tbuckley/cabot-search huggingface dataset:
Abstract 479: Targeting tumor initiating cells inhibits tumor growth and serial transplantation ability in soft-tissue sarcomas
Authors: Qingxia Wei, Chang Ye Yale Wang, Feifei Zheng, Phil Zhang, Weishi Wang, Jay S. Wunder, Benjamin A. Alman
Journal: Cancer Research (2011)

Abstract Tumors contain heterogeneous cell populations. There is a subpopulation of cells enriched for tumor initiating potential in sarcomas, which excludes Hoechst dye, and resides in the “side population” when subjected to flow cytometry (SP cells). These cells possess multi-potent differentiation potential, and as such they behave as “cancer stem cells” (CSCs), while the remainder of tumor cells act as “transient amplifying” cells. Because traditional cancer therapies may not target these tumor initiating cells, the persistence of SP cells could be responsible for relapse or a failed response to therapy. To detect signaling pathways that are differentially regulated in SP cells versus the remainder (non-SP) of the cells, we used gene profiling by microarray to compare their differences. RNA expressions were compared between these two cell populations from six malignant fibrous histiocytoma (MFH) samples using microarray. Differentially regulated genes were then analyzed by compiling a list of genes that showed a fold change greater than 1.25 in at least five of the six samples all in the same direction, and identifying if the list is enriched for genes involved in common molecular pathways, using Genespring® analysis tool. Two of the differentially regulated pathways detected were the Hedgehog signaling pathway and the Notch signaling pathway. Differential target gene expression for both pathways was verified using quantitative PCR. Triparanol (an agent that inhibits hedgehog signaling) and DAPT (an agent that inhibits Notch signaling) were used to treat eight primary MFH xenografts established in NOD-SCID mice. The xenografts produced visible tumors six weeks after subcutaneous transplantation, after which the mice were treated with one of the agents or a carrier as a control. At the end of the treatment, the tumors were harvested; their growth and SP% were assessed and compared; and the cells harvested from the treated xenografts were again implanted into mice to study the rate of re-growth upon secondary transplantation. Both triparanol and the Notch blocker DAPT treatment suppressed these pathways in tumor cells, depleted the abundance of SP cells, and reduced tumour growth. Intriguingly, treatment substantially inhibited the tumour-initiating potential of the treated sarcoma cells upon secondary transplantation. The data provides support that SP cells act as tumour initiating cells in sarcomas and shows that targeting the SP (in this case by targeting the Hh and Notch pathways) is an enticing approach for sarcoma therapy. 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 479. doi:10.1158/1538-7445.AM2011-479
Reversal by Phenylephrine of the Beneficial Effects of Intravenous Nitroglycerin in Patients with Acute Myocardial Infarction
Authors: Patricia C. Come, John T. Flaherty, Michael G. Baird, Jacques R. Rouleau, Myron L. Weisfeldt, H. Leon Greene, Lewis Becker, Bertram Pitt
Journal: New England Journal of Medicine (1975)

Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 ± 6 to 85 ± 6 mm Hg (P < 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 ± 2 to 11 ± 2 mm Hg (P < 0.001). ∑ST, the sum of ST-segment elevations in 16 precordial leads, decreased (P < 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 ± 4 mm Hg (P < 0.001) for 30 minutes, increased left ventricular filling pressure to 17 ± 2 mm Hg (P < 0.05)and also significantly increased ∑ST (P < 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction. (N Engl J Med 293:1003–1007, 1975)
In Vivo Selection of Hepatocytes Transduced with Adeno-Associated Viral Vectors
Authors: S J Chen, J Tazelaar, A D Moscioni, J M Wilson
Journal: Molecular Therapy (2000)

A murine model for hereditary tyrosinemia Type I (HTI) was evaluated for in vivo gene therapy with adeno-associated viral (AAV) vectors expressing the enzyme fumarylacetoacetate hydrolase. Transduction of a limited number of hepatocytes was accomplished following infusion of vector into the portal circulation. Corrected hepatocytes were expanded in vivo by withdrawing a drug which prevents the accumulation of toxic metabolites. The liver was eventually repopulated with hepatocytes harboring a functional and apparently integrated AAV provirus. Recipient animals regained normal liver function and architecture and the underlying metabolic derangements were normalized. After 9 months, vector-treated animals showed benign hepatomas, whereas in untreated animals areas of marked dysplasia were present within hepatomas.
Long-Term Growth in Juvenile Acquired Hypothyroidism:
Authors: S A Rivkees, H H Bode, J D Crawford
Journal: New England Journal of Medicine (1988)

It has been suggested that complete catch-up growth is achieved with treatment in patients with juvenile acquired hypothyroidism. We tested this assumption by examining long-term growth in 18 girls (mean [+/- SD] age, 11.4 +/- 2.7 years; bone age, 6.2 +/- 3.1 years) and 6 boys (age, 10.6 +/- 4.7 years; bone age, 6.4 +/- 2.7 years) with severe primary hypothyroidism (serum thyroxine level 1.1 +/- 0.3 micrograms per deciliter [13 +/- 4 nmol per liter]). At diagnosis, heights were 4.04 +/- 0.5 and 3.15 +/- 0.4 SD below the mean heights for age of normal girls and boys, respectively. The patients were treated with levothyroxine (3.4 +/- 0.3 micrograms per kilogram of body weight per day) to maintain normal thyroid function. During the first 18 months of therapy, the children's skeletal maturation exceeded the maturation expected for their statural growth, regardless of whether or not they were undergoing pubertal development. Predictions of decreased adult height were based on these observations. At maturity, girls and boys stood approximately 2 SD below normal adult stature, at 149 +/- 5.0 cm and 168 +/- 5.1 cm, respectively. Heights at maturity were also lower than midparental heights (P less than 0.01) and lower than pre-illness standard-deviation scores for height (P less than 0.01). The deficit in adult stature was significantly related to the duration of hypothyroidism before treatment (P less than 0.01). We conclude that despite treatment, prolonged juvenile acquired hypothyroidism results in a permanent height deficit related to the duration of thyroxine deficiency before treatment.
Primary Care for Survivors of Breast Cancer
Authors: H J Burstein, E P Winer
Journal: New England Journal of Medicine (2000)

There are more than 2 million women in the United States alone who are living with a history of breast cancer.1,2 Screening programs have increased the number of women in whom invasive or noninvasive breast cancer has been diagnosed, and earlier detection and better treatment have led to improved prognosis. Thus, although the average U.S. woman has a 12.6 percent lifetime risk of breast cancer — a percentage that has risen in recent years — her risk of death from breast cancer has remained constant at 3.6 percent. Most women in whom breast cancer is diagnosed do not die . . .
Abstract 1277: Differential roles of TRAIL death receptors during TRAIL-induced signaling pathways
Authors: So Y. Kim, Seeun Oh, Bo K. Sun, Hye J. Choi, Joo-Hyuk Sohn, Jae J. Song, Joo-Hang Kim
Journal: Cancer Research (2010)

Abstract In this paper, we demonstrate that TRAIL death receptors (DR4, DR5) have their own distinctive function during TRAIL treatment. For the examination of each receptor's role, FACS analysis, biotin labeling to plasma membrane and siRNA technique were used. Previously, we have shown that TRAIL has induced anti-apoptotic signals as well as apoptotic signals. Here, we investigated whether TRAIL death receptors (DR4 and DR5) have their own unique function. In TRAIL-sensitive cell line (DU-145), TRAIL induced much more rapid degradation of DR4 than that of DR5. On the other hand, in TRAIL-resistance cell line (SK-BR-3) with higher level of ErbB2/pAkt, DR5 was rarely expressed, while DR4 was distinctively expressed. We also have shown that relatively much more amount of c-Cbl in SK-BR-3 has played a role of supplying additional pAkt which can be also persistently provided by ErbB2. These phenomena are confirmed by knock down of c-Cbl expression using adenovirus expressing si-c-Cbl. Taken together, we suggest that DR4 functions to transmit apoptosis signals with a favor for anti-apoptosis signals, whereas DR5 functions to transmit apoptosis signals without a favor for anti-apoptosis signals. Correspondance: Jae J. Song (jjs109@yuhs.ac) and Joo-Hang Kim (kjhang@yuhs.ac) 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 1277.
PTU-150 Quality of life before and after intestinal transplantation
Authors: C Pither, S Duncan, H Tincknell, C Hanson, B Chukualim, J Woodward, A Butler, S Middleton
Journal: Gut (2012)

<h3>Introduction</h3> Survival following intestinal transplantation has substantially improved over the last decade and if this trend continues quality of life (QOL) may be considered as a major indication for transplantation. It is important to establish if QOL can be enhanced by transplantation and whether some aspects are more inclined to improve than others. <h3>Methods</h3> QOL was assessed using Short form 36 (SF36) in a cohort of consecutive patients who had either been assessed for, undergone or, were awaiting transplantation. Data were scored using validated criteria for different QOL functions. The statistical package SPSS (IBM) was used to analyse the data. <h3>Results</h3> 62 data sets were available, 26 pre-transplant and 36 post-transplant. Grouped data showed significantly better physical function (p=0.03*), social functioning (p=0.01*), general health (p=0.006*) and emotional role limitation (p=0.02*) in the post-transplant group. Paired pre and post-operative data were available for eight patients: function scores improved significantly for general health (p0.04**). Improvements in physical function, social functioning, emotional role limitations, energy/fatigue, emotional well-being and pain were seen but this did not reach statistical significance. Physical role limitation was the only function to decline. Of the eight pairs, two patients had significantly better overall scores post transplant (p=0.02, p=0.01**) and four had improved overall scores not reaching statistical significance. *independent T test **Wilcoxon signed rank. <h3>Conclusion</h3> In this small experience there was an overall trend for better quality of life after transplantation, but certain QOL parameters appear to improve more than others. If quality of life is to be an indication for transplantation it will be important to select patients on the basis of quality of life parameters that are known to improve after transplantation. Longer term and larger studies are required. <h3>Competing interests</h3> None declared.
Fatal cerebral air embolism complicating esophageal dilation
Authors: E. Zampeli, E. Tsagalou, I. Kanakakis, C. Giannopoulos, A. Tzanetaki, K. Vemos, S. Michopoulos
Journal: Endoscopy (2013)

We present the case of a 72-year-old man with cardiac adenocarcinoma treated with a metal stent and radiation therapy for pulmonary metastases. After 6 months of this treatment he developed a malignant esophageal stricture. Endoscopy was carried out under moderate sedation and constant monitoring. Dilation with an over-the-scope balloon dilator (CRE single-use, wire-guided esophageal dilation balloon, 240 cm, balloon length 5.5 cm, outer diameter 10 – 12 mm, Boston Scientific, Natick, Massachusetts, USA) was carried out. The patient's vital signs and oxygen saturation were normal throughout the procedure. However, when flumazenil was administered the patient did not recover. Neurological examination revealed a Glasgow Coma Scale score of 4/15 points, pupils equal and reactive to light, and no focal neurological signs. Cardiac and respiratory functions were stable. Brain computed tomography (CT) revealed bilateral multifocal cerebral air embolism with air bubbles within the sagittal sinus, straight sinus, great vein of Galen, and the cerebral venous network of the cortex ([Fig. 1]), and 24 hours later the patient died.
INSULIN PROVISION THERAPY AND INCREASED MORTALITY IN ELDERLY PATIENTS WITH DIABETES MELLITUS AND STABLE ISCHEMIC HEART DISEASE: INSIGHTS FROM BARI-2D TRIAL
Authors: Abdulla Damluji, Erin R. Cohen, Robert Myerburg, Mauricio Cohen, Mauro Moscucci, Michael Rich, Daniel Forman
Journal: Journal of the American College of Cardiology (2015)
Giant liver cyst caused by tuberculosis infection and masquerading as malignant peritonitis
Authors: Takeshi Ogura, Yoshitaka Kurisu, Daisuke Masuda, Akira Imoto, Saori Onda, Rieko Kamiyama, Nobu Nishioka, Kazuhisa Uchiyama, Kazuhide Higuchi
Journal: Endoscopy (2014)

Liver involvement in tuberculosis infection is rare, and the radiological findings have previously been interpreted as multiple liver tumors, hemangioma, abscess, or cirrhosis [1] [2] [3]. Conversely, hepatic cyst is a common benign liver tumor that is usually easy to diagnose as a simple hepatic cyst. Despite advances in imaging techniques, differentiating complicated hepatic cysts from other tumors, including malignancies, sometimes remains challenging. We describe a rare case of a giant liver cyst caused by tuberculosis and masquerading as malignant peritonitis.
Optimal Imaging Time for Delayed Images in the Diagnosis of Abnormal Parathyroid Tissue With Tc-99m Sestamibi
Authors: JOSEFINA JOFRÉ, PATRICIO GONZÁLEZ, TERESA MASSARDO, AQUILES ZAVALA
Journal: Clinical Nuclear Medicine (1999)

Double-phase scintigraphy with Tc-99m sestamibi is a good method to detect hyperfunctioning parathyroid glands. This study tried to determine the best time for delayed images: 2 or 4 hours.Fifty-six patients were studied, and 35 of them had primary hyperparathyroidism (mean age, 53 +/- 13 years; 54% were women). Cervical ultrasonography was performed on 29 of 56 (52%) patients and surgery in 16 of 56 (29%) patients. The dose was 740 MBq (20 mCi) given intravenously, and the acquisition was performed at 10 minutes, 2 h, and 4 h using anterior views, including the mediastinum. Studies that had positive results were analyzed blindly by two independent observers, who selected the best definition for abnormal activity.Nineteen of 56 (34%) studies were negative and 37 of 56 (66%) were positive, 25 of them with one focus and 12 with two or more parathyroid foci. Analysis revealed 76% agreement between the observers (the rest was classified by consensus). In 70% of the cases, the best delayed image was obtained at 2 hours, in 16% at 4 hours (P < 0.00001), and in 14% both images were similar. In those cases with better images at 4 hours, the 2-hour images also showed the lesions. In two patients, lesions were seen only at 2 hours. These results could be explained by tracer decay, washout of parathyroid activity, or both.The best protocol should include the early 10-minute image and the 2-hour delayed view. Further controls do not appear necessary. This may be important for patient throughput.
SAT0304 Long-Term Costs of Biologics in the Treatment of Psoriatic Arthritis in the United States
Authors: S. Cure, H. Cawston, V. Damera, T. Tencer, F. Zhang, S. R. Feldman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The introduction of biologic therapies has dramatically changed the management of psoriatic arthritis (PsA), however, these therapies are more expensive than previous treatments. To our knowledge, there is little information about the economic impact of biologic use over a long-term period. <h3>Objectives</h3> The study aimed to estimate long-term costs of biologics in the treatment of PsA patients in the United States. <h3>Methods</h3> We developed a 10-year Markov model describing the treatment pathway of patients with PsA who had failed prior oral DMARD therapy, using monthly cycles. Clinical efficacy data were obtained from published pivotal study results and literature. Costs, resource utilisation and treatment pathways were obtained from the literature and expert opinion. Patients transitioned through two lines of biologics (etanercept, infliximab, golimumab or adalimumab as first or second line) followed by best supportive care. Response to therapy was defined as the probability of PsARC response at the end of the trial period. Patients transitioned to the next line of therapy in case of non-response or discontinuation due to other causes (a short-term annual drop-out rate of 32% and a long-term rate of 16.5% were assumed). All-cause death was included and adjusted to reflect the increased mortality associated with PsA. Treatment and administration, monitoring, and hospitalisation costs were included. An annual discount rate of 3% was used. Probabilistic sensitivity analysis was conducted on key model parameters. For each first-line biologic option, average results across second-line biologic therapies were reported. <h3>Results</h3> From a third-party payer's perspective, the estimated 10-year cumulative direct costs per patient were $214,642 (95% CrI: $214,171; $221,074) with etanercept as first-line biologic therapy, $203,140 (95% CrI: 202,632; $208,398) with infliximab, $218,703 (95% CrI: $217,992; $224,255) with golimumab and $208,840 (95% CrI: $208,192; $215,014) with adalimumab. Across scenarios, drug costs represented between 89.4% and 91.1% of total costs, monitoring costs between 4.5% and 6.3%, and hospitalisation costs between 4.3% and 4.9%. <h3>Conclusions</h3> Biologic therapies represent a significant cost burden to payers over a 10-year period. First line therapy with infliximab produced the lowest overall costs. <h3>Disclosure of Interest</h3> S. Cure Consultant for: Celgene Corporation, Employee of: OptumInsight, H. Cawston Consultant for: Celgene Corporation, Employee of: OptumInsight, V. Damera Consultant for: Celgene Corporation, Employee of: OptumInsight, T. Tencer Employee of: Celgene Corporation, F. Zhang Employee of: Celgene Corporation, S. Feldman Grant/research support from: Celgene, Abbott, Amgen, Janssen, Consultant for: Celgene, Abbott, Amgen, Janssen
Arthur Levin Brian Robert Blakemore Lumb John Callender ("Jack") Nicholson John Lawrence Pearce Allan Thomas Marsh Roberts David Anthony Slessor Gordon Cunningham Taylor Arthur Leslie Tulk David Wilson Wallace John Michael Wilson
Authors: G. Levin, M R Lumb, F. Assinder, G. Seddon, M. White, A. B Otlet, G. Atkin, M. Whittet, W E Brooke, R. G H Wallace, A. Bird
Journal: BMJ (1999)

Early in the war he was appointed to the Royal Masonic Hospital, which was an officers' hospital.Later he served with the Royal Army Medical Corps in India and the Far East.After the war he entered general practice
Suspected new wave of muscular sarcocystosis in travellers returning from Tioman Island, Malaysia, May 2014
Authors: D Tappe, A Stich, A Langeheinecke, F von Sonnenburg, B Muntau, J Schäfer, G Slesak
Journal: Eurosurveillance (2014)

In May 2014, six patients presented in Germany with a Sarcocystis-associated febrile myositis syndrome after returning from Tioman Island, Malaysia. During two earlier waves of infections, in 2011 and 2012, about 100 travellers returning to various European countries from the island were affected. While the first two waves were associated with travel to Tioman Island mostly during the summer months, this current series of infections is associated with travel in early spring, possibly indicating an upcoming new epidemic.
P137 Practise and Effects of Autoimmune Screening in Pulmonary Fibrosis
Authors: L Anning, MA Gibbons
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> Patients with pulmonary fibrosis can have features of autoimmune disorders that do not meet criteria for connective tissue disease (CTD), sometimes referred to as autoimmune-featured interstitial lung disease (AIF-ILD). Incorrect diagnosis and labelling could have important implications for treatment and prognosis. We analysed the prevalence and type of immune profile performed to investigate patients with pulmonary fibrosis to determine what effect it had on subsequent management, and to assess variations in clinical practise. <h3>Methods</h3> Retrospective review of patients attending the ILD and general respiratory clinics at our centre (n=75) with a diagnosis of pulmonary fibrosis, not known to be due to a CTD, or to be caused by a drug reaction, hypersensitivity, or sarcoidosis. <h3>Results</h3> Seventy-five cases were reviewed (76% male). Age range was 55–88 years (median 73 years). Eighty percent of patients (n=60) had immune tests performed, with 13% (n=10) having two tests, 5% (n=4) having three, and 61% (n=46) having four or more. Twenty-eight percent (n=21) had a positive immune test. A positive immune screen partly directed the introduction of anti-inflammatory therapy in 24% of patients (n=5). One of these patients had a lung biopsy. In 38% of patients with a positive immune screen (n=7) it was unclear if the result contributed to clinical decision making. Lung biopsies were performed in 19% of patients with a positive immune screen, whereas only 8% of the total had a lung biopsy. <h3>Conclusions</h3> These results show there is considerable variability in immune screen testing: which tests are performed, how positive tests are interpreted and whether they affect management. Our data hint at the usefulness of immune profiling, particularly where a lung biopsy has not been undertaken, and suggest that an abnormal immune profile increases the rate of lung biopsy. We suggest that a multi-centre, prospective, longitudinal study is required to further define AIF-ILD in terms of incidence, natural history, response to therapy and outcome. Whether AIF-ILD and the other idiopathic interstitial pneumonias are truly distinct remains to be determined, but clearly there is a need for advanced definitions, diagnostic algorithms, and management strategies.