tbuckley/cabot-search huggingface dataset:
GMSC endorses registrars' recommendations on summative assessment Juniors' contracts will have local flexibility Waiting list figures published GMSC wants discussions over violence against doctors Doctors given guide on assessing mental capacity Expert group will look at transplanting animal organs to humans
Authors: L. Beecham
Journal: BMJ (1996)

# GMSC endorses registrars' recommendations on summative assessment {#article-title-2}

The General Medical Services Committee has endorsed the recommendations of its registrars subcommittee on summative assessment and agreed that unless and until the regulations are amended trainers should be informed by the summative assessment process but should not be bound by it.

At the end of last year the GMSC, the Royal College of General Practitioners, the Joint Committee on Postgraduate Training for General Practice, and the Committee of Regional Advisers in General Practice in England agreed a way forward for summative assessment. This proposes that, although not legally mandatory, the process should be introduced during 1996. The general practice registrars subcommittee, however, remains concerned about the flawed method of introducing the scheme, including its introduction mid-way through many registrars' training, the undue haste of implementation, and the poor quality of advice given to registrars.

The GMSC has endorsed the subcommittee's wish that no registrar or trainer should have their accreditation or training state questioned if they decide not to participate in summative assessment. It agrees that universal regulatory summative assessment should be postponed until 1997 at the earliest, subject to satisfactory validation and the necessary regulation changes.

The subcommittee insists that all components of the summative assessment package should be implemented at the same time in every region and that all doctors entering the hospital component of vocational training should have clear and comprehensive information about …
Genetic Linkage of a Polymorphism in the Type II Procollagen Gene (COL2A1) to Primary Osteoarthritis Associated with Mild Chondrodysplasia
Authors: Robert G. Knowlton, Paul L. Katzenstein, Roland W. Moskowitz, Eric J. Weaver, Charles J. Malemud, Mini N. Pathria, Sergio A. Jimenez, Darwin J. Prockop
Journal: New England Journal of Medicine (1990)

OSTEOARTHRITIS is a clinically heterogeneous disease characterized by a progressive degeneration of the articular cartilages of both weight-bearing and non-weight-bearing joints.1 Some forms of the disease are due to environmental or systemic events, such as trauma, infections, and metabolic disorders, but most patients have primary osteoarthritis for which there is no identifiable cause. At the same time, the inheritance of the disease in some families is well documented.2 , 3 We analyzed restriction-fragmentlength polymorphisms (RFLPs) to show that one allele of the gene for Type II procollagen (COL2A1), the precursor of the major protein of cartilage,4 , 5 is inherited with a precocious form . . .
AB0123 Antibodies to Porphyromonas Gingivalis in Patients with Rheumatoid Arthritis
Authors: D.T. Archimandriti, G.A. Somarakis, T.E. Markatseli, M.P. Migkos, D. Lappin, P.V. Voulgari, A.A. Drosos
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is characterized by antibodies to citrullinated protein antigens (ACPA). Porphyromonas gingivalis (PG) is a major pathogen in periodontitis which possesses a citrullinated enzyme, peptidylarginine deiminase with the potential to generate antigens leading the autoimmune response. <h3>Objectives</h3> The aim of the study was to examine the existence of antibodies to PG in patients with RA. <h3>Methods</h3> Antibodies to PG were measured using ELISA as previously described.<sup>1</sup> Thus, Dynatech Immunolon IB microtitre plates (ThermoFisher) were coated overnight with PG strain W83 fixed in formalin cells. Correlations between PG antibody values and clinical parameters were performed using IBM SPSS statistics 20 Non-parametric Mann Whitney U test and Spearman correlation test were used for statistical analysis. <h3>Results</h3> Thirty-six RA patients (10 men and 26 women) were studied. Sera from individuals with periodontitis and healthy subjects were used as controls. The mean age and disease duration of RA patients were 66.76±13.66 years and 20.06±11.01 years respectively. All the RA patients had ACPA while 30/36 (83.3%) had positive rheumatoid factor (RF). The mean DAS28 score was 4.58±1.37 and the mean HAQ score was 0.7±0.64. Twenty five out of 36 (69.4%) had anti-PG antibodies. There was no statistical difference between RA patients with and without anti-PG concerning DAS28 and HAQ scores. Thirteen out of 25 RA patients with anti-PG had lung involvement, 11/25 had sicca syndrome, 9/25 had rheumatoid nodules, 3/25 had Raynaud9s and 4/25 had peripheral neuropathy. Patients with anti-PG had statistically more lung involvement (p&lt;0.009) and more sicca syndrome (p&lt;0.039). All the individuals with active periodontitis had positive anti-PG antibodies and negative ACPA and negative RF. <h3>Conclusions</h3> RA patients with anti-PG had more frequently extraarticular manifestations especially lung involvement and sicca syndrome. The immune response to PG supports the hypothesis that a bacterial infection might contribute to the broken tolerance in RA. <h3>References</h3> Lappin DF, Apatzidou D, Quirke AM, Oliver-Bell J, Butcher JP, Kinane DF, Riggio MP, Venables P, McInnes IB, Culshaw S. Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres. J Clin Periodontol. 2013 Oct;40(10):907-15. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5077
Abstract SY26-02: Targeting lipogenesis in EGFR-activated glioblastomas
Authors: Paul S. Mischel
Journal: Cancer Research (2011)

Abstract Cancer is a disease characterized by mutational activation and enhanced dependence on oncogenic signal transduction cascades. Cancer is also characterized by major shifts in cellular metabolism, including glucose utilization and uptake, energy metabolism and lipogenesis. The molecularly circuitry linking oncogenic signal transduction cascades and therapeutically targetable metabolic circuits is only beginning to be understood. This talk will focus on glioblastoma, the most common malignant primary brain tumor of adults and one of the most lethal of all cancers. Glioblastoma is characterized by nearly universal PI3K pathway hyperactivation, including EGFR amplification and mutation. Studies leading to molecular dissection of the signaling networks linking mutated EGFR with enhanced lipogenesis will be discussed, including integration of studies performed in cell lines, in vivo models and tumor tissue from patients treated with targeted inhibitors. The talk will describe the identification of a therapeutically targetable, novel EGFR/PI3K/SREBP-1 dependent prosurvival metabolic signaling pathway, as well as recent studies linking this pathway to altered fatty acid synthesis and cholesterol homeostasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY26-02. doi:10.1158/1538-7445.AM2011-SY26-02
Endoscopic Ligation plus Argon Plasma Coagulation for Esophageal Variceal Bleeding in Non-alcoholic Patients with Cirrhosis
Authors: YS Sigaeva
Journal: Endoscopy (2011)

Background and Study Aims: Esophageal variceal bleeding (EVB) is a severe complication of cirrhosis leading to significant morbidity and mortality. The aim of this study was to determine whether endoscopic variceal ligation (EVL) and argon plasma coagulation (APC) are effective procedures for initial hemostasis, rate of rebleeding, mortality and reducing variceal recurrence.
The False-Positive Finding of Left Pulmonary Kimura Disease on 18F-FDG PET/CT
Authors: Dong Li, Ya-Jun Li, Feng-Hua Zhan, Chun-Jiang Dang
Journal: Clinical Nuclear Medicine (2013)

Kimura disease is a chronic inflammatory disorder that occurs mainly in Asians. We present a patient with pulmonary Kimura disease assessed by whole-body 18F-FDG PET/CT examination and proved by pathologic findings. Chest x-ray detected left pulmonary hilum enlargement in a 49-year-old Chinese man. CT showed a soft tissue mass with punctate calcifications in the left pulmonary hilum, which obviously and homogeneously accumulated tracer on FDG PET. Histopathology findings showed characteristic of Kimura disease. Kimura disease should be included in the differential diagnosis of a pulmonary hilar tumor.
Cellular Sensitivity to Collagen in Thromboangiitis Obliterans
Authors: Raphael Adar, Moshe Z. Papa, Zamir Halpern, Mark Mozes, Shmuel Shoshan, Batya Sofer, Heidy Zinger, Molly Dayan, Edna Mozes
Journal: New England Journal of Medicine (1983)

We studied 39 patients with thromboangiitis obliterans to determine their cellular and humoral immune responses to native human collagen Type I and Type III, which are constituents of blood vessels. Cell-mediated sensitivity to these collagens was measured by an antigen-sensitive thymidine-incorporation assay. The mean stimulation index--the ratio of thymidine incorporation in the presence of antigen to that in its absence--with both Type I and Type III collagens used as antigens was significantly higher in patients with thromboangiitis obliterans than in patients with arteriosclerosis obliterans or in healthy male controls. Lymphocytes from 77 per cent of the patients with thromboangiitis obliterans exhibited cellular sensitivity to human Type I or Type III collagens (or both). Furthermore, in 17 of 39 serum samples from the patients with thromboangiitis obliterans a low but significant level of anticollagen antibody activity was detected, whereas there was no antibody activity in serum samples from controls. These results suggest that there is a distinct etiologic factor in this disease and also raise the possibility of differentiating between thromboangiitis obliterans and arteriosclerosis obliterans by immunologic means.
Transgastric and percutaneous transhepatic rendezvous maneuver for the treatment of difficult intrahepatic stones
Authors: Erik-Sebastian Fuchs, Bettina Hartmann, Ralf Jakobs
Journal: Endoscopy (2014)

Interventional therapy of hepatic biliary stones is challenging if the patient has been subject to previous gastric or biliary surgery. Several variations have been reported for the endoscopic and endoscopic ultrasound (EUS)-guided transgastric approach to the biliary tract as salvage techniques after the failure of peroral endoscopic drainage [1]. A success rate of 89 % has been reported, with complications seen in 12.5 % of cases [2] [3].
Abstract 4751: Peptide vaccine induces apoptosis of antigen-specific CD8+ T cells
Authors: Muraoka Daisuke, Hiroyoshi Nishikawa, Takuma Kato, Linan Wang, Yuka Maeda, Naozumi Harada, Takuro Noguchi, Yutaka Kawakami, Hiroshi Shiku
Journal: Cancer Research (2010)

Abstract CD8+ cytotoxic T lymphocytes (CTL) play a critical role in anti-tumor immunity. Although multiple trials of cancer vaccines, particularly using short peptides recognized by CD8+ T cells, have resulted in the development of measurable immune responses, only a minority of patients has experienced clinical benefit such as tumor regression. On the other hand, accumulating data show that peptide immunization induces either tolerance or activation of peptide-specific T cells depending on doses, routes and frequency of peptide administration. In some experiments, vaccination with peptides recognized by CD8+ T cells caused enhanced tumor outgrowth associated with peptide-induced tolerance. However, the detailed mechanism(s) involved in this unfavorable immune response by peptide vaccinations has not been determined. In the present study, we analyzed NY-ESO-1 peptide vaccinations using a new tumor model of BALB/c transplanted tumors expressing NY-ESO-1, which is a cancer/testis (CT) antigen discovered by SEREX (serological identification of antigens by recombinant expression cloning) using the serum of an esophageal cancer patient. Whereas peptide immunization with an H2-Dd-restricted CTL epitope derived from NY-ESO-1 (NY-ESO-1 p81-88) induced NY-ESO-181–88-specific CD8+ T cells in draining lymph nodes and spleens, tumor growth was significantly enhanced. Single cell analysis of specific CD8+ T cells revealed that peptide immunization induced apoptosis of &amp;gt; 80% of NY-ESO-181–88-specific CD8+ T cells at tumor sites and repetitive immunization further diminished the number of specific CD8+ T cells. This phenomenon was associated with elevated surface expression of Fas and PD-1. When peptide vaccination was combined with an adjuvant, a TLR9 ligand CpG, the elevated Fas and PD-1 expression and apoptosis induction were not observed, and resulted in strong tumor growth inhibition. These augmented anti-tumor responses were correlated with CpG-induced DC maturation, as CpG-matured DCs, but not immature DCs could reduced Fas and PD-1 expression on the surface of antigen-specific CD8+ T cells. Taken together, selection of appropriate adjuvants is essential for development of effective cancer vaccines, with protection of effector T cells from peptide vaccine-induced apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4751.
SAT0129 Whole Body DXA Bone Tissue and Cardiovascular Risk in Rheumatoid Arthritis
Authors: C. Popescu, V. BOJINCĂ, D. OPRIŞ, R. Ionescu
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Atherosclerosis and osteoporosis share an age-independent bidirectional correlation.[1] Rheumatoid arthritis (RA) represents a risk factor for both conditions. So far, only hip and lumbar spine indices were used in clinical studies.[2] <h3>Objectives</h3> The study aims to evaluate the connection between the estimated cardiovascular risk (CVR) and the loss of whole body bone tissue in RA patients. <h3>Methods</h3> Prospective cross-sectional design; female in-patients with RA or without autoimmune diseases; bone tissue was measured using whole body dual X-ray absorptiometry (wbDXA); CVR was estimated using SCORE charts and PROCAM applications. <h3>Results</h3> There were 75 RA women and 66 normal women of similar age. The wbDXA bone indices correlate significantly, negatively and age-independently with the estimated CVR. The whole body bone percent (wbBP) was a significant predictor of estimated CVR, explaining 26% of SCORE variation along with low density lipoprotein (p&lt;0.001) and 49.7% of PROCAM variation along with glycemia and menopause duration (p&lt;0.001). Although obese patients had less bone relative to body composition (wbBP), in terms of absolute quantity their bone content was significantly higher than that of non-obese patients (p&lt;0.001). <h3>Conclusions</h3> Female patients with RA and female patients with cardiovascular morbidity have a lower whole body bone percent. Obese female individuals have higher whole body bone mass than non-obese patients. The study suggests a common pathogenic process involving whole body bone tissue and atherosclerosis. <h3>References</h3> Farhat GN, Cauley JA. The link between osteoporosis and cardiovascular disease. Clin Cases Miner Bone Metab 2008; 5(1): 19-34. Shibuya K, Hagino H, Morio Y et al., Cross-sectional and longitudinal study of osteoporosis in patients with rheumatoid arthritis. Clin Rheumatol 2002; 21(2): 150-8. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3671
Phase I studies of anti-ENPP3 antibody drug conjugates (ADCs) in advanced refractory renal cell carcinomas (RRCC).
Authors: John A. Thompson, Robert Motzer, Ana M. Molina, Toni K. Choueiri, Elisabeth I. Heath, Christian K. Kollmannsberger, Bruce G. Redman, Randeep S. Sangha, D. Scott Ernst, Roberto Pili, Anna Butturini, Aya Wiseman, Fabio Trave, Banmeet Anand, Yao Huang, Leonard M. Reyno
Journal: Journal of Clinical Oncology (2015)

2503 Background: ENPP3 is expressed in greater than 90% of clear cell (CC) and 70% of papillary (PAP) RCC and represents an interesting target in this disease. Hybridoma-derived AGS-16M8F and CHO-derived AGS-16C3F are fully human IgG2k monoclonal antibodies (mAbs), conjugated to microtubule disrupting agent MMAF via a plasma-stable linker, which bind to ENPP3. The 2 ADCs have similar pharmacokinetic and toxicologic profiles. Methods: Two phase I studies were conducted sequentially to test safety, PK, and antitumor activity (RECIST v1.1) of AGS-16M8F and AGS-16C3F in CC and PAP RRCC (median prior systemic therapies = 3). ADCs were given q3w until PD or unacceptable toxicity. Results: AGS-16M8F and AGS-16C3F studies treated 26 and 34 subjects in dose range 0.6 - 4.8 and 1.8 - 4.8 mg/kg, respectively. Fatigue was the most common adverse event (AE) in both studies. In the AGS-16M8F study, maximum tolerated dose (MTD) was not reached, but 3/8 subjects at 4.8 mg/kg discontinued for ocular toxicity (OT). OTs were most commonly reversible keratopathy. In the AGS-16C3F study, the initial dose of 4.8 mg/kg exceeded MTD; 2/2 subjects had dose-limiting toxicities (DLTs); 1 was grade 4 OT. OTs were also observed at lower doses, usually after 2 doses. This led to a successive de-escalation to 3.6, 2.7, and 1.8 mg/kg. Thrombocytopenia (TCP) was frequently reported but a DLT in only 1 subject at 3.6 mg/kg (AGS-16C3F). PK of both ADCs was comparable. Serum concentrations decreased multi-exponentially; exposure was dose proportional. In both studies, the mean terminal half-life was approx. 7-8 days for the intact drug and approx. 4 days for MMAF. Conclusions: Both ADCs tested had associated OT but it was more prominent with AGS-16C3F. However AGS-16C3F was well tolerated at 1.8 mg/kg and showed antitumor activity as evidenced by median disease control of 23+ weeks and durable PR in 2/10 of CC and 1/3 PAP RRCC. A phase II study is planned with AGS-16C3F at 1.8 mg/kg. Clinical trial information: NCT01672775. AGS-16M8F AGS-16C3F AGS-16C3F All All 1.8 mg/kg N 26 34 13 Median prior systemic therapies 3 (0-8) 3 (0-9) 3 (2-7) Relevant AEs (All / ≥ grade 3) OT 8 / 1 29 / 10 12 / 2 TCP 8 / 3 11 / 6 2 / 1 Fatigue/asthenia 12 / 1 26 / 6 12 / 3 Median wks on therapy 12 (1-80) 9 (1-66) 18 (9-48+) ORR 1 PR, 9 SD 3 PR, 17 SD 3 PR, 9 SD Median Disease Control (PR+SD, wks) 21 (12-80) 18 (6 - 66) 23+ (9- 48+)
Idiopathic Biliary Ductopenia in Adults without Symptoms of Liver Disease
Authors: Alberto Moreno, Vicente Vicente Carreño, Ana Cano, Cecilia González
Journal: New England Journal of Medicine (1997)

Idiopathic adulthood ductopenia is a severe cholestatic liver disease of unknown cause characterized by loss of the interlobular bile ducts in more than 50 percent of the portal tracts. In most reported cases, cirrhosis and liver failure develop.
Successful treatment of a large choledochal inflammatory polyp in a patient with cutaneous neurofibromatosis
Authors: Fatih Karaahmet, Sahin Coban, Omer Basar, Osman Yuksel
Journal: Endoscopy (2014)

A 48-year-old woman was admitted to the hospital with a 1-month history of dyspeptic complaints and right upper quadrant pain. She had a 20-year history of cutaneous neurofibromatosis ([Fig. 1 a]). Vital signs were within normal limits. Physical examination revealed a distended abdomen with no palpable mass.
NONINVASIVE LOCALIZATION OF SEIZURE FOCI - CORRELATION OF SURFACE EEG. TC-99M HMPAO SCINTIGRAPHY.
Authors: B. Engelstad, K. Laxer, H. Dickson, K. Cooper, J. Huberty, O. White
Journal: Clinical Nuclear Medicine (1987)

Engelstad, B. CT AND MR; Laxer, K.; Dickson, H.; Cooper, K.; Huberty, J.; White, O. Author Information
728 DISCORDANCE BETWEEN LIVER BIOPSY AND FIBROTEST IN ASSESSING LIVER FIBROSIS IN CHRONIC HEPATITIS B
Authors: M.S. Park, B.K. Kim, J.Y. Cheong, D.J. Kim, J.Y. Park, D.Y. Kim, S.H. Ahn, K.-H. Han, C.Y. Chon, S.U. Kim
Journal: Journal of Hepatology (2013)
SPECT/CT Imaging of Retroperitoneal Extraskeletal Osteosarcoma
Authors: Bin Hu, Yan Liu, Lixia Cheng, Wei Li, Xiaozheng Cao
Journal: Clinical Nuclear Medicine (2013)

The condition of a 52-year-old man was diagnosed with unresectable retroperitoneal extraskeletal osteosarcoma. SPECT/CT demonstrated a retroperitoneal extraskeletal osteosarcoma adjacent to the right upper ureter with large calcifications and increased 99mTc-MDP accumulation. Multiple hepatic capsular, renal fascial, and peritoneal metastases were noted. Four months later, multiple peritoneal metastases were noted at the second-look surgery. A histopathologic examination confirmed osteosarcoma.
Abstract 2109: Activation of multiple cellular stresses by the NO generating antineoplastic agent JS-K.
Authors: Imit Kaur, Moises Terrazas, Ken M. Kosak, Paul J. Shami
Journal: Cancer Research (2013)

Abstract The NO prodrug O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate or JS-K is active against acute myeloid leukemia (AML), multiple myeloma, hepatocellular carcinoma, prostate cancer, glioma and non-small lung cancer. We have developed a nanoscale micelle formulation for JS-K (P123/JS-K) using Pluronic® P123 polymers to stabilize and solubilize the drug. In the present study, the mechanism of action of JS-K was investigated. We speculated that, being a NO-releasing drug, JS-K causes nitrosative/oxidative stress. We therefore hypothesized that JS-K causes multiple stress responses that ultimately trigger apoptosis in the cell. We also hypothesized that JS-K affects the “intrinsic component” (defined as cell cycle, survival and stress pathways in the cell) of leukemic cells. In this work, using human myeloid leukemia HL-60 cells, we studied the effect of JS-K on two major cellular stresses, namely ER stress and nitrosative/oxidative stress. On treating HL-60 cells with 5μM JS-K formulated in DMSO (JS-K) or P123/JS-K for 4-8 hours, activation of both GRP-78 and CHOP (markers of ER stress) was observed using western blot analysis. ER stress could also be triggered by phosphorylation of JNK protein. Again, using western blot analysis, JNK phosphorylation was observed when HL60 cells were treated with JS-K or P123/JS-K for 4-6 hours. Oxidative stress was studied by quantifying intracellular levels of reactive oxygen/reactive nitrogen species (ROS/RNS) using the ROS/RNS sensitive fluorophore 5-(and-6)-chloromethyl-2’-7’-dichlorodihydrofluorescein diacetate. Treatment of HL-60 cells with 5μM of JS-K or P123/JS-K for 30, 60 or 120 minutes lead to increased levels of ROS/RNS. These experiments show that JS-K activates the intrinsic component of cell death by producing ER stress and oxidative stress. JS-K is at an advanced stage of pre-clinical development. Its novel and multiple mechanisms of action make it an attractive therapy for the treatment of AML and other malignancies. Citation Format: Imit Kaur, Moises Terrazas, Ken M. Kosak, Paul J. Shami. Activation of multiple cellular stresses by the NO generating antineoplastic agent JS-K. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2109. doi:10.1158/1538-7445.AM2013-2109