tbuckley/cabot-search huggingface dataset:
Mortality in Adult-Onset Autoimmune Diabetes Is Associated With Poor Glycemic Control
Authors: Lisa Olsson, Valdemar Grill, Kristian Midthjell, Anders Ahlbom, Tomas Andersson, Sofia Carlsson
Journal: Diabetes Care (2013)

Knowledge on mortality in autoimmune diabetes with adult onset is limited. We compared mortality in adult-onset autoimmune diabetes and type 2 diabetes, taking into account metabolic risk factors, HbA1c, lifestyle, and socioeconomic factors.Participants of the population-based HUNT2 Study (second survey of the Norwegian HelseUndersøkelsen i Nord-Trøndelag Study; n = 64,264) were followed up prospectively for mortality in the Cause of Death Registry (1995-2009). Diabetes with onset ≥35 years was classified as autoimmune diabetes in adults if anti-GAD was positive (n = 208) and as type 2 diabetes if anti-GAD was negative (n = 2,425). Hazard ratios (HRs) of mortality from all-causes, cardiovascular disease (CVD), and ischemic heart disease (IHD) were calculated using the Cox proportional hazards model.Prevalence of the metabolic syndrome was lower in autoimmune diabetes than in type 2 diabetes (55 vs. 77%, P < 0.001). Still, autoimmune diabetes was associated with an increased risks of mortality from all-causes (HR 1.55 [95% CI 1.25-1.92]), CVD (1.87 [1.40-2.48]), and IHD (2.39 [1.57-3.64]), equally high as in type 2 diabetes in analyses where individuals without diabetes were used as the reference group. The increased risk was not explained by overweight, lifestyle, socioeconomic position, or presence of the metabolic syndrome. Excess mortality was primarily observed in individuals with elevated HbA1c.Mortality in autoimmune diabetes was as high as in type 2 diabetes, despite a more favorable baseline metabolic risk profile. Excess risk was associated with poor glycemic control. The results from this study, the largest so far on mortality in autoimmune diabetes in adults, underscore the importance of optimal treatment modalities to improve survival in adult-onset autoimmune diabetes.
Inhibition of the sonic hedgehog pathway at the primary cilium prevents the effect of TGF-beta 1 on alveolar epithelial cells
Authors: Elika Farrokhi Moshai, Arnaud Mailleux, Valérie Besnard, Stéphanie Brayer, Monique Dehoux, Bruno Crestani
Journal: European Respiratory Journal (2012)

Introduction.  The mesenchymal differentiation of alveolar epithelial cells induced by Transforming Growth Factor-beta1 (TGF-beta1), also called Epithelial Mesenchymal Transition (EMT), may contribute to Idiopathic Pulmonary Fibrosis (IPF). The Sonic Hedgehog (SHH) pathway is involved in epithelial cells-fibroblasts interaction during fetal lung development and lung fibrogenesis in adult lung. Previously, our laboratory has demonstrated that the SHH pathway is necessary to the action of TGF-beta 1 in human pulmonary fibroblasts (Cigna et al. in revision).   Aims. We hypothesized that the SHH pathway could play a role in mesenchymal differentiation of alveolar epithelial cells induced by TGF-beta 1.   Methods.  The A549 cell line or primary alveolar epithelial murine cells are pre-treated 1h with agonists (recombinant SHH, Smoothened Agonist) or with inhibitors of the pathway (Cyclopamine, HPI-4, GANT61) in the absence or presence of TGF-beta 1 (1-5 ng/ml) for 48h in serum-free medium. The expression of E-Cadherin, N-Cadherin, and fibronectin is evaluated by real-time PCR, Western blotting and immunocytochemistry. The migratory capacity of A549 is also measured in these conditions.   Results.  Inhibition of the pathway via SMO/GLI abolishes the effect of TGF-beta 1 on the migration of epithelial cells but do not influence the effect of TGF-beta 1 on cell differentiation. By contrast, the inhibition of the HH pathway in the primary cilium with HPI-4 prevents and reverts the effect of TGF-beta 1 on epithelial cell differentiation.   Conclusions.  Our results indicate that the primary cilium controls the effect of TGF-beta 1 on A549 cells in vitro.
Risk factors for long-term persistence of serum hepatitis B surface antigen following acute hepatitis B virus infection in Japanese adults
Authors: Kiyoaki Ito, Hiroshi Yotsuyanagi, Hiroshi Yatsuhashi, Yoshiyasu Karino, Yasuhiro Takikawa, Takafumi Saito, Yasuji Arase, Fumio Imazeki, Masayuki Kurosaki, Takeji Umemura, Takafumi Ichida, Hidenori Toyoda, Masashi Yoneda, Eiji Mita, Kazuhide Yamamoto, Kojiro Michitaka, Tatsuji Maeshiro, Junko Tanuma, Yasuhito Tanaka, Masaya Sugiyama, Kazumoto Murata, Naohiko Masaki, Masashi Mizokami
Journal: Hepatology (2013)

The proportion of patients who progress to chronicity following acute hepatitis B (AHB) varies widely worldwide. Moreover, the association between viral persistence after AHB and hepatitis B virus (HBV) genotypes in adults remains unclear. A nationwide multicenter study was conducted throughout Japan to evaluate the influence of clinical and virological factors on chronic outcomes in patients with AHB. For comparing factors between AHB patients with viral persistence and those with self-limited infection, 212 AHB patients without human immunodeficiency virus (HIV) coinfection were observed in 38 liver centers until serum hepatitis B surface antigen (HBsAg) disappeared or a minimum of 6 months in cases where HBsAg persisted. The time to disappearance of HBsAg was significantly longer for genotype A patients than that of patients infected with non-A genotypes. When chronicity was defined as the persistence of HBsAg positivity for more than 6 or 12 months, the rate of progression to chronicity was higher in patients with genotype A, although many cases caused by genotype A were prolonged cases of AHB, rather than chronic infection. Multivariate logistic regression analysis revealed only genotype A was independently associated with viral persistence following AHB. A higher peak level of HBV DNA and a lower peak of alanine aminotransferase (ALT) levels were characteristics of AHB caused by genotype A. Treatment with nucleotide analogs (NAs) did not prevent progression to chronic infection following AHB overall. Subanalysis suggested early NA initiation may enhance the viral clearance.Genotype A was an independent risk factor for progression to chronic infection following AHB. Our data will be useful in elucidating the association between viral persistence after AHB, host genetic factors, and treatment with NAs in future studies.
Prediction of Risk of Distant Recurrence Using the 21-Gene Recurrence Score in Node-Negative and Node-Positive Postmenopausal Patients With Breast Cancer Treated With Anastrozole or Tamoxifen: A TransATAC Study
Authors: Mitch Dowsett, Jack Cuzick, Christopher Wale, John Forbes, Elizabeth A. Mallon, Janine Salter, Emma Quinn, Anita Dunbier, Michael Baum, Aman Buzdar, Anthony Howell, Roberto Bugarini, Frederick L. Baehner, Steven Shak
Journal: Journal of Clinical Oncology (2010)

Purpose To determine whether the Recurrence Score (RS) provided independent information on risk of distant recurrence (DR) in the tamoxifen and anastrozole arms of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trial. Patients and Methods RNA was extracted from 1,372 tumor blocks from postmenopausal patients with hormone receptor–positive primary breast cancer in the monotherapy arms of ATAC. Twenty-one genes were assessed by quantitative reverse transcriptase polymerase chain reaction, and the RS was calculated. Cox proportional hazards models assessed the value of adding RS to a model with clinical variables (age, tumor size, grade, and treatment) in node-negative (N0) and node-positive (N+) women. Results Reportable scores were available from 1,231 evaluable patients (N0, n = 872; N+, n = 306; and node status unknown, n = 53); 72, 74, and six DRs occurred in N0, N+, and node status unknown patients, respectively. For both N0 and N+ patients, RS was significantly associated with time to DR in multivariate analyses (P &lt; .001 for N0 and P = .002 for N+). RS also showed significant prognostic value beyond that provided by Adjuvant! Online (P &lt; .001). Nine-year DR rates in low (RS &lt; 18), intermediate (RS = 18 to 30), and high RS (RS ≥ 31) groups were 4%, 12%, and 25%, respectively, in N0 patients and 17%, 28%, and 49%, respectively, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients. Conclusion This study confirmed the performance of RS in postmenopausal HR+ patients treated with tamoxifen in a large contemporary population and demonstrated that RS is an independent predictor of DR in N0 and N+ hormone receptor–positive patients treated with anastrozole, adding value to estimates with standard clinicopathologic features.
EPIDEMIC DIARRHEAL DISEASE OF SUCKLING MICE
Authors: Alwin M. Pappenheimer, F. Sargent Cheever
Journal: The Journal of Experimental Medicine (1948)

1. Cytoplasmic inclusions were found in the epithelial cells of the small intestine in a major proportion of suckling mice suffering from the spontaneous or experimentally produced diarrheal disease now prevalent in this laboratory. 2. They were not found in healthy stock mice of corresponding age. 3. Feeding of intestinal extract from healthy mice did not produce diarrhea or inclusions. 4. Feeding of boiled extract from diarrheal mice did not lead to the formation of cytoplasmic inclusions, when precautions were taken to prevent accidental infection. 5. The inclusions were regularly present only in the first few days of the disease. The inclusion-bearing cells desquamated. There was no inflammatory reaction. 6. Attention is called to the frequent presence of large numbers of Gram-positive coccoid bodies in the intestinal contents of suckling mice with diarrhea.
Echocardiographic left ventricular hypertrophy in Chinese endurance athletes.
Authors: Y S Lo, M K Chin
Journal: British Journal of Sports Medicine (1990)

Most echocardiographic data on the athletic heart syndrome originate from the United States and Western Europe. There are no published data on echocardiographically documented left ventricular hypertrophy in Asian athletes. We investigated the echocardiographic changes which take place with endurance training by studying eight Hong Kong national cyclists. This study confirms that left ventricular hypertrophy and increased left ventricular end-diastolic dimensions are common findings in Chinese endurance athletes as in their Caucasian counterparts. Calculated left ventricular muscle mass exceeded the 95th percentile in seven of eight subjects.
Measurement of Optic Disc Compliance by Digitized Image Analysis in the Normal Monkey Eye
Authors: Claude F. Burgoyne, Harry A. Quigley, Hilary W. Thompson, Susan Vitale, Rohit Varma
Journal: Ophthalmology (1995)

Purpose: To characterize the compliance of the normal monkey optic disc under conditions of induced short-term fluctuations in intraocular pressure (IOP). Methods: In 10 monkeys, one eye was compliance tested on three separate days followed by a single test of the contralateral eye (40 compliance tests). In a testing session, the optic disc was imaged at 2 and 47 minutes (baseline time point) after IOP was lowered to 10 mmHg; then at 2, 17, 32, and 47 minutes after IOP was elevated to 45 mmHg; then at 2, 47, and, in some cases, 92 minutes after IOP was lowered back to 10 mmHg. Eight digitized images were analyzed at each time point, yielding two parameters to characterize the position of the disc: the Mean Position of the Disc(MPD) and the Change from MPDBaseline(the value of MPD at a given time point minus the value for MPD at the baseline time point of that testing session). Analysis of variance (ANOVA) testing was used to evaluate the overall effect of IOP on both parameters while taking into account the effects of variability due to different monkeys and repetitions of the test as well as differences between the two eyes of an individual monkey. With the addition of data from 11 compliance tests performed on eight additional monkeys, the overall results were calculated in terms of the mean Change from MPDBaselineat each time point for a total of 51 compliance testing sessions. Results: The mean Change from MPDBaselinewas -28 μm (95% confidence interval, -23 to -33 μm) 47 minutes after elevation of IOP. The disc surface returned to its baseline position 92 minutes after IOP was lowered back to 10 mmHg. Elevation of IOP within a compliance test had a significant effect on the position of the optic disc surface (P= 0.0002, ANOVA), as characterized by the parameter Change from MPDBaseline-Neither the difference in the amount of movement between -the two eyes of an individual monkey nor the variability within the three repetitions of the test in a given eye was statistically significant. Conclusion: Small, reversible (elastic) posterior deformations of the optic disc surface follow acute elevations of IOP in the normal monkey eye. Detection of acute IOP-induced deformations of the optic disc surface may represent a means by which to mechanically test the deeper load-bearing tissues of the optic nerve head.
Procholecystokinin as Marker of Human Ewing Sarcomas
Authors: Jean Claude Reubi, Pernille Koefoed, Thomas v. O. Hansen, Edouard Stauffer, Daniel Rauch, Finn C. Nielsen, Jens F. Rehfeld
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Ewing sarcoma is a rapidly growing mesenchymal tumor in young adults. Although it was shown previously to express the cholecystokinin (CCK) gene, it is unknown whether CCK gene expression is detectable at protein level in Ewing sarcoma tumor cell lines, in tumor tissue, and in plasma from Ewing sarcoma patients, and, if so, whether CCK peptides might play a role as tumor markers. Experimental Design: CCK gene expression was evaluated with in situ hybridization or reverse transcription-PCR in tumor tissue. CCK precursors and bioactive CCK were measured with specific RIAs in tumor tissue, in cell culture medium, and in plasma of Ewing sarcoma patients before and after chemotherapy as well as after tumor recurrence. Results: CCK mRNA was identified in 12 Ewing sarcoma biopsies sampled in two series and in four Ewing sarcoma cell lines but not in unrelated neoplasia. Immunoreactive proCCK was identified in the culturing medium of all Ewing sarcoma cell lines but not in the media from unrelated tumor cell lines. Moreover, in plasma from Ewing sarcoma patients, precursors and mature forms of CCK, in particular proCCK, were detected; several fold elevation of the total proCCK product was found in plasma from patients before treatment and after tumor recurrence, whereas successful chemotherapy reduced proCCK to basal concentrations. Plasma concentrations of proCCK paralleled the respective tumor size. Conclusions: This is the first study that consistently documents an altered CCK metabolism in human cancer; Ewing sarcomas synthesize and secrete proCCK that can be identified in plasma as circulating tumor marker.
Palliative Sedation in End-of-Life Care and Survival: A Systematic Review
Authors: Marco Maltoni, Emanuela Scarpi, Marta Rosati, Stefania Derni, Laura Fabbri, Francesca Martini, Dino Amadori, Oriana Nanni
Journal: Journal of Clinical Oncology (2012)

Purpose Palliative sedation is a clinical procedure aimed at relieving refractory symptoms in patients with advanced cancer. It has been suggested that sedative drugs may shorten life, but few studies exist comparing the survival of sedated and nonsedated patients. We present a systematic review of literature on the clinical practice of palliative sedation to assess the effect, if any, on survival. Methods A systematic review of literature published between January 1980 and December 2010 was performed using MEDLINE and EMBASE databases. Search terms included palliative sedation, terminal sedation, refractory symptoms, cancer, neoplasm, palliative care, terminally ill, end-of-life care, and survival. A manual search of the bibliographies of electronically identified articles was also performed. Results Eleven published articles were identified describing 1,807 consecutive patients in 10 retrospective or prospective nonrandomized studies, 621 (34.4%) of whom were sedated. One case-control study was excluded from prevalence analysis. The most frequent reason for sedation was delirium in the terminal stages of illness (median, 57.1%; range, 13.8% to 91.3%). Benzodiazepines were the most common drug category prescribed. Comparing survival of sedated and nonsedated patients, the sedation approach was not shown to be associated with worse survival. Conclusion Even if there is no direct evidence from randomized clinical trials, palliative sedation, when appropriately indicated and correctly used to relieve unbearable suffering, does not seem to have any detrimental effect on survival of patients with terminal cancer. In this setting, palliative sedation is a medical intervention that must be considered as part of a continuum of palliative care.
Me and Mrs Jones
Authors: Liam Farrell
Journal: BMJ (2005)

When I woke up in the morning she'd be lying there beside me, golden hair cascading on the pillow, white founts falling in the courts of the sun, eyes as blue as cornflowers, her pearl-pale hand in mine. We were children of the 1960s, Woodstock, Janis Joplin, Country Joe and the Fish, the summer of peace, love, and rock'n'roll.

We had to be discreet, of course, but, in those days we were a united profession and we had plenty of …
Hepatopulmonary syndrome caused by sarcoidosis of the liver treated with transjugular intrahepatic portosystemic shunt
Authors: Markus W Nistal, Andrea Pace, Hans Klose, Daniel Benten, Ansgar W Lohse
Journal: Thorax (2012)

<h3>Background</h3> Patients with active systemic lupus erythematosus (SLE) are considered to have raised erythrocyte sedimentation rate (ESR) rather than raised C-reactive protein (CRP). Yet published evidence is low for this statement. DsDNA-antibodies, C3 complement, ferritin and proteinuria are also commonly applied to assess SLE. <h3>Objectives</h3> Firstly, to assess how ESR correlates with above mentioned laboratory parameters: in general, in the presence of clinical activity and/or infection or in the absence of both. Secondly, to determine if these parameters are associated with disease flare or infections. <h3>Methods</h3> A retrospective analysis of patients of a tertiary referral centre with SLE who underwent inpatient treatment between 2006 and 2015. Data on laboratory parameters, infection and disease flare, judged by the treating physician, were extracted. Patients were divided in four SLE groups: flare only (n=147), infection only (n=48), both (n=23), and neither infection nor flare (n=153). ESR was correlated to CRP, ferritin, proteinuria, C3-reduction and raised dsDNA-antibodies for the whole cohort and within each SLE group. Further, the association between all laboratory parameters and a) disease activity with and without infection, b) the presence of infection with and without disease activity, was tested. <h3>Results</h3> We identified 203 SLE patients, 26 males, with a total of 371 visits. Mean age was 45.6 years (SD± 16.5 years). Table 1 (top part) shows the correlation coefficients of ESR with the other laboratory parameters. ESR correlated moderately with CRP amongst all groups (r=0.47–0.58); weakly with ferritin in the general and the flare group (r=0.26); and very weakly with C3-reduction and raised dsDNA-antibodies (r&lt;0.2) in each group. Concerning proteinuria, the correlation was weak for all, for flaring and for silent patients (r=0.22 – 0.35), moderate for patients with both infection and activity (r=0.56). There was no correlation in infected patients (r &lt;0.06). Table 1 (bottom part) displays the p-values for the association of parameters with disease activity or infection, respectively. ESR, reduction of C3, proteinuria and raised dsDNA-antibodies were all associated with disease activity in the whole cohort and in the non-infected group; CRP only in non-infected patients. In the infected group, raised dsDNA-antibodies and proteinuria were the only parameters showing significant relation to disease activity. ESR and CRP were significantly associated with infections when looking at all or at inactive patients, but not in active patients. <h3>Conclusions</h3> Both, ESR and CRP are elevated in patients with SLE flare and are weakly correlated with other laboratory activity parameters. Thus, while normal CRP argues against infection elevation of ESR and CRP is not sufficient to distinguish between SLE flare and infection. <h3>Disclosure of Interest</h3> None declared
New Insights Into the Genetics of Autoimmune Myasthenia Gravis
Authors: Robert P. Lisak, Lisa Barcellos
Journal: JAMA Neurology (2015)

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Increased morbidity and mortality related to asthma among asthmatic patients who use major tranquillisers
Authors: K S Joseph, L. Blais, P. Ernst, S. Suissa
Journal: BMJ (1996)

To assess the potentially increased risk of death or near death from asthma in asthmatic patients with psychosis.Case-control study.The computerised health databases of the Canadian province of Saskatchewan.131 cases of death or near death from asthma identified within a cohort of asthmatic patients; 3930 matched non-cases. EXPOSURE AND OUTCOME MEASURES: The exposure of interest was the use of major tranquillisers in the period before an outcome event. Outcomes included death or near death from asthma.Crude analyses showed that asthmatic patients who had used major tranquillisers in the previous 12 months were at a 3.2 (95% confidence interval 1.4 to 7.5) times greater risk of death or near death from asthma than asthmatic patients who did not use major tranquillisers. Past users of major tranquillisers who had recently discontinued use were at a particularly high risk (relative risk 6.6; 2.5 to 17.6). Adjustment for use of antiasthma drugs and other confounders abolished this excess risk.Asthmatic patients who use major tranquillisers seem to be at an increased risk of death or near death from asthma. Physicians treating asthmatic patients with a history of use of major tranquillisers should exercise greater caution with regard to management of such patients.