tbuckley/cabot-search huggingface dataset:
Increased lipolysis and its consequences on gluconeogenesis in non-insulin-dependent diabetes mellitus.
Authors: N Nurjhan, A Consoli, J Gerich
Journal: Journal of Clinical Investigation (1992)

The present studies were undertaken to determine whether lipolysis was increased in non-insulin-dependent diabetes mellitus (NIDDM) and, if so, to assess the influence of increased glycerol availability on its conversion to glucose and its contribution to the increased gluconeogenesis found in this condition. For this purpose, we infused nine subjects with NIDDM and 16 age-, weight-matched nondiabetic volunteers with [2-3H] glucose and [U-14C] glycerol and measured their rates of glucose and glycerol appearance in plasma and their rates of glycerol incorporation into plasma glucose. The rate of glycerol appearance, an index of lipolysis, was increased 1.5-fold in NIDDM subjects (2.85 +/- 0.16 vs. 1.62 +/- 0.08 mumol/kg per min, P less than 0.001). Glycerol incorporation into plasma glucose was increased threefold in NIDDM subjects (1.13 +/- 1.10 vs. 0.36 +/- 0.02 mumol/kg per min, P less than 0.01) and accounted for twice as much of hepatic glucose output (6.0 +/- 0.5 vs. 3.0 +/- 0.2%, P less than 0.001). Moreover, the percent of glycerol turnover used for gluconeogenesis (77 +/- 6 vs. 44 +/- 2, P less than 0.001) was increased in NIDDM subjects and, for a given plasma glycerol concentration, glycerol gluconeogenesis was increased more than two-fold. The only experimental variable significantly correlated with the increased glycerol gluconeogenesis after taking glycerol availability into consideration was the plasma free fatty acid concentration (r = 0.80, P less than 0.01). We, therefore, conclude that lipolysis is increased in NIDDM and, although more glycerol is thus available, increased activity of the intrahepatic pathway for conversion of glycerol into glucose, due at least in part to increased plasma free fatty acids, is the predominant mechanism responsible for enhanced glycerol gluconeogenesis. Finally, although gluconeogenesis from glycerol in NIDDM is comparable to that of alanine and about one-fourth that of lactate is terms of overall flux into glucose, glycerol is probably the most important gluconeogenic precursor in NIDDM in terms of adding new carbons to the glucose pool.
Detection of input sequences in the cerebellum: Clinical and neuroimaging aspects
Authors: P. Trillenberg, K. Wessel
Journal: Behavioral and Brain Sciences (1997)

We add evidence from functional imaging supporting the concept of activation of coronally oriented zones corresponding to parallel fibers. Braitenberg et al.'s suggestion that there is an operating mode of the cerebellum relies on the idea introduced by Eccles and refined by the concept of tidal waves which Heck found in vitro. Recent evidence from functional imaging has shown zones of activation in accordance with this model and hence provides support for Braitenberg et al.'s hypothesis from the intact and healthy human cerebellum. In a second section, we discuss vulnerability of the structures described by Braitenberg et al. with respect to slow and fast movements in the context of clinical symptoms in cerebellar disease.
Abstract 2415: TGF-ß signaling inactivation inhibits the formation of hepatocellular carcinomas induced by loss of p53
Authors: Shelli M. Morris, Ji Yeon Baek, Amanda Koszarek, Samornmas Kanngurn, Sue E. Knoblaugh, William M. Grady
Journal: Cancer Research (2011)

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most deadly forms of cancer and results from the accumulation of mutated or altered tumor suppressor genes and/or oncogenes. The tumor suppressor and oncogenes commonly affected include growth factors, receptors and downstream signaling components. Inactivation of the TGF-ß signaling pathway and mutation of TP53, the gene for p53, are common in HCCs suggesting they may cooperate in HCC formation. Thus, we assessed whether inactivation of TGF-ß signaling, by deletion of the TGF-ß receptor type II, TGFBR2, affects the formation of HCCs arising secondary to loss of p53. Aim: To determine if loss of TGFBR2 and p53 cooperate in vivo to affect HCC formation. Methods and Results: Albumin-cre (Alb-Cre) transgenic mice were crossed with mice homozygous for floxed Tgfbr2 (Tgfbr2flx/flx) and/or floxed Trp53 (Trp53flx/flx) to generate mice lacking TGFBR2 and/or p53 in the liver. Deletion of Tgfbr2 alone did not induce liver tumors, while inactivation of both Tgfbr2 and Trp53 resulted in a subset of mice (19%) that developed liver tumors by 65 weeks of age. Surprisingly, deletion of p53 alone, in the context of intact TGF-ß receptors, resulted in an increased number of mice developing tumors (38%), as well as increased morbidity (42 weeks of age). Interestingly, in both genotypes, Alb-Cre;Trp53flx/flx;Tgfbr2flx/flx and Alb-Cre;Trp53flx/flx;Tgfbr2wt/wt, the mice develop both hepatocellular carcinomas (HCC) and cholangiocarcinomas (CC), suggesting these tumors originate from a common liver stem cell population. Quantitative RT-PCR analysis of tumor and non-tumor tissue demonstrated a subset of Alb-Cre;Trp53flx/flx;Tgfbr2wt/wt (p53 null) tumors express significantly increased levels of alpha-fetoprotein mRNA, a clinical marker for HCC. Additionally, tumors from the Alb-Cre;Trp53flx/flx;Tgfbr2wt/wt displayed increased TGFβ-1 protein levels as compared to tumors from Trp53 and Tgfbr2 null mice. Furthermore, increased phosphorylated ERK1/2 expression was also present in the tumors from the p53 null mice and correlated with a slight up-regulation in beta-catenin expression, another common molecular event observed in human HCC. Conclusions: The Alb-Cre;Trp53flx/flx;Tgfbr2flx/flx mouse model recapitulates many molecular features of human HCC and demonstrates that TGF-ß signaling is oncogenic in the setting of loss of p53 in the liver. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2415. doi:10.1158/1538-7445.AM2011-2415
Acellular Pertussis Vaccine Scores High in Trial
Authors: Charles Marwick
Journal: JAMA (1995)

A UNIQUE monovalent acellular pertussis vaccine composed only of detoxified pertussis toxin (toxoid) has passed its first efficacy field trial with flying colors. In a study involving nearly 3500 children, the vaccine, which had earlier undergone smaller safety and efficacy studies (<i>JAMA</i>. 1992;268:958-959), was shown to be more than 70% effective and elicited no serious adverse effects. The trial was randomized, double blind, and placebo controlled. It was conducted in Göteborg, Sweden, under the supervision of Birger Trollfors, MD, and John Taranger, MD, both of whom are professors of pediatrics at the University of Göteborg. Taranger reported the latest findings at the 95th meeting of the American Society for Microbiology, held in Washington, DC. "In the vaccinated children who did acquire pertussis, the disease was less severe and lasted for a shorter period than among nonvaccinated controls," he said. <h3>First Field Trial Results</h3> This study marks the first results in
Cancer in Primary Care
Authors: David Seamark
Journal: Journal of the Royal Society of Medicine (2004)

Edited by a general practitioner and a cancer specialist, Cancer in Primary Care aims to provide a single reference point for primary healthcare team members to access basic information necessary for holistic cancer care. Most of the text is directed to specific types of cancer, with each chapter dealing with a specific site and providing concise descriptions of incidence, pathology, diagnosis and staging and management. HIV-associated cancer is dealt with in a separate chapter. The data are up-to-date for a 2003 publication and for the most part presented in colourful and graphic format. The chapter on children's cancer is particularly helpful because the conditions are rare and usually managed in regional centres. The five-year actuarial survival curves provide an encouraging visual representation of the progress made in the treatment of childhood leukaemias and I found the table relating to common presenting signs and symptoms of childhood malignancy, with associated differential diagnoses, a useful aide-memoire. The introductory section of the book deals with organizing a cancer service and does not appear immediately relevant to a busy health professional with a specific question. I liked the chapter on managing side effects of cancer therapy, compressing a lot of data into a short readable essay. The book finishes with a comprehensive listing of information and support sources for cancer patients, which provides general national and disease-specific information with web addresses.

A subject now fraught with difficulties for the general practitioner is prostate cancer—especially with regard to the place of prostate specific antigen (PSA) estimation. I took issue with the statement that ‘men who present with prostatism should be assessed initially with digital rectal examination and PSA estimation’. This is not the consensus in the UK and such a policy, if followed blindly, can lead to a series of further investigations not necessarily in the patient's best interest. That point aside, the prostate chapter does offer a balanced discussion of the treatment options of localized and metastatic prostate cancer with recent trial results presented in an accessible manner which clarified some issues for me.

Does a book of this sort serve a useful purpose in an age of rapid change in screening technology, imaging and treatment options? Will the text be ‘dipped into’ by the primary healthcare team as the authors hope, or will the internet and nationally agreed statements be the preferred route. The long-term future, I suspect, is for such texts to be available electronically with regular updates.
Breast-milk jaundice and the pill.
Authors: D Barnardo, I Stothers, M Sharratt
Journal: BMJ (1972)

The term breast-milk jaundice was used in a previously reported (wong and wood) claim of a high indicence of jaundice in breast-fed infants whose mothers previously had taken the oral contraceptive pills.  This study selected 120 newborns from 1968-1971 clinically jaundiced during the first 10 days of life having serum bilirubin over 10 mcg/100 ml but without low birth weight illness or positive direct Coombs test.  Mothers were questioned on use of oral contraceptives: 82 replied and 82 control mothers were also questioned.  The results showed 15 mothers of jaundiced breast-fed babies used the pill; 9 mothers of jaundiced bottle-fed babies used the pill; 23 mothers of jaundiced breast-fed babies had not used the pill.  In comparison 8 mothers of nonjaundiced breast-fed babies used the pill; 12 mothers of nonjaundiced bottle-fed babies used the pill; and 25 mothers of nonjaundiced breast-fed babies had not used the pill.  These differences were not significant by the chi-square test.
Patients Who Amplify Bodily Sensations
Authors: ARTHUR J. BARSKY
Journal: Annals of Internal Medicine (1979)

Patients troubled by symptoms, regardless of the degree of demonstrable disease, are subject to forces that cause them to amplify, focus upon, and worry about these bodily perceptions. These forces are psychological, sociocultural, or part of the medical care process. Optimal management of the symptomatic and somatizing patient thus entails obtaining psychological information about emotional precipitants, relevant childhood experiences, psychiatric disorders, and the personal meaning of the symptom; searching for the somatizing personality themes of masochism and guilt, hostility, and dependence; understanding the patient's goals in obtaining medical care, such as information and explanation, psychological counseling, or social and administrative intervention; and assessing situational stress, secondary gain, and ethnic and cultural forces that foster the amplification of physical symptoms.
Thymectomy in Myasthenia Gravis
Authors: Robert S. Schwab, Earle W. Wilkins, John M. Head, Henning Pontoppidan, Henry R. Viets
Journal: JAMA (1964)

EXPERIENCE WITH THYMECTOMY for myasthenia gravis at Massachusetts General Hospital was fully described in 1960.<sup>1</sup>Since then, several changes have been made in our postoperative regimen. As a result, patients have shown a smoother and more comfortable postoperative course and mortality has been reduced. Therefore, the changes in postoperative care are worthy of record and will serve as an extension to the book. Thymectomy for myasthenia gravis has incurred a postoperative mortality of 7% to 10% during the past 15 years. In our experience, most of the complications and deaths have resulted from pulmonary complications which usually occur acutely during the first two to three days after operation. This has been manifest by copious upper respiratory secretions and weakness and inability to clear the airway, followed by inadequate gas exchange, atelectasis, and hypoxia. If untreated or compounded by intractable bronchospasm, this sequence of events has proved fatal. We feel
Relationships Between the Release and Tissue Depletion of Norepinephrine from the Heart by Guanethidine and Reserpine
Authors: DONALD C. HARRISON, CHARLES A. CHIDSEY, ROBERT GOLDMAN, EUGENE BRAUNWALD
Journal: Circulation Research (1963)

The release of norepinephrine from the heart of anesthetized open-chest dogs has been determined both after the intravenous administration of guanethidine (15 mg/kg) and after reserpine (3 mg/kg) by measuring the plasma norepinephrine concentration with the fluorometric method (THI) in bloods obtained simultaneously from the coronary sinus and femoral artery. In four dogs following the administration of guanethidine, norepinephrine release into the coronary sinus blood occurred and persisted for two to three hours. This release of norepinephrine was accompanied by and adrenergic response of similar duration. The norepinephrine content of atrial appendage was reduced by 24% of control at four hours in these dogs and to extremely low levels in three other dogs 24 hours after guanethidine administration. Thus, the reduction of the tissue content of norepinephrine continued after measurable release of norepinephrine into the coronary sinus blood had ceased. In four dogs following reserpine administration the adrenergic response was consistently smaller, and detectable release of norepinephrine into the coronary sinus blood was found transiently only in one dog. However, the norepinephrine content of atrial appendage was reduced by an average of 65% of control values at four hours. These findings suggest a difference in the mechanism of norepinephrine depletion in the period immediately after administration of guanethidine and reserpine.
Plasma biomarkers of lower gastrointestinal and liver acute GVHD
Authors: Andrew C. Harris, James L. M. Ferrara, Thomas M. Braun, Ernst Holler, Takanori Teshima, John E. Levine, Sung W. Choi, Karin Landfried, Koichi Akashi, Mark Vander Lugt, Daniel R. Couriel, Pavan Reddy, Sophie Paczesny
Journal: Blood (2012)
(12) An acne naevus
Authors: B.R. Hughes, W.J. Cunliffe
Journal: British Journal of Dermatology (1987)

Journal Article (12) An acne naevus Get access B.R. Hughes, B.R. Hughes The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar W.J. Cunliffe W.J. Cunliffe The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue s32, 1 June 1987, Pages 60–61, https://doi.org/10.1111/j.1365-2133.1987.tb12053.x Published: 01 June 1987
Micropuncture study of water, electrolytes, and urea movements along the loops of henle in psammomys
Authors: C. de Rouffignac, F. Morel
Journal: Journal of Clinical Investigation (1969)

The mechanism by which the osmotic pressure increases in tubular fluid along the descending limb of the loop of Henle was examined in Psammomys undergoing salt diuresis. In two series of experiments, micropuncture samples were collected either from proximal and distal convolutions at the surface of the cortex, or from loops of Henle and collecting ducts at the surface of the extrarenal part of the papilla. Inulin-(3)H, urea-(14)C, Na(+), and K(+) concentrations, as well as osmotic pressure, were determined in all micropuncture samples.Net movements of water along the descending and ascending limbs of the loop could not be deduced by comparing inulin data obtained from convoluted tubules and from loops of Henle, since there appeared to be a large difference in the filtration rate of the superficial glomeruli (9 nl/min) and the deep ones (21.4 nl/min) under the conditions of these experiments. The results indicate that no large net movement of water occurred along the loop since a) only 23% of the filtrate was reabsorbed along the loop of Henle (including pars recta) of superficial nephrons despite the fact that all these loops reached markedly hypertonic regions; b) there was no positive correlation between (F/P)(In) in early distal samples and the simultaneous osmotic pressure of the urine; c) when (F/P)(In) and (F/P)(Osm) in loop samples were correlated, the increase in inulin concentration accounted only for 15% of the increase in osmotic pressure. Therefore, 85% of the concentrating process taking place along the descending limb must have resulted from net addition of solutes; this was directly supported by Na(+) and K(+) measurements in the loop samples, which showed that, at the tip of the loops, the Na(+) and K(+) flow rates were correlated to the osmotic pressure. Moreover, since the load of Na(+) urea flow rate in superficial early distal tubules was constant and independent of the urinary osmotic pressure, it is suggested that a medullary recycling of both ions occurred between ascending and descending limbs.Urea-(14)C concentration in the loop samples indicates a net addition of urea into the descending limb; the mean and K(+) delivered to the distal superficial tubules was 4.18 times its filtration rate, suggesting a recycling of urea from collecting ducts to Henle's loops. The permeability properties of the wall of the thin descending limb are discussed in relation to the obtained results.
AB0545 Magnetic resonance imaging of the hands and knees in patients with inflammatory bowel disease and arthralgia – a pilot study
Authors: L. Brakenhoff, W. Stomp, F. van Gaalen, H. Fidder, J. Bloem, D. van der Heijde, M. Reijnierse, D. Hommes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Arthralgia (joint pain without clinical synovitis) frequently occurs in patients with inflammatory bowel disease (IBD), resulting in a reduced quality of life compared to those without arthralgia [ref]. The underlying cause of arthralgia in IBD is unknown. <h3>Objectives</h3> To assess whether subclinical inflammatory changes can be detected on MRI in patients with IBD and arthralgia. <h3>Methods</h3> In this pilot study, painful hand (MCP, PIP and/or DIP) or knee joints, with continuous pain for more than 6 weeks, were scanned on a 1.5T extremity MRI in 15 IBD patients (12 Crohn’s disease and 3 ulcerative colitis) between 18 and 45 years of age. In addition, the same joints were scanned in a control group of 15 IBD patients without joint pain who were matched for type and disease duration of IBD, gender and age. All patients were clinically examined by a rheumatologist for the presence of pain and absence of arthritis. MR imaging was performed according to a standard arthritis protocol with intravenous contrast administration on the same day of the clinical examination. MR images blinded for clinical information were evaluated by two readers in consensus for the presence of joint fluid, synovitis, tenosynovitis, enthesitis, erosions, cartilage defects and bone marrow edema. <h3>Results</h3> The mean age was 37.7 ± 5.4 years for IBD patients with arthralgia and 39.3 ± 5.3 years for the controls. MR imaging of the hand, either both MCP 2-5 and PIP 2-5 or PIP 2-5 and DIP 2-5 joints, was performed in 11 patients and matched controls, MRI of the knee in 4 patients and matched controls. In total 57 joints, 53 hand joints and 4 knee joints, were evaluated in both groups. Enthesitis was seen in three hand joints (MCP 2, MCP 3, PIP 3) of 2/11 (18%) arthralgia patients and in none of the control group (p=0.48). A small amount of subchondral bone-marrow edema was seen in the metacarpal head of two controls. In one (25%) patient with knee arthralgia, joint fluid and synovitis was appreciated, no abnormalities were observed in the matched controls (p=1.00). <h3>Conclusions</h3> Synovitis was present in one IBD patient with knee arthralgia and enthesitis in two IBD patients with hand arthralgia on MRI. However, this was not statistically significant different from non-painful joints of IBD patients without arthralgia. <h3>References</h3> Palm O et al. J Rheumatol 2005;32:1755-9 <h3>Disclosure of Interest</h3> None Declared
Physiological Transport Forces Govern Drug Distribution for Stent-Based Delivery
Authors: Chao-Wei Hwang, David Wu, Elazer R. Edelman
Journal: Circulation (2001)

Background The first compounds considered for stent-based delivery, such as heparin, were chosen on the basis of promising tissue culture and animal experiments, and yet they have failed to stop restenosis clinically. More recent compounds, such as paclitaxel, are of a different sort, being hydrophobic in nature, and their effects after local release seem far more profound. This dichotomy raises the question of whether drugs that have an effect when released from a stent do so because of differences in biology or differences in physicochemical properties and targeting. Methods and Results We applied continuum pharmacokinetics to examine the effects of transport forces and device geometry on the distribution of stent-delivered hydrophilic and hydrophobic drugs. We found that stent-based delivery invariably leads to large concentration gradients, with drug concentrations ranging from nil to several times the mean tissue concentration over a few micrometers. Concentration variations were a function of the Peclet number (Pe), the ratio of convective to diffusive forces. Although hydrophobic drugs exhibited greater variability than hydrophilic drugs, they achieved higher mean concentrations and remained closer to the intima. Inhomogeneous strut placement influenced hydrophilic drugs more negatively than hydrophobic drugs, dramatically affecting local concentrations without changing mean concentrations. Conclusions Because local concentrations and gradients are inextricably linked to biological effect, our results provide a potential explanation for the variable success of stent-based delivery. We conclude that mere proximity of delivery devices to tissues does not ensure adequate targeting, because physiological transport forces cause local concentrations to deviate significantly from mean concentrations.