scott E. Kasner, Andrew M. Demchuk, Nira Koren-Morag, Sandra Hanson, Martin Grond, Steven R. Levine
Journal: Circulation (2002)

Background — Intravenous recombinant tissue plasminogen activator (rtPA) is an effective therapy for acute ischemic stroke, but it is associated with risk of intracerebral hemorrhage (ICH). Our aim was to identify, in a large cohort of patients, readily available baseline factors that are associated with thrombolysis-related ICH. Methods and Results — In a multicenter retrospective and prospective investigation of individual data from 1205 patients treated in routine clinical practice with intravenous rtPA within 3 hours of stroke symptom onset, 72 patients (6%) developed symptomatic ICH and 86 additional patients (7%) had asymptomatic ICH identified on a routine follow-up CT. In analyses based on clinical variables alone, the main attributes associated with ICH were a history of diabetes mellitus and cardiac disease, increasing stroke severity, advancing age, use of antiplatelet agents other than aspirin before stroke onset, and elevated pretreatment mean blood pressure. In additional analyses that incorporated baseline CT and laboratory findings (in a subset of patients), the main associations were early ischemic CT changes, in particular if exceeding one third of middle cerebral artery territory; increasing stroke severity; diabetes mellitus or elevated serum glucose; and lower platelet counts. Final independent attributes associated with parenchymatous hematoma, defined by purely radiologically based criteria, were similar to those of symptomatic ICH. Conclusions — Readily available factors can identify acute ischemic stroke patients at high and low risk for rtPA-related ICH. These factors require confirmation in a prospective cohort before clinical implementation.
An Address ON THE PHYSICIAN AND THE PATHOLOGIST ON HEART FAILURE
Authors: T. C. Allbutt
Journal: BMJ (1912)

IN my youth it was a common jest to ask what N. or M. died of, the witty answer being "shortness of breath of course.The jest has vanished, but the platitude remains, witlh somle alterationa of the formula, which, instead of "shortness of breath," now runs "' of heart failure."In the obituary notices of our current journals we read daily of these deaths by the half-dozen, that N. or M. died of " hleart failure "; and the vogue of appendicitis is tlhreatened.Now, do we owe this new fashion to the physician or to the pathologist?for it is often worth while to examine the straws floating in the wind; we may learn something from some of tlhem.Is this a parrot phrase put up as a kind of slhortlhand between the doctor and the registrar of deatlhs ?or does it, like appendicitis, signify a fresh point in pathology, claiming its catchword?Does the phrase miiean that a snap of the heart stopped the whole machine, otherwise capable of working on, as a snap of a connecting rod may stop the engines of the Olympic.? or does it mean that the hleart was the ultizmumn mnoriens, and that, so long as this central organ lheld to it, death was kept at bay?In this case to say that one died of "heart failure" is surely as empty a truism as 4to say that he died of " shortness of breath."On the other hand, as it is true that we
Radiological changes of short and flat bones in primary hypertrophic osteoarthropathy
Authors: Z. JAJIC, I. JAJIC
Journal: Annals of the Rheumatic Diseases (1998)

In order to evaluate the effect of somatostatin in the treatment of massive upper gastrointestinal bleeding a randomised double blind trial of 95 patients has been undertaken during a 28 months period. Patients with oesophageal varices have been excluded as well as patients with diabetes. All patients were endoscoped within eight hours of admission to the hospital, whereupon the source of bleeding and types of stigmata were assessed. Forty six patients, chosen at random, were given a 72 hour infusion of somatostatin, while the remaining 49 patients received infusion of placebo. The two groups were well matched for sex, age, and source of bleeding. On the day after admission, an additional endoscopy was performed at which eight patients in the somatostatin group and 16 in the placebo group were found to have a persistent bleeding. A total of five patients in the somatostatin group and 14 in the placebo group underwent surgery (Fisher9s exact test, 2-tail, p = 0.04). Rebleeding occurred in six patients in the somatostatin group, of whom five experienced rebleeding after completion of the somatostatin treatment. In the placebo group, rebleeding occurred in five patients, of whom four rebled on the day after admission. The need for blood transfusions and the mortality rate did not differ significantly between the two groups. No toxic side effects were found as a result of the infusion of somatostatin. In this study, somatostatin reduced the number of patients needing surgery with massive upper gastrointestinal bleeding.
4843delC of the BRCA1 gene is a possible founder mutation in Southern Italy (Sicily)
Authors: A. Russo, V. Calò, C. Augello, L. Bruno, V. Agnese, V. Schirò, F. Barbera, S. Cascio, E. Foddai, G. Badalamenti, C. Intrivici, M. Cajozzo, G. Gulotta, E. Surmacz, G. Colucci, N. Gebbia, V. Bazan
Journal: Annals of Oncology (2007)
Sepsis Induces Diaphragm Electron Transport Chain Dysfunction and Protein Depletion
Authors: Leigh A. Callahan, Gerald S. Supinski
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Sepsis significantly alters skeletal muscle mitochondrial function, but the mechanisms responsible for this abnormality are unknown.We postulated that endotoxin elicits specific changes in electron transport chain proteins that produce derangements in mitochondrial function. To examine this issue, we compared the effects of endotoxin-induced sepsis on mitochondrial ATP (adenosine triphosphate) formation and electron transport chain protein composition.Diaphragm mitochondrial oxygen consumption and mitochondrial nicotinamide adenine dinucleotide, reduced form, oxidase assays were measured in control rats (n=13) and rats given endotoxin (8 mg/kg/d) for 12 (n=14), 24 (n=14), 36 (n=14), and 48 h (n=13). Electron transport chain subunits from Complexes I, III, IV, and V were isolated using Blue Native polyacrylamide gel electrophoresis techniques.Endotoxin administration: 1) elicited large reductions in mitochondrial oxygen consumption (e.g., 201+/-3.9 SE natoms O/min/mg for controls and 101+/-4.5 SE natoms O/minutes/mg after 48 h endotoxin, p<0.001), in nicotinamide adenine dinucleotide, reduced form, oxidase activity (p<0.002), and in uncoupled respiration (p<0.001) and 2) induced selective reductions in two subunits of Complex I, three subunits of Complex III, one subunit of Complex IV, and one subunit of Complex V. The time course of depletion of protein subunits mirrored alterations in oxygen consumption.Our data indicate that endotoxin selectively depletes critical components of the electron transport chain that diminishes electron flow, reduces proton pumping and decreases ATP formation.
Immunohistochemical localization of cellular NFATc1 does not predict clinical responses to ciclosporin in subcutaneous panniculitis-like T-cell non-Hodgkin lymphoma
Authors: S. Tauro, S. MacCallum, M.J. Groves, P. Rojnuckarin, T. Assanasen, A.L. Feldman, A. Robson, M. Marschalkó, H. Kini, A.A. Alzolibani, A. Al Robaee, H.A. Al Shobaili, S. Alfawzan, J.R. Goodlad, N. Kernohan, M. Hummel, W. Sterry, C. Assaf
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, Many patients with subcutaneous panniculitis‐like T‐cell non‐Hodgkin lymphoma (SPTCL) experience benefits with immunosuppressive treatment and avoidance of chemotherapy.1 Among immunosuppressive agents, prednisolone is commonly used to treat SPTCL, but durable responses have also been reported with ciclosporin.2, 3 Ciclosporin inhibits calcineurin, a serine‐threonine phosphatase that dephosphorylates cytoplasmic NFAT (nuclear‐factor‐activated T cells) transcription factors, following T‐cell receptor (TCR) activation.4 Dephosphorylated NFAT translocates into the nucleus and initiates transcription of genes including those producing inflammatory cytokines. In experimental models of human T‐cell malignancies, ciclosporin induces remission by inhibiting calcineurin‐NFAT in malignant cells,5 suggesting abnormalities of this signalling pathway in the neoplastic process. The predominant nuclear localization of the NFAT isoform NFATc1 in some patients with diffuse large B‐cell lymphoma and Burkitt lymphoma (BL)6 further suggests a role for calcineurin‐NFAT in the pathogenesis of lymphoid malignancies. Based on the clinical responses to ciclosporin in SPTCL, we hypothesized a role for NFAT in this rare lymphoma with possible over‐activity of pro‐oncogenic calcineurin‐dependent intracellular signal transduction. If so, one would expect predominant localization of NFAT in the nuclei of the tumour cells. This study was therefore undertaken to investigate if NFAT is expressed in SPTCL and whether nuclear NFAT can be detected in ciclosporin responders.
Phase I trial of the selective mitochondrial toxin MKT 077 in chemo-resistant solid tumours
Authors: D.J. Propper, J.P. Braybrooke, D.J. Taylor, R. Lodi, P. Styles, J.A. Cramer, W.C.J. Collins, N.C. Levitt, D.C. Talbot, T.S. Ganesan, A.L. Harris
Journal: Annals of Oncology (1999)
Very large gastric ulcer with a round lesion
Authors: Y Tatsumi, K Inoue, H Kanemasa, A Toma, K Tsukamoto, Y Kajita
Journal: Gut (2009)

A 56-year-old Japanese woman was admitted to our hospital with a 1-month history of abdominal fullness and a 1-year history of body weight loss of 10 kg. There was no significant family history nor history of previous abdominal surgery. There was …