tbuckley/cabot-search huggingface dataset:
Augmentation of central arterial pressure in type 1 diabetes.
Authors: B Brooks, L Molyneaux, D K Yue
Journal: Diabetes Care (1999)

OBJECTIVE: Atherosclerosis is more severe in individuals with diabetes. Whether diabetic subjects have accelerated arterial hardening (i.e., arteriosclerosis) is less clear. Arteriosclerosis increases pulse-wave velocity and can augment central arterial pressure due to early wave reflection. The aim of this study was to determine whether subjects with type 1 diabetes had evidence of increased arterial stiffness by using pulse-wave analysis. RESEARCH DESIGN AND METHODS: Radial artery pressure waveforms were obtained noninvasively by applanation tonometry (PWV Medical Blood Pressure Analysis System, Sydney). A central aortic waveform can be derived by using a transfer function used in previous studies during cardiac catheterization. A total of 89 subjects with type 1 diabetes (46 men and 43 women, aged 34.0 +/- 11.0 years, duration of diabetes 13.1 years [interquartile range 5.8-24.3], HbA1c 8.2 +/- 1.7%) and 95 control subjects (44 men and 51 women, aged 36.1 +/- 12.0 years) were studied. The central aortic waveform allowed the determination of 1) the aortic augmentation index (AAI), a parameter that reflects the degree to which central arterial pressure is augmented by wave reflection, and 2) the subendocardial viability ratio (SEVR), which is a measure of myocardial perfusion relative to cardiac workload. RESULTS: In multivariate analysis, diabetes was an important determinant of AAI (P = 0.001). The higher AAI was mainly evident in the men, for whom diabetes was a highly significant covariate (P = 0.006); this was not the case for diabetic women (P = 0.2). Nondiabetic men had a lower AAI than nondiabetic women (103.7 +/- 18.6 vs. 117.0 +/- 22.3%, respectively, P = 0.002), but this difference was abolished by diabetes (110.7 +/- 18.5 vs. 116.1 +/- 18.7%, respectively, P = 0.2). Subjects with type 1 diabetes had a significantly lower mean SEVR compared with control subjects (139.2 +/- 28.3 vs. 163.6 +/- 27.4%, respectively, P &amp;lt; 0.0001). In multivariate analysis, diabetes was an important determinant of SEVR (P = 0.001). A significant interaction between diabetes and age was evident (P = 0.0001), which suggests that the effect of age is modified by diabetes. CONCLUSIONS: These findings suggest that central systolic blood pressure is increased in relatively young individuals with type 1 diabetes, although myocardial perfusion related to cardiac workload is decreased. These changes can be explained by more rapid pulse-wave velocity resulting from arterial stiffening.
<i>TGFBR1*</i>6A Enhances the Migration and Invasion of MCF-7 Breast Cancer Cells through RhoA Activation
Authors: Diana S. Rosman, Sharbani Phukan, Chiang-Ching Huang, Boris Pasche
Journal: Cancer Research (2008)

Abstract TGFBR1*6A is a common hypomorphic variant of the type 1 transforming growth factor β receptor (TGFBR1), which has been associated with increased cancer risk in some studies. Although TGFBR1*6A is capable of switching TGF-β growth-inhibitory signals into growth-stimulatory signals when stably transfected into MCF-7 breast cancer cells, the biological effects of TGFBR1*6A are largely unknown. To broadly explore the potential oncogenic properties of TGFBR1*6A, we assessed its effects on NIH-3T3 cells as well as its effect on the migration and invasion of MCF-7 cells. We found that TGFBR1*6A has decreased oncogenic properties compared with TGFBR1. However, TGFBR1*6A significantly enhances MCF-7 cell migration and invasion in a TGF-β signaling–independent manner. Gene expression profiling studies identified two down-regulated genes involved in cell migration and invasion: ARHGAP5, encoding ARHGAP5, and FN1, encoding fibronectin-1 (FN1). ARHGAP5 and FN1 expression was similarly down-regulated in MCF-7 cells stably transfected with a kinase-inactivated TGFBR1*6A construct. Functional assays show that TGFBR1*6A-mediated decreased ARHGAP5 expression is associated with higher RhoA activation, a crucial mediator of cell migration. Extracellular signal-regulated kinase (ERK) activation is also higher in cells that harbor the TGFBR1*6A allele. We conclude that TGFBR1*6A is not an oncogene but enhances MCF-7 cell migration and invasion through RhoA and ERK pathway activation and down-regulates two crucial mediators of this phenotype. These results provide the first evidence that TGFBR1*6A may contribute to cancer progression in a TGF-β signaling–independent manner. [Cancer Res 2008;68(5):1319–28]
Specific Induction Of CD203c Expression In Blood Basophils Discriminates Between CF patients With Aspergillus Colonization And Those With CF-ABPA
Authors: Y. Gernez, C. Everson, E. Mitsunaga, C. Dunn, L. Herzenberg, R. Tirouvanziam, R. Moss
Journal: Journal of Allergy and Clinical Immunology (2012)
Short form 36 (SF36) health survey questionnaire: normative data for adults of working age.
Authors: C Jenkinson, A Coulter, L Wright
Journal: BMJ (1993)

To gain population norms for the short form 36 health survey questionnaire (SF36) in a large community sample and to explore the questionnaire's internal consistency and validity.Postal survey by using a booklet containing the SF36 and several other items concerned with lifestyles and illness.The sample was drawn from computerised registers of the family health services authorities for Berkshire, Buckinghamshire, Northamptonshire, and Oxfordshire.13,042 randomly selected subjects aged 18-64 years.Scores for the eight health dimensions of the SF36.The survey achieved a response rate of 72% (n = 9332). Internal consistency of the different dimensions of the questionnaire was high. Normative data broken down by age, sex, and social class were consistent with those from previous studies.The SF36 is a potentially valuable tool in medical research. The normative data provided here may further facilitate its validation and use.
Unrecognized Non-Q-Wave Myocardial Infarction: Prevalence and Prognostic Significance in Patients with Suspected Coronary Disease
Authors: Han W. Kim, Igor Klem, Dipan J. Shah, Edwin Wu, Sheridan N. Meyers, Michele A. Parker, Anna Lisa Crowley, Robert O. Bonow, Robert M. Judd, Raymond J. Kim
Journal: PLoS Medicine (2009)

Background Unrecognized myocardial infarction (UMI) is known to constitute a substantial portion of potentially lethal coronary heart disease. However, the diagnosis of UMI is based on the appearance of incidental Q-waves on 12-lead electrocardiography. Thus, the syndrome of non-Q-wave UMI has not been investigated. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can identify MI, even when small, subendocardial, or without associated Q-waves. The aim of this study was to investigate the prevalence and prognosis associated with non-Q-wave UMI identified by DE-CMR. Methods and Findings We conducted a prospective study of 185 patients with suspected coronary disease and without history of clinical myocardial infarction who were scheduled for invasive coronary angiography. Q-wave UMI was determined by electrocardiography (Minnesota Code). Non-Q-wave UMI was identified by DE-CMR in the absence of electrocardiographic Q-waves. Patients were followed to determine the prognostic significance of non-Q-wave UMI. The primary endpoint was all-cause mortality. The prevalence of non-Q-wave UMI was 27% (50/185), compared with 8% (15/185) for Q-wave UMI. Patients with non-Q-wave UMI were older, were more likely to have diabetes, and had higher Framingham risk than those without MI, but were similar to those with Q-wave UMI. Infarct size in non-Q-wave UMI was modest (8%±7% of left ventricular mass), and left ventricular ejection fraction (LVEF) by cine-CMR was usually preserved (52%±18%). The prevalence of non-Q-wave UMI increased with the extent and severity of coronary disease on angiography (p<0.0001 for both). Over 2.2 y (interquartile range 1.8–2.7), 16 deaths occurred: 13 in non-Q-wave UMI patients (26%), one in Q-wave UMI (7%), and two in patients without MI (2%). Multivariable analysis including New York Heart Association class and LVEF demonstrated that non-Q-wave UMI was an independent predictor of all-cause mortality (hazard ratio [HR] 11.4, 95% confidence interval [CI] 2.5–51.1) and cardiac mortality (HR 17.4, 95% CI 2.2–137.4). Conclusions In patients with suspected coronary disease, the prevalence of non-Q-wave UMI is more than 3-fold higher than Q-wave UMI. The presence of non-Q-wave UMI predicts subsequent mortality, and is incremental to LVEF. Trial Registration Clinicaltrials.gov NCT00493168
Women in Labour
Authors: K. G. Lloyd-Williams
Journal: BMJ (1945)

We report the unusual case of a patient found to have a low glycosylated haemoglobin (HbA1c) despite having recently been diagnosed with diabetes mellitus type 2. The patient, who was not anaemic, with no symptoms or family history of haematological conditions, was subsequently found to have an elevated reticulocyte count, inferring increased red cell turnover as the culprit for the discordant HbA1c result. A diagnosis of hereditary spherocytosis was made based on characteristic peripheral blood film appearances and confirmed by eosin-5-maleimide binding test. Exposure of an undiagnosed haemolytic anaemia by virtue of a low HbA1c is uncommon. However, conditions that distort HbA1c measurements are not infrequent. This case should serve to remind clinicians of the limitations of HbA1c in specified situations, and to remain vigilant when interpreting results.
UK study will reimburse egg donors for costs of in vitro fertilisation
Authors: Susan Mayor
Journal: BMJ (2007)

Women will be reimbursed about half the cost of their in vitro fertilisation in return for donating “surplus” eggs for stem cell research, in the first study funded by the UK Medical Research Council (MRC) that will pay participants.

The MRC announced last week that it is funding a research proposal from the North East England Stem Cell Institute (NESCI), based in Newcastle, to find ways of improving the efficiency of therapeutic cloning. This technique is designed to create stem cells specific to a patient that might eventually be used to treat conditions in which new cells could be therapeutic—such as diabetes, heart disease, and Parkinson's disease.

Out of the funding of £470 000 (€680 000; $950 000) for the research, the MRC will provide £150 000 to reimburse part of the cost of treatment for women …
Serological Abnormalities in Patients with Liver Disease
Authors: I. A. D. Bouchier, K. Rhodes, S. Sherlock
Journal: BMJ (1964)

Patients with active cirrhosis of the liver may show evidence of multiple system involvement (Read, Sherlock, and Harrison, 1963).The suggestion has also been made that in such patients autoimmune phenomena play an important part in the patho- genesis of the disease (Mackay, Taft, and Cowling, 1956).These findings prompted us to undertake an investigation into the frequency with which antinuclear factors (A.N.F.) and other autoantibodies occur in the sera of patients with various types of liver disease. Patients Studied and Diagnostic GroupsA total of 116 cases of liver disease were studied, of which 104 were shown to have some form of cirrhosis.Alcoholic Cirrhosis.-Thisgroup comprised 10 patients- seven males and three females.Their ages varied from 30 to 69, with a mean of 50.5 years.All gave a history of excessive alcohol intake and many showed peripheral neuropathy, parotid enlargement, and gynaecomastia.Liver biopsies revealed portal cirrhosis with a variable degree of fatty infiltration: Mallory's hyaline was present in some."7uvenile" Cirrhosis.-Therewere 38 patients-18 males and 20 females-in this group.Their ages varied from 6 to 67, with a mean of 27 years.The term " juvenile " cirrhosis describes a group of patients showing all or most of the follow- ing features: marked hypergammaglobulinaemia, elevated serum transaminase and serum bilirubin levels, and cirrhosis, usually post-necrotic in character (Read et al., 1963).A prominent feature of the liver histology is the plasma-cell and lymphocytic infiltration and the tendency for the liver cells to take up a rosette-like formation.This group resembles those cases described by Bearn, Kunkel, and Slater (1956), and called plasma-cell hepatitis, active chronic hepatitis, and lupoid hepatitis (Mackay and Wood, 1962).Primary Biliary Cirrhosis.-Therewere 12 patients in this group, all females.Their ages ranged from 33 to 59, with a mean of 48 years.Pruritus, intrahepatic cholestasis, and an elevated serum cholesterol were prominent features of the illness (Sherlock, 1959).The majority had undergone a previous laparotomy, when the patency of the biliary tree had been established.Liver histology was characterized by aggressive, infiltrating fibrosis in the portal zones, inconspicuous bile- ductules, and foci of lymphocytes.Virus Hepatitis.-Therewere 12 patients in this group-five males and seven females.Their ages varied from 26 to 61, with a mean of 36 years.All had been admitted in the second or third week of their illness, the majority because of severe cholestasis.This group therefore does not represent the usual type of virus hepatitis. InvestigationsLiver histology, obtained by percutaneous liver biopsy or at operation, was available on all the patients studied except the
Diathermy Treatment of Angiomata
Authors: D. Aiken
Journal: BMJ (1951)

MEDICAL JOULNALand heart-block, complete or incomplete, by Laubry et al. (1921), Gallavardin (1922), Coffen (1930), Tuohy and Boman (1931), and others.But, so far as we can ascer- tain, this is the first case on record of atypical right bundle-branch block with anterior wall infarction arising as the result of a chest-wall injury and attended by clinical recovery.Summary A case report is presented of anterior wall infarction with atypical right bundle-branch., block, arising directly after a crush injury to the chest wall, in a perfectly healthy young4 man and attended by clinical recovery.So far as can be ascertained, this is the first case of its kind in the medical literature.A short review is presented of present-day views on the subject of traumatic heart disease.
ICAM-1 Has a Critical Role in the Regulation of Metastatic Melanoma Tumor Susceptibility to CTL Lysis by Interfering with PI3K/AKT Pathway
Authors: Ahmed Hamaï, Franck Meslin, Houssem Benlalam, Abdelali Jalil, Maryam Mehrpour, Florence Faure, Yann Lecluse, Philipe Vielh, Marie-Françoise Avril, Caroline Robert, Salem Chouaib
Journal: Cancer Research (2008)

Human primary melanoma cells (T1) were found to be more susceptible to lysis by a Melan-A/MART-1-specific CTL clone (LT12) than their metastatic derivative (G1). We show that this differential susceptibility does not involve antigen presentation by target cells, synapse formation between the metastatic target and CTL clone, or subsequent granzyme B (GrB) polarization. Although PI-9, an inhibitor of GrB, was found to be overexpressed in metastatic G1 cells, knockdown of the PI-9 gene did not result in the attenuation of G1 resistance to CTL-induced killing. Interestingly, we show that whereas T1 cells express high levels of intercellular adhesion molecule-1 (ICAM-1), a dramatically reduced expression was noted on G1 cells. We also showed that sorted ICAM-1+ G1 cells were highly sensitive to CTL-induced lysis compared with ICAM-1- G1 cells. Furthermore, incubation of metastatic G1 cells with IFN-gamma resulted in the induction of ICAM-1 and the potentiation of their susceptibility to lysis by LT12. More importantly, we found that the level of ICAM-1 expression by melanoma cells correlated with decreased PTEN activity. ICAM-1 knockdown in T1 cells resulted in increased phosphorylation of PTEN and the subsequent activation of AKT. We have additionally shown that inhibition of the phosphatidylinositol (3,4,5)-triphosphate kinase (PI3K)/AKT pathway by the specific inhibitor wortmannin induced a significant potentiation of susceptibility of G1 and ICAM-1 small interfering RNA-treated T1 cells to CTL-induced lysis. The present study shows that a shift in ICAM-1 expression, which was associated with an activation of the PI3K/AKT pathway, can be used by metastatic melanoma cells to escape CTL-mediated killing.
Adaptative bile duct proliferative response in experimental bile duct ischemia
Authors: Marc Beaussier, Dominique Wendum, Laura Fouassier, Colette Rey, Véronique Barbu, Elisabeth Lasnier, André Lienhart, Jean-Yves Scoazec, Olivier Rosmorduc, Chantal Housset
Journal: Journal of Hepatology (2004)
The protease-activated receptor-2 agonist induces gastric mucus secretion and mucosal cytoprotection
Authors: Atsufumi Kawabata, Mitsuhiro Kinoshita, Hiroyuki Nishikawa, Ryotaro Kuroda, Minoru Nishida, Hiromasa Araki, Naoki Arizono, Yasuo Oda, Kazuaki Kakehi
Journal: Journal of Clinical Investigation (2001)

Protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, modulates smooth muscle tone and exocrine secretion in the salivary glands and pancreas. Given that PAR-2 is expressed throughout the gastrointestinal tract, we investigated effects of PAR-2 agonists on mucus secretion and gastric mucosal injury in the rat. PAR-2–activating peptides triggered secretion of mucus in the stomach, but not in the duodenum. This mucus secretion was abolished by pretreatment with capsaicin, which stimulates and ablates specific sensory neurons, but it was resistant to cyclo-oxygenase inhibition. In contrast, capsaicin treatment failed to block PAR-2–mediated secretion from the salivary glands. Intravenous calcitonin gene–related peptide (CGRP) and neurokinin A markedly elicited gastric mucus secretion, as did substance P to a lesser extent. Specific antagonists of the CGRP1 and NK2, but not the NK1, receptors inhibited PAR-2–mediated mucus secretion. Pretreatment with the PAR-2 agonist strongly prevented gastric injury caused by HCl-ethanol or indomethacin. Thus, PAR-2 activation triggers the cytoprotective secretion of gastric mucus by stimulating the release of CGRP and tachykinins from sensory neurons. In contrast, the PAR-2–mediated salivary exocrine secretion appears to be independent of capsaicin-sensitive sensory neurons.
Tazmamart: Fort-Militaire-Secret du Maroc. Consequences d'un Internement du 18 Annees
Authors: D Summerfield
Journal: BMJ (1994)

Evelyne van Ginneken, Ronald Rijnders Johannes Wier Foundation for Health and Human Rights, pp 118 ISBN 90-73550-10-6

Tazmamart tells a kind of Gothic horror story, one that is still unwinding. After unfair trials on charges of sedition, 59 former soldiers “disappeared” from Morocco's official prison system and were sent to a secret detention centre, Tazmamart, in the Atlas mountains. For 18 years they were held incommunicado and in almost complete darkness in small single cells which they never left. They were exposed to extremes of temperature, with poor food, little water, and no medical care. Thirty one died during this ordeal, and survivors' accounts suggest that at least 12 of these had pulmonary tuberculosis and 10 a terminal psychosis. One committed suicide a …
Artificial and Bioartificial Support Systems for Acute and Acute-on-Chronic Liver Failure
Authors: Lise L. Kjaergard, Jianping Liu, Bodil Als-Nielsen, Christian Gluud
Journal: JAMA (2003)

<h3>Context</h3> Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation. <h3>Objective</h3> To evaluate the effect of artificial and bioartificial support systems for acute and acute-on-chronic liver failure. <h3>Data Sources</h3> Randomized trials on any support system vs standard medical therapy were included irrespective of publication status or language. Nonrandomized studies were included in explorative analyses. Trials were identified through electronic searches (Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Library, MEDLINE, EMBASE, and the Chinese Medical Database), bibliographies, and contact with experts. Searches were conducted of the entire databases through September 2002. <h3>Study Selection</h3> Of 528 references identified, 12 randomized trials with 483 patients were included. Eight nonrandomized studies were included in explorative analyses. <h3>Data Extraction</h3> Data were extracted and trial quality was assessed independently by 3 reviewers (L.L.K., J.L., B.A-N.). The primary outcome measure was all-cause mortality. Results were combined on the risk ratio (RR) scale. Random-effects models were used. Sources of heterogeneity were explored through meta-regression and stratified meta-analyses. <h3>Data Synthesis</h3> Of the 12 trials included, 10 assessed artificial systems for acute or acute-on-chronic liver failure and 2 assessed bioartificial systems for acute liver failure. Overall, support systems had no significant effect on mortality compared with standard medical therapy (RR, 0.86; 95% confidence interval [CI], 0.65-1.12). Meta-regression indicated that the effect of support systems depended on the type of liver failure (<i>P</i>= .03). In stratified meta-analyses, support systems appeared to reduce mortality by 33% in acute-on-chronic liver failure (RR, 0.67; 95% CI, 0.51-0.90), but not in acute liver failure (RR, 0.95; 95% CI, 0.71-1.29). Compared with randomized trials, nonrandomized studies produced significantly larger estimates of intervention effects (<i>P</i>= .01). <h3>Conclusion</h3> This review suggests that artificial support systems reduce mortality in acute-on-chronic liver failure compared with standard medical therapy. Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure.