tbuckley/cabot-search huggingface dataset:
Clinical and Immunologic Predictors of Scleroderma Renal Crisis in Japanese Systemic Sclerosis Patients With Anti–RNA Polymerase III Autoantibodies
Authors: Yasuhito Hamaguchi, Masanari Kodera, Takashi Matsushita, Minoru Hasegawa, Yuki Inaba, Toshikazu Usuda, Masataka Kuwana, Kazuhiko Takehara, Manabu Fujimoto
Journal: Arthritis & Rheumatology (2014)

Objective To identify predictive factors for scleroderma renal crisis (SRC) in patients with anti–RNA polymerase III (anti–RNAP III) antibodies. Methods A total of 583 adult Japanese patients with systemic sclerosis (SSc) were screened for anti–RNAP III using a commercially available enzyme‐linked immunosorbent assay (ELISA) kit. RNAP subsets were further identified by immunoprecipitation (IP) assays. The association of clinical and immunologic factors with SRC was examined by logistic analyses. Results In this cohort, 37 patients (6%) were positive for anti–RNAP III, as determined by anti–RNAP III–specific ELISA. Further IP assays revealed that 19 patients were positive for anti–RNAP I/III, 17 for anti–RNAP I/II/III, and 1 for anti‐RNAP III. SRC occurred in a total of 17 (2.9%) of 583 patients, with a significantly higher frequency in anti–RNAP III–positive SSc patients (9 of 37 [24%]) than those without anti–RNAP III (8 of 546 [1%]) (odds ratio [OR] 21.6 [95% confidence interval (95% CI) 7.8–60.3], P &lt; 0.00001). Our multivariate analyses using the Cox proportional hazards regression model revealed that anti–RNAP I/II/III positivity (OR 11.0 [95% CI 1.6–222.8], P = 0.0118) and an ELISA index for anti–RNAP III of ≥157 (OR 2.4 × 10 9 [95% CI 2.1–uncalculated], P = 0.0093) were independent factors associated with the development of SRC. Conclusion Our findings indicate that anti–RNAP III is associated with SRC, as reported previously. In addition, the presence of anti–RNAP II in combination with anti–RNAP I/III (anti–RNAP I/II/III) and a higher ELISA index for anti–RNAP III may be associated with the development of SRC in SSc patients with anti–RNAP III.
Transmission of Rabies Virus from an Organ Donor to Four Transplant Recipients
Authors: Arjun Srinivasan, Elizabeth C. Burton, Matthew J. Kuehnert, Charles Rupprecht, William L. Sutker, Thomas G. Ksiazek, Christopher D. Paddock, Jeannette Guarner, Wun-Ju Shieh, Cynthia Goldsmith, Cathleen A. Hanlon, James Zoretic, Bernard Fischbach, Michael Niezgoda, Waleed H. El-Feky, Lillian Orciari, Edmund Q. Sanchez, Anna Likos, Goran B. Klintmalm, Denise Cardo, James LeDuc, Mary E. Chamberland, Daniel B. Jernigan, Sherif R. Zaki
Journal: New England Journal of Medicine (2005)

In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause.We reviewed the medical records of the organ donor and the recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice.The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat.This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.
HIV testing for the non-specialist
Authors: M Hamill, S Wright, K Kemp, S de Silva
Journal: Journal of the Royal Society of Medicine (2006)

Since the introduction of highly active antiretroviral therapy the landscape of HIV has changed dramatically with greatly improved prognosis.1 The incidence of HIV infections continues to rise,2 with many patients undiagnosed until they present with a potentially preventable late complication or opportunistic infection. Current Health Protection Agency estimates are of 58 300 cases of HIV in the UK, a third of whom have not yet been diagnosed. Of these, 71% of infections are in adults aged 15-39 years.3 Many of those at risk of HIV will present to a variety of services—in particular accident and emergency, psychiatry, primary care, drug and alcohol services, genito-urinary medicine and other medical specialities. There are already examples of services where HIV testing is seen as a `routine' test (e.g. in obstetrics and genito-urinary medicine); this needs to be emulated and built upon (Box 1). The key to earlier diagnosis and treatment is to increase HIV testing uptake by the demystification of testing and a high clinical index of suspicion. This will involve consideration of testing of those not in the traditional high-risk groups.

If HIV disease is not considered early then it may be overlooked until the patient presents with advanced disease or with an opportunistic infection. Late presenters, following multiple presentations to medical services, remain a common problem.4
A Randomized Controlled Trial of Insulin Pump Therapy in Young Children With Type 1 Diabetes
Authors: Larry A. Fox, Lisa M. Buckloh, Shiela D. Smith, Tim Wysocki, Nelly Mauras
Journal: Diabetes Care (2005)

OBJECTIVE—This study assesses the effects of insulin pump therapy on diabetes control and family life in children 1–6 years old with type 1 diabetes. RESEARCH DESIGN AND METHODS—Twenty-six children with type 1 diabetes for ≥6 months were randomly assigned to current therapy (two or three shots per day using NPH insulin and rapid-acting analog) or continuous subcutaneous insulin infusion (CSII) for 6 months. After 6 months, current therapy subjects were offered CSII. Changes in HbA1c, mean blood glucose (MBG), hypoglycemia frequency, diabetes-related quality of life (QOL), and parental adjustment were recorded. RESULTS—Eleven subjects from each group completed the trial (age 46.3 ± 3.2 months [means ± SE]). At baseline, there were no differences between groups in HbA1c, MBG, age, sex, diabetes duration, or parental QOL. Mean HbA1c, MBG, and parental QOL were similar between groups at 6 months. Mean HbA1c and MBG did not change from baseline to 6 months in either group. The frequency of severe hypoglycemia, ketoacidosis, or hospitalization was similar between groups at any time period. Subjects on CSII had more fasting and predinner mild/moderate hypoglycemia at 1 and 6 months. Diabetes-related QOL improved in CSII fathers from baseline to 6 months. Psychological distress increased in current therapy mothers from baseline to 6 months. All subjects continued CSII after study completion. CONCLUSIONS—CSII is safe and well tolerated in young children with diabetes and may have positive effects on QOL. CSII did not improve diabetes control when compared with injections, despite more mild/moderate hypoglycemia. The benefits and realistic expectations of CSII should be thoroughly examined before starting this therapy in very young children.
Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I
Authors: Jenelle M. Timmins, Ji-Young Lee, Elena Boudyguina, Kimberly D. Kluckman, Liam R. Brunham, Anny Mulya, Abraham K. Gebre, Jonathan M. Coutinho, Perry L. Colvin, Thomas L. Smith, Michael R. Hayden, Nobuyo Maeda, John S. Parks
Journal: Journal of Clinical Investigation (2005)

Patients with Tangier disease exhibit extremely low plasma HDL concentrations resulting from mutations in the ATP-binding cassette, sub-family A, member 1 (ABCA1) protein. ABCA1 controls the rate-limiting step in HDL particle assembly by mediating efflux of cholesterol and phospholipid from cells to lipid-free apoA-I, which forms nascent HDL particles. ABCA1 is widely expressed; however, the specific tissues involved in HDL biogenesis are unknown. To determine the role of the liver in HDL biogenesis, we generated mice with targeted deletion of the second nucleotide-binding domain of Abca1 in liver only (Abca1–L/–L). Abca1–L/–L mice had total plasma and HDL cholesterol concentrations that were 19% and 17% those of wild-type littermates, respectively. In vivo catabolism of HDL apoA-I from wild-type mice or human lipid-free apoA-I was 2-fold higher in Abca1–L/–L mice compared with controls due to a 2-fold increase in the catabolism of apoA-I by the kidney, with no change in liver catabolism. We conclude that in chow-fed mice, the liver is the single most important source of plasma HDL. Furthermore, hepatic, but not extrahepatic, Abca1 is critical in maintaining the circulation of mature HDL particles by direct lipidation of hepatic lipid-poor apoA-I, slowing its catabolism by the kidney and prolonging its plasma residence time.
miR326 Maturation Is Crucial for VEGF-C–Driven Cortactin Expression and Esophageal Cancer Progression
Authors: Chih-Chen Hong, Pai-Sheng Chen, Jean Chiou, Ching-Feng Chiu, Ching-Yao Yang, Michael Hsiao, Yi-Wen Chang, Yang-Hao Yu, Mien-Chie Hung, Nai-Wen Hsu, Shine-Gwo Shiah, Nan-Yung Hsu, Jen-Liang Su
Journal: Cancer Research (2014)

Esophageal cancer is an aggressive human malignancy with increasing incidence in the developed world. VEGF-C makes crucial contributions to esophageal cancer progression that are not well understood. Here, we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin (CTTN), a regulator of the cortical actin cytoskeleton. Upregulation of CTTN expression by VEGF-C enhanced the invasive properties of esophageal squamous cell carcinoma in vitro and tumor metastasis in vivo. Mechanistic investigations showed that VEGF-C increased CTTN expression by downregulating Dicer-mediated maturation of miR326, thereby relieving the suppressive effect of miR326 on CTTN expression. Clinically, expression of Dicer and miR326 correlated with poor prognosis in patients with esophageal cancer. Our findings offer insights into how VEGF-C enhances the robust invasive and metastatic properties of esophageal cancer, which has potential implications for the development of new biomarkers or therapies in this setting.
Sex-related Differences in Cough Reflex Sensitivity in Patients with Chronic Cough
Authors: Jack A. Kastelik, Rachel H. Thompson, Imran Aziz, Josephine C. Ojoo, Anthony E. Redington, Alyn H. Morice
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Among patients attending specialist cough clinics there is an excess of females, but the reason for this sex difference is unknown. We tested the hypothesis that the sensitivity of the cough reflex is greater in female compared with male patients with chronic cough. Inhalation cough challenges with capsaicin and citric acid were performed in a large group of patients with chronic cough. The concentrations of tussive agent causing two (C2) and five (C5) coughs were calculated. Measurements of capsaicin cough reflex sensitivity (median [interquartile range]) were significantly lower for female patients compared with male patients (C2: 1.9 [0.5 to 5.5] versus 5.3 [2.2 to 11.5] μM, p = 0.0026; C5: 8.6 [2.2 to 34.0] versus 51.2 [7.2 to > 100] μM, p = 0.0007). Similarly for citric acid challenge, values were significantly lower for female compared with male patients (C2: 53.5 [17.3 to 145.4] versus 118.1 [41.4 to 381.7] mM, p = 0.0064; C5: 300.0 [97.1 to > 1,000] versus 830.4 [300.0 to > 1,000] mM, p = 0.032). There were significant correlations between capsaicin and citric acid C2 values (rs = 0.54, p < 0.0001) and C5 values (rs = 0.57, p < 0.0001). These findings indicate a sex difference in cough sensitivity in patients with chronic cough, as previously reported in healthy volunteers. This may explain the female preponderance in cough clinics.
A 37-year observation of mortality in Chinese chrysotile asbestos workers
Authors: Xiaorong Wang, Eiji Yano, Hong Qiu, Ignatius Yu, Midori N Courtice, L A Tse, Sihao Lin, Mianzhen Wang
Journal: Thorax (2011)

<h3>Objectives</h3> This 37-year prospective cohort study was undertaken to provide additional evidence for mortality risks associated with exposure to chrysotile asbestos. <h3>Methods</h3> 577 asbestos workers and 435 control workers in original cohorts were followed from 1972 to 2008, achieving a follow-up rate of 99% and 73%, respectively. Morality rates were determined based on person-years of observation. Cox proportional hazard models were constructed to estimate HRs of cause-specific mortality, while taking into account age, smoking and asbestos exposure level. <h3>Results</h3> There were 259 (45%) deaths identified in the asbestos cohort, and 96 died of all cancers. Lung cancer (n=53) and non-malignant respiratory diseases (n=81) were major cause-specific deaths, in contrast to nine lung cancers and 11 respiratory diseases in the controls. Age and smoking-adjusted HRs for mortality by all causes and all cancers in asbestos workers were 2.05 (95% CI 1.56 to 2.68) and 1.89 (1.25 to 2.87), respectively. The risks for lung cancer and respiratory disease deaths in asbestos workers were over threefold that in the controls (HR 3.31(95% CI 1.60 to 6.87); HR 3.23 (95% CI 1.68 to 6.22), respectively). There was a clear exposure–response trend with asbestos exposure level and lung cancer mortality in both smokers and non-smokers. <h3>Conclusion</h3> Data from this prospective cohort provide strong evidence for increased mortality risks, particularly from lung cancer and non-malignant respiratory diseases, associated with exposure to chrysotile asbestos, while taking into account of the smoking effect.
Do Quality Improvement Organizations Improve the Quality of Hospital Care for Medicare Beneficiaries?
Authors: Claire Snyder, Gerard Anderson
Journal: JAMA (2005)

Quality improvement organizations (QIOs) are charged with improving the quality of medical care for Medicare beneficiaries.To explore whether the quality of hospital care for Medicare beneficiaries improves more in hospitals that voluntarily participate with Medicare's QIOs compared with nonparticipating hospitals. DESIGN, SETTING, AND DATA: Data from 4 QIOs charged with improving the quality of care in 5 states (Maryland, Nevada, New York, Utah, and Washington) and the District of Columbia were used. Hospitals participate with the QIOs on quality improvement on a voluntary basis. A retrospective study was conducted comparing improvement in the quality of care of patients in hospitals that actively participated with the QIOs vs hospitals that did not. The medical records of approximately 750 Medicare beneficiaries per state in each of 5 clinical areas (atrial fibrillation, acute myocardial infarction, heart failure, pneumonia, and stroke) were abstracted at baseline (1998) and follow-up (2000-2001).Fifteen quality indicators associated with improved outcomes in the prevention or treatment of the 5 clinical areas were used as quality of care measures. These 15 indicators were specifically targeted by the QIOs for quality improvement during the study period.Hospitals that voluntarily participate with the QIOs are more likely to be larger than nonparticipating hospitals (P<.05). At baseline, there were statistically significant (P<.05) differences between participating and nonparticipating hospitals on 5 of 15 quality indicators, with participating hospitals performing better on 3 of 5. There was no statistically significant difference in change from baseline to follow-up between participating and nonparticipating hospitals on 14 of 15 quality indicators. The one exception was that participating hospitals improved more on the pneumonia immunization indicator than nonparticipating hospitals (P = .005).Hospitals that participate with the QIO program are not more likely to show improvement on quality indicators than hospitals that do not participate.
The British Association of Dermatologists audit of atopic eczema management in secondary care. Phase 3: audit of service outcome
Authors: K.W. Shum, S. Lawton, H.C. Williams, G. Docherty, J. Jones
Journal: British Journal of Dermatology (2000)

Service outcome was examined by a preconsultation (part 1) and a 6-week postconsultation (part 2) patient questionnaire in 29 hospital dermatology departments randomly selected from an original sample of 187 centres across the U.K. The outcome measures were: quality of life as measured by the Dermatology Life Quality Index (DLQI) and Children’s DLQI (CDLQI), improvement in sleep loss, improvement in worse aspect of skin disease and return to work or school. Three hundred and fifty-two questionnaires (115 adults, 237 children) were completed for part 1, and 235 (67%) replied to part 2. The mean DLQI at initial consultation was 12·5, dropping to 9·7 at 6 weeks (P = 0·001). The mean CDLQI at initial consultation was 10·5, dropping to 8·7 at 6 weeks (P < 0·001). Forty-nine per cent of adults and 44% of children had a > 25% relative improvement in score, which did not meet the 60% working standard. Forty-four per cent of adults and 47% of children had an improvement in sleep loss at 6 weeks, falling short of the 70% working standard. Sixty-one per cent of adults and 59% of children had an improvement in the worst aspect of their skin condition at 6 weeks, falling short of the 80% working standard. Of the 20 adults and eight children off work/school during part 1, 70% of adults and 87·5% of children had returned to work/school by 6 weeks. This met the 80% working standard for children but not for adults. On a national scale, only one of the eight working standards for service outcome was met, although most of the working standards were met by at least one of the 11 National Health Service administrative areas. This study presents the first national data on the outcomes of a representative sample of atopic eczema patients seen in secondary care. Small sample sizes, instruments which may be insensitive to change, as well as local factors such as case-mix, baseline severity and staff to patient ratios need to be taken into account when interpreting these results. Nevertheless, the results of this baseline audit suggest that the outcome of patients with atopic eczema following secondary care consultation may not be as good as some doctors believe. This suggests that an improvement in practice, a re-evaluation of the working standards, or both, is needed and should be examined in future audit cycles.
The Liver and Systemic Disease
Authors: J NEUBERGER
Journal: Gut (1998)

The Liver and Systemic Disease. Gitlin N. (Pp 300; illustrated; £95.00.) Edinburgh: Churchill Livingstone, 1997. ISBN 0-443-05546-7.

All hepatologists and right-thinking physicians are well aware that the liver is not only the largest internal organ but also the most important. In systemic diseases, the liver is often affected and liver function disturbed; conversely, primary liver disease can affect every other organ system. While most of the major medical and hepatological textbooks have sections on the liver in systemic disease, …
Paralympic athlete's health
Authors: Peter Van de Vliet
Journal: British Journal of Sports Medicine (2012)

l-3,4-Dihydroxy-6-<sup>18</sup>F-fluoro-phenyl-alanine (<sup>18</sup>F-FDOPA) is an amino acid analog used to evaluate presynaptic dopaminergic neuronal function. Evaluation of tumor recurrence in neurooncology is another application. Here, the kinetics of <sup>18</sup>F-FDOPA in brain tumors were investigated. <b>Methods:</b> A total of 37 patients underwent 45 studies; 10 had grade IV, 10 had grade III, and 13 had grade II brain tumors; 2 had metastases; and 2 had benign lesions. After <sup>18</sup>F-DOPA was administered at 1.5–5 MBq/kg, dynamic PET images were acquired for 75 min. Images were reconstructed with iterative algorithms, and corrections for attenuation and scatter were applied. Images representing venous structures, the striatum, and tumors were generated with factor analysis, and from these, input and output functions were derived with simple threshold techniques. Compartmental modeling was applied to estimate rate constants. <b>Results:</b> A 2-compartment model was able to describe <sup>18</sup>F-FDOPA kinetics in tumors and the cerebellum but not the striatum. A 3-compartment model with corrections for tissue blood volume, metabolites, and partial volume appeared to be superior for describing <sup>18</sup>F-FDOPA kinetics in tumors and the striatum. A significant correlation was found between influx rate constant K and late uptake (standardized uptake value from 65 to 75 min), whereas the correlation of K with early uptake was weak. High-grade tumors had significantly higher transport rate constant k<sub>1</sub>, equilibrium distribution volumes, and influx rate constant K than did low-grade tumors (<i>P</i> &lt; 0.01). Tumor uptake showed a maximum at about 15 min, whereas the striatum typically showed a plateau-shaped curve. Patlak graphical analysis did not provide accurate parameter estimates. Logan graphical analysis yielded reliable estimates of the distribution volume and could separate newly diagnosed high-grade tumors from low-grade tumors. <b>Conclusion:</b> A 2-compartment model was able to describe <sup>18</sup>F-FDOPA kinetics in tumors in a first approximation. A 3-compartment model with corrections for metabolites and partial volume could adequately describe <sup>18</sup>F-FDOPA kinetics in tumors, the striatum, and the cerebellum. This model suggests that <sup>18</sup>F-FDOPA was transported but not trapped in tumors, unlike in the striatum. The shape of the uptake curve appeared to be related to tumor grade. After an early maximum, high-grade tumors had a steep descending branch, whereas low-grade tumors had a slowly declining curve, like that for the cerebellum but on a higher scale.
A human lung explant model for the study of antiviral drugs
Authors: Ben Nicholas, Karl Staples, Stefan Moese, Jon Ward, Patrick Dennison, Tom Havelock, Timothy Hinks, Khalid Amer, Edwin Woo, Martin Chamberlain, Neeta Singh, Malcolm North, Sandy Pink, Tom Wilkinson, Ratko Djukanovic
Journal: European Respiratory Journal (2013)

Influenza A causes considerable morbidity and mortality. Growing viral resistance to therapeutics that target viral proteins, such as neuraminidase and M2-channel inhibitors, has led to increased interest in anti-viral compounds with effects on host-cell mechanisms. We report a novel experimental approach that circumvents the inter-species differences in immune responses to respiratory viruses which limit the value of animal models for the development of anti-viral drugs that target host defences. Using genome-wide siRNA screening in the A549 human epithelial cell line, we first identified vacuolar ATPases (vATPases) as a key host mechanism for influenza infection. A specific vATPase inhibitor was found markedly to attenuate influenza-A infection in monolayer cultures. We next developed a human lung explant model to test the effectiveness of the vATPase inhibitor when compared with the current frontline anti-influenza therapeutic, oseltamivir. Using flow cytometry in conjunction with anti-viral nucleoprotein antibody applied to collagenase-dispersed bronchial and lung parenchymal tissues, infection was localised to epithelial cells and macrophages. The vATPase inhibitor completely inhibited epithelial cell infection, virus shedding and the associated induction of pro-inflammatory cytokines/chemokines, whereas oseltamivir was only partially effective. This study, therefore, demonstrates the value of the human lung explant model for pre-clinical development of anti-viral therapeutics.