tbuckley/cabot-search huggingface dataset:
Posttraumatic Stress Disorder and Health-Related Quality of Life in Long-Term Survivors of Acute Respiratory Distress Syndrome
Authors: Hans P Kapfhammer, Hans B Rothenhäusler, Till Krauseneck, Christian Stoll, Gustav Schelling
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Intensive care often means exposure to physical and psychological stress, with long-lasting emotional sequelae for most patients. Psychiatric morbidity and negative effects on health-related quality of life were assessed in long-term survivors of acute respiratory distress syndrome. METHOD: Forty-six long-term survivors were enrolled in a psychiatric follow-up study. All patients had received standard, protocol-driven treatment during intensive care. The median follow-up time was 8 years after treatment. DSM-IV was used for psychiatric diagnosis. Psychological tests were performed to measure posttraumatic stress symptoms; depression; state anxiety; somatization; symptoms regarding concentration, attention, and short-term memory; social support; and health-related quality of life. RESULTS: At time of discharge, 20 of the patients suffered from posttraumaatic stress disorder (PTSD) and four from sub-PTSD. At follow-up, 11 patients continued to suffer from PTSD and eight from sub-PTSD. The patients with PTSD demonstrated a pronounced tendency for somatization and state anxiety. Among the groups with PTSD, sub-PTSD, and no PTSD, there were no statistically significant differences regarding social support and symptoms of cognitive dysfunction. Those with PTSD showed major impairments in some dimensions of health-related quality of life, whereas those without PTSD had scores that were in the range of the general population. Except for duration of stay on the intensive care unit, neither age, gender, sociodemographic variables, premorbid psychopathology, nor initial severity of illness discriminated between the groups. CONCLUSIONS: Long-term survivors of acute respiratory distress syndrome seem to face a major risk of PTSD and major impairments in health-related quality of life in the long term.
Smoking in pregnancy slows growth of baby's head
Authors: Roger Dobson
Journal: BMJ (2007)

The heads of fetuses of women who smoke during pregnancy grow less than those of fetuses whose mothers don't smoke, a study concludes. But mothers who give up smoking as soon as their pregnancy is confirmed have babies whose head circumference grows as much as those of women who never smoke during pregnancy, it says.

With the help of ultrasound images taken during pregnancy, the researchers found that the circumference of the heads of fetuses of women who smoked throughout pregnancy grew half a millimetre less a week during late pregnancy than those of non-smokers. Femur lengths and abdominal circumferences also increased more slowly in the fetuses of smokers, …
Promotion to hospital consultant: regression analysis using NHS administrative data
Authors: Kostas Mavromaras, Anthony Scott
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To examine factors influencing promotion to hospital consultant. <b>Design</b> Multivariate logistic regression analysis of NHS administrative data between 1991 and 2000. <b>Setting</b> Hospitals in NHS Scotland. <b>Population</b> All registrars, senior registrars, and specialist registrars in Scotland. <b>Main outcome measure</b> The proportion of doctors promoted to NHS consultant. <b>Results</b> Compared with doctors who graduated in Scotland, graduates from the rest of the United Kingdom and from overseas were less likely to be promoted to consultant (odds ratio 0.65, 95% confidence interval 0.52 to 0.82; and 0.37, 0.28 to 0.50, respectively). Promotion and holding an honorary contract before promotion were positively associated (1.37, 1.03 to 1.83); and the number of years since graduation (5.98 per year, 4.94 to 7.23). Women were less likely to be promoted (0.73, 0.60 to 0.90), as were doctors who worked part time (0.27, 0.17 to 0.42). Probabilities of promotion did not have a clear time trend between 1993 and 2000, and NHS boards in non-metropolitan areas of Scotland were more likely to offer promotions than NHS boards in metropolitan areas, presumably reflecting a higher gap between demand and supply in these boards. <b>Conclusion</b> As the proportion of women in hospital medicine increases, government targets for the recruitment of consultants are unlikely to be met unless the promotion process is examined. It is unclear whether more recent reforms of the medical career structure will deal with these issues.
A Validated Prediction Model for All Forms of Acute Coronary Syndrome
Authors: Kim A Eagle, Michael J Lim, Omar H Dabbous, Karen S Pieper, Robert J Goldberg, Frans Van de Werf, Shaun G Goodman, Christopher B Granger, P Gabriel Steg, Joel M Gore, Andrzej Budaj, Alvaro Avezum, Marcus D Flather, Keith A A Fox
Journal: JAMA (2004)

LINICAL PREDICTION MODELS may be helpful for medical decision making 1 as patients judged to be at higher risk may receive more aggressive surveillance and/or earlier treatment, while patients estimated to be at lower risk may be reassured and managed less aggressively. 2,3By using simple yet valid risk calculations, clinicians can accurately advise patients about their likelihood of an event, and how this likelihood translates into treatment decisions.The acute coronary syndrome (ACS) encompasses a continuum of conditions ranging from ST-segment elevation myocardial infarction (STEMI) to non-ST-segment elevation myocardial infarction (NSTEMI) and unstable an-
Reduction of Blood Cholesterol in Man
Authors: O. J. POLLAK
Journal: Circulation (1953)

Dietary cholesterol contributes to the development and maintenance of hypercholesteremia in man. Intake of sitosterol prevents cholesterol resorption. This results in lowering of blood cholesterols to a basal endogenous level. Upon cessation of sitosterol intake hemocholesterols return to the original level. Excess supply of plant sterol was required in clinical experiments because the material used contained but 75 to 80 per cent of sitosterol and because of the large amount of endogenous cholesterol which has to be inactivated by the sitosterol, besides exogenous cholesterol.
A case of superior vena cava syndrome caused by Klebsiella pneumoniae
Authors: JY Kim, CM Lim, Y Koh, KH Choe, WS Kim, WD Kim
Journal: European Respiratory Journal (1997)

A 27 yr old man presented with productive cough, fever and manifestations of superior vena cava syndrome. He was an alcoholic but had been in good health until 3 days prior to admission. The physical examination, the chest radiograph and the results of the sputum culture were compatible with Klebsiella pneumoniae pneumonia of the right upper lobe. The superior vena cava scintigram using technetium-99m showed near total occlusion of the superior vena cava, while sputum cytology, chest computed tomography, and bronchoscopy were all negative for malignant aetiology. Antibiotic therapy brought about slow resolution of the pneumonia and also of the superior vena caval obstruction. The follow-up scintigram showed normalized venous flow of the superior vena cava. To our knowledge, this is the first case of superior vena cava syndrome developed in probable association with Klebsiella pneumoniae pneumonia.
LEUKAEMIC RELAPSE AFTER CAMPATH 1 TREATED BONE MARROW TRANSPLANTATION FOR LEUKAEMIA
Authors: C.M. Pollard, R.L. Powles, J.L. Millar, V. Shepherd, S. Milan, A. Lakhani, A. Zuiable, J. Treleaven, G. Helenglass
Journal: The Lancet (1986)
Microarray Analysis Reveals Complex Remodeling of Cardiac Ion Channel Expression With Altered Thyroid Status
Authors: Sabrina Le Bouter, Sophie Demolombe, Arnaud Chambellan, Chloé Bellocq, Franck Aimond, Gilles Toumaniantz, Gilles Lande, Sepideh Siavoshian, Isabelle Baró, Amber L. Pond, Jeanne M. Nerbonne, Jean J. Léger, Denis Escande, Flavien Charpentier
Journal: Circulation Research (2003)

Although electrophysiological remodeling occurs in various myocardial diseases, the underlying molecular mechanisms are poorly understood. cDNA microarrays containing probes for a large population of mouse genes encoding ion channel subunits (“IonChips”) were developed and exploited to investigate remodeling of ion channel transcripts associated with altered thyroid status in adult mouse ventricle. Functional consequences of hypo- and hyperthyroidism were evaluated with patch-clamp and ECG recordings. Hypothyroidism decreased heart rate and prolonged QTc duration. Opposite changes were observed in hyperthyroidism. Microarray analysis revealed that hypothyroidism induces significant reductions in KCNA5, KCNB1, KCND2, and KCNK2 transcripts, whereas KCNQ1 and KCNE1 expression is increased. In hyperthyroidism, in contrast, KCNA5 and KCNB1 expression is increased and KCNQ1 and KCNE1 expression is decreased. Real-time RT-PCR validated these results. Consistent with microarray analysis, Western blot experiments confirmed those modifications at the protein level. Patch-clamp recordings revealed significant reductions in I to,f and I K,slow densities, and increased I Ks density in hypothyroid myocytes. In addition to effects on K + channel transcripts, transcripts for the pacemaker channel HCN2 were decreased and those encoding the α1C Ca 2+ channel (CaCNA1C) were increased in hypothyroid animals. The expression of Na + , Cl − , and inwardly rectifying K + channel subunits, in contrast, were unaffected by thyroid hormone status. Taken together, these data demonstrate that thyroid hormone levels selectively and differentially regulate transcript expression for at least nine ion channel α- and β-subunits. Our results also document the potential of cDNA microarray analysis for the simultaneous examination of ion channel transcript expression levels in the diseased/remodeled myocardium.
Cyclin A1 expression in leukemia and normal hematopoietic cells.
Authors: Rong Yang, Tsuyoshi Nakamaki, Michael Lübbert, Jonathan Said, Akiko Sakashita, Bettina S. Freyaldenhoven, Susan Spira, Vong Huynh, Carsten Müller, H. Phillip Koeffler
Journal: Blood (1999)
THE CARDIOTOXIC ACTION OF PREPARATIONS CONTAINING THE OXYGEN-LABILE HEMOLYSIN OF STREPTOCOCCUS PYOGENES
Authors: Alan W. Bernheimer, G. L. Cantoni
Journal: The Journal of Experimental Medicine (1945)

1. A study has been made of the effect on the isolated frog's heart of a preparation derived from the supernatant fluid of cultures of hemolytic streptococcus. 2. The streptococcal preparation was found to induce systolic contracture, the contracture usually developing only after the second of two administrations of the preparation. It was found that a single application of the streptococcal preparation sensitized the heart to a second application. 3. The properties of the cardiotoxic factor so far as they have been studied were found to be identical with those of the oxygen-labile hemolysin of streptococci. The capacity of normal and of immune sera to neutralize the cardiotoxic action paralleled the antihemolytic potency of the sera.
In Vivo Administration of a Nuclear Transcription Factor-κB Decoy Suppresses Experimental Crescentic Glomerulonephritis
Authors: NARUYA TOMITA, RYUICHI MORISHITA, HUI Y. LAN, KEI YAMAMOTO, MASAHIDE HASHIZUME, MITSUE NOTAKE, KAORU TOYOSAWA, BUICHI FUJITANI, WEI MU, DAVID J. NIKOLIC-PATERSON, ROBERT C. ATKINS, YASUFUMI KANEDA, JITSUO HIGAKI, TOSHIO OGIHARA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Glomerular expression of cytokines, interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α), together with leukocytic infiltration, are prominent features in crescentic glomerulonephritis. Because these cytokines are targets for nuclear transcription factor-κB (NF-κB), the use of NF-κB decoy oligodeoxynucleotide (ODN) treatment was evaluated in an experimental disease model. Crescentic glomerulonephritis was induced in primed Wistar rats by injection of sheep antiglomerular basement membrane serum. Thirty minutes after injection, rats were anesthetized and the left kidney was perfused with NF-κB decoy ODN or scrambled ODN control mixed with a virus-liposome complex, and then killed 7 d later. Animals given the scrambled control ODN developed severe glomerulonephritis by day 7 with heavy proteinuria, glomerular crescents and interstitial lesions, marked leukocytic infiltration, and upregulated renal expression of cytokines (IL-1 and TNF-α) and adhesion molecules (intercellular adhesion molecule-1). In contrast, NF-κB decoy ODN treatment substantially inhibited the disease with a 50% reduction in proteinuria, a threefold reduction in histologic damage, a 50% reduction in leukocytic infiltration, and a 50 to 80% reduction in the renal expression of cytokines and leukocyte adhesion molecules. In conclusion, this study has demonstrated that NF-κB plays a key role in cytokine-mediated renal injury and that NF-κB decoy ODN treatment has clear therapeutic potential in rapidly progressive glomerulonephritis.
Id-1 and Id-2 Proteins as Molecular Markers for Human Prostate Cancer Progression
Authors: Jean-Philippe Coppe, Yoko Itahana, Dan H. Moore, James L. Bennington, Pierre-Yves Desprez
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Id proteins are dominant-negative regulators of basic helix-loop-helix transcription factors that control malignant cell behavior in many different tissues. This study aimed to identify the potential role of Id-1 and Id-2 proteins as molecular makers for prostate cancer progression. Experimental Design: Using the technique of immunohistochemistry, we determined Id-1 and Id-2 expression in a panel of 67 human prostate biopsies. We also manipulated Id-1 and Id-2 expression in LNCaP and PC3 prostate cancer cell lines and determined the effects on invasion in vitro, matrix metalloproteinase secretion, and proliferation. Results: Both Id-1 and Id-2 proteins were up-regulated during human prostate cancer progression in vivo and were overexpressed in highly aggressive prostate cancer cells. In vitro, constitutive expression of Id-1, and to a lesser extent Id-2, converted nonaggressive LNCaP prostate cancer cells into more proliferative and invasive cells and increased their secretion of matrix metalloproteinases. Conversely, the down-regulation of Id-2 expression in highly metastatic PC3 cells reduced their growth potential and invasiveness. Conclusions: We propose that both Id-1 and Id-2 proteins control prostate cancer cell phenotypes and could serve as molecular markers of aggressive human prostate cancer.
Thyroid and other autoantibodies in British and Japanese women: an epidemiological study of breast cancer.
Authors: I Mittra, J Perrin, S Kumaoka
Journal: BMJ (1976)

To define the role of asymptomatic autoimmune thyroiditis in the cause of breast cancer, the presence of circulating thyroid autoantibodies was studied in two populations, one with a high risk of breast cancer (British women) and one with a low risk (Japanese women). Ostensibly healthy women and patients with breast cancer from both countries were studied. There was no difference in the incidence of thyroid autoantibodies between women with breast cancer and healthy women in either race. The incidence of thyroid autoantibodies in healthy British women, however, was two to three times that in healthy Japanese women. The incidence of reticulin antibodies, was considerably higher in both groups of Japanese women. No remarkable differences in the incidence of antinuclear, smooth-muscle, antimitochondrial, gastric parietal cell, or liver-kidney microsomal antibodies were found between women with breast cancer and healthy women or between the two races. Only the incidence of antinuclear antibodies was marginally higher in Japanese patients with advanced cancer. These results indicate that asymptomatic autoimmune thyroid disease is more prevalent among British than among Japanese women, but they fail to provide direct evidence that autoimmune thyroid disease is associated with breast cancer. Prospective studies of women with autoimmune thyroiditis and studies of young women from low-risk and high-risk populations are needed.
Journal editors must play their part in checking timing of clinical trial registration
Authors: A. L. Abrams, T. Kredo
Journal: BMJ (2015)

Clinical trial registration is pivotal to understanding the research landscape and for ensuring research accountability. But what do we do when protocols to ensure public access to information are in place but chains of responsibility fail?

Prospective clinical trial registration is mandated by the International Committee of Medical Journal Editors’ (ICMJE) uniform requirements for manuscripts as a pre-condition for publication.1 …
Reviewer selection: author or editor knows best?
Authors: J R Hurst
Journal: Thorax (2005)

Differential behaviour of author and editor suggested reviewers

T horax is now the second highest ranked respiratory journal and submissions are increasing year on year.1 To attract high quality manuscripts, authors must have confidence in our editorial process and we are committed to continuing and improving the transparency, efficiency, and fairness of peer review.

When the current Editors took over the journal in 2003, Thorax changed to online manuscript submission2 and, for the first time, authors were formally invited to suggest up to four suitable peer reviewers for their work. Indeed, we encourage authors to suggest reviewers, as set out in our advice to contributors.3 Peer review is a vital step in the editorial process, guiding the selection of appropriate papers for publication and providing constructive comments for authors to improve their work. So, …
Increased Carotid Intima-Media Thickness and Serum Inflammatory Markers in Obstructive Sleep Apnea
Authors: Kenji Minoguchi, Takuya Yokoe, Toshiyuki Tazaki, Hideko Minoguchi, Akihiko Tanaka, Naruhito Oda, Shinji Okada, Shin Ohta, Hirokuni Naito, Mitsuru Adachi
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Increased carotid intima-media thickness (IMT) and increased serum levels of inflammatory markers, such as C-reactive protein (CRP), interleukin (IL)-6, and IL-18, are associated with an increased risk of cardiovascular and cerebrovascular diseases. The aim of this study was to evaluate whether carotid IMT, a useful marker for early atherosclerosis, is associated with these inflammatory markers in patients with obstructive sleep apnea (OSA). Carotid IMT was investigated with ultrasonography in 36 patients with OSA and 16 obese control subjects. Serum levels of CRP, IL-6, and IL-18 were measured at 5:00 A.M. Carotid IMT (p < 0.001) and serum levels of CRP (p < 0.003), IL-6 (p < 0.005), and IL-18 (p < 0.03) of patients with OSA were significantly higher than those of obese control subjects. Carotid IMT was significantly correlated with serum levels of CRP (r = 0.61, p = 0.0001), IL-6 (r = 0.41, p = 0.01), and IL-18 (r = 0.45, p = 0.005), duration of OSA-related hypoxia (r = 0.60, p = 0.0001), and severity of OSA (r = 0.50, p = 0.002). In addition, the primary factor influencing carotid IMT was duration of hypoxia during total sleep time (p = 0.036). These results suggest that OSA-related hypoxia and systemic inflammation might be associated with the progression of atherosclerosis and thus might increase the risks of cardiovascular and cerebrovascular morbidity in patients with OSA.
Cytomegalovirus generates long-lived antigen-specific NK cells with diminished bystander activation to heterologous infection
Authors: Gundula Min-Oo, Lewis L. Lanier
Journal: The Journal of Experimental Medicine (2014)

Natural killer (NK) cells play a key role in the host response to cytomegalovirus (CMV) and can mediate an enhanced response to secondary challenge with CMV. We assessed the ability of mouse CMV (MCMV)–induced memory Ly49H+ NK cells to respond to challenges with influenza, an acute viral infection localized to the lung, and Listeria monocytogenes, a systemic bacterial infection. MCMV-memory NK cells did not display enhanced activation or proliferation after infection with influenza or Listeria, as compared with naive Ly49H+ or Ly49H− NK cells. Memory NK cells also showed impaired activation compared with naive cells when challenged with a mutant MCMV lacking m157, highlighting their antigen-specific response. Ex vivo, MCMV-memory NK cells displayed reduced phosphorylation of STAT4 and STAT1 in response to stimulation by IL-12 and type I interferon (IFN), respectively, and IFN-γ production was reduced in response to IL-12 + IL-18 compared with naive NK cells. However, costimulation of MCMV-memory NK cells with IL-12 and m157 antigen rescues their impaired response compared with cytokines alone. These findings reveal that MCMV-primed memory NK cells are diminished in their response to cytokine-driven bystander responses to heterologous infections as they become specialized and antigen-specific for the control of MCMV upon rechallenge.
Glycogen Synthase Kinase 3 Inhibition Slows Mitochondrial Adenine Nucleotide Transport and Regulates Voltage-Dependent Anion Channel Phosphorylation
Authors: Samarjit Das, Renee Wong, Nishadi Rajapakse, Elizabeth Murphy, Charles Steenbergen
Journal: Circulation Research (2008)

Inhibition of glycogen synthase kinase (GSK)-3 reduces ischemia/reperfusion injury by mechanisms that involve the mitochondria. The goal of this study was to explore possible molecular targets and mechanistic basis of this cardioprotective effect. In perfused rat hearts, treatment with GSK inhibitors before ischemia significantly improved recovery of function. To assess the effect of GSK inhibitors on mitochondrial function under ischemic conditions, mitochondria were isolated from rat hearts perfused with GSK inhibitors and were treated with uncoupler or cyanide or were made anoxic. GSK inhibition slowed ATP consumption under these conditions, which could be attributable to inhibition of ATP entry into the mitochondria through the voltage-dependent anion channel (VDAC) and/or adenine nucleotide transporter (ANT) or to inhibition of the F(1)F(0)-ATPase. To determine the site of the inhibitory effect on ATP consumption, we measured the conversion of ADP to AMP by adenylate kinase located in the intermembrane space. This assay requires adenine nucleotide transport across the outer but not the inner mitochondrial membrane, and we found that GSK inhibitors slow AMP production similar to their effect on ATP consumption. This suggests that GSK inhibitors are acting on outer mitochondrial membrane transport. In sonicated mitochondria, GSK inhibition had no effect on ATP consumption or AMP production. In intact mitochondria, cyclosporin A had no effect, indicating that ATP consumption is not caused by opening of the mitochondrial permeability transition pore. Because GSK is a kinase, we assessed whether protein phosphorylation might be involved. Therefore, we performed Western blot and 1D/2D gel phosphorylation site analysis using phos-tag staining to indicate proteins that had decreased phosphorylation in hearts treated with GSK inhibitors. Liquid chromatographic-mass spectrometric analysis revealed 1 of these proteins to be VDAC2. Taken together, we found that GSK-mediated signaling modulates transport through the outer membrane of the mitochondria. Both proteomics and adenine nucleotide transport data suggest that GSK regulates VDAC and that VDAC may be an important regulatory site in ischemia/reperfusion injury.