tbuckley/cabot-search huggingface dataset:
Hemophilia A
Authors: Stylianos E. Antonarakis, Pamela G. Waber, Smita D. Kittur, Achyut S. Patel, Haig H. Kazazian, Maria A. Mellis, Richard B. Counts, George Stamatoyannopoulos, E.J. Walter Bowie, David N. Fass, Debra D. Pittman, John M. Wozney, John J. Toole
Journal: New England Journal of Medicine (1985)

To understand the molecular basis of hemophilia A and to provide heterozygote detection and prenatal diagnosis by DNA analysis, we used cloned factor VIII:C DNA fragments to study 10 affected families. In four of these families, inhibitors of factor VIII:C had developed in affected persons. In one such family a deletion of approximately 80 kb within the factor VIII:C gene was identified. Carriers of the deletion were identified through detection of an abnormal DNA fragment located at the deletion end points. In another family a single nucleotide change in the coding region of the factor VIII:C gene produced a nonsense codon leading to premature termination of factor VIII:C synthesis. Carrier detection was performed in eight female members of this four-generation family. In a third family a small change in the size of a restriction-endonuclease fragment correlated with the presence of the mutant gene, and in the other seven families the molecular defect has not yet been identified. In addition, we used two common polymorphic sites in the factor VIII:C gene to differentiate the normal from the defective gene in four of six obligate female carriers from families with patients in whom inhibitors did not develop. Carrier detection was possible in other members of these families. These data suggest that DNA analysis of the factor VIII:C gene provides an accurate method of carrier detection and, potentially, of prenatal diagnosis in at least 50 per cent of the pedigrees affected by hemophilia A.
Familial Aggregation of Parkinson's Disease in Iceland
Authors: Sigurlaug Sveinbjörnsdóttir, Andrew A. Hicks, Thorlákur Jónsson, Hjörvar Pétursson, Grétar Guðmundsson, Michael L. Frigge, Augustine Kong, Jeffrey R. Gulcher, Kári Stefánsson
Journal: New England Journal of Medicine (2000)

The role of genetics in early-onset Parkinson's disease has been established, but whether there is a genetic contribution to the more common, late-onset form remains uncertain.
Effect of age and temporal patterns over 5 years in a Magnetic Resonance Imaging (MRI)-based breast surveillance study for BRCA mutation carriers
Authors: E. Warner, D. Plewes, K. Hill, P. Causer, G. Deboer, S. Narod, M. Cutrara, E. Ramsay, R. Jong, J. Wong
Journal: Journal of Clinical Oncology (2004)

9500 Background: With mammography (M) –based screening for BRCA mutation carriers, interval cancer rates are 44–56% and node +ve rates are 23–56%. (Brekelmans JCO 2001, Scheuer JCO 2002). Breast MRI is more sensitive than M but less specific (Robson ASCO 2002), and a reduction in breast cancer mortality is yet unproven. Methods: Since 11/97 BRCA mutation carriers ages 25 to 65 have been enrolled in a 5 year surveillance study of annual M, ultrasound (US), MRI, and semi-annual clinical breast examination (CBE). Results: 279 women (57% BRCA1, 39% previously affected) have had at least 1 round of screening, with 30 screen-detected cancers in 29 women and only 1 interval cancer (3%). Overall sensitivity of MRI was 84%, M 32% (p=0.005), US 40%, CBE 7%. These differences in sensitivity were almost identical for the 14 women ≥ age 50 vs. 17 women < age 50 at diagnosis, and for the 10 in-situ (DCIS) vs. 21 invasive cancers, and did not vary significantly over the 5 years. (See table below.) Conclusions: 1. MRI is significantly more sensitive than mammography independent of age. 2. MRI specificity improves more than ultrasound over time and is acceptable after the 1st year. 3. The extremely low interval cancer rate and tumour stage compared to historical controls, and the decrease in cancer detection rate and tumour stage after the first screen, all predict that MRI-based surveillance will likely lower cancer mortality rates in BRCA mutation carriers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Canadian Breast Cancer Research Alliance; Amersham Health; (Canadian) National Breast Cancer Fund; (US) NIH
Case 9-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Neil R. Feins, Robert E. Scully
Journal: New England Journal of Medicine (1971)

Presentation of CaseA two-year-old girl was admitted to the hospital because of abdominal pain.The child had been in good health until three days before admission, when she complained of abdominal pain and vomited once. On the following day she vomited three times and continued to complain of pain. The frequency of urination did not change; she passed no stool. A cathartic was administered, and on the following day a hard stool of normal color was passed. The patient took small feedings without vomiting but continued to experience abdominal pain. On the day of admission the abdominal pain became . . .
PTH-085 The use of 5-asa in inflammatory bowel disease: national population based study
Authors: V Chhaya, S Saxena, E Cecil, V Subramanian, V Curcin, A Majeed, R Pollok
Journal: Gut (2015)

<h3>Introduction</h3> 5-aminosalicylates (5-ASA) have a proven efficacy in induction and maintenance of ulcerative colitis (UC). The evidence that 5-ASAs have efficacy in the induction and maintenance of remission in Crohn’s disease (CD) is weak and not supported by recent meta-analyses<sup>1</sup>or current guidelines. Our aim was to determine if patients with CD and UC were being appropriately prescribed 5-ASAs <h3>Method</h3> We constructed an incident cohort of patients with CD and UC diagnosed between 1990 and 2009 using the Clinical Practice Research Datalink (CRPD), a validated research database representing an 8% sample of the UK population. We divided our cohort to compare patterns between era: era 1 (1990–1993), era 2 (1994–1997), era 3 (1998–2001), era 4 (2002–2005) and era 5 (2006–2009). We performed a Kaplan-Meier survival analysis to quantify the 3 year probability of receiving a 5-ASA. We identified patients with “prolonged 5-ASA use” defined as use for greater than 12 months duration to determine whether patients were inappropriately maintained on 5-ASAs for CD. We compared the proportion (number of users/total number within the era) of prolonged 5-ASA use between time periods using the 2-group proportion test. <h3>Results</h3> In CD, there were 6997 patients who met our inclusion criteria. The 3 year cumulative probability of receiving a 5-ASA was 40.5% (95% CI: 35.9–45.4), 49.7% (95% CI: 45.7–53.8), 50.8% (95% CI: 48.0–53.6), 52.5% (95% CI: 50.1–54.9) and 61.8% (95% CI: 58.9–64.8) for era 1, 2, 3, 4 and 5 respectively. Prolonged oral 5-ASA use was prevalent throughout the study period in CD, although decreased between era 3 and era 5 from 59.2% to 47.2% (p &lt; 0.001). In UC, there were 16,512 patients who met our inclusion criteria. The 3 year cumulative probability of receiving a 5-ASA was 31.7% (95% CI: 29.3–34.3), 36.6% (95% CI: 34.3–39.0), 42.9% (95% CI: 41.0–44.7), 46.2% (95% CI: 44.6–47.8) and 55.4% (95% CI: 53.4–57.4) for era 1, 2, 3, 4 and 5 respectively. Prolonged oral 5-ASA use was increasing throughout the study period in UC, 43.3% to 53.0% between era 1 and era 4 (p &lt; 0.001). <h3>Conclusion</h3> In CD, 5-ASA use remains common with over 50% of patients receiving the medication, including maintenance therapy, despite a lack of evidence to support this clinical practice. In UC, 5-ASA use has increased appropriately although not all patients appeared to be maintained on these drugs. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Ford AC, Kane S V, Khan KJ, Achkar J-P, Talley NJ, Marshall JK, Moayyedi P. Efficacy of 5-aminosalicylates in Crohn’s disease: systematic review and meta-analysis. Am J Gastroenterol 2011;106:617–29
Early palliative care (PC) in advanced non-small cell lung cancer (NSCLC) is feasible
Authors: J. S. Temel, J. A. Billings, V. A. Jackson, C. Reid, C. M. Dahlin, A. B. Kornblith, M. K. Buss, S. D. Block, F. Panagiotis, T. J. Lynch
Journal: Journal of Clinical Oncology (2005)

8070 Background: Delaying palliative care (PC) until after cancer-directed therapy has failed leads to poor symptom management and unnecessary suffering. EPC at the time of diagnosis may result in improved management of cancer-related symptoms and enhanced QOL. The goal of this study is to assess the feasibility of EPC in patients with advanced NSCLC and to obtain baseline QOL data for this group. Methods: We are performing a multicenter pilot study to assess the feasibility of EPC in PS 0–1 patients with newly diagnosed stage IIIb and IV NSCLC. Participants are required to meet with the PC team and complete QOL questionnaires monthly until the time of hospice referral. QOL is assessed using the FACT-Lung (FACT-L) and Hospital Anxiety and Depression Scale (HADS). We specified that EPC is a feasible model of care if at least 64% of participants meet with the PC team and complete the FACT-L at least 50% of the time they are scheduled to do so for the first 6 months of study participation. Results: Between October 2003 and November 2004, 39 patients entered into the study and we have 6-month follow-up data on 20 of them. The median age is 65 years and the majority of patients have stage IV disease (95%) and PS 1 (72%). The median follow-up is 5.3 months and the one-year survival is 55%. All of the first 20 participants (100%) met with the PC team at least 50% of the time they were scheduled to do so. 95% of patients completed the FACT-L at more than half of their scheduled assessment times. The FACT-L was completed at 12 weeks and 6 months in 93% and 87% of patients, respectively. QOL scores indicated that patients were quite symptomatic at the time of study entry, especially in lung cancer-specific symptoms and functional status. The HADS revealed anxiety and depression in 35% and 20% of patients, respectively. Conclusions: EPC is a feasible model in patients with advanced NSCLC. The compliance rate with the PC intervention exceeded our goal and the rate of completion of the FACT-L is among the highest reported for a metastatic lung cancer population. We have begun planning a randomized study comparing EPC versus standard PC in patients with advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
Two- and Four-Hour Tests Differ in Capture of C-Peptide Responses to a Mixed Meal in Type 1 Diabetes
Authors: Karen D. Boyle, Lynette Keyes-Elstein, Mario R. Ehlers, James McNamara, Mark R. Rigby, Stephen E. Gitelman, Lia J. Weiner, Kristen L. Much, Kevan C. Herold
Journal: Diabetes Care (2016)

Mixed-meal tolerance tests (MMTTs) are used in clinical trials to evaluate β-cell function in patients with new-onset type 1 diabetes (1,2). Some trials use a 4-h MMTT, whereas others use an abbreviated (2-h) protocol to reduce investigator and subject burden. In the T1DAL (Inducing Remission in Type 1 Diabetes With Alefacept) trial of patients with new-onset type 1 diabetes, the primary analysis using the 2-h test failed to reach statistical significance ( P = 0.065), but a 4-h test did ( P = 0.019) (3). We investigated the effect of abbreviating the test using data from 186 patients participating in three clinical trials conducted by the Immune Tolerance Network (3–5). Trials were approved by institutional review boards at the participating institutions. Written informed consent or assent was obtained.

Each patient contributed up to three 4-h MMTTs, conducted yearly, for a total of 506 paired 2- and 4-h observations. For this analysis, the 4-h assessment, which captures more of the complete hormonal response, was selected as the reference. The percent of the total 4-h C-peptide area under the curve (AUC) captured in the first 2 h ranged from 28% to 72%. Mean AUCs (mAUCs) were computed as 2- or 4-h AUCs divided by duration, 120 or 240 min, respectively. The correlation between the 2- and 4-h mAUCs was 0.98. Generally, the variability of the 2-h test was greater than that of the 4-h test (Fig. 1 A ). After adjusting for baseline, however, the variability was similar.



Figure 1 
Analysis of 2- and 4-h C-peptide AUCs during MMTTs. The C-peptide …
Response to Letter Regarding Article, “MicroRNA-155 Exerts Cell-Specific Antiangiogenic but Proarteriogenic Effects During Adaptive Neovascularization”
Authors: Franziska Pankratz, Xavier Bemtgen, Robert Zeiser, Franziska Leonhardt, Sheena Kreuzaler, Ingo Hilgendorf, Christian Smolka, Thomas Helbing, Imo Hoefer, Jennifer S. Esser, Max Kustermann, Martin Moser, Christoph Bode, Sebastian Grundmann
Journal: Circulation (2015)
Early stage epithelial ovarian cancer (EOC): Role of conservative surgery
Authors: L. Kumar, R. Hariprasad, S. Kumar, R. Dawar
Journal: Journal of Clinical Oncology (2005)

5149 Background: We analyzed case records of 109 patients with early stage EOC diagnosed between Jan 1991 and Dec 2002 at our Institute to determine the outcome. Patients and Methods: Patient’s median age was 46 years, ranging from 15–76 years.15% of patients were nulliparous. Clinical presentation included - abdominal pain (74%), abdominal distension (50%), menstrual irregularities (27%),pelvic mass (85%), abdominal mass (60%),& ascites (15%). FIGO stage:1A -28(25.7%),IB -6(5.5%), IC-53(48.6%),IIA-21.8%),IIB-6(5.5%), IIC-14(12.8%. 15(15.8%)patients underwent conservative surgery in view of young age and nulliparity. Histopathology: serous-45%,mucinous -27.5%,endometroid-10.1%,clear cell-3.7%, undifferentiated - 2.8% and adenocarcinoma - 10%. Tumor grade (n=96) revealed: Grade 1–36(37.5%), II-16(16.7%),and IIIin 44(45.8%) patients. Post surgery, residual disease was nil in 92%, less than 0.5cm in 2 (both Stage II C) and 0.5–1 cm in 7 patients (Stage IIB - 1,IIC-6). Results: 84 of 109 patients received adjuvant chemotherapy using either cisplatin + cyclophosphamide(CP)-55 (65.5%), CP+Adriamycin(CAP)-10(11.9%), Taxol + Carboplatin -5(6%),carboplatin alone - 9 (10.7%) and melphalan - 5(6%) as per the existing protocols during these years. Currently, 89 (81.7%) patients are alive at a median follow up of 46 months. Kaplan and Meier probability of 5 and 10 years survival are 81%& 78% for stage I and 80% & 60% for stage II, respectively. Twenty-three (21%) patients had relapsed (Stage IA - 5,IC-12, IIA-3,IIC -3), the median time to relapse being 22 months (range6–90). Following salvage chemotherapy, 9(40%) patients are alive, disease-free, 4 are on treatment & 10 have died of progressive disease. Of 15 patients who underwent conservative surgery(stage I-13,stage II- 2),12 received adjuvant chemotherapy. Six patients conceived & delivered healthy babies. 2 of these 15 patients have relapsed of whom one patient died of progressive disease. Conclusions: Present study confirms the better outcome for patients with early stage EOC. A small number of adequately staged IA patients with careful selection can be considered for conservative surgery followed by chemotherapy with similar outcome. No significant financial relationships to disclose.
Case 10-2011
Authors: Lawrence M. Tierney, Ashraf Thabet, Ha Nishino
Journal: New England Journal of Medicine (2011)

A 60-year-old woman was admitted to the hospital with confusion, fever, liver failure, anemia, and thrombocytopenia. She had recently begun treatment for hepatitis C. Serum levels of ferritin and triglycerides were elevated. A diagnostic procedure was performed.
William Leo McGuire, MD 1937–1992
Authors: C. Kent Osborne
Journal: Journal of Clinical Oncology (1992)

Article Tools IN MEMORIAM Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1992.10.9.1377 Journal of Clinical Oncology - published online before print September 21, 2016 William Leo McGuire, MD 1937–1992 C. Kent OsbornexC. Kent OsborneSearch for articles by this author Show More The University of Texas, Health Science Center at San Antonio, San Antonio, TX https://doi.org/10.1200/JCO.1992.10.9.1377 PDF "William Leo McGuire, MD 1937–1992." Journal of Clinical Oncology, 10(9), pp. 1377–1378© 1992 by American Society of Clinical Oncology
PROMOTING PHYSICAL ACTIVITY WITHIN SCOTTISH HOSPITAL SETTINGS
Authors: D White
Journal: British Journal of Sports Medicine (2015)

Aim To embed the routine promotion of physical activity (PA) across secondary care settings in Scotland; to enable and inspire the workforce to contribute to national targets; and to encourage innovative and collaborative approaches across various clinical settings. Methods A simple, validated screening tool for inactivity was developed, and set within the new ‘National Physical Activity Pathway’. Poor staff confidence and expertise on the topic was identified through national engagement, and this was addressed with the development of an educational resource suite (DVD &amp; facilitator notes; e-learning modules, etc).1 Revision of patient documentation was encouraged to increase opportunities for implementation of the PA Pathway. Facilitated local collaboration between clinical leads, health improvement staff, and Quality Improvement (QI) teams fostered new partnerships for action. A bespoke QI package was developed to support small-scale, developmental practice guided through improvement science, enabling systematic sharing and up-scaling of good practice. National guidance was issued to all health boards, detailing their obligations and the support available. Results A total of 3979 secondary care staff were trained in PA promotion and behaviour change within 12 months of the launch of the PA Pathway. The 'routine' promotion of physical activity increased from in only 9 clinical settings across 6 health boards, to 67 settings across all 15 Scottish health boards within the year. Documentation had been amended in 69 clinical settings. Conclusions Supporting the secondary care workforce to promote PA has seen early progress across a range of clinical settings and specialties. With PA promotion growing across Scottish hospital settings, evidencing the effectiveness of impact of this intervention is a priority allowing further momentum in the NHS contribution to a more active Scotland. Newly established local partnerships and national networks should allow for sustained progress moving forward.
OP0093 The Natural History of Thrombotic Events in Systemic Lupus Erythematosus and Associated Risk Factors: Table 1.
Authors: K. Hickman, L. Magder, M. Petri
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Prospective cohort studies of the natural history of thrombosis in SLE, including events before diagnosis are rare. No previous study has identified risk factors prospectively for both venous and arterial thrombosis. <h3>Objectives</h3> In this study we used a large prospective SLE cohort to assess the natural history of both arterial and venous thrombosis before and after the diagnosis of SLE. <h3>Methods</h3> 2305 SLE patients were enrolled in a prospective cohort. Medical records were reviewed to identify the occurrence of arterial and venous thrombosis prior to cohort entry. During participation in the Lupus Cohort, arterial thrombosis was diagnosed by patient history, diagnostic enzymes tests and imaging, including arteriogram, and venous thrombosis by ultrasound, CT or venography. We calculated the rate of thrombosis per person-year in periods of follow-up defined by time since diagnosis with SLE. <h3>Results</h3> The highest rates of both venous thrombosis and arterial thrombosis were observed in the 2 years before and the 2 years after diagnosis: 8.9-10.5 per 1000 patient years for arterial thrombosis and 11.4-12.5 per 1000 patient years for venous thrombosis. A second peak in incidence of arterial thrombosis (11.8 per 1000 patient years) was observed later in the course of SLE. <h3>Conclusions</h3> This large cohort study indicated that prevention of both venous and arterial thrombosis is important around the time of diagnosis of SLE. Monitoring for thrombosis should occur throughout the disease course, being mindful of the arterial thrombosis risk with longer duration of SLE. Our results suggest that the mechanism of events before diagnosis is not accelerated atherosclerosis as suggested by some investigators. Accelerated atherosclerosis would not explain the increase in both arterial and venous events that occurs before and at diagnosis. <h3>Disclosure of Interest</h3> None declared
Radiotherapy for breast cancer: Can the heart be protected with respiratory gating in patients with left-sided breast cancer?
Authors: C. Von Briel
Journal: Journal of Clinical Oncology (2009)

e11572 Background: Because there are hints for an increased risk of cardiovascular diseases after radiotherapy of the left chest wall the dose to the heart should be reduced as far as possible. With respiratory gating technique irradiation can be restricted only in the inspiratory plateau phase and so the distance between heart and chest wall will be increased. As a result the dose to the heart, in particular to the anterior wall, can be reduced. We investigated in all patients with left sided breast cancer dose reduction to the heart when treated only in the inspiration phase compared with not gated treatments. Methods: Between September 2004 and March 2008 97 pat. with left sided breast cancer were treated with respiratory gating technique. We irradiate only in maximum inspiration with a range between 10% - 20%. For the investigation of real dose reduction to the heart we performed for all of these patients a normal and a respiratory gated planning CT. DVH for the entire heart and the anterior wall of the left ventricle wall were calculated. 96/97 of these pat. were treated with 2 Gy single dose to a total dose of 50 Gy to the entire left breast, 1 pat with 1.8 Gy single dose to 50.4 Gy. 72 pat. had an additional boost of 10 Gy. The PTV was in 75 pat. after breast conserving surgery the left breast, in 22 pat. after mastectomy the left chest wall. Results: To median dose to the anterior ventricle wall was 2.3 Gy (0.5 Gy - 7.9 Gy) without and 1.3 Gy (0.1 Gy - 5.6 Gy) with respiratory gating (p = 0.001). The median maximal dose to the anterior wall was 45.2 Gy (5.5 Gy - 52.3 Gy) without and 4.5 Gy (0.9Gy - 50.6 Gy) with respiratory gating (p = 0.000). In 72 pat. the maximal dose reduction to the anterior wall was &gt; 20 Gy. In this pat. the mean movement of the diaphragma was 26mm against 16 mm for pat. with dose reduction &lt;20 Gy (p = 0.000). The mean up and down movements ot the chest wall were 7.9mm (&gt;20 Gy) and 5.2 mm (&gt;20Gy) (p = 0.05). Conclusions: Respiratory gating and irradiation only in the inspiratory phase reduce radiation dose to the heart and especially to the anterior wall of the heart significantly. Pat breathing with diaphragm seems to profite mostly from treating only in inspiratory phase. No significant financial relationships to disclose.