tbuckley/cabot-search huggingface dataset:
Mechanisms and prediction of drug-induced liver disease.
Authors: P Berthelot
Journal: Gut (1973)

Progress reportMechanisms and prediction of drug-induced liver diseaseThe hepatic microsomal enzymd system plays an outstanding role in the metabolism and detoxication of most drugs" 2, whereas the frequency of drug-induced liver disease increases steadily as 'a penalty for progress'3.Two main questions therefore arise: (1) Why do some drugs, ie, by which cellular mechanism(s), provoke side effects upon the liver, and (2) how might we predict them?The purpose of this review is to define the relations between drugs and the liver.The recent metabolic and molecular aspects of drug hepatotoxicity will be emphasized, as well as the limits of animal testing. Hepatic Response to DrugsThe response of the liver to drugs can be classified into four main types:(1) idiosyncrasy, which might in fact correspond either to hypersensitivity or abnormality of drug metabolism; (2) drug interactions, including enzyme induction; (3) direct hepatotoxicity; (4) interferences with bilirubin disposal.Animal testing appears to be of help in predicting the three latter types as well as many abnormalities of drug metabolism.Unfortunately, it provides no information concerning hypersensitivity, which probably yields in man the highest incidence of liver injuries4'5, sometimes severe.In addition, the in- cidence of such side effects caused by a certain drug is usually low, so that they may be missed for years.As an example, a convincing report of hepatic disorder due to papaverine6 came as a surprise more than half a century after its first use in man7.Moreover, as far as hypersensitivity is concerned, there is no definite relation between the chemical structure of a compound and its effects on the liver.Yet the existence of a few cross sensitivities may be of some help in prediction: sensitivity to chlorpromazine may be associated with sensitivity to promethazine8; sensitivity to halothane9 could resemble that due to other halogenated anaesthetics, eg, methoxyflurane'0 and fluroxenell.Such facts, however, could sometimes be better explained on the basis of possible metabolic peculiarities which will be considered further. FACTORS INFLUENCING THE HEPATIC RESPONSE TO DRUGSThere are considerable individual variations in the response to drugs to be considered before any conclusion can be reached from animal testing2"12'13.They mainly depend on dose, species, sex, age, nutrition, associated drugs, preexisting liver function, and genetic factors.According to species, the hepatic disposal of a given compound may be entirely different.For example, rifampicin is highly toxic in the dog, which is unable to desacetylate it efficiently, compared with man whose liver excretes more than 80% of rifampicin as desacetyl-metabolites'4.Another example is
Mutations in CEP57 cause mosaic variegated aneuploidy syndrome
Authors: Katie Snape, Sandra Hanks, Elise Ruark, Patricio Barros-Núñez, Anna Elliott, Anne Murray, Andrew H Lane, Nora Shannon, Patrick Callier, David Chitayat, Jill Clayton-Smith, David R FitzPatrick, David Gisselsson, Sebastien Jacquemont, Keiko Asakura-Hay, Mark A Micale, John Tolmie, Peter D Turnpenny, Michael Wright, Jenny Douglas, Nazneen Rahman
Journal: Nature Genetics (2011)
When a Uniquely Effective Drug is Teratogenic
Authors: R S Stern
Journal: New England Journal of Medicine (1989)

Isotretinoin is a uniquely effective oral agent for the treatment of severe cystic acne.1 Typically a patient uses the medicine for 20 weeks, and in most cases enters a prolonged remission. First marketed in the United States in 1982, isotretinoin had been used by more than 800,000 people by the end of 1987. About 40 percent of these were women.2 , 3 The substantial teratogenic effect of retinoic acid in animals has been known for many years. As a result, the package insert for isotretinoin included from the beginning a warning against its use during pregnancy. In spite of this precaution, within . . .
Complexity effects are found in all relative-clause sentence forms
Authors: Glenda Andrews, Graeme S. Halford
Journal: Behavioral and Brain Sciences (1999)

We argue that if a different definition of sentence complexity is adopted and processing capacity is assessed in a way that is consistent with that definition, then the Caplan &amp; Waters distinction between interpretive versus postinterpretive processing is unnecessary insofar that it applies to the thematic role assignment in relative-clause sentences.
Platelet-Poor Blood in Open-Heart Surgery
Authors: Alfred J. Grindon, Paul J. Schmidt
Journal: New England Journal of Medicine (1969)

THE thrombocytopenia seen at this institution after open-heart surgery has been shown to be unrelated to the age of the blood used for perfusion.1 We have used 48-hour-old blood, containing few viable platelets,2 , 3 for perfusion during cardiopulmonary bypass. Since the platelets in such blood are wasted, it would be desirable to remove them when fresh for use in other patients. The present report compares stored whole blood with blood from which platelets have been removed as transfusion fluids in open-heart surgery.Materials and MethodsPlatelet-poor blood (PPB) was prepared by removal of 60 to 80 per cent of the original . . .
Renal Vein Thrombosis as a Cause of Excess Renal Accumulation of Bone Seeking Agents
Authors: LAMK M. LAMKI, JACK K. WYATT
Journal: Clinical Nuclear Medicine (1983)

LAMKI, LAMK M. M.D., F.R.C.P. (C)*; WYATT, JACK K. M.D., F.R.C.S. (C)† Author Information
SEBUM CHANGES IN ACNE VULGARIS TREATED WITH TETRACYCLINE
Authors: G. W. BEVERIDGE, E. W. POWELL
Journal: British Journal of Dermatology (1969)

SUMMARY.— Samples of sebum from 6 young men with acne vulgaris were analysed before and after systemic treatment with tetracycline for 4 and for 8 weeks. The rate of sebum production was not significantly changed. At 4 weeks there was a consistent fall in the free fatty acids and a slight rise in the triglycerides. After 8 weeks there was a marked fall in the aliphatic alcohol ester fraction.
Effect of Once-Weekly Oral Alendronate on Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer
Authors: Susan L. Greenspan, Joel B. Nelson, Donald L. Trump, Neil M. Resnick
Journal: Annals of Internal Medicine (2007)

Background: Androgen deprivation therapy (ADT) in men with prostate cancer is associated with bone loss and fractures. Objective: To determine whether once-weekly oral bisphosphonate can prevent bone loss and reduce bone turnover in men receiving ADT. Design: Randomized, double-blind, placebo-controlled, partial crossover trial. First-year, preplanned analysis of a 2-group, parallel-design phase. Setting: University medical center. Patients: 112 men with nonmetastatic prostate cancer receiving ADT. Intervention: Alendronate, 70 mg once weekly, or placebo. All patients received calcium and vitamin D supplementation. Measurements: Bone mineral density of the spine and hip and markers of bone resorption and formation. Results: At baseline, 39% of men had osteoporosis and 52% had low bone mass. In men treated with alendronate, bone mineral density increased over 1 year by 3.7% (95% CI, 2.8% to 4.6%; P < 0.001) at the spine and 1.6% (CI, 0.4% to 2.8%; P = 0.008) at the femoral neck. Men in the placebo group had losses of 1.4% (CI, −2.7% to − 0.03%; P = 0.045) at the spine and 0.7% (CI, −1.5% to 0.01%; P = 0.081) at the femoral neck. At 12 months, the difference between the 2 groups was 5.1 percentage points (CI, 3.5 to 6.7 percentage points; P < 0.001) at the spine and was 2.3 percentage points (CI, 1.0 to 3.7 percentage points; P < 0.001) at the femoral neck. Bone turnover statistically significantly decreased with active therapy compared with placebo. The groups did not differ in adverse events. Limitations: The study was short (1 year) and was not powered to detect differences in the frequency of fractures. Conclusions: Bone loss that occurred with ADT was prevented and improved with once-weekly oral alendronate. Because most men have low bone mass or osteoporosis, physicians should assess their patients' bone density and provide preventive and therapeutic measures as appropriate. ClinicalTrials.gov registration number: NCT00048841.
Hypertension and Renal Insufficiency Due to Renovascular Disease
Authors: Kim Eagle, Richard P. Cambria
Journal: New England Journal of Medicine (1992)

The images illustrate renovascular hypertension and renal insufficiency in a 57-year-old woman. Arteriography (Panel A) reveals severe bilateral renal-artery stenoses (arrows). A photograph taken during transaortic bilateral renal-artery endarterectomy (Panel B) shows the specimen being removed; the aortotomy is evident (large arrow) in the background. A close-up of the specimen (Panel C) shows the tongues of atheroma (arrows) that extended into and obstructed the renal arteries. A postoperative arteriogram (Panel D) demonstrates widely patent renal arteries (arrows). After surgery the patient no longer required antihypertensive medications, and her serum creatinine level decreased from 2.1 to 1.2 mg per deciliter (186 . . .
A Quantitative Framework to Evaluate Modeling of Cortical Development by Neural Stem Cells
Authors: Jason L. Stein, Luis de la Torre-Ubieta, Yuan Tian, Neelroop N. Parikshak, Israel A. Hernández, Maria C. Marchetto, Dylan K. Baker, Daning Lu, Cassidy R. Hinman, Jennifer K. Lowe, Eric M. Wexler, Alysson R. Muotri, Fred H. Gage, Kenneth S. Kosik, Daniel H. Geschwind
Journal: Neuron (2014)
Should Young Adults with a Positive Tuberculin Test Take Isoniazid?
Authors: WILLIAM C. TAYLOR
Journal: Annals of Internal Medicine (1981)

We used decision analysis to determine the benefits and risks of preventive therapy with isoniazid for young adults whose only risk factor for the development of active tuberculosis was a positive tuberculin skin test. We assumed that the risk of developing active tuberculosis over the next 20 years ranged from 0.56% to 1.30% for such persons; that isoniazid can reduce this risk by 30% to 70%; and that the risk of developing isoniazid-related hepatitis ranged from 0.3% to 1.1%. Among 100 000 such persons, treatment with isoniazid could prevent from 168 to 910 cases of tuberculosis over 20 years. However, from 300 to 1100 cases of isoniazid-related hepatitis would occur in the year of treatment. The benefits of preventive therapy in this group do not appear clearly to outweigh the risks. We disagree with the recommendation of the American Thoracic Society and the Centers for Disease Control that all such patients take isoniazid.
BACILLUS PROTEUS PNEUMONIAS
Authors: MARK L. ENTMAN
Journal: Annals of Internal Medicine (1968)

Letters and Comments1 May 1968BACILLUS PROTEUS PNEUMONIASMARK L. ENTMAN, M.D.MARK L. ENTMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1137_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:In the article, "Characteristics of Pneumonias Caused by Bacillus Proteus" (Ann. Intern. Med. 68: 287, 1968), the authors compare the roentgenographic picture of proteus and klebsiella pneumonias. A statement is made that ipsilateral tracheal deviation and atelectasis are common features of these two entities. The referred article by Drs. Ritvo and Martin (1) states that edematous expansion of the infected lobe with dense consolidation and contralateral mediastinal shift is the rule in acute klebsiella pneumonia. I would be interested to know if the authors' experience has been different in the age of broad-spectrum antibiotics....References1. TILLOTSON JR and LERNER AM: Characteristics of pneumonias caused by Bacillus proteus. Ann. Intern. Med. 68: 287, 1968. LinkGoogle Scholar2. HOLMES RB: Friedländer's pneumonia. Amer. J. Roentgen. 75: 728, 1956. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MARK L. ENTMAN, M.D.Affiliations: Duke University Medical Center Durham, N. C. 27706 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1137-1138KeywordsAntibioticsBacillusKlebsiellaPneumonia ePublished: 1 December 2008 Issue Published: 1 May 1968 PDF downloadLoading ...
Cigarettes Exceed Perrier's Benzene Level, But Are Not Regulated
Authors: K. Broder, T. Hensley
Journal: JNCI Journal of the National Cancer Institute (1990)

Cigarettes Exceed Perrier's Benzene Level, But Are Not Regulated Karen Broder, Karen Broder Search for other works by this author on: Oxford Academic PubMed Google Scholar Tim Hensley Tim Hensley Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 9, 2 May 1990, Pages 735–736, https://doi.org/10.1093/jnci/82.9.735 Published: 02 May 1990
Click chemistry reactions in medicinal chemistry: Applications of the 1,3‐dipolar cycloaddition between azides and alkynes
Authors: Gian Cesare Tron, Tracey Pirali, Richard A. Billington, Pier Luigi Canonico, Giovanni Sorba, Armando A. Genazzani
Journal: Medicinal Research Reviews (2007)

Abstract In recent years, there has been an ever‐increasing need for rapid reactions that meet the three main criteria of an ideal synthesis: efficiency, versatility, and selectivity. Such reactions would allow medicinal chemistry to keep pace with the multitude of information derived from modern biological screening techniques. The present review describes one of these reactions, the 1,3‐dipolar cycloaddition (“click‐reaction”) between azides and alkynes catalyzed by copper (I) salts. The simplicity of this reaction and the ease of purification of the resulting products have opened new opportunities in generating vast arrays of compounds with biological potential. The present review will outline the accomplishments of this strategy achieved so far and outline some of medicinal chemistry applications in which click‐chemistry might be relevant in the future. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 2, 278–308, 2008
Loss of tolerance and overdose mortality with detoxification: Results of study need clarification
Authors: W. Caan
Journal: BMJ (2003)

EDITOR—Strang et al reported fatal overdose in three former inpatients among 137 who attempted to detoxify from heroin dependence in south London.1 They claim that overdose deaths up to four months after discharge occurred only among the detoxified patients who completed their 28 day programme, who at the time of death were assumed to have none of their former …
Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study
Authors: B. Sabayan, L. W. Wijsman, J. C. Foster-Dingley, D. J. Stott, I. Ford, B. M. Buckley, N. Sattar, J. W. Jukema, M. J. P. van Osch, J. van der Grond, M. A. van Buchem, R. G. J. Westendorp, A. J. M. de Craen, S. P. Mooijaart
Journal: BMJ (2013)

<b>Objective</b> To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age (&gt;70 years). <b>Design</b> Prospective cohort study. <b>Setting</b> PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, a collaboration between centres in Ireland, Scotland, and the Netherlands. <b>Participants</b> 5461 participants, mean age 75.3 years, who were at risk of cardiovascular disease. Blood pressure was measured every three months during an average of 3.2 years. Visit-to-visit variability in blood pressure was defined as the standard deviation of blood pressure measurements between visits. <b>Main outcome measures</b> Four domains of cognitive function, testing selective attention, processing speed, and immediate and delayed memory. In a magnetic resonance imaging substudy of 553 participants, structural brain volumes, cerebral microbleeds, infarcts, and white matter hyperintensities were measured. <b>Results</b> Participants with higher visit-to-visit variability in systolic blood pressure had worse performance on all cognitive tests: attention (mean difference high versus low thirds) 3.08 seconds (95% confidence interval 0.85 to 5.31), processing speed −1.16 digits coded (95% confidence interval −1.69 to −0.63), immediate memory −0.27 pictures remembered (95% confidence interval −0.41 to −0.13), and delayed memory −0.30 pictures remembered (95% confidence interval −0.49 to −0.11). Furthermore, higher variability in both systolic and diastolic blood pressure was associated with lower hippocampal volume and cortical infarcts, and higher variability in diastolic blood pressure was associated with cerebral microbleeds (all P&lt;0.05). All associations were adjusted for average blood pressure and cardiovascular risk factors. <b>Conclusion</b> Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age.
Eliminating Inpatient Sliding-Scale Insulin: A Reeducation Project With Medical House Staff
Authors: Ali A. Rizvi
Journal: Diabetes Care (2005)

The study by Baldwin et al. (1) had the laudable intention of training house staff in moving away from inpatient sliding-scale insulin in favor of a basal-bolus approach or active titration of oral agents. However, some key points in their report remain unexplained. The authors state that in insulin-treated patients, the premeal short-acting insulin (usually regular) in combination with a basal insulin (usually NPH) was used. However, no details are given as to how the NPH was titrated and what parameters, if any, were used for adjustment. Even more notable …
Abdominal Vascular Sounds
Authors: Arthur U. Rivin
Journal: JAMA (1972)

Auscultation of the abdomen in a consecutive series of 500 patients demonstrated that 18% of normal people had vascular murmurs. In the age group under 25, 44% had murmurs. These physiologic murmurs arise from the abdominal aorta at the epigastrium and from the interior vena cava. Aortic murmurs may be heard over the lower precordium and be confused with cardiac murmurs. The caval murmur is a high-pitched continuous hum heard best to the right of the umbilicus. Murmurs heard far laterally into the upper abdomen, in the flank, or in the lower quadrants are probably pathologic and represent vascular abnormalities. Radiation of cardiac valvular murmurs into the abdomen is most common with those arising from the aortic valve area.
Significance of epicardial Q waves as an acute marker of myocardial necrosis in dogs
Authors: L. MICKLEBOROUGH, I. HUTTNER, J. SYMES, N. POIRIER, A. D. SNIDERMAN
Journal: Cardiovascular Research (1978)

This study examines the significance of epicardial Q waves as a marker of myocardial cell necrosis. Ischaemia was produced in dogs by two methods: coronary artery occlusion sustained for 24 h (Group 1) and occlusion for 1 h followed by reperfusion (Group 2). Q waves did not appear until after 3 h of sustained occlusion, but were present within 40 min of reperfusion. In both groups, Q waves were not transient but persisted for at least 24 h. CPK levels were determined at 24 h in specimens from each lead site. In Group I, Q sites had 66.6 ± 5.9% (mean± SEM) less CPK than R wave sites (P<0.005). In Group 2, Q sites had only 28.2 ± 4.5% less CPK than R sites. These results suggest that the extent of necrosis was greater at Q sites with sustained occlusion than with reperfusion. A similar relationship existed for the levels of ATP and CP determined at Q and R sites at 24 h. Histological examination by light and electron microscopy confirmed that in both groups, Q sites corresponded to areas of necrosis, while R sites indicated normal myocardium. However, the type of necrosis depended on the pathogenesis. Our results demonstrated that epicardial Q waves were a reliable marker of cell death, but that the morphological picture and extent of cell death depended on the mechanism and manner of injury. These conclusions were tested in a final series (Group 3) in which propranolol was given before and with release of the occlusion (0.5 mg·kg−1 at each time). In 47 sites at risk, in five dogs only two Q waves appeared. In each of these two, cell death was confirmed by evidence of CPK depletion and morphological alteration. In the remaining sites, no CPK depletion occurred. Histological examination revealed only infrequent small islands of subendocardial necrosis. The results confirm the validity of the epicardial electrocardiographic findings and illustrate the role of propranolol in preventing reperfusion necrosis.
Abstract 5448: Pharmacogenetics of drug transporters may be useful to identify chronic myeloid leukemia patients who are less likely to achieve molecular responses to imatinib: Implications for treatment optimization in the era of new tyrosine kinase inhibitors
Authors: Simona Soverini, Sabrina Angelini, Matt Barnett, Gloria Ravegnini, Fabrizio Pane, Timothy P. Hughes, Deborah White, Dong-Wook Kim, Giuseppe Saglio, Gianantonio Rosti, Richard Woodman, Richard Woodman, Patrizia Hrelia, Guido Biasco, Michele Baccarani, Giovanni Martinelli
Journal: Cancer Research (2011)

Abstract The availability of multiple options for chronic myeloid leukemia (CML) treatment is not paralleled by the availability of biological predictors of outcome allowing to identify patients (pts) who are more likely to benefit from dasatinib or nilotinib rather than imatinib (IM). We thus investigated a panel of 20 SNPs in ABCB1, ABCG2, SLC22A1, OCTN1, CYP3A4 and CYP3A5 genes that can be hypothesized to influence IM transport and metabolism in 189 newly diagnosed CML pts enrolled in the TOPS phase III trial (Cortes et al, J Clin Oncol 2010). Median age was 46 yrs; male to female ratio was 103:86; 156 (83%) pts were Caucasian and 23 (12%) were Asian; low, intermediate and high Sokal risk pts were 84 (44.4%), 65 (34.4%) and 40 (21.2%), respectively. Baseline demographic/clinical features did not differ significantly from those of the entire population enrolled. Treatment outcomes (major molecular response [MMR]; complete molecular response [CMR]) were compared according to i) each candidate genotype ii) summary measures based on combinations of SNPs in the same gene and iii) summary measures based on combinations of SNPs in functionally related genes (uptake; efflux). Additive models, with SNPs represented as number of major alleles, were used. Significant results are summarized in the Table below and will be presented in detail. Cumulative incidence plots were also analysed, with similar results. Our data suggest that in CML pts, genotyping should be taken into account in an attempt to further individualize treatment, with the aim of enhancing efficacy in terms of MMR and CMR achievement. On the basis of our findings, stratification of pts according to genotypes may be proposed for selection between IM and second generation TKIs, and represents an attractive opportunity for new clinical trials. Supported by Novartis, TOPS Correlative Studies Network Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5448. doi:10.1158/1538-7445.AM2011-5448
ON A CONVENIENT METHOD OF PREPARING EUSOL
Authors: J. L. Smith, J. Ritchie, T. Rettie
Journal: BMJ (1917)

paramount importance.This may be briefly outlined as follows:I.On the first day of treatment the patielnt is given a lhot batlh and provicled witlh plenty of soft soap and a large, moderately stiff nail-bruslh.(a) Before enterina tlle batlh, lhe rubs himuself tlhorouglhly all over witlh the soap, mnassaging it into the skin, and paying particular attention to the fingers, toes, wrists, penis, and axillae.This slhould be continued for at least ten minutes.