tbuckley/cabot-search huggingface dataset:
Effects of Pancreatic Transplantation on Diabetic Neuropathy
Authors: William R. Kennedy, Xavier Navarro, Frederick C. Goetz, David E.R. Sutherland, John S. Najarian
Journal: New England Journal of Medicine (1990)

Reestablishment of the euglycemic state by successful transplantation of the pancreas might halt or reverse diabetic neuropathy. To test this possibility we evaluated neurologic function by clinical examination, nerve conduction studies, and autonomic-function tests in patients with insulin-dependent (Type I) diabetes mellitus before and after successful pancreatic transplantation. Sixty-one patients were studied before and 12 months after transplantation, 27 again after 24 months, and 11 again after 42 months. A control group of patients with Type I diabetes treated with insulin underwent the same studies at similar intervals — 48 patients before and after 12 months had elapsed, 21 again after 24 months, and 12 again after 42 months.
Cellular Sensitivity to Collagen in Rheumatoid Arthritis
Authors: David E. Trentham, Roselynn A. Dynesius, Ross E. Rocklin, John R. David
Journal: New England Journal of Medicine (1978)

We examined patients with rheumatoid arthritis for cellular sansitivity to native human Types I, II and III collagens. Mononuclear cells from 50 patients with rheumatoid arthritis, 21 with other inflammatory arthritides, 20 with osteoarthritis and 20 normal subjects were evaluated for the in vitro production of leukocyte inhibitory factor in response to collagen and a control antigen, streptokinase-streptodornase. By this assay, cells from 37 (74 per cent) and 39 (78 per cent) of the patients with rheumatoid arthritis responded to Types II and III collagens, respectively. In contrast, cells from the 41 patients with other kinds of arthritis and the normal group did not produce this lymphokine to collagens. There was no response to Type I collagen or to denatured alpha chains of these collagens. All four groups responded equivalently to streptokinase-streptodornase. These data demonstrate that most patients with rheumatoid arthritis exhibit cellular sensitivity to Types II and III collagens.
PTU-025 How accurately is rockall score calculated for patients with acute upper gastrointestinal bleeding (AUGIB)?
Authors: S Gupta, V Lam, A Taranath
Journal: Gut (2015)

<h3>Introduction</h3> Documentation of Rockall score (RS) in patients with AUGIB should be accurate in order to prioritise patients for gastroscopy. We conducted a pilot study in 2012 which showed that RS was calculated incorrectly in 46% patients. We investigated this further with a larger cohort of patients. <h3>Method</h3> Information was collected retrospectively on patients who presented with presented with AUGIB from February 2012 to February 2013. Patients who had out-of-hours gastroscopy excluded. Demographics, time to perform gastroscopy, RS documented by the doctor requesting the gastroscopy, RS calculated by analysing patient records (including A&amp;E, paramedic records) were collected. We analysed patients whose RS was either underscored or overscored by the requesting doctor (this was compared to the actual score calculated by us) and correlated the calculated RS with the need for endoscopic intervention. <h3>Results</h3> There were 248 patients with 149 (60%) males, age 16 to 98 years (mean 69). Presenting symptoms were melaena in 129 (51%), haemetemesis 35 (14%), coffee ground vomiting 64 (25%), rectal bleed 17 (7%), melaena and haematemesis 4. RS was calculated incorrectly in 194 (78%) patients with 110 (44%) over scored (Group A), 84 (34%) underscored (Group B). Mean RS on request form for Group A patients was 3.64 ± 1.97 while the calculated RS was 1.85 ± 1.61. In Group B, mean RS documented was 1.8 ± 0.96 while the calculated RS was 3.9 ± 1.04. Mean time from electronic booking to gastroscopy was 2.02 days – 1.67 days for Group A and 2.04 days in Group B. FY1s calculated incorrect scores in 83 (43%) patients, FY2s in 20 (10%), SHOs in 81 (42%), registrars in 7 (4%) and consultants 3 (2%). Of the 111 FY1s (45%) who calculated the RS, 46 (41%) overscored, 37 (33%) underscored and 28 (25%) calculated RS correctly. The numbers for 27 FY2 (11%) were 11 (41%), 9 (33%) and 7 (26%) respectively. Of the 95 (38%) SHOs, 47 (50%) overscored, 34 (36%) underscored and 14 (15%) calculated RS correctly. There were 11 specialist registrars (4 correct, 4 overscored and 3 underscored) and 4 Consultant request forms (3 incorrect). Of the 248 patients, 37 (15%) required endoscopic intervention. In Group A, 16 (15%) needed endoscopic intervention, compared to 11 (13%) in Group B. Ten (19%) of the 54 patients scored correctly required endoscopic therapy. <h3>Conclusion</h3> This study shows that it is important to document the RS at the time of first presentation of AUGIB rather than at the time when the patient is seen by the admitting doctor. This study however does not show a direct correlation between the RS and endoscopic intervention. It emphasises the fact that all doctors should be educated about the importance of documenting the correct RS as more than three quarter of the RS on request forms were found to be inaccurate. <h3>Disclosure of interest</h3> None Declared.
128O Phase I study of S-trans, trans-farnesylthiosalicylic acid (salirasib), a novel oral RAS inhibitor in Japanese patients with advanced solid tumors
Authors: T. Shimizu, N. Okano, T. Kurata, D. Naruge, Y. Fujisaka, H. Kitamura, F. Nagashima, K. Nakagawa, J. Furuse
Journal: Annals of Oncology (2015)
Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014)
Authors: Ari Gnanasakthy, Carla DeMuro, Marci Clark, Emily Haydysch, Esprit Ma, Vijayveer Bonthapally
Journal: Journal of Clinical Oncology (2016)

To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials.FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010.Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated.Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging.
Ambulatory heart rate changes in patients with panic attacks
Authors: C B Taylor, J Sheikh, W S Agras, W T Roth, J Margraf, A Ehlers, R J Maddock, D Gossard
Journal: American Journal of Psychiatry (1986)

Of 33 "panic" attacks reported by patients wearing an ambulatory solid-state heart rate/activity monitor for 6 days, 19 (58%) occurred at heart rates disproportionate to activity levels and different enough from surrounding heart rates to indicate a distinct physiologic state. Intense panic attacks with three or more symptoms were the most readily identified. ECG monitoring found the elevated heart rates to be sinus tachycardias. Heart rate elevation did not occur during anticipatory anxiety episodes. Ambulatory heart rate recordings confirm the presence of major physiologic changes during self-reported panic attacks.
Development of a novel dalotuzumab/AKT inhibitor combination therapy for the treatment of cetuximab refractory colorectal cancer (CRC).
Authors: G. Naumov, E. Valentine, S. Howard, A. Seeley, S. Jha, J. F. Reilly, A. Bloecher, R. S. Wexler, H. Keihack, C. Winter, S. Sathyanarayanan
Journal: Journal of Clinical Oncology (2011)

e13590 Background: Rational combination of 2 or more investigational compounds is a novel concept in oncology. We have entered phase I clinical development in patients with solid tumors with novel doublet combinations of dalotuzumab/MK-2206 and dalotuzumab/MK-0752. The preclinical rationale supporting one such combination of dalotuzumab and MK-2206 (an AKT inhibitor) in refractory CRC is described. Dalotuzumab is an inhibitor of IGF-1R and demonstrates activity in KRAS mutant cetuximab refractory pre-clinical models. This activity was enhanced by addition of MK-2206. The mechanism of action of this novel dalotuzumab/MK-2206 combination is based on a novel PI3K-signaling feedback loop. Methods: Anchorage independent growth assay for in vitro sensitivity. Xenograft models for in vivo efficacy. Results: MK-2206 treatment results in a dose-dependent inhibition of AKT phosphorylation and increases IGF-1R levels/activity in a subset of cancer cells. Thus, induction of IGF-1R signaling pathway may limit the efficacy of AKT inhibition. The consequence of co-targeting AKT and IGF-1R was assessed by an anchorage independent growth of CRC cells. The combination significantly reduces colony formation at multiple MK-2206 concentrations, compared to the single agent treatments. Neither single agent treatment produces > 50% growth inhibition. However, the combination therapy produces >80% growth inhibition. In vivo efficacy evaluation of the dalotuzumab/MK-2206 combination results in tumor regression in 1 of 3 CRC models. The combination efficacy was always superior to cetuximab treatment in all 3 models. Consistent with the in vitro studies, analysis of the PI3K and IGF-1R signaling components following MK-2206 treatment reveals a feedback activation of IGF-1R signaling, as measured by phosphorylation of IGF1R. The enhanced PI3K targeting by the combination therapy is evident from the inhibition of the AKT regulated phosphorylation of PRAS40, a regulator of mTORC1. Conclusions: This novel MK-MK doublet exerts activity in CRC models and thus may have utility in treating cetuximab-refractory KRAS/BRAF mutant CRC patients, a hypothesis currently under phase I evaluation.
Clival chordoma molecular subtypes and clinical behavior
Authors: D. M. Park, D. M. Prevedello, P. Gardner, D. Lee, S. Henry, C. Snyderman, R. Carrau, C. Horbinski, R. L. Hamilton, A. B. Kassam
Journal: Journal of Clinical Oncology (2009)

10538 Background: Chordoma is a primary bone cancer of the axial skeleton with predilection for local invasion. Primary treatment modalities consist of surgery and radiation therapy with limited role for chemotherapy. Because patients with chordoma exhibit heterogeneous clinical history and response to therapy, we investigated potential markers predictive of clinical behavior. Methods: This study analyzed 35 clival chordoma specimens with documented immunohistochemistry (IHC) staining for Ki-67 proliferation index from 29 patients. Detailed additional pathologic studies were performed prospectively on 12 consecutive patients. This consisted of the following: IHC for brachyury, cytokeratin, p53, and epidermal growth factor receptor (EGFR); fluorescent in situ hybridization (FISH) analysis for EGFR amplification and presence of 1p36, 9p21, and 19q13 loci; polymerase chain reaction based loss of heterozygosity analysis (LOH) of 1p, 9p, 10q, 17p, and 19p loci. Results: All confirmed chordoma specimens were positive for brachyury and negative for amplification of EGFR. Increase in Ki-67 index was associated with recurrence in 5 of 6 cases. Out of the 12 patients with detailed molecular pathologic studies, 5 had loss of 1p, 2 had deletion of 9p21 (p16), and 2 had loss of 10q (PTEN). The loss of 1p and 9p were detected via both FISH and LOH analyses. 3 of the 12 patients’ tumor specimens showed a Ki-67 index of greater than 10%; the remaining specimens were less than 5%. All 3 patients with high Ki-67 index had loss of either 9p (p16) or 10q (PTEN). The tumor specimen from these 3 patients also exhibited enhanced in vitro propagation. Conclusions: Subtyping of clival chordomas based on molecular phenotype may provide prognostic information. The prospective nature of this study in concert with assessment of residual disease after surgery may allow for identification of distinct subpopulations of patients at greater risk of disease recurrence for consideration of adjuvant therapy. The correlative in vitro study will provide an opportunity to evaluate targeted therapies customized to individual molecular subgroups. No significant financial relationships to disclose.
Half Cow's Milk-Induced Food Protein Induced Enterocolitis Syndrome (FPIES) Require Amino Acid Feeding
Authors: Sibylle Blanc, Delphine Deboissieu, Nicolas Kalach, Pascale Soulaines, Florence Campeotto, Marie-Pierre Cordier-Collet, Clara Malka, Isabelle Montaudié-Dumas, Carole Piccini-Bailly, Lisa Giovannini-Chami, Thierry Bourrier, Christophe Dupont
Journal: Journal of Allergy and Clinical Immunology (2016)
Poor premorbid adjustment and CT scan abnormalities in chronic schizophrenia
Authors: D R Weinberger, E Cannon-Spoor, S G Potkin, R J Wyatt
Journal: American Journal of Psychiatry (1980)

The authors evaluated the premorbid adjustment of 51 chronic schizophrenic patients by retrospective chart analysis using a novel scale. Those patients with CT evidence suggestive of brain atrophy had significantly worse premorbid scores, particularly during childhood, than did the patients with normal scans. This finding provides further support for the clinical relevance of CT findings in chronic schizophrenic patients and implicates a neuropathological process that occurs early in development.
Minimally invasive laser-induced thermal therapy (LITT) for head and neck cancer: A comprehensive review
Authors: M. B. Paiva, M. Bublik, S. Wong, K. E. Blackwell, J. A. Sercarz
Journal: Journal of Clinical Oncology (2006)

5572 Background: Laser induced thermal therapy (LITT) has been developed in a step-wise fashion at UCLA as a minimally invasive treatment for head and neck cancer. Initial Phase-I studies demonstrated the feasibility and safety of using the Nd:YAG laser (near infra-red nm) for thermal ablation of tumors as a palliative treatment in 62 patients. This was followed by the current Phase II study that confirmed such finding using higher laser power densities (P.D. = 1,600–2,200 J/cm 2 ). Patients and Methods: This was a single group study in patients with recurrent carcinoma of the head and neck, who failed at least one treatment modality, and had a Karnofsky performance status ≥ 70%, and ECOG performance status ≤ 2. The primary end points of the study were objective tumor response, and survival. Prognostic values were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. Results: In this Phase II study, we review our results on 104 patients with recurrent head and neck cancer that were treated by LITT. Best results were seen in oral cavity tumors where Kaplan Meyer curves showed average survival of 20.3 months (10.7–30 mo; 95% CI) compared to neck (avg. = 14.4 months, 7.5–20.7 mo; 95% CI) and other tumor sites, (avg. = 18 months, 13.8–22.3 mo; 95% CI). Further analysis of neck treatments showed that tumors away from the common carotid in cervical lymph nodes located in levels I, IV, and V had median survival of 25.9 months (mean = 37.7 mo), compared to 11.4 months (mean = 10.9 mo) in patients with tumors near, or encroaching the carotid in upper and lower jugular levels II and III. In univariate analysis, a trend toward a better survival was observed when tumor proximity to carotid artery was considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, and reconstruction using free flap transfer, but not age and histology, were retained as independent prognostic variables (P &lt; .001). Conclusion: LITT Patients tolerated LITT well on an outpatient basis, and were successfully palliated for periods ranging from 39 days to 90 months post-treatment. Based on the findings of this study it was possible to show that proximity to the carotid artery was the most relevant factor in projecting patient survival. No significant financial relationships to disclose.
Noninvasive Imaging to Evaluate Women With Stable Ischemic Heart Disease
Authors: Lauren A. Baldassarre, Subha V. Raman, James K. Min, Jennifer H. Mieres, Martha Gulati, Nanette K. Wenger, Thomas H. Marwick, Chiara Bucciarelli-Ducci, C. Noel Bairey Merz, Dipti Itchhaporia, Keith C. Ferdinand, Carl J. Pepine, Mary Norine Walsh, Jagat Narula, Leslee J. Shaw
Journal: JACC. Cardiovascular imaging (2016)
Abstract 2235: miR-200c reduces P-gp mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colon cancer
Authors: Qi Li
Journal: Cancer Research (2015)

Abstract MicroRNA-200c (miR-200c) recently emerged as an important regulator of tumorigenicity and cancer metastasis, however, its role in regulating multidrug resistance (MDR) remains unknown. In the current study, we found that the expression levels of miR-200c in recurred and metastatic colorectal cancers (CRC) were significantly lower, while the JNK2 expression was higher compared to primary tumors. We showed that in MDR CRC cells, miR-200c targeted the 3′UTR of JNK2 gene. Over-expression of miR-200c attenuated the levels of p-JNK, p-c-Jun, P-gp and MMP-2/-9, the downstream factors of JNK signaling pathway, resulting in increased sensitivity to chemotherapeutic drugs, which was accompanied by heightened apoptosis and decreased cell invasion and migration. Moreover, in an orthotopic MDR CRC mouse model, we demonstrated that over-expression of miR-200c effectively inhibited the tumor growth and metastasis. At last, in the tumor samples from locally advanced CRC patients with routine post-surgical chemotherapy, we observed an inverse correlation between the levels of mRNA expression of miR-200c and JNK2, ABCB1, MMP-9 thus predicting patient therapeutic outcomes. In summary, we found that miR-200c negatively regulated the expression of JNK2 gene and increased the sensitivity of MDR CRC cells to chemotherapeutic drugs, via inhibiting the JNK2/p-JNK/p-c-Jun/ABCB1 signaling. Restoration of miR-200c expression in MDR CRC may serve as a promising therapeutic approach in MDR induced metastasis. Citation Format: Qi Li. miR-200c reduces P-gp mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2235. doi:10.1158/1538-7445.AM2015-2235
Ectopia Lentis
Authors: Deniz Çebi Olgun, Fatih Kantarci
Journal: New England Journal of Medicine (2015)

A 31-year-old woman with Marfan's syndrome presented with amblyopia and a history of gradual bilateral vision loss over the previous 3 to 4 months. She had also had mild sensorineural hearing loss within the previous 2 weeks.
Cytotoxic-T-Cell Responses, Viral Load, and Disease Progression in Early Human Immunodeficiency Virus Type 1 Infection
Authors: Luwy Musey, James Hughes, Timothy Schacker, Theresa Shea, Lawrence Corey, M. Juliana McElrath
Journal: New England Journal of Medicine (1997)

Early in human immunodeficiency virus type 1 (HIV-1) infection there is a decline in viral replication that has been attributed to host immunity, but the components of this response, particularly the ability of cytotoxic T lymphocytes to control viral burden and influence the outcome of disease, are poorly understood.
Sentinel-Lymph-Node Biopsy for Breast Cancer — Not Yet the Standard of Care
Authors: Kelly M. McMasters, Armando E. Giuliano, Merrick I. Ross, Douglas S. Reintgen, Kelly K. Hunt, David R. Byrd, V. Suzanne Klimberg, Pat W. Whitworth, Lorraine C. Tafra, Michael J. Edwards
Journal: New England Journal of Medicine (1998)

A sentinel lymph node is the first lymph node to receive lymphatic drainage from a tumor. It can be detected by injection of a blue dye or radioactive colloid around the primary tumor, which travels to and identifies the first draining (sentinel) node. Biopsy of a sentinel lymph node can reveal whether there are lymphatic metastases, thereby obviating the need for extensive dissection of the regional lymph-node basin. Sentinel-lymph-node biopsy has become a standard technique for determining the nodal stage of disease in patients with melanoma. Initial studies of this method in patients with breast cancer suggest that sentinel-lymph-node biopsy . . .