tbuckley/cabot-search huggingface dataset:
What would be the observable consequences if phospholipid bilayer diffusion of drugs into cells is negligible?
Authors: Douglas B. Kell
Journal: Trends in Pharmacological Sciences (2014)

•What if drugs do not enter cells significantly via bilayers in real membranes?•One set of consequences relates to the bilayer itself.•Other consequences reflect the role of protein transporters.•A third set of consequences revolves around the chemical structures themselves.•No evidence refutes the view that phospholipid bilayer diffusion of drugs in vivo is negligible. For drug transport across (i.e., through) an intact biological membrane, two main routes are possible: drugs may cross (i) through the phospholipid bilayer portion of the membrane, and/or (ii) via proteinaceous pores or transporters. Perhaps surprisingly, there is in fact no direct scientific evidence that the first of these takes place at any significant rate because, in the experiments performed to date, it has neither been varied as an independent variable nor measured directly as a dependent variable. Using a standard hypothetico-deductive framework, I assess the intellectual and observable consequences of assuming that, for drugs, phospholipid bilayer diffusion is negligible – 'PBIN' – (i.e., may be neglected, relative to transporter-mediated transmembrane fluxes). Predictions and postdictions of the PBIN hypothesis are not refuted by available experimental evidence. For drug transport across (i.e., through) an intact biological membrane, two main routes are possible: drugs may cross (i) through the phospholipid bilayer portion of the membrane, and/or (ii) via proteinaceous pores or transporters. Perhaps surprisingly, there is in fact no direct scientific evidence that the first of these takes place at any significant rate because, in the experiments performed to date, it has neither been varied as an independent variable nor measured directly as a dependent variable. Using a standard hypothetico-deductive framework, I assess the intellectual and observable consequences of assuming that, for drugs, phospholipid bilayer diffusion is negligible – 'PBIN' – (i.e., may be neglected, relative to transporter-mediated transmembrane fluxes). Predictions and postdictions of the PBIN hypothesis are not refuted by available experimental evidence.
Quantitative graphical description of portocentral gradients in hepatic gene expression by image analysis
Authors: W H Lamers, W J Geerts, A Jonker, F J Verbeek, G T Wagenaar, A F Moorman
Journal: Hepatology (1997)

The liver consists of numerous repeating, randomly oriented, more or less cylindrical units, the lobules. Although enzyme-histochemical or microbiochemical assays accurately reflect zonal differences in lobular enzyme content, their results cannot be directly compared to biochemical assays. This is because section-based assays typically sample along a linear portocentral column of cells, even though periportal regions contribute substantially more to hepatic volume than pericentral regions. We have developed a time-efficient approach that depends on image analysis to determine the prevalence of hepatocytes (pixels) with a defined cellular concentration of a particular gene product (absorbance), and that generates a graph with the average absorbance per hepatocyte on the ordinate and the percentage of hepatocytes with absorbances in each of a predetermined range of absorbances incrementally summed on the abscissa. The direction of the gradient is read directly from the section. The gradient is a graphical representation of the two-dimensional distribution pattern of the gene product between the portal tracts and the central veins. The total surface area underneath the resulting graph represents the integrated absorbance and is equivalent to the outcome of a biochemical assay. The typical linear portocentral gradient can be derived from that representing the two-dimensional distribution if we assume that liver lobules are uniformly cylindrical or prismatic. The analysis, therefore, yields a quantitative description of the relation between the enzymatic phenotype of hepatocytes and their position on a normalized portocentral radius. We have used the procedure to compare portocentral gradients of different enzymes in the same liver and of the same enzyme in different livers. In addition, bipolar portocentral gradients of the same enzyme in the same liver were analyzed.
Perspectives on the Value of American Society of Clinical Oncology Clinical Guidelines as Reported by Oncologists and Health Maintenance Organizations
Authors: Charles L. Bennett, Mark R. Somerfield, David G. Pfister, Cecilia Tomori, Sofia Yakren, Peter B. Bach
Journal: Journal of Clinical Oncology (2003)

Although the American Society of Clinical Onoclogy's (ASCO) Health Services Research (HSR) committee activities have primarily focused on clinical guideline development, little is known about the value placed on these guidelines by the desired end users. ASCO members and Health Maintenance Organizations (HMOs) were surveyed on the value and implementation of ASCO guidelines. In this article, we summarize our findings.ASCO members (n = 1500) were queried about whether they had read ASCO's first four clinical guidelines and technology assessment; whether they agreed with the recommendations; whether they used guidelines in clinical practice; and how guidelines had affected reimbursement. HMOs (n = 131) were queried on how they identify, implement, and value the first four ASCO clinical guidelines.The membership survey indicated that ASCO guidelines were read more often by physicians in private healthcare settings compared with physicians in academic practices (P <.02). Disagreement rates were low for all guidelines (range, 1% to 7%). One quarter of respondents reported that the guidelines were difficult to find and difficult to apply to the practice setting, and approximately one tenth of respondents indicated that the guidelines were difficult to evaluate, interpret, or read. The HMO survey indicated that one third of HMOs reported use of ASCO guidelines, with higher rates of usage by larger HMOs and by those with higher National Committee on Quality Assurance (NCQA) ratings. Respondent HMOs valued guidelines for various purposes and used multiple methods of guideline identification and implementation.ASCO guidelines are generally highly supported by physicians and HMOs. Additional studies are needed to identify implementation barriers and to see whether guidelines have resulted in improvements in healthcare.
Neuropathologic Basis of Age-Associated Brain Atrophy
Authors: Deniz Erten-Lyons, Hiroko H. Dodge, Randall Woltjer, Lisa C. Silbert, Diane B. Howieson, Patricia Kramer, Jeffrey A. Kaye
Journal: JAMA Neurology (2013)

While brain volume changes are used as surrogate markers for Alzheimer disease neuropathology in clinical studies, the extent to which these changes are due to pathologic features of Alzheimer disease in the aging brain is not well established. This study aims to clarify the neuropathologic correlates of longitudinal brain atrophy.To examine the association between brain atrophy during life and neuropathology in an elderly population.Autopsy study of a cohort of elderly individuals.Community-based population.Seventy-one healthy elderly individuals were selected from participants of the Oregon Brain Aging Study for having an autopsy, more than 1 magnetic resonance imaging scan, and the last magnetic resonance imaging scan within 36 months of death.The associations between brain volume trajectories (ventricular, total brain, and hippocampal) and time interaction terms for neurofibrillary tangles, neuritic plaques, gross infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE ε4 presence, and clinical diagnosis (no cognitive impairment, mild cognitive impairment, or dementia as time-varying covariates) were examined in mixed-effects models, adjusting for duration of follow-up and age at death.Ventricular volume trajectory was significantly associated with age, presence of infarcts, neurofibrillary tangle and neuritic plaque scores, APOE ε4 allele presence, and dementia diagnosis. Total brain volume trajectory was significantly associated with age and mild cognitive impairment diagnosis. Hippocampal volume trajectory was significantly associated with amyloid angiopathy.Ventricular volume trajectory is more sensitive than total brain and hippocampal volume trajectories as a marker of accruing Alzheimer disease and vascular pathology in elderly individuals. The association between brain volume trajectories and cognitive impairment (mild cognitive impairment and dementia) remained after controlling for the degree of neuropathology and other covariates. This suggests that there may be other factors not measured in this study that could be contributing to brain atrophy in those with cognitive impairment.
Reviews and Notes: Marihuana, the Forbidden Medicine
Authors: Eric A. Voth
Journal: Annals of Internal Medicine (1994)

Literature of Medicine15 February 1994Reviews and Notes: Marihuana, the Forbidden MedicineEric A. Voth and Daniel BrookoffEric A. VothSt. Francis Chemical Dependency Services, Topeka, KS 66606. University of Tennessee, Memphis, TN 38103.Search for more papers by this author and Daniel BrookoffSt. Francis Chemical Dependency Services, Topeka, KS 66606. University of Tennessee, Memphis, TN 38103.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-4-199402150-00033 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Marihuana, the Forbidden MedicineLester Grinspoon and James B. Bakalar. 184 pages. New Haven, Connecticut: Yale University Press; 1993. $22.50.Danny was 14 years old in 1971 when he began receiving chemotherapy for acute lymphocytic leukemia. The treatments caused severe nausea and vomiting, which were not alleviated by the standard antiemetics. Danny's father was shocked when his wife suggested that they obtain marijuana for Danny. He dismissed it because it was illegal and because it might embarrass the doctors at the hospital, who had been so remarkable in their commitment to Danny's care. Danny's father recalls one treatment that surprised ... Author, Article, and Disclosure InformationAffiliations: St. Francis Chemical Dependency Services, Topeka, KS 66606. University of Tennessee, Memphis, TN 38103. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMarihuana and Its Reviews 15 February 1994Volume 120, Issue 4Page: 348KeywordsAlcoholsCancer treatmentDrugsMarijuanaNauseaPrecursor cellsPruritusPsychiatry and mental healthStaphylococcusVomiting ePublished: 15 August 2000 Issue Published: 15 February 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies
Authors: Aude Servais, Laure-Hélène Noël, Lubka T. Roumenina, Moglie Le Quintrec, Stephanie Ngo, Marie-Agnès Dragon-Durey, Marie-Alice Macher, Julien Zuber, Alexandre Karras, François Provot, Bruno Moulin, Jean-Pierre Grünfeld, Patrick Niaudet, Philippe Lesavre, Véronique Frémeaux-Bacchi
Journal: Kidney International (2012)
Double-blind controlled trial of cimetidine in the healing of gastric ulcer.
Authors: P J Ciclitira, R J Machell, J G Farthing, A P Dick, J O Hunter
Journal: Gut (1979)

Sixty patients with gastric ulcers were treated for four weeks with either 1 g cimetidine per day or with identical tablets containing lactose. The healing rate, assessed by endoscopy, was 23 out of 35 (66%) in the patients given cimetidine and 13 out of 25 (52%) in those given placebo. The difference between the groups is not significant. During each of the four weeks of the study the cimetidine group experienced significantly fewer attacks of pain and consumed less antacids than the placebo treated patients.
Mitral valve prolapse in short-term experimental coronary occlusion: a possible mechanism of ischemic mitral regurgitation.
Authors: C Tei, T Sakamaki, P M Shah, S Meerbaum, S Kondo, K Shimoura, E Corday
Journal: Circulation (1983)

Experimental coronary occlusions were carried out in 12 closed-chest dogs to investigate the functional anatomic characteristics of the mitral valve complex during acute myocardial ischemia. Two-dimensional echocardiography was used to assess left ventricular function, the mitral valve complex, and left atrial size. Presence of mitral regurgitation was assessed by left ventricular contrast echocardiography. Thirty-seven coronary occlusions of up to 10 min in duration were carried out in proximal or distal locations in the left anterior descending and the left circumflex coronary arteries. Mitral regurgitation, which was mild in severity as judged by a small rise in pulmonary artery wedge pressures, was observed in 15 of 37 brief coronary occlusion experiments. Mitral valve prolapse was noted in all 15 experiments, as well as in four additional studies in which mitral regurgitation was not seen. The development of experimental mitral valve prolapse was explained by measurements that demonstrated a relative displacement of the papillary muscle tips toward the mitral orifice. We conclude that mitral valve prolapse is a common sequela of short-term coronary occlusion and is often associated with mild mitral regurgitation. Relative displacement of ischemic papillary muscles toward the mitral orifice appears to be a likely mechanism of acute ischemic mitral valve prolapse.
Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation
Authors: Holden Higginbotham, Jiami Guo, Yukako Yokota, Nicole L Umberger, Chen-Ying Su, Jingjun Li, Nisha Verma, Joshua Hirt, Vladimir Ghukasyan, Tamara Caspary, E S Anton
Journal: Nature Neuroscience (2013)
Radiation-Induced Prevention of Erlotinib-Induced Skin Rash Is Transient: A New Aspect Toward the Understanding of Epidermal Growth Factor Receptor Inhibitor–Associated Cutaneous Adverse Effects
Authors: Peter Arne Gerber, Elaine Enderlein, Bernhard Homey, Anja Muller, Edwin Boelke, Wilfried Budach
Journal: Journal of Clinical Oncology (2007)
Review: Interventions for patient transition from hospital to primary care may improve outcomes
Authors: Joel M. Schectman
Journal: Annals of Internal Medicine (2013)

ACP Journal Club15 January 2013Review: Interventions for patient transition from hospital to primary care may improve outcomesJoel M. Schectman, MD, MPHJoel M. Schectman, MD, MPHUniversity of Virginia Health System, Charlottesville, Virginia, USA (J.M.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-2-201301150-02012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHesselink G, Schoonhoven L, Barach P, et al. Improving patient handovers from hospital to primary care: a systematic review. Ann Intern Med. 2012;157:417-28. https://pubmed.ncbi.nlm.nih.gov/22986379Clinical Impact RatingsGIM/FP/GP: Hospitalists: Geriatrics: Author, Article, and Disclosure InformationAffiliations: University of Virginia Health System, Charlottesville, Virginia, USA (J.M.S.)This article was published at Annals.org on 1 January 2013. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNursing Care Management 15 January 2013Volume 158, Issue 2Page: JC12KeywordsAdverse eventsHospitalistsPatientsPrimary careQuality of lifeSafetySafety studiesSpecificitySystematic reviews ePublished: 15 January 2013 Issue Published: 15 January 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Single-lung transplants to resume soon with cyclosporin A therapy
Authors: Phil Gunby
Journal: JAMA (1982)

The first human single-lung transplant in which cyclosporin A is used as an immunosuppressive agent probably will be performed sometime this year. The likely surgeon? Frank J. Veith, MD, chief of vascular surgery and director of the transplant program at Montefiore Hospital and Medical Center, Bronx, NY, who attempted five lung transplants between 1969 and 1973. In a recent interview with<i>JAMA</i>MEDICAL NEWS, Veith conceded that his team is ready and in effect has the green light from the Food and Drug Administration and Sandoz, Inc, maker of cyclosporin A. However, he added: "I think we'll have to wait at least six months to get a suitable donor." Thirty-eight human single-lung transplants were attempted between June 11, 1963, when James D. Hardy, MD, performed the first one, and May 13, 1977, when a team from the University of Toronto performed the last reported one. All 38 were performed before cyclosporin
Malignancy, weight loss, and the small intestinal mucosa
Authors: R. E. Barry
Journal: Gut (1974)

The mucosal architecture and mucosal dynamics of the small bowel have been studied in patients with malignant disease not of the gastrointestinal tract but associated with severe weight loss. Mucosal changes in malignant disease are demonstrated by stereomicroscopy, mucosal architectural measurement, and decreased lactose utilization. Measurement of the epithelial DNA loss rate indicates, in association with mucosal measurement, that the architectural changes are caused by a hypoplasia of the epithelium. Similar findings are demonstrated in patients with profound weight loss due to other non-malignant wasting diseases. Although mucosal changes undoubtedly occur in malignant disease, the changes are not specific for malignancy and the concept of ;cancer enteropathy' is not tenable. It is suggested that mucosal changes are the effect of and not the cause of cachexia.
Protein kinase C–catalyzed phosphorylation of an inhibitory phosphoprotein of myosin phosphatase is involved in human platelet secretion
Authors: Yasuyuki Watanabe, Masaaki Ito, Yoshiyuki Kataoka, Hideo Wada, Mutsumi Koyama, Jianhua Feng, Hiroshi Shiku, Masakatsu Nishikawa
Journal: Blood (2001)
Developmental expression of myostatin in cardiomyocytes and its effect on foetal and neonatal rat cardiomyocyte proliferation
Authors: G MCKOY, K BICKNELL, K PATEL, G BROOKS
Journal: Cardiovascular Research (2007)

Objectives: Myostatin, a member of the transforming growth factor-beta (TGF-β) family, plays a key role in skeletal muscle myogenesis by limiting hyperplastic and hypertrophic muscle growth. In cardiac muscle, myostatin has been shown to limit agonist-induced cardiac hypertrophic growth. However, its role in cardiac hyperplastic growth remains undetermined. The aim of this study was to characterise the expression of myostatin in developing myocardium, determine its effect on cardiomyocyte proliferation, and explore the signalling mechanisms affected by myostatin in dividing cardiomyocytes.
BMA Annual Representative Meeting: Allowing private companies to commission services is “a step too far”
Authors: Annabel Ferriman
Journal: BMJ (2006)

A government plan to extend the role of commissioning healthcare services to private companies is a “step too far,” James Johnson, chairman of the BMA, told the association's annual meeting this week.

“You don't have to be a financial wizard to work out that that if a private company runs the hospitals and also commissions the services, it adds up to a licence to print money,” he told the 550 representatives.

“You hear politicians say there's no difference between GPs, who are independent contractors commissioning services, and private organisations doing so. There is one …
Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: long-term follow-up of a phase 1/2 study
Authors: Leo I. Gordon, Arturo Molina, Thomas Witzig, Christos Emmanouilides, Andrew Raubtischek, Mohamed Darif, Russell J. Schilder, Greg Wiseman, Christine A. White
Journal: Blood (2004)
The Triangle Splint in the Treatment of Compound Fractures of the Humerus
Authors: P. Turner
Journal: BMJ (1918)

I TL 7T1 1O'Coonnor workinig at Alexandria (about 12 per cent.).But, on the other hiand, it may be myientioned that amongost E.L.C. men and Turkislh prisoners of war, comiing from Mesop)otarnia, and examined wlile in the quarantine camps near Suez, I found nearly 12 per cent.to be Infected witlh E. hi8solytica.Conversely, out of over fifty prisoners fromn the Hedjaz (Arabia) I did not find a single carrier.In the summer of 1917 I was transferred to Kantara, slnd dealt there entirely with cases of dlysentery, etc., occurring amongst troops east of the canal, in the nortlhern coastal district alluded to.And I soon founid, as expected, that there was a distinctly hiiglher incidence of am-oebic inifections amongst the Britislh troops tliani I liad imet witlh iln the soutlhern canal area.For the correspond(ing seasoln (April-October),-* the percentage of arnoebic dysen terics- that is, witlh active histolyt'ic4.--was 7per cent. of tlhe total dysenterics, as against 2i, per cent.; and the percenitage of Kisiolytica findings (all forms) in the total stools examined (oxer 2,000) was 5.2 per cent., conipared with slighitly unl(ler 2 per cent.On tlhe otlher lhanid, thje percentage of dieflinite bacillary dysenterics to the total stools was milucl less than at Suez-niamely, 37 per cent., compared withl 75 per cent.-tlhefly cami-paign being probably nore Vigorous and effective.Thrinking it would prove inistructive to comopare the variations in the amnoebic finidings witlh the variations in the relative lhumlidity, I requested the Phiysical Departmnent ot the Public Healtht Bureau, Cairo, to let mne liave, if possible, tab!cs shoWving thle melative lhumidity at Port Sail (thie niearest station available iti tIme niortlherni (listrict) for tle corresponding seasoni in tIme two years 1916 and 1917 respectively.Tlhis informlationi was very courteously afforded nme, and1A.r8T M -NTH - C I find that whlile L-1K..,9 A.it m run A_ [ tIme averaoe mean SUM5ERPERCOG MEA relative humidity
Press: Close encounters of an alternative kind
Authors: J. Diamond
Journal: BMJ (2000)

John Diamond, who has oral cancer, last week received the 2000 Health Watch Award for informing the public about reliable cancer treatments. This is an edited version of his acceptance speech.

I must have written my standard piece about the nature of scientific endeavour and the intellectual folly that is alternative medicine some 100 times now for various papers. Each time I get equally standard replies from outraged alternativists.

The last time I gave the piece its regular outing I got a letter, among the others, from an upset Liverpudlian. He was a practitioner in alternative medicine and “knew” it worked. And what's more, he said, he also knew that orthodox medicine simply didn't work. He didn't say it didn't work as well as doctors thought it did or as well as patients were suckered into believing it did by the grasping medical establishment. No, all orthodox medicine, he said, is a sham.

Bored with whatever it was I was doing—probably writing yet another piece on the folly that is alternative medicine—I made the mistake of emailing him. “If orthodox medicine doesn't work,” I wrote, “how come life expectancy since the turn of the century has almost doubled?” His reply was the one that the alternativists usually give: life expectancy has increased only because infant mortality has decreased. Take all those dead babies out of the equation and your average Victorian with his little liver pills and tiger balm lived just as long as your 21st century pill popper.

But life expectancy at 20 is also up, I wrote back. And at 30 and 40. A 50 year old with access to a reasonably sober general practitioner and a branch of Boots has a greater chance of living to 80 or 90 than his father or grandfather did. And these …