tbuckley/cabot-search huggingface dataset:
Report calls for better evaluation of pharmcogenetic tests
Authors: R. Moynihan
Journal: BMJ (2003)

The marketing of pharmacogenetic tests may be moving much faster than the underlying medical science, warns a study published this week.

“There is widespread recognition that pharmacogenetics may have been oversold … The basic science is still substantially uncertain,” argues its author, David Melzer, and colleagues from the Department of Public Health and Primary Care at the University of Cambridge. Funded by the Wellcome Trust, the study was based on interviews and focus groups involving key experts on pharmacogenetics and major stakeholders in the United States and …
The Performance of a Risk Score as a Screening Test for Undiagnosed Hyperglycemia in Ethnic Minority Groups
Authors: Annemieke M.W. Spijkerman, Matthew F. Yuyun, Simon J. Griffin, Jacqueline M. Dekker, Giel Nijpels, Nicholas J. Wareham
Journal: Diabetes Care (2004)

OBJECTIVE—To assess the performance of the Cambridge Risk Score (CRS) to predict undiagnosed hyperglycemia in Caribbean and South Asian people living in the U.K. RESEARCH DESIGN AND METHODS—The CRS uses routinely available data from primary care records to identify people at high risk for undiagnosed type 2 diabetes. The sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve for the CRS cut point of 0.199 were 77, 72, and 80% (95% CI 68–91), respectively. The risk score was calculated for 248 Caribbean and 555 South Asian participants aged 40–75 years in the 1999 Health Survey for England. Undiagnosed hyperglycemia was considered present if fasting plasma glucose was ≥7.0 mmol/l or HbA1c was ≥6.5%. Sensitivity, specificity, and predictive values were calculated for various cut points of the risk score, and ROC curves were constructed. RESULTS—The area under the ROC curve was 67% (59–76) and 72% (67–78) for Caribbeans and South Asians, respectively. The optimal cut point in Caribbean participants was 0.236, sensitivity was 63% (46–77), and specificity was 63% (56–69). In the South Asian population, the optimal cut point was and 0.127, sensitivity was 69% (60–78), and specificity was 64% (60–69). CONCLUSIONS—The CRS, using routinely available data, can be used in a strategy to detect undiagnosed hyperglycemia in Caribbean and South Asian populations. The existence of ethnic group–specific cut points must be further established in future studies.
Stem Cell Marking With Promotor-deprived Self-inactivating Retroviral Vectors Does Not Lead to Induced Clonal Imbalance
Authors: Kerstin Cornils, Claudia Lange, Axel Schambach, Martijn H Brugman, Regine Nowak, Michael Lioznov, Christopher Baum, Boris Fehse
Journal: Molecular Therapy (2008)

Stable genetic modification of stem cells holds great promise for gene therapy and marking, but commonly used gamma-retroviral vectors were found to influence growth/survival characteristics of hematopoietic stem cells (HSCs) by insertional mutagenesis. In this article, we show that promoter-deprived gamma-retroviral self-inactivating (pd-SIN) vectors allow stable genetic marking of serially reconstituting murine HSC. In contrast to findings with gamma-retroviral long terminal repeat (LTR) vectors, serial transplantation of pd-SIN-marked HSC in a sensitive mouse model was apparently not associated with induced clonal imbalance of gene-marked HSC. Furthermore, insertions of pd-SIN into protooncogenes, growth-promoting and signaling genes occurred significantly less frequent than in control experiments with LTR vectors. Also, transcriptional dysregulation of neighboring genes potentially caused by the pd-SIN insertion was rarely seen and comparatively weak. The integration pattern of promotor-deprived SIN vectors in reconstituting HSC seems to depend on the transcriptional activity of the respective gene loci reflecting the picture described for LTR vectors. In conclusion, our data strongly support the use of SIN vectors for gene-marking studies and suggest an increased therapeutic index for vectors lacking enhancers active in HSC.
Abnormal leukotriene C4 released by unaffected jejunal mucosa in patients with inactive Crohn's disease.
Authors: F Casellas, F Guarner, M Antolin, R Rodriguez, A Salas, J R Malagelada
Journal: Gut (1994)

The mucosal release of inflammatory mediators is enhanced in active inflammatory bowel disease. This study examines whether leukotriene C4 production occurs in apparently unaffected segments of the gut. The intraluminal release of leukotriene C4 was determined by jejunal perfusion in seven healthy controls, in nine patients with chronic ulcerative colitis, and in 13 patients with Crohn9s disease (six with ileal disease, and seven with only colonic). All patients were in clinical remission and none of them had evidence of jejunal involvement. Mild intraluminal irritation with a 2.5 mmol/l deoxycholic acid solution was induced to stimulate local inflammatory mechanisms. The release of DNA (a marker of mucosal desquamation) and prostaglandin E2 (PGE2) was simultaneously measured. Jejunal release of DNA was higher in Crohn9s disease patients than in ulcerative colitis or healthy controls. Basal release of PGE2 was similar in the three groups of patients. Basal release of leukotriene C4 was considerably enhanced, however, in Crohn9s disease patients compared with healthy controls. In ulcerative colitis patients, basal leukotriene C4 release was non-significantly different from controls. Bile acid perfusion stimulated PGE2, leukotriene C4, and DNA release in all groups studied, but leukotriene C4 release was significantly higher in Crohn9s disease patients. It is concluded that in inactive Crohn9s disease there is an enhanced intraluminal release of leukotriene C4 in apparently unaffected segments of proximal small bowel, which may reflect fundamental changes in the function of the gut mucosal barrier.
Cost-shifting in Oregon-Reply
Authors: David M. Eddy
Journal: JAMA (1992)

<h3>In Reply.</h3> —Dr Witten makes a good point. There is little doubt that for some treatments, physicians will simply offer the treatment and end up swallowing the costs themselves. This is indeed a form of cost-shifting. However, the burden this will place on physicians will be mitigated by several factors. First, the cost-shifting is most likely to occur only for treatments that can be administered during a single office visit, and that do not require any special tests, procedures, or drugs. It is unlikely to occur for any of the expensive treatments (eg, treatment for anencephaly or infertility treatments), or for any treatments that require repeated visits, tests, or procedures. Second, physicians themselves will determine the extent to which the cost-shifting will occur. Third, this cost-shifting will not mean that Oregon's physicians will bear all the burden of Oregon's program: they will merely join Oregon's businesses, consumers, and taxpayers in
RADIATION THERAPY OF TONSILS
Authors: LEILA CHARLTON KNOX
Journal: JAMA (1930)

In modern medicine the treatment of the tonsils occupies a particularly strategic position not only because these structures are especially prone to local infection, but because they are so frequently associated with a host of general infections and other obscure conditions, possibly infectious. The internist, in a search for the cause of these, used the empiric method, and a vast amount of surgical treatment was carried out with varying results. But removal of the tonsil, like every other surgical procedure, has its limitations and since 1913, when Regaud and Nogier<sup>1</sup>first reported the results of irradiation of the tonsils and pharynx, it has been apparent that a useful method of combating throat infections in some patients had been instituted. The early phase of enthusiasm for the x-rays as a general therapeutic agent complicated the situation, but we are returning to a period of sanity in which the proper sphere
Government insists NHS pays for drugs approved by NICE
Authors: Z. Kmietowicz
Journal: BMJ (2001)

From January 2002, patients in England should be able to pick up a prescription for any drug approved by the National Institute for Clinical Excellence (NICE) within three months of the ruling being issued provided that their doctor recommends it, the government said last week.

The health minister Philip Hunt announced that health managers should ensure that they have budgeted for treatments in their general annual allocations that had been approved by the institute, so that all those …
Do insulin and the insulin like growth factors (IGFs) stimulate growth of the exocrine pancreas?
Authors: J Mossner, C D Logsdon, I D Goldfine, J A Williams
Journal: Gut (1987)

Previous in vivo studies have suggested a long term regulatory role for insulin in the exocrine pancreas. Furthermore, we reported that pancreatic acini have specific receptors for IGF I and II, and using different techniques (acid washing, trypsinisation, electron microscope autoradiography), that CCK8 reduces the internalisation of IGF II. To now directly study the long term role for IGF and insulin in the exocrine pancreas we used AR42J cells, a rat cell line that is derived from a transplantable tumour of the acinar pancreas. Hormone binding studies with 125I-labelled hormones indicated that those cells have insulin receptors, relatively fewer receptors for IGF II but in contrast with normal acini no detectable IGF I receptors. Insulin at concentrations as low as 1 nm stimulated the growth of AR42J cells, as measured by an increase in cell number, DNA and protein content. At 100 nM insulin had maximal effects stimulating the growth by about 50%. IGF I and II had only very weak growth promoting effects probably due to their interaction with the insulin receptor. Additionally insulin increased amylase synthesis over the same concentration range that it stimulated growth. But immunoprecipitation studies revealed that insulin induced a selective increase of amylase synthesis over general protein synthesis. These studies indicate, therefore, that insulin is a growth promoting hormone for AR42J cells and that additionally it seems to specifically regulate amylase synthesis. The role for the IGFs in the exocrine pancreas, however, still remains to be determined.
The moral character of clinicians or the best interests of patients?
Authors: L. Doyal
Journal: BMJ (1999)

<i>Following the acquittal of an English doctor, Dr David Moor, who had given a dying patient a lethal dose of diamorphine, we invited tw ethicists to debate the issue at the centre of the case: that of giving a drug with the intention of relieving suffering even though it may hasten death. Professor Raanan Gillon argues that the difference between intending and foreseeing is all important, while Professor Le Doyal argues that the effect of this is to raise the moral character of a clinician above the best interests of his or her patients</i>
OBSERVATIONS ON RENAL PROTEIN METABOLISM
Authors: Willoughby Lathem, Alvin D. Benjamin
Journal: The Journal of Experimental Medicine (1956)

No significant difference was demonstrated in the free and total alpha amino nitrogen content of arterial, renal venous, and inferior vena caval blood of normal anesthetized dogs during fasting and following the administration of 3 to 6 gm. of hemoglobin. These results do not provide evidence of renal protein reabsorption and metabolism in the dog under the conditions employed in this study.
Insulin Sensitivity of Forearm Tissues in Prediabetic Man
Authors: Thomas Pozefsky, Martin R. Santis, J. Stuart Soeldner, Robert G. Tancredi
Journal: Journal of Clinical Investigation (1973)

In genetic prediabetic subjects (the glucose tolerant offspring of two diabetic parents or the identical twin of a known diabetic) serum insulin concentrations after glucose administration are subnormal. Maintenance of glucose tolerance in this setting is apparently paradoxical, suggesting increased tissue insulin sensitivity. Accordingly, forearm tissue insulin sensitivity in nine genetic prediabetic males was compared with that of seven males without familial diabetes. Diabetes was excluded in all subjects by preliminary oral glucose tolerance testing. On the preliminary 3 h oral glucose tolerance test (OGTT) the sum of increments in blood glucose above fasting was greater in prediabetic than in control subjects. Conversely, the sum of increments in serum insulin was subnormal for the first 2 h. The insulin index (the sum of increments in insulin divided by the sum of increments in glucose) was significantly lower in prediabetics throughout the test. High physiologic levels of insulin were produced in the forearm by intrabrachial arterial insulin infusion (100 muU/kg per min for 26 min). Balances of glucose and amino acids across forearm muscle became more positive, as did balances of glucose and free fatty acids across adipose tissue plus skin. There were no differences in response between prediabetic and normal subjects.Hence, the insulin sensitivity of peripheral tissues is normal in genetic prediabetes. Increased tissue insulin sensitivity is not essential to explain coexisting euglycemia and insulinopenia in prediabetes because blood glucose values on the OGTT are, in fact, elevated although still within the range considered normal.
Differential Effects of Interleukin-1 Receptor Antagonist and Tumor Necrosis Factor Binding Protein on Fatty-Streak Formation in Apolipoprotein E–Deficient Mice
Authors: R. Elhage, A. Maret, M.-T. Pieraggi, J. C. Thiers, J. F. Arnal, F. Bayard
Journal: Circulation (1998)

Background —The cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) are secreted by the different cell populations of the vascular wall and have been suggested to promote atherosclerosis. Methods and Results —Their respective roles in fatty-streak formation in apolipoprotein E–deficient mice were investigated by use of IL-1 receptor antagonist and TNF binding protein. Estradiol-17β was used as a positive control. Blocking TNF seemed to be active in female animals but not in males. IL-1 receptor antagonist was as effective as or more effective than estradiol in both sexes. Conclusions —IL-1 plays a crucial role in the initial step of the atherosclerotic process in this animal model, and blocking the activity of this cytokine should be considered as a therapeutic possibility.
1030 TRANS-ARTERIAL CHEMO-EMBOLIZATION (TACE) IS SAFE AND EFFICIENT FOR ELDERLY PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA (HCC): RESULTS FROM AN INTERNATIONAL META-DATABASE
Authors: M.J. Cohen, I. Levy, O. Barak, A.I. Bloom, M. Fernández Ruiz, M. Di Maio, F. Perrone, R. Poon, D. Shouval, T. Yau, O. Shibolet
Journal: Journal of Hepatology (2012)
Christopher Wrey Savile
Authors: I. Savile, J. Surtees, J. Prosser
Journal: BMJ (2010)

Born into a military family in Hampshire, Christopher Wrey Savile was educated at Wellington College and trained in medicine at Trinity Hall, Cambridge, where he excelled in rowing. His national service was mainly in the Middle East. He was visiting Eastbourne for a conference when he heard about a GP vacancy that couldn’t be advertised. …
A New Detail in a Complex Case
Authors: RAPHAEL ZAHLER
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 May 1983A New Detail in a Complex CaseRAPHAEL ZAHLER, M.D.RAPHAEL ZAHLER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-5-674_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the January 1983 issue, Goldstein and Keiser (1) describe the intricate case of a 29-year-old woman whose many symptoms remained undiagnosed despite an extensive neuroendocrine work-up but who responded to opiate antagonists. Nowhere in the case report, however, is it mentioned whether the diagnosis of porphyria was considered in this patient with abdominal pain, skin changes, and psychosis. Could the authors shed some light on this matter?...Reference1. GOLDSTEINKEISER DH. A case of episodic flushing and organ psychosis: reversal by opiate antagonists. Ann Intern Med. 1983;98:30-4. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: City of Boston Department of Health and Hospitals Boston, MA 02118 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1983Volume 98, Issue 5_Part_1Page: 674-675KeywordsAbdominal painOpiatesPorphyria Issue Published: 1 May 1983 PDF DownloadLoading ...
Relationship between Resting Hypercapnia and Physiologic Parameters before and after Lung Volume Reduction Surgery in Severe Chronic Obstructive Pulmonary Disease
Authors: DANIEL SHADE, FRANCIS CORDOVA, YAROSLAV LANDO, JOHN M. TRAVALINE, SATOSHI FURUKAWA, ANNE MARIE KUZMA, GERARD J. CRINER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Patients with severe chronic obstructive pulmonary disease (COPD) have varying degrees of hypercapnia. Recent studies have demonstrated inconsistent effects of lung volume reduction surgery (LVRS) on PaCO2 ; however, most series have excluded patients with moderate to severe hypercapnia. In addition, no study has examined the mechanisms responsible for the reduction in PaCO2 post-LVRS. We obtained spirometry, body plethysmography, diffusion capacity, respiratory muscle strength, 6-min walk test, and incremental symptom-limited maximal exercise data in 33 consecutive patients pre- and 3 to 6 mo post-LVRS, and explored the relationship between changes in PaCO2 and changes in the measured physiologic variables. All patients underwent bilateral LVRS via median sternotomy and stapling resection by the same cardiothoracic surgeon. Patients were 57 ± 8 yr of age with severe COPD, hyperinflation, and air trapping (FEV1, 0.73 ± 0.2 L; TLC, 7.3 ± 1.6 L; residual volume [RV], 4.8 ± 1.4 L), and moderate resting hypercapnia (PaCO2 , 44 ± 7 mm Hg; range, 32 to 56 mm Hg). Post-LVRS, PaCO2 decreased by 4% (PaCO2 pre 44 ± 7 mm Hg, PaCO2 post 42 ± 5 mm Hg; p = 0.003). Patients with higher baseline values of PaCO2 had the greatest reduction in PaCO2 post-LVRS (r = − 0.61, p < 0.001). Significant correlations existed between reduction in PaCO2 and changes in FEV1 (r = − 0.56; p = 0.0007), maximal inspiratory pressure (Pi max) (r = − 0.46; p = 0.009), diffusing capacity of the lungs for carbon monoxide (Dl CO) (r = − 0.47; p = 0.008), and RV/TLC (r = 0.41; p = 0.02). Correlation existed also between reduction in PaCO2 and breathing pattern at maximal exercise: maximal minute ventilation (V˙ e max) (r = − 0.47; p = 0.009), and tidal volume (Vt) (r = − 0.40; p = 0.02). The changes in PaCO2 post-LVRS showed marked intersubject variability. We conclude that LVRS, by reducing hyperinflation, air trapping, and improving respiratory muscle function, enables the lung and chest wall to act more effectively as a pump, thereby increasing alveolar ventilation and reducing baseline resting PaCO2 . In addition, patients with higher baseline levels of PaCO2 demonstrate the greatest reduction in PaCO2 post-LVRS, and should not be excluded from receiving LVRS.
Pharmacokinetics of Amantadine Hydrochloride in Subjects with Normal and Impaired Renal Function
Authors: VICTOR W. HORADAM
Journal: Annals of Internal Medicine (1981)

Amantadine is useful for the prevention and treatment of influenza A and for the treatment of Parkinson's disease and drug-induced extrapyramidal disorders. We have compared the pharmacokinetics of amantadine in patients with impaired or negligible renal function to that in normal subjects. The half-life of elimination in subjects with normal renal function was 11.8 ± 2.1 hours (range, 9.7 to 14.5 h). Eight patients with various degrees of renal insufficiency (creatinine clearance from 43.1 to 5.9 mL/min · 1.73 m2) had half-lives of elimination from 18.5 h to 33.8 days. We also studied 10 patients on thrice-weekly hemodialysis. Assuming complete bioavailability of the drug, less than 5% of the dose was removed by each 4-hour hemodialysis. The mean half-life of elimination during chronic hemodialysis was 8.3 days (range, 7.0 to 10.3). We present guidelines for use of amantadine in patients with impaired renal function, including those on maintenance hemodialysis.
Hemodynamic response to carbon monoxide.
Authors: D G Penney
Journal: Environmental Health Perspectives (1988)

Historically, and at present, carbon monoxide is a major gaseous poison responsible for widespread morbidity and mortality. From threshold to maximal nonlethal levels, a variety of cardiovascular changes occur, both immediately and in the long term, whose homeostatic function it is to renormalize tissue oxygen delivery. However, notwithstanding numerous studies over the past century, the literature remains equivocal regarding the hemodynamic responses in animals and humans, although CO hypoxia is clearly different in several respects from hypoxic hypoxia. Factors complicating interpretation of experimental findings include species, CO dose level and rate, route of CO delivery, duration, level of exertion, state of consciousness, and anesthetic agent used. For example, tachycardia is commonly observed, although bradycardia also can result from myocardial and/or central nervous system (CNS) hypoxemia at high carboxyhemoglobin (COHb) saturations, as can electrocardiographic abnormalities. Augmented cardiac output usually observed with moderate COHb may be compromised in more severe poisoning for the same reasons, such that regional or global ischemia result. The hypotension usually seen in most animal studies is thought to be a primary cause of CNS damage resulting from acute CO poisoning, yet the exact mechanism(s) remains unproven in both animals and humans, as does the way in which CO produces hypotension. This review briefly summarizes the literature relevant to the short- and long-term hemodynamic responses reported in animals and humans. It concludes by presenting an overview using data from a single species in which the most complete work has been done to date.
Targeting the Notch Pathway: Twists and Turns on the Road to Rational Therapeutics
Authors: Jon C. Aster, Stephen C. Blacklow
Journal: Journal of Clinical Oncology (2012)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2012.42.0992 Journal of Clinical Oncology - published online before print May 14, 2012 PMID: 22585704 Targeting the Notch Pathway: Twists and Turns on the Road to Rational Therapeutics Jon C. AsterxJon C. AsterSearch for articles by this author Stephen C. BlacklowxStephen C. BlacklowSearch for articles by this author Show More Brigham and Women's Hospital, Boston, MADana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.2012.42.0992 First Page Full Text PDF Figures and Tables © 2012 by American Society of Clinical Oncology
Commentary: Liquid automation refreshes Dr Papanicolaou
Authors: Geoff Watts
Journal: BMJ (2007)

That the Papanicolaou test has been modified so little during the greater part of its existence is surely a tribute to the insight and inventiveness of the physician scientist from whom it takes its name. When change began to be mooted in the 1980s it was because new levels of computing power were making it realistic to think of automating the microscopic examination of cells from the cervix. But to do so reliably depended on first improving the quality of the smears. This prompted the development of liquid based cytology—and with it a need for realistic comparative assessments: of the performance of the new technique as …