tbuckley/cabot-search huggingface dataset:
PWE-254 Is the macroscopically normal mucosa (MNM) around colorectal cancer really ‘normal’?: Abstract PWE-254 Table 1
Authors: A Patel, Y Fang, J Moore, N Williams, G Tripathi, R Arasaradnam
Journal: Gut (2015)

<h3>Introduction</h3> Field cancerisation refers to the process whereby cells acquire pro-tumourigenic mutations that predispose to malignant transformation but do not produce morphological change.<sup>1</sup>Previous colorectal cancer studies have assumed that the macroscopically normal mucosa (MNM) adjacent to a cancer is biologically unaltered. The aim of this study was to determine if the genetic expression profile of the MNM around a cancer or adenoma is different to that found in healthy controls. <h3>Method</h3> 15 patients undergoing colonoscopy were recruited over 12 months; 5 healthy controls, 5 with colorectal adenomas and 5 with adenocarcinoma. Two mucosal pinch biopsies were taken in the rectum, right colon and adjacent to polyp or cancer. mRNA was extracted and gene expression was assessed using standard whole genome micro-array analysis. Differentially expressed genes were identified using three methods of analysis: LIMMA (fold change ratio &gt;1.5 and p value &lt;0.05), Robust Regression (RR) (adjusted p value &lt;0.05) and genes that ‘overlap’ when LIMMA (p value &lt;0.001) and RR (adjusted p value &lt;0.1) are used. Functional analysis was performed using DAVID<sup>2</sup>software to identify important biological processes that were dysregulated. <h3>Results</h3> A large number of genes were dysregulated in the MNM adjacent to cancer or adenoma compared with controls (Table 1). Interestingly, the greatest differences were seen between MNM adjacent to cancer and polyp in chromatin organisation, nucleosome processing, nuclear transport and histone assembly. The most significantly upregulated genes consisted of FUT2, CTSA, MUC2 and SDS and downregulated genes consisted of GREM1, SFRP, HIST1H, IL17B and TFF1. <h3>Conclusion</h3> The MNM adjacent to a cancer or adenoma has a different gene expression profile to the MNM found in healthy controls. Further characterisation of this field defect could aid in early diagnosis of patients with colorectal cancer and help risk stratify patients undergoing surgery who are at greater risk of recurrence. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Luo Y, Yu M, Grady WM. Field cancerization in the colon: a role for aberrant DNA methylation?<i>Gastroenterol Rep (Oxf). </i>2014;2(1):16–20 Huang DW, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protocols. 2009;4(1):44–57
Treatment of Chronic Renal Failure by Prolonged Peritoneal Dialysis
Authors: Russell A. Palmer, John E. Newell, E. John Gray, Wayne E. Quinton
Journal: New England Journal of Medicine (1966)

KIDNEY substitutes that are effective in the management of chronic renal failure are hemodialysis and peritoneal dialysis. Scribner's technic for hemodialysis developed in 1958–59,1 employing an arteriovenous bypass, has been successfully used in a number of North American and European centers2 since 1960, maintaining selected patients in a relatively asymptomatic state; a number have been able to return to employment and ordinary activities. Apparatus suitable for home treatment is now being used by a few patients in Seattle and Boston.The method of closed intermittent peritoneal dialysis developed in 1951 by Grollman et al.3 for the treatment of acute renal . . .
Effects of the Toll-like Receptor 4 (TLR4) Agonist Glucopyranosyl Lipid a (GLA) on Allergen-Induced Inflammation and Anaphylaxis in a Mouse Model of Peanut Allergy
Authors: Keith Graver, George Qian, Xiaying Wu, Li Li, Dongling Chen, Mayra Fernandez, Timothy J. Soos, Christopher Arendt, El-Bdaoui Haddad
Journal: Journal of Allergy and Clinical Immunology (2016)
Case 28-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Alan M. Sugar, Anthony R. Mattia
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 51-year-old man was admitted to the hospital because of a nonhealing finger lesion with regional lymphadenopathy.The patient had been well until one month earlier, when a splinter abraded the dorsal aspect of the proximal interphalangeal joint of the left third finger while he was chopping wood. Two weeks later he observed enlargement and ulceration of the wound and consulted a physician. Radiographs of the hand were reported to be normal, and the patient took an unknown antibiotic for seven days, without improvement. Nine days before admission, he came to the emergency department of this hospital, . . .
S117 RSIV. F/HN-mediated gene therapy enables lungs to produce therapeutically relevant levels of FVIII
Authors: KM Pytel, MC Paul-Smith, J McIntosh, M Chan, C Meng, I Pringle, L Davis, M Inoue, M Hasegawa, SC Hyde, DR Gill, AC Nathwani, EWFW Alton, U Griesenbach
Journal: Thorax (2015)

<h3></h3> We have previously shown that lung when treated with Sendai virus-mediated gene transfer can produce secreted proteins and release them into the circulation (Griesenbach<i> et al.</i>, Mol Therapy 2002). Despite the high levels of transduction efficiency the gene expression is transient and repeated administration is not feasible due to induction of immune responses. To overcome these barriers we developed a lentiviral vector specifically pseudotyped with the Sendai virus envelope proteins F and HN (rSIV. F/HN) to allow efficient transduction of the airways. Stable expression for &gt;20 months after a single dose and efficient transduction after repeated administration despite detection of anti-rSIV. F/HN neutralising antibodies make the vector an attractive candidate for a large range of disease indications. Here, we first transduced mouse lung with rSIV. F/HN carrying the secreted reporter gene Gaussia luciferase (GLux) or a control virus by nasal instillation (1e6 transduction units (TU)/mouse, n = 5 –6/group). Persistent levels of GLux expression were detectable in lung (3 logs above control) and broncho-alveolar lavage fluid (BALF, 4 logs above control) for at least 12 months. Importantly, even this modest dose of virus lead to significant (p &lt; 0.01) levels of GLux in serum (274 ± 72 RLU/ul, control: 41 ± 6 RLU/ul) which persisted for at least 12 months further supporting the hypothesis that the lung is a suitable, non-invasive factory for production of secreted proteins. Gene therapy strategies for haemophilia have focussed on intravenous or intramuscular delivery of the gene transfer agent. Here, we treated the murine lung with rSIV. F/HN carrying the FVIII cDNA (1.6e8–3.4e8 TU/mouse,) or placebo and assessed whether therapeutically relevant levels of FVIII can be produced. Significant (p &lt; 0.05) and dose-related levels of FVIII were detectable in lungs and BALF 10 and 28 days post-transduction. Dose-related levels of FVIII were also detectable in plasma, which reached a therapeutically relevant level of 3% of normal 1 month after gene transfer. These data support the concept that rSIV. F/HN-mediated transduction of lungs can produce therapeutically relevant and persistent levels of recombinant protein in blood. <h3>Reference</h3> 1 Griesenbach U, Cassady RL, Ferrari S <i>et al</i>. The nasal epithelium as a factory for systemic protein delivery. <i>Mol Ther</i>. 2002;<b>5</b>:98–103
Impact of timing of initiation of adjuvant chemotherapy on survival after resection of colorectal cancer
Authors: I. Ahmad, G. Anan, R. Alvi, K. Haider, A. Sami, S. Yadav, F. Arnold, L. McLeann, S. Popkin, S. Ahmed
Journal: Journal of Clinical Oncology (2007)

4054 Background: Based on the results of intergroup trials, adjuvant chemotherapy has become the standard of care for patients with Duke stage C colon and Duke stages B and C rectal cancer. Although initiation of adjuvant chemotherapy soon after recovery from surgery is desirable, only few studies have examined whether a delay in starting adjuvant chemotherapy affect clinical outcomes. Our objective in this study is to determine the impact of timing of adjuvant chemotherapy on survival after resection of Duke stage C colon and Duke stages B and C rectal cancer. Methods: Study involves use of the information available from patients chart review in the province of Saskatchewan, Canada. Patients 18 years of age and older (median age 66 years), diagnosed with Duke Stage C colon and Duke stages B and C rectal cancer between 1993 and 2000 were included. Median followup was 54.8 months. All patients with rectal cancer received radiation treatment as per institution policy. Cox proportional hazards models were used to analyze the impact of timing of adjuvant chemotherapy on survival. Results: Among 701 patients eligible for study, 453 (64.6%) patients received adjuvant chemotherapy within 56 days of surgery (group I) and 248 patients (35.3 %) received adjuvant chemotherapy after 56 days of surgery (group II). Median time interval between surgery and the initiation of adjuvant chemotherapy in group I, and II were 41 days and 70 days respectively. Five year DFS for group I was 39% as compared to 37% for group II (HR 0.94, CI 0.76–1.16, p = 0.58). Median OS for group I was 97.5 months as compared to 68.9 months (HR 1.08, CI 0.85–1.37, p= 0.54). Age, histology and number of lymph nodes analyzed, were identified as independent prognostic factors in multivariate analysis. Conclusions: In this study, patients with Duke stage C colon and Duke stages B and C rectal cancer who received adjuvant chemotherapy within 56 days of resection has similar outcomes as compared to patients who received adjuvant chemotherapy after 56 days of resection. [Table: see text]
The clinical governance model (UFA-ONCO-EMA model) for anticancer drugs delivering of the ARNAS Garibaldi: third year experience
Authors: G.E. Fassari, R. Bordonaro, D. Sambataro, M. Mattina, S. Impera, D. Caudullo, O. Pitocchi, O. Comandatore, C. Martines, A. Buemi, U. Consoli, G. Murolo
Journal: Annals of Oncology (2015)
Losses and Physiologic Requirements for Water and Electrolytes after Extensive Burns in Children
Authors: Jack Metcoff, Harvey Buchman, Morad Jacobson, Harry Richter, Ernest D. Bloomenthal, Marjorie Zacharias
Journal: New England Journal of Medicine (1961)

BURNS are among the most common accidental injuries of infants and children and, when extensive, have mortality rates in excess of 50 per cent. When the burned area involves more than 20 or 30 per cent of the body surface the acute trauma is usually associated with a period of hypotension and generalized circulatory disturbance characterized as a shocklike state. Subsequently, alteration of circulatory hemodynamics in such vital organs as the brain and kidneys, tendency for accumulation of fluids in the burned areas, seepage from the traumatized surface and secondary adjustments of the extracellular and intracellular fluids to both injury . . .
What Heterosexual Adults Believe about Condoms
Authors: Kyung-Hee Choi, Richard Rickman, Joseph A. Catania
Journal: New England Journal of Medicine (1994)

To the Editor: Beliefs about condoms are powerful correlates of condom use among adolescents,1 adults,2 heterosexuals,3 injection-drug users,4 and homosexual men5. However, information on these bel...
A Study of the Effect of Vitamin C and of an Antihistaminic Drug on Gingival Hyperplasia Occurring in Patients Receiving Diphenylhydantoin Sodium
Authors: J. H. Rose, W. J. Buffaloe, R. M. Dunham
Journal: New England Journal of Medicine (1961)

THERE has been much interest in the etiology and treatment of gingival hyperplasia occurring in patients receiving diphenylhydantoin sodium¶ since the effectiveness of the drug as an anticonvulsant was reported by Merritt and Putnam1 in 1938. In recent years there have been conflicting reports as to the effect of antihistaminic drugs on gingival hyperplasia.2 3 4 Only one of these reports was very encouraging. Owing to the conflicting conclusions and the small number of subjects used in these studies, we have conducted the following study in an attempt to determine if an antihistamine (diphenhydramine hydrochloride) ∥ or vitamin C, a commonly used drug . . .
Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group
Authors: Y Morishima, Y Morishita, M Tanimoto, R Ohno, H Saito, K Horibe, N Hamajima, K Naito, K Yamada, S Yokomaku
Journal: Blood (1989)
Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis
Authors: Julian D. Gillmore, Mathew S. Maurer, Rodney H. Falk, Giampaolo Merlini, Thibaud Damy, Angela Dispenzieri, Ashutosh D. Wechalekar, John L. Berk, Candida C. Quarta, Martha Grogan, Helen J. Lachmann, Sabahat Bokhari, Adam Castano, Sharmila Dorbala, Geoff B. Johnson, Andor W.J.M. Glaudemans, Tamer Rezk, Marianna Fontana, Giovanni Palladini, Paolo Milani, Pierluigi L. Guidalotti, Katarina Flatman, Thirusha Lane, Frederick W. Vonberg, Carol J. Whelan, James C. Moon, Frederick L. Ruberg, Edward J. Miller, David F. Hutt, Bouke P. Hazenberg, Claudio Rapezzi, Philip N. Hawkins
Journal: Circulation (2016)

Background— Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed because of the limited specificity of echocardiography and the traditional requirement for histological confirmation. It has long been recognized that technetium-labeled bone scintigraphy tracers can localize to myocardial amyloid deposits, and use of this imaging modality for the diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicenter study to ascertain the diagnostic value of bone scintigraphy in this disease. Methods and Results— Results of bone scintigraphy and biochemical investigations were analyzed from 1217 patients with suspected cardiac amyloidosis referred for evaluation in specialist centers. Of 857 patients with histologically proven amyloid (374 with endomyocardial biopsies) and 360 patients subsequently confirmed to have nonamyloid cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was &gt;99% sensitive and 86% specific for cardiac ATTR amyloid, with false positives almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly, the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and the absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100% (positive predictive value confidence interval, 98.0–100). Conclusions— Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without the need for histology in patients who do not have a monoclonal gammopathy. We propose noninvasive diagnostic criteria for cardiac ATTR amyloidosis that are applicable to the majority of patients with this disease.
Latex as a Food Allergen
Authors: William Franklin, Josephine Pandolfo
Journal: New England Journal of Medicine (1999)

To the Editor: Since 1985, when the use of latex gloves by health care workers became common, 5 to 10 percent of health care workers have been sensitized to latex.1 We report a case in which dermatitis, nasal congestion, and asthma developed in a 46-year-old periodontist on exposure to latex about five years after she began to use latex gloves routinely in her work. Her sensitivity to latex was confirmed by a radioallergosorbent test. She also had an acute reaction, which was characterized by vaginal itching, itching of the abdomen, wheezing, shortness of breath, and hypotension, when a latex-contaminated probe . . .
Effect of ERK on tumorigenesis and on inhibition of FOXO3a via MDM2-mediated degradation
Authors: J. Yang
Journal: Journal of Clinical Oncology (2008)

11101 Background: The constitutive activation of certain signal transduction cascades leads to the development of tumors and the resistance of tumors to clinical therapy. The RAS-ERK triggers one of these cascades and governs many important functions in human disease, such as cancer. Approximately 30% of Human tumors frequently harbor activated RAS with a point mutation and contribute to several aspects of the malignant phenotype, in regulation of tumor cell growth, apoptosis, invasion, and angiogenesis. FOXO transcription factors, contains a conserved DNA binding domain, activate p27 and Bim to induce cell cycle arrest and apoptosis, respectively. Inhibition of FOXO3a expression promotes cell transformation, tumor progression. Method and Result: From our breast cancer patient samples, we found that in both IKK and AKT negative samples, FOXO3a was either absent or located at the cytoplasm. This suggests that there is another mechanism besides IKK and AKT that is involved in FOXO3a regulation. In this study, we found that ERK downregulated FOXO3a through directly interacting with and phosphorylating FOXO3a and consequently translocate FOXO3a from nuclear to cytoplasm and reduced FOXO3a protein stability through MDM2 mediated degradation. The nonphosphorylated FOXO3a mimic mutant, compared to the phosphorylated FOXO3a mimic mutant, exhibits more resistance to the interaction and degradation by MDM2, resulting in a strong inhibition of cell proliferation and tumorigenesis. Conclusion: We showed that ERK downregulates FOXO3a through directly interacting with and phosphorylating FOXO3a. The ERK phosphorylated FOXO3a was degraded via an MDM2-mediated degradation pathway and thereby consequently enhanced cell proliferation and tumorigenesis. However, the nonphosphorylated FOXO3a mutant was resistant to the interaction and degradation by MDM2. Thus, we identified a novel pathway involving the downregulation of FOXO3a expression by RAS/ERK and MDM2, which leads to promotion of cell growth and tumorigenesis. No significant financial relationships to disclose.
Further evidence of a dose-response threshold for haloperidol in psychosis
Authors: C K Stone, D L Garve, J Griffith, J Hirschowitz, J Bennett
Journal: American Journal of Psychiatry (1995)

The authors' goal was to determine whether higher doses of haloperidol improve antipsychotic response.During a 2-week, double-blind, randomized fixed-dose study, 24 psychotic patients were given 4, 10, or 40 mg/day of haloperidol.No clinically relevant difference between groups in favor of the higher antipsychotic doses could be detected.Doses of 4 mg/day of haloperidol appear to be as effective as higher doses in the treatment of psychosis.
Rubella Embryopathy
Authors: G. C. Liggins, L. I. Phillips
Journal: BMJ (1963)

OBLITERATIVE PULMONARY HYPERTENSIONBEDIBORNaL 711A diagnosis of obliterative pulmonary hypertension of unknown cause, presumed thrombo-embolic, postibly secondary to vasoconstriction, was made, and she was started on phenindione.She returned to Egypt and has not been seen since.Comment.-The physical signs were most unusual in this patient, the loud ejection murmur and soft pulmonary closure being unexplained.A long, loud systolic murmur arising from the pulmonary artery is exceptional in severe pulmonary hypertension with low cardiac output.However, the delay in pulmonary closure may have been due to a partial defect of conduc-tion in the right bundle branch resulting from right ventricular enlargement, and the pansystolic murmur to tricuspid insufficiency.The history of symptoms from an early age suggests that the condition may have started as " idiopathic" pulmonary hypertension but was succeeded by thrombosis or embolic occlusion.In either event, anticoagulant treatment seemed to offer the only hope of relief.
The internship year in psychiatry: a status report
Authors: M K Crowder, H B Roback
Journal: American Journal of Psychiatry (1981)

The reinstitution of the "internship" requirement by the American Board of Psychiatry and Neurology resulted in the development of a 4-year residence by most residency programs. The authors distributed a questionnaire to more than 200 psychiatry residency directors to collect data concerning the new "internship" year. Their results indicate that there is considerable diversity in the content of the "internship" and general satisfaction with the quality of the experience.
P75 Cluster classification as a predictor of adverse radiological outcomes in allergic fungal airways disease (AFAD)
Authors: K Woolnough, C Newby, M Richardson, AJ Wardlaw
Journal: Thorax (2015)

<h3>Introduction</h3> The relationship between immunological biomarkers and evidence of lung damage has not been established in asthmatics that are sensitised to fungi. We sought to determine what features of allergic fungal airways disease were related to adverse radiological outcomes by the use of cluster analysis. <h3>Method</h3> Factor analysis was used to determine the significance of different clinical and immunological variables, the number of clusters present and cluster membership (n = 423). The presence of radiological indicators of lung damage and inflammation were then assessed between these groups. <h3>Results</h3> Three clusters were identified. Cluster 1 (37.1%) were obese, had late onset and minimal eosinophilic disease, cluster 2 (40.9%) had late onset eosinophilic disease and cluster 3 (22%) had early onset, atopic disease. Sensitisation to <i>A. fumigatus</i> was more prevalent in cluster 3 (94.2%; sIgE <i>A. fumigatus</i> 10.2 kUA/L (1.31–35.4)), compared to cluster 1 (44.9%; sIgE <i>A. fumigatus</i> 0.16 kUA/L (0.03–0.94)) and cluster 2 (45.7%; sIgE <i>A. fumigatus</i> 0.25 kUA/L (0.06–1.36)). Cluster 3 had a greater degree of airflow obstruction (p &lt; 0.001), bronchiectasis (69%, p &lt; 0.001), tree in bud (32.4%, p &lt; 0.001), collapse/consolidation (48.6%, p0.007) and fibrosis (31.7%, p &lt; 0.05) than any of the other groups. <h3>Conclusion</h3> This cluster analysis demonstrates that sensitisation to <i>A. fumigatus</i>, in addition to the other known clinical phenotypes, identifies asthmatics most at risk of developing fixed airflow obstruction and radiological features of airway inflammation and damage.
Effect of Sodium Nitroprusside on Mortality in Acute Myocardial Infarction
Authors: Joseph D. Durrer, Kong Ing Lie, Frans J. L. van Capelle, Dirk Durrer
Journal: New England Journal of Medicine (1982)

We gave sodium nitroprusside by intravenous infusion to 163 randomly selected patients during the first 24 hours after hospitalization for typical acute myocardial infarction, and we studied its effects on mortality at one week, on the incidence of cardiogenic shock, on clinical signs of left ventricular failure, and on peak levels of creatine kinase isoenzyme MB. A control group of 165 patients received standard medical treatment and infusion of 5 per cent glucose. The end point of the study was a significant reduction in mortality in the nitroprusside group; this was reached when five deaths had occurred in this group, as compared with 18 among the controls (P<0.05). The incidence of cardiogenic shock, clinical signs of left-heart failure, and mean peak levels of creatine kinase isoenzyme MB were all reduced (P<0.05). The results indicate that infusion of nitroprusside in the early phase of acute infarction limits complications, possibly by reducing infarct size. The drug was particularly effective in anterior-wall infarction. (N Engl J Med. 1982; 306:1121–8.)
Case 6-2006
Authors: Paula D. Ryan, Mukesh Harisinghani, Melinda F. Lerwill, Donald S. Kaufman
Journal: New England Journal of Medicine (2006)

A 71-year-old woman with the recent onset of urinary incontinence was found to have bilateral adnexal masses in the pelvis and a mass in the bladder. A diagnosis of transitional-cell carcinoma was made, and treatment with cystectomy and chemotherapy was advised. The patient sought a second opinion. She had been well except for a history of carcinoma of the breast 22 years earlier. A diagnostic procedure was performed.