tbuckley/cabot-search huggingface dataset:
OP0006 Eular evidence-based recommendations on the management of medium to high dose systemic glucocorticoid therapy in rheumatic diseases
Authors: N. Duru, M.C. van der Goes, J.W. Jacobs, T. Andrews, M. Boers, F. Buttgereit, N. Caeyers, M. Cutolo, S. Halliday, J.A. da Silva, J.R. Kirwan, D. Ray, J. Rovensky, G. Severijns, R. Westhovens, J.W. Bijlsma
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To develop recommendations for the management of medium to high dose systemic glucocorticoid (GC) therapy in rheumatic diseases. <h3>Methods</h3> A multidisciplinary EULAR task force was formed, comprising of 8 rheumatologists, 1 endocrinologist, 1 rheumatologist–epidemiologist, 4 patients and 2 research fellows from 7 European countries. Each participant contributed 10 propositions describing key clinical points concerning the safe use of medium to high dose GCs. The final recommendations were developed using a Delphi consensus approach and the wording was improved by a native speaker. A systematic literature search of PUBMED, EMBASE and Cochrane Library was used to identify the best available research evidence to support each of the propositions. The strength of recommendation was given according to research evidence, clinical expertise and patient preference. <h3>Results</h3> The 10 final propositions included the topics patient education and informing general practitioners, preventive measures for osteoporosis, optimal GC starting dosages, risk-benefit ratio of GC treatment, GC sparing therapy, screening for co morbidity, and monitoring for adverse events. Most of the propositions were only indirectly supported by evidence from literature. The strength of each recommendation differed according to the level of evidence and clinical expertise, but was generally low because available literature on medium to high dose GC therapy was limited. <h3>Conclusions</h3> Ten recommendations for the management of medium to high dose systemic GC therapy in rheumatic diseases were formulated, and strengths of recommendation were provided. Robust evidence was often lacking and items in need for further research were defined. <h3>Disclosure of Interest</h3> None Declared
Could tumour necrosis factor blockers inhibit the progression of future structural damage in ankylosing spondylitis?
Authors: N Gaspersic, I Sersa, V Jevtic, M Tomsic, S Praprotnik
Journal: Annals of the Rheumatic Diseases (2007)

We read with great interest the editorial article by Schett et al ,1 where the authors discuss the role of tumour necrosis factor (TNF) α blockers in reducing new bone formation in ankylosing spondylitis (AS). They described the pathophysiological process, where TNF-α is a key proinflammatory cytokine, but is also a potent inhibitor of bone formation. Therefore, it is unlikely that TNF-α blockers are effective in reducing syndesmophyte growth and bridging. In other words, would TNF-α blockers inhibit the progression of structural damage even though they are proven to be very efficient in diminishing the clinical parameters of AS activity, acute-phase reactants and also active …
α-Tocopherol Induces Expression of Connective Tissue Growth Factor and Antagonizes Tumor Necrosis Factor-α–Mediated Downregulation in Human Smooth Muscle Cells
Authors: Luis Villacorta, Aurélio V. Graça-Souza, Roberta Ricciarelli, Jean-Marc Zingg, Angelo Azzi
Journal: Circulation Research (2003)

The effect of alpha-tocopherol treatment on gene expression in human aortic vascular smooth muscle cells was analyzed by gene expression arrays. The expression of the connective tissue growth factor (CTGF) gene was induced by alpha-tocopherol 1.8-fold in gene array experiments, and similar results were also obtained by RT-PCR (1.7-fold) and at the protein level (1.4-fold). The antioxidants beta-tocopherol and N-acetylcysteine did not induce CTGF gene expression, suggesting a nonantioxidant mechanism for alpha-tocopherol action. Protein kinase C (PKC) inhibition by alpha-tocopherol has been previously described. However, PKC downregulation did not prevent CTGF induction by alpha-tocopherol, and inhibition of PKC activity with several inhibitors did not increase its expression, suggesting an alternative pathway for the alpha-tocopherol effect. On the other hand, tumor necrosis factor-alpha reduced the expression of CTGF, an effect that was reversed by antioxidants. The data suggest that tumor necrosis factor-alpha inhibition of CTGF gene expression is prevented in an antioxidant-sensitive process and that alpha-tocopherol increases CTGF expression by a PKC-independent, nonantioxidant mechanism. Because CTGF stimulates the synthesis of extracellular matrix, the normalization of CTGF gene expression by alpha-tocopherol may accelerate wound repair and tissue regeneration during atherosclerosis.
Compensatory Renal Growth after Unilateral Nephrectomy in the Ovine Fetus
Authors: Rebecca Douglas-Denton, Karen M. Moritz, John F. Bertram, E. Marelyn Wintour
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Unilateral nephrectomy of the adult animal results in compensatory renal growth but does not involve formation of new nephrons. It is not clear whether compensatory growth can occur during the period of active nephrogenesis in utero and if so, whether more nephrons can be formed. Male ovine fetuses (n = 20) underwent unilateral nephrectomy (n = 10) or sham nephrectomy (n = 10) at 100 d of gestation (term, 150 d). After 27 to 34 d, ewes and fetuses were killed and the right kidney of each fetus was removed and weighed. The wet weight of the right kidney was greater in the unilaterally nephrectomized fetuses (16.3 ± 1.3 g compared with 12.2 ± 0.7 g; mean ± SEM, P < 0.05) as was the kidney to body weight ratio (5.2 ± 0.3 g/kg compared with 3.8 ± 0.2 g/kg; P < 0.001). Nephron number in the right kidney was estimated by an unbiased stereologic technique. There was a 45% increase in the number of nephrons in the kidneys from unilaterally nephrectomized animals compared with the kidneys from sham-operated animals (530,763 ± 37,136 nephrons in the unilaterally nephrectomized group compared with 365,672 ± 36,016 nephrons in the sham-operated group; P < 0.01). Mean glomerular volume was lower in the unilaterally nephrectomized group; however, total glomerular volume per kidney was not different between groups. This study demonstrates that there is a significant amount of compensatory growth and nephron endowment in a remaining kidney after unilateral nephrectomy during the period of active nephrogenesis in the sheep. This is the first time such events have been shown to occur in utero.
Hepatitis C virus replication and antibody responses toward specific hepatitis C virus proteins
Authors: Nobukazu Yuki, Norio Hayashi, Akinori Kasahara, Hideki Hagiwara, Kazuyoshi Ohkawa, Hideyuki Fusamoto, Takenobu Kamada
Journal: Hepatology (1994)

We assessed the correlation between hepatitis C virus replication and antibody responses toward hepatitis C virus core (C22-3), NS3 (C33C), NS4 (5-1-1 and C100-3) and NS5 proteins in 59 virus carriers. The concentration of serum hepatitis C virus RNA was determined by a competitive reverse transcription-polymerase chain reaction assay. All 50 patients with high viremic levels of > or = 10(6) copies/mL had antibodies to C22-3 and C33C. Antibodies to 5-1-1, C100-3 and NS5 proteins were detected less frequently (p < 0.01) in 72% (36 of 50), 78% (39 of 50) and 84% (32 of 38) of such patients, respectively. As for the nine patients with low viremic levels of < 10(6) copies/mL, antibodies to C22-3, C33C, 5-1-1 and NS5 proteins were detected in only one patient (11%), which was significantly less than the frequency for highly viremic patients (p < 0.01). Antibody to C100-3 was also found less frequently in only four patients (44%) (p < 0.05). Thus, only four (44%) of the nine low viremic patients tested positive for any antibody compared with all 50 highly viremic patients (p < 0.01). These results indicate that highly viremic carriers can be detected by the presence of hepatitis C virus antibodies, but a considerable proportion of low viremic carriers may not show any serological evidence of hepatitis C virus infection.
The early erosive vesicular stage of lipoid proteinosis: clinical and histopathological features
Authors: T.I. Kaya, U. Tursen, A. Kokturk, G. Ikizoglu, D. Dusmez
Journal: British Journal of Dermatology (2003)

Sir, Lipoid proteinosis (LP) is a rare autosomal recessively inherited disorder, which is characterized by the deposition of hyaline‐like material in the skin, mucous membranes and other tissues.1–3 The presenting manifestation of LP is hoarseness due to involvement of the larynx, which remains throughout life.4 The skin lesions usually appear during the first 2 years of life and occur in two overlapping stages. In the first stage, vesicles, bullae and haemorrhagic crusts appear spontaneously, and resolve with scarring. In the second stage, the skin becomes thickened and yellowish due to the deposits, and waxy papules and plaques develop predominantly on the face, scrotum and axillae.1–3, 5, 6 As detail about the evolution and histopathology of early lesions of LP is lacking, we describe the early erosive vesicular lesions in detail both clinically and histologically. A 4‐year‐old girl presented with eroded lesions. She had been followed up for 3 years following the diagnosis of LP. In this period of time the disease course showed fluctuations and she had some severe activations, especially in summer. A life‐threatening exacerbation of LP in this patient was reported previously.7 Several small haemorrhagic crusts, measuring 3–5 mm in diameter, had been observed at almost every visit.
Effectiveness of trans-arterial embolisation of liver neuroendocrine tumour metastases
Authors: D. S. Mandair, H. Bridgestock, T. Shah, K. Mangat, S. Olliff, B. Mahon, S. Hussain, P. Johnson, D. Palmer
Journal: Gut (2011)

<h3>Introduction</h3> Neuroendocrine tumours (NET) with liver metastases have a poor prognosis and are difficult to palliate. Transarterial embolisation (TAE) is increasingly used to improve symptoms and reduce tumour size. We sought to investigate the outcome of patients treated with TAE in the last 5 years and to look at long-term survival after TAE. <h3>Methods</h3> We identified all patients who received TAE within the last 5 years. Using a pre-developed proforma, we looked at case notes and e-records for the number of TAE treatments and checked for symptom improvement, biochemical and radiological response. We also looked at survival time defined as from time TAE to date of death or most recent follow-up. <h3>Results</h3> 22 NET patients received TAE (13F/9F) with mean age at diagnosis of 52.9 (1–71). 16 patients had carcinoid, 1 had NET of ovarian origin, 2 pancreatic, 1 stomach. Symptoms were: 15 diarrhoea, 17 flushing, 10 abdominal pain. All patients reported symptom improvement, mean no. of diarrhoea episodes fell from 6.1 (1–10) to 1.8 (0–5), mean no. flushing episodes fell 4.1 (1–10) to 0.6 (0–3). The decrease in 5HIAA in 14 patients was 47.1% (21.6–85.5). Radiological improvement was seen in 18 (81.9%) 1 year survival was 100%. Mean survival after TAE was 25.7 months (8–48). <h3>Conclusion</h3> TAE improves symptoms, and there is evidence of improvement in radiology and biochemistry.
Hypomagnesaemia due to malabsorption is not always responsive to oral magnesium oxide supplementation alone
Authors: R P Arasaradnam
Journal: Gut (2002)

Hypomagnesaemia due to malabsorption is not always responsive to oral magnesium oxide supplementation aloneWe read with interest the Gut File report by Dr Ross and colleagues of hypomagnesaemia due to malabsorption, eventually responding to oral magnesium oxide supplementation (Gut 2001;48:857-8).Our experience however has been different.For the past seven years we have managed a 65 year old woman with short bowel syndrome (right hemicolectomy for Duke's C colorectal carcinoma and thereafter a terminal ileal resection for abscess formation).High ileostomy output was initially difficult to manage (after excluding infection, secreting gut hormone tumours by normal hormone levels, and despite dietary and pharmacological modifications).Clinical signs of hypomagnesaemia and hypocalcaemia ensued.An initial trial with magnesium glycerophosphate (September 1992 to December 1993) was insufficient to sustain her serum magnesium levels requiring frequent "top ups" of intravenous magnesium. 1In December 1993, she was switched to magnesium oxide supplementation but despite this the frequency of intravenous magnesium "top ups" were not reduced.Compliance was not deemed to be an issue with our patient.Since then we have managed this woman while still taking magnesium oxide supplements with almost 3-6 monthly (fig 1) intravenous magnesium replacement through a peripheral line and have avoided insertion of a Hickman line and all its associated complications. 2 While we agree that a trial of magnesium oxide is prudent and until the pharmacokinetics are better understood, this preparation may not be sufficient, especially in patients with extensive resection of the small bowel, as demonstrated in our patient.
Long-term use of standardised ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial
Authors: Bruno Vellas, Nicola Coley, Pierre-Jean Ousset, Gilles Berrut, Jean-François Dartigues, Bruno Dubois, Hélène Grandjean, Florence Pasquier, François Piette, Philippe Robert, Jacques Touchon, Philippe Garnier, Hélène Mathiex-Fortunet, Sandrine Andrieu
Journal: The Lancet Neurology (2012)
Wall Tension Is a Potent Negative Regulator of In Vivo Thrombomodulin Expression
Authors: Jason L. Sperry, Clayton B. Deming, Ce Bian, Peter L. Walinsky, David A. Kass, Frank D. Kolodgie, Renu Virmani, Antony Y. Kim, Jeffrey J. Rade
Journal: Circulation Research (2003)

Thrombomodulin (TM), a key component of the anticoagulant protein C pathway, is a major contributor to vascular thromboresistance. We previously found that TM protein expression is dramatically reduced in autologous vein grafts during the first two weeks after implantation, coincident to a local inflammatory response, and remains suppressed for at least 6 weeks. To determine the proximate cause of TM loss, in vivo gene expression was quantified by real-time PCR. TM gene expression in vein grafts declined &gt;85% during the first postoperative week and remained suppressed &gt;55% at 6 weeks, accounting for the observed changes in protein expression. The effects of vein graft inflammation were evaluated in animals rendered leukopenic with vinblastine before graft implantation. Abrogating the local inflammatory response affected neither TM protein nor gene expression. To determine how hemodynamic forces might modulate TM expression, the surgical protocol was modified to alter blood flow and pressure-induced vessel distension. TM protein and gene expression did not correlate to changes in shear stress but highly correlated to changes in wall tension, both acutely and over time. We conclude that the primary stimulus for altered TM expression in vein grafts is the exposure to arterial pressure. Furthermore, these data identify strain as a novel and important pathway for in vivo TM gene regulation.
DNA Methylation as a Therapeutic Target in Cancer
Authors: Jean-Pierre J. Issa
Journal: Clinical Cancer Research (2007)

Abstract Targeting DNA methylation for cancer therapy has had a rocky history. The first reports on DNA methylation changes in cancer described global loss of methylation, which has been suggested to drive tumorigenesis through activation of oncogenic proteins or induction of chromosomal instability. In this context, reducing DNA methylation was viewed as a tumor-promoting event rather than a promising cancer therapy. The idea of inhibiting DNA methylation therapeutically emerged from subsequent studies showing that, in parallel to global decreases in methylation, several genes (including many critical to the tumor phenotype) displayed gains of methylation in their promoters during tumorigenesis, a process associated with epigenetic silencing of expression and loss of protein function. This led to revival of interest in drugs discovered decades ago to be potent inhibitors of DNA methyltransferases. These drugs have now been approved for clinical use in the United States in the treatment of myelodysplastic syndrome, thus opening the floodgate for a whole new approach to cancer therapy—epigenetic therapy.
Racial Differences in Surgical Evaluation, Treatment, and Outcome of Locoregional Esophageal Cancer: A Population-Based Analysis of Elderly Patients
Authors: Ewout W. Steyerberg, Craig C. Earle, Bridget A. Neville, Jane C. Weeks
Journal: Journal of Clinical Oncology (2005)

Purpose We investigated racial disparities in access to surgical evaluation, receipt of surgery, and survival among elderly patients with locoregional esophageal cancer. Methods We selected 2,946 white patients and 367 black patients who were older than 65 years and had clinically locoregional esophageal cancer in the Surveillance, Epidemiology, and End Results (SEER) registry (1991 to 1999). Treatment and outcome data were obtained from the linked SEER-Medicare databases. We used logistic regression analysis to estimate odds ratios (ORs) for being seen by a surgeon and for undergoing surgery. Cox proportional hazards analyses were performed to estimate hazard ratios (HRs) for survival adjusted for medical, nonmedical, and treatment characteristics. Results The rate of surgery for black patients was half that of white patients (25% v 46%; OR, 0.38; P &lt; .001), which was caused by both a lower rate of seeing a surgeon (70% v 78%; OR, 0.66; P &lt; .001) and a lower rate of surgery once seen (35% v 59%; OR, 0.38; P &lt; .001). These racial disparities were only partly explained by differences in patient and cancer characteristics, and not by nonmedical factors, such as socioeconomic status. The 2-year survival rate was lower for black patients (18% v 25%; HR, 1.18; P = .004), but this racial difference disappeared when corrected for treatment received (adjusted HR, 1.02; P = .80). Conclusion Underuse of potentially curative surgery is an important potential explanation for the poorer survival of black patients with locoregional esophageal cancer. Barriers to surgical evaluation and treatment need to be reduced, whether related to patient or healthcare system factors.
Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients
Authors: John P. Stein, Gary Lieskovsky, Richard Cote, Susan Groshen, An-Chen Feng, Stuart Boyd, Eila Skinner, Bernard Bochner, Duriayai Thangathurai, Maged Mikhail, Derek Raghavan, Donald G. Skinner
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node–negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node–negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node–negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P &lt; .001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45% , respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P &lt; .001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%) . The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.
Angiogenesis-independent cardioprotection in FGF-1 transgenic mice
Authors: A Buehler
Journal: Cardiovascular Research (2002)

This study was performed to evaluate the cardioprotective role of acidic fibroblast growth factor-1 (FGF-1) in transgenic mice with cardiac-specific overexpression of human FGF-1.Mice were subjected to coronary artery occlusion for 15-75 min with a continuously recorded 3-lead electrocardiogram (ECG). Infarct size was measured and ERK-1 and -2 activity was assessed by Western blot analysis. Creatine kinase and lactate dehydrogenase activity as marker for cell viability were measured in isolated ventricular myocytes subjected to simulated ischemia.Infarct development was markedly delayed in transgenics with first signs of myocardial infarction visible at 45 min after coronary artery occlusion compared to 15 min in wildtype. Maximal infarct size (60% of risk area) did not differ, but transgenics reached maximal infarction after 75 min compared to 45 min in wildtype animals. ECG revealed delayed Q-wave development and delayed ST-segment elevation in transgenics. Creatine kinase and lactate dehydrogenase release was significantly attenuated from isolated transgenic myocytes at 4 and 8 h after simulated ischemia. The delay in infarct development is partially due to a constitutive higher expression of the extracellular signal-regulated kinases ERK-1 and -2 in the myocardium of transgenics. Additionally, injection of the ERK-1/2 inhibitor UO126 decreased the cardioprotective effect of FGF-1.Cardiac specific overexpression of FGF-1 provides cardioprotection at the level of the cardiac myocyte, independent from angiogenesis, and at least partially mediated via activation of the mitogen activated protein kinase (MAP) ERK-1 and -2.
Casual Versus Heavy Use of Marijuana: A Redefinition of the Marijuana Problem
Authors: STEVEN M. MIRIN, LEO M. SHAPIRO, ROGER E. MEYER, RICHARD C. PILLARD, SEYMOUR FISHER
Journal: American Journal of Psychiatry (1971)

Twelve heavy and 12 casual users of marijuana generally found the experience to be a pleasurable one. In contrast to casual smokers, heavy users of marijuana tended to use multiple drugs and demonstrated a significant incidence of psychic dependence on marijuana. Their search for insight or for a meaningful affective experience colored their motivation for drug use. Experience with multiple drugs was also associated with poor social and work adjustment; goal-directed activity and ability to master new problems were diminished.