tbuckley/cabot-search huggingface dataset:
Case 17-2011
Authors: Beth A. Overmoyer, Janie M. Lee, Melinda F. Lerwill
Journal: New England Journal of Medicine (2011)

A 49-year-old woman presented with a 12-cm mass in the right breast, fixed to the chest wall. The overlying skin was erythematous and edematous. A core-biopsy specimen showed infiltrating ductal carcinoma.
Abstract 4750: Overcoming DDP resistance using folic acid-heparin-DDP nanoparticles
Authors: Xianghong Peng, Yiqing Wang, Zuo (Georgia) Chen, Shuming Nie, Dong M. Shin
Journal: Cancer Research (2012)

Abstract Cisplatin (DDP) has been widely used in the treatment of different cancers. However, resistance to DDP limits its clinical application. Since reduced intracellular DDP accumulation is one of the main causes for DDP resistance, increasing the accumulation of DDP may overcome drug resistance. The folate receptor (FR) is overexpressed on the surface of many human tumors including breast, ovarian and lung cancer, but is found at low levels in normal tissues. In this study, folic acid (FA) was conjugated to heparin-DDP (FHDDP) nanoparticles to target FR. In vitro cellular uptake experiments showed that the accumulation of FHDDP nanoparticles in FR-expressing DDP-resistant KB-CP.5 cancer cells (selected from KB3-1 cells, and showing a 36-fold increase in resistance to DDP compared with KB3-1) was significantly higher than that of free DDP (9.31±2.2 ng Pt/106 cells vs 0.98±0.25 ng Pt/106 cells, Pt:0.5ug/ml, 4 hrs at 37°C). Further, the level of platinum DNA-adducts in the resistant cells treated with FHDDP nanoparticles was about 4-fold greater than in cells treated with free DDP (24.21±5.32 pg Pt/ug DNA vs 97.9±22.5 pg Pt/ug DNA). Nude mice bearing KB-CP.5 cell tumors receiving FHDDP nanoparticles (2.5mg/kg, tail vein injection, twice weekly, 5 times) showed enhanced antitumor effects as compared with mice treated with free DDP (tumor volume: 823±221mm3 vs 1450±392mm3, 21 days after treatment), while non-targeted heparin-DDP nanoparticles did not show significant difference compared with free DDP. Our results suggest that FHDDP nanoparticles have the potential to be used for overcoming DDP resistance.(This research was supported by the National Cancer Institute award 5 P50 CA128613) 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 4750. doi:1538-7445.AM2012-4750
P155 Compliance With Guidelines For The Management Of Theophylline In Patients With Acute Exacerbations Of Copd
Authors: M. Ullah, D. Anshur, S. Lugg, S. Gompertz
Journal: Thorax (2014)

<h3>Introduction</h3> Theophylline therapy has a role in COPD patients who fail to respond adequately to inhaled bronchodilators and show symptomatic benefit from a trial of the drug. Treatment is complicated by drug interactions and its narrow therapeutic range (10–20 mg/L). High serum levels increase the risk of toxicity, demonstrating numerous symptoms such as nausea, vomiting, headaches, dyspepsia, insomnia and behavioural disturbances. Serious adverse effects such as cardiac arrhythmias and epileptic seizures tend to occur at serum levels above this reference range. NICE guidelines for COPD state that a theophylline level should be measured on admission in patients admitted for acute exacerbation of COPD (AE-COPD).<sup>1</sup> The aim of this study was to audit compliance with these guidelines. <h3>Methods</h3> Patients with a diagnosis of AE-COPD were retrospectively analysed over a 6-month period (June–December 2013) at a university hospital. Those who were prescribed theophylline within 24 h of admission were included in the study. Further information was gathered including theophylline level, date of request, and subsequent dose adjustment. Paper and computerised medical and prescribing records were reviewed using a set pro-forma. <h3>Results</h3> Of a total of 54 patients in the study, 23 patients (43%) had theophylline levels checked during their hospital admission. Only 5 (9%) patients had theophylline levels within 24 h of admission, with the mean number of days from admission to assessment being 4.69 (SD+ 5.29). Of those patients, 13 patients (56.5%) had a level within subtherapeutic range (&lt;10 mg/L), and 8 patients (61%) receiving subsequent dose adjustment. There were no patients found to have a theophylline level above therapeutic range (&gt;20 mg/l). <h3>Conclusion</h3> Improvement is needed in compliance with guidelines for the theophylline monitoring in patients with AE-COPD, as more than half of patients did not have levels checked during their hospital admission. Furthermore, dose adjustments were made in only 2 of 3 patients. Changes can be implemented through education to junior doctors, implementation of electronic prescribing alerts, and adding this to our MDT COPD bundle checklist. Further prospective audit cycle will be performed to assess improvements. <h3>Reference</h3> NICE Guidelines [CG101]2010
Case 25-1996
Authors: Mark S. Drapkin, Eugene J. Mark
Journal: New England Journal of Medicine (1996)

Presentation of CaseA 38-year-old man was admitted to the hospital because of fever, cough, and sweats.The patient had been in excellent health until three weeks earlier, when he began to have a continuous fever; he did not take his temperature and was unaware of accompanying symptoms. Two weeks before admission, drenching night sweats developed. Twelve days before admission, a sensation of chilliness, without frank rigors, and a dry cough developed. He was referred to this hospital.The patient was an unemployed native of Honduras who had immigrated to the United States three years before admission. A tuberculin skin . . .
Family Management in the Prevention of Exacerbations of Schizophrenia
Authors: Ian R. H. Falloon, Jeffrey L. Boyd, Christine W. McGill, Javad Razani, Howard B. Moss, Alexander M. Gilderman
Journal: New England Journal of Medicine (1982)

Environmental stress has been implicated as an important factor in the relapse of schizophrenic patients receiving optimal drug therapy. In a randomized controlled study, we compared at-home family therapy with clinic-based individual supportive care in the community management of schizophrenia in 36 patients taking neuroleptic maintenance medications. The family-treatment approach sought to enhance the stress-reducing capacity of the patient and his or her family through improved understanding of the illness and training in behavioral methods of problem solving. The results at the end of nine months revealed the superiority of this approach in preventing major symptomatic exacerbations. Only one family-treated patient (6 per cent of all patients) was judged to have had a clinical relapse, as compared with eight patients (44 per cent) treated individually. Family-treated patients averaged 0.83 days in the hospital, as compared with 8.39 days for the comparison group. Significantly lower levels of schizophrenic symptomatology on blind rating-scale assessments supported these clinical observations of the superiority of family management. (N Engl J Med. 1982; 306:1437–40.)
Development of esophageal adenocarcinoma on buried glands following radiofrequency ablation for Barrett's esophagus
Authors: E. Chabrun, M. Marty, F. Zerbib
Journal: Endoscopy (2012)

Radiofrequency ablation (RFA) of Barrett’s esophagus mucosa is associated with high rates of complete eradication of intestinal metaplasia and dysplasia [1]. RFA can be combined with endoscopic mucosal resection (EMR) when superficial adenocarcinoma is present. After RFA the likelihood of buried glands under the layer of neosquamous epithelium is lower than after photodynamic therapy or argon plasma coagulation [2].
Bone Scintigraphy in a Patient With Progressive Diaphyseal Dysplasia
Authors: NORIYUKI SHUKE, TETSUYA TAKASHIO, WAKAKO YAMAMOTO, KOUKI USUI, TAMIO ABURANO, NORIE SAKURABA, AKIMASA OKUNO
Journal: Clinical Nuclear Medicine (1997)

A 24-year-old woman who had been treated as having progressive diaphyseal dysplasia (Engelmann's disease) was admitted to the hospital for tachycardia and bone pain in the forearms. For the purpose of a bone survey, bone scintigraphy with Tc-99m HMDP was performed. Whole-body scintigraphy showed the characteristic appearance of this disease and the involved regions were well-manifested as areas of increased uptake.
EXPERIENCIA INICIAL EN EL USO DE PROTESIS BIODEGRADABLES AUTOEXPANDIBLES COMO TRATAMIENTO DE ESTENOSIS BENIGNAS REFRACTARIAS DE TRACTO GASTROINTESTINAL
Authors: B López Viedma, R Lorente Poyatos, F Domper Bardají, E De la Santa Belda, R Patón Arenas, M Galván Fernández, MJ Rodríguez-Sánchez, M LaBlanca Alonso, J Olmedo Camacho, E Rodriguez Sánchez
Journal: Endoscopy (2010)

Introducción: El uso de prótesis biodegradables autoexpandibles como alternativa a las dilataciones sucesivas de las estenosis benignas refractarias está por definir.
Abstract 1631: Cav1 is a key mediator of tumor-stromal interactions in melanoma.
Authors: Casey Trimmer, Franco Capozza
Journal: Cancer Research (2013)

Abstract Several lines of experimental evidence have demonstrated the importance of the tumor microenvironment in controlling melanoma tumor growth and melanoma metastasis. Caveolin1 (Cav1), the main structural component of the plasma membrane microdomains termed Caveolae, is emerging as an important signaling molecule in the stroma of several tumor types. However, Cav1’s function in the melanoma microenvironment of primary tumors and of metastasis remains largely unexplored. Here, we devise various experimental approaches to elucidate the function of stromal Cav1 in the development of melanoma in mice. We show that loss of Cav1 (but not Cav2) in mice promotes the growth of orthotopically implanted melanoma cells. We use cocultures of fibroblasts and melanoma cells coupled with cytokine analysis to identify various Cav1 regulated factors that function in a paracrine fashion in melanoma. Cav1KO fibroblasts secrete increased amount of ShhN, bFGF, and MMP2/3, cytokines known to promote proliferation of melanoma cells and remodeling of the tumor stroma during melanomagenesis. Intradermal xenografts of fibroblasts and melanoma cells (5:1 ratios) confirmed the tumor promoting role of fibroblasts lacking Cav1. Interestingly, constitutive inhibition of the Shh pathway in melanoma cells reverses the growth and tumor-promoting effects of Cav1KO fibroblasts in co-culture or co-injection experiments suggesting a Cav1 mediated Shh heterotypic interaction between fibroblasts and melanoma cells. In summary, these studies reveal previously undefined functions for Cav1 in the melanoma microenvironment that could potentially be targeted for therapy. Citation Format: Casey Trimmer, Franco Capozza. Cav1 is a key mediator of tumor-stromal interactions in melanoma. [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 1631. doi:10.1158/1538-7445.AM2013-1631 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 4436: The down-regulation of ferritin heavy chain as an adjuvant therapy in human glioma.
Authors: Min Pang, A.B. Madhankumar, Becky Webb, Xiaoli Liu, James R. Connor
Journal: Cancer Research (2013)

Abstract Increased iron requirements and heightened iron metabolism is among the key characteristics of highly proliferative cancer cells. As the major iron storage protein, ferritin expression is elevated in cancer cells and we have previously shown that ferritin down-regulation in human glioblastoma cells increases their sensitivity to chemotherapeutic agent both in vitro and in vivo. In this study, we report that the sensitization of H-ferritin down-regulation in glioma cells against radiation and suggest the potential of H-ferritin down-regulation as an adjuvant therapy in human glioma. Down-regulation of H-ferritin was performed in human glioma cell line U251 through a nanotechnology-based transfection platform and effective knockdown efficiency was achieved. A transient decrease in transferrin receptor level was also observed, suggesting a release of intracellular iron with loss of ferritin. This iron release in turn produced intracellular oxidative stress, demonstrated by protein oxidation damage, as well as a decrease in the stability of hypoxia-inducible factors (HIFs), which is an indicator of radioresistance. In U251 cells, exposure to radiation resulted in protein oxidation which could be exacerbated by H-ferritin down-regulation. Previously we have demonstrated a DNA protection role for H-ferritin. Here we report that the down-regulation of H-ferritin is associated with increased DNA vulnerability when cells were exposed to ionizing radiation. Moreover, the activation of DNA repair mechanisms was impaired when H-ferritin was absent. The in vitro data suggest a synergistic effect of radiation and H-ferritin down-regulation. Additionally, we expand our research into CD133-positive glioma stem cells (GSCs), which are notoriously resistant to anti-cancer treatment. Down-regulation of H-ferritin in these cells inhibited cell proliferation in vitro. With an intracranial glioma model established by GSC implantation, we demonstrated that the survival was significantly prolonged by H-ferritin siRNA transfection through intravenous injection, in tumor bearing mice treated with first-line drug Temodar. This study supports the potential of H-ferritin siRNA as an adjuvant therapy in glioma treatment. Citation Format: Min Pang, A.B. Madhankumar, Becky Webb, Xiaoli Liu, James R. Connor. The down-regulation of ferritin heavy chain as an adjuvant therapy in human glioma. [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 4436. doi:10.1158/1538-7445.AM2013-4436
Abstract 716: O6-Methylguanine DNA methyl transferase (MGMT) and tamoxifen resistance in patients with breast cancer
Authors: Santhi D. Konduri, Sreeram Maddipatla, Joshua Smith, Beth Isley, Maria-Lourdes M. Caparas, Susan M. Constantino, Nikita Shah, Said Baidas
Journal: Cancer Research (2011)

Abstract Tamoxifen is an estrogen receptor antagonist in breast tissue. It has been used as a hormonal therapy for early and advanced breast cancer both in premenopausal and postmenopausal patients with estrogen receptor positive breast cancer. Acquired resistance to tamoxifen therapy is a common therapeutic encounter. Different mechanisms for Tamoxifen resistance have been postulated. In the present study we investigated if over expression of MGMT causes tamoxifen resistance in breast cancer patients. Purpose: We sought to determine MGMT expression levels in various breast cancer cell lines as well as in breast cancer patient's samples before and after treatment with tamoxifen. Experimental Design: MGMT expression levels were compared in breast cancer tissue samples obtained from patients before starting treatment with Tamoxifen and after tumor progression due to development of Tamoxifen resistance. MGMT expression level was evaluated using western blot and immunohistochemical assays. Several commercial breast cell lines were evaluated for expression of MGMT. Results: We found that MGMT is over expressed in the majority of breast cancer cell lines compared to normal breast epithelial cells. Compared to pre Tamoxifen treatment, post Tamoxifen treated breast cancer patient samples have significantly higher levels of MGMT expression. Conclusion: Collectively, our results demonstrate that breast cancer cells showed significantly higher levels of MGMT expression and furthermore, Tamoxifen treatment induces further MGMT over expression in breast cancer patients. According to our results over expression of MGMT is a possible cause for Tamoxifen resistance. Inhibition of MGMT might overcome Tamoxifen resistance and restore breast cancer sensitivity to Tamoxifen treatment. 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 716. doi:10.1158/1538-7445.AM2011-716
AB0547 Prevalence of Osteopenia and Osteoporosis in A Cohort of 160 Patients with Systemic Lupus Erythematosus
Authors: R. Fonseca, G. Terroso, D. Gonçalves, J. Abelha-Aleixo, F. Aguiar, P. Madureira, R. Vieira, M. Bernardes, L. Costa
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Low bone mineral density (BMD) is highly prevalent in patients with systemic lupus erythematosus (SLE). However, determinants of BMD changes in SLE are still largely unknown. <h3>Objectives</h3> The aim of this study was to describe the clinical characteristics of SLE patients submitted to a dual energy X-ray absorptiometry (DEXA), evaluating the prevalence of osteopenia/osteoporosis and searching for possible predictors of bone loss in these patients. <h3>Methods</h3> Retrospective observational study of 160 SLE patients of our Rheumatology department, was performed. Demographic, clinical data and BMD measurements (g/cm<sup>2</sup>) of the lumbar spine (LS) and total hip (TH) were collected. The DEXA results were classified according to WHO criteria for osteoporosis. Statistical analyses was performed using t-test, Mann-Whitney U-test, and Spearman correlation (SPSS 21.0). <h3>Results</h3> Out of 160 SLE patients, 148 (92,5%) were female with a mean age 44,23±12,5 years. The median SLEDAI was 2 [0-23], median SLICC was 0,2 [0-5]. 74 (56%) patients were taking vitamin D supplements, 56 (35%) were taking calcium supplements and 24 (15%) received bisphosphonate therapy. Only 81 (50,6%) had a DEXA done. Patients with DEXA were older (47.28±12.7 vs 41.09±11.8 years, p&lt;0.01), had a longer disease duration (13.8±9 vs. 10.6±8 years, p=0.02), high SLICC score (2,0 vs 0,0 p=0,04) and were taking a higher dose of steroids (7 vs 5; p=0,01). No significant differences were found between gender, SLEDAI, serum vitamin D, complement levels, erythrocyte sedimentation rate or c-reactive protein. Of the 81 patients with DEXA, 34 (42%) had osteopenia, 13 (16%) had osteoporosis and 34 (42%) had normal BMD. The mean lumbar spine BMD was 0.96±0.12 g/cm<sup>2</sup> and the mean total hip BMD was 0.87±0.13 g/cm<sup>2</sup>. Statistically significantly correlation was found between age and lumbar spine BMD (r=-0,256; p=0,02), age and total hip BMD (r=-0,262; p=0,02), SLICC score and lumbar spine DMO (r=-0,230; p=0,04) and SLICC score and total hip BMD (r=-0,279; p=0,04). <h3>Conclusions</h3> In our cohort, SLE patients referred for a DEXA have more traditional risk factors, take a higher dose of corticosteroids and have a higher disease damage access by SLICC score. The prevalence of osteopenia and osteoporosis in our SLE-patients was greater than in general population. In addition to age, disease damage access by SLICC score was associated with low BMD. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4635
FRI0347 Predictive factors of long-term clinical outcome in patients with ocular involvement secondary to behcet’s disease.
Authors: C. Ferrari, R. Talarico, C. Stagnaro, A. d’Ascanio, C. Tani, C. Baldini, L. Bazzichi, M. Mosca, S. Bombardieri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Behçet's disease (BD) is a multisystemic, chronic relapsing inflammatory disease classified among the vasculitis. Eye involvement represent one of the most serious manifestation of BD and occurs in half of all patients. It seems more frequent and severe among young males and, unluckily, it still represents a significant cause of morbidity. <h3>Objectives</h3> The aims of the study was to identify factors able to predict long-term outcome in patients with BD <h3>Methods</h3> Forty-seven patients (29 males and 18 females; mean age at the onset 29±5 years) with a diagnosis of BD according the ISG criteria were studied. The probability of clinical relapse after remission of the first ocular attack was calculated using the Kaplan-Meier method. Predictors of long-term outcome were identified by univariate analysis using the log-rank test and by multivariate analysis using Cox proportional hazards regression models. <h3>Results</h3> The mean time between the first initial symptoms of BD and the onset of eye lesions was 3±2 years. The number of ocular attacks were the following: 32 posterior uveitis, 27 anterior uveitis, 21 retinal vasculitis, while panuveitis developed in 17 subjects. Medical treatments received at time of the study were: cyclosporine A (n=21), infliximab (n=13, azathioprine (11), adalimumab (2). The cumulative relapse rates at 1 year, 3 years, and 5 years after remission of the first ocular attack were 20%, 38.7%, and 42%, respectively. On multivariate analysis, a younger age (&lt;30 years) at the onset of ocular involvement, male sex and medical treatments other than biological agents represent independent predictive factors for relapse in BD patients with ocular involvement. <h3>Conclusions</h3> As awaited, the use of anti TNF alpha agents seems to be associated with a positive effect on maintaining remission in ocular involvement due to BD. However, as literature data suggest, younger age and male sex represent predictive factors of poor long-term clinical outcome. <b>Disclosure of Interest</b>: None Declared
A Comparison of Electroencephalography and Brain Scan in Supratentorial Tumors
Authors: J. T. Murphy, P. Gloor, Y. L. Yamamoto, W. Feindel
Journal: New England Journal of Medicine (1967)

ALTHOUGH the clinical value and limitations of electroencephalography and brain scan as diagnostic tools in brain tumors have frequently been studied independently, the timing of the 2 methods and what is accepted as "localizing" in each, especially with regard to the electroencephalogram, have not heretofore been directly compared. In this study an attempt was made to define more precisely the success and scope of each method in a group of patients with a variety of supratentorial brain tumors. In addition, differing successes with each method in the localization of the different types of tumor were observed. A corollary purpose of . . .