tbuckley/cabot-search huggingface dataset:
The McMurray Osteotomy for Nonunited Hip Fractures
Authors: Otto J. Hermann
Journal: New England Journal of Medicine (1945)

IN OCTOBER, 1939, I1 reported on a small series of hip reconstructions done for painful, nonunited fractures of the femoral neck under the various prevalent standard procedures. These included the Colonna modification2 of the Whitman method, the Magnuson modification3 of the Brackett operation, direct bone graft and hip fusion. On the whole, the percentage of good end results was discouraging, except, perhaps, for those obtained from the hip-fusion method. The temptation to adopt this procedure as the one of general choice was great, but I believed that it should not be done. After reading McMurray's4 paper on fractures of the . . .
Vibratory Urticaria Associated with a Missense Variant in<i>ADGRE2</i>
Authors: Steven E. Boyden, Avanti Desai, Glenn Cruse, Michael L. Young, Hyejeong C. Bolan, Linda M. Scott, A. Robin Eisch, R. Daniel Long, Chyi-Chia R. Lee, Colleen L. Satorius, Andrew J. Pakstis, Ana Olivera, James C. Mullikin, Eliane Chouery, André Mégarbané, Myrna Medlej-Hashim, Kenneth K. Kidd, Daniel L. Kastner, Dean D. Metcalfe, Hirsh D. Komarow
Journal: New England Journal of Medicine (2016)

Patients with autosomal dominant vibratory urticaria have localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum. We identified a previously unknown missense substitution in ADGRE2 (also known as EMR2), which was predicted to result in the replacement of cysteine with tyrosine at amino acid position 492 (p.C492Y), as the only nonsynonymous variant cosegregating with vibratory urticaria in two large kindreds. The ADGRE2 receptor undergoes autocatalytic cleavage, producing an extracellular subunit that noncovalently binds a transmembrane subunit. We showed that the variant probably destabilizes an autoinhibitory subunit interaction, sensitizing mast cells to IgE-independent vibration-induced degranulation. (Funded by the National Institutes of Health.).
Abstract P3-12-05: Clinical features and outcomes of leptomeningeal metastasis in patients with breast cancer: a single center experience
Authors: J-C Jo, MJ Kang, J-H Ahn, KH Jung, JE Kim, G Gong, HH Kim, SD Ahn, SS Kim, BH Son, SH Ahn, S-B Kim
Journal: Cancer Research (2012)

Abstract Background: Leptomeningeal metastasis (LM) is one of the major problems in managing metastatic breast cancer because of LM typically carries a devastating prognosis and often represents a terminal event. We analyzed the clinical features and outcomes of LM in patients with breast cancer. Methods: We retrospectively reviewed the medical records of patients who were diagnosed with LM from breast cancer between 2002 and 2012 at Asan Medical Center. Results: Of the 95 LM patients by cytologically proven (n = 81) or radiologically diagnosed (n = 14), 57 (60%) had an ECOG performance status (PS) ≥ 3, and the median age was 47 years (range, 26–72 years). The patients were diagnosed with LM after a median of 10.3 months (95% CI, 5.5–15.0 months) from the time of diagnosis of metastatic breast cancer. LM was present in 2 patients at the time of initial diagnosis. Twenty-three patients (24.2%) had isolated CNS metastasis, and 6 (6.3%) had only LM without any detectable metastasis sites. At the time of diagnosis of LM, 46 patients (48.4%) presented with coincidental failure of systemic disease control. Seventy-eight patients (82.1%) underwent intrathecal chemotherapy (methotrexate; n=78, thiotepa; n=11), resulting in one-third of cytologic negative conversion (n = 26), and 41 (43.2%) received systemic chemotherapy. The overall median survival time was 3.3 months (95% CI, 2.5–4.2 months) and 7.8% of the patients survived for more than 1 year. Overall survival tended to be better in patients who achieved cytologic negative conversion to intrathecal chemotherapy than those did not (median 4.5 months versus 3.2 months, P = 0.241). Overall survival was not different according to subtypes; hormone receptor (+), HER2 (+), and triple negative (median 3.6 months, 3.3 months, and 3.2 months, P = 0.937). Multivariate analysis demonstrated that ECOG PS ≥ 3 (HR = 2.09, 95% CI 1.21–3.58, P = 0.007), coincidental failure of systemic disease control at LM (HR = 3.01, 95% CI 1.76–5.15, P &amp;lt; 0.001), and systemic chemotherapy after LM (HR = 0.40, 95% CI 0.24–0.68, P = 0.001) were independent factors associated with survival. Conclusions: The prognosis for patients with LM from breast cancer was still poor. Systemic chemotherapy in addition to intrathecal chemotherapy might confer a survival benefit, even after the detection of LM. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-05.
PWE-270 Unrevealing a novel association of cholesterol ester storage disease (CESD) and non-alcoholic fatty liver disease (NAFLD)—a similar clinical spectrum with different aetiology a prospective clinical study
Authors: P Basu, T Nair, S Farhat, M Jafri, K Mittimani, N James Shah, L Ang
Journal: Gut (2012)

<h3>Introduction</h3> NAFLD is the most evolving global morbidity progresses to cirrhosis, liver cancer and Transplantation. Clinical Spectrum is heterogeneous with biochemical and histological diversity. CESD is a part of metabolic storage disease with an intrinsic Lysosomal Acid Lipase deficiency (LAL) mimicking clinical overlap with NAFLD. This clinical pilot study evaluates the clinical overlap of similar metabolic syndromes with diverse aetiology And outcome. <h3>Methods</h3> Three hundred (n=300) patients with fatty liver disease with Hepatomegaly, splenomegaly or Both with Mean BMI 27%, Mean (Anthropometric assay W/H ratio mean 0.9, HDL 28, LDL 148, Triglyceride 187, HbA1c 5.9, HOMA Score 2.2, CRP 2.3, ALT 67, RBP 2.3, Homocystein 11, Leptin 3.6, Adiponectin 1.1 TNF-α 1,2, IL10 1.2, IL12 0.8. MELD 4). All under went Abdominal Sonogram and carotid artery Doppler. Serum Fibro sure, NASH score was measured and liver biopsy was performed in NASH group. Patients were divided into Group A (n=100) control with mean BMI 27.8% and no hepato-splenomegaly, Group B (n=100) NAFLD with low BMI &lt;26%, and Group C, NASH (n=100) with NAFLD with BMI &gt;30%. <h3>Results</h3> <h3>Conclusion</h3> Estimated prevalence of LAL 8.3% compared to the historical data (25 in 1 million) LAL has heterogeneity with an overlap WITH NAFLD and NASH. LAL deficiency has peripheral atherogenic potential with significant clinical morbidities with high Steatotic, Fibrogenic, and inflammatory scores than NAFLA or NASH. CESD is an integral part of Fatty liver disease. <h3>Competing interests</h3> None declared.
Abstract 222: Differential p73 isoform expression profile in non-Hodgkin's lymphoma with 1p36 chromosomal abnormality modulates angiogenic phenotype
Authors: Hesham M. Hassan, Michelle L. Varney, Smrati Jain, Shantaram S. Joshi, Rakesh K. Singh, Bhavana J. Dave
Journal: Cancer Research (2011)

Abstract Alteration of tumor suppressor gene function often leads to imbalance in expression of angiogenic and angiostatic factors facilitating disease progression. TP73, a member of the p53 tumor suppressor gene family, regulates many important cellular pathways and has been shown to be abnormally expressed in non-Hodgkin's lymphoma (NHL). TP73 gene function is controlled by harmony between two isoforms with opposing functions, the full length TAp73 protein (pro-apoptotic) and the NH2-terminally truncated ΔNp73 protein (anti-apoptotic through antagonizing both TAp73 and p53). We have observed differential ΔNp73 up-regulation and increase in ΔNp73:TAp73 expression ratio among NHL cases with 1p36 chromosomal disruption as compared to NHL cases without 1p36 disruption, which is associated with aggressiveness. To decipher whether deregulated p73 isoforms expression modulates the angiogenic potential in NHL we examined the mRNA expression of angiogenic factors (VEGF-A, FGF-2, and angiogenic chemokine CXCL-8) and angiostatic factors (TSP-1 and Endostatin) in NHL cases with and without chromosome 1p36 abnormality by real-time PCR. We observed higher levels of expression of angiogenic factors (VEGF-A, FGF-2, and CXCL-8) and lower levels of angiostatic factors (TSP-1 and Endostatin) in NHL cases with 1p36 abnormality as compared to NHL cases without 1p36 abnormality. Next, we performed a non-parametric bivariate correlation analysis (Kendall's tau_b and Spearman's rho) to examine whether ΔNp73:TAp73 expression ratio correlates with the expression of angiogenic and angiostatic factors. We observed a significant correlation between ΔNp73:TAp73 expression ratio with the expression of VEGF-A (r=0.900, p&amp;lt;0.001), FGF-2 (r=0.620, p&amp;lt;0.05) and TSP-1 (r=−0.873, p&amp;lt;0.001). To further elucidate the relationship between differential p73 isoforms expression and the expression pattern of angiogenic and angiostatic factors, we stably transfected an NHL cell line with 1p36 disruption, Granta-519 (TAp73 non expressor) with a wild type TAp73 mammalian expression vector. We observed an up-regulation of TSP-1 and Endostatin expression among Granta-519 cells transfected with TAp73 vectors compared to isogenic control vector transfected cells. Our data highlights the molecular and functional consequences of the differential p73 isoforms expression pattern caused by 1p36 chromosomal disruption on angiogenic phenotype in NHL. 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 222. doi:10.1158/1538-7445.AM2011-222
EFICACIA DIAGNOSTICA DE LA CAPSULA ENDOSCOPICA EN LA PROVINCIA DE LAS PALMAS: ESTUDIO RETROSPECTIVO DE 434 CAPSULAS
Authors: A Castellot Martín, C Sánchez Vilar, M Lorente Arencibia, A Cruz Bonilla, L Betancor Hernandez, A Monescillo Francia, E Jiménez Mutiloa, JM Marrero Monroy, V Malo De Molina Zamora, A Sierra Hernández
Journal: Endoscopy (2013)

Introducción: La cápsula endoscópica (CE) ha cambiado el diagnóstico y manejo de la patología del intestino delgado. Objetivo: Evaluar la utilidad y seguridad de la CE como prueba diagnóstica en distintas patologías de intestino delgado en nuestro medio. Material y Método: Se analizaron de forma retrospectiva los estudios de CE realizados en nuestro centro desde mayo de 2006 a mayo de 2013. Se administraron dos tipos de cápsula: Pillcam y Mirocam, de forma aleatoria no controlada, con preparación igual. Los datos epidemiológicos y del estudio de CE se recogieron en una base de datos diseñada para tal fin. La lectura de la cápsula se realizó por una única endoscopista. Para el diagnóstico de enfermedad inflamatoria intestinal se aplicó el índice de Lewis con punto de corte > 135. Resultados: Se incluyeron en el estudio 434 cápsulas (355 Pillcam y 79 Mirocam) en 428 pacientes, 54% mujeres con edad media: 54 ± 19 (7 – 90). Indicaciones: anemia (48%), enfermedad inflamatoria (27%), hemorragia digestiva de origen oscuro (20%) y otros (5%). Se encontraron lesiones en 314 casos (72%), 102 estudios fueron normales (23%) y 18 fueron no diagnósticas (4%) (mala preparación (13), no alcanzar ciego (3) y problemas técnicos (2)). Los hallazgos observados fueron malformaciones vasculares (149 pacientes), enfermedad inflamatoria (52 pacientes), enteropatía por AINEs (26 pacientes), lesiones inespecíficas (39 pacientes), tumores (8 pacientes), pólipos intestinales (10 pacientes) y una enfermedad celiaca. Se diagnosticó patología esofágica, gastrodudenal y colónica no detectada con endoscopia convencional en 16 casos (4%). Hubo retención de la cápsula en 4 casos (0,9%), de los que 3 precisaron cirugía y uno se resolvió con tratamiento conservador. Conclusiones: La CE es un método eficaz y seguro para el estudio de intestino delgado.
Abstract 5002: Comprehensive DNA methylation profiling of human hepatocellular carcinoma
Authors: Takafumi Nishimura, Naoshi Nishida
Journal: Cancer Research (2012)

Abstract &amp;lt;Background and aim&amp;gt; Transcriptional inactivation of several tumor suppressor genes via epigenetic mechanism has been reported in many types of cancers, including hepatocellular carcinoma (HCC), and thus has been considered as critical events in multistage carcinogenesis. We conducted a comprehensive genome-wide analysis to elucidate distribution and characteristics of genes that subject to cancer-related DNA methylation in human HCC, especially on the context of development of methylation alteration in early stage of human hepatocarcinogenesis. &amp;lt;Materials and methods&amp;gt; With written informed consent, five well-differentiated HCC tissues and two corresponding matched non-cancerous liver tissues were obtained at the time of hepatectomy (2 tumors) or orthotopic living-donor liver transplantation (3 tumors and 2 non-tumors). After bisulfite modification, the converted DNA was subject to hybridization on Infinium Human Methylation BeadChip 450K (Illumina, Inc., San Diego, CA) that includes 485,764 cytosine positions of the human genome including gene promoters and repetitive DNA elements. The methylation level for each CpG dinucleotides was represented as a beta value according to the fluorescent intensity ratio. In order to identify alteration of methylation profile between well-differntiated HCC and non-tumor liver, difference of average beta values between tumor and non-tumor was calculated. &amp;lt;Results&amp;gt; Of 25,978 CpG loci that represent each gene, differences of average beta values of 24,805 loci (95.5%) were within 30%. These were considered as constitutively methylated or unmethylated. Tumor-specific demethylation was found at 589 loci representing 414 genes. Of these, 85.0% were located outside CpG islands, shore or shelf. Tumor-specific demethylation rarely occurred within CpG islands (3.4%). On the other hand, tumor-specific DNA methylation was found at 137 loci representing 108 genes. Of these, 65.7% were located within CpG islands. According to previously published information (Lee, TI. et. al. Cell 125:301-313, 2006), 39 genes (36%) out of these 108 genes with tumor-specific methylation have been reported to be occupied with polycomb group protein SUZ12 in embryonic stem cells. &amp;lt;Conclusion&amp;gt; Tumor-specific methylation occurring at CpG islands, especially of polycomb target genes, may contribute to hepatocarcinogenesis. This finding further suggests an importance of epigenetic mechanism on developing human HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5002. doi:1538-7445.AM2012-5002
Neonatal Cyanosis from a Hemoglobin Variant
Authors: Robert J. Ostrander, Nancy S. Green
Journal: New England Journal of Medicine (2011)

Neonatal Cyanosis from a Hemoglobin Variantto the editor: In their article on a hemoglobin variant associated with neonatal cyanosis and anemia, Crowley et al. (May 12 issue) 1 describe their use of testing of arterial blood gases, a re view of family medical history, and other tailored testing for wellappearing newborns with cyanosis.Universal screening in the nursery for cyanotic congenital heart disease with the use of pulse oximetry was recently recommended by a federal advisory committee. 2Although the condition de scribed by Crowley et al. is rare, routine neonatal screening for low oxygen saturation will inevita bly uncover more patients with hemoglobinopa thies with low oxygen affinity. 3 We describe another inherited hemoglobinop athy in a patient presenting with neonatal cyano sis.Shortly after delivery in 1991, a term female infant with cyanosis was found to be nonanemic and to have oxygen saturation and a partial pres sure of oxygen in arterial blood of 88%.Exten sive cardiologic evaluation, including angiogra phy, did not reveal cardiac disease.Eventually, hemoglobin analysis confirmed a rare hemoglo binopathy, hemoglobin Titusville. 3,4 Twenty years later, when this patient became pregnant, advance information was provided to the obstetrical and nursery teams.Cyanosis de veloped in the patient's infant in association with crying and feeding, along with a low oxygen saturation.Cardiologic evaluation was not deemed to be warranted, and analysis confirmed the inherited hemoglobinopathy.The baby continues to do well, albeit with continued periodic circum oral cyanosis.An awareness of these conditions among physicians can spare newborns and their families from unnecessary evaluation and worry.
Treatment of Hepatic Coma by Exchange Blood Transfusion
Authors: Charles Trey, Derrick G. Burns, Stuart J. Saunders
Journal: New England Journal of Medicine (1966)

IN recent years numerous publications have dealt with the pathogenesis and treatment of hepatic coma. The protean nature of the neurologic disturbances associated with liver failure and the absence of specific neuropathological findings suggest that "hepatic coma" is metabolic in origin.1 Although deranged nitrogen metabolism and the effects of ammonia and amines on brain cells have been implicated in the pathogenesis of this encephalopathy2 it is clear that the syndrome is not due to any single agent. However, the management of these patients is based upon the known biochemical abnormalities3 and includes the elimination of all protein from the diet . . .
Abstract 5660: Vaccinia virus GLV-1h153 in combination with 131I-iodine shows increased efficiency in treating triple-negative breast cancer <i>in vivo</i>
Authors: Sepideh Gholami, Chun-Hao Chen, Emil Lou, Andrew A. Marano, Kelly M. Mojica, Nanhai G. Chen, Richard J. Aguilar, Laurence J. Belin, Valerie A. Longo, Pat Zanzonico, Aladar A. Szalay, Yuman Fong
Journal: Cancer Research (2012)

Abstract BACKGROUND: Triple-negative breast cancers (TNBC) are aggressive tumors due to their inherent biology and the lack of receptors for hormonal/targeted therapy, namely estrogen, progesterone, and Her2/neu. The human sodium iodide symporter (hNIS) is a naturally occurring protein in some human breast and thyroid tissue which enables cells to concentrate iodine, including radioiodide. In this study, we investigated the therapeutic efficacy of a new oncolytic vaccinia virus, GLV-1h153 carrying the hNIS, in combination with radioiodine in a TNBC murine model. METHODS: GLV-1h153, a replication-competent vaccinia virus, was tested against the TNBC cell lines MDA-MB-231, MDA-MB-468, HCC-1937, and HCC-1143 at multiplicities of infections (MOI) of 0.1, 1.0, and 5. Cytotoxicity and viral replication were determined. Mammary fat pad tumors were generated in athymic nude mice with MDA-MB-231 cells. A subset of xenografts were infected with GLV-1h153 and ∼150 μCi of 124I-iodine was administered. Serial Focus 120 microPET were obtained for 131I dosimetry calculations. For the combination therapy study, 14 days after cell implantation, xenografts were treated with intratumoral injection of GLV-1h153 or PBS. One week after viral injection (day 21), xenografts were further randomized into 4 treatments groups: GLV-1h153 alone, GLV-1h153 and iodine (∼5 mCi of 131I), iodine alone, or PBS and followed for tumor growth. RESULTS: Greater than 90% cell kill was achieved in all cell lines within 5 days at an MOI of 5.0. GLV-1h153 replicated efficiently in all cell lines with a peak titer of 2.6 x107 viral plaque forming units per ml (&amp;gt;1300-fold increase from the initial viral dose) by day 4 in cell line MDA-MB-468. Only infected tumors were identified via PET scanning compared to controls. In vivo, administration of systemic radioiodine in combination with GLV-1h153 resulted in greater tumor regression, 24 mm3 compared to 146 mm3 for the viral-treated group only (p&amp;lt;0.05; days 21-40), a six-fold difference. CONCLUSION: GLV-1h153 infected, replicated in, and killed all TNBC cell lines effectively. This study is the first to our knowledege to demonstrate killing of TNBC by a novel vaccinia virus in combination with radioactive 131I-iodine in an in vivo xenograft model. Our results suggest that GLV-1h153 is a promising therapeutic agent in combination with 131I and merits further testing in the clinical setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5660. doi:1538-7445.AM2012-5660
Tc-99m DMSA (V) Uptake in Multiorgan Amyloidosis
Authors: ASEEM BHATNAGAR, MAHESHWAR SAHOO, VIJAY SINGH NIJHAWAN, KRISHAN SAWROOP, ANUPAM MONDAL
Journal: Clinical Nuclear Medicine (1996)

The authors present an unusual Tc-99m DMSA (V) scan showing sites of abnormal uptake in the thyroid gland oropharynx, both parotid and submandibular glands, bilateral axillary nodes, and the myocardium in a patient with a solitary thyroid nodule. Most of these sites were later shown to be amyloid deposits without any metastatic spread. The report suggests the advantage of amyloidosis scintigraphy with DMSA (V) because of whole body coverage and identification of unsuspected sites of involvement.
VAMP8 facilitates cellular proliferation and temozolomide resistance in human glioma cells
Authors: Yuanyuan Chen, Delong Meng, Huibo Wang, Ruochuan Sun, Dongrui Wang, Shuai Wang, Jiajun Fan, Yingjie Zhao, Jingkun Wang, Song Yang, Cong Huai, Xiao Song, Rong Qin, Tao Xu, Dapeng Yun, Lingna Hu, Jingmin Yang, Xiaotian Zhang, Haoming Chen, Juxiang Chen, Hongyan Chen, Daru Lu
Journal: Neuro-Oncology (2014)

Malignant glioma is a common and lethal primary brain tumor in adults. Here we identified a novel oncoprotein, vesicle-associated membrane protein 8 (VAMP8), and investigated its roles in tumorigenisis and chemoresistance in glioma. The expression of gene and protein were determined by quantitative PCR and Western blot, respectively. Histological analysis of 282 glioma samples and 12 normal controls was performed by Pearson's chi-squared test. Survival analysis was performed using the log-rank test and Cox proportional hazards regression. Cell proliferation and cytotoxicity assay were conducted using Cell Counting Kit-8. Autophagy was detected by confocal microscopy and Western blot. VAMP8 was significantly overexpressed in human glioma specimens and could become a potential novel prognostic and treatment-predictive marker for glioma patients. Overexpression of VAMP8 promoted cell proliferation in vitro and in vivo, whereas knockdown of VAMP8 attenuated glioma growth by arresting cell cycle in the G0/G1 phase. Moreover, VAMP8 contributed to temozolomide (TMZ) resistance by elevating the expression levels of autophagy proteins and the number of autophagosomes. Further inhibition of autophagy via siRNA-mediated knockdown of autophagy-related gene 5 (ATG5) or syntaxin 17 (STX17) reversed TMZ resistance in VAMP8-overexpressing cells, while silencing of VAMP8 impaired the autophagic flux and alleviated TMZ resistance in glioma cells. Our findings identified VAMP8 as a novel oncogene by promoting cell proliferation and therapeutic resistance in glioma. Targeting VAMP8 may serve as a potential therapeutic regimen for the treatment of glioma.