tbuckley/cabot-search huggingface dataset:
Regulation of bile acid metabolism: New insights from inside
Authors: Pablo Quintero, Marco Arrese
Journal: Hepatology (2013)

Sayin SI, Wahlstrom A, Felin J, Jantti S, Marschall HU, Bamberg K, et al . Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 2013;17:225-235. (Reprinted with permission). Abstract Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition throughout the enterohepatic system in germfree (GF) and conventionally raised (CONV-R) mice. We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice. Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7a-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. Importantly, we identified tauroconjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.
483. Acoustically Active Liposomes for Oligonucleotide/Drug Encapsulation; Delivery Agents with Capacity for Ultrasound-Triggered Release
Authors: Shao-Ling Huang, David D. McPherson, Robert C. MacDanold
Journal: Molecular Therapy (2004)

Liposomes can carry many different kinds of therapeutic agents. Acoustically active liposomes (AAL), which contain small amounts of air within their bilayers, were previously developed by our group. These AAL also have the potential to carry oligonucleotides and their acoustic activity could enable them to respond to local ultrasound stimulation by releasing their contents at a disease site. Liposomes were composed of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, and cholesterol at a molecular ratio of 69:8:8:15 and made acoustically active with a procedure involving hydrating the lipid film, sonication, freezing in the presence of mannitol, lyophilization, and rehydration. A FITC-labeled oligonuleotide (ODN, 12 bp) was added at the hydration step. Encapsulation efficiency was measured after Sepharose 4B chromotography. For other encapsuation as well as for release measurements, calcein was used as a test molecule because it is a convenient fluorescent probe for uptake and leakage determinations. The procedure of freeze-drying in the presence of mannitol has been found to be a superior method for oligonucleotide encapsulation. Approximally 25% encapsulation was obtained with one freeze-thaw cycle (Figure 1), which is similar to the encapsulation of calcein (20%). One MHz ultrasound at 2 W/cm2, 100% duty cycle, was applied to loaded, acoustically active liposomes for 10s intervals and caused 32% release of calcein. Six such applications released 62% of original contents. Release of contents was highly correlated with the loss of air (Figure 2) induced either by ultrasound or rapid pressure reduction, indicating that pressure-induced stress on liposome-associated air pockets is responsible for ultrasound-triggered drug release. This encapsulation and release technique should also be applicable to siRNA's, since recent research has found that delivery methods developed for ODN are also efficient for siRNA. The ultrasound-sensitive liposomes provides the distinct advantage of allowing control and localization of the release of nucleotide-based and other hydrophilic therapeutic agents. Furthermore, the destruction of microbubbles may facilitate nucleotide transport across biological membranes. Ultrasound image enhancement by these liposomes may also facilitate identification of regions of disease, allowing further improvements in site-specific delivery.
Genotype Doesn’t Affect Response to Naltrexone for Alcohol Dependence
Authors: Anita Slomski
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
MASSIVE DOSAGE OF PENICILLIN ADMINISTERED BY CONTINUOUS INTRAMUSCULAR INFUSION
Authors: R L FISHER, M ZUKERMAN
Journal: Annals of Internal Medicine (1948)

Article1 June 1948MASSIVE DOSAGE OF PENICILLIN ADMINISTERED BY CONTINUOUS INTRAMUSCULAR INFUSIONRALPH LEE FISHER, A.B., M.D., F.A.C.P., MORRIS ZUKERMAN, A.B., M.D.RALPH LEE FISHER, A.B., M.D., F.A.C.P.Search for more papers by this author, MORRIS ZUKERMAN, A.B., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-28-6-1143 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWe wish to present a review of our experience with 24 patients treated with a massive dosage of penicillin by continuous intramuscular infusion.The dose varied from 500,000 to 2,000,000 units of penicillin administered daily for a period of three to 19 days. The first nine patients were given crude penicillin and the last 15 penicillin G.Technic of Administration:The penicillin was dissolved in 500 c.c. of 5 per cent glucose in water. A No. 20 gauge spinal needle was inserted in the lateral aspect of the thigh after infiltration with 1 per cent procaine hydrochloride. Ten c.c. of...Bibliography1. HIRSCHDOWLING HLHF: Observations on the continuous intramuscular method of administering penicillin, Am. Jr. Med. Sci., 1945, ccx, 435. CrossrefGoogle Scholar2. MCADAM : Quoted by Hirsch and Dowling.1 Google Scholar3. SMITHHARFORD ROCG: The administration of penicillin by continuous intramuscular drip, Jr. Lab. and Clin. Med., 1945, xxx, 502-509. Google Scholar4. JONESWILLIAMS ANGE: Aseptic necrosis at sites of continuous intramuscular penicillin infusions, Lancet, 1945, ii, 817. CrossrefGoogle Scholar5. MORGANCHRISTIEROXBURGH HVRVIA: Experience in the systemic administration of penicillin, Brit. Med. Jr., 1944, i, 515. CrossrefGoogle Scholar6. KEEFER cited by Gordon.8 Google Scholar7. MOORE cited by Gordon.8 Google Scholar8. GORDON EJ: Delayed serum sickness reaction to penicillin, Jr. Am. Med. Assoc., 1946, cxxxi, 727. CrossrefGoogle Scholar9. BAKERLYONS cited by Gordon.8 Google Scholar10. TUCKERROBINSON HARC: Neurosyphilitic patients treated with penicillin: probable Herxheimer reactions, Jr. Am. Med. Assoc., 1946, cxxxii, 281. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Michigan*Received for publication September 10, 1947.From the Department of Medicine, Riverside Clinic, Detroit, Michigan. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1948Volume 28, Issue 6Page: 1143-1149KeywordsGlucosePenicillin ePublished: 1 December 2008 Issue Published: 1 June 1948 PDF downloadLoading ...
Abstract 4728: Higher Maximal Stent Inflation Pressure During Drug Eluting Stent Implantation is Protective Against MACE and Stent Thrombosis: Three Year Data From the Montreal Heart Institute DES Registry
Authors: Hasan Jilaihawi, Jean-Francois Tanguay, Raoul Bonan, Nosib Shravankumar, Stephane Noble, Richard Gallo, Jacques Crepeau, Pierre DeGuise, Gilbert Gosselin, Jean Gregoire, Michel Joyal, Philippe L'Allier, Anita Asgar, Reda Ibrahim, Hung Ly, Serge Doucet
Journal: Circulation (2009)
943. Loss of Neoplastic Phenotype by Specific Inhibition of RET Oncogene Signalling in a Transgenic Model of Primary Medullary Thyroid Carcinoma
Authors: Matthias Drosten, Gero Hilken, Florian Rodicker, Miriam Bockmann, Carmen C. Theseling, Nikica Mise, Aaron N. Cranston, Andreja Frilling, Bruce A. Ponder, Brigitte M. Putzer
Journal: Molecular Therapy (2004)

Background: Dominant activating mutations in the RET proto-oncogene trigger the development of medullary thyroid carcinoma (MTC). These mutations render the RET receptor independent of ligand-induced stimulation and turn it into a dominant acting oncoprotein by inducing constitutive trans-autophosphorylation. Methods: To study effects related to endogenous RET autophosphorylation in MTC cells and orthotopic MTCs in RET transgenic mice, we constructed adenoviral vectors expressing a dominant-negative truncated form of the receptor (RETDTK). Results: Expression of RETDTK in MTC cells impaired the autophosphorylation activity leading to decreased cell survival. This effect was specific to oncogenic RET expressing cells as RET-negative cells did not exhibit any treatment related cytoxicity. To delineate mechanisms responsible for the observed effect, we analyzed downstream targets potentially implicated in RET mediated transformation. We show that phosphorylation of Akt and ERK, as the major contributors to RET triggered transformation, is abolished after RETDTK expression. RETDTK mediated inactivation of Akt and ERK signaling is further accompanied by reduced cell cycle progression (through downregulation of cyclin D1 and upregulation of p21CIP1/WAF1 and p27KIP1) and stimulation of apoptosis (through downregulation of Bcl-2) in MTC derived cells. Furthermore, we demonstrate that tumor growth and maintenance of orthotopic MTCs in transgenic mice expressing oncogenic RET in their germline is significantly affected after inhibition of oncogenic RET through RETDTK expression (p<0,0001; two-sided unpaired Student's t test). Conclusion: Our results indicate that targeted therapy by selective disruption of oncogenic RET signaling responsible for cellular transformation can be an effective new treatment for primary MTC in vivo
Abstract 20249: Staphylococci Endocarditis: Metagenomics and Ultrastructural Analysis in Surgically Treated Patients
Authors: Andreas Oberbach, Stefan Feder, Jochen Neuhaus, Nadine Schlichting, Stefanie Lehmann, Sven Lehmann, Farhad Bakthiary, Max Lühr, Friedrich Willhelm Mohr, Yvonne Kullnick
Journal: Circulation (2014)

Introduction: Staphylococci are the most common cause for surgically treated infective endocarditis. No long-term cohort studies of infected endocarditis in cardiac surgery are known yet. Therefore we investigate the occurrence of staphylococci within this population and its phylogenetic species. Because of surgical valve removement, we were able to investigate pathophysiologic condition of involved valves by metagenomic analysis and 3D-electron microscopy. Hypothesis: Metagenome analysis revealed more sensitive analysis of Staphylococci related species than standard microbiology methods. Methods: All patient undergoing surgery at our hospital due to infected endocarditis from 2000-2013 were investigated. Scanning electron microscopy (SEM) of infected material was conducted. Furthermore focused ion beam SEM was used to create 3D image-stacks. In four cases bacterial (16S) rRNA was extracted. Metagenomic analysis by next generation sequencing was conducted, using V1-3 and V3-5 primer pairs. Results: In a 1...
Brave new technologies issue : November (with apologies to Thomas Hood)
Authors: James A S Dickson
Journal: BMJ (2000)

No sun—no moon! No morn—no noon! No dawn—no dusk! No fruits, no flowers, no leaves, no  birds—November.No scientific editorials—no news! No papers—no book reviews! No letters, no fillers, no obits, Minerva alone to serve our wits. No proper time of day, No proper BMJ. November 13th brought no satisfaction.1 Please not again—no repetition!
Abstract 18078: Strain rather than Diastolic Parameters correlates with Heart Failure Risk Factors
Authors: Hong Yang, Kazuaki Negishi, Mark Nolan, Ying Wang, Leah Wright, Thomas Marwick
Journal: Circulation (2014)

Background: Stage B heart failure (SBHF) is currently defined by structural heart disease (previous MI, LV remodelling, hypertrophy and low EF). The roles of functional measures (global longitudinal strain [GLS] and diastolic dysfunction [DD]) as markers of SBHF are undefined. Method: Pts &gt;65 yo with ≥1 HF risks (hypertension, type 2 diabetes, obesity, previous chemotherapy, F/H of HF or previous cardiac history) were recruited from the local community. All subjects underwent questionnaires, 6-minute walk (6MW) and echocardiography. Abnormal echo was defined by GLS (-18%), LV mass index (LVMI) (95 for female, 115 for male, g/m2), 6MW (455 meters), E/e’ (12, medial), DecT (&lt;140 or &gt;240 ms) and LAVI (≥32 ml/m2). Results: Of 236 pts (age 71±5, 47% men), 22% had one, 42% had two and 36% had &gt;2 listed HF risk factors. There were significant associations of #HF risks with reduced GLS (p=0.008 for trend), increased LVMI (p=0.002) and shorter 6MW (p=0.004). There were no significant associations with diastology measurements, including increased mitral annular E/e’ (p=0.67), deceleration time (p=0.61) and mitral E/A (p=0.46) (Table). The relative risk of abnormal GLS in those with more than one risk is 1.38 (95%CI 1.05-1.81; p=0.019), increased LVMI 1.31 (1.00-1.74; p=0.055), shorter 6MW 1.22 (0.99-1.49; p=0.059). Conclusion: In asymptomatic pts with HF risks, GLS (but not DD) showed an association with number of risks, similar to LVMI and 6MW distance.
Abstract 18519: Withdrawal of Antiplatelet Therapy Results in Worse Short-term Prognosis in Patients Undergoing Elective Major Noncardiac Surgery
Authors: Jesús álvarez-García, Miquel Vives-Borrás, Joan I Llao, Andreu Ferrero-Gregori, Marc Bausili, Rubén Díaz, María A Gil, Victoria Moral, Pilar Paniagua, Mireia Rodriguez, Mónica C Urrutia, Alessandro Sionis, Xavier Pelaez
Journal: Circulation (2014)

Background: The decision whether to discontinue antiplatelet therapy in patients undergoing major noncardiac surgery can be clinically challenging. There is insufficient clinical evidence to establish comprehensive guidelines and most of recommendations are based on expert consensus. Objective: To evaluate the effectof withdrawal of antiplatelet therapy on 30-day postoperative outcome in subjects undergoing elective major noncardiac surgery. Methods: A retrospective cohort study was performed in 1630 patients, 40 years and older, who underwent major noncardiac surgery. Age, gender, risk factors, previous chronic heart or lung disease, renal function, anemia and concomitant treatment were used in a binary logistic regression to determine the impact of withdrawal of antiplatelet therapy on prognosis. The primary outcome measure was a composite of 30-day postoperative mortality or cardiovascular events (cardiac arrest, myocardial infarction, stroke or pulmonary embolism). Results: Five percent of patients presented the composite primary outcome measure of 30-day postoperative mortality or cardiovascular events. Antiplatelet therapy was withdrawn in 11.4% of patients (table). Discontinuation of antiplatelet therapy was associated with a significant increase in the primary outcome measure (OR 2.27; CI95%: 1.16-4.46). Conclusions: In a contemporary cohort of patients undergoing noncardiac surgery, withdrawal of antiplatelet therapy was associated with a worse short-term prognosis. There is an urgent need for further research in this field.
Key statistical and analytical issues for evaluating treatment effects in periodontal research
Authors: Yu‐Kang Tu, Mark S. Gilthorpe
Journal: Periodontology 2000 (2012)

Statistics is an indispensible tool for evaluating treatment effects in clinical research. Due to the complexities of periodontal disease progression and data collection, statistical analyses for periodontal research have been a great challenge for both clinicians and statisticians. The aim of this article is to provide an overview of several basic, but important, statistical issues related to the evaluation of treatment effects and to clarify some common statistical misconceptions. Some of these issues are general, concerning many disciplines, and some are unique to periodontal research. We first discuss several statistical concepts that have sometimes been overlooked or misunderstood by periodontal researchers. For instance, decisions about whether to use the t-test or analysis of covariance, or whether to use parametric tests such as the t-test or its non-parametric counterpart, the Mann-Whitney U-test, have perplexed many periodontal researchers. We also describe more advanced methodological issues that have sometimes been overlooked by researchers. For instance, the phenomenon of regression to the mean is a fundamental issue to be considered when evaluating treatment effects, and collinearity amongst covariates is a conundrum that must be resolved when explaining and predicting treatment effects. Quick and easy solutions to these methodological and analytical issues are not always available in the literature, and careful statistical thinking is paramount when conducting useful and meaningful research.
Extraction and quantification of amino acids in human stratum corneum <i>in vivo</i>
Authors: J.-P. Sylvestre, C.C. Bouissou, R.H. Guy, M.B. Delgado-Charro
Journal: British Journal of Dermatology (2010)

Background Amino acid (AA) levels in stratum corneum (SC) are potential biomarkers of skin health while their systemic levels may be used to diagnose inherited metabolic diseases. Objectives To examine reverse iontophoresis, in human volunteers, as a minimally invasive tool to analyse AAs within the skin and subdermally. Methods In four volunteers, the amounts of iontophoretically extracted AAs were compared with those determined in the SC following repetitive tape stripping and with the plasma concentrations. Glucose levels, evaluated in the different compartments, were used as a control. Results SC concentrations of 13 essentially zwitterionic AAs were ∼100‐fold higher than the respective plasma levels. Passive and reverse iontophoretic extraction for 4 h did not deplete the SC depot of AAs, a fact reinforced by postextraction tape stripping, which revealed that AAs remained in the SC at this time. In contrast, glucose was much less abundant in the SC and was fully and relatively quickly extracted by reverse iontophoresis. Conclusions It follows that reverse iontophoresis is useful for quantifying AAs in the SC and these data are highly correlated with levels obtained by tape stripping. However, reverse iontophoresis is impractical for the routine monitoring of AA plasma concentrations (unlike the situation for glucose, the skin reservoir of which is much smaller).
Abstract 14681: Uber Analysis of Cardiopulmonary Exercise Test Variables and Mortality in Patients with Heart Failure: the Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) Project
Authors: Ali Shafiq, Clinton A Brawner, Heather E Aldred, Raakesh Hassan, Stepahanie Vasko, Jonathan K Ehrman, Yelena Selektor, Christina Tita, Mauricio Velez, Celeste T Williams, David E Lanfear, Steven J Keteyian
Journal: Circulation (2014)

Introduction: Numerous metrics derived from the cardiopulmonary exercise test (CPX) are associated with outcomes among patients with heart failure with reduced ejection fraction (HFrEF). However few studies have examined the independent prognostic value of all variables assessed simultaneously. Purpose: Retrospective analysis to describe the relationship between all CPX measures and the composite outcome of mortality, left ventricular assist device (LVAD), or cardiac transplant (CT). Methods: Patients (n= 1,201; 33% female; age= 55 ± 13 y) with a CPX between 1997 and 2010 and confirmed HFrEF (ejection fraction [EF] &lt; 40%) were identified. Death data through 2011 was obtained from the National Death Index. The association with the composite endpoint was evaluated separately for 30 CPX measures with adjustment for age, gender, EF, and beta-blocker therapy using Cox regression. Forward stepwise Cox regression was performed to identify which of the CPX variables contribute the most to outcome prediction. Results: During a median follow-up of 3.75 years there were 576 (48%) events. When tested separately, nearly all CPX variables (except heart rate reserve/metabolic reserve and peak respiratory exchange ratio) were associated (p&lt;0.05) with the composite endpoint. The top 5 predictors are shown in the Table. Stepwise Cox regression revealed that only % predicted peak oxygen uptake (VO 2 , Wald= 76.1), ventilatory power (peak systolic blood pressure/V E -VCO 2 slope, Wald= 58.0), and EF (Wald= 27.0) independently predicted outcomes. Conclusion: When considering all variables measured during a CPX test, % predicted peak VO 2 was the variable with the strongest independent association to outcomes in this cohort of patients with HFrEF. The % predicted peak VO 2 may represent a key variable in determining when to consider a patient for an LVAD or CT.
The hospital of the future: International trends in the provision and utilisation of hospital care
Authors: M. Hensher, N. Edwards, R. Stokes
Journal: BMJ (1999)

This article examines the pattern of change in hospital provision in established market economies, the countries of eastern Europe and the former Soviet Union, and lower income countries. Despite the great differences between these areas, hospitals in all systems have to deal with rising expectations and, more often than not, a need to contain the costs of health care. Outside the developing countries the generic response to this has been to reduce hospital stays and to improve the efficiency of the system, a strategy which seems to be at least partly successful. The experience of the health systems in the United States and the United Kingdom shows that cost pressures and changes in healthcare delivery mean that this strategy will lead to hospital mergers and closures in the longer term.

#### Summary points

Increasing rates of admission are not just a British phenomenon

Some countries have experienced reductions in admissions

Almost all developed countries have made substantial reductions in beds, and in many places there is still further scope for this

Eastern Europe and the former Soviet Union still have an overdeveloped hospital sector

Hospitals are more of a growth industry in developing countries, but care is needed if the right investment is to be made

Medical practice, hospital management, and technology have undergone great changes over the past 20 years. This has led to substantial shifts in demand for secondary care facilities and notable changes in the types of facilities required. Hospital costs are the largest component of health expenditure in most countries in the Organisation for Economic Cooperation and Development (OECD), and they have therefore been a key focus in the drive for increased efficiency in the health sector.1 While this financial pressure has played a part in developments in the provision of secondary care, the influence of technology and …