tbuckley/cabot-search huggingface dataset:
S139 A Paradoxical Rise In Rectus Femoris Myostatin (gdf-8) And Gdf-15 In Response To Neuromuscular Electrical Stimulation In Critical Care
Authors: S. Bloch, T. Syburrah, U. Rosendahl, P. Kemp, M. Griffiths, M. Polkey
Journal: Thorax (2014)

<h3>Introduction</h3> Neuromuscular electrical stimulation (NMES) is widely used in rehabilitation and muscle disease. Recently there is increasing interest in its use as a prevention and treatment for intensive care unit acquired weakness (ICUAW). ICUAW is a common and often devastating disease resulting as a consequence of critical illness. The molecular mechanisms are not understood, however early mobilisation and rehabilitation are to date the most effective treatments. NMES has been shown to help prevent muscle wasting in some clinical studies in the ICU setting, however the evidence is inconclusive. We hypothesised that the NMES of a single leg in critical care patients would be associated with reduced muscle wasting and down regulation of molecular pathways involved in muscle breakdown. Specifically myostatin (GDF-8), a potent negative regulator of muscle mass, and GDF-15, a potential novel driver of muscle atropy. <h3>Methods</h3> We conducted a single-blinded, single leg, contralateral controlled trial of NMES in patients admitted to a specialist cardiothoracic ICU. Patients were recruited prior to elective high-risk cardiac surgery or during ICU admission. Baseline bilateral rectus femoris cross sectional area (RF<sub>csa</sub>) was measured by ultrasound and rectus femoris biopsies were taken. 2 × 1 hour sessions of NMES were then conducted for 1 week and ultrasound and biopsies were repeated. Biopsy specimens were examined for mRNA expression of genes of interest and results analysed in paired analysis relative to baseline. (NCT01321320). <h3>Results</h3> 12 patients completed the study protocol. Myostatin and GDF-15 mRNA expression were both significantly elevated in NMES legs compared to baseline (p = 0.03 and p = 0.04 respectively), but remained unchanged in control legs. There was no significant change in RF<sub>csa</sub>. <h3>Discussion</h3> It is believed that NMES will have beneficial effects in the ICU setting in terms of preservation of muscle function. However it is recognised to also have potential to cause muscle damage. In the setting of sedated patients who cannot report pain or those in whom the nutritional and metabolic status of the muscle may be expected to be poor, researchers should be aware that NMES may promote muscle breakdown.
The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin
Authors: Bernd Greiner, Michel Eichelbaum, Peter Fritz, Hans-Peter Kreichgauer, Oliver von Richter, Johannes Zundler, Heyo K. Kroemer
Journal: Journal of Clinical Investigation (1999)

Recent data point to the contribution of P-glycoprotein (P-gp) to digoxin elimination. On the basis of clinical observations of patients in whom digoxin levels decreased considerably when treated with rifampin, we hypothesized that concomitant rifampin therapy may affect digoxin disposition in humans by induction of P-gp. We compared single-dose (1 mg oral and 1 mg intravenous) pharmacokinetics of digoxin before and after coadministration of rifampin (600 mg/d for 10 days) in 8 healthy volunteers. Duodenal biopsies were obtained from each volunteer before and after administration of rifampin. The area under the plasma concentration time curve (AUC) of oral digoxin was significantly lower during rifampin treatment; the effect was less pronounced after intravenous administration of digoxin. Renal clearance and half-life of digoxin were not altered by rifampin. Rifampin treatment increased intestinal P-gp content 3.5 ± 2.1–fold, which correlated with the AUC after oral digoxin but not after intravenous digoxin. P-gp is a determinant of the disposition of digoxin. Concomitant administration of rifampin reduced digoxin plasma concentrations substantially after oral administration but to a lesser extent after intravenous administration. The rifampin-digoxin interaction appears to occur largely at the level of the intestine. Therefore, induction of intestinal P-gp could explain this new type of drug-drug interaction.
The three-year incidence of fracture in chronic kidney disease
Authors: Kyla L. Naylor, Eric McArthur, William D. Leslie, Lisa-Ann Fraser, Sophie A. Jamal, Suzanne M. Cadarette, Jennie G. Pouget, Charmaine E. Lok, Anthony B. Hodsman, Jonathan D. Adachi, Amit X. Garg
Journal: Kidney International (2014)
The ε Subtype of Protein Kinase C Is Required for Cardiomyocyte Connexin-43 Phosphorylation
Authors: Bradley W. Doble, Peipei Ping, Elissavet Kardami
Journal: Circulation Research (2000)

Abstract —Gap junctions (GJs), composed of connexins, are intercellular channels ensuring electric and metabolic coupling between cardiomyocytes. We have shown previously that an endogenous mitogenic and cardioprotective protein, fibroblast growth factor-2 (FGF-2), decreases cardiomyocyte GJ permeability by stimulating phosphorylation of connexin-43 (Cx43). Identifying the kinase(s) phosphorylating cardiac Cx43 may thus provide a way of modulating cardiac intercellular communication. Because FGF-2 activates receptors linked to protein kinase C (PKC) and mitogen-activated protein kinase, we first investigated participation of these enzymatic systems in Cx43 phosphorylation. The inhibitor PD98059 blocked activation of mitogen-activated protein kinase, but it did not prevent the FGF-2 effects on GJs. In contrast, the PKC inhibitor chelerythrine blocked the effects of FGF-2 on Cx43 phosphorylation and permeability. Because the ε-isoform of PKC localizes to plasma membrane sites, we examined whether it is directly involved in the FGF-2–induced Cx43 phosphorylation. In nonstimulated myocytes, PKCε displayed a discontinuous pattern of localization at intercellular contact sites and partial colocalization with Cx43. Treatment with FGF-2 or phorbol 12-myristate 13-acetate induced a more continuous pattern of PKCε distribution, whereas the anti-Cx43 staining appeared to overlap extensively with that of PKCε. In immunoprecipitation experiments using specific anti-Cx43 antibodies, PKCε but not PKCα coprecipitated with Cx43. FGF-2 increased levels of coprecipitated PKCε, suggesting increased association between PKCε and Cx43 on stimulation. Transient gene transfer and overexpression of cDNAs coding for truncated or mutated dominant-negative forms of PKCε decreased cardiomyocyte Cx43 phosphorylation significantly. We conclude that PKC mediates the FGF-2–induced effects on cardiac GJs and that PKCε likely interacts with and phosphorylates cardiac Cx43 at sites of intercellular contact.
Willingness-to-pay and quality of life in patients with vitiligo
Authors: M.A. Radtke, I. Schäfer, A. Gajur, A. Langenbruch, M. Augustin
Journal: British Journal of Dermatology (2009)

Vitiligo is a chronic pigmentary disorder of the skin, affecting 1-2% of the general population. Although not life threatening, vitiligo may considerably influence patients' health-related quality of life (QoL) and psychological well-being. Willingness-to-pay (WTP) is a construct reflecting disease burden and QoL reduction which has not yet been used in vitiligo.To assess the WTP and the QoL of patients with vitiligo.Patients with vitiligo were included in a nationwide German postal survey. WTP was assessed by two standardized items, and QoL was evaluated using the Dermatology Life Quality Index (DLQI) and the EuroQol (EQ-5D) questionnaire. QoL data were compared with n = 1,511 patients from a national survey on psoriasis.The questionnaire was completed by 1,023 patients (71.5% women, mean age 44.4 years, mean disease duration 20.3 years) with vitiligo. The mean DLQI was 7.0 (7.5 in women, 5.5 in men) compared with 8.6 in psoriasis. Of the patients with vitiligo, 24.6% had a DLQI > 10 which indicates severe QoL reductions, compared with 34.1% in patients with psoriasis. The highest mean DLQI value was observed in the patient group aged 20-29 years. EQ-5D mean score was 83.6 compared with 75.3 in psoriasis. Of the patients with vitiligo, 32.9% would pay more than 5,000 Euro in order to achieve complete disease remission. WTP was highest among middle-aged patients (30-60 years). There was a significant correlation between DLQI scores and WTP (chi(2) = 65.43, P < 0.001). Moreover, WTP significantly correlated with duration of disease, and with body surface area affected (P < 0.001).Vitiligo causes substantial disease burden as reflected by QoL impairment and high WTP, especially in women. These results should draw the attention of physicians to this disease, as appropriate education and treatment are likely to improve the QoL of patients with vitiligo and may support patients' compliance and empowerment.
"LATERAL CURVATURE OF THE SPINE IN PERINEPHRITIC ABSCESS"
Authors: John R. Carty
Journal: JAMA (1928)

To the Editor:  —I have read the articles by Drs. Philip J. Lipsett and Edwin Beer inThe Journal, April 28, in which they describe a lateral curvature of the spine in perinephritic abscess and state that a search of the literature has failed to reveal any previously published communication regarding this sign. In an article entitled The Diagnostic Significance of Lateral Curvature of the Spine Caused by Muscular Spasm published, Sept. 30, 1926, in the Boston Medical and Surgical Journal , I called attention to this sign, which also occurs in other pathologic conditions of the kidney, and called it spasmodic scoliosis. In December, 1925, an extensive study was undertaken with the assistance of Dr. H. M. Imboden, professor of roentgenology at the Cornell Medical College, which resulted in the foregoing publication.
Prevention and Treatment of Influenza
Authors: Robert B. Couch
Journal: New England Journal of Medicine (2000)

Influenza is a disease known since antiquity that continues to afflict large numbers of people and cause many deaths throughout the world. The annual epidemic and the continued threat of a pandemic constitute a major infectious-disease problem.18 Although the prevention of the spread of virus by ill persons and the removal of virus in transit in the environment could theoretically contribute to the control of influenza, effective control requires the optimal use of vaccines and antiviral drugs. At present, a vaccine and four antiviral drugs are approved in the United States and many other countries for the prevention and . . .
Procainamide-Induced Lupus Erythematosus
Authors: Anthony T. Ladd
Journal: New England Journal of Medicine (1962)

THERE have been several reports of "allergy" or "reactions" to procainamide hydrochloride in which fever,1 , 2 chills,3 malaise, headache,4 skin rashes,5 muscle pains, arthralgias,6 generalized lymphadenopathy, leukopenia7 and eosinophilia are described, each appearing either singly or in various combinations as manifestations of the drug sensitivity. According to these reports, all the symptoms or signs of "reaction to procainamide" listed above subsided quite rapidly after the medication was withdrawn. I have been unable to uncover evidence of polyserositis, arteritis or proteinuria or the occurrence of a positive lupus-cell preparation in any of the aforementioned reports. The following case supports the thesis that . . .
Health effects of fossil fuel combustion products: report of a workshop.
Authors: C L Comar, N Nelson
Journal: Environmental Health Perspectives (1975)

Judgemental positions are presented on research priorities in regard to the health effects from stationary sources of fossil fuel combustion products. Hopefully, they can provide guidance for efforts to ensure that national energy needs are met with minimum environmental and economic burdens on the public. The major areas include epidemiological studies, controlled biological studies, mutagenesis and carcinogenesis, trace elements, monitoring and analysis.
Evolution of α2-Fucosyltransferase Genes in Primates: Relation Between an Intronic Alu-Y Element and Red Cell Expression of ABH Antigens
Authors: Pol-André Apoil, Francis Roubinet, Stéphanie Despiau, Rosella Mollicone, Rafael Oriol, Antoine Blancher
Journal: Molecular Biology and Evolution (2000)

Coding sequences of the paralogous FUT1 (H), FUT2 (Se), and Sec1 alpha 2-fucosyltransferase genes were obtained from different primate species. Analysis of the primate FUT1-like and FUT2-like sequences revealed the absence of the known human inactivating mutations giving rise to the h null alleles of FUT1 and the se null alleles of FUT2. Therefore, most primate FUT1-like and FUT2-like genes potentially code for functional enzymes. The Sec1-like gene encodes for a potentially functional alpha 2-fucosyltransferase enzyme in nonprimate mammals, New World monkeys, and Old World monkeys, but it has been inactivated by a nonsense mutation at codon 325 in the ancestor of humans and African apes (gorillas, chimpanzees). Human and gorilla Sec1's have, in addition, two deletions and one insertion, respectively, 5' of the nonsense mutation leading to proteins shorter than chimpanzee Sec1. Phylogenetic analysis of the available H, Se, and Sec1 mammalian protein sequences demonstrates the existence of three clusters which correspond to the three genes. This suggests that the differentiation of the three genes is rather old and predates the great mammalian radiation. The phylogenetic analysis also suggests that Sec1 has a higher evolutionary rate than FUT2 and FUT1. Finally, we show that an Alu-Y element was inserted in intron 1 of the FUT1 ancestor of humans and apes (chimpanzees, gorillas, orangutans, and gibbons); this Alu-Y element has not been found in monkeys or nonprimate mammals, which lack ABH antigens on red cells. A potential mechanism leading to the red cell expression of the H enzyme in primates, related to the insertion of this Alu-Y sequence, is proposed.
Cardiovascular Disease Risk Prediction Factors
Authors: Allan D. Sniderman, Curt D. Furberg
Journal: JAMA (2012)

To the Editor: The Emerging Risk Factors Collaboration (ERFC) reported on the addition of lipid-related markers to total cholesterol and high-density lipoprotein cholesterol (HDL-C) in the prediction of cardiovascular disease. We attempted to replicate the findings of eTable 1, which summarized the 26 studies that compared apolipoprotein B with the cholesterol markers. Many discrepancies with the primary publications were found. First, 4 eligible studies, including the Framingham Offspring Study, were not included. Second, 5 studies did not meet the entry criteria, which included approved definitions and recording of both fatal and nonfatal cardiovascular events. The Whitehall I study recorded only fatal ischemic heart disease and so should not have been eligible. Yet strokes were listed in eTable 1 even though they were not a protocol outcome. Third, in 19 of the 26 studies, the number of participants differed substantially between eTable 1 and the primary publication. In 14 studies, there were fewer participants whereas in 5 studies, there were more participants. For example, the ERFC study listed 1293 patients for the Quebec Cardiovascular Study vs the actual tally of 2072. The ERFC study listed 23 175 for the Women’s Health Study vs 15 632 in the primary report. Fourth, the values for apolipoprotein B in 4 study reports differed substantially from those given by the ERFC and neither the methods to measure apolipoprotein B nor the results were given in 4 other studies. Furthermore, in at least 2 studies, apolipoprotein B was measured many years after collection with no documentation of adequate sample preservation. Fifth, the methods and results of 11 studies have not been recorded in the public domain. We assume there are reasonable explanations for the discrepancies but, even so, the ERFC publication is difficult to reconcile with the primary material. Given the apparent deficiencies and discrepancies, the validity of the ERFC findings and their recommendations need to be reexamined. Additional details are available from the author on request.
The other war
Authors: R. Kirk
Journal: BMJ (2003)

We live in extraordinary times. I work in Singapore, which is one of the countries that has so far been hardest hit by severe acute respiratory syndrome (SARS). Only six weeks ago I was worrying about flight schedules for conferences, planning our family vacation in China, and looking forward to our Easter visitors—now such activities seem trivial and our visitors, rightly, have stayed away.

What has been the impact on our daily lives? In short SARS has affected every aspect—work, home, and social. At the hospital all entrances except the main one are sealed off and the admittance procedure is comparable to that of a high security prison. Visitors are only allowed through once they have made their purpose clear and their identity details, and contact, travel, and health information have been recorded. Their temperatures are taken and they are issued with masks. Corridors and outpatient areas usually bustling with patients, visitors, and staff are eerily empty. Entry to any patient area is through a triage desk …
THE CLINICAL RELEVANCE OF THE SIMPLIFIED PULMONARY VASCULAR RESISTANCE TO SYSTEMIC VASCULAR RESISTANCE RATIO USING THE TRANSPULMONARY AND TRANSSYSTEMIC PRESSURE GRADIENTS AND QP/QS RATIO IN PATIENTS WITH PULMONARY HYPERTENSION
Authors: Cihangir Kaymaz, Tugba Aktemur, Nertila Poci, Selcuk Ozturk, Ozgur Y Akbal, Fatih Yilmaz, Hacer Ceren Tokgoz, Ibrahim Halil Tanboga, Nihal Ozdemir
Journal: Journal of the American College of Cardiology (2014)
O38 PREDICTORS OF TERLIPRESSIN RELATED ADVERSE EFFECTS IN LIVER CIRRHOSIS AND ITS INFLUENCE ON SURVIVAL
Authors: A.K. Choudhury, C.K. Kedarisetty, P. Wagle, H. Garg, C. Chitranshu, R. Maiwall, S.K. Sarin
Journal: Journal of Hepatology (2014)
Human Liver Plasma Membrane Ca–Atpase: Identification and Sensitivity to Calcium Antagonists
Authors: Sophie Lotersztajn, Philippe Mavier, Jeanne Clergue, Daniel Dhumeaux, Françoise Pecker
Journal: Hepatology (1982)

A high–affinity calcium–stimulated ATPase (Ca–ATPase) was identified in a plasma membrane subcellular fraction from human liver. The subcellular distribution of the enzyme corresponds to that of classical plasma membrane markers, and its kinetic parameters are identical to those of the Ca–ATPase identified in rat liver plasma membranes in that: (i) calcium activation of ATPase activity followed a cooperative mechanism (Hill number = 1.2), half–maximal activation occurring at 4.5 ± 2.0 nm free calcium; (ii) K 0.5 of the enzyme for ATP was 54 ± 5 μ M , and kinetic studies indicated that two interacting sites were involved; (iii) micromolar concentrations of MgCl 2 had an inhibitory effect on enzyme activity, and (iv) the enzyme did not require potassium for activation by calcium and was not sensitive to ouabain or oligomycin. These properties are characteristic of Ca–ATPases coupled to calcium pumps in plasma membranes. The effects of the local anesthetic, tetracaine, and three calcium antagonists bepridil, verapamil, nifedipine, were investigated. Bepridil at 50 μ M caused 75% inhibition of Ca–ATPase activity by decreasing the maximal velocity of the enzyme reaction; its action was immediate and reversible. Verapamil (0.5 μ M ) also induced 75% inhibition of the Ca–ATPase, but its affinity for the system was a third of that of bepridil. The enzyme was much less sensitive to nifedipine and tetracaine. The method described in the present paper for measuring Ca–ATPase activity in small human liver biopsies will permit the study of this enzyme during the course of hepatic disorders.
A Test for Patency of the Cystic Duct in Acute Cholecystitis
Authors: Edward A. Eikman, John L. Cameron, Martin Colman, T. K. Natarajan, Paul Dugal, Henry N. Wagner
Journal: Annals of Internal Medicine (1975)

A procedure was devised to quickly and reliably determine the patency of the cystic duct in patients suspected of having acute cholecystitis. First the gallbladder was stimulated to empty by a cholecystokinin injection. Thirty minutes later a radiolabeled biliary marker, either 150 µCi 131I rose bengal or 2 mCi 99mTc dihydrothioctic acid, was injected, and the accumulation of radioactivity in the liver and gallbladder regions was monitored by external gamma emission imaging and recording devices. The images of diagnostic importance were obtained between 60 and 90 minutes after injection of the tracer. Thirty-nine patients with acute abdominal pain were studied. Ten patients who had acute cholecystitis failed to show gallbladder accumulation of radioactivity, reflecting the cystic duct obstruction that initiates this disease. Twenty-nine patients having a variety of other diseases all showed gallbladder accumulation of activity, indicating in each patient that the cystic duct was patent. No significant adverse effects were noted. We conclude that the procedure is a useful adjunct to the clinical and roentgenographic evaluation of patients with acute abdominal pain.
Myopathy and Metabolic Bone Disease.
Authors: Gerald Stern
Journal: Annals of Internal Medicine (1968)

s1 May 1968Myopathy and Metabolic Bone Disease.Gerald Stern, M.R.C.P., Roger Smith, M.R.C.P.Gerald Stern, M.R.C.P.Search for more papers by this author, Roger Smith, M.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1190_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA retrospective clinical and biochemical study of 136 patients with metabolic bone disease has shown that 6 out of 91 patients with primary hyperparathyroidism and at least 20 out of 45 patients with osteomalacia developed remediable proximal muscle weakness. Myopathy may occur as a presenting complaint in the absence of symptoms or signs of bone disease and may deceptively simulate primary muscular disorders. Proximal muscular weakness was independent of plasma calcium and electrolyte concentrations. The rarity of focal weakness in uncomplicated primary hyperparathyroidism and the much more common association with osteomalacia is stressed; it is suggested that the presence of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: London, PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1190-1191KeywordsBlood plasmaBoneCalciumHyperparathyroidismMetabolic disordersMusclesMuscular diseasesMuscular weaknessRetrospective studiesSigns and symptoms Issue Published: 1 May 1968 PDF DownloadLoading ...