tbuckley/cabot-search huggingface dataset:
A6.09 Nk cells as biosensors for responsiveness to etanercept in ankylosing spondylitis (Morbus Bechterew)
Authors: U Schulte-Wrede, T Sörensen, JR Grün, U Syrbe, J Sieper, T Häupl, A Radbruch, A Grützkau
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Therapeutic targeting of TNF is approved to be highly effective in ankylosing spondylitis patients who fail to respond to conventional anti-inflammatory drugs. However, only around two-thirds of anti-TNFa treated AS patients show an adequate response according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) independently from the biological used. Therefore, there is an urgent need for biomarkers which would aid in treatment choice and treatment outcome separating responders and non-responders to such expensive therapies and to avoid side effects induced by inefficient drugs. Thus, the aim of this study was to identify cell-based biosensors in peripheral blood by multiparametric flow cytometry that can be used for an early treatment stratification of AS patients. <h3>Methods</h3> A multiparametric flow cytometric approach, including 50 monoclonal antibodies combined to 10 staining cocktails, was applied to identify useful baseline predictors in 38 AS patients with active disease before treatment with the TNF blocker Adalimumab, Etanercept, Golimumab or Infliximab. BASDAI response criteria were used to determine therapeutic success after 1 to 6 month. Automated clustering of flow data, correlation analysis and receiver operator characteristics were accomplished to appoint auspicious candidate phenotypes. <h3>Results</h3> Out of multiple potentially significant parameters, which are involved both in acquired and adaptive immunity the NK cell compartment revealed most promising subsets that are predictive for a successful therapy response to Etanercept in AS. Correlation analyses showed an error-free classification of responders and non-responders for Etanercept but not for Adalimumab-treated patients. <h3>Conclusions</h3> This is the first study demonstrating that the composition of the NK cell compartment has predictive power with respect to classify AS patients whether they will respond or fail to the treatment by Etanercept. These results also shed some new light on the mode of action comparing TNF-alpha neutralising antibodies and soluble TNF alpha-receptors. In conclusion, these data make it reasonable to assume that monitoring of particular NK cell phenotypes can be used in terms of a companion diagnostic to realise the concept of personalised medicine in the field of rheumatology.
Aldosterone Synthesis in Salt-Wasting Congenital Adrenal Hyperplasia with Complete Absence of Adrenal 21-Hydroxylase
Authors: Phyllis W. Speiser, Levon Agdere, Hajime Ueshiba, Perrin C. White, Maria I. New
Journal: New England Journal of Medicine (1991)

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a disorder of cortisol and aldosterone biosynthesis that results from mutations in the CYP21 gene encoding the adrenal 21-hydroxylase P-450c21. It can cause severe salt wasting in newborns that requires long-term treatment with glucocorticoids and mineralocorticoids. We describe a spontaneous partial recovery from this disorder in a 19-year-old woman who had discontinued treatment.
290β-3 adrenoreceptors protect from hypertrophic remodelling through nitric oxide synthase &amp; AMP-activated protein kinase dependent signaling pathways
Authors: E Dubois-Deruy, R Gelinas, J Hammond, K Gotz, V Nikolaev, B Manoury, H Esfahani, C Dessy, L Bertrand, JL Balligand
Journal: Cardiovascular Research (2014)

Background: Moderate overexpression of β3AR in cardiomyocytes attenuates hypertrophic remodeling in hearts after neurohormonal stress, without impairement of cardiac function. Methods: Functional analyses were carried out in wild type (WT) and heterozygote transgenic mice with cardiac myocyte-specific over-expression of human β3AR (hβ3TG) treated for 10 days with isoproterenol (Iso: 30mg/kg/day), angiotensin II (AngII: 2mg/kg/day), with/without L-NAME (2mg/mL). In vitro hypertrophic responses to phenylephrine (PE) were analyzed in neonatal rat ventricular myocytes (NRVM) infected with a recombinant adenovirus expressing the human β3AR (AdVhβ3). Results: We further dissected the underlying signaling in isolated cardiomyocytes and tissues from hβ3TG mice. Cell fractionation and Proximity Ligation Assay experiments revealed co- localization of β3AR with constitutive NOS isoforms, eNOS and nNOS and with caveolin-3 in lipid rafts/caveolae, which was unperturbed in hypertrophic myocytes. Adult cardiomyocytes from hβ3TG mice co-expressing β3AR with the cGMP-sensitive FRET sensor, redcGES-DE5 exhibited higher constitutive, ODQ-sensitive cGMP production compared with WT, whereas the opposite was observed in cells from sensor-expressing β3AR KO mice. Non-specific NOS inhibition (L-NAME) abrogated the β3AR-mediated protection from hypertrophic remodeling under low dose Iso in vivo and in NRVM. Interestingly, we observed a L-NAME independent increase in protein synthesis in control cells (152±16 (veh)vs230±27 (PE); p<0.01), but not in the AdVhβ3 infected NRVM (130±11 (veh) vs 103±12 (PE); p=ns). As AMP-activated protein kinase (AMPK) is a known inhibitor of cardiac hypertrophy and protein synthesis, we examined its activation by β3AR. First, we observed a colocalization of AMPK with β3AR, eNOS and cav-3. P-Thr162-AMPK was decreased by the PE (0.5 ± 0.1), but restored in β3AR expressing cells (0.9 ± 0.3 of ctl; P<0.05). siRNA targeting of AMPK also partly abrogated the anti-hypertrophic effect of β3AR in response to PE. Moreover, AMPK is also an inducer of autophagy. In NRVM, β3AR overexpression restored autophagy that was decreased by PE in ctl cells in vitro, as measured by LC3-II/LC3-I and p62 abundance; likewise autophagy was restored in hβ3TG mice after TAC compared with WT (LC3II/I ratio: 0.5±0.1 (WT), 1.3±0.3 (hβ3TG), p<0.05). Conclusions: We conclude that β3AR is part of a caveolar signalosome involving nNOS, eNOS and AMPK in cardiomyocytes, from which it activates both cGMP/PKG and AMPK-dependent pathways to prevent hypertrophic remodeling and maintain autophagy in the face of neurohormonal stress.
THE EFFECTS OF 180° ACQUISITION ON THALLIUM-201 MYOCARDIAL PERFUSION TOMOGRAPHIC STUDIES.
Authors: R. L. Eisner, D. Nowak, A. Mulick, W. Fajman, E. McClees, J. A. Malko, H. Berger
Journal: Clinical Nuclear Medicine (1984)

Eisner, R. L.; Nowak, D.; Mulick, A.; Fajman, W.; McClees, E.; Malko, J. A.; Berger, H. Author Information
AB0375 Success rates of assisted reproductive techniques in patients with inflammatory rheumatic disease
Authors: E. Trujillo, E. Padrόn, M. Flores, J.M. Viotti, C. de la Rosa, J.J. Bethencourt, S. Bustabad
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Women with chronic inflammatory diseases increasingly solicit assisted reproductive techniques (ART) due to infertility, but there is little information about success rates of these techniques in such patients. <h3>Objectives</h3> To analyze pregnancy rates after artificial insemination (AI) and <i>in vitro</i> fertilization-intracytoplasmic sperm injection (IVF-ICSI) in patients with inflammatory rheumatic disease. <h3>Methods</h3> Patients: 17 women with inflammatory rheumatic disease: 6 rheumatoid arthritis, 2 spondyloarthritis, 8 systemic lupus erythematosus and 1 Behcet disease, monitored by our department.Mean age 33 years (range 24-40) and 6±2 years from diagnosis of disease, currently inactive or with low clinical activity.Due to infertility, these patients underwent ART: 7 with AI and 9 with IVF-ICSI. Method: We analyzed success rates of both techniques according to patient age, one of the factors that most influence outcome. <h3>Results</h3> Pregnancy rate per cycle of AI was 12% with a cumulative rate of 32% after four cycles.In patients over 35 years the pregnancy rate per cycle was reduced to 6%. The pregnancy rate per attempt using IVF-ICSI was 21% with a cumulative rate of 34% after three attempts. In women over 35 years the success rate was 19%. <h3>Conclusions</h3> The pregnancy rates of both AI and IVF-ICSI were lower in this series of patients with inflammatory rheumatic disease than those reported for the general population. <h3>Disclosure of Interest</h3> None Declared
Longitudinal Assessment of Neurocognitive Function after Coronary-Artery Bypass Surgery
Authors: Mark F. Newman, Jerry L. Kirchner, Barbara Phillips-Bute, Vincent Gaver, Hilary Grocott, Robert H. Jones, Daniel B. Mark, Joseph G. Reves, James A. Blumenthal
Journal: New England Journal of Medicine (2001)

Cognitive decline complicates early recovery after coronary-artery bypass grafting (CABG) and may be evident in as many as three quarters of patients at the time of discharge from the hospital and a third of patients after six months. We sought to determine the course of cognitive change during the five years after CABG and the effect of perioperative decline on long-term cognitive function.In 261 patients who underwent CABG, neurocognitive tests were performed preoperatively (at base line), before discharge, and six weeks, six months, and five years after CABG surgery. Decline in postoperative function was defined as a drop of 1 SD or more in the scores on tests of any one of four domains of cognitive function. (A reduction of 1 SD represents a decline in function of approximately 20 percent.) Overall neurocognitive status was assessed with a composite cognitive index score representing the sum of the scores for the individual domains. Factors predicting long-term cognitive decline were determined by multivariable logistic and linear regression.Among the patients studied, the incidence of cognitive decline was 53 percent at discharge, 36 percent at six weeks, 24 percent at six months, and 42 percent at five years. We investigated predictors of cognitive decline at five years and found that cognitive function at discharge was a significant predictor of long-term function (P<0.001).These results confirm the relatively high prevalence and persistence of cognitive decline after CABG and suggest a pattern of early improvement followed by a later decline that is predicted by the presence of early postoperative cognitive decline. Interventions to prevent or reduce short- and long-term cognitive decline after cardiac surgery are warranted.
AI-09 * PATTERNS OF SALVAGE TREATMENT FOR HIGH GRADE GLIOMA IN THE TEMOZOLOMIDE ERA
Authors: F. E. Escorcia, M. R. Folkert, D. E. Spratt, Z. Zumsteg, T. Chan, A. M. Omuro, K. Beal, P. H. Gutin, J. Yamada
Journal: Neuro-Oncology (2014)

PURPOSE: High grade gliomas (HGGs) are aggressive malignancies that recur despite trimodality treatment with surgery, radiation therapy (RT), and temozolomide (TMZ). We analyzed patients treated at our institution for factors associated with mortality in recurrent disease following trimodality therapy. METHODS: From 1/2000 to 9/2012, 437 consecutive patients with HGG (92 Grade III and 345 Grade IV) received trimodality therapy. Bevacizumab (Bev) was given in 11.7%. Initial RT schema was full-course to 56-60 Gy in 76%, whole-brain in 3%, short-course in 12%, and high-dose hypofractionated in 9%. Patient, tumor, upfront and salvage treatment-related factors were assessed. Survival rates were calculated by Kaplan-Meier methods, and Cox-regression modeling was utilized to calculate hazard ratios (HR); all confidence intervals (CI) are 95%. RESULTS: The median follow-up was 14 months; 17 months for surviving patients. The 1-year local control was 36.8% (31.8-41.8%), 59% (50.2-69.8%), and 30.7% (25.3-35.4%) for the entire cohort, Grade III, and Grade IV patients, respectively (P < .001). Salvage surgery was performed in 27.6%, salvage RT in 11.3%, and salvage chemotherapy (CT) in 83.1% of patients. Salvage CT included Bev in 41.6% and TMZ in 52.3% of patients. Factors associated with overall survival (OS) after LF included age at diagnosis (P < .001), KPS (P < .001), initial surgery (P < .001), initial uni- vs. bilateral disease (P < .001), grade (P < .001), initial RT schema (P < .001), salvage RT (P = .024), salvage Bev (P = .006), and salvage TMZ (P < .001). On multivariable analysis, the only treatment-related factor that retained significance for reduced mortality in patients with LF was use of salvage Bev [HR 0.65 (43-.97), P = .036]. CONCLUSIONS: In this large retrospective series of patients with HGG treated with trimodality therapy, local failure was common. Bevacizumab was the only physician-controlled factor associated with improved survival after failure. However, only 11.3% of our cohort received salvage RT. Further controlled studies are necessary to determine optimal salvage therapy.
98 norUDCA AMELIORATES CHOLEMIC NEPHROPATHY IN LONG-TERM COMMON BILE DUCT LIGATED MICE
Authors: E. Krones, M.J. Pollheimer, A. Deutschmann, K. Kinslechner, F. Durchschein, K. Eller, A. Rosenkranz, M. Trauner, P. Fickert
Journal: Journal of Hepatology (2013)
PTU-052 Long Term outcome of Patients with Reflux Symptoms and Symptomatic Esophageal Dysfunction during and after a Standardized Test Meal:a High-Resolution Manometry Study
Authors: R Sweis, G Brady, A Anggiansah, A Lee, A Valdes, T Wong, M Fox
Journal: Gut (2013)

<h3>Introduction</h3> Recently we presented novel methodology for the assessment of oesophageal function and symptoms during and after a standard test meal.<sup>1</sup> In the absence of a “gold standard”, outcome data provides insight into the clinical impact of this test in patients with reflux symptoms <h3>Methods</h3> 18 patients referred for investigation of reflux symptoms and 10 healthy volunteers underwent High Resolution Manometry (HRM) with 5ml water, 200ml water drink and test meal followed by 10min post-prandial observation. 24hr pH studies were performed in patients. The number of Symptoms Associated with oesophageal Dysfunction(SAD) was calculated. HRM findings and initial diagnosis were compared with the final diagnosis and outcome at 2 years <h3>Results</h3> No symptoms occurred with 5ml water. 12/18(67%) patients had SAD (mean SAD 2(range 0–7)) during/after the meal. Compared to 5ml water, manometric diagnosis was altered in 12/18(67%). No healthy volunteers had SAD. 11/18 patients had GORD on pH studies. By 2 years, 5/11 had anti-reflux surgery with excellent outcome. All 5 exhibited dysmotility (e.g. hypotensive/failed peristalsis) during the meal with symptomatic postprandial reflux events (transient lower oesophageal sphincter relaxation + common cavity). Of the 6/11 with GORD who did not have surgery, 2 declined it despite pathological pH results and symptomatic reflux events after the meal; both remain symptomatic despite acid-reducing therapy. The remaining 4 of 6 patients also had symptomatic dysmotility but were not offered surgery. 2 with severe hypotensive dysmotility and symptomatic reflux responded to acid suppression. 1 with (peptic) outlet obstruction and 1 with diffuse spasm did not respond to medication. Of the 7 with functional heartburn (negative pH results), 2 who had normal HRM responded to dietary/stress management. 2 with symptomatic reflux during HRM had good response to acid-suppression (i.e. false neg pH study). The final 3 with reflux-like symptoms had outflow obstruction identified only during the meal; 1 had good outcome after dilatation, 1 was too frail for therapy and remains symptomatic and the last was lost to follow-up. <h3>Conclusion</h3> HRM studies which include a test meal and post-prandial observation provide an objective explanation for symptoms in the majority of patients referred for investigation of “reflux” symptoms. Long-term follow-up suggests this information can guide management especially in patientswithout definitive diagnosis following standard 5 ml water HRM and negative pH-studies <h3>Disclosure of Interest</h3> None Declared <h3>Reference</h3> Sweis R <i>et al. Gastro</i><i></i> 2011; <b>140</b>
A Case of Discontinued Proximal Limb of a Ventriculoperitoneal Shunt With Patent Fibrous Tract
Authors: Mohammed Bermo, Alan S. Leung, Manuela Matesan
Journal: Clinical Nuclear Medicine (2016)

Radionuclide shuntogram is important in the evaluation of cerebrospinal fluid (CSF) shunts complications such as mechanical failure, malpositioning, pseudocyst, or overdrainage. We present here a case of congenital hydrocephalus and posterior fossa cyst with multiple shunt procedures and revisions with breakage of the proximal tube of the ventriculoperitoneal shunt but preserved CSF drainage through the patent fibrous tract. Careful correlation with SPECT/CT images helped confirm the breakage and exclude CSF leak outside of the tract, which was suspected on planar images.
Alexander George Seaman
Authors: M. Seaman
Journal: BMJ (2014)

Alexander George Seaman (“Alex”) and his family moved to Norwich in 1928, where he attended the Norwich Grammar School (now the Norwich School). He qualified as a doctor in October 1941 from St Thomas’ Hospital, London, at the age of 23 years. During the war students were expected to qualify as soon as possible, and therefore any degree course was not completed until after the war.

The year after he qualified, Seaman devoted to house appointments, the first at the King Edward Memorial hospital, Ealing, as house physician to Dr Harman, a general physician on the consultant staff of St Thomas’ hospital with an interest in venerology. He then took an appointment as house surgeon to …
Case 2-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Daryl R. Gress, John H. Eichhorn
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 60-year-old woman was admitted to the hospital after two seizures.The patient was well until 1 1/2 years earlier, when arthralgia developed and she consulted a rheumatologist. The erythrocyte sedimentation rate was 74 mm per hour; a test for antinuclear antibodies was positive in a titer of 1:128, with a homogeneous pattern; a test for antinative DNA antibodies was negative. A presumptive diagnosis of systemic lupus erythematosus was made, and hydroxychloroquine and ibuprofen were prescribed, with partial relief of her symptoms. An ophthalmologist later found evidence of early pigmentary maculopathy, and hydroxychloroquine was discontinued. A repeated . . .
P678 UTILITY OF QUANTITATIVE HEPATITIS B E ANTIGEN AND SURFACE ANTIGEN IN THE PREDICTION OF HEPATITIS B E ANTIGEN SEROCONVERSION FOLLOWING PREGNANCY IN HBV
Authors: V. Nguyen, A. Glass, K. Jackson, A. Greenup, S. Davison, S.A. Locarnini, M.T. Levy
Journal: Journal of Hepatology (2014)
Acute Subpectoral Abscess: A Surgical Emergency
Authors: Knowles B. Lawrence, Thomas J. Anglem
Journal: New England Journal of Medicine (1947)

CASE reports of acute subpectoral abscess and suppurative lymphadenitis — or "subpectoral phlegmon," as it is sometimes called — have appeared occasionally in both the American1 2 3 and the foreign4 , 5 medical literature. The authors usually state that the condition is of relative infrequency, a contention seemingly borne out by a lack of any collected series. A review of the surgical records of the Massachusetts Memorial Hospitals for the past fifteen years reveals a group of 5 cases of acute subpectoral abscess or suppurative lymphadenitis, and 1 case is added from private practice.Because the nature and behavior of this form of . . .
P3-01-03: The Hominoid-Specific Gene SHON Is Oncogenic in Human Mammary Carcinoma.
Authors: Y Jung, BG Shastri, X-J Kong, T Zhu, JK Perry, PE Lobie, D-X Liu
Journal: Cancer Research (2011)

Abstract Breast cancer is still the most common malignancy and the leading cause of cancer deaths in both developed and under developed countries. Molecular targeted therapy, in particular monoclonal antibody-based treatment, has emerged as a promising approach to treat this disease because of its high specificity and reduced toxicity. As a consequence, identification of novel molecular therapeutic targets is of crucial importance. In an effort to discover new targets for monoclonal antibody-based targeted therapy, we have identified a novel and secreted hominoid-specific molecule, SHON (secreted hominoid-specific oncogene), in the human mammary carcinoma cell line, MCF-7. Like other hominoid-specific genes, SHON has no known orthologs outside of the primate lineage. It is highly expressed in all cancer cell lines tested so far including breast, lung, liver, stomach, colon and prostate cancer as determined at the mRNA level by RT-PCR and at the protein level by western blotting. Forced expression of SHON in MCF-7 cells significantly increased cell proliferation and survival as demonstrated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and Annexin V/propidium iodide apoptosis assays, respectively. Forced expression of SHON also promoted MCF-7 cell anchorage independent growth in soft agar and enhanced cell migration and invasion. Moreover, forced expression of SHON in MCF-7 cells increased tumour volume in a xenograft model of human breast cancer in immunodeficient mice. Furthermore, depletion of endogenous SHON expression using small interfering RNAs, or functional inhibition using an inhibitory rabbit anti-SHON polyclonal antibody, decreased MCF-7 cell proliferation and survival, and reduced MCF-7 oncogenicity and invasiveness. Therefore, SHON is a novel oncogene for mammary carcinoma cells which may be useful as a therapeutic target for the treatment of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-03.