tbuckley/cabot-search huggingface dataset:
Effect of a 5-lipoxygenase inhibitor on leukotriene generation and airway responses after allergen challenge in asthmatic patients.
Authors: K P Hui, I K Taylor, G W Taylor, P Rubin, J Kesterson, N C Barnes, P J Barnes
Journal: Thorax (1991)

The effect of a single oral dose (800 mg) of zileuton (A-64077), a specific 5-lipoxygenase inhibitor, on the early and late airway responses to inhaled allergen was studied in a randomised, double blind, placebo controlled, and crossover trial in nine subjects with atopic asthma. Leukotriene generation was also assessed in vivo by measuring urinary leukotriene (LT) E4 excretion, and ex vivo by measuring calcium ionophore stimulated whole blood LTB4 production. Zileuton almost completely inhibited ex vivo LTB4 production but reduced urinary excretion of LTE4 by only about half. There was a trend for the early asthmatic response to be less on the day of zileuton treatment, but this did not reach statistical significance (p = 0.08). The zileuton induced reduction in maximum fall in FEV1 in the early asthmatic response was, however, significantly related to the reduction in urinary LTE4 excretion (r = 0.8), but not to the reduction in LTB4 generation ex vivo. There was no significant change in the allergen induced late asthmatic response, or in the increase in airway responsiveness to methacholine following antigen. The results provide some support for the hypothesis that the cysteinyl leukotrienes have a role in the allergen induced early asthmatic response. More complete in vivo inhibition of 5-lipoxygenase may be needed to produce a significant reduction in airway response to allergen challenge.
Management of Migraine
Authors: John R. Graham
Journal: New England Journal of Medicine (1961)

THERAPY for human ailments usually improves A with enlarged concepts of the nature of the disease that is to be treated. Recent developments in the knowledge of the local physiologic changes that occur in migraine, combined with observations from the past on the natural history of this malady, make possible a working hypothesis regarding its mechanism that lends itself to concepts of therapy.This hypothesis, subject to revision as knowledge advances, suggests that migraine is one of a group of familial paroxysmal human disorders that occur periodically in response to a number of varied stimuli, act primarily on one target . . .
A Randomized Comparison of Pulmonary Vein Isolation With Versus Without Concomitant Renal Artery Denervation in Patients With Refractory Symptomatic Atrial Fibrillation and Resistant Hypertension
Authors: Evgeny Pokushalov, Alexander Romanov, Giorgio Corbucci, Sergey Artyomenko, Vera Baranova, Alex Turov, Natalya Shirokova, Alexander Karaskov, Suneet Mittal, Jonathan S. Steinberg
Journal: Journal of the American College of Cardiology (2012)
Diamond–Blackfan anemia associated with β-thalassemia trait
Authors: Betül Tavil, Mualla Çetin, Barış Kuşkonmaz, Fatma Gümrük
Journal: American Journal of Hematology (2006)

A 14-month-old boy was referred to our hospital for evaluation of severe anemia. In the bone marrow aspiration smear, normal cellularity with severe erythroblastopenia (3%) was observed. The hemoglobin electrophoresis of the patient and his father were compatible with the beta-thalassemia trait. Because macrocytosis of Diamond-Blackfan anemia (DBA) is masked by microcytosis of beta-thalassemia trait, the diagnosis of DBA co-existing with beta-thalassemia trait might be challenging. We report herein a case of DBA co-existing with beta-thalassemia trait in a Turkish boy.
Should Subgroup Analysis of Randomized Clinical Trials Have a Direct Impact on Clinical Practice?
Authors: Emilio Bria, Massimo Di Maio, Federica Cuppone, Cecilia Nisticò, Francesco Cognetti, Diana Giannarelli
Journal: Journal of Clinical Oncology (2007)

We agree with Dr Atkin's description of the conclusions from the report of the International Workshop on Screening for Breast Cancer. 1 The statement reporting a mortality benefit described for women older than age 40 years is supported by a meta-analysis that included several randomized trials and specifically evaluated benefits for women age 40 to 49 years. 2 We regret that this additional reference was not attached to this statement.We agree with Dr Atkins that there remains uncertainty regarding long-term radiation exposure from mammography, particularly in high-risk women who begin screening earlier than age 40 years.As we hoped to convey, we feel that alternative imaging modalities, such as breast magnetic resonance imaging, which do not involve radiation exposure may ultimately replace mammography in individualized programs for breast cancer prevention. 3
First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors
Authors: Timothy A. Yap, Li Yan, Amita Patnaik, Ivy Fearen, David Olmos, Kyriakos Papadopoulos, Richard D. Baird, Liliana Delgado, Adekemi Taylor, Lisa Lupinacci, Ruth Riisnaes, Lorna L. Pope, Simon P. Heaton, George Thomas, Michelle D. Garrett, Daniel M. Sullivan, Johann S. de Bono, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2011)

AKT signaling is frequently deregulated in human cancers. MK-2206 is a potent, oral allosteric inhibitor of all AKT isoforms with antitumor activity in preclinical models. A phase I study of MK-2206 was conducted to investigate its safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics (PDs), and preliminary antitumor efficacy.Patients with advanced solid tumors received MK-2206 on alternate days. Paired tumor biopsies were mandated at the MTD for biomarker studies. PD studies incorporated tumor and hair follicle analyses, and putative predictive biomarker studies included tumor somatic mutation analyses and immunohistochemistry for phosphatase and tensin homolog (PTEN) loss.Thirty-three patients received MK-2206 at 30, 60, 75, or 90 mg on alternate days. Dose-limiting toxicities included skin rash and stomatitis, establishing the MTD at 60 mg. Drug-related toxicities included skin rash (51.5%), nausea (36.4%), pruritus (24.2%), hyperglycemia (21.2%), and diarrhea (21.2%). PKs (area under the concentration-time curve from 0 to 48 hours and maximum measured plasma concentration) were dose proportional. Phosphorylated serine 473 AKT declined in all tumor biopsies assessed (P = .015), and phosphorylated threonine 246 proline-rich AKT substrate 40 was suppressed in hair follicles at 6 hours (P = .008), on days 7 (P = .028) and 15 (P = .025) with MK-2206; reversible hyperglycemia and increases in insulin c-peptide were also observed, confirming target modulation. A patient with pancreatic adenocarcinoma (PTEN loss; KRAS G12D mutation) treated at 60 mg on alternate days experienced a decrease of approximately 60% in cancer antigen 19-9 levels and 23% shrinkage in tumor measurements. Two patients with pancreatic neuroendocrine tumors had minor tumor responses.MK-2206 was well tolerated, with evidence of AKT signaling blockade. Rational combination trials are ongoing to maximize clinical benefit with this therapeutic strategy.
ASSOCIATION BETWEEN PLAQUE VULNERABILITY AND EICOSAPENTAENOIC ACID TO ARACHIDONIC ACID IN NON-HYPERCHOLESTEROLEMIA PATIENTS
Authors: Maoto Habara, Kenya Nasu, Mitsuyasu Terashima, Tomohiko Teramoto, Masashi Kimura, Yoshihisa Kinoshita, Etsuo Tsuchikane, Tetsuo Matsubara, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2014)
P07 Socio-demographic and behavioural determinants of abnormal liver function in a multi ethnic population in the UK: the LOLIPOP study
Authors: S. D. S. Fraser, J. Parkes, P. J. Roderick, J. S. Kooner, J. Chambers
Journal: Gut (2011)

<h3>Introduction</h3> Fatty liver disease (FLD) is common, with an estimated prevalence between 10 and 24% of the general population. Most patients are asymptomatic, and identified via incidental abnormal liver function tests, particularly alanine transaminase (ALT) and γ-glutamyltransferase (GGT). There are few population data on the prevalence or determinants of abnormal liver function. <h3>Aim</h3> To determine the characteristics and associations of people with elevated values 1.5 times normal of both ALT and GGT in a population sample (upper limit of normal (ULN)=ALT ♂37 ♀31 IU/l; GGT ♂55 ♀38 IU/l) as an indicator of FLD. <h3>Method</h3> The London Life Sciences Prospective Population Study (LOLIPOP study) is a population based cohort study of cardiovascular risk and outcomes in west London, an area with a high ethnic minority population. Adults aged 35–74 from 58 general practices were invited to cardiovascular screening which included questionnaire, clinical measurement and blood sampling. Response rate was 62%. Cross sectional data were obtained on 31 507, European white (n=9222), Indian Asian (n=19 769) and Black (n=2516). ALT and GGT were measured from a single serum sample. To identify key socio-demographic variables and potentially modifiable lifestyle factors, including BMI and alcohol intake, we used logistic regression models examining associations with elevated ALT and GGT. <h3>Results</h3> The number with GGT and ALT measures was 31 465 (99.9% of total). The prevalence of elevated GGT above 1.5 times the ULN (GGT 1.5) was 10.4% (3265/31 465), for ALT 8% (2517/31 465) and for both 3.2% (996/31 465). 40% of those with ALT1.5 had GGT1.5, and 32% of those with GGT 1.5 had ALT 1.5. The independent odds of having both raised were increased in: younger people (OR 3.00 (95% CI 2.28 to 3.94) for 35–44 compared to 65–74 age group), south Asians (OR 1.29 (95% CI 1.10 to 1.51) compared to White), greater alcohol intake (OR 6.52 (95% CI 5.36 to 7.95) for &gt;28 units per week compared to no alcohol), raised BMI (OR 2.34 (95% CI 1.94 to 2.83) obese compared to normal), and diabetes (OR 1.32 (95% CI 1.07 to 1.63), with a dose related gradient for alcohol consumption. Gender, deprivation, and taking statin were not significantly associated, and no interaction observed between alcohol and gender or BMI. <h3>Conclusion</h3> The prevalence of abnormal liver function tests, suggesting FLD, was common (directly standardised prevalence of 3.3% in this age group in the England and Wales population). BMI, and alcohol independently increased risk across the range of their values, highlighting the importance of considering both in preventing severe liver disease and counselling patients.
Reply to J.E. Battley et al
Authors: David G. Pfister, Shrujal S. Baxi
Journal: Journal of Clinical Oncology (2014)

cancer are using the higher, more costly dose.A direct comparison of dosing regimens might permit more patients to receive this agent if equivalence is demonstrated.For targeted agents that have demonstrated significant benefit, such as imatinib or traztuzumab, more attention should be devoted to strategies to optimize dosing 4,5 or treatment duration, 6 respectively, which could reduce treatment costs and increase the global impact of these therapies for appropriately selected patients.Where predictive biomarkers exist for these targeted agents, strategies to improve patient selection for molecular testing may minimize cancer management costs. 7 Cost-effectiveness of cancer treatment is often related directly to drug costs rather than to diagnostic testing.In many tumor groups, targeted agents may have demonstrated clinical benefit in small patient subsets such as crizotinib in lung cancer in which the incidence of the target aberration echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearrangement (EML4-ALK) is present in approximately 4% of all patients. 8High costs of drug treatment are often attributed, in part, to the drug development process.However, modifications in trial design may allow earlier identification of appropriate biomarkers to focus on specific target populations and expedite drug development-as was the case with crizotinib 9 -thereby potentially reducing costs.At the present time, the improvements in cancer care discussed at the American Society of Clinical Oncology Annual Meeting are only applicable to 10% of the world population.Reducing the cost of new treatment advances through clinical trials of equivalence, modifying trial design to optimize efficiency of drug development, and using enrichment strategies for biomarker testing would increase this percentage.
Ophthalmologist–Patient Communication, Self-efficacy, and Glaucoma Medication Adherence
Authors: Betsy Sleath, Susan J. Blalock, Delesha M. Carpenter, Robyn Sayner, Kelly W. Muir, Catherine Slota, Scott D. Lawrence, Annette L. Giangiacomo, Mary Elizabeth Hartnett, Gail Tudor, Jason A. Goldsmith, Alan L. Robin
Journal: Ophthalmology (2014)
Horizontal Gene Transfer of Chlamydial-Like tRNA Genes into Early Vascular Plant Mitochondria
Authors: Nils Knie, Monika Polsakiewicz, Volker Knoop
Journal: Molecular Biology and Evolution (2014)

Mitochondrial genomes of lycophytes are surprisingly diverse, including strikingly different transfer RNA (tRNA) gene complements: No mitochondrial tRNA genes are present in the spikemoss Selaginella moellendorffii, whereas 26 tRNAs are encoded in the chondrome of the clubmoss Huperzia squarrosa. Reinvestigating the latter we found that trnL(gag) and trnS(gga) had never before been identified in any other land plant mitochondrial DNA. Sensitive sequence comparisons showed these two tRNAs as well as trnN(guu) and trnS(gcu) to be very similar to their respective counterparts in chlamydial bacteria. We identified homologs of these chlamydial-type tRNAs also in other lycophyte, fern, and gymnosperm DNAs, suggesting horizontal gene transfer (HGT) into mitochondria in the early vascular plant stem lineages. These findings extend plant mitochondrial HGT to affect individual tRNA genes, to include bacterial donors, and suggest that Chlamydiae on top of their recently proposed key role in primary chloroplast establishment may also have participated in early tracheophyte genome evolution.
Positive discrimination in India's medical schools
Authors: L R Murmu, S. Kant, K R P R. Rao
Journal: BMJ (1993)

explains the increased sensitivity of whole cell inclusion immunofluorescence, which detects genus specific and species specific antibody.3Antigenic diversity within species has also led to a serious failure of microimmunofluorescence to detect many C psittaci infections.The specificity of microimmunofluorescence has been questioned owing to reports of cross reactivity between species4 and the demonstration of both species specific and genus specific epitopes being expressed on elementary bodies.Serological approaches are used variably by some clinicians investigating respiratory infections, highlighting the need for non-invasive diagnostic alternatives.The value of routinely used com- mercial enzyme linked immunoassays to detect chiamydia in sputum has been shown in laboratory diagnosis provided that reactive samples are confirmed with direct immunofluorescence.5Genome detection of chlamydia in sputum, although promising, is currently unsuitable for hospital laboratories.Undoubtedly, future techniques will focus on molecular approaches.It would be foolhardy to be overwhelmed by the hyperbole surrounding C pneumoniae and to ignore, within our current knowledge, the clinically more important respiratory pathogen-Cpsittaci.
Prostate Cancer Incidence and Disease-Specific Survival of Men with Initial Prostate-Specific Antigen Less Than 3.0ng/ml Who Are Participating in ERSPC Rotterdam
Authors: Meelan Bul, Pim J. van Leeuwen, Xiaoye Zhu, Fritz H. Schröder, Monique J. Roobol
Journal: European Urology (2011)

The European Randomised Study of Screening for Prostate Cancer (ERSPC) applies a prostate-specific antigen (PSA) cut-off value ≥3.0 ng/ml as an indication for lateralised sextant biopsy.To analyse the incidence and disease-specific mortality for prostate cancer (PCa) in men with an initial PSA <3.0 ng/ml.From November 1993 to December 1999, a total of 42,376 men identified from population registries in the Rotterdam region (55-74 yr of age) were randomised to an intervention or control arm. A total of 19,950 men were screened during the first screening round.A PSA <3.0 ng/ml was below the biopsy threshold. PCa cases were identified at rescreens every 4 yr or as interval cancers.Distribution of incidence, aggressiveness, and disease-specific mortality of PCa per PSA range was measured. Causes of death were evaluated by an independent committee, and follow-up was complete until 31 December 2008.From 1993 to 2008, 915 PCa cases were diagnosed in 15,758 men (5.8%) with an initial PSA <3.0 ng/ml and a median age of 62.3 yr. Median overall follow-up was 11 yr. PCa incidence increased significantly with higher initial PSA levels. Aggressive PCa (clinical stage ≥T2c, Gleason score ≥8, PSA >20 ng/ml, positive lymph nodes, or metastases at diagnosis) was detected in 66 of 733 screen-detected PCa cases (9.0%) and 72 of 182 interval-detected PCa cases (39.6%). Twenty-three PCa deaths occurred in the total population (0.15%), with an increasing risk of PCa mortality in men with higher initial PSA values.The risk of PCa, aggressive PCa and PCa mortality in a screening population with initial PSA <3.0 ng/ml increases significantly with higher initial PSA levels. These results contribute to the risk stratification and individual management of men in PSA-based screening programmes.
French Journal Now Accepting Articles in English
Authors: M. Pestel
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 August 1988French Journal Now Accepting Articles in EnglishM. Pestel, MD, EditorM. Pestel, MD, EditorSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-109-3-255 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor:The Editorial Board of theAnnales de Medecine Interne(Masson, Paris; 8 issues yearly) will now accept articles by English-speaking authors for publication in English. These articles will be accompanied by a summary in French.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Annales de Medecine Interne 75005 Paris France PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1988Volume 109, Issue 3Page: 255-255 ePublished: 1 December 2008 Issue Published: 1 August 1988 PDF downloadLoading ...
Preclinical experimental models of drug metabolism and disposition in drug discovery and development
Authors: Donglu Zhang, Gang Luo, Xinxin Ding, Chuang Lu
Journal: Acta Pharmaceutica Sinica B (2012)

Drug discovery and development involve the utilization of in vitro and in vivo experimental models. Different models, ranging from test tube experiments to cell cultures, animals, healthy human subjects, and even small numbers of patients that are involved in clinical trials, are used at different stages of drug discovery and development for determination of efficacy and safety. The proper selection and applications of correct models, as well as appropriate data interpretation, are critically important in decision making and successful advancement of drug candidates. In this review, we discuss strategies in the applications of both in vitro and in vivo experimental models of drug metabolism and disposition.
Taking On the Fat of the Land: Cholesterol and Health
Authors: Lawrence Grouse
Journal: JAMA (1986)

As studies continue to document the substantial health benefits of lowering serum cholesterol levels,<sup>1</sup>medical and public health organizations are advocating an aggressive role for physicians in treating patients with hypercholesterolemia and preventing it in the population at large.<sup>2</sup>Still, even with the strong pathological and epidemiologic evidence of the crucial role of hypercholesterolemia in atherogenesis, only about 30% of physicians believe its control is as important as the control of hypertension or smoking.<sup>3</sup>New national survey data (Basil Rifkind, MD, unpublished data, October 1986) suggest that both physicians and patients underestimate the health risk that hypercholesterolemia poses. This issue ofThe Journalattempts to assist physicians in the diagnosis and treatment of hypercholesterolemia by presenting authoritative data on its many clinical dimensions. Because the National Institutes of Health have taken a leading role in funding key clinical and basic scientific research in hypercholesterolemia, it is appropriate
The Public and the War on Illicit Drugs
Authors: Robert J. Blendon
Journal: JAMA (1998)

This article presents what Americans think about the policies subsumed under the label of the "War on Drugs." It is based on an analysis of 47 national surveys conducted between 1978 and 1997. The major results are that most Americans rely on the mass media for information about the scope of the drug abuse problem; Americans do not think that the Wars on Drugs have succeeded, but they do not want to quit on these efforts; weak support exists for increasing funding for drug treatment; support for preventive education has increased during the 1990s; criminal justice responses remain very popular; for many, illicit drug use is a moral rather than a public health issue; the public supports allowing physicians to prescribe marijuana for severe illness, but opposes the general legalization of marijuana and other illicit drugs; and needle exchange programs are supported by a bare majority, but only when they are told that the American Medical Association supports these programs.
Brain SPECT Imaging Using Three Different Tracers in Subacute Cerebral Infarction
Authors: JUN HASHIMOTO, TAKAHIRO SASAKI, YOSHIAKI ITOH, KAYOKO NAKAMURA, ATSUSHI KUBO, TAKAHIRO AMANO, YASUO FUKUUCHI
Journal: Clinical Nuclear Medicine (1998)

Two patients with subacute cerebral infarction underwent benzodiazepine receptor imaging using I-123-iomazenil and cerebral perfusion imaging with Tc-99m HMPAO and Tc-99m ECD. Iomazenil early images resembled HMPAO images, which demonstrated increased uptake in a part of the infarcted site. Iomazenil delayed images and ECD images showed reduced accumulation in the same area. Crossed cerebellar diaschisis was observed in HMPAO, ECD, and iomazenil early images, but it was not remarkable in iomazenil delayed images. These cases suggest that sequential iomazenil images visualized increased uptake with relatively impaired viability in the infarcted site and hypoperfusion with preserved viability in the contralateral cerebellar hemisphere, which could not be recognized without using both HMPAO and ECD in the subacute phase of cerebral infarction.
Lineage-Specific Evolutionary Rate in Mammalian mtDNA
Authors: Carmela Gissi, Aurelio Reyes, Graziano Pesole, Cecilia Saccone
Journal: Molecular Biology and Evolution (2000)

The existence of a lineage-specific nucleotide substitution rate in mammalian mtDNA has been investigated by analyzing the mtDNA of all available species, that is, 35 complete mitochondrial genomes from 14 mammalian orders. A detailed study of their evolutionary dynamics has been carried out on both ribosomal RNA and first and second codon positions (P12) of H-strand protein-coding genes by using two different types of relative-rate tests. Results are quite congruent between ribosomal and P12 sites. Significant rate variations have been observed among orders and among species of the same order. However, rate variation does not exceed 1.8-fold between the fastest (Proboscidea and Primates) and the slowest (Perissodactyla) evolving orders. Thus, the observed mitochondrial rate variations among taxa do not invalidate the suitability of mtDNA for drawing mammalian phylogeny. Dependence of evolutionary rate differences on variations in mutation and/or fixation rates was examined. Body size, generation time, and metabolic rate were tested, and no significant correlation was observed between them and the taxon-specific evolutionary rates, most likely because the latter might be influenced by multiple overlapping variable constraints.