tbuckley/cabot-search huggingface dataset:
Joseph Andre Maudar
Authors: David Brooks
Journal: BMJ (2016)

Joseph Andre Maudar was born in Mauritius in 1933. He was educated there until he was accepted as a medical undergraduate in Dublin. His first language was French, and although he spoke English fluently, he always maintained that he thought in French. He certainly did retain a slight French accent. After qualifying he moved to England, to Accrington Victoria Hospital, where he met his wife to be, Joan, a theatre sister. 

He originally …
Is EUS Diagnosis Using a Small Soft Balloon Useful in Determining the Depth of Invasion in Superficial Esophageal Cancer?
Authors: T Iizuka, N Yahagi, Y Kinoshita
Journal: Endoscopy (2006)

Objective: It is important to accurately determine the depth of invasion in superficial esophageal cancer because it is directly related to the therapeutic policy. In the present study, we verified the accuracy of the EUS diagnosis for superficial esophageal cancer in order to assess the utility of the small soft balloon method (SSB) method. Subjects: Included in the present study were 149 lesions for which the depth of invasion could be histologically evaluated from 139 patients with superficial esophageal cancer treated in this facility between March 2000 and December 2005. Methods: The diagnosis was undertaken by the SSB method (effective length of the soft balloon (SB): 1cm) using the fine probe UMS30–25R (Olympus Corporation). The depth of invasion diagnosis performance for superficial cancer and the MM identification rate were evaluated. In addition, the esophagus was divided into 3 segments (Upper, Middle and Lower) and the precision of the depth of invasion diagnosis was compared between the 3 segments. Results: Identification of the lamina muscularis mucosae (MM) was possible for 140 of the 149 lesions (94%). Based on MM, the correct depth of invasion diagnosis rate was 86% (56/65) for M and 75% (56/75) for SM. By site of esophageal cancer, the MM identification rate was 92%, 95%, and 91%, respectively, at U, M, and L. The correct depth of invasion diagnosis rate was 77% (27/35), 82% (68/83), and 81% (17/21), at U, M, and L, respectively. Conclusion: The identification of MM was possible in 94% of cases, and based on MM, the diagnosis of the depth of invasion was correct in 80% of cases. The correct depth of invasion diagnosis rate did not differ significantly depending on the site of esophageal cancer, and a stable correct diagnosis rate could be obtained using the SSB method regardless of factors such as physiological stenosis in the esophagus and cardiac beat.
Abstract 4286: Essential Roles of Jab1 in Cell Survival, Spontaneous DNA Damage, and DNA Repair
Authors: Francois Claret
Journal: Cancer Research (2011)

Abstract Jun activation domain-binding protein 1 (JAB1) is a multifunctional protein that participates in the control cell proliferation and the stability of multiple proteins. JAB1 overexpression has been implicated in the pathogenesis of human cancer. JAB1 regulates several key proteins and thereby produces varied effects on cell cycle progression, genome stability, and cell survival. However, the biological significance of JAB1 activity in these cellular signaling pathways is unclear. Therefore, we developed mice that were deficient in Jab1 and analyzed the null embryos and heterozygous cells. This disruption of Jab1 in mice resulted in early embryonic lethality due to accelerated apoptosis. Loss of Jab1 expression sensitized both mouse primary embryonic fibroblasts and osteosarcoma cells to gamma radiation-induced apoptosis, with an increase in spontaneous DNA damage and homologous recombination (HR) defects, both of which correlated with reduced levels of the DNA repair protein Rad51 and elevated levels of p53. Furthermore, the accumulated p53 directly binds to Rad51 promoter, inhibited its activity, and represent a major mechanism underlying the HR repair defect in Jab1-deficient cells. These results indicate that Jab1 is essential for efficient DNA repair and mechanistically link Jab1 to the maintenance of genome integrity and to cell survival. 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 4286. doi:10.1158/1538-7445.AM2011-4286
Hepatic and Splenic Uptake on Bone Scintigraphy in Patients With Intravenous Administration of 99mTc Methylene Diphosphonate Prior to Gadolinium-Containing Contrast
Authors: Wenjie Zhang, Biling Chen, Houfu Deng, Tianxia Yang, XiaoHong Ou
Journal: Clinical Nuclear Medicine (2013)

Earlier studies indicate that abnormal liver and spleen uptake on bone scan has been observed in association with intravenous injection of Gd-DTPA contrast for MRI. All of these patients, however, received Gd-DTPA injection prior to (99m)Tc MDP administration. We report herein 3 patients with hepatic and splenic uptake on bone scan; all were administered (99m)Tc MDP before Gd-DTPA. Thus, we can conclude that Gd-DTPA after (99m)Tc MDP administration may also induce increased hepatic and splenic radioactivity on bone scan.
THU0281 A Multicentre Clinical Study of Umbilical Cord Mesenchymal Stem Cells Transplantation in Active Systemic Lupus Erythematosus
Authors: L. Sun, D. Wang, J. Li, M. Zhang, Y. Zhang, X. Li
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Umbilical cord (UC) derived mesenchymal stem cells (MSCs) have shown safety profile and therapeutic effect in severe and refractory systemic lupus erythematosus (SLE) in our single-centre pilot study. <h3>Objectives</h3> The present multicentre clinical trial was undertaken in China to assess the efficacy and safety of allogenic UC MSCs transplantation (MSCT) in active SLE patients. <h3>Methods</h3> Forty patients (aged ≥16 years) with active SLE (SLE Disease Activity Index &gt;6) were enrolled from 4 clinical centres in China. All patients gave informed consents before transplantation, and allogenic UC MSCs were infused intravenously on days 0 and 7. Adverse event was monitored during and after MSCs transplantation. Primary efficacy endpoints were major clinical response (MCR), partial clinical response (PCR) and relapse at 6 and 12 months. Secondary endpoints were improvement in SLEDAI score, British Isles Lupus Assessment Group (BILAG) score, serum levels of creatinine, urea nitrogen, complements and albumin pre- and post-MSCT. <h3>Results</h3> Fourteen and fifteen patients achieved MCR (14/40, 35.0%) and PCR (15/40, 37.5%) at 6 months follow-up, respectively. Three and four patients experienced disease relapse at 9 (7.5%) and 12 (10%) months follow-up, respectively, after a prior clinical response. SLEDAI score significantly decreased at 3 (7.43±3.93), 6 (6.30±3.63), 9 (6.40±3.84) and 12 months (6.48±3.52) follow-up (<i>P</i> all &lt;0.05 <i>vs.</i> baseline 10.83±4.63). Total BILAG score markedly decreased 3 months after MSCT, and continued to decrease in the following visit times. BILAG score for renal and hematopoietic system significantly improved. For those with lupus nephritis, 24-hour proteinuria declined after transplantation, with statistical differences at 9 (1.24±1.09 mg) and 12 months (1.41±1.33 mg, <i>P</i>&lt;0.05 <i>vs.</i> baseline 2.24±1.43 mg). Serum creatinine and urea nitrogen decreased to the lowest level at 6 months, while slightly increased at 9 and 12 months due to the 7 relapsed cases. Additionally, Serum levels of albumin, complements 3 and 4 increased after MSCT, peaked at 6 months visit, then slight declined at 9 and 12 months. Serum anti-nuclear antibody (ANA) and anti-double strand DNA (dsDNA) antibody decreased after MSCT, with statistical differences at 3 months follow-up. Furthermore, hemoglobin and platelet counts increased after MSCT in those with hematopoietic involvement. UC-MSCT was well tolerated and no adverse event was observed. <h3>Conclusions</h3> Our findings indicate that UC MSCT results in satisfactory clinical responses in SLE. However, several cases experienced disease relapse after 6 months visit, which suggests the necessity for repeated MSCT after 6 months in some patients. <h3>Disclosure of Interest</h3> None Declared
P285 Assessing The Impact Of Varenicline Initiation During Acute Hospital Admission For Current Smokers With Respiratory Diseases: 18-month Experience From An Inner City District Teaching Hospital
Authors: A. Ainley, E. Pang, B. Coleman, M. Stern, L. Restrick
Journal: Thorax (2014)

<h3>Introduction</h3> Smoking is a significant cause of respiratory disease and risk factor for chronic obstructive pulmonary disease (COPD) and asthma admissions. 70% of smokers admitted to hospital want to quit and quit smoking interventions during acute admission are NICE recommended.<sup>1</sup> Many patients with respiratory disease are highly nicotine-dependent and varenicline is an effective treatment<sup>1,2 </sup>but is not routinely initiated during admission. <h3>Method</h3> We retrospectively reviewed the notes of all patients prescribed varenicline during in-patient stay on the respiratory ward over 18 months (August 2012–January 2014). Baseline data included demographics, disease details (diagnosis, spirometry) and smoking history (tobacco/cannabis use, pack/joint-years). The primary outcomes were carbon monoxide (CO) validated quit rates at 4-weeks and self-reported quit rates at 6-months and 1-year. All patients were seen on the ward by a smoking cessation advisor and after discharge as per NICE guidance.<sup>1</sup> Nicotine withdrawal during varenicline initiation was treated with standard combination nicotine replacement therapy.<sup>1</sup> <h3>Results</h3> 44 patients (17M:27F) were prescribed varenicline during admission. Mean (range) age was 61 (23–81) years with median (range) 50 (8–180) pack-years. 8/44 (18%) also smoked cannabis. 29 (66%) had COPD, 7 (16%) asthma, and 8 (18%) had both. Mean (SD) FEV<sub>1</sub> was 1.18 (0.52)L (n = 40) with FEV<sub>1</sub>%predicted 47 (21)% (n = 26). 7 patients (16%) died; all from smoking-related diseases, within 18 months of admission with mean (range) age at death 71 (61–78) years. 2 were lost to follow-up. CO-validated 4-week quit rate was 48% (21/44). Self-reported 6-month and 1-year quit rates were 41% (18/44) and 20% (9/44) respectively. Only 4/44 (9%) stopped varenicline early due to side-effects (nausea/headache). <h3>Conclusion</h3> Varenicline was safe and well-tolerated when initiated in hospital. The 4-week 48% quit rate for these ‘sick’ smokers was almost as high as the 52% national target for ‘well’ smokers. Self-reported 6-month quit rates were almost as good as the best published rates with intensive support in COPD (41% cf 49%).<sup>2</sup> Varenicline should be used as a treatment for smokers admitted with respiratory disease.<sup>1</sup> <h3>References</h3> NICE PH guidance 48. <i>Smoking cessation in secondary care. </i>2013 Jiménez Ruiz <i>et al</i>. Nicotine and Tobacco Research. 2012;14(9):1035-1039
<i>Notes from the Field</i>: Imported Cases of Malaria — Puerto Rico, July–October 2015
Authors: Emilio Dirlikov, Carmen Rodríguez, Shirley Morales, Laura Castro Martínez, Juan B. Mendez, Anibal Cruz Sanchez, Jesús Hernández Burgos, Zobeida Santiago, Rosa Ivette Cuevas-Ruis, Sheila Adorno Camacho, Enid Román Mercado, Jessica Falcón Guzmán, Kyle Ryff, Carolina Luna-Pinto, Paul M. Arguin, Stella M. Chenet, Luciana Silva-Flannery, Dragan Ljolje, Julio Cadiz Velázquez, Dana Thomas, Brenda Rivera Garcia
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On July 16 2015, the Puerto Rico Department of Health (PRDH) was notified of a case of malaria, diagnosed by a hospital parasitology laboratory in a student who had traveled to Punta Cana, Dominican Republic, during late June for a school-organized graduation trip. Malaria is a mosquito-borne parasitic infection, characterized by fever, shaking chills, headaches, muscle pains, nausea, general malaise, and vomiting (1). Malaria can be clinically difficult to distinguish from other acute febrile illnesses, and a definitive diagnosis requires demonstration of malaria parasites using microscopy or molecular diagnostic tests. The student's initial diagnosis on July 10 was suspected dengue virus infection. Puerto Rico eliminated local malaria transmission during the mid-1950s (2); however, reintroduction remains a risk because of the presence of a competent vector (Anopheles albimanus) and ease of travel to areas where the disease is endemic, including Hispaniola, the island shared by the Dominican Republic and Haiti, and the only island in the Caribbean with endemic malaria (3). During 2014, the Dominican Republic reported 496 confirmed malaria cases and four associated deaths; Haiti reported 17,662 confirmed cases and nine deaths (4). During 2000-2014, Puerto Rico reported a total of 35 imported malaria cases (range = 0-7 per year); three cases were imported from Hispaniola. During June-August 2015, eight confirmed malaria cases among travelers to the Dominican Republic were reported to CDC's National Malaria Surveillance System (CDC, unpublished data, 2015).
FIRST CLINICAL EVALUATION OF A DIGITAL HEALTH OFFERING TO OPTIMIZE TREATMENT IN PATIENTS WITH UNCONTROLLED HYPERTENSION AND TYPE 2 DIABETES
Authors: Lars Osterberg, Naunihal Virdi, Yoona Kim, Praveen Raja, Miriam Cruz, George Savage, Jeffrey Unger, Marina Raikhel, Juan Frias
Journal: Journal of the American College of Cardiology (2016)
The Efficacy of Sestamibi Parathyroid Scintigraphy for Directing Surgical Approaches Based on Modified Interpretation Criteria
Authors: Chun K Kim, Suzy Kim, Borys R Krynyckyi, Josef Machac, William B Inabnet
Journal: Clinical Nuclear Medicine (2002)

With the increasing use of targeted parathyroidectomy, the accuracy of sestamibi parathyroid scintigraphy (SPS) in determining the best surgical approach has become more clinically relevant than its sensitivity for detecting all abnormal glands. The reported accuracy of SPS does not represent the true efficacy of SPS for directing targeted parathyroidectomy, because many authors reported accuracy on the basis of abnormal glands. The authors assessed the efficacy of SPS based on modified interpretation criteria to determine specifically whether SPS influences the surgeon's choice of a targeted versus a conventional approach to parathyroidectomy.The authors reviewed the SPS studies (both dual-isotope subtraction and Tc-99m sestamibi dual-phase techniques) performed in 80 patients with primary hyperparathyroidism. All patients had surgery with histologic diagnoses, intraoperative PTH assays, and clinical follow-up.Of 75 patients with solitary adenomas, 9 SPS studies were negative, equivocal, or showed two or more foci, and 66 studies showed a solitary focus on the correct side. Of these 66 studies, 63 showed a lesion in the correct quadrant (e.g., superior or inferior) and 3 predicted the correct side only but a wrong quadrant. The positive-predictive value of SPS was 100% for correctly identifying the side of the adenoma (thus correctly directing unilateral surgery) and 95.5% for correctly identifying the quadrant of the solitary adenoma.The positive-predictive value of SPS for directing the surgical approach (but not for detecting individual lesions) that reveals a single focus is very high based on our modified interpretation criteria.
Determination of Molecular Profiles of <i>BRCA1</i> and <i>BRCA2</i> Breast Cancers.
Authors: G. Banneau, M. Guedj, R. Schiappa, F. Petel, N. Sevenet, I. De Mascarel, G. Mac Grogan, M. Longy, F. Bonnet
Journal: Cancer Research (2009)

Abstract BackgroundBRCA1 and BRCA2 genes are known to be the target of germline mutations in familial breast cancers, which represent 5% of the total breast cancer population. Mutation screening of these genes is performed in suspected familial breast cancer cases but a causative mutation is found in only 30% of patients. Therefore the development of additional methods to identify good candidates for BRCA1 and BRCA2 analysis would increase the efficacy of diagnostic mutation screening. With this in mind, we developed a study to determine molecular signatures of BRCA1 - or BRCA2 - mutated breast cancers.Material and MethodsArray-CGH and transcriptomic analysis were performed on a series of 103 familial breast cancers. The series included 7 breast cancers with a BRCA1 mutation and 5 breast cancers with a BRCA2 mutation. The remaining 91 cases were obtained from 73 families selected on the bases of at least 3 affected first degree relatives or at least 2 affected first degree relatives with breast cancer at an average age of 45 years. Tumoral DNA was co-hybridized with pooled normal blooded DNA from 21 individuals on a 4407 BAC-array (CIT-V8) provided by the CIT program and manufactured by Integragen. Transcriptomic analyses were performed using an Affymetrix Human Genome U133 Plus 2.0 chip. Clinical, pathological and genomic data were retrieved through Annotator, the CIT cancer database and the analysis was performed by using the R statistical software along with the CIT R packages.ResultsUsing supervised clustering analyses we identified 2 transcriptomic signatures, one for BRCA1-mutated breast cancers consisting of 600 probes sets and another for BRCA2-mutated breast cancers also consisting of 600 probes sets. We also defined CGH-array signatures, based on a presence of specific genomic rearrangements, one for BRCA1-mutated breast cancers and one for BRCA2-mutated breast cancers.ConclusionThis study has identified molecular signatures of breast cancers with BRCA1 or BRCA2 germline mutations. Genes present in these signatures could be exploited to find new markers for such breast cancers. Moreover, we identified specific genomic rearrangements in these breast cancers which could be screened for in a diagnostic setting using FISH thus improving patient selection for BRCA1 and BRCA2 molecular genetic analysis. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6132.
Abstract 1996: Anticancer efficacy and mechanism of action of novel ginsenoside 25-OCH3-PPD, a natural product MDM2 inhibitor
Authors: Wei Wang, Hui Wang, Ruiwen Zhang
Journal: Cancer Research (2012)

Abstract Ginseng and related herbs have been used for various health benefits in over 2000 years. However, their mechanisms of action are not fully understood. In our laboratory, we have been isolating and characterizing ginsenosides as anticancer agents. 20(S)-25-methoxyl-dammarane-3α, 12α, 20-triol (25-OCH3-PPD), a newly identified natural product from Panax notoginseng, has shown activities against a variety of cancer cells in vitro and in vivo. However, the mechanisms of action for the novel anticancer agent are largely unknown. In this study, we discovered a novel mode of action for 25-OCH3-PPD: direct inhibition of the MDM2 oncoprotein. It is well established that the MDM2 oncogene plays a major role in human cancer development and progression. Its tumorigenic properties are associated with both p53-dependent and -independent pathways. We first demonstrated that, in a dose-dependent manner, 25-OCH3-PPD inhibited MDM2 expression in human breast cancer cell lines with different p53 backgrounds, including MCF-7 (p53 wild type and p53 knockout) and MDA-MB-468 (p53 mutate) cells. We further found that 25-OCH3-PPD inhibited MDM2 expression at the transcriptional level, affecting MDM2 promoter activity. We also observed that 25-OCH3-PPD decreased the survival, inhibited proliferation, induced apoptosis and led to G1 cell cycle arrest in the test breast cancer cells. The anti-cancer activities of 25-OCH3-PPD were reduced in MCF7 inducible MDM2-overexpression cells, further supporting the relevance of the MDM2 inhibitory effect to its anti-cancer activity. Moreover, 25-OCH3-PPD inhibited the growth of breast cancer xenograft tumors in vivo which was associated with its MDM2 inhibitory effects. 25-OCH3-PPD demonstrated low toxicity to non-cancer cells, and did not have any observable toxicity in animals. In summary, our preclinical data indicate that 25-OCH3-PPD is a potential therapeutic agent and that further preclinical and clinical development of this agent is warranted. These results also provide an example of a natural product/oncogene interaction as a novel mechanism of action for chemotherapeutic agents. (This work was supported by NIH/NCI grants R01 CA112029 and R01 CA121211 and a grant (BCTR070731) from Susan G Komen for the Cure.) 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 1996. doi:1538-7445.AM2012-1996
Abstract 2191: Development of a phylogenetic tree model to investigate the role of genetic mutations in a single endometrial tumor
Authors: Donghai Dai, Brandon B. Beck, Guoyi Zhang, Wentao Luo, Fan Wu, Stephen F. Kingsmore
Journal: Cancer Research (2010)

Abstract Modern genome sequencing technology has identified thousands of mutations in human tumors, but analysis of the role of genetic mutations in tumor development, utilizing prevalence information from many tumors, has yet to define in patients the functional contribution of genetic mutations, individually and collectively. To understand the genetic basis of human endometrial cancer, the fourth most common cancer in women, transcriptome sequencing was performed on an endometrial tumor paired with normal cervical tissue, and 26 non-synonymous somatic mutations were confirmed in the tumor genome DNA. A phylogenetic tree illustrating the mutational timeline was developed based upon the distribution of 26 mutations in 30 randomly-selected laser-captured single cells from the tumor sections. Five ubiquitous mutations were identified that are presumed to occur in the cancer founder cell of the tumor, which may collectively play critical roles in endometrial oncogenesis. However, further testing in 10 additional endometrial tumors failed to show overlapping mutations, indicating the lack of a single common oncogenic pathway for these endometrial tumors. Furthermore, we developed a mathematical and phylogenetic calculation of the cell population produced by a mutated ancestor cell, which quantifies the role of tumor-specific individual genetic mutations in cancer cell proliferation in a single resected patient tumor, without relying on prevalence information from other patients. This novel approach will be further tested in a larger sample set to determine whether multiple genetic mutations’ quantitative contributions can be used to predict patient outcomes.Functional contribution of individual mutationsmutant genesgenetic timeoffspring (million cells)ScoreC10orf26, GMPPA CREBL1 PPP2R2D SLCO2A13010000.997DDEF1 LOC728069298330.025LDLRAP1 PLEC129167−0.06MYST1286670.025GORASP2 ILKAP, LOC72942328100−0.07INCENP, ME22867−0.09PDZD8274000.011AP1G227267−0.01POLE4, SDC2263000.025PIF1, XYL226100−0.04TOR3A251670.01LOC642934251330CCDC50, CIZ12467−0.01LOC645634241000.014 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 2191.