tbuckley/cabot-search huggingface dataset:
Alpha-Adrenergic Receptor Subtypes
Authors: Brian B. Hoffman, Robert J. Lefkowitz
Journal: New England Journal of Medicine (1980)

CATECHOLAMINES modulate a host of diverse responses in man. These responses are initiated by the interaction of catecholamines with discrete sites located on the plasma membrane of cells. Adrenergic receptors, like other hormone receptors, are responsible for the selective recognition and binding of specific molecular structures, in this case catecholamines such as epinephrine and related drugs. The demarcation between alpha-adrenergic and beta-adrenergic receptors has long been appreciated,1 as has the existence of beta-adrenergic receptor subtypes (beta1 and beta2).2 Recent advances in the understanding of alpha-adrenergic receptors have led to the appreciation of the existence of subtypes of . . .
Case 36-2005
Authors: Bradford C. Dickerson, David Holtzman, P. Ellen Grant, Di Tian
Journal: New England Journal of Medicine (2005)

A 62-year-old, previously healthy woman had a seizure, which was followed by persistent aphasia. Imaging studies showed bright lesions on T2-weighted and diffusion-weighted imaging, involving the cortex and the white matter, with normal perfusion. A brain biopsy showed changes consistent with ischemia. Over the course of the next year, hearing loss and slowly progressive dementia developed. A diagnostic procedure was performed.
The Hepatic Friction Rub
Authors: Herbert L. Fred, George R. Brown
Journal: New England Journal of Medicine (1962)

A HEPATIC friction rub has certain diagnostic implications that are useful in the approach to the patient with intra-abdominal disease. This fact was impressed upon us recently by a patient in whom a friction rub over the liver was caused by a hepatoma. Since the hepatic friction rub has received little attention in the literature we questioned several veteran observers about the significance of this sign.1 2 3 4 5 6 7 8 9 10 11 The purpose of this report is to describe our patient and to discuss the hepatic friction rub.Case ReportA 76-year-old man entered the Salt Lake County General Hospital because of stupor and abdominal . . .
Hematology and oncology fellows' attitude and knowledge in cancer pain management.
Authors: Fade A. Mahmoud, Konstantinos Arnaoutakis, Pooja Motwani, Liudmila N. Schafer, Paulette Mehta, Issam Makhoul
Journal: Journal of Clinical Oncology (2015)

178 Background: The American Society of Clinical Oncology considers palliative care an integral part of cancer therapy. Our Hematology and Oncology fellowship at the University of Arkansas for Medical Sciences (UAMS) began a year-long palliative care curriculum to improve symptom management education. In this pilot study we evaluate fellows’ attitude and knowledge in cancer pain management before and after implementing a pain management curriculum. Methods: Hematology and Oncology Fellows were divided into three groups. Each group delivered a one hour lecture in pain management for a total of 3 didactic lectures. We adopted “Evidence based Practice of Palliative Medicine by Goldstein and Morrison” as the main textbook. Fellows answered a 30 item questionnaire to address attitudes and knowledge in pain management. Answers were scored using a 5 point Likert scale (1 = strongly disagree and 5 = strongly agree). Results: 11 fellows participated; six males, five females, median age 34 (R 28-40), one US graduate, and ten foreign graduates. More fellows felt comfortable managing acute (M = 4.3, SD = 0.48) compared to chronic (M = 3.8, SD 0.78) cancer related pain. Most believe that if they were taught the principle of pain management they would feel more comfortable managing pain (M = 4.6, SD = 0.51). Post pain management module, there was a statistically significant improvement in fellow’s knowledge in pain management in the setting of renal failure (P = 0.02) and bone pain (P = 0.006), and a trend towards statistically significant in both opioid rotation and conversion (P = 0.06). Fellows did poorly on opioid-drugs interaction and management of neuropathic pain. Fellows valued palliative medicine service as a great resource for their patients but most believe that they should not refer all their patients to palliative medicine for pain management. Conclusions: Pain management skills are eroding among Oncology fellows and efforts should be made to enhance symptom and pain management education in oncology training programs. This curriculum improved knowledge and self-efficacy in pain management and revealed areas for further improvement. More research is needed to address whether fellows use and apply pain management skills in the clinical setting.
Antithymocyte Globulin (Rabbit) Enhanced The Efficacy Of Tacrolimus and Mycophenolate For Graft-Versus-Host Disease Prophylaxis In Recipients Of Unrelated Stem Cell Transplant Resulting In Improvement Of Survival
Authors: Voravit Ratanatharathorn, Abhinav Deol, Lois Ayash, Divaya Bhutani, Lawrence G Lum, Zaid Al-Kadhimi, Muneer H. Abidi, Marie Ventimiglia, Kendra Mellert, Joseph P. Uberti
Journal: Blood (2013)
Promotion of 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Mammary Tumorigenesis by High Dietary Fat in the Rat: Possible Role of Intercellular Communication&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C F Aylsworth, C Jone, J E Trosko, J Meites, C W Welsch
Journal: JNCI Journal of the National Cancer Institute (1984)

The effect of high levels of dietary fat on the promotion phase of rat mammary tumorigenesis and the effect of unsaturated and saturated fatty acids on metabolic cooperation in hamster cells were examined. Female Sprague-Dawley rats were given iv injections of 5 mg 7,12-dimethylbenz[a]anthracene (DMBA) and subsequently placed on 20% high-fat (HF) and 4.5% corn oil control (CF) diets. Rats treated with DMBA and fed HF diet for the entire duration of the experiment developed more tumors with shorter latency than rats fed CF diet for the entire experiment. Rats fed HF diet for 3 weeks at different times after DMBA treatment showed similar, enhanced mammary tumor development. Lengthening the duration of HF diet treatment (0, 3, 6, 16 wk) increased mammary tumor development, suggesting a time dose-response relationship. Removal of the HF diet treatment partially reversed its stimulatory effects on tumor development. These results indicate that dietary fat acts as a classical tumor promoter to enhance mammary tumorigenesis. The influence of unsaturated and saturated fatty acids on metabolic cooperation between 6-thioguanine-sensitive (6-TGS) and 6-thioguanine-resistant (6-TGr) Chinese hamster V79 cells was examined. Linoleic acid, palmitoleic acid, and arachidonic acid significantly increased the recovery of 6-TGr cells at noncytotoxic concentrations. Stearic acid, palmitic acid, and arachadic acid had no effect on the recovery of 6-TGr cells at either cytotoxic or noncytotoxic concentrations. These results demonstrate that unsaturated fatty acids but not saturated fatty acids can inhibit metabolic cooperation between Chinese hamster V79 cells, and suggest, mechanistically, that high dietary levels of polyunsaturated fat could promote tumorigenesis by inhibition of intercellular communication.
Clinical Recovery from Acute Ischemic Stroke after Early Reperfusion of the Brain with Intravenous Thrombolysis
Authors: Andrew M. Demchuk, Robert A. Felburg, Andrei V. Alexandrov
Journal: New England Journal of Medicine (1999)

To the Editor: A 1995 study found that treatment with tissue plasminogen activator (t-PA) was efficacious for intravenous thrombolysis if given within three hours after the onset of ischemic stroke...
Rearrangements of Genes for the Antigen Receptor on T Cells as Markers of Lineage and Clonality in Human Lymphoid Neoplasms
Authors: Thomas A. Waldmann, Mark M. Davis, Kathleen F. Bongiovanni, Stanley J. Korsmeyer
Journal: New England Journal of Medicine (1985)

The T alpha and T beta chains of the heterodimeric T-lymphocyte antigen receptor are encoded by separated DNA segments that recombine during T-cell development. We have used rearrangements of the T beta gene as a widely applicable marker of clonality in the T-cell lineage. We show that the T beta genes are used in both the T8 and T4 subpopulations of normal T cells and that Sézary leukemia, adult T-cell leukemia, and the non-B-lineage acute lymphoblastic leukemias are clonal expansions of T cells. Furthermore, circulating T cells from a patient with the T8-cell-predominantly lymphocytosis associated with granulocytopenia are shown to be monoclonal. Finally, the sensitivity and specificity of this tumor-associated marker have been exploited to monitor the therapy of a patient with adult T-cell leukemia. These unique DNA rearrangements provide insights into the cellular origin, clonality, and natural history of T-cell neoplasia.
Pulmonary Complications of the Flow-Directed Balloon-Tipped Catheter
Authors: George A. Foote, Stephen I. Schabel, Morrison Hodges
Journal: New England Journal of Medicine (1974)

Retrospective analysis of the course of 125 patients in whom flow-directed balloon-tipped catheters were employed showed that in nine (7.2 per cent), pulmonary ischemic lesions appeared to have occurred as a direct result of the use of the catheter. Mechanisms of the pulmonary ischemia included persistent wedging of the catheter tip in a peripheral artery (six cases), obstruction of a more central pulmonary artery by an inflated balloon (one case), and pulmonary embolism from venous thrombosis developing around the catheter (two cases). Awareness of the tendency for spontaneous wedging of the catheter to occur and of the possibility of air remaining in the balloon after use should reduce the frequency of these complications. (N Engl J Med 290:927–931, 1974)
Tick-Borne Infection Caused by<i>Rickettsia africae</i>in the West Indies
Authors: Philippe Parola, Jacques Jourdan, Didier Raoult
Journal: New England Journal of Medicine (1998)

To the Editor: Tick-borne rickettsioses have been suspected but not documented well in the Americas.1 We report a case of Rickettsia africae infection in the West Indies. In July 1997, a 50-year-old French woman was bitten by a tick on her right foot while on the island of Guadeloupe. A few days later she noted a 0.5-cm erythematous nodular lesion at the bite site, erythema of the right groin, and a low-grade fever. One month later, when back in France, she consulted one of us for fatigue and a low-grade fever. Her physical examination was normal, but the nodular lesion . . .
The News Media and the Doctor–Patient Relationship
Authors: Malcolm H. Rourk, Robert A. Hock, Joye S. Pursell, David Jones, Alexander Spock
Journal: New England Journal of Medicine (1981)

Two developments within our society have changed or will change the traditional physicianpatient relationship: the growing practice of the news media to report new research and developments in health-related fields, and the public's increasing conviction that as patients they have a right to know all facts about their disease. This right extends beyond an explanation of the disease, its treatment, and its prognosis, to the right to be informed accurately and promptly of new information relating to the disease. Physicians are just beginning to appreciate their responsibilities in this area, and although discussion is increasing in the literature, the immediate . . .
Neoadjuvant docetaxel (T), carboplatin (C), with or without trastuzumab (H) for T3 and T4 breast cancer
Authors: H. R. Chang, D. Slamon, L. Chap, S. Apple, J. Glaspy, P. Lee, J. Malin, M. Pegram, D. Chung
Journal: Journal of Clinical Oncology (2005)

845 Background: The neoadjuvant systemic treatment for locally advanced breast cancer offers the best treatment and provides an ideal opportunity to study the anti-tumor activity of novel therapy. In recent years, taxanes and targeted therapy are gaining popularity in treating breast cancer. This study examines the efficacy of neoadjuvant docetaxel (Taxotere)/ carboplatin/ trastuzumab (Herceptin) in treating women with T3/T4 breast cancer. Methods: Twenty-eight women enrolled between Oct 2002 and June 2004 have successfully completed the neoadjuvant phase of their treatment consisting of four cycles of T/C with or without Herceptin. Results: Nineteen (67.9%) had T3 and nine (32.1%) had T4 breast cancer. Twenty-three (82.1%) had infiltrating ductal cancer and five (17.9%) had infiltrating lobular cancer with 20 (71.4%) high grade, six (21.4%) intermediate grade and two low grade (7.1%) according to the MBR scores. Sixteen (57.1%) were hormone receptor positive and twelve (42.9%) were ER-/PR-. Twelve (42.9%) had HER-2 amplified tumor. Clinical complete response (cCR) were observed in 11 (39.3%), partial response (cPR) in 16 (57.1%) and marginal response in one (3.6%). All five pathological complete response (pCR) were observed in patients with T3 breast cancer (26.3%). Six patients with HER-2 amplified tumor were randomized to receive preoperative T/C/H and the other six received T/C. Only one received T/C/H was among the pCR and the two in the T/C group had minimal residual tumor ≤ 0.1mm. Eight were converted from the originally planned mastectomy to breast conservation surgery and all had achieved tumor-free margins. Conclusion: Our study suggests T/C ± H is effective in treating women with locally advanced breast cancer. Supported by: PHS/NCI RO1 CA 93736–01A, Aventis Pharmaceuticals, Genentech, Inc., and “Friends of the Breast Program at UCLA” Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Genentech
Chemically Induced Tumors of Rat Olfactory Epithelium: A Model for Human Esthesioneuroepithelioma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Vollrath, M Altmannsberger, K Weber, M Osborn
Journal: JNCI Journal of the National Cancer Institute (1986)

N-Nitrosopiperidine (CAS: 100-75-4) and 2,6-dimethylnitrosomorpholine induced tumors of the olfactory epithelium in white Wistar rats. Some tumors were serially transplanted to NMRI nude mice (nu/nu) and passaged up to 16 times in a 1-year period. Tumor tissues from rats and mice were analyzed by conventional pathological stains, by electron microscopy, and by immunofluorescence microscopy with the use of antibodies specific for different intermediate filaments. Both carcinogens induced tumors built of undifferentiated small, round cells in which neuroblastic (Homer-Wright) rosettes and ependymal (Flexner) rosettes were visible. In some tumors areas of squamous cell metaplasia could be observed, which sometimes differentiated toward squamous cell carcinoma. Electron microscopy showed neurosecretory granules in some tumor cells, and biochemical studies of plasma showed in some instances elevated ACTH and calcitonin levels. Intermediate filament typing showed that in general the undifferentiated tumor cells lack intermediate filaments, although in 6 of 29 tumors a few cells that stained positively for neurofilaments were found. Flexner rosettes, the areas showing squamous cell differentiation, and occasional single tumor cells were positive with keratin antibodies. Neurofilament expression was observed in a minor population of tumor cells placed in tissue culture. These findings are used to argue that the chemically induced rat tumors are a model for human esthesioneuroepithelioma and furthermore that the light basal cells of the epithelium may be the stem cells of the rat tumors as well as of its rare counterparts in humans.
Efficacy and Toxicity of Heparin in Relation to Age and Sex
Authors: Hershel Jick, Dennis Slone, Ivan T. Borda, Samuel Shapiro
Journal: New England Journal of Medicine (1968)

In 97 consecutive patients who received heparin, efficacy, as assessed by a clinically satisfactory response, was not related to sex or age. Adverse reactions occurred in 18 out of 56 women (32 per cent) and six out of 41 men (15 per cent). Average age of patients with reactions was 66 years versus 55 years for the remainder. The p values for association by sex and age were respectively less than 0.05 and 0.02. The increased toxicity in women appeared to be limited to those over the age of 60. In these, the risk was 50 per cent. Corresponding figures for men over 60, women under 60 and men under 60 were 19 per cent, 14 per cent and 10 per cent, respectively. All but one of the reactions were due to bleeding. Death from massive intrapulmonary hemorrhage was attributed to heparin in one case. There appears to be a higher risk of bleeding, without a corresponding improvement in efficacy, in women over the age of 60 who receive heparin.
The role of the RAS pathway in iAMP21-ALL
Authors: S L Ryan, E Matheson, V Grossmann, P Sinclair, M Bashton, C Schwab, W Towers, M Partington, A Elliott, L Minto, S Richardson, T Rahman, B Keavney, R Skinner, N Bown, T Haferlach, P Vandenberghe, C Haferlach, M Santibanez-Koref, A V Moorman, A Kohlmann, J A E Irving, C J Harrison
Journal: Leukemia (2016)

Intrachromosomal amplification of chromosome 21 (iAMP21) identifies a high-risk subtype of acute lymphoblastic leukaemia (ALL), requiring intensive treatment to reduce their relapse risk. Improved understanding of the genomic landscape of iAMP21-ALL will ascertain whether these patients may benefit from targeted therapy. We performed whole-exome sequencing of eight iAMP21-ALL samples. The mutation rate was dramatically disparate between cases (average 24.9, range 5-51) and a large number of novel variants were identified, including frequent mutation of the RAS/MEK/ERK pathway. Targeted sequencing of a larger cohort revealed that 60% (25/42) of diagnostic iAMP21-ALL samples harboured 42 distinct RAS pathway mutations. High sequencing coverage demonstrated heterogeneity in the form of multiple RAS pathway mutations within the same sample and diverse variant allele frequencies (VAFs) (2-52%), similar to other subtypes of ALL. Constitutive RAS pathway activation was observed in iAMP21 samples that harboured mutations in the predominant clone (⩾35% VAF). Viable iAMP21 cells from primary xenografts showed reduced viability in response to the MEK1/2 inhibitor, selumetinib, in vitro. As clonal (⩾35% VAF) mutations were detected in 26% (11/42) of iAMP21-ALL, this evidence of response to RAS pathway inhibitors may offer the possibility to introduce targeted therapy to improve therapeutic efficacy in these high-risk patients.
Abstract IA32: BCL-2 inhibition–An example of translational medicine–Update.
Authors: Gary B. Gordon
Journal: Clinical Cancer Research (2015)

Abstract Apoptosis, a conserved and carefully regulated cell suicide event, is the principal mechanism used by the organism to remove senescent, damaged, and redundant cells in order to maintain cellular homeostasis. Tumors dysregulate this pathway by perturbing the dynamic balance between pro-apoptotic and pro-survival members of the BCL-2 family proteins and as such, these proteins are compelling targets for the development of cancer therapeutics. Synthesizing small molecules capable of disrupting protein-protein interactions, however, has posed a major challenge for the field. Early BCL-2 antagonists, while active in the pre-clinical models, had failed to demonstrate efficacy in the clinic. Structure-activity based drug design has led to development of several new selective inhibitors of the BCL-2 and BCL-XL including navitoclax, ABT-199, and S-55746 with all three exhibiting activity in pre-clinical testing. Navitoclax has demonstrated tumor growth inhibition in select hematological malignancies but its utility was limited by accompanying thrombocytopenia. The next generation molecule, ABT-199, is an oral BCL-2-selective inhibitor that has shown activity in the clinic. This presentation will review the journey of drug discovery and development from the mechanism-based postulate and preclinical work to the translational studies and ultimately to the bedside. Citation Format: Gary B. Gordon. BCL-2 inhibition–An example of translational medicine–Update. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA32.
PTU-092 Crohn’s disease: strictureplasty and risks for further surgery
Authors: D Chan, D Kumar, M Mendall
Journal: Gut (2015)

<h3>Introduction</h3> Surgery plays an important role in the treatment of Crohn’s disease. Strictureplasty in particular is a practical and attractive treatment for Crohn’s disease, conserving bowel length. Only a few large surgical series have been published in the literature. We describe our own experience and factors that determine risk of reoperation or death over a ten year period. <h3>Method</h3> All the Crohn’s disease strictureplasties for a specialist IBD surgeon at St George’s Hospital from 1st January 2005 to 31st December 2014 were identified. Information was collected for weight, height, gender, smoking status as well as their medical and surgical management. Patients whose records were incomplete were contacted for further information. <h3>Results</h3> There were a total of 53 cases of strictureplasty, with just under 3,400 months of follow-up. 22 had concurrent bowel resection. 32 were male. Mean age of diagnosis was 24 years and 10 months. Mean time from diagnosis to first ever surgery was 6 years and 3 months. Mean number of prior surgeries was 1. Total number of further surgery in the follow-up period was 11, with mean time to reoperation 42 months. No patients died during in the follow-up period. 86.54% were non smokers. At the time of surgery 30.25% had a low BMI, 60.45% had a normal BMI and 9.3% had a high BMI. 72.55% were receiving treatment with the immunomodulators: azathioprine, 6-mercaptopurine or methotrexate. Kaplan Meier survival analysis was used to compare those that had strictureplasties and those that had strictureplasty and concurrent bowel resection, with further surgery or death up to 31st December 2014 as the endpoint. Log rank test for trend did not find that there was any significant difference between the two groups and probability of further surgery. Cox regression analysis was used to assess for risk for further surgery: age of diagnosis, number of previous surgeries, time from diagnosis to first ever surgery, treatment with immunomodulators, concurrent bowel resection, sex, BMI and smoking status. Significant risk for further surgery was found in those that had ever smoked (hazard ratio 4.775, p = 0.003) and those patients with a low BMI who had concurrent bowel resection as well as strictureplasty (hazard ratio 6.31, p = 0.002). Importantly previous surgery and age of diagnosis were not a risk factor for recurrent surgery (hazard ratios 1.016 and 1.198 respectively). <h3>Conclusion</h3> We review a decade of strictureplasties in the management of Crohn’s disease and have identified significant risks for further surgery of smoking and low BMI as well as concurrent bowel resection. We show that strictureplasty remains a viable and attractive management for stricturing Crohn’s disease with no deaths resulting from the surgery and a low number of reoperations. <h3>Disclosure of interest</h3> None Declared.
Clinical Trials of Hepatitis B Immune Globulin
Authors: James K. Roche, James M. Stengle
Journal: New England Journal of Medicine (1972)

The National Blood Resource Branch of the National Heart and Lung Institute initiated on July 1, 1972, controlled clinical studies to evaluate the efficacy of hepatitis B immune globulin (HBIC) for the prevention and treatment of hepatitis Type B. Three patient populations are being investigated: subjects with acute fulminant hepatitis; persons with a known, accidental parenteral exposure to hepatitis B antigen (HBAg) contained in blood or blood products; and patients and staff newly arrived on chronic renal-dialysis units. Co-ordinating centers have been established for each patient population to be studied. Working with these centers, in clinical trials investigators affiliated with . . .