tbuckley/cabot-search huggingface dataset:
Hemobilia as a rare complication after endoscopic ultrasound-guided fine-needle aspiration for hilar cholangiocarcinoma
Authors: K. Kawakubo, H. Isayama, N. Takahara, N. Yamamoto, H. Kogure, T. Sasaki, K. Hirano, N. Sasahira, M. Tada, K. Koike
Journal: Endoscopy (2011)

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a useful and safe procedure for obtaining tissue samples for the diagnosis of lesions adjacent to the gastrointestinal tract [1] [2]. We describe a first case of hemobilia presenting as obstructive jaundice after EUS-FNA for hilar cholangiocarcinoma.
A Smooth Patch on the Tongue
Authors: Prasanta Basak, Stephen Jesmajian
Journal: New England Journal of Medicine (2010)

A smooth, well-demarcated patch without papillae on the posterior portion of the tongue was discovered incidentally while the oropharynx of a 65-year-old woman was being examined. On inquiry, she said that she had been aware of the unusual appearance of her tongue since childhood and that the lesion's size and shape had been stable since that time. She reported no tongue pain, dysphagia, dysarthria, or bleeding. There was no evidence of candidiasis on the tongue or adjacent structures. There was no regional lymphadenopathy, and the patient reported no constitutional symptoms such as fever or weight loss. There was no history . . .
Abstract 2922: Stoichiometric depletion of glutathione by anticancer agent JS-K.
Authors: Ryan J. Holland, Anna E. Maciag, Robert Y.-S. Cheng, Luis G. Rodriguez, Joseph E. Saavedra, Lucy M. Anderson, Larry K. Keefer
Journal: Cancer Research (2013)

Abstract JS-K is a nitric oxide (NO)-releasing drug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models. It is activated for NO release by reaction with glutathione (GSH), a step that consumes an equivalent of GSH, effectively irreversibly. The two equivalents of NO thus released can be oxidized intracellularly, leading to S-nitrosylation and S-glutathionylation of GSH in a cascade of further reactions that consume additional equivalents of GSH and generate GSH disulfide (GSSG). The GSH/GSSG redox couple is the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. Here we show that depletion of GSH on treating U937 leukemia cells with JS-K markedly raises the reduction potential of the cell, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. The data indicate that multiplicative depletion of reduced GSH and deregulation of intracellular redox balance are important steps in the mechanism of JS-K's cytotoxic action. An additional GSH-consuming pathway was found to occur with Double JS-K, an aryl bis(diazeniumdiolate) created with the purpose of doubling the payload of NO. Double JS-K caused pronounced protein glutathionylation, in contrast to its monovalent counterpart. Serving as a bivalent electrophile, Double JS-K irreversibly crosslinked GSH to protein thiols through its aromatic linker. The results provide a previously unrecognized component of the multifaceted mechanism of action of bivalent electrophiles of the arylated diazeniumdiolate class. Citation Format: Ryan J. Holland, Anna E. Maciag, Robert Y.-S. Cheng, Luis G. Rodriguez, Joseph E. Saavedra, Lucy M. Anderson, Larry K. Keefer. Stoichiometric depletion of glutathione by anticancer 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 2922. doi:10.1158/1538-7445.AM2013-2922
Abstract P2-09-11: Response of Invasive Lobular Cancers to Neoadjuvant Therapy
Authors: RA Mukhtar, ES Hwang, C Livasy, LJ. Esserman
Journal: Cancer Research (2010)

Abstract Background Invasive lobular carcinoma (ILC) makes up 10-15% of all breast cancer. While neoadjuvant therapy (NAC) is increasingly used in locally advanced invasive cancers, some evidence suggests that ILC does not respond to NAC. The I-SPY trial has shown an association between expression of high risk gene signatures and increased pathologic complete response (pCR) to NAC. We hypothesized that compared to invasive ductal carcinoma (IDC), ILC would have decreased expression of high risk gene signatures, and decreased rates of pCR. Methods We analyzed data from 221 patients in the I-SPY trial, a prospective, multicenter neoadjuvant breast cancer trial with serial pathology, imaging, and expression arrays. A dedicated breast pathologist at each site reviewed histology, and e-cadherin staining was performed centrally on cases identified as ILC. We compared rates of wound healing signature activation, NKI (Netherlands Cancer Institute) profile status, and proportion of pCR in ILC compared to IDC. Other comparisons were the presence of p53 mutations, molecular subtype, and MRI phenotype. We used the chi-squared test, Fisher's exact test, and Student's t-test for comparisons. Results Of 221 patients, histology on core biopsy was ductal in 195 (88%), lobular in 18 (8%), and mixed ducto-lobular in 8 (3.6%); the last cases were included in the IDC group. ILC and IDC cases were similar by tumor size, age at diagnosis, and race. Expression array data were available on 12 of 18 (67%) ILC and 149 of 203 (73%) IDC. The proportion of p53 mutations, basal subtype and NKI high risk did not differ significantly. However, ILCs were significantly less likely to express the activated wound healing signature compared to IDCs (50% vs 80%, p = 0.03) and had different imaging phenotypes, with most ILCs appearing multinodular or diffuse on MRI (p = 0.028). Three of 18 (17%) ILCs had a pCR, compared to 55/197 (28%) IDCs. Of the 18 ILC, 11 of 15 tested were e-cadherin negative (73%). Of 18 ILCs, 16 (89%) were hormone receptor (HR) positive, and comparison to HR+ IDC showed similar rates of pCR in the two groups (19% pCR in HR+ ILC vs 14% pCR in HR+ IDC). There was no significant difference in expression of the activated wound healing signature when comparing ILCs to HR+ IDC. Conclusions There is significant heterogeneity within ILC, such that no one molecular subtype or genetic expression signature identifies all ILCs. The rates of pCR among ILC are similar to those seen in HR+ cancers. Although larger studies are needed to confirm these findings, we saw no evidence that ILC differs from IDC in response to NAC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-11.
Personalised medicine and National Health Service culture
Authors: Edward H. Reynolds
Journal: Journal of the Royal Society of Medicine (2013)

I was surprised to read that personalised medicine and healthcare has now become a genetical and pharmacological concept.1 There is a much older and more important concept of personalised medicine and healthcare, not least because many patients do not need any medication at all. Nearly all patients greatly value the personal attention of a trusted healthcare worker, medically qualified or otherwise; someone who has the time and communication skills to listen to their varied and sometimes irrational needs, anxieties and beliefs, and is also willing to address the family, psychological and social aspects of their disorder, whether or not they have a physical illness. This personal relationship has a powerful therapeutic effect even if we do not understand the mechanism. It can reduce the need for medication in many clinical situations.

It is a paradox of modern Western scientific medicine that it has been associated with an enormous growth in alternative medicine. This is at least in part due to the personal care provided by alternative practitioners, while at the same time our modern evidence-based scientific medicine has become increasingly multidisciplinary and impersonal. The latter is a contributory factor to the culture problems in the NHS, which have been highlighted by the Francis report.2 One way of addressing this culture is to re-introduce the older and neglected concept of personalised medicine into the NHS, including continuity of care. Individualised medication perhaps, but personalised medicine and healthcare as traditionally understood please.
Kidney injury and hematuria as a result of duodenal perforation by an ingested toothpick
Authors: Hong-Ze Zeng, Qi-Ming Wang, Wei Liu, Yi Mou, Hang Yi, Shui-Fang Wang, Bing Hu
Journal: Endoscopy (2014)

A 49-year-old man presented to our hospital with upper abdominal pain which had lasted for the previous 5 days. The pain was not accompanied by nausea or emesis but was more intense after he had consumed dry, hard food. Gastroscopy at another hospital showed a toothpick embedded in the duodenal flexure ([Fig. 1]). When admitted to our hospital, the patient reported hematuria without urinary frequency, urgency or odynuria. His vital signs were stable and his abdomen was soft. There was slight tenderness on the left upper quadrant with no rebound tenderness. Complete blood count and blood chemistry were normal. An abdominal computed tomography (CT) scan showed a hyperdense needle-shaped structure penetrating the duodenal wall and into the right kidney ([Fig. 2]). Contrast enhanced CT demonstrated no vessel injury or hematoma. An attempt to remove the toothpick endoscopically was unsuccessful because the toothpick was not located ([Fig. 3]). A repeat abdominal CT showed that the toothpick was still present in the duodenum ([Fig. 4]). The patient then underwent exploratory laparotomy and duodenorrhaphy. During surgery, a 6.5-cm toothpick was found ([Fig. 5]). His post-operative recovery was uneventful and he was discharged after a week.
Abstract 564: Bim-independent apoptosis by benzyl isothiocyanate in human breast cancer cells is mediated by PUMA
Authors: Marie Lue Antony, Su-Hyeong Kim, Shivendra V. Singh
Journal: Cancer Research (2012)

Abstract Benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetables, is a promising agent for chemoprevention of breast cancer as evidenced by efficacy against xenografted breast cancer cells (e.g., MDA-MB-231 cells) and in a transgenic mouse model (MMTV-neu). We have shown previously that mammary cancer chemoprevention with dietary BITC administration in the MMTV-neu mice is associated with apoptosis induction. In cellular models of human breast cancer (MCF-7 and MDA-MB-231 cells), the BITC-induced apoptosis is initiated by reactive oxygen species (ROS) resulting from inhibition of complex III of the mitochondrial respiratory chain. The present study builds upon these observations to provide insights into the molecular circuitry of BITC-induced apoptosis downstream of ROS production. Because BITC-induced apoptosis in different cell types is associated with activation of c-Jun N-terminal kinase (JNK), we initially focused on Bim as this protein is a downstream mediator of JNK-regulated apoptosis. Bim protein expression (extra-long form) was increased by about 2-3-fold upon 24-hour treatment of MDA-MB-231 cells with pharmacologically relevant concentrations of BITC (2.5 and 5 μM BITC). However, RNA interference of Bim had no effect on BITC-induced apoptosis as judged by analysis of cytoplasmic histone-associated DNA fragment release into the cytosol. Moreover, the BITC-treated MCF-7 cells exhibited a marked decrease in Bim (extra-long form) protein level. BITC treatment resulted in induction of PUMA in both MCF-7 and MDA-MB-231 cells, but as expected, this response was more pronounced in the MCF-7 cells which express wild-type p53. The BITC-induced apoptosis was partially but statistically significantly attenuated by RNA interference of PUMA in MCF-7 cells. Consistent with these observations, genetic depletion of PUMA in HCT-116 cells conferred partial but significant protection against BITC-induced apoptosis. Attenuation of BITC-induced apoptosis in PUMA knockout cells was accompanied by enhanced G2/M phase cell cycle arrest compared with isogenic wild-type HCT-116 cells. The BITC-mediated inhibition of MDA-MB-231 xenograft growth in vivo was associated with PUMA induction in the tumor as evidenced by immunohistochemistry and western blotting. In conclusion, these results indicate that Bim-independent apoptosis by BITC is partly mediated by PUMA. This investigation was supported by the US PHS grant CA129347 awarded by the National Cancer Institute. 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 564. doi:1538-7445.AM2012-564
131I-SPECT/CT Found an Ovarian Metastasis Covered by Iliac Metastasis on 131I Whole-Body Scan in a Patient With Papillary Thyroid Carcinoma
Authors: Yan-Hong Xu, Xue-Mei Huang, Hong-Jun Song, Zhong-Ling Qiu, Quan-Yong Luo
Journal: Clinical Nuclear Medicine (2011)

Ovarian metastasis from differentiated thyroid carcinoma is very exceptional. In this study, we describe a case of a 42-year-old woman with an 131I-uptake lesion in the left pelvic cavity from papillary thyroid carcinoma incidentally found by 131I-SPECT/CT, which was concealed by the iliac metastasis on 131I whole-body scan. Pelvic MRI indicated that the lesion was most likely to be an ovarian mass. Finally, the mass in the pelvic cavity was histologically confirmed to be an ovarian metastasis from papillary thyroid carcinoma. The presented case highlights that 131I-SPECT/CT is more effective for the localization and identification of metastases from differentiated thyroid carcinoma than planar 131I whole-body scan.
Long-Term Results of Intracoronary Bone Marrow Cell Transplantation
Authors: Milan Kaminek, Jaroslav Meluzin, Roman Panovský, Iva Metelkova, Miroslava Budikova, Marek Richter
Journal: Clinical Nuclear Medicine (2010)

This study assessed the effect of different levels of tracer uptake in the infarcted area on improvement of left ventricular function in patients treated by intracoronary mononuclear bone marrow cell (BMC) transplantation during long-term (12-month) follow-up.Thirty-seven patients with irreversible injury after their first acute myocardial infarction, as confirmed by dobutamine echocardiography and sestamibi single-photon emission computed tomography/fluorodeoxyglucose positron emission tomography underwent BMC transplantation (1 × 10(8) cells), whereas 36 similar patients were randomly assigned to a control group.In 16 BMC-treated patients with very low sestamibi uptake (<30% of maximum) in the infarcted area, the mean baseline left ventricular ejection fraction (LVEF) increased at 3- and 12-month follow-up by 3% and 4% only, and mean end-diastolic/end-systolic volumes (EDV/ESV) enlarged by 20/7 mL and 23/9 mL, respectively (P = NS vs. controls). In 21 BMC-treated patients with higher sestamibi uptake (31%-50% of maximum), the LVEF improved by 6% and 7%, and EDV/ESV decreased by 4/13 mL and 1/13 mL, respectively (P < 0.05 vs. BMC-treated subgroup with low uptake and control subjects). There was no statistically significant difference in LVEF, EDV, or ESV changes between controls with low versus higher sestamibi uptake.During long-term follow-up, the post-transplant improvement of left ventricular function remained significant only in BMC-treated patients with higher sestamibi uptake.
Screening methods for thyroid hormone disruptors.
Authors: M DeVito, L Biegel, A Brouwer, S Brown, F Brucker-Davis, A O Cheek, R Christensen, T Colborn, P Cooke, J Crissman, K Crofton, D Doerge, E Gray, P Hauser, P Hurley, M Kohn, J Lazar, S McMaster, M McClain, E McConnell, C Meier, R Miller, J Tietge, R Tyl
Journal: Environmental Health Perspectives (1999)

The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen.
PTH-062 Emergency Admissions For Alcohol Related Conditions: Making Sense Of Routine Data
Authors: P Lekharaju, E Thompson, M Shawihdi, M Pearson, S Hood, K Bodger
Journal: Gut (2014)

<h3>Introduction</h3> Alcohol-related emergency admissions (ARA) are a major and rising hospital burden, resulting from conditions that range from short-term toxicity to end-stage organ damage, notably liver disease. We report a project to develop analyses of routine coding data, with a particular focus on metrics related to ‘frequent flyers’ (FFs) as targets for new service interventions. <h3>Methods</h3> Sources of data: Hospital Episode Statistics for all English hospitals (2006–2008); Inpatient coding data and AED attendances for our Trust (2006–2013). Analysis: Screening of all non-emergency episodes for alcohol-related codes at any position to flag ARAs; linkage of individual cases to extract all admissions and order chronologically; allocation of each admission to a category based on primary and lower order diagnoses (flagging LIVER and NON-LIVER admissions); identification of frequent flyers (FFs) based on various definitions of admission count; linkage of ARAs to all-cause AED attendances in local data; funnel-plot analyses of patterns across English Trusts; longitudinal trends in local data. <h3>Results</h3> Nationally: 219,158 ARAs in 139,077 patients (2006–2008), <i>mean age</i> (sd): 49.5 yrs (16); <i>males</i>: 99,271 (71%); <i>Deprivation</i><sup>:</sup> Quintile 1 (most deprived) 36.4%, Quintile 5 (least): 9.4%; <i>Co-morbidity</i> (Charlson), 0.44 (0.68); <i>LoS</i>: 7 (14) days; <i>Inpatient death</i>: 6,656 (4.8%). No. admissions ranged from 1–60 per individual. <i>Frequent Flyers</i>: In two years, a cut-off of 5+ admissions identified 5,404 FFs (4% of patients; accounting for 18% of ARAs nationally) whereas 10+ identified 909 FFs (1% of patients; 6% of ARAs). Mean ARAs per Trust was 927 (range: 235–3930) with 6-fold variation in% of FFs (1.3% to 7.7%) and 4-fold variation in% with liver disease across English hospitals (range: 7.6–30.2%). As expected, FFs coded with liver disease had significantly higher LoS and mortality risk consistent with end-stage organ damage and “unavoidable” admissions. Locally: 21,308 ARAs in 16,305 patients (2006–2012), with annual number of cases rising from 1,615 to 4,603. Defining FFs as 5+ ARAs per year, there were 320 FFs (2% of patients; 10% of ARAs). There was a year-on-year rise in ARAs (2,454–5,510) and AED attendances without admission (2,499–5,979). However, FFs (5+ admissions) declined from 64 to 47 between 2006 and 2012 and non-liver FFs from 25 to 12, suggesting a positive impact of new local services on multiple attenders, especially those lacking established liver disease. <h3>Conclusion</h3> We have developed a set of candidate metrics focussed on FFs, short stays and selected baskets of conditions to provide data to support front-line acute alcohol services. <h3>Disclosure of Interest</h3> None Declared.
Abstract 2158: Loss of heterozygosity at chromosome 3p in ductal and lobular breast carcinomas
Authors: Marcia Maria Costa de Oliveira, Luciane R. Cavalli, Cícero Andrade Urban, Rubens Silveira de Lima, Enilze Maria de Souza Fonseca Ribeiro, Iglenir João Cavalli
Journal: Cancer Research (2010)

Abstract The two main histological types of infiltrating breast cancer, lobular (ILC) and the more common ductal (IDC) carcinoma are morphologically and clinically distinct revealing different patterns of chromosomal aberrations and gene expression. Loss of heterozygosity (LOH) at chromosome 3p is frequently observed in breast tumors and a whole genome study utilizing a SNP array assay found a significantly higher frequency of LOH on 3p in ductal than lobular tumors. In order to investigate the molecular alterations at 3p associated with these breast cancer subtypes we analyzed LOH in 118 IDC and 18 ILC samples using seven microsatellite markers. Genomic DNA was obtained from frozen tumor tissue and peripheral blood was used as a normal reference. All samples were genotyped on a MegaBace® system and analyzed using Fragment Profiler® Version 2.1 software. Significance was determined using Chi-square test (X2). A significant higher frequency of LOH was observed in IDC (62.7%) when compared with ILC (38.9%) (X2=4.60 P&amp;lt;0.05). When the markers were analyzed separately, LOH at three of them, D3S1307 in 3p26.3, D3S1286 in 3p24.3 and D3S1300 (intragenic FHIT) in 3p14.2, were significantly more frequent in ductal than lobular tumors (X2= 4.66 P&amp;lt;0.05; X2= 3.99 P&amp;lt;0.05 and X2= 5.43 P&amp;lt;0.025, respectively). D3S1307 marker showed the highest frequency of LOH in IDC (47.8%) and associations between loss of this marker and loss of estrogen and progesterone receptors were found in these samples (X2= 4.61 P&amp;lt;0.05 and X2= 4.49 P&amp;lt;0.05, respectively) suggesting that there are genes on this region involved in the control of differentiation of ductal tumors. For lobular tumors, the highest loss (53.3%) was seen for D3S1274 on 3p12.3 (intragenic DUTT1). In addition to confirm previous studies these findings suggest that specific losses on 3p (3p26.3, 3p24.3 and 3p14.2) are more common in IDC when compared with ILC breast tumors. 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 2158.