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https://www.readbyqxmd.com/read/28818358/black-toenail-sign-in-melas-syndrome
#1
Matthew T Whitehead, Michael Wien, Bonmyong Lee, Nancy Bass, Andrea Gropman
BACKGROUND: Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder often causing progressive brain injury that is not confined to large arterial territories. Severe insults ultimately lead to gyral necrosis affecting the cortex and juxtacortical white matter; the neuroimaging correlate is partial gyral signal suppression on T2/FLAIR sequences that resemble black toenails. We aimed to characterize the imaging features and the natural history of MELAS-related gyral necrosis...
July 12, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28816632/the-liver-circadian-clock-modulates-biochemical-and-physiological-responses-to-metformin
#2
Emma Henriksson, Anne-Laure Huber, Erin K Soto, Anna Kriebs, Megan E Vaughan, Drew Duglan, Alanna B Chan, Stephanie J Papp, Madelena Nguyen, Megan E Afetian, Katja A Lamia
Metformin is widely used in the treatment of type 2 diabetes to lower blood glucose. Although metformin is a relatively safe and effective drug, its clinical efficacy is variable and under certain circumstances it may contribute to life-threatening lactic acidosis. Thus, additional understanding of metformin pharmacokinetics and pharmacodynamics could provide important information regarding therapeutic use of this widely prescribed drug. Here we report a significant effect of time of day on acute blood glucose reduction in response to metformin administration and on blood lactate levels in healthy mice...
August 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28811861/importance-of-distinguishing-between-mitochondrial-encephalomyopathy-with-elderly-onset-of-stroke-like-episodes-and-cerebral-infarction
#3
Syuichi Tetsuka, Asako Tagawa, Tomoko Ogawa, Mieko Otsuka, Ritsuo Hashimoto, Hiroyuki Kato
The most common disease-causing mitochondrial DNA (mtDNA) mutation in mitochondrial encephalomyopathy (ME) with lactic acidosis and stroke-like episodes (MELAS) is m.3243A>G. In the future, the incidence of patients with cerebral infarction and diabetes mellitus is expected to increase tremendously. Additionally, the A3243G mutation typical of diabetes is estimated to be present in approximately 2% of all diabetes patients, which suggests that the potential disease population with a mitochondrial disorder is greater than previously thought, and there may have been many cases among the elderly that were misdiagnosed...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28804536/combined-respiratory-chain-deficiency-and-uqcc2-mutations-in-neonatal-encephalomyopathy-defective-supercomplex-assembly-in-complex-iii-deficiencies
#4
René G Feichtinger, Michaela Brunner-Krainz, Bader Alhaddad, Saskia B Wortmann, Reka Kovacs-Nagy, Tatjana Stojakovic, Wolfgang Erwa, Bernhard Resch, Werner Windischhofer, Sarah Verheyen, Sabine Uhrig, Christian Windpassinger, Felix Locker, Christine Makowski, Tim M Strom, Thomas Meitinger, Holger Prokisch, Wolfgang Sperl, Tobias B Haack, Johannes A Mayr
Vertebrate respiratory chain complex III consists of eleven subunits. Mutations in five subunits either mitochondrial (MT-CYB) or nuclear (CYC1, UQCRC2, UQCRB, and UQCRQ) encoded have been reported. Defects in five further factors for assembly (TTC19, UQCC2, and UQCC3) or iron-sulphur cluster loading (BCS1L and LYRM7) cause complex III deficiency. Here, we report a second patient with UQCC2 deficiency. This girl was born prematurely; pregnancy was complicated by intrauterine growth retardation and oligohydramnios...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28798316/the-proton-sensing-g-protein-coupled-receptor-t-cell-death-associated-gene-8-tdag8-shows-cardioprotective-effects-against-myocardial-infarction
#5
Akiomi Nagasaka, Chihiro Mogi, Hiroki Ono, Toshihide Nishi, Yuma Horii, Yuki Ohba, Koichi Sato, Michio Nakaya, Fumikazu Okajima, Hitoshi Kurose
Myocardial infarction (MI) is an ischaemic heart condition caused by the occlusion of coronary arteries. Following MI, lactic acid from anaerobic glycolysis increases and infiltrating immune cells produce severe inflammation, which leads to acidosis in the ischaemic heart. However, the physiological implication of this pH reduction remains largely unknown. T-cell death-associated gene 8 (TDAG8) is a proton-sensing G protein-coupled receptor found on cardiac macrophages that recognise increases in extracellular protons...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797958/quantification-of-paracetamol-and-5-oxoproline-in-serum-by-capillary-electrophoresis-implication-for-clinical-toxicology
#6
Tomáš Hložek, Tomáš Křížek, Petr Tůma, Miroslava Bursová, Pavel Coufal, Radomír Čabala
High anion gap metabolic acidosis frequently complicates acute paracetamol overdose and is generally attributed to lactic acidosis or compromised hepatic function. However, metabolic acidosis can also be caused by organic acid 5-oxoproline (pyroglutamic acid). Paracetamol's toxic intermediate, N-acetyl-p-benzoquinoneimine irreversibly binds to glutathione and its depletion leads to subsequent disruption of the gamma glutamyl cycle and an excessive 5-oxoproline generation. This is undoubtedly an underdiagnosed condition because measurement of serum 5-oxoproline level is not readily available...
July 26, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28789699/oral-pyridoxine-can-substitute-for-intravenous-pyridoxine-in-managing-patients-with-severe-poisoning-with-isoniazid-and-rifampicin-fixed-dose-combination-tablets-a-case-report
#7
M D S A Dilrukshi, C A P Ratnayake, C A Gnanathasan
BACKGROUND: Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka...
August 8, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28776081/metformin-historical-overview
#8
EDITORIAL
Clifford J Bailey
Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28774273/thrombotic-microangiopathy-associated-with-valproic-acid-toxicity
#9
Sean A Hebert, Timothy P Bohan, Christian L Erikson, Rita D Swinford
BACKGROUND: Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA...
August 3, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28762753/migraine-in-mitochondrial-disorders-prevalence-and-characteristics
#10
Catello Vollono, Guido Primiano, Giacomo Della Marca, Anna Losurdo, Serenella Servidei
Background Migraine is a well-known feature of mitochondrial disorders (MDs). However, no systematic epidemiological data are available in large populations of patients. Aims The aim of this cross-sectional cohort study was to describe the prevalence and migraine characteristics in a large cohort of patients with mitochondrial encephalomyopathies. Methods We studied 93 consecutive patients with characterised MDs referred to our Neuromuscular Unit during a 12-month period. All patients (age range = 16-78 years; 31 men; 58 progressive external ophthalmoplegia [PEO], 12 myoclonic epilepsy with ragged red fibres [MERRF], eight mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes [MELAS], two mitochondrial neurogastrointestinal encephalomyopathy [MNGIE] and 13 other MDs) underwent a structured diagnostic headache interview using an operational diagnostic tool following the IHS criteria...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28761217/metformin-use-in-practice-compliance-with-guidelines-for-patients-with-diabetes-and-preserved-renal-function
#11
Gregory J Salber, Yu-Bo Wang, John T Lynch, Karen M Pasquale, Thiruchandurai V Rajan, Richard G Stevens, James J Grady, Anne M Kenny
IN BRIEF Several contraindications limit the use of metformin, most notably the risk of lactic acidosis. This article reports on an examination of a population of patients with diabetes with preserved renal function to evaluate provider compliance with guidelines on metformin use and to identify factors that contributed when practice diverged from recommendations. It found that metformin was withheld from approximately one-third of these patients because of 1) an existent contraindication to metformin, 2) patient behavior or preference, or 3) provider preference or bias based on patient or personal factors...
July 2017: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/28749752/high-anion-gap-metabolic-acidosis-induced-by-cumulation-of-ketones-l-and-d-lactate-5-oxoproline-and-acute-renal-failure
#12
Laura Heireman, Boris Mahieu, Mark Helbert, Wim Uyttenbroeck, Jan Stroobants, Marian Piqueur
INTRODUCTION: Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed. CASE PRESENTATION: A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus, underwent gastric bypass surgery in the past and was chronically treated with high doses of paracetamol and fosfomycin...
July 27, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28748724/acid-base-and-electrolyte-disorders-associated-with-the-use-of-antidiabetic-drugs
#13
Theodosios Filippatos, Eleftheria Tzavella, Christos Rizos, Moses Elisaf, George Liamis
The use of antidiabetic drugs is expected to substantially increase since diabetes mellitus incidence rises. Currently used antidiabetic drugs have a positive safety profile, but they are associated with certain acid-base and electrolyte abnormalities. The aim of the review is to present the current data regarding the antidiabetic drugs-associated acid-base and electrolyte abnormalities. Areas covered: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been linked with the scarce, but serious, complication of euglycemic diabetic ketoacidosis, as well as with an increase in serum potassium, magnesium and phosphorus levels...
August 4, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28748471/evaluation-of-mitochondrial-respiration-in-cultured-rat-hepatocytes
#14
Jean-Pierre Marchandeau, Gilles Labbe
Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28746158/lactate-serum-concentrations-during-treatment-with-nucleos-t-ide-analogues-in-hepatitis-b-with-or-without-cirrhosis
#15
Christos Triantos, Maria Kalafateli, Ioanna Aggeletopoulou, Martha Mandellou, Stelios Assimakopoulos, Paraskevi Tselekouni, Dimitra Taprantzi, Giorgos Tsiaoussis, Georgia Vourli, Evangelos D Anastassiou, Charalambos Gogos, Chrisoula Labropoulou-Karatza, Konstantinos Thomopoulos
OBJECTIVE: The aim of this study is to evaluate the clinical implications of lactate concentrations in patients with hepatitis B with or without cirrhosis during treatment with nucleos(t)ide analogues. PATIENTS AND METHODS: One hundred and seven consecutive patients with chronic hepatitis B and median age 57 (24-85) years were prospectively included. Lactate concentrations were measured at baseline and at 12, 24, 36, 48, and 60 months following the baseline measurements...
September 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28737598/epidemiology-and-outcomes-of-cardiac-arrest-in-pediatric-cardiac-icus
#16
Jeffrey A Alten, Darren Klugman, Tia T Raymond, David S Cooper, Janet E Donohue, Wenying Zhang, Sara K Pasquali, Michael G Gaies
OBJECTIVES: In-hospital cardiac arrest occurs in 2.6-6% of children with cardiac disease and is associated with significant morbidity and mortality. Much remains unknown about cardiac arrest in pediatric cardiac ICUs; therefore, we aimed to describe cardiac arrest epidemiology in a contemporary multicenter cardiac ICU cohort. DESIGN: Retrospective analysis within the Pediatric Cardiac Critical Care Consortium clinical registry. SETTING: Cardiac ICUs within 23 North American hospitals...
July 21, 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/28736735/arginine-and-citrulline-for-the-treatment-of-melas-syndrome
#17
Ayman W El-Hattab, Mohammed Almannai, Fernando Scaglia
MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO) deficiency occurs in MELAS syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS syndrome...
January 2017: Journal of Inborn Errors of Metabolism and Screening
https://www.readbyqxmd.com/read/28736433/diabetes-mellitus-complex-interplay-between-metformin-aki-and-lactic-acidosis
#18
Connie M Rhee, Kamyar Kalantar-Zadeh
No abstract text is available yet for this article.
September 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28736054/low-sensitivity-of-anion-gap-to-detect-clinically-significant-lactic-acidosis-in-the-emergency-department
#19
Q Xu, S HowlettClyne, A Fuezery, G S Cembrowski
INTRODUCTION: Lactic acidosis represents the pathologic accumulation of lactate and hydrogen ions. It is important to efficiently diagnose lactic acidosis as delayed treatment will lead to poor patient outcomes. As plasma lactate levels may not be rapidly available, some physicians may use elevated anion gaps to test for the need to measure lactate. All Edmonton metropolitan hospitals have Radiometer blood gas/electrolyte instruments in the ED or close by. As lactate is measured for each set of electrolytes, we were able to determine the effectiveness of a screening anion gap for lactic acidosis...
July 20, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28722461/-disorders-of-water-and-electrolyte-metabolism-and-changes-in-acid-base-balance-in-patients-with-ascitic-liver-cirrhosis
#20
Halima Gottfriedová, Miroslava Horáčková, Milena Čáslavská, Julius Špičák, Otto Schück
In patients with advanced cirrhosis with ascites disorders of water and electrolyte metabolism are often present and they are associated with changes in acid-base balance. These changes can be very complicated, their diagnosis and treatment difficult. Dilutional hyponatremia is the most common disorder. Hyponatremia in these patients is associated with increased morbidity and mortality before and after liver transplantation. Other common disorders include hyperchloremic acidosis, hypokalemia, metabolic alkalosis, lactic acidosis, respiratory alkalosis...
2017: Casopís Lékar̆ů C̆eských
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