tbuckley/cabot-search huggingface dataset:
AT-01 * THERAPEUTIC TARGETING OF INI1 DEFICIENCY IN PEDIATRIC ATRT: A PRE-CLINICAL STUDY UTILIZING PATIENT DERIVED ORTHOTOPIC XENOGRAFT (PDOX) MODELS
Authors: H. Lindsay, M. Kogiso, L. Qi, J. Murray, L. Perlaky, J. Su, P. Baxter, A. Adesina, D. Parsons, M. Chintagumpala, X.-N. Li
Journal: Neuro-Oncology (2015)

INTRODUCTION: Atypical teratoid rhabdoid tumors (ATRTs) are molecularly-defined by deletions or mutations in tumor suppressor INI1. INI1 deficiency causes dysfunction of chromatin-remodeling complexes which normally oppose EZH2, a epigenetic gene silencing protein. In the setting of INI1 deficiency, EZH2 is over-expressed, leading to ATRT oncogenesis. Using novel patient-derived orthotopic xenograft (PDOX) models, we investigated the pre-clinical utility of therapeutic EZH2 inhibition in ATRT using the drug DZNep. METHODS: Two PDOX models of ATRT were established by directly implanting tumor cells into mouse brains in the matched location with patient tumor. For in vitro testing, ATRT cells were exposed to DZNep at doses from 78 to 5000 nM for 2 weeks; cell viability was measured every 1- 3 days. For in vivo testing, 40 mice were divided into 4 treatment groups: control, DZNep (5 mg/kg i.p. daily x 14 days), standard of care (cranial radiation 2 Gy daily x 5 days, cisplatin 5 mg/kg i.p. on days 8 and 11), and combination therapy. Survival times were compared using log-rank analysis. RESULTS: DZNep showed dose- and time-dependent in vitro inhibition of tumor cell viability in both ATRT models tested. One of these models (IC-L1115ATRT) was then subjected to in vivo studies. ATRT tumors were present at the time of xenograft death in all 4 treatment groups including DZNep- and combination therapy-treated animals. Survival time did not differ between the control- and DZNep-treated groups or the standard of care- and combination therapy-treated groups (P > 0.05). CONCLUSIONS: While the EZH2 inhibitor DZNep is effective in vitro in killing ATRT tumor cells, it does not appear to have effects in vivo when tested in PDOX models of pediatric ATRT acting alone or in combination with combined chemo- and radio-therapies. Extensive further pre-clinical evidence should be obtained before an EZH2 inhibitor is brought into pediatric clinical trials.
Sickle Cell Crisis And Urea
Authors: Paul R. McCurdy
Journal: JAMA (1974)

<h3>To the Editor.—</h3> As one of the investigators involved in the studies that failed to demonstrate efficacy for urea in the treatment of the painful crisis of sickle cell anemia, I should like to respond to the letter from Drs. Nalbandian and Henry (229:1285, 1974). Although the Blodgett-Wayne protocol was not followed in every detail for our studies (228:1125, 1974), we did test the hypothesis that rapid elevation of the blood urea concentration to or above a critical level (150 mg/100 ml) would abort a sickle cell painful crisis. The protocol used was based on our own preliminary evaluation begun very soon after Dr. Nalbandian's original studies. Our data suggested that the intravenous urea treatment was worthy of further carefully controlled study (<i>N Engl J Med</i>285:992, 1971). The Blodgett-Wayne 30% urea solution was connected to a central venous catheter through a Y tube, the other arm of which was
O'Connor's Textbook of Arthroscopic Surgery
Authors: Letha Y. Hunter
Journal: JAMA (1985)

This is an updated multiauthored version of O'Connor's original text,<i>Arthroscopy</i>. After Dr O'Connor's untimely death, Dr Heshmat Shahriaree assumed the duties of editor. The initial chapters present an excellent historical review of the development of arthroscopy, discuss the anatomy and clinical examination of the knee, and describe general equipment needed by the arthroscopist. This last section is not as complete as it could be and tends to favor Wolfe instrumentation. There is also a chapter at the end of this text that deals with arthroscopy of joints other than the knee. However, most of the book is devoted to a general review of knee pathology in which the use of the arthroscope may be beneficial and includes torn menisci, symptomatic plica, osteochondritis dissecans, loose bodies, degenerative arthritis, tibial compression fractures, the acutely injured knee, the unstable knee, intra-articular adhesions, and synovial diseases. The discussion of each of these entities
Wheezing in a High Risk Cohort Predicts an Increased Prevalence of Positive Skin Test Results Relative to a General Population Sample
Authors: K.T. Sullivan Dillie, E.L. Anderson, D.F. DaSilva, M. Evans, R. Gangnon, T.E. Pappas, L.E. Pleiss, K.A. Roberg, C.J. Tisler, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2006)
P317 Hsp72 OVEREXPRESSION PROTECTS FROM ACETAMINOPHEN AND DDC-ASSOCIATED LIVER INJURY BUT ENHANCES MALLORY–DENK BODY FORMATION
Authors: K. Levada, N. Guldiken, C. Pfaff, F.R. Mo, P. Lahiri, C. Trautwein, P. Strnad
Journal: Journal of Hepatology (2014)
Doctor Jekyll and Mister Assad
Authors: T. Dalrymple
Journal: BMJ (2012)

Everyone knows the story of Dr Jekyll and Mr Hyde , and understands the moral: that there is, lurking within even the best and most benevolent of us, a ravening beast, an evil monster, that requires very little encouragement to emerge. Whether or not this is literally the case, it is a powerful metaphor for the sudden change in character, usually for the worse, that whole populations, and all the more so, individuals, can undergo.

That is why, perhaps, a book about one of our colleagues, one Dr Bashar Al Assad, written by a French journalist called Jean-Marie Quemener, is titled Doctor Bashar, Mister Assad . How is …
The Concept of Stratified Medical Care
Authors: Irving S. Wright
Journal: JAMA (1972)

There appears to be emerging a remarkable unanimity from both professional and public sources that medical service must be reorganized in the immediate future. The simple approach which first occurs to some is to provide more funds in the hopes of quickly producing medical facilities and personnel and greatly improved medical service. Those who are experienced in this problem recognize that funding is indeed essential but that instant results are not to be expected. It takes years and not months to train physicians, nurses, and technical personnel. It also takes many months, often several years, to plan, fund, and develop new or renovated facilities and to assemble and pretest the rather complex equipment and units now considered essential for modern medical care. In order to provide quality care for large numbers of our population, considerable restructuring of the use of our resources will be essential. For the past three years
X-ray Treatment of Goiter
Authors: G. W. GRIER
Journal: Annals of Internal Medicine (1927)

Article1 October 1927X-ray Treatment of GoiterG. W. GRIER, M.D.G. W. GRIER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-1-4-241 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe indication for radiation treatment in goiter is hyperthyroidism, the contraindication is a normal or a minus metabolic rate. The exceptions to this rule are malignancy of the thyroid or inoperable intrathoracic thyroid. In the first instance, radiation may be used to supplement operative measures or as a primary treatment. In either case the prognosis is very grave. In intrathoracic goiter either with or without hyperthyroidism if operation is considered inadvisable, radiation should be instituted in an effort to reduce the size of the gland and relieve the pressure symptoms. In all other conditions of the thyroid gland radiation should... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pittsburgh, Penna. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPreoperative and postoperative treatment of the toxic thyroid 1 October 1927Volume 1, Issue 4Page: 241-246KeywordsHyperthyroidismThyroid ePublished: 1 December 2008 Issue Published: 1 October 1927 PDF downloadLoading ...
EFFECT OF SUBMAXIMAL EXERCISE HEART RATE ON THE RESULTS OF QUANTITATIVE THALLIUM-201 STRESS TESTING
Authors: F. L. Murphy, J. Maddahi, T. Bateman, A. Becerra, M. Steuer, S. A. Reisman, A. Kimchi, A. Rozanski, E. Garcia, H. J.C. Swan, D. Berman
Journal: Clinical Nuclear Medicine (1982)

Murphy, F. L.; Maddahi, J.; Bateman, T.; Becerra, A.; Steuer, M.; Reisman, S. A.; Kimchi, A.; Rozanski, A.; Garcia, E.; Swan, H. J.C.; Berman, D. Author Information
THE USE OF PARATHYROID EXTRACT IN HEMORRHAGE
Authors: BURGESS GORDON
Journal: JAMA (1927)

There is perhaps no manifestation of disease which arouses so much concern as hemorrhage. It points without question to the presence of diseased or injured tissue, and not infrequently life depends on the early recognition of the cause and its effective control. When superficial structures are involved, ligation, cautery, pressure and local hemostatic agents are usually efficient means of therapy. However, in hemorrhage from internal sources these are of doubtful value, obviously because certain parts are inaccessible or unsatisfactory for local treatment. Furthermore, the general condition of the patient may not justify surgical intervention. It may be wiser to utilize conservative measures and to aid the normal protective mechanisms of the body. A mechanism of great importance is that of blood coagulation. Failure of this mechanism to function normally may lead to prolonged and fatal bleeding. It is well, therefore, always to consider its efficiency, whether or not surgical methods
Treating Acute Acetaminophen Poisoning With Acetylcysteine
Authors: Robert G. Peterson
Journal: JAMA (1977)

A patient ingested 15.6 gm acetaminophen and sought medical attention after seven hours. At that time, her plasma acetaminophen level was 217μg/ml. Treatment with acetylcysteine was begun eight hours after the ingestion. The clinical course of this patient was characterized by a mild illness with a minor elevation of liver enzyme values. A number of factors predicted severe hepatotoxicity for this patient had she not received treatment. (<i>JAMA</i>237:2406-2407, 1977)
Recognition and assessment of coeliac disease in children and adults: summary of NICE guidance
Authors: R. Richey, P. Howdle, E. Shaw, T. Stokes
Journal: BMJ (2009)

Coeliac disease is an autoimmune condition that can be diagnosed at any age. Although it has been traditionally associated with mainly gastrointestinal signs and symptoms, its non-gastrointestinal features have been increasingly recognised. Given its varied clinical manifestations and the historical belief that it is relatively uncommon,1 2 concern has been raised that coeliac disease—and its possible long term consequences—is being underdiagnosed. It has also been shown to be more prevalent in people with other autoimmune conditions.3 This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the recognition and assessment of coeliac disease.4 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Who should be offered serological testing for coeliac disease? [Based on moderate quality evidence from cohort studies]
Pulmonary arterial hypertension in patients treated with interferon
Authors: Laurent Savale, Marie-Camille Chaumais, Olivier Sitbon, Marc Humbert
Journal: European Respiratory Journal (2015)

We read with interest the correspondence by Prella and colleagues reporting yet another case of pulmonary arterial hypertension (PAH) suspected to be induced by long-term interferon (IFN)-β therapy in a patient with multiple sclerosis. As discussed by Prella and colleagues, IFN-α and IFN-β are regarded as “possible” risk factors for PAH [1]. This was justified by the publication of case reports of IFN-induced PAH in the past decade [2–10] and the experience recently reported by the French Referral Centre for Pulmonary Hypertension [11]. Despite strong clinical and temporal suspicion, it remains a great challenge to definitively confirm the causal role of IFN in the development PAH because many patients (especially those treated with IFN-α for hepatitis C) have concomitant PAH risk factors such as portal hypertension and/or HIV infection. In these patients, IFN therapy may potentially act as an additional trigger for portopulmonary and/or HIV-associated PAH. Accumulating clinical and experimental data argue for a possible causal link between IFN therapy and PAH <http://ow.ly/Ttsqv>
Selective vulnerability of the medullary thick ascending limb to anoxia in the isolated perfused rat kidney.
Authors: M Brezis, S Rosen, P Silva, F H Epstein
Journal: Journal of Clinical Investigation (1984)

A specific anatomical lesion sharply localized to the cells of the medullary thick ascending limbs (mTAL) and characterized by mitochondrial swelling progressing to nuclear pyknosis and cell death is elicited reproducibly in isolated rat kidneys perfused for 15 or 90 min with cell-free albumin-Ringer's medium gassed with 5% CO2, 95% O2 (O2 content, 1.5 vol/100 ml). The lesion, involving about half of mTALs, appears first in mTALs removed from vascular bundles and near the inner medulla, areas most likely to be anoxic. Hypoxic perfusion (O2 content 0.12 vol/100 ml) exaggerates the lesion, wiping out gradations of damage and extending it to all mTALs. O2-enriched perfusions using rat erythrocytes (O2 content 7.1 vol/100 ml) completely eliminates the lesion (unless gassed with carbon monoxide). Similarly, supplementation of the perfusion medium with a purified hemoglobin (O2 content 5.8 vol/100 ml) prevents mTAL injury. Perfusion with a fluorinated hydrocarbon blood substitute, Oxypherol (O2 content 4.3 vol/100 ml) also attenuates the lesion. These findings suggest that the mTAL is exquisitely susceptible to anoxic damage because of low O2 supply imposed by the medullary vascular system and the high rate of metabolism mandated by active reabsorption of sodium chloride. The vulnerability of the mTAL to anoxic injury could play a key role in the pathogenesis of ischemic renal injury.
Cancer researcher convicted of child pornography charges is spared erasure after showing remorse
Authors: C. Dyer
Journal: BMJ (2014)

A histopathologist and noted cancer researcher will keep his medical registration despite a conviction for viewing child pornography on the internet. The Medical Practitioners Tribunal Service chose not to apply the usual sanction of erasure to Dana Faratian, instead suspending him for one year.

Faratian, 35, whom the MPTS panel acknowledged had “made singular contributions within the UK and beyond in relation to molecular and other laboratory analysis for the sophisticated diagnosis of cancers” lost his job at Edinburgh University and his funding from Medical Research Scotland after his conviction in October 2012. …
The Role of State Medical Associations in Continuing Medical Education
Authors: Richard W. Opfell
Journal: JAMA (1973)

State medical associations must define the role they are to play in the continuing education of their members. The production or stimulation of more programs in continuing medical education—programs that are designed to transfer information—is unlikely to help a profession that is drowning in a flood of information. "Opening the floodgates further is unlikely to help a drowning man." The ultimate goal of continuing medical education is continually improving patient care. One cannot realistically design a program to improve patient care unless there is an agreement on exactly what there is about correct patient care that needs improving, and one cannot evaluate the effectiveness of the continuing medical education without measuring the impact on the quality of patient care. There is no expert, text, or other person that has a priori knowledge of what a physician should be doing to improve the quality of care he provides for his patients.
The effect of bile salts on carbonic anhydrase
Authors: David E. Milov, Wou-Seok Jou, Rachel B. Shireman, Paul W. Chun
Journal: Hepatology (1992)

Bile salts are potent inhibitors of bovine carbonic anhydrase and human carbonic anhydrase I and human carbonic anhydrase II. To further characterize the binding of bile salts to carbonic anhydrase, rate constants for the CO2 hydration reaction in the presence of deoxycholate, cholate, glycocholate and taurocholate were determined using stop-flow experiments. Values for the Michaelis-Menton dissociation constant for bovine carbonic anhydrase, human carbonic anhydrase I and human carbonic anhydrase II were found to be 5.2, 9.2 and 13.2 mmol/L, respectively. The inhibition constant values for the various bile salts tested ranged from 0.1 to 1 mmol/L for bovine carbonic anhydrase, 1.6 to 2.4 mmol/L for human carbonic anhydrase I and 0.09 to 0.7 mmol/L for human carbonic anhydrase II. Our results suggest a mechanism of noncompetitive carbonic anhydrase inhibition for bile salts. Bile-salt binding to carbonic anhydrases as measured by scanning molecular sieve chromatography resulted in an increase in partition radius, molecular volume and surface area. The partition radius increased from 24 A to 28 A in the presence of 2.5 mmol/L sodium deoxycholate at critical micelle concentration. As determined by sedimentation equilibrium measurements, approximately 1 gm of carbonic anhydrase will bind 0.03 gm of deoxycholate, suggesting three to six binding sites for bile salt on the carbonic anhydrase molecule. The conformational changes and inhibition of carbonic anhydrases resulting from bile-salt binding may be important to the regulation of enzymatic activity in tissues along the enterohepatic circulation; by limiting bicarbonate availability this interaction may also contribute to the metabolic derangements seen in patients with cholestatic liver disease.
Nuclear weapons are another post-communist health hazard
Authors: Nick Wilson
Journal: BMJ (2005)

A tale of two Germanys Health problems in eastern Germany are clearly related to transitionEditor-The fall of the Berlin Wall in 1989 marked the beginning of the end of communism in eastern Europe and in eastern Germany.As McKee and Fister point out, 1 certain constellations of epidemiological and demographic variables characterise the resultant process of political and economic transition: low or even decreasing life expectancy (especially for men) and higher prevalences of alcoholism and obesity.This has happened in the postcommunist Länder (federal states) of eastern Germany.East Germany is different from other east European countries in that its healthcare sector was not deconstructed, with periods of severe dysfunction: it simply adopted the healthcare system of West Germany.Despite this, life expectancy at birth is still lower in eastern Germany than in western Germany, although the difference had diminished at the end of the 1990s. 2 Alcoholic disease is a feature of the typical transition process.The number of people discharged from hospital with alcoholic disease was higher in eastern Germany in 1994 and 1999 than in western Germany. 3 Obesity is another transition related problem and a risk factor for many diseases. 4 The proportion of the population with obesity (body mass index > 29.9) is higher in eastern Germany than in western Germany.This difference has remained for over 10 years after the fall of the Berlin Wall.In the medium term, the situation is set to even out.But it is remarkable that in spite of the same, well equipped (curative) health system, health care does not strongly modify mainly lifestyle linked health effects in a population that is exposed to transition after communism.For eastern Germany, the end of this transition process is in sight.
Effect of aflatoxin metabolism and DNA adduct formation on hepatocellular carcinoma among chronic hepatitis B carriers in Taiwan
Authors: Ming-Whei Yu, Ju-Ping Lien, Yueh-Hsya Chiu, Regina M. Santella, Yun-Fan Liaw, Chien-Jen Chen
Journal: Journal of Hepatology (1997)

Aflatoxins (AFs) are established hepatic carcinogens in several animal species. This study was performed to establish whether aflatoxin exposure may affect the risk of developing hepatocellular carcinoma in chronic hepatitis B virus carriers.Urinary AF metabolites were measured for 43 HCC cases and 86 matched controls nested in a cohort of 7342 men in Taiwan. Thirty hepatocellular carcinoma cases and 63 controls were also tested for AFB1-albumin adducts.There was a dose-response relationship between urinary AFM1 levels and risk of hepatocellular carcinoma in chronic hepatitis B virus carriers. Comparing the highest with the lowest tertile of urinary AFM1 levels, the multivariate-adjusted odds ratio (OR) was 6.0 (95% confidence interval (CI) = 1.2-29.0). The hepatocellular carcinoma risk associated with AFB1 exposure was more striking among the hepatitis B virus carriers with detectable AFB1-N7-guanine adducts in urine. Compared with chronic hepatitis B virus carriers who were negative for AFB1-albumin adducts and urinary AFB1-N7-guanine, no elevated risk was observed for those who were positive for either marker. But an extremely high risk of hepatocellular carcinoma among those having both markers was found (OR = 10.0, 95% CI = 1.6-60.9). The proportion of AFB1 converted to AFM1 decreased with the progress of liver disease, whereas the formation of AFP1 increased. The difference in patterns of AFB1 metabolite formation was an independent risk factor for hepatocellular carcinoma after adjustment for total AFB1 excretion. There was a synergistic interaction between glutathione S-transferase M1 genotype and AFB1 exposure in hepatocellular carcinoma risk.AFB1 intake and expression of enzymes involved in AFB1 activation/detoxification may play an important role in hepatitis B virus-related hepatocarcinogenesis.