tbuckley/cabot-search huggingface dataset:
SP0149 Endothelial Damage in Anca-Associated Vasculitis (AAV)
Authors: C. Kallenberg
Journal: Annals of the Rheumatic Diseases (2015)

The AAV are characterized by necrotizing vasculitis of small and medium-sized blood vessels in conjunction with the presence of autantibodies directed to proteinase-3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The kidneys are frequently involved with fibrinoid necrosis and paucity of immune deposits. In vitro studies show that primed neutrophils can be activated by ANCA to produce reactive oxygen species and release lytic enzymes. Together with monolayers of endothelial cells this leads to endothelial damage. In an in vitro flow system ANCA stabilize adhesion and promote migration of neutrophils on endothelial cells. In vivo models of MPO-ANCA vasculitis show the pathogenic potential of MPO-ANCA to induce necrotizing glomerulonephritis and pulmonary capillaritis. Also in vivo MPO-ANCA augments leukocyte-microvascular interactions resulting in microvascular injury. In these models as well as in human AAV the complement system plays a major role, in particular the alternative pathway of complement activation and the strong chemo-attractive degranulation product C5a. Also PR3-ANCA appears able, in an animal model, to induce necrotizing vasculitis, although less clear than MPO-ANCA. Cellular immunity may be involved as well in AAV, particularly in PR3-ANCA associated disease. CD4-positive T-cells expressing NKG2D are increased in PR3-ANCA disease in conjunction with increased levels of IL-15, a pro-inflammatory cytokine that, amongst others, induces expression of NKG2D on CD4-positive T-cells enabling these cells to interact with MIC-A/MIC-B on endothelial cells resulting in damage of the latter cells. In conclusion, ANCA are able to induce endothelial damage in AAV but an additional role of T-cells is suggested as well. Ref.: Kallenberg et al, Am J Kidney Dis 2013;62:1176-87 <h3>Disclosure of Interest</h3> None declared
A Phase I Study Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Activity of the Hepcidin Antagonist PRS-080#022. Results from a Randomized, Placebo Controlled, Double-Blind Study Following Single Administration to Healthy Subjectsa
Authors: Ulrich Moebius, Werner Feuerer, Edgar Fenzl, Rachel van Swelm, Dorine W. Swinkels, Andreas Hohlbaum
Journal: Blood (2015)
Mebendazole induces apoptosis in distinct melanoma subtypes via Bcl-2 dependent mechanism
Authors: N. A. Doudican, A. Rodriguez, A. C. Pavlick, R. L. Shapiro, I. Osman, S. J. Orlow
Journal: Journal of Clinical Oncology (2008)

20008 Background: In a screen of 2,000 natural products and marketed drugs, we identified 10 compounds that inhibit growth of chemoresistant, metastatic melanoma cell lines, yet are largely non-toxic to spontaneously immortalized, non-tumorigenic melanocytes. Strikingly, 4 of the 10 compounds belong to the benzimidazole class of structurally related, tubulin-disrupting drugs. Based upon its history of safe oral use and favorable pharmacokinetic profile, mebendazole was prioritized to characterize its mechanism of growth inhibition in several cell lines representing a spectrum of melanoma biological subtypes. Methods: Growth inhibition was assessed by MTT assay in a panel of cell lines: melanocytes (melan-a), nodular melanoma (WM278, WM39), superficial spreading melanoma (WM35, WM1552C), and metastatic melanoma (M-14, SK-Mel-19, Yusac-2). Effects of mebendazole on tubulin structure were analyzed by immunofluorescence microscopy. The apoptotic response of mebendazole-treated cells was characterized by annexin V staining, western blotting, and immunoprecipitation. Bcl-2 protein levels were reduced by siRNA techniques. Results: Mebendazole inhibits growth and induces apoptosis in metastatic and superficial spreading melanoma cells with an IC50 of 0.32μM. However, mebendazole fails to significantly inhibit growth in melanocytes and nodular melanoma cells which display an IC50 of 6-fold higher (2.1 μM). After 18 hours of mebendazole treatment, microtubule structure is disrupted in all cell lines. The apoptosis regulatory protein Bcl-2, a key mediator of microtubule damage, is rapidly phosphorylated in mebendazole-sensitive melanoma cells, but not in resistant cells. Phosphorylation of Bcl-2 reduces its interaction with pro-apoptotic Bax by 46%, thereby promoting apoptosis in mebendazole-sensitive melanoma cells. Mebendazole-resistant cells can be sensitized through reduction of Bcl-2 protein levels. Conclusions: Our data identify Bcl-2 as a critical mediator of the differential cellular response to mebendazole treatment in various biological subtypes of melanoma. Our results also suggest that nodular melanoma may represent a distinct, chemoresistant biological subtype of melanoma. No significant financial relationships to disclose.
Thoracoscopic Lobectomy Produces Long-Term Survival Similar to That with Open Lobectomy in Cases of Non–Small Cell Lung Carcinoma: A Propensity-Matched Analysis Using a Population-Based Cancer Registry
Authors: Bing-Yen Wang, Jing-Yang Huang, Ching-Hsiung Lin, Jiunn-Liang Ko, Chen-Te Chou, Yu-Chung Wu, Sheng-Hao Lin, Yung-Po Liaw
Journal: Journal of Thoracic Oncology (2016)
SAT0553 Anti-Interleukin-1 Therapies and Pregnancy Outcome: an International Cohort
Authors: T. Youngstein, T. Lane, D. Rowczenio, H. Ozdogan, S. Ugurlu, P. Hoffmann, S. Riminton, A.P. Headley, J. Ryan, L. Harty, J. Roesler, N. Blank, C. Michler, P.N. Hawkins, H.J. Lachmann
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Women with auto-inflammatory disease on long-term IL-1 blockade increasingly ask about the safety and outcomes of pregnancy but little data is available. <h3>Objectives</h3> To analyse the outcomes of pregnancy in women on long-term anti-IL-1 therapy. <h3>Methods</h3> We obtained the clinical details and pregnancy outcomes of women exposed to anti-IL-1 agents in 7 countries. <h3>Results</h3> We identified 13 women aged 16 – 38 years, with a total of 15 pregnancies exposed to IL-1 blockade. 9 women had CAPS, 2 Adult Onset Stills Disease, 1 TRAPS, 1 FMF and 1 Idiopathic Pericarditis. 4 received canakinumab, 2 stopped treatment after conception, 2 switched to anakinra. 13 foetuses were exposed to anakinra. 3 women started anakinra during pregnancy, 3 stopped treatment following conception. All pregnancies were completed. The shortest term was 35 weeks. APGAR score was 9-10 at 10 mins in all cases. Birth weight range 2.02-3.94 kilos. 5 were breast fed for 3 – 40 weeks. Age at last contact was from 1 week – 8 years. Only 1 child had developmental abnormalities; growth hormone deficiency due to ectopic neurohypophysis and unilateral renal agenesis. We also identified 11 children with paternal exposure to anti-IL-1 therapies, all developmentally normal to date. <h3>Conclusions</h3> These successful pregnancies significantly extend our knowledge of pregnancy outcomes in parents receiving anti-IL-1 therapies. A co-author has previously reported the intrauterine death of a foetus (of a twin pregnancy) with bilateral renal agenesis exposed to anakinra. The surviving twin is developmentally normal. Although numbers are small the data provide reassurance to physicians caring for these patients. The relationship between IL-1 inhibition and renal agenesis requires further study. Each pregnancy should be assessed and risks and benefits of maintaining therapy individually discussed with potential parents. <h3>Disclosure of Interest</h3> None declared
Is there a relationship between eating disorder and affective disorder? New evidence from sleep recordings
Authors: J L Katz, A Kuperberg, C P Pollack, B T Walsh, B Zumoff, H Weiner
Journal: American Journal of Psychiatry (1984)

There is evidence that patients with anorexia nervosa (particularly those who also have bulimia) and patients with affective disorder share many features. The authors present sleep polygraph data from 20 young women with anorexia nervosa (17 also bulimic) and 10 age-matched normal women. Their urinary free cortisol levels were determined, and the subjects with eating disorders were also rated for depression. The findings suggest the existence of a subgroup of patients who show sleep abnormalities, in addition to clinical and possibly endocrine abnormalities, that indicate concurrent affective disorder. The authors present several models that could account for this relationship.
SAT0022 Leptin as Prognostic Marker in Osteoarthritis Patients
Authors: L. Seewordova, B. Zavodovsky, J. Polyakova, Y. Akhverdyan, V. Kravtsov, E. Simakova
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> In recent years, much attention is paid to the study of the relationship between degenerative joint diseases and adipokines. It is supposed that imbalance of adipokines may influence on the course of osteoarthritis (OA). <h3>Objectives</h3> To study the clinical and pathogenetic significance of leptin determination in serum of OA patients. <h3>Methods</h3> We observed 130 OA patients aged 34 to 78 years (78 women and 52 men). The control group consisted of 25 women and 20 men aged 26 to 58 years with no complaints of pain in the joints, and without clinical manifestations of OA. Groups did not differ by sex and age (t =0,54, p&gt;0,05; t =0,29, p&gt;0,05, respectively). To assess the state of the joints we used WOMAC, Lequesne, Dreiser functional indexes. Intensity of pain, duration and severity of stiffness, functional capacity of the patient were assessed by visual analogue scale (VAS). The indices were evaluated by questionnaire responses with gradation on a point system, the results were taken into account by the amount of indicators. All patients underwent X-ray and ultrasound examination of the joints. Leptin level in serum were determined by ELISA test (BioVendor, cat No. CAN-L-4260) before and after treatment.In recent years, much attention is paid to the study of the relationship between degenerative joint diseases and adipokines. It is supposed that imbalance of adipokines may influence on the course of osteoarthritis (OA). <h3>Results</h3> Leptin level in serum of healthy men was 3,8±0,21 ng/ml, in healthy women 7,4±0,37 ng/ml (here and further M±m). Gender differences were statistically significant (p&lt;0,001, t=7,91). Elevated leptin level was detected in 33 OA female patients (25.4%). Leptin in women with OA was 14,4±0,32 ng/ml. Elevated leptin levels was detected in nine men with OA (6.9%). Leptin levels in men with OA was 6,2±0,25 ng/ml. As men as woman with OA and high levels of leptin (more than 11.1 ng/ml and 5.6 ng/ml respectively) was more likely to have Heberden and Bouchard nodes, secondary synovitis, duration of disease more than 10 years, higher radiographic stage and functional impairment of the joints. We revealed statistically significant relationship between leptin levels in serum of patients with OA and concentration of C-reactive protein, erythrocyte sedimentation rate, WOMAC and Lequesne indexes. <h3>Conclusions</h3> Thus, we revealed elevated leptin level in serum of 42 patients with OA (32.3%). As men and women with OA with increased leptin levels had severe form of the disease. Thus leptin may have important significance in pathogenesis of OA. <h3>Disclosure of Interest</h3> None declared
Expression of epiregulin and amphiregulin and K-RAS mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab (Erbitux ®)
Authors: Shirin Khambata Ford, Christopher Garrett, Edwin Clark, Mark Basik, Christopher Harbison, Tai Wong, Xin Huang, Shujian Wu, Chris Takimoto, Andrew Godwin, Manuel Hidalgo, Jose Baselga, Neal Meropol, David Mauro
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

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The anti-epidermal growth factor receptor (EGFR) antibody cetuximab shows activity in multiple epithelial tumor types; however, responses are seen in only a subset of patients. Whereas EGFR protein levels and EGFR mutations do not correlate with response to cetuximab in colorectal cancer (CRC), it is unclear whether an increased number of gene copies for EGFR may be predictive. This study was conducted to identify predictive markers that can be used for the selection of patients most likely to respond to cetuximab treatment. One hundred eleven patients with metastatic colorectal cancer were enrolled in a clinical trial of cetuximab monotherapy. Transcriptional profiling was conducted on RNA from pre-treatment metastatic site biopsies obtained from all patients to identify genes whose expression correlates with best clinical responses. EGFR , B-RAF and K-RAS mutation analyses and EGFR gene copy number analyses were performed on DNA from the pre-treatment biopsies. Analysis of gene expression profiles of pre-treatment tumor biopsies showed that patients with tumors that express high levels of the EGFR ligands epiregulin and amphiregulin are more likely to have disease control (complete or partial response, stable disease) with cetuximab therapy ( EREG p = 1.5e-05; AREG p = 2.5e-05). In addition, patients whose tumors do not have K-RAS mutations have a significantly higher disease control rate than those with K-RAS mutations (p= 0.0003). Furthermore, patients with tumors that have high gene expression levels of EREG or AREG were found to have a significantly longer progression-free survival (PFS) time ( EREG Log-Rank p = 0.0002, HR 0.47, 95% CI 0.24-0.64 and median PFS 103.5 days vs 57 days; AREG Log-Rank p < 0.0001, HR 0.44, 95% CI 0.20-0.57 and median PFS 115.5 days vs 57 days). In conclusion, patients with tumors that have high gene expression levels of epiregulin and amphiregulin and patients with wild type K-RAS were identified as those most likely to have disease control on treatment with cetuximab. The identified predictive markers should be developed further to select patients for cetuximab therapy.
AB1114 Prevalence of HLA-B27 in a Cohort of Transplant of a University Hospital in Colombia:
Authors: C. Villota, O. Roa, M. Díaz, J. Gutiérrez, D.G. Fernández-Avila
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The Human Leukocyte Antigen HLA B 27; is a class I antigen from MHC that is strongly associated with ankylosing spondylitis (AS) and other spondyloarthritis (SPA), with positivities for HLA-B27 in the population from 80 to 95% worldwide. The prevalence of HLA-B27 in the general population varies by geographic area, with ratios ranging between 2-4% in African/African American compared to 8% in Caucasian populations <sup>1</sup> <h3>Objectives</h3> To determine the proportion of positive HLA B 27 in the population of transplanted and donors treated at the San Ignacio University Hospital; their clinical characteristics and relationship to the presence of spondyloarthritis. <h3>Methods</h3> It was performed a descriptive cross-sectional study of 465 individuals typed for HLA of a cohort of transplants in a university hospital in Colombia including donors and receivers. Designing a database in Excel to include data relevant to the study. The search was performed in hospital records and telephone contact for family not treated at the hospital to extract information. <h3>Results</h3> 465 individuals with an age range between 10 and 80 years with a mean of 44.9 years (SD: 14.04); finding 21 positive cases for HLA B 27 indicating a prevalence of 4.5% positivity for HLA-B27 in this population. At evaluating the behavior by gender, a proportion of HLA B 27 of 6,5% was found in the group of men (n=261; 56.1%) compared with 2.0% in women. Of the 21 patients positive for HLA B 27 it was found that 4 of them (19%) had joint pain of small and large joints so they were referred to evaluation by the Rheumatology service at Hospital where the presence of spondyloarthritis or other autoinmune disease was discarted. <h3>Conclusions</h3> It has been described in the literature the prevalence of HLA B 27 in ranges from 2% to 8%, according to the region evaluated; it was found in our study a ratio of 4.5% of the total population and comparing by gender a higher proportion in males (6.5% compared with 2% in women). Spondylitis or other autoimmune disease were not detected in any patient of the series evaluated in our study; although 19% of the populatinon with positive HLA B 27 was referred to rheumatology for articular symptoms discarding the presence of it. San Ignacio Universitary Hospital is a reference center of the city to perform transplants, so it is important to emphasize the prevalence found in our study that fits within international parameters reported. <h3>Disclosure of Interest</h3> None declared
Soundings: CAMRA shy?
Authors: James Owen Drife
Journal: BMJ (2004)

Gynaecologists are expected to enjoy gin and tonic and know about wine. Most of us manage the first without difficulty (off duty, of course) and bluff our way through the second. I have colleagues who really can tell their Pouilly Fuisse from their Pouilly Fume, and jolly impressive they are too. It is like watching a table conjurer—entertaining but faintly irritating.
PTH-285 Anastomotic leaks after malignant colorectal surgery: a single centre experience
Authors: MA Gok, KI Malik, K Amin, A Jeff, UA Khan
Journal: Gut (2015)

<h3>Introduction</h3> Anastomotic leakage is a serious adverse event and is reported to occur in &lt;10% of restorative colorectal surgery. Anastomotic leakage and its subsequent management may adversely affect long term survival. The aim of the study is to assess the management of malignant colorectal anastomotic leaks at a single centre. <h3>Method</h3> This is a retrospective study carried out at Macclesfield District General Hospital since 2008. Descriptive demography and post-operative features were collected for all malignant colorectal resections. <h3>Results</h3> See Table 1 <h3>Conclusion</h3> Anastomotic leaks occurred in 5.1% of malignant colorectal rectal resections, 65.1% in males, 67.5% occurred in the left colon, whereas surgical intervention was carried out in 51.2% cases. Despite a prolonged hospital stay (p &lt; 0.05), there was no difference in patient survival (Logrank p = NS). <h3>Disclosure of interest</h3> None Declared.
Patient safety
Authors: Des Spence
Journal: BMJ (2007)

A colleague is stabbed a few miles from where I work. Thankfully she is alive and I hope that she will make a full recovery. Our thoughts are with her family and friends. I feel sadness and anger in equal measure that these things should happen. Then predictably and selfishly I fret about my own vulnerability, and “what ifs” pace the floor of my consciousness. Irrespective of where you work, general practice is harsher than many people believe—a small firm for printing antibiotic prescriptions and sick notes before golf it is certainly not.

We live in a polarised world in which medicine is often the only interface with society's forgotten people. Family medicine is the lowest common denominator where all of society's woes are legally dumped. Amid the debris there are medical emergencies and diagnoses to be made. I like it, but it is not for everyone.

The inner cities in particular are a distillation of debilitating ailments, heaped together in highrise concrete cages of social housing. Addiction, poverty, unemployment, and chronic mental problems—the most vulnerable people are left exposed to the elements. Violence is endemic in this environment and is seen a legitimate form of communication.

GPs are literally at the frontline. I have been threatened, had a hammer pulled on me, been shown knives, and been chased by a gang while on a house call. Instinctively and constantly I scan for those non-verbal cues of aggression—the narrowing of the eyes, the intake of breath, and the change in body stance. Long ago I learnt never to raise my voice and to steer well clear of the rocks of direct confrontation. My experience is common to many GPs.

Our practice's panic button system is only ever activated by children while I am distracted by their ill parents. The only response is a stampede of panic in the reception area. Pressing the panic button is perhaps the last thing I would consider, as this merely ups the stakes. Courses in dealing with violence and abusive patients are a health and safety tickbox affair, unrealistic and offered by those who have no insight into our working environment.

So how to protect us? Tougher sentencing may feel like more justice but would not deter attacks. More security may make GPs feel safer but would not prevent the determined nor the random attacker, and we would lose our greatest strength—accessibility. As doctors we have to accept the unacceptable—that we live in a violent society. No well chosen soundbite or magic pills can heal our violently sick society. We are so obsessed with the unimportant, and we are blind to the fundamental similarities and collective values that we share. The solution is simple but difficult—to put others before oneself. This is the only way to re-establish the protection that is community.
Biological correlates of mental activity studied with PET
Authors: N D Volkow, L R Tancredi
Journal: American Journal of Psychiatry (1991)

The development of newer imaging techniques that allow direct investigation of the function of the human brain under normal and pathological conditions has affected the way in which we conceive of the mind/brain relation. In this report the authors use examples from findings obtained with positron emission tomography (PET) to illustrate the highly interactive organization of the brain. Because operations in the brain require the participation of various brain areas, a model that does not require a one-to-one relationship between the physical and mental, but rather allows an association between clusters of physical processes and one or more mental phenomena, may reflect better the relation between physical brain phenomena and mental activities.
PTU-197 To bowel prep or not to bowel prep?: a 5 year retrospective study
Authors: M Elsharif, R James, A Singh
Journal: Gut (2015)

<h3>Introduction</h3> A number of factors including gender, smoking, radiotherapy, and length of surgery have traditionally been associated with a higher risk of developing anastamotic leak. However, recent studies have indicated that unprepared bowel does not increase the incidence of anastamotic leaks. The aim of this study was to see if the introduction of a ‘no bowel preparation’policy in our unit impacted on leak rates. <h3>Method</h3> A retrospective review of all cases undergoing colorectal resections between May 2006 and May 2011 were included in this study. An Enhanced Recovery Programme was introduced in April 2010 for all colorectal patients and as part of this left sided colorectal resections received a phosphate enema instead of a full mechanical bowel preparation. Right hemicolectomy patients did not receive any bowel preparation throughout the study period. <h3>Results</h3> 514 colorectal resections were performed during the study period. Of these, 30 patients had an anastomotic leak, 5.9% were following right hemicolectomy, 1.9% following left hemicolectomy or sigmoid colectomy and 11.7% following anterior resection. Following the introduction of ‘no bowel preparation’ policy, the leak rate was unchanged for left hemicolectomy and sigmoid colectomy. However, we found a marked increase in leak rates following anterior resections from 6.6% to 20% (p value = 0.023). A defunctioning ileostomy appeared to reduce the effects of the anastomotic leak and all of these (n = 5) were managed conservatively with no mortality compared to those without ileostomy, the majority of whom required a laparotomy and had a mortality rate of 16.6%. The overall elective mortality was 5.8%. <h3>Conclusion</h3> The Introduction of a no bowel preparation policy resulted in a significant increase in anastomotic leak rates following anterior resections. Therefore, we recommend the use of full mechanical bowel preparation for rectal surgery. Use of a covering ileostomy should be considered in high risk patients. <h3>Disclosure of interest</h3> None Declared.