tbuckley/cabot-search huggingface dataset:
Abstract IA26: Oncogenic mechanisms in diffuse intrinsic pontine gliomas
Authors: Andre B. Silveira, Lawryn H. Kasper, Jon D. Larson, Xiaoyan Zhu, Alexander K. Diaz, Suzanne J. Baker
Journal: Cancer Research (2016)

Abstract Diffuse intrinsic pontine glioma (DIPG) is a devastating disease with no effective cures. DIPG arises in the brainstem and is found almost exclusively in children. Mutations in canonical cancer signalling pathways including the RTK/RAS/PI3K pathway, the Tp53 pathway, and the CDK4/6 G1 checkpoint occur in DIPGs, targeting different effectors within these pathways and resulting in significant genetic heterogeneity between tumors. However, genome-wide studies provided abundant evidence that unique selective pressures drive HGG in children compared to adults, identifying novel oncogenic mutations connecting tumorigenesis and chromatin regulation as well as developmental signaling pathways. Recurrent mutations of the BMP receptor ACVR1/ALK2 are found in 25-30% of DIPGs, and are further restricted to the youngest patients, highlighting critical connections between development and gliomagenesis. The molecular hallmark of DIPGs is frequent recurrent somatic mutation in histone H3. Mutually exclusive somatic heterozygous H3F3A or HIST1H3B mutations encoding a K27M variant of histone H3.3 or H3.1, respectively, are found in nearly 80 percent of DIPGs. These recurrent mutations provide clear evidence of an important role for chromatin regulation in DIPG disease pathogenesis, and present a unifying molecular mechanism driving DIPG. We have evaluated the contribution of H3.3 K27M mutation to DIPG tumor growth in vitro to gain insights into molecular mechanisms of oncogenic activity, and to assess the potential of histone H3 mutation as a therapeutic sensitivity in this incurable brain tumor. Citation Format: Andre B. Silveira, Lawryn H. Kasper, Jon D. Larson, Xiaoyan Zhu, Alexander K. Diaz, Suzanne J. Baker. Oncogenic mechanisms in diffuse intrinsic pontine gliomas. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr IA26.
A Controlled Trial of a Single Dose of Azithromycin for the Treatment of Chlamydial Urethritis and Cervicitis
Authors: David H. Martin, Tomasz F. Mroczkowski, Z.A. Dalu, James McCarty, Robert B. Jones, Scott J. Hopkins, Raymond B. Johnson
Journal: New England Journal of Medicine (1992)

Currently, there is no single-dose therapy that is effective in the treatment of urethral or endocervical infections with Chlamydia trachomatis. Azithromycin is a new azalide antibiotic that has substantial activity against C. trachomatis, is concentrated intracellularly, and has a long half-life in serum and tissue.
Influence of Disodium Etidronate on Clinical and Laboratory Manifestations of Paget's Disease of Bone (Osteitis Deformans)
Authors: Roy D. Altman, C. Conrad Johnston, M.R.A. Khairi, H. Wellman, A. N. Serafini, R. R. Sankey
Journal: New England Journal of Medicine (1973)

A six-month double-blind controlled study was performed to determine effectiveness and dose response of disodium etidronate on Paget's disease (osteitis deformans). Forty-seven subjects were studied with pain related to radiologically documented Paget's bone sites as well as marked elevation of serum alkaline phosphatase and hydroxyproline excretion. There was significant (p<0.05) reduction of alkaline phosphatase, hydroxyproline and radiofluoride or radiostrontium uptake over Paget's bone lesions after orally administered disodium etidronate at doses of 5, 10 and 20 mg per kilogram per day for six months. There was a dose-response relation of administered disodium etidronate to improvement of pain, with moderate or marked improvement of pain in six of seven subjects on 20 mg per kilogram per day. In all dosage groups the most marked relief of pain was at sites of Paget's involvement of long bones. Apparent side effects were limited to occasional abdominal cramps. (N Engl J Med 289:1379–1384, 1973)
Mucormycosis of the Hand and Forearm
Authors: C Lidor, J A Nunley
Journal: New England Journal of Medicine (1997)

Figure 1. Mucormycosis of the hand and forearm occurred in a 28-year-old woman after a thermal burn of the right thumb caused by tap water (Panel A). The patient had mild diabetes mellitus that had been treated with 10 mg of glyburide per day for four years. Hyphal invasion (arrows) and propagation through the blood vessels (Panel B, ×600) resulted in necrosis of the hand and forearm (Panel A) and was life threatening, necessitating amputation of her arm to above the elbow 26 days after the injury. The infection was caused by nonseptate hyphae of Rhizopus oryzae, 3 to 15 . . .
X-ray and Ultrasound Localization of Non-Palpable Breast Lesions and Difficulties in Management
Authors: J J T Tate, G T Royle, P McDonald, P B Guyer, I Taylor
Journal: Journal of the Royal Society of Medicine (1987)

Seventy-four patients who have had biopsy of a non-palpable breast lesion are reviewed. A double-dye localization technique was used in 88% while in 12% localization of the lesion was best achieved by ultrasound mammography. Biopsy was successful in 70 patients (95%) at the first attempt. The overall incidence of malignancy was 20%, being greater in asymptomatic patients (32%) than in patients with mastalagia (16%). Re-excision of the biopsy site in these patients showed residual cancer in 33%. It is suggested that both careful examination of the operative specimen and postoperative mammography may be necessary to ensure that the original lesion has been removed. Re-excision of the biopsy site appears to be necessary when the histology is malignant.
Variation in Approval by Insurance Companies of Coverage for Autologous Bone Marrow Transplantation for Breast Cancer
Authors: William P. Peters, Mark C. Rogers
Journal: New England Journal of Medicine (1994)

The proper evaluation of new forms of technology depends on the results of clinical trials. However, the treatment of patients in grant-sponsored clinical trials of cancer therapy usually requires that the proposed treatment be approved in advance by an insurance carrier in a process called predetermination.
Nephrogenic Diabetes Insipidus in North America — The<i>Hopewell</i>Hypothesis
Authors: Hans H. Bode, John D. Crawford
Journal: New England Journal of Medicine (1969)

Nephrogenic diabetes insipidus is prevalent among the descendants of the so-called Ulster Scot who settled in Nova Scotia during the eighteenth century. The folklore description of its mode of inheritance implies X-linked transmission. This is in conformity with analyses of previously published data and five new pedigrees. In the latter all 12 sons of eight affected males were healthy, but each of their 21 examined daughters were heterozygotes. Among the 221 offspring of 53 heterozygous females close to the expected half (121) were gene carriers. Historical data suggest that female carriers were among the 1761 settlers arriving at Halifax aboard the ship Hopewell. Since it has been possible to link both the new and several previously published pedigrees from other parts of the Continent to these immigrants, it is tempting to propose that most North American patients suffering from this disorder are among the progeny of the Ulster Scot.
Liver Necrosis after Halothane Anesthesia
Authors: John P. Bunker, Charles M. Blumenfeld
Journal: New England Journal of Medicine (1963)

IN 1956, after extensive pharmacologic studies, a new, potent and nonexplosive volatile anesthetic agent, halothane (Fluothane), or 2-bromo-2-chloro-1,1,1-trifluoroethane, was introduced into clinical practice.1 , 2 Today, it is one of the most popular and widely used of all inhalation anesthetics. The danger that this compound, in common with other halogenated hydrocarbons such as chloroform, tribromoethanol and carbon tetrachloride, might damage the liver has been recognized, but to date only a handful of cases of possible halothane-induced toxic hepatitis have been reported.3 4 5 6 7 Two additional cases occurring in the practice of one of us (C.M.B.) are the subject of this report.Case ReportsCase . . .
Natural History of Pulmonary Subsolid Nodules: A Prospective Multicenter Study
Authors: Ryutaro Kakinuma, Masayuki Noguchi, Kazuto Ashizawa, Keiko Kuriyama, Akiko Miyagi Maeshima, Naoya Koizumi, Tetsuro Kondo, Haruhisa Matsuguma, Norihisa Nitta, Hironobu Ohmatsu, Jiro Okami, Hiroshi Suehisa, Taiki Yamaji, Ken Kodama, Kiyoshi Mori, Kouzo Yamada, Yoshihiro Matsuno, Sadayuki Murayama, Kiyoshi Murata
Journal: Journal of Thoracic Oncology (2016)
Management strategies for women at high risk for breast and ovarian cancer: Are women satisfied?
Authors: S. N. Westin, C. C. Sun, K. H. Lu, K. M. Schmeler, P. T. Soliman, K. G. White, M. S. Daniels, B. K. Arun, S. K. Peterson, D. C. Bodurka
Journal: Journal of Clinical Oncology (2007)

1524 Background: Women at high risk for breast and ovarian cancer have two major management options to reduce their risk of ovarian cancer, periodic screening (PS) or prophylactic oophorectomy (PO). Little is known regarding patient satisfaction levels with choice of risk reduction strategy. Our objective was to determine levels of patient satisfaction with PO versus PS and to identify factors which may influence satisfaction. Methods: As part of a larger study, women who received BRCA1/2 testing before July 2005 were sent a follow-up patient questionnaire packet. We are reporting on the Cancer Worry Scale and Satisfaction With Decision (SWD) scale (range of possible scores, 6–30). The lowest 10 th percentile of the SWD score (21) was used to define low satisfaction. Chi-square, t-Test and Mann-Whitney tests were used for statistical analyses. Results: A total of 540 surveys were mailed and 309 responses were received (57%). We excluded 127 patients due to history of an oophorectomy for benign or malignant indications or incomplete SWD scale. The median age of respondents was 48.2. 60/182 women (33%) had BRCA mutations and 64/182 (35.2%) underwent PO. The overall satisfaction rate among respondents was high (median score 29, range 14–30). Median SWD score was significantly higher in patients in the PO group compared to the PS group (30.0 vs. 26.5, p&lt;.001). Patients with BRCA mutations had higher median SWD scores, regardless of management type (30.0 vs. 28.0, p=.013). Low satisfaction scores were associated with the perception that the decision between PO and PS was difficult to make (p=.001). Patients who expressed ongoing difficulty in their decision-making also had lower satisfaction scores (p=.016). Satisfaction was unrelated to demographics, clinical factors, or concerns of cancer risk. Conclusions: In our study, the majority of women at high risk for breast and ovarian cancer were satisfied with their choice of risk reduction strategy. In particular, women who chose PO had higher levels of overall satisfaction. Difficulty with decision-making was associated with lower satisfaction levels. Improved education and support of these women through the decision-making process may enhance overall levels of satisfaction with risk reduction strategy. No significant financial relationships to disclose.
Case 34-2002
Authors: Paula Ravin, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 55-year-old right-handed man was admitted to the hospital because of difficulty with his handwriting and motor problems in his right leg.The patient, who was a teacher, had been well until five months earlier, when he began to experience numbness and a sensation of “swelling” in the feet, without obvious edema, as if his shoes were too tight; this sensation persisted. Three days before admission, he noted subtle difficulty in steering his automobile. Later the same day, he found his handwriting to be awkward while he was grading his students' papers; his right foot felt “clumsy” . . .
The Publication of Sponsored Symposiums in Medical Journals
Authors: Lisa A. Bero, Alison Galbraith, Drummond Rennie
Journal: New England Journal of Medicine (1992)

An increasing proportion of spending by the pharmaceutical industry has gone to funding symposiums that are published by peer-reviewed medical journals. This study tests the hypothesis that such sponsorship, particularly by a single pharmaceutical company, is associated with a promotional orientation of the symposium and a distortion of the peer-review process.
Host-Specific Interleukin-2–Secreting Donor T-Cell Precursors as Predictors of Acute Graft-versus-Host Disease in Bone Marrow Transplantation between HLA-Identical Siblings
Authors: Matthias Theobald, Thomas Nierle, Donald Bunjes, Renate Arnold, Hermann Heimpel
Journal: New England Journal of Medicine (1992)

Acute graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation from an HLA-identical sibling. There is no practical test before transplantation that gives sufficient information to predict the degree of allogeneic reactivity between HLA-identical siblings.
Measurement of soluble Programmed Death-Ligand 1 (soluble PD-L1) to predict survival in biliary tract cancer patients treated with chemotherapy.
Authors: Hyerim Ha, Ah-Rong Nam, Ju-Hee Bang, Younak Choi, Do-Youn Oh, Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2015)

11094 Background: Programmed death-ligand 1 (PD-L1) expression in cancer cells or tumor microenvironment is under investigation as a candidate biomarker in the new drug development of immuno-oncology field. Preparation of tumor tissues for PD-L1 expression has some challenges. The soluble form of PD-L1 (sPDL1) is suggested as retaining immunosuppressive activity. In this study, we measure the levels of sPDL1 in serum and evaluate its role in prediction of overall survival (OS) in biliary tract cancer (BTC) patients. Methods: Seventy seven BTC patients’ serum was collected before initiation of standard palliative chemotherapy. sPDL1 was measured using an enzyme-linked immunosorbent assay. Clinical data including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII, neutrophil X platelet/lymphocyte) were collected. Cut-off of each variable for OS prediction was determined by ROC curve. Results: The primary site of BTCs were;30IHCC, 28 GB ca, 8 EHBTC, 11 AoV ca. OS of all patients was 10.7 months (95% CI; 8.53- 14.93) and 1-year overall survival rate was 46.8%. Median sPDL1 level was 1.20 ng/ml (range 0.02-7.3, mean 1.48, SD 1.19). Median values of NLR, PLR, SII were 2.34, 8.81 and 514.8 respectively. High level of sPDL-1 ( > 1.10 ng/ml) conferred poor prognosis (OS 7.7 m vs 17.7 m, p = 0.001). High levels of NLR ( > 2.10), PLR ( > 9.5), SII ( > 650) were also significant factors for poor OS (P = 0.029, P = 0.015, P = 0.002). However, in multivariate analysis, only sPDL1 predicts worse survival (HR 2.16, p = 0.008). Patients with high sPDL1 showed decreased albumin level, high NLR, PLR, SII. Among 77 patients, 19 outliers with longer survival (OS > 20m) had lower levels of sPDL1 (P = 0.007). Conclusions: The soluble form of PD-L1 (sPDL1) can be measured in the serum of BTC patients, and it has significant impact on the prognosis of BTC patients treated with standard chemotherapy.
PTH-047 Differences in luminal distribution and clinical characteristics of crohn’s disease in south asians and white british in the north of england
Authors: MA Khan, W Newman, WJ Hill
Journal: Gut (2015)

<h3>Introduction</h3> Inflammatory bowel diseases (IBD) are inflammatory conditions that affect the gastrointestinal tract and may have extra intestinal manifestations. The two main subtypes are Crohn’s disease (CD) and ulcerative colitis (UC). The incidence of IBD has traditionally been higher in Caucasian populations in Europe, North America and Australia compared to other regions of the world. There is now evidence of increasing incidence in all populations worldwide. Studies from the UK, North America, Malaysia and Singapore have observed a 2–3 times higher incidence of IBD in South Asian immigrant populations compared to local cohorts. However, few studies have described the diseas phenotype and mucosal distribution in the South Asian immigrant population. <h3>Method</h3> Ethics approval was obtained ref: O5/Q1407/274. Patients were recruited prospectively in 11 centres in the North Of England. Inclusion criteria were diagnosis of CD and age &gt;16 years. Exclusion criteria were Diagnosis of IBDU or IDC and Age &lt;16 years. Information was collected from using a standard clinical proforma. Data was stored on and analysed on a FileMaker Pro database. Chi Squared analysis was used to compare groups. <h3>Results</h3> In total, 128 South Asians (SA) and 426 White British. In the South Asian cohort more males than females were affected compared to White British cohort, which had the opposite trend. South Asians were most likely to be diagnosed with Colonic disease (L2) compared to White British (50% vs. 24% respectively), which was highly statistically significant (p = 1 × 10<sup>–6</sup>). Differences in each luminal distribution group (L1–L4) were statistically significant in both groups. In addition differences in disease behaviour were statistically significant for B1 and B2 disease but was not significant for B3 disease. South Asians were less likely to be diagnosed over the age of 40 (A3) compared to White British which was statistically significant (p = 0.02). There was no statistical difference in positive family history or EIM’s between groups. South Asians were less likely to need surgery compared to Caucasians (29% vs. 58%), which was highly significant. <h3>Conclusion</h3> There are significant differences in luminal distribution, age of diagnosis and need for surgery between groups. South Asians are less likely to need surgery suggests a less severe phenotype compared to White British. These differences may represent differences in disease pathogenesis in particular genetic susceptibility or environmental factors. This information will help inform current and future genotype studies. <h3>Disclosure of interest</h3> None Declared.
P149 Once-daily tiotropium Respimat® add-on to at least ICS in adult patients with symptomatic asthma: pooled safety analysis: Abstract P149 Table 1
Authors: D Dusser, R Buhl, M Castro, HAM Kerstjens, P Paggiaro, M Engel, P Moroni-Zentgraf, A Unseld, ED Bateman
Journal: Thorax (2015)

<h3>Background</h3> A high proportion of patients with asthma are symptomatic despite at least ICS maintenance therapy. Five trials aimed to evaluate the safety of tiotropium Respimat® compared with placebo Respimat®, each as add-on to at least ICS in adult patients with symptomatic asthma. <h3>Methods</h3> Five Phase III and one Phase II randomised, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-asthma® (48 weeks): tiotropium Respimat® 5 µg add-on to ICS + LABA (≥800 µg budesonide or equivalent); MezzoTinA-asthma® (24 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on to ICS (400–800 µg budesonide or equivalent); GraziaTinA-asthma® (12 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on to ICS (200–400 µg budesonide or equivalent); Study 342 (16 weeks): tiotropium Respimat® 5 µg add-on to ICS (400–800 µg budesonide or equivalent). Pooled safety data are presented. <h3>Results</h3> 1929 patients received tiotropium Respimat® (PrimoTinA-asthma®, n = 456; MezzoTinA-asthma®, n = 1036; GraziaTinA-asthma®, n = 309; Study 342, n = 128). Frequency of AEs in &gt;2% of patients was comparable in the tiotropium Respimat® 5 µg, tiotropium Respimat® 2.5 µg and placebo Respimat® groups (Table 1). No deaths occurred. 110 (5.7%) and 55 (4.4%) patients receiving tiotropium Respimat® and placebo Respimat®, respectively, reported drug-related AEs (cardiac AEs were rare: tiotropium Respimat®, 7 [0.4%]; placebo Respimat®, 3 [0.2%]). One drug-related serious AE (asthma) was reported with tiotropium Respimat®. <h3>Conclusion</h3> Once-daily tiotropium Respimat® add-on to at least ICS maintenance therapy in adult patients demonstrates a safety profile comparable with that of placebo and is well tolerated across severities of symptomatic asthma.
Severe Cryptococcal Pneumonia
Authors: G R Robinson
Journal: New England Journal of Medicine (1995)

A 68-year-old man who had had biopsy-proved cryptococcal pneumonia 19 years earlier after cleaning a pigeon-infested barn was admitted to the hospital with increasing dyspnea, nonproductive cough, reduced exercise tolerance, and fever. His earlier episode of pneumonia had been treated with amphotericin B, but he was able to receive only a total of 1.5 g of the drug, because renal tubular acidosis, azotemia, and electrolyte disorders developed. He had been asymptomatic in the intervening years.On admission, a chest radiograph showed five-lobe alveolar infiltrates (Panel A). Flexible fiberoptic bronchoscopy revealed cryptococci. Despite treatment with large doses of amphotericin B and . . .