tbuckley/cabot-search huggingface dataset:
Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.
Authors: C J Rebouche, A G Engel
Journal: Journal of Clinical Investigation (1984)

The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and "other tissues") was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract.
THE COMMERCE OF SURGERY.
Authors: FERNAND HENROTIN
Journal: JAMA (1905)

"It is further to be observed that just as the self-assertion necessary to the maintenance of society against the state of nature will destroy that society if it is allowed free operation within, so the self-restraint, the essence of the ethical process, which is no less an essential condition of the existence of every polity may, by excess, become ruinous to it. "In a large proportion of cases, crime and pauperism have nothing to do with heredity; but are the consequence partly of circumstances and partly of the possession of qualities which under different conditions of life might have excited esteem and even admiration. The benevolence and openhanded generosity which adorn a rich man may make a pauper of a poor one; the energy and courage to which the successful soldier owes his rise, the cool and daring subtlety to which the great financier owes his fortune may very easily
Cardiac Resynchronization Therapy as a Therapeutic Option in Patients With Moderate-Severe Functional Mitral Regurgitation and High Operative Risk
Authors: Rutger J. van Bommel, Nina Ajmone Marsan, Victoria Delgado, C. Jan Willem Borleffs, Eva P.M. van Rijnsoever, Martin J. Schalij, Jeroen J. Bax
Journal: Circulation (2011)

Functional mitral regurgitation (MR) is a common finding in heart failure patients with dilated cardiomyopathy and has important prognostic implications. However, the increased operative risk of these patients may result in low referral or high denial rate for mitral valve surgery. Cardiac resynchronization therapy (CRT) has been shown to have a favorable effect on MR. Aims of this study were to (1) evaluate CRT as a therapeutic option in heart failure patients with functional MR and high operative risk and (2) investigate the effect of MR improvement after CRT on prognosis.A total of 98 consecutive patients with moderate-severe functional MR and high operative risk underwent CRT according to current guidelines. Echocardiography was performed at baseline and 6-month follow-up; severity of MR was graded according to a multiparametric approach. Significant improvement of MR was defined as a reduction ≥ 1 grade. All-cause mortality was assessed during follow-up (median 32 [range 6.0 to 116] months). Thirteen patients (13%) died before 6-months follow-up. In the remaining 85 patients, significant reduction in MR was observed in all evaluated parameters. In particular, 42 patients (49%) improved ≥ 1 grade of MR and were considered MR improvers. Survival was superior in MR improvers compared to MR nonimprovers (log rank P<0.001). Mitral regurgitation improvement was an independent prognostic factor for survival (hazard ratio 0.35, confidence interval 0.13 to 0.94; P=0.043).Cardiac resynchronization therapy is a potential therapeutic option in heart failure patients with moderate-severe functional MR and high risk for surgery. Improvement in MR results in superior survival after CRT.
A novel point mutation of keratin 17 (<i>KRT17</i>) in a Japanese family with pachyonychia congenita type 2: an RNA-based genetic analysis using a single hair bulb
Authors: T. Tsuda, C. Ishikawa, N. Nakagawa, H. Konishi, M. Tarutani, M. Matsuki, K. Yamanishi
Journal: British Journal of Dermatology (2008)
Animal models of human response to dioxins.
Authors: J A Grassman, S A Masten, N J Walker, G W Lucier
Journal: Environmental Health Perspectives (1998)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in all cancers and suggest that they may also alter immune and endocrine function. In contrast, the health effects of low-level environmental exposure have not been established. Experimental animal models can enhance the understanding of the effects of low-level dioxin exposure, particularly when there is evidence that humans respond similarly to the animal models. Although there are species differences in pharmacokinetics, experimental animal models demonstrate AhR-dependent health effects that are similar to those found in exposed human populations. Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects. The information gained from animal models is important for developing mechanistic models of dioxin toxicity and critical for assessing the risks to human populations under different circumstances of exposure.
The Framingham Offspring Study: a commentary1150th AnniversaryHistorical ArticleINTRODUCTIONIn this edition of the Journal, we release the fifth in a series of reviews of influential articles that have been previously published in ACC journals, including the American Journal of Cardiology(from 1958 to 1982) and JACC(from 1983 to the present). The publication of these articles is only one aspect of the ACC’s 50th anniversary commemoration, which highlights 50 years of leadership in …
Authors: H.J.C Swan
Journal: Journal of the American College of Cardiology (1999)
Abstract 958: Recruitment of tumor-associated macrophages by cooperation of PGE2 pathway and infectious stimulation
Authors: Hiroko Oshima, Keisuke Oguma, Masanobu Oshima
Journal: Cancer Research (2010)

Abstract Gastric cancer development is tightly associated with Helicobacter infection, which induces expression of COX-2 and mPGES-1 resulting in activation of PGE2 pathway in gastric mucosa. It has been established that PGE2 pathway plays a key role in chronic inflammation and tumorigenesis in the stomach. However, mechanisms of PGE2 or PGE2-induced inflammation underlying tumorigenesis have not been fully understood yet. On the other hand, tumor associated macrophages play an important role in tumorigenesis through expression of growth factors, induction of angiogenesis, remodeling and suppression of acquired immunity. We previously showed that macrophage infiltration was enhanced in K19-C2mE transgenic mouse stomach, in which PGE2 pathway is induced by expression of COX-2 and mPGES-1. Moreover, accumulated macrophages in gastric mucosa were activated, which was suppressed by treatment of the mice with antibiotics. These results suggested that both PGE2 pathway and infectious stimulation are important for macrophage infiltration and activation during tumorigenesis. To investigate the effect of PGE2 and infectious stimuli in gastric tumorigenesis, we generated germfree colony of K19-Wnt1/C2mE transgenic mice and examined gastric phenotypes. K19-Wnt1/C2mE mice develop dysplastic gastric tumors caused by simultaneous activation of Wnt signaling and PGE2 pathway. Importantly, germfree K19-Wnt1/C2mE mice showed significant suppression of gastric tumor development with decreased macrophage infiltration. Moreover, Helicobacter infection to germfree K19-Wnt1/C2mE mice induced gastric tumor development. These results indicate that infectious stimuli to gastric mucosa are required for tumor formation. We also found that PGE2 pathway together with bacterial infection induced expression of monocyte-attractant chemokine CCL2 in the gastric mucosa and macrophage cell line. Notably, infiltrated macrophages showed “alternatively” activated M2 properties, which are characteristics of tumor-associated macrophages. Finally, inhibition of COX-2/PGE2 pathway in K19-Wnt1/C2mE mice caused significant suppression of macrophage infiltration and gastric tumorigenesis. These results suggest that PGE2 signaling and bacterial infectious stimulation cooperatively recruit protumorigenic macrophages through induction of chemokines, and that recruitment of tumor-associated macrophages is one of the important mechanisms of PGE2 signaling in tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 958.
Metropolitan Provident Medical Association
Authors: F. H. Corbyn
Journal: BMJ (1888)

Regular patient assessment is essential for the management of chronic diseases, such as pulmonary arterial hypertension (PAH). Comprehensive patient assessment and risk stratification in PAH are important to guide treatment decisions and to monitor disease progression as well as patients9 response to treatment. Approaches for assessing risk in PAH patients include the use of risk variables, as recommended in the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension (PH) guidelines, and the application of risk equations and scores, such as the French registry risk equation and the REVEAL registry risk score. Risk stratification and risk scores are both useful predictors of survival on a population basis, and provide an estimate for individual patients9 risk. The 2015 ESC/ERS PH guidelines recommend regular assessment of multiple variables at an expert centre. The respective merits and limitations of different risk assessment methods in PAH are discussed in this article, as well as some considerations that can be taken into account in the future development of risk assessment tools.
Anesthesia in Otolaryngology and Ophthalmology
Authors: Deryck Duncalf
Journal: JAMA (1982)

This text contains much useful information in two areas of anesthesia. It stems from the extensive experience of an anesthesiologist who for many years has specialized in anesthesia for otolaryngology and ophthalmology. Frequently in the practice of anesthesiology, there may be several options available in the selection of anesthetic agents and techniques. However, in this book, the impression is given that the author has limited his recommendations to his own particular preferences. The middle sections on anesthesia in otolaryngology and ophthalmology contain useful descriptions of the surgical procedures involved and the special anesthetic requirements that must be met to ensure a successful outcome. Since many ophthalmic procedures can be performed under local anesthesia, the chapter on "Topical, Infiltration, and Nerve Block Anesthesia" provides a background of information that will be helpful to both anesthesiologists and ophthalmologists in the choice of local or general anesthesia. Section 1, "General Considerations," is a
UK and US governments must monitor Iraq casualties
Authors: Owen Dyer
Journal: BMJ (2005)

An international group of public health experts has called on the US and UK governments to commission an independent inquiry into Iraqi war related casualties.

“We believe that the joint US-UK failure to make any effort to monitor Iraqi casualties is, from a public health perspective, wholly irresponsible,” says the public statement, signed by 23 experts in public health and epidemiology from the United Kingdom, the United States, Canada, Spain, and Australia. “We have waited too long for this information.”

The British government's reliance on Iraqi Ministry of Health figures is “unacceptable,” argue the signatories. These figures “are likely seriously to underestimate casualties,” as they cover only April 2004 to October 2004, include only violent …
Improved superoxide-generating ability by interferon γ due to splicing pattern change of transcripts in neutrophils from patients with a splice site mutation inCYBB gene
Authors: Fuminari Ishibashi, Tomoyuki Mizukami, Shiro Kanegasaki, Lena Motoda, Ryota Kakinuma, Fumio Endo, Hiroyuki Nunoi
Journal: Blood (2001)
Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis
Authors: Mark K Slifka, Donald Y M Leung, Erika Hammarlund, Hans-Peter Raué, Eric L Simpson, Susan Tofte, Shahana Baig-Lewis, Gloria David, Henry Lynn, Rob Woolson, Tissa Hata, Henry Milgrom, Jon Hanifin
Journal: Journal of Allergy and Clinical Immunology (2013)
Inadequate data mean UK nations are failing to learn from each other
Authors: O. Mashta
Journal: BMJ (2009)

Comparative NHS healthcare data from the four nations of the United Kingdom have been lacking since devolution, the NHS Confederation (the representative body for NHS organisations) said this week.

As a result valuable opportunities for mutual learning in the health systems of England, Wales, Scotland, and Northern Ireland are being lost, the confederation believes.

It said: “We should attempt to learn from the experiment taking place in our own backyard. Studies comparing patients’ experience in the four UK nations are remarkably scarce, and statistics are rarely published in a comparable form, yet these studies are an unprecedented opportunity to learn what happens when policy approaches diverge—an opportunity not to be missed.”

It believes that …
Katherine Beryl Worley
Authors: Anne Wiles
Journal: BMJ (2007)

Katherine Beryl Worley (“Kath”) was born near Bradford and remained in West Yorkshire until she gained her MB ChB from Leeds in 1952. She fought hard to gain and maintain a university place as a woman in the immediate postwar era, particularly as she had lost her father to septicaemia at the age of 3. This determination, inherited from …
ABC of resuscitation. Ventricular fibrillation.
Authors: D Chamberlain
Journal: BMJ (1986)

The hopeful phase: three shocks at 160J, 160J, 320J (200J, 200J, 400J). The struggling phase: three shocks at 320J (400J) after, respectively, lignocaine, adrenaline, bicarbonate. Patient intubated if possible. The desperate phase: three shocks at 320J (400J) with different electrode position or different defibrillator. While improvements will doubtless be made as skill in resuscitation increases, the guidelines can ensure that relatively few treated patients die in ventricular fibrillation and only those with irreversible myocardial damage are likely to be converted to intractible asystole.
Transesophageal Echocardiography: Useful Tool or Expensive Toy?
Authors: Clive Kearon
Journal: Annals of Internal Medicine (1998)

Letters1 November 1998Transesophageal Echocardiography: Useful Tool or Expensive Toy?Clive Kearon, PhD, FRCP(C)Clive Kearon, PhD, FRCP(C)Henderson General Hospital; Hamilton, Ontario L8V 1C3, CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-9-199811010-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The Embolism in Left Atrial Thrombi (ELAT) [1] and Stroke Prevention in Atrial Fibrillation (SPAF-III) [2] study groups recently published prospective studies that identified relations between transesophageal echocardiography (TEE) findings and risk for embolism in patients with nonvalvular atrial fibrillation. In the accompanying editorial [3], Manning and Douglas suggest that risk shown by TEE may supersede clinical risk with regard to clinical management and prognosis in patients with atrial fibrillation. However, the findings of the two original studies do not seem to justify this hypothesis.The ELAT investigators found that the clinical risk factors of hypertension, previous ...References1. Stollberger C, Chnupa P, Kronik G, Brainin M, Finsterer J, Schneider B, et al. Transesophageal echocardiography to assess embolic risk in patients with atrial fibrillation. Ann Intern Med. 1998; 128:630-8. Google Scholar2. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Ann Intern Med. 1998; 128:639-47. Google Scholar3. Manning WJ, Douglas PS. Transesophageal echocardiography and atrial fibrillation: added value or expensive toy? [Editorial] Ann Intern Med. 1998; 128:685-7. Google Scholar4. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized trials. Atrial Fibrillation Investigators. Arch Intern Med. 1994; 154:1449-57. Google Scholar5. Guyatt GH, Tugwell PX, Feeny DH, Haynes RB, Drummond M. A framework for clinical evaluation of diagnostic technologies. Can Med Assoc J. 1986; 134:587-94. Google Scholar Author, Article, and Disclosure InformationAffiliations: Henderson General Hospital; Hamilton, Ontario L8V 1C3, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1998Volume 129, Issue 9Page: 748-749KeywordsAtrial fibrillationEchocardiographyFactor analysisForecastingHypertensionMedical risk factorsProspective studiesStroke Issue Published: 1 November 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
ON ELIMINATION THROUGH THE MUCOSA OF THE URINARY BLADDER
Authors: Israel S. Kleiner
Journal: The Journal of Experimental Medicine (1913)

In a previous communication (Journal of Exper. Medicine, XIV, 274, 1911), I stated that after intravenous injections of large amounts of dextrose the intestine contained on the average 1.2 per cent. of the injected amount of destrose and in nephrectomized animals the dextrose content of the intestine reached the average of 2.2 per cent. The question arose then whether in the presence of a strong hyperglycemia, and especially after double nephrectomy, all mucous membranes are slightly permeable to this substance. The presence of measurable quantities of dextrose in the gastro-intestinal canal is no evidence for the permeability of the mucosa as such, since the mucous membrane of this organ is studded with numerous glandular structures which may readily be instrumental in the removal from the blood of substances present there in excess. In the experiments I wish to communicate here, I selected, therefore, the bladder for the study of this problem since the mucous lining of this organ is practically the only...
Compliance Is Nonlinear over Tidal Volume Irrespective of Positive End-Expiratory Pressure Level in Surfactant-Depleted Piglets
Authors: MICHAEL LICHTWARCK-ASCHOFF, GEORG MOLS, ANDERS J. HEDLUND, VOLKER KESSLER, AGNETA M. MARKSTRÖM, JOSEF GUTTMANN, GÖRAN HEDENSTIERNA, ULF H. SJÖSTRAND
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Between the lower and the upper inflection point of a quasistatic pressure–volume (PV) curve, a segment usually appears in which the PV relationship is steep and linear (i.e., compliance is high, with maximal volume change per pressure change, and is constant). Traditionally it is assumed that when positive end-expiratory pressure (PEEP) and tidal volume (V t) are titrated such that the end-inspiratory volume is positioned at this linear segment of the PV curve, compliance is constant over Vt during ongoing ventilation. The validity of this assumption was addressed in this study. In 14 surfactant-deficient piglets, PEEP was increased from 3 cm H2O to 24 cm H2O, and the compliance associated with 10 consecutive volume increments up to full Vt was determined with a modified multiple-occlusion method at the different PEEP levels. With PEEP at approximately the lower inflection point, compliance was minimal in most lungs and decreased markedly over Vt, indicating overdistension. Compliance both increased and decreased within the same breath at intermediate PEEP levels. It is concluded that a PEEP that results in constant compliance over the full Vt range is difficult to find, and cannot be derived from conventional respiratory-mechanical analyses; nor does this PEEP level coincide with maximal gas exchange.
PDK1 Deficiency in POMC-Expressing Cells Reveals FOXO1-Dependent and -Independent Pathways in Control of Energy Homeostasis and Stress Response
Authors: Bengt F. Belgardt, Andreas Husch, Eva Rother, Marianne B. Ernst, F. Thomas Wunderlich, Brigitte Hampel, Tim Klöckener, Dario Alessi, Peter Kloppenburg, Jens C. Brüning
Journal: Cell Metabolism (2008)