tbuckley/cabot-search huggingface dataset:
Guidelines for liver transplantation for patients with non-alcoholic steatohepatitis
Authors: Philip Noel Newsome, M E Allison, P A Andrews, G Auzinger, C P Day, J W Ferguson, P A Henriksen, S G Hubscher, H Manley, P J McKiernan, C Millson, D Mirza, J M Neuberger, J Oben, S Pollard, K J Simpson, D Thorburn, J W Tomlinson, J S Wyatt
Journal: Gut (2012)

Non-alcoholic steatohepatitis (NASH) is an increasing cause of liver disease necessitating liver transplantation.In patients with advanced NASH, there are often coexistent clinical issues that impact on the outcome of liver transplantation.There are no guidelines for the assessment and management of patients with NASH undergoing liver transplantation.A group was therefore invited by the Council of the British Transplant Society (BTS) to prepare guidelines for the management of NASH before and after liver transplantation.
Wound healing in the oral mucosa of the acutely insulin deprived rat
Authors: MARK JOLLY, NIGEL T. COOKE
Journal: British Journal of Dermatology (2006)

Standard wounds were produced on the palates of streptozotocin-induced ‘diabetic’ and normal rats. Healing, as estimated by the extent of epithelial migration after 24 h, was found to be identical in the two groups. The accumulation of glycogen and PAS positive, diastase-resistant material in the epithelium at the wound margins was far greater in the diabetic animals than in the controls. Indirect evidence is presented suggesting that the passage of glucose into epithelial cells is independent of insulin control. The investigation was planned to assess two aspects of wound healing in the mouths of ‘diabetic’ rats compared with normal controls: (1) The ability of epithelium to migrate across a wound. (2) The accumulation of glycogen in the epithelium at the wound margins.
Discoid lupus erythematosus with secondary amyloidosis
Authors: A.M. Powell, S. Albert, B. Bhogal, M.M. Black
Journal: British Journal of Dermatology (2005)

Secondary localized cutaneous amyloidosis is a clinically unapparent phenomenon associated with various cutaneous pathologies, usually tumours of epidermal origin. The amyloid is thought to be derived from keratinocytes.To characterize the amyloid deposition observed incidentally within lesional biopsies from three patients with discoid lupus erythematosus (DLE), and retrospectively to study the phenomenon within DLE skin samples.Localized amyloid deposition was observed in three cases of DLE by immunofluorescence studies, and these cases were further studied by histology and immunohistochemistry using a monoclonal anticytokeratin antibody. Retrospective histological review of DLE tissue specimens archived over 12 months was performed to look for evidence of previously undetected amyloid.Amyloid deposition was confirmed histologically in the three index cases by staining with Congo red and thioflavin T. Positive staining with an anticytokeratin antibody demonstrated the epidermal origin of the amyloid protein. Of the 18 archived cases reviewed amyloid was retrospectively detected in one sample.Secondary cutaneous amyloidosis of keratinocyte origin can be seen in DLE lesions. It may be a not infrequent occurrence and may remain under-reported. We discuss the possible role of disease chronicity and colloid body degradation in the pathogenesis of amyloidosis.
Treatment of chronic hepatitis C in HIV/HCV-coinfection with interferon α-2b+ full-course vs. 16-week delayed ribavirin
Authors: Norbert Bräu, Maribel Rodriguez-Torres, Dale Prokupek, Maurizio Bonacini, Carol A. Giffen, Jeffery J. Smith, Kevin R. Frost, Jay R. Kostman
Journal: Hepatology (2004)

Human immunodeficiency virus (HIV)-infected patients increasingly experience the consequences of chronic hepatitis C virus (HCV) coinfection. This trial randomized 107 patients coinfected with HIV and HCV to receive 48 weeks of interferon alfa-2b (IFN) 3 million units three times weekly plus either a full course of ribavirin (RBV) at 800 mg/day (group A; n = 53) or 16 weeks of placebo, followed by RBV (group B; n = 54). The primary endpoint of sustained viral response (SVR) rate (undetectable HCV RNA at posttreatment week 24) was not different between groups A (11.3%) and B (5.6%; P = .32). Within group A, the SVR rate was lower in genotype 1 (2.5%) than in genotypes 2 through 4 (41.7%; P = .002). Fifty-five patients discontinued therapy prematurely, mostly because of adverse events or patient decisions. At treatment week 12, the percentage of CD4+ cells rose in group A (+4.1%; P &lt; .001), but not in group B (−0.3%). A significant proportion (22%) of patients who were HIV viremic at baseline had undetectable HIV RNA at week 12. By week 16, the hemoglobin level decreased more in group A (−2,52 g/dL) than in group B (−1.02 g/dL; P &lt; .001). In group A, the hemoglobin decline was steeper in patients receiving zidovudine (azidothymidine [AZT], −3.64 g/dL vs. no AZT, −2.08 g/dL), and patients receiving zidovudine had more anemia-related RBV dose reductions (AZT, 60% vs. no AZT, 16%). In conclusion, HCV therapy with IFN plus RBV is relatively safe in patients coinfected with HIV and HCV, but frequent treatment discontinuations and anemia-related RBV dose reductions contribute to a poor SVR rate. Control of HIV infection improves rather than worsens during therapy. (Hepatology 2004;39:989-998.)
New Approaches in the Treatment of Hypertension
Authors: Suzanne Oparil, Roland E. Schmieder
Journal: Circulation Research (2015)

Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ damage and prevents cardiovascular disease outcomes. Despite a plethora of available treatment options, a substantial portion of the hypertensive population has uncontrolled blood pressure. The unmet need of controlling blood pressure in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. In this Compendium Review, we discuss new drugs and interventional treatments that are undergoing preclinical or clinical testing for hypertension treatment. New drug classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in phase II/III of development, while inhibitors of aminopeptidase A, dopamine β-hydroxylase, and the intestinal Na + /H + exchanger 3, agonists of components of the angiotensin-converting enzyme 2/angiotensin(1–7)/Mas receptor axis and vaccines directed toward angiotensin II and its type 1 receptor are in phase I or preclinical development. The two main interventional approaches, transcatheter renal denervation and baroreflex activation therapy, are used in clinical practice for severe treatment resistant hypertension in some countries. Renal denervation is also being evaluated for treatment of various comorbidities, eg, chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel interventional approaches in early development include carotid body ablation and arteriovenous fistula placement. Importantly, none of these novel drug or device treatments has been shown to prevent cardiovascular disease outcomes or death in hypertensive patients.
Rescue Screens with Secreted Proteins Reveal Compensatory Potential of Receptor Tyrosine Kinases in Driving Cancer Growth
Authors: Fred Harbinski, Vanessa J. Craig, Sneha Sanghavi, Douglas Jeffery, Lijuan Liu, Kelly Ann Sheppard, Sabrina Wagner, Christelle Stamm, Andreas Buness, Christian Chatenay-Rivauday, Yao Yao, Feng He, Chris X. Lu, Vito Guagnano, Thomas Metz, Peter M. Finan, Francesco Hofmann, William R. Sellers, Jeffrey A. Porter, Vic E. Myer, Diana Graus-Porta, Christopher J. Wilson, Alan Buckler, Ralph Tiedt
Journal: Cancer Discovery (2012)

The overall power of kinase inhibitors is substantially overshadowed by the acquisition of drug resistance. To address this issue, we systematically assessed the potential of secreted proteins to induce resistance to kinase inhibitors. To this end, we developed a high-throughput platform for screening a cDNA library encoding 3,432 secreted proteins in cellular assays. Using cancer cells originally dependent on either MET, FGFR2, or FGFR3, we observed a bypass of dependence through ligand-mediated activation of alternative receptor tyrosine kinases (RTK). Our findings indicate a broad and versatile potential for RTKs from the HER and FGFR families as well as MET to compensate for loss of each other. We further provide evidence that combined inhibition of simultaneously active RTKs can lead to an added anticancer effect.
Vitreous Levels of Vascular Cell Adhesion Molecule and Vascular Endothelial Growth Factor in Patients With Proliferative Diabetic Retinopathy
Authors: Cristina Hernández, Rosa Burgos, Ana Cantón, José García-Arumí, Rosa María Segura, Rafael Simó
Journal: Diabetes Care (2001)

OBJECTIVE—To evaluate the intravitreous concentration of vascular cell adhesion molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor (VEGF). RESEARCH DESIGN AND METHODS—Serum and vitreous fluid samples were obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with PDR and 20 nondiabetic control subjects with nonproliferative ocular disease. Both groups were matched by serum levels of VCAM-1 and VEGF. VCAM-1 and VEGF were determined by enzyme-linked immunosorbent assay. Statistics were determined using the Mann-Whitney U test and Spearman’s rank correlation test. RESULTS—The intravitreous concentration of VCAM-1 was significantly elevated in diabetic patients with PDR compared with control subjects (26 ng/ml [19–118] vs. 22 ng/ml [20–47], P &amp;lt; 0.05). A direct correlation between VCAM-1 and total vitreous proteins was detected in diabetic patients (r = 0.64, P = 0.003), but not in control subjects. After adjusting for total intravitreous proteins, VCAM-1 was significantly lower in diabetic patients with PDR than in control subjects (8.2 ng/ml [4–31.4] vs. 43.1 ng/ml [9.7–100], P &amp;lt; 0.001). Intravitreous VEGF concentrations were higher in patients with PDR than in control subjects in absolute terms (1.34 ng/ml [0.16–6.22] vs. 0.009 ng/ml [0.009–0.044], P &amp;lt; 0.0001) and after correcting for total vitreal proteins (0.33 ng/ml [0.01–2.3] vs. 0.013 ng/ml [0.003–0.035], P = 0.0001). Finally, the vitreous ratio of VCAM-1 to proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic patients (r = 0.74, P = 0.001) and control subjects (r = 0.84, P = 0.005). CONCLUSIONS—The low proportion of VCAM-1 in relation to total vitreal proteins observed in diabetic patients with PDR suggests that VCAM-1 is quenched by diabetic retina. In addition, the direct correlation detected between VCAM-1 and VEGF suggests that cellular adhesion and neovascularization may be linked processes.
Empagliflozin Reduces Blood Pressure in Patients With Type 2 Diabetes and Hypertension
Authors: Ilkka Tikkanen, Kirsi Narko, Cordula Zeller, Alexandra Green, Afshin Salsali, Uli C. Broedl, Hans J. Woerle
Journal: Diabetes Care (2014)

To investigate the efficacy, safety, and tolerability of empagliflozin in patients with type 2 diabetes and hypertension.Patients (N = 825) with type 2 diabetes and hypertension (mean seated systolic blood pressure [SBP] 130-159 mmHg and diastolic blood pressure [DBP] 80-99 mmHg) were randomized (double blind) to 10 mg or 25 mg empagliflozin or placebo once daily for 12 weeks.At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h SBP (ambulatory blood pressure monitoring [ABPM]) was -3.44 mmHg (95% CI -4.78, -2.09) with 10 mg empagliflozin and -4.16 mmHg (-5.50, -2.83) with 25 mg empagliflozin (both P < 0.001). At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h DBP (ABPM) was -1.36 mmHg (95% CI -2.15, -0.56) with 10 mg empagliflozin and -1.72 mmHg (95% CI -2.51, -0.93) with 25 mg empagliflozin (both P < 0.001). Changes in office BP were consistent with ABPM. Adjusted mean difference versus placebo in change from baseline in HbA1c at week 12 was -0.62% (95% CI -0.72, -0.52) (-6.8 mmol/mol [95% CI -7.9, -5.7]) with 10 mg empagliflozin and -0.65% (95% CI -0.75, -0.55) (-7.1 mmol/mol [95% CI -8.2, -6.0]) with 25 mg empagliflozin (both P < 0.001). Empagliflozin was well tolerated. One patient on placebo and one patient on 10 mg empagliflozin reported events consistent with volume depletion.Empagliflozin was associated with significant and clinically meaningful reductions in BP and HbA1c versus placebo and was well tolerated in patients with type 2 diabetes and hypertension.
Combination of MRI-detected bone marrow oedema with 2010 rheumatoid arthritis classification criteria improves the diagnostic probability of early rheumatoid arthritis
Authors: Mami Tamai, Junko Kita, Yoshikazu Nakashima, Takahisa Suzuki, Yoshiro Horai, Akitomo Okada, Tomohiro Koga, Shin-ya Kawashiri, Naoki Iwamoto, Kunihiro Ichinose, Kazuhiko Arima, Satoshi Yamasaki, Hideki Nakamura, Tomoki Origuchi, Masataka Uetani, Aya Fukushima, Kiyoshi Aoyagi, Katsumi Eguchi, Atsushi Kawakami
Journal: Annals of the Rheumatic Diseases (2014)

Efficient methods for distinguishing rheumatoid arthritis (RA) at an earlier phase from other diseases are strongly desired since early therapeutic intervention improves clinical and radiographic outcomes of RA.1–4 The clinical 2010 RA classification criteria was established based upon the consensus that RA is an inflammatory disease that develops persistent and/or erosive arthritis.2 ,3 Our series of studies as well as the article describing European League Against Rheumatism recommendations for the use of imaging for the clinical management of RA mention that MRI can be used to improve the certainty of a diagnosis of RA above clinical criteria.5 ,6 The present study was undertaken to investigate whether MRI findings of wrist and finger joints improve the diagnostic performance of 2010 RA classification criteria. One hundred sixty-six patients with early arthritis, who do not fulfil the 1987 RA criteria or other international criteria for rheumatic disease at entry …
Cancer prevention in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013
Authors: Arb-aroon Lertkhachonsuk, Cheng Har Yip, Thiravud Khuhaprema, Ding-Shinn Chen, Martyn Plummer, Sun Ha Jee, Masakazu Toi, Sarikapan Wilailak
Journal: The Lancet Oncology (2013)
Mast Cell Basic Fibroblast Growth Factor in Silicosis
Authors: HIRONOBU HAMADA, VAL VALLYATHAN, CARLYNE D. COOL, ELIZABETH BARKER, YOSHIKAZU INOUE, LEE S. NEWMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To investigate the role of mast cells (MC) and their fibrogenic growth factors in silicosis, we performed quantitative immunohistochemistry for MC tryptase and for basic fibroblast growth factor (bFGF) in lung tissue from silicotic and control subjects. Anti-bFGF antibody was bound to lung MC, basement membrane, endothelial cells, and smooth-muscle cells. Morphometric analysis revealed that the volume density (Vv) of MC was increased in silicotic lung and that the Vv of bFGF-positive (bFGF+) cells was significantly higher than normal in silicotic lung. Most MC contained bFGF ( ρ = 0.88, p < 0.001). The Vv of collagen/reticulin fibers was increased in silicosis and correlated with the Vv of bFGF+ cells ( ρ = 0.81, p < 0.001). Immature silicotic nodules contained bFGF+ MC throughout the loose array of collagen/reticulin fibers. In large, mature nodules, the density of collagen/reticulin fibers was higher, and bFGF+ MC were found only in the nodule periphery. Because of this circumferential MC alignment in silicotic nodules, we observed a negative correlation between the Vv of bFGF+ MC and the density of collagen/reticulin fibers in silicotic nodules ( ρ = − 0.80, p < 0.001) and between the Vv of all other nodule-associated cells and the density of collagen/reticulin fibers in the hypocellular nodule centers ( ρ = − 0.84, p < 0.001). We conclude that MC that produce bFGF may play an important role in the development of silicosis.
IMPACT OF ALCOHOL INTAKE ON THROMBOEMBOLIC EVENTS FOLLOWING CATHETER ABLATION FOR ATRIAL FIBRILLATION
Authors: Sanghamitra Mohanty, Prasant Mohanty, Chintan Trivedi, Luigi Di Biase, Rong Bai, Pasquale Santangeli, John Burkhardt, Rodney Horton, Joe Gallinghouse, Javier Sanchez, Jason Zagrodzky, Shane Bailey, Patrick Hranitzky, Amin Al-Ahmad, Richard Hongo, Richard Hongo, Salwa Beheiry, Andrea Natale
Journal: Journal of the American College of Cardiology (2014)
Electron microscopy of rejected human liver allografts
Authors: Robert H. Fennell, John M. Vierling
Journal: Hepatology (1985)

Recognition by biopsy of liver allograft rejection has been less successful than diagnosis of rejection of cardiac and kidney allografts. In a study of 138 failed liver allografts, we recognized damage to small interlobular bile ducts by lymphocytes as the most useful indicator of the presence of rejection. This is a report of the electron microscopic features of three patients with unequivocal allograft rejection. Lymphocytes and occasional granulocytes penetrated the epithelia of interlobular bile ducts. Ducts with diameters of 30 to 60 μ M were preferentially affected but ducts up to 120 μ M were also occasionally involved. Point contacts between infiltrating inflammatory cells and bile duct epithelial cells were observed occasionally. Degenerative changes of bile duct epithelial cells were conspicuous and involved nuclei and cellular organelles. Degeneration was often accompanied by aggregation of dense bundles of filaments in the cytoplasm. In severely affected ducts, epithelial cell disintegration was noted. In all involved bile ducts, the basement membrane was markedly thickened. Hepatocytes were well–preserved but contained lipid vacuoles, pigment granules, and blunted canalicular microvilli. The similarity between these observations and those seen in primary biliary cirrhosis and chronic graft–versus–host disease is striking.
Challenging cytomegalovirus data in glioblastoma
Authors: Wolfgang Wick, Antje Wick, Michael Platten
Journal: Neuro-Oncology (2013)

Dear Editor,

The trial of add-on valganciclovir in glioblastoma therapy published by the authors did not provide evidence for activity of the anti-cytomegalovirus therapy.1 Why do the presented data2 differ substantially from the data of the controlled trial?

The authors created a long-term benefiting subgroup of patients mixed from both arms of the original trial and patients from compassionate use. This cohort was heterogeneous and not protected from selection bias. By selecting for patients with valganciclovir exposure of >6 months, it is deliberately enriched for favorable outcome. A comparison with a cohort with dismal outcome3,4 and unknown prognostic factors is not justified.5

How was low- or high-grade cytomegalovirus infection assessed? Expression of the immediate early antigen2 does not prove an infection; high- and low-grade “infection” is not defined. The status of benefiting patients is unclear. Is there a valganciclovir effect in the tissue at recurrence, especially considering potential off-target effects? With the limitations outlined, this report is undue publicity for a concept that so far has failed in a controlled trial.
A Single Breath Method to Assess the Relative Contribution of Central and Peripheral Airways to Overall Exhaled Breath Temperature
Authors: Todor A. Popov, Diana Hristova, Tanya Kralimarkova, Dimitar Popov, Andrey Popov, Simeon Uzunov, Vasil Dimitrov, Lawrence M. DuBuske
Journal: Journal of Allergy and Clinical Immunology (2015)
Differences Between Black and White Women With Breast Cancer in Time From Symptom Recognition to Medical Consultation
Authors: R. J. Coates, D. D. Bransfield, M. Wesley, B. Hankey, J. W. Eley, R. S. Greenberg, D. Flanders, C. P. Hunter, B. K. Edwards, M. Forman, V. W. Chen, P. Reynolds, P. Boyd, D. Austin, H. Muss, R. S. Blacklow
Journal: JNCI Journal of the National Cancer Institute (1992)

Studies in the United States have reported that Black women have higher fatality rates than White women following a diagnosis of breast cancer and are more likely to be diagnosed with late-stage cancers.To evaluate reasons for these racial differences, we explored the difference between Black and White women in the length of time from symptom recognition to initial medical consultation. We also evaluated the extent to which other factors related to the length of this interval might contribute to any observed racial difference.As part of a collaborative study of differences in the survival rates of Black patients and White patients with cancer, we interviewed a sample of 410 Black women and 325 White women from Atlanta, New Orleans, and San Francisco/Oakland who were newly diagnosed in 1985 or 1986 with invasive breast cancer. Retrospective data were collected on symptoms, dates of symptom recognition and initial medical consultation, and several other factors which may affect the interval between symptom recognition and medical consultation. Data were analyzed as if from a follow-up study, using product limit procedures and proportional hazards regression.At diagnosis, Black women with breast cancer were two times more likely to have stage IV breast cancer and one and one-half times more likely to have stage III breast cancer than White women with breast cancer and were only approximately one-half as likely to have stage I breast cancer. Similarly, Black women were almost twice as likely as White women to have tumors that were larger than 5 cm or tumors that had extensions to the chest wall or skin at presentation. However, the average rate at which Black women with breast cancer obtained an initial medical consultation lagged behind that for White women by only a slight but statistically significant difference (15%). The median time between symptom recognition and medical consultation was slightly longer for Black women (16 days) than for White women (14 days) (P = .06). Adjustment for other characteristics predictive of the length of this interval had little effect on racial differences. The racial differences tended to vary somewhat by age and metropolitan area, suggesting that the results may not apply equally to all demographic subgroups and regions in the United States.This small difference in the time from symptom recognition to medical consultation is unlikely to account for the large racial differences in survival rates and in stage of disease at the time of diagnosis.
ADAM-9 is a novel mediator of tenascin-C-stimulated invasiveness of brain tumor–initiating cells
Authors: Susobhan Sarkar, Franz J. Zemp, Donna Senger, Stephen M. Robbins, V. Wee Yong
Journal: Neuro-Oncology (2015)

BackgroundTenascin-C (TNC), an extracellular matrix protein overexpressed in malignant gliomas, stimulates invasion of conventional glioma cell lines (U251, U87). However, there is a dearth of such information on glioma stemlike cells. Here, we have addressed whether and how TNC may regulate the invasiveness of brain tumor–initiating cells (BTICs) that give rise to glioma progenies.
Richard Francis Pearson
Authors: Mary Pearson
Journal: BMJ (2006)

Former pathologist and general practitioner North London (b 1920; q Cambridge/University College Hospital, London, 1947), d 5 July 2006.

Richard Pearson was registrar in pathology at the Royal Hampshire County Hospital, Winchester, from 1952 to 1954 and at the Radcliffe Infirmary, Oxford, from 1954 to 1956. After postgraduate studies he became a general practitioner, ending his career in a practice in Holloway Road, North London, in 1982. He leaves a wife, Mary, and three children.