Science.gov

Sample records for myoglobinuria

  1. Mitochondrial anomalies in a Swiss family with autosomal dominant myoglobinuria

    SciTech Connect

    Martin-du Pan, R.C.; Favre, H.; Junod, A.

    1997-04-14

    We report on a Swiss family in which 10 individuals of both sexes in 4 successive generations suffered from myoglobinuria, precipitated by febrile illness. It is the second family described with autosomal dominant inheritance of myoglobinuria. Four individuals suffered acute renal failure, which in two was reversible only after dialysis. In a recent case, a mitochondrial disorder was suspected because of an abnormal increase in lactate levels during an exercise test and because of a subsarcolemmal accumulation of mitochondria in a muscle biopsy, associated with a lack of cytochrome C oxidase in some muscle fibers. No mutation in the mitochondrial DNA was identified. Along with the inheritance pattern, these findings suggest that the myoglobinuria in this family is caused by a nuclear-encoded mutation affecting the respiratory chain. 22 refs., 2 figs.

  2. Myoglobinuria with acute renal failure and hot kidneys seen on bone imaging

    SciTech Connect

    Sheth, K.J.; Sty, J.R.; Johnson, F.; Tisdale, P.

    1984-09-01

    We report a case of myoglobinuria secondary to prolonged seizures. The child showed ''hot kidneys'' with bone scintigraphy. The disease entity and etiologies of nontraumatic rhabdomyolysis are discussed.

  3. Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood.

    PubMed

    Zeharia, Avraham; Shaag, Avraham; Houtkooper, Riekelt H; Hindi, Tareq; de Lonlay, Pascale; Erez, Gilli; Hubert, Laurence; Saada, Ann; de Keyzer, Yves; Eshel, Gideon; Vaz, Frédéric M; Pines, Ophry; Elpeleg, Orly

    2008-10-01

    Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2-7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. Of six individuals who developed statin-induced myopathy, one was a carrier for Glu769Gly, a pathogenic mutation in the LPIN1 gene. Analysis of phospholipid content disclosed accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the more severe genotype. Mutations in the LPIN1 gene cause recurrent rhabdomyolysis in childhood, and a carrier state may predispose for statin-induced myopathy.

  4. Rhabdomyolysis and acute kidney injury after acupuncture sessions.

    PubMed

    Papasotiriou, Marios; Betsi, Grigoria; Tsironi, Maria; Assimakopoulos, Georgios

    2014-05-01

    Rhabdomyolysis is usually caused by muscle injury, drugs or alcohol and presents with muscle weakness and pain. It is characterized by rise in serum creatine kinase, aminotransferases and electrolytes as well as myoglobinuria. Myoglobinuria may cause acute kidney injury by direct proximal tubule cytotoxicity, renal vasoconstriction, intraluminal cast formation and distal tubule obstruction. Muscle pain and weakness as well as vascular injury have been reported after acupuncture. We report a case of severe rhabdomyolysis and acute kidney injury after acupuncture sessions.

  5. Case Report: Red Urine After Day Care Strabismus Surgery.

    PubMed

    Caroline, Pregardien; Marie-Cécile, Nassogne; Demet, Yuksel; Francis, Veyckemans

    2017-02-15

    In the absence of surgery on the urinary tract, the emission of red urine after anesthesia should be considered as a diagnostic emergency because it can be a sign of hematuria, hemoglobinuria, blood transfusion reaction, significant myoglobinuria, or porphyria.This case describes the management of a 12-year-old boy who presented red urine at the day care unit after strabismus surgery.

  6. Endpoint measures in the mdx mouse relevant for muscular dystrophy pre-clinical studies

    PubMed Central

    Kobayashi, Yvonne M.; Rader, Erik P.; Crawford, Robert W.; Campbell, Kevin P.

    2011-01-01

    Loss of mobility influences the quality of life for patients with neuromuscular diseases. Common measures of mobility and chronic muscle damage are the six-minute walk test and serum creatine kinase. Despite extensive pre-clinical studies of therapeutic approaches, characterization of these measures is incomplete. To address this, a six-minute ambulation assay, serum creatine kinase, and myoglobinuria were investigated for the mdx mouse, a dystrophinopathy mouse model commonly used in pre-clinical studies. Mdx mice ambulated shorter distances than normal controls, a disparity accentuated after mild exercise. An asymmetric pathophysiology in mdx mice was unmasked with exercise, and peak measurements of serum creatine kinase and myoglobinuria were identified. Our data highlights the necessity to consider asymmetric pathology and timing of biomarkers when testing potential therapies for muscular dystrophy. PMID:22154712

  7. Severe Fever with Thrombocytopenia Syndrome Presenting with Rhabdomyolysis

    PubMed Central

    Hong, Sang-Bum; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness. While many kinds of severe complications including acute renal failure have been reported, rhabdomyolysis is rarely reported in association with SFTS. A 54-year-old female farmer was admitted with fever and diffuse myalgia. Laboratory finding showed thrombocytopenia, leukopenia, azotemia, extremely elevated muscle enzyme levels and myoglobinuria. We describe a fatal case of rhabdomyolysis with acute renal failure complicated by SFTS. PMID:28271645

  8. "Abdominal crunch"-induced rhabdomyolysis presenting as right upper quadrant pain.

    PubMed

    Haas, D C; Bohnker, B K

    1999-02-01

    A young, active duty sailor presented with right upper quadrant abdominal pain. History, physical, and laboratory findings initially suggested cholecystitis or related disease. Further evaluation found myoglobinuria and a recently increased exercise program, leading to the diagnosis of exercise-induced right upper abdominal wall rhabdomyolysis. Although not a common cause of abdominal pain, this diagnosis should be considered in the patient with abdominal pain and a recently increased exercise program, particularly exercises of the abdominal wall such as "abdominal crunches."

  9. Toxicity in Rhesus Monkeys Following Administration of the 8-Aminoquinoline 8-[(4-amino-l-methylbutyl)amino]-5(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511)

    DTIC Science & Technology

    2008-09-01

    Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with...arteriolar fibin thrombi. Pathology interpretation The histopathological results strongly suggest that the lesions in the liver and kidney of both...x100) (Animal 7). Figure 6: Kidney with tubular epithelial degeneration and necrosis, and intratubular cellular, granular, or hemoglobin casts

  10. Severe rhabdomyolysis without renal injury associated with lightning strike.

    PubMed

    Navarrete, Norberto; Aldana, Norberto Navarrete

    2013-01-01

    Lightning strikes cause injuries in multiple systems and organs. Early recognition of lightning injury syndromes and anticipation of harmful complications can improve outcomes for these patients. The author has presented a case report of a patient who was struck by lightning and exhibited extensive soft tissue injury with myoglobinuria. He was treated with delayed fasciotomy and had evidence of severe muscle injury with markedly elevated creatine kinase levels that gradually improved with aggressive fluid infusion. The patient did not require alkalinization of urine, mannitol, or dialysis, and his renal function remained normal.

  11. PubMed Central

    Dallaire, M; Chamberland, M

    1994-01-01

    Combinations of lovastatin and other drugs have been reported to cause rhabdomyolysis and myoglobinuria. The authors report such a case in a 72-year-old man who had been receiving atenolol, acetylsalicylic acid (ASA), dipyridamole, lovastatin, danazol, prednisone and doxycycline. The ASA, lovastatin and danazol were discontinued. The symptoms resolved, and laboratory test results were normal within 2 weeks. Lovastatin was strongly suspected; danazol was the most likely potentiator by diminishing the metabolism of lovastatin and its metabolites in the liver or by having a direct toxic effect on the muscles. PMID:8199978

  12. [Rhabdomyolysis in a well-trained woman after unusually intense exercise].

    PubMed

    Larsen, Christian; Jensen, Mogens Pfeiffer

    2014-06-16

    A 35-year-old woman was acutely hospitalized with oedema of the upper limbs, reduced force, severe movement reduction and muscle pain in both upper extremities. Her symptoms started after three days of intense exercise doing kayaking and a lot of pull-ups in crossfit. Rhabdomyolysis is a syndrome, characterized by muscle necrosis. Usually there is a marked elevation of creatine kinase (CK) concentration with symptoms as described and myoglobinuria (dark coloured urine). After hard muscular work there will often be asymptomatic, but significant elevations in CK concentration, and in rare cases life-threatening rhabdomyolysis with electrolyte imbalances and acute kidney failure.

  13. Factors in delayed muscle soreness.

    PubMed

    Abraham, W M

    1977-01-01

    The possible causes of delayed muscle soreness which occur 24 to 48 hr after exercise were examined from three different approaches, each designed to test an existing hypothesis. Surface electromyograms were used to evaluate the muscle spasm theory; the possibility of actual muscle cell damage was monitored by the presence of myoglobinuria, while the ratio of hydroxyproline/creatinine (OHP/Cr) in 24 hr urine collection was used as a marker for connective tissue involvement. In the first study, although all volunteers developed muscle soreness 24 and 48 hr after exercise, no change in the EMG activity of the sore muscles was observed. Myoglobin excretion was found in 88% of the subjects who developed soreness. However, in a second study, 92% of the subject who performed both moderate and heavy exercise but did not develop muscle soreness had myoglobinuria. In contrast, during a third experiment subjects on gelatin-free diets showed an increase (P less than .1) in the OHP/Cr between control (.020+/-.001) and 48 hr post-exercise (.002+/-.001, X+/-SE). Soreness resulted in all cases. When the OHP/Cr value is taken for the day of maximal soreness, the post-exercise mean increases to .024+/-.001 and the level of significance rises (P less than .005). These observations support the concept that exercise induced soreness may be related to disruption of the connective tissue elements in the muscle and/or their attachments.

  14. Rhabdomyolysis and Cardiomyopathy in a 20-Year-Old Patient with CPT II Deficiency

    PubMed Central

    Vavlukis, M.; Eftimov, A.; Zafirovska, P.; Caparovska, E.; Pocesta, B.; Kedev, S.; Dimovski, A. J.

    2014-01-01

    Aim. To raise the awareness of adult-onset carnitite palmitoyltransferase II deficiency (CPT II) by describing clinical, biochemical, and genetic features of the disease occurring in early adulthood. Method. Review of the case characteristics and literature review. Results. We report on a 20-year-old man presenting with dyspnea, fatigue, fever, and myoglobinuria. This was the second episode with such symptoms (the previous one being three years earlier). The symptoms occurred after intense physical work, followed by a viral infection resulting in fever treated with NSAIDs. Massive rhabdomyolysis was diagnosed, resulting in acute renal failure necessitating plasmapheresis and hemodialysis, acute hepatic lesion, and respiratory insufficiency. Additionally, our patient had cardiomyopathy with volume overload. After a detailed workup, CPT II deficiency was suspected. We did a sequencing analysis for exons 1, 3, and 4 of the CPT II gene and found that the patient was homozygote for Ser 113 Leu mutation in exon 3 of the CPT II gene. The patient recovery was complete except for the cardiomiopathy with mildly impaired systolic function. Conclusion. Whenever a patient suffers recurrent episodes of myalgia, followed by myoglobinuria due to rhabdomyolysis, we should always consider the possibility of this rare condition. The definitive diagnose of this condition is achieved by genetic testing. PMID:24563797

  15. Familial combined deficiency of muscle carnitine and carnitine palmityl transferase (CPT).

    PubMed

    Skard Heier, M; Dietrichson, P; Landaas, S

    1986-12-01

    Two patients, brother and sister, aged 19 and 16, with combined, partial deficiency of carnitine palmityltransferase (CPT) are reported. Both patients had recurrent exercise-related myoglobinuria. The brother had also experienced an episode of transient renal failure associated with myoglobinuria. Both had elevated CK and myoglobin in plasma between attacks. There was a normal production of lactate in ischaemic forearm exercise, but elevated levels of NH3, resulting in an increased NH3/lactate ratio; 48-h fasting caused no significant changes in cholesterol, triglycerides or glucose, no rise of CK, and a normal ketogenic response, indicating no hepatic enzyme deficiency. Muscle biopsy showed slight changes of myopathy in both patients, with scattered atrophic fibres, but no lipid accumulation or other specific changes. Biochemical analysis of muscle tissue revealed a reduction of carnitine to 48% and 40% and a reduction of CPT to 55% and 59% of normal values, which is similar to the findings in the only previous report of combined partial carnitine and CPT deficiency. The heterogeneity of the laboratory findings in CPT deficiencies and the value of the various diagnostic procedures in metabolic myopathies are discussed.

  16. [McArdle disease presenting with rhabdomyolisis and acute kidney injury].

    PubMed

    Costa, Rui; Castro, Rui; Costa, Alexandre; Taipa, Ricardo; Vizcaíno, Ramon; Morgado, Teresa

    2013-01-01

    McArdle disease typically presents in childhood or young adults with myalgia, exercise intolerance, cramps and myoglobinuria. Deficiency of myophosphorylase enzyme results in inability to degrade glycogen stores, causing glycogen accumulation in muscle tissue and energy deficit. Evolution with rhabdomiolysis may occur and can be complicated with acute kidney injury but rarely, in about 11% of cases, is the initial disease manifestation. We report a case of McArdle Disease in a 38-year-old male patient. The disease went unrecognized despite previous symptoms (myalgia, exercise intolerance and single myoglobinuria episode) until an episode of rhabdomyolisis complicated with oliguric acute kidney injury requiring hemodialysis. The kidney biopsy showed evidence of acute tubular necrosis. Despite normalization of renal function, muscle lysis markers remained abnormal. Metabolic myopathy was suspected and a muscle biopsy was performed. It showed subsarcolemic glycogen deposition and absence of myophosphorylase activity. This case-report underlines the importance of considering metabolic myopathy in patients with acute kidney injury and severe rhabdomyolisis.

  17. Inborn Errors of Energy Metabolism Associated with Myopathies

    PubMed Central

    Das, Anibh M.; Steuerwald, Ulrike; Illsinger, Sabine

    2010-01-01

    Inherited neuromuscular disorders affect approximately one in 3,500 children. Structural muscular defects are most common; however functional impairment of skeletal and cardiac muscle in both children and adults may be caused by inborn errors of energy metabolism as well. Patients suffering from metabolic myopathies due to compromised energy metabolism may present with exercise intolerance, muscle pain, reversible or progressive muscle weakness, and myoglobinuria. In this review, the physiology of energy metabolism in muscle is described, followed by the presentation of distinct disorders affecting skeletal and cardiac muscle: glycogen storage diseases types III, V, VII, fatty acid oxidation defects, and respiratory chain defects (i.e., mitochondriopathies). The diagnostic work-up and therapeutic options in these disorders are discussed. PMID:20589068

  18. A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia.

    PubMed

    Mamoune, Asmaa; Bahuau, Michel; Hamel, Yamina; Serre, Valérie; Pelosi, Michele; Habarou, Florence; Nguyen Morel, Marie-Ange; Boisson, Bertrand; Vergnaud, Sabrina; Viou, Mai Thao; Nonnenmacher, Luc; Piraud, Monique; Nusbaum, Patrick; Vamecq, Joseph; Romero, Norma; Ottolenghi, Chris; Casanova, Jean-Laurent; de Lonlay, Pascale

    2014-11-01

    Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease.

  19. Acute renal failure following massive attack by Africanized bee stings.

    PubMed

    Bresolin, Nilzete L; Carvalho, Lígia C; Goes, Eduardo C; Fernandes, Regina; Barotto, Adriana M

    2002-08-01

    Bee venom is a complex substance, which acts in several tissues. Although severe allergic reactions have occurred after one or more stings, several deaths have been reported without allergic manifestations, emphasizing the toxic effects of massive poisoning. A number of about 500 stings have been considered necessary to cause death by direct toxicity, but as few as 30-50 stings have proved fatal in children. Among the major toxic effects are hemolytic anemia, acute renal failure (ARF), and shock. ARF may be due to a common toxic-ischemic mechanism with hypovolemic or anaphylactic shock, pigment tubulopathy (myoglobinuria and hemoglobinuria), or acute tubular necrosis (ATN) from a direct kidney toxicity of the venom. We present a case of rhabdomyolysis and hemolysis with consequent ARF which developed after about 800 bee stings. The patient recovered completely after peritoneal dialysis.

  20. Clinical protocol for the management of malignant hyperthermia.

    PubMed

    Kollmann-Camaiora, A; Alsina, E; Domínguez, A; Del Blanco, B; Yepes, M J; Guerrero, J L; García, A

    2017-01-01

    Malignant hyperthermia is a hypermetabolic syndrome that appears in susceptible patients after exposure to certain anaesthetic drugs (succinylcholine, inhalation anaesthetics). Its incidence in Spain is 1 in 40,000 adults, with a 10% mortality rate. It is induced by an abnormal regulation of the ryanodine receptors, producing a massive release of calcium from the sarcoplasmic reticulum in the striate muscle. Clinical manifestations include: CO2 increase, tachycardia, haemodynamic instability, metabolic and respiratory acidosis, profuse sweating, hyperpyrexia, CPK increase, myoglobinuria, kidney failure, disseminated intravascular coagulation (DIC), and ending in cardiac arrest. Dantrolene sodium is a ryanodine receptor antagonist, and inhibits the release of intracellular calcium. Definitive diagnosis is achieved by the exposure of muscle fibres to caffeine and halothane. Protocols can help guarantee a reliable and secure management when this severe event occurs.

  1. A Thermolabile Aldolase A Mutant Causes Fever-Induced Recurrent Rhabdomyolysis without Hemolytic Anemia

    PubMed Central

    Mamoune, Asmaa; Bahuau, Michel; Hamel, Yamina; Serre, Valérie; Pelosi, Michele; Habarou, Florence; Nguyen Morel, Marie-Ange; Boisson, Bertrand; Vergnaud, Sabrina; Viou, Mai Thao; Nonnenmacher, Luc; Piraud, Monique; Nusbaum, Patrick; Vamecq, Joseph; Romero, Norma; Ottolenghi, Chris; Casanova, Jean-Laurent; de Lonlay, Pascale

    2014-01-01

    Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease. PMID:25392908

  2. Spinning Out of Control: A 19-Year-Old Female with Spinning-Related Exertional Thigh Compartment Syndrome

    PubMed Central

    Gould, Daniel J; Han, Sukgu; Wong, Alex K

    2016-01-01

    Thigh compartment syndrome (TCS) is a rare condition caused by high pressures within the fascial compartments of the thigh, impeding capillary flow and leading to decreased perfusion, tissue hypoxia, and necrosis. TCS is most frequently associated with trauma and anticoagulation but has also rarely been associated with exercise-related injury. We present the case of a 19-year-old female who reported painful swelling in her thighs and darkening of her urine after participating in a spinning class. On physical examination, the patient was found to have tight, painful thigh compartments with extreme tenderness on passive motion. Labs revealed a marked elevation of creatine kinase and leukocytosis. The patient was diagnosed with TCS and underwent emergent decompression fasciotomy and aggressive IV fluids for protection against myoglobinuria. Due to high clinical suspicion, prompt diagnosis, and early surgery, the patient experienced excellent recovery without functional deficits.  PMID:28123920

  3. McArdle disease: a case report and review

    PubMed Central

    Leite, Alberto; Oliveira, Narciso; Rocha, Manuela

    2012-01-01

    McArdle disease (glycogen storage disease type V) is a pure myopathy caused by an inherited deficit of myophosphorylase. The disease exhibits clinical heterogeneity, but patients typically experience exercise intolerance, acute crises of early fatigue, and contractures, sometimes with rhabdomyolysis and myoglobinuria, triggered by static muscle contractions or dynamic exercise. We present the case of a 54-year-old man with a lifelong history of fatigability, worsening on exertion. Laboratory evaluation revealed significant elevations in levels of creatine kinase (7924 U/L), lactate dehydrogenase (624 U/L), and myoglobulin (671 ng/mL). A muscle biopsy confirmed the presence of McArdle disease. This case report illustrates how, due to embarrassment, the patient hid his symptoms for many years and was eventually extremely relieved and “liberated” once McArdle disease was diagnosed 40 years later. PMID:23754915

  4. McArdle Disease Misdiagnosed as Meningitis

    PubMed Central

    Scalco, Renata Siciliani; Chatfield, Sherryl; Junejo, Muhammad Hyder; Booth, Suzanne; Pattni, Jatin; Godfrey, Richard; Quinlivan, Ros

    2016-01-01

    Patient: Female, 44 Final Diagnosis: McArdle disease Symptoms: Exercise intolerance • muscle contracture • myalgia • myoglobinuria • recurrent rhabdomyolysis Medication: — Clinical Procedure: — Specialty: Neurology Objective: Rare disease Background: McArdle disease is a glycogen storage disorder mainly characterized by exercise intolerance. Prolonged muscle contracture is also a feature of this condition and may lead to rhabdomyolysis (RM), which is a serious event characterized by acute skeletal muscle damage. Case Report: A 44-year-old female patient presented with an acute contracture of the posterior neck muscles, causing severe nuchal rigidity. The contracture was induced during a dental extraction as she held her mouth open for a prolonged period, with her neck in a rigid position. She presented with severe pain in her ear and head, as well as fever, vomiting, and confusion. Based on her symptoms, she was initially misdiagnosed with bacterial meningitis and experienced an acute allergic reaction to the systemic penicillin she was subsequently administered. Lumbar puncture results were normal. High serum creatine kinase (CK) levels, recurrent exercise-related muscle symptoms, and a previous history of recurrent myoglobinuria raised the suspicion of an underlying neuromuscular condition. McArdle disease was confirmed by muscle biopsy and a genetic test, which revealed that the patient was homozygous for the R50X mutation in the PYGM gene. Conclusions: This case illustrates that even seemingly innocuous movements, if rapid isotonic or prolonged isometric in nature, can elicit a muscle contracture in McArdle disease patients. Here, we highlight the need for careful management in this patient population even during routine healthcare procedures. The allergic reaction to antibiotics emphasises that misdiagnoses may result in iatrogenic harm. PMID:27899787

  5. Unveiling the Metabolic Changes on Muscle Cell Metabolism Underlying p-Phenylenediamine Toxicity

    PubMed Central

    Marín de Mas, Igor; Marín, Silvia; Pachón, Gisela; Rodríguez-Prados, Juan C.; Vizán, Pedro; Centelles, Josep J.; Tauler, Romà; Azqueta, Amaya; Selivanov, Vitaly; López de Ceraín, Adela; Cascante, Marta

    2017-01-01

    Rhabdomyolysis is a disorder characterized by acute damage of the sarcolemma of the skeletal muscle leading to release of potentially toxic muscle cell components into the circulation, most notably creatine phosphokinase (CK) and myoglobulin, and is frequently accompanied by myoglobinuria. In the present work, we evaluated the toxicity of p-phenylenediamine (PPD), a main component of hair dyes which is reported to induce rhabdomyolysis. We studied the metabolic effect of this compound in vivo with Wistar rats and in vitro with C2C12 muscle cells. To this aim we have combined multi-omic experimental measurements with computational approaches using model-driven methods. The integrative study presented here has unveiled the metabolic disorders associated to PPD exposure that may underlay the aberrant metabolism observed in rhabdomyolys disease. Animals treated with lower doses of PPD (10 and 20 mg/kg) showed depressed activity and myoglobinuria after 10 h of treatment. We measured the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) in rats after 24, 48, and 72 h of PPD exposure. At all times, treatment with PPD at higher doses (40 and 60 mg/kg) showed an increase of AST and ALT, and also an increase of lactate dehydrogenase (LDH) and CK after 24 h. Blood packed cell volume and hemoglobin levels, as well as organs weight at 48 and 72 h, were also measured. No significant differences were observed in these parameters under any condition. PPD induce cell cycle arrest in S phase and apoptosis (40% or early apoptotic cells) on mus musculus mouse C2C12 cells after 24 h of treatment. Incubation of mus musculus mouse C2C12 cells with [1,2-13C2]-glucose during 24 h, subsequent quantification of 13C isotopologues distribution in key metabolites of glucose metabolic network and a computational fluxomic analysis using in-house developed software (Isodyn) showed that PPD is inhibiting glycolysis, non-oxidative pentose

  6. Unveiling the Metabolic Changes on Muscle Cell Metabolism Underlying p-Phenylenediamine Toxicity.

    PubMed

    Marín de Mas, Igor; Marín, Silvia; Pachón, Gisela; Rodríguez-Prados, Juan C; Vizán, Pedro; Centelles, Josep J; Tauler, Romà; Azqueta, Amaya; Selivanov, Vitaly; López de Ceraín, Adela; Cascante, Marta

    2017-01-01

    Rhabdomyolysis is a disorder characterized by acute damage of the sarcolemma of the skeletal muscle leading to release of potentially toxic muscle cell components into the circulation, most notably creatine phosphokinase (CK) and myoglobulin, and is frequently accompanied by myoglobinuria. In the present work, we evaluated the toxicity of p-phenylenediamine (PPD), a main component of hair dyes which is reported to induce rhabdomyolysis. We studied the metabolic effect of this compound in vivo with Wistar rats and in vitro with C2C12 muscle cells. To this aim we have combined multi-omic experimental measurements with computational approaches using model-driven methods. The integrative study presented here has unveiled the metabolic disorders associated to PPD exposure that may underlay the aberrant metabolism observed in rhabdomyolys disease. Animals treated with lower doses of PPD (10 and 20 mg/kg) showed depressed activity and myoglobinuria after 10 h of treatment. We measured the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) in rats after 24, 48, and 72 h of PPD exposure. At all times, treatment with PPD at higher doses (40 and 60 mg/kg) showed an increase of AST and ALT, and also an increase of lactate dehydrogenase (LDH) and CK after 24 h. Blood packed cell volume and hemoglobin levels, as well as organs weight at 48 and 72 h, were also measured. No significant differences were observed in these parameters under any condition. PPD induce cell cycle arrest in S phase and apoptosis (40% or early apoptotic cells) on mus musculus mouse C2C12 cells after 24 h of treatment. Incubation of mus musculus mouse C2C12 cells with [1,2-(13)C2]-glucose during 24 h, subsequent quantification of (13)C isotopologues distribution in key metabolites of glucose metabolic network and a computational fluxomic analysis using in-house developed software (Isodyn) showed that PPD is inhibiting glycolysis, non-oxidative pentose

  7. Influence of the Environment on Body Temperature of Racing Greyhounds

    PubMed Central

    McNicholl, Jane; Howarth, Gordon S.; Hazel, Susan J.

    2016-01-01

    Heat strain is a potential risk factor for racing greyhounds in hot climates. However, there have been limited studies into the incidence of heat strain (when excess heat causes physiological or pathological effects) in racing greyhounds. The aim of this study was to determine if heat strain occurs in racing greyhounds, and, if so, whether environmental factors (e.g., ambient temperature and relative humidity) or dog-related factors (e.g., sex, bodyweight, color) are associated with the risk of heat strain. A total of 229 greyhounds were included in over 46 race meetings and seven different race venues in South Australia, Australia. Rectal temperatures of dogs were measured pre- and postrace and urine samples collected for analysis of myoglobinuria. Ambient temperature at race times ranged between 11.0 and 40.8°C and relative humidity ranged from 17 to 92%. There was a mean increase in greyhound rectal temperature of 2.1°C (range 1.1–3.1°C). A small but significant association was present between ambient temperature and increase in rectal temperature (r2 = 0.033, P = 0.007). The mean ambient temperature at race time, of dogs with postrace rectal temperature of or exceeding 41.5°C, was significantly greater than at race time of dogs with a postrace rectal temperature ≤41.5°C (31.2 vs. 27.3°C, respectively, P = 0.004). When the ambient temperature reached 38oC, over one-third (39%) of dogs had a rectal temperature >41.5°C. Over half of postrace urine samples were positive by Dipstick reading for hemoglobin/myoglobin, and of 77 urine samples positive for Dipstick readings, 95% were positive for myoglobin. However, urinary myoglobin levels were not associated with ambient temperature or postrace rectal temperatures. The mean increase in rectal temperature was greater in dark (black, blue, brindle) than light (fawn and white) colored greyhounds. The results suggest heat strain occurs in racing greyhounds, evidenced by postrace rectal temperatures

  8. A diagnostic algorithm for metabolic myopathies.

    PubMed

    Berardo, Andres; DiMauro, Salvatore; Hirano, Michio

    2010-03-01

    Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1). Fig. 1 Clinical algorithm for patients with exercise intolerance in whom a metabolic myopathy is suspected. CK-creatine kinase; COX-cytochrome c oxidase; CPT-carnitine palmitoyl transferase; cyt b-cytochrome b; mtDNA-mitochondrial DNA; nDNA-nuclear DNA; PFK-phosphofructokinase; PGAM-phosphoglycerate mutase; PGK-phosphoglycerate kinase; PPL-myophosphorylase; RRF-ragged red fibers; TFP-trifunctional protein deficiency; VLCAD-very long-chain acyl-coenzyme A dehydrogenase.

  9. Paraphenylenediamine Containing Hair Dye: An Emerging Household Poisoning.

    PubMed

    Patra, Ambika Prasad; Shaha, Kusa Kumar; Rayamane, Anand P; Dash, Shreemanta Kumar; Mohanty, Manoj Kumar; Mohanty, Sachidananda

    2015-09-01

    Paraphenylenediamine poisoning is among one of the emerging causes of poisoning in Asian countries, because it is a constituent of hair dye formulations and is easily available in market at low cost. Hair dyes are rampantly used in Asian households compared with the western world. Locally, hair dye constituents may have allergic adverse effects, and acute systemic poisoning presents with characteristic angioedema, upper airway obstruction, rhabdomyolysis, methemoglobinemia, myoglobinuria, and acute renal failure. This study reports about the death of a 24-year-old Indian housewife who committed suicide by taking hair dye emulsion. She had an argument with her husband, and because of fit of rage, took a bowlful (80 mL) of hair dye emulsion kept prepared for the use by husband. She developed angioedema, cervical swelling, and rhabdomyolysis and died of acute renal failure within 24 hours. Toxicological analysis of viscera and blood revealed varying levels of paraphenylenediamine. Histopathological samples of kidney showed features of acute tubular necrosis and myoglobin casts in renal tubules. The aim of the study is to create awareness about the adverse effects of the hair dye, its poisoning outcome, and possible preventive measures.

  10. Rhabdomyolysis and respiratory failure: rare presentation of carnitine palmityl-transferase II deficiency.

    PubMed

    Gentili, A; Iannella, E; Masciopinto, F; Latrofa, M E; Giuntoli, L; Baroncini, S

    2008-05-01

    Carnitine palmityl-transferase (CPT) II deficiency is a rare disorder of the fatty acid beta-oxidation cycle. CPT II deficiency can be associated with rhabdomyolysis in particular conditions that increase the requirement for fatty acid oxidation, such as low-carbohydrate and high-fat diet, fasting, exposure to excessive cold, lack of sleep and prolonged exercise. The best known CPT II deficiency is the muscular form with episodic muscle necrosis and paroxysmal myoglobinuria after prolonged exercise. We report a case of a four-year-old male child, who, after one day of hyperthermia and fasting, developed a massive rhabdomyolysis beginning with acute respiratory failure and later complicated by acute renal failure. Appropriate management in Pediatric Intensive Care Unit (PICU) (mechanical ventilatory support, fluid supply combined with mannitol and bicarbonate infusions, administration of acetaminophen and antibiotics, and continuous venovenous haemofiltration) brought about complete resolution with an excellent outcome. Biochemical investigation of muscle biopsy and genetic analysis showed a deficiency of CPT II. The onset of CPT II deficiency with respiratory failure is extremely rare, but a correct and early diagnosis of rhabdomyolysis is the key to successful treatment. A metabolic myopathy such as CPT II deficiency should be suspected in children affected by rhabdomyolysis if trauma, crash, infections, drugs or extreme exertion can be excluded.

  11. [Overactive muscles: it can be more serious than common myalgia or cramp].

    PubMed

    Molenaar, Joery P F; Snoeck, Marc M J; Voermans, Nicol C; van Engelen, Baziel G M

    2016-01-01

    Positive muscle phenomena are due to muscle overactivity. Examples are cramp, myalgia, and stiffness. These manifestations have mostly acquired causes, e.g. side-effects of medication, metabolic disorders, vitamin deficiency, excessive caffeine intake or neurogenic disorders. We report on three patients with various positive muscle phenomena, to illustrate the clinical signs that indicate an underlying myopathy. Patient A, a 56-year-old man, was diagnosed with muscle cramp in the context of excessive coffee use and previous lumbosacral radiculopathy. Patient B, a 71-year-old man, was shown to have RYR1-related myopathy. Patient C, a 42-year-old man, suffered from Brody myopathy. We propose for clinicians to look out for a number of 'red flags' that can point to an underlying myopathy, and call for referral to neurology if indicated. Red flags include second wind phenomenon, familial occurrence of similar complaints, marked muscle stiffness, myotonia, muscle weakness, muscle hypertrophy, and myoglobinuria. Establishing a correct diagnosis is important for proper treatment. Certain myopathies call for cardiac or respiratory screening.

  12. [Non-infective neurologic complications associated to heroin use].

    PubMed

    Pascual Calvet, J; Pou, A; Pedro-Botet, J; Gutiérrez Cebollada, J

    1989-01-01

    The spectrum of neurological complications associated with heroin addiction has changed in the past six years because of the progressive knowledge of the neurological complications related to HIV infection. We reviewed 48 heroin addicts with neurological complications and 452 heroin overdose who were seen in the Emergency Unit of our hospital during 1988 and the publications since 1967. Regarding the overdose we present the results of a prospective study leading to determine the causes. We emphasize the relationship with the level of total morphine in serum, instead of conjugate morphine, and with the presence of high levels of benzodiazepines found in the plasma rather than an hypothetic hypersensitivity phenomenon. We resume the neurological complications related with heroin addiction: spongiform leukoencephalopathy, epileptic seizures, stroke, transverse myelopathy and neuromuscular complications such mononeuropathy, plexopathy, acute inflammatory demyelinating polyradiculoneuropathy, rhabdomyolysis, fibrosing myopathy, musculoskeletal syndrome and acute bacterial myopathy. Some of such complications (i.e. transverse myelitis, polyradiculoneuropathy, leucoencephalopathy) must rise the suspicion of an HIV infection. Likewise, in patients assisted for overdosage we believe it's necessary rule out myoglobinuria by means of CPK serum levels and detection of urine hematic pigments without red blood cels in the urine sediment, in order to prevent and treat the renal failure. We report the results of muscular biopsy found in the musculoskeletal syndrome, which are similar to those found in alcoholic myopathy. Finally, we describe the clinical and diagnostic aspects in an unusually neuromuscular complication: the acute bacterial myopathy.

  13. PubMed Central

    Logerfo, Annalisa; Simoncini, Costanza; Papi, Riccardo; Franzoni, Ferdinando; Dell'Osso, Giacomo; Servadio, Adele; Masoni, Maria Chiara

    2015-01-01

    McArdle's disease is the most common metabolic myopathy of muscle carbohydrate metabolism, due to deficiency of myophosphorylase and alteration of glycogen breakdown in muscle. The clinical manifestations usually begin in young adulthood, with exercise intolerance, exercise-induced muscle cramps, pain and recurrent episodes of myoglobinuria. Many patients experience the second wind phenomenon, characterized by an improved tolerance for aerobic exercise approximately after eight minutes of motor activity, secondary to the increased availability of blood glucose and free fatty acids associated to an enhanced glucose uptake by muscle cells. In this study, we aimed to test a multi-parametric protocol in order to detect the impairment of muscular metabolism and motor performance in patients with McArdle's disease. We enrolled 5 patients and 5 age-matched healthy subjects, that were evaluated by: (01) monitoring of physical activity with an electronic armband; (02) testing of cardiopulmonary, metabolic and respiratory responses to exercise with a cardiopulmonary exercise test and analyzing muscle fatigue during exercise test by surface electromyography (04) evaluating blood lactate and oxidative stress biomarkers at rest and during exercise. The patients were tested at baseline and after three days of carbohydrate-rich diet integrated with tricarboxylic acid cycle intermediate and creatine. The multiparametric protocol proved to be useful to detect the oxidative capacity impairment and the second wind phenomenon of patients. We did not observe any significant differences of muscle metabolic response during the exercise test after three days of carbohydrate-rich diet. PMID:27199539

  14. Coexistence of VHL Disease and CPT2 Deficiency: A Case Report

    PubMed Central

    Ferrara, Alfonso Massimiliano; Sciacco, Monica; Zovato, Stefania; Rizzati, Silvia; Colombo, Irene; Boaretto, Francesca; Moggio, Maurizio; Opocher, Giuseppe

    2016-01-01

    von Hippel-Lindau (VHL) disease is an inherited syndrome manifesting with benign and malignant tumors. Deficiency of carnitine palmitoyltransferase type II (CPT2) is a disorder of lipid metabolism that, in the muscle form, manifests with recurrent attacks of myalgias often associated with myoglobinuria. Rhabdomyolytic episodes may be complicated by life-threatening events, including acute renal failure (ARF). We report on a male patient who was tested, at 10 years of age, for VHL disease because of family history of VHL. He was diagnosed with VHL but without VHL-related manifestation at the time of diagnosis. During childhood, the patient was hospitalized several times for diffuse muscular pain, muscle weakness, and dark urine. These recurrent attacks of rhabdomyolysis were never accompanied by ARF. The patient was found to be homozygous for the mutation p.S113L of the CPT2 gene. To the best of our knowledge, this is the first report of the coexistence of VHL disease and CPT2 deficiency in the same individual. Based on findings from animal models, the case illustrates that mutations in the VHL gene might protect against renal damage caused by CPT2 gene mutations. PMID:27034144

  15. Coexistence of VHL Disease and CPT2 Deficiency: A Case Report.

    PubMed

    Ferrara, Alfonso Massimiliano; Sciacco, Monica; Zovato, Stefania; Rizzati, Silvia; Colombo, Irene; Boaretto, Francesca; Moggio, Maurizio; Opocher, Giuseppe

    2016-10-01

    von Hippel-Lindau (VHL) disease is an inherited syndrome manifesting with benign and malignant tumors. Deficiency of carnitine palmitoyltransferase type II (CPT2) is a disorder of lipid metabolism that, in the muscle form, manifests with recurrent attacks of myalgias often associated with myoglobinuria. Rhabdomyolytic episodes may be complicated by life-threatening events, including acute renal failure (ARF). We report on a male patient who was tested, at 10 years of age, for VHL disease because of family history of VHL. He was diagnosed with VHL but without VHL-related manifestation at the time of diagnosis. During childhood, the patient was hospitalized several times for diffuse muscular pain, muscle weakness, and dark urine. These recurrent attacks of rhabdomyolysis were never accompanied by ARF. The patient was found to be homozygous for the mutation p.S113L of the CPT2 gene. To the best of our knowledge, this is the first report of the coexistence of VHL disease and CPT2 deficiency in the same individual. Based on findings from animal models, the case illustrates that mutations in the VHL gene might protect against renal damage caused by CPT2 gene mutations.

  16. PYGM expression analysis in white blood cells: a complementary tool for diagnosing McArdle disease?

    PubMed

    de Luna, Noemí; Brull, Astrid; Lucia, Alejandro; Santalla, Alfredo; Garatachea, Nuria; Martí, Ramon; Andreu, Antoni L; Pinós, Tomàs

    2014-12-01

    McArdle disease is caused by an inherited deficiency of the enzyme myophosphorylase, resulting in exercise intolerance from childhood and acute crises of early fatigue and contractures. In severe cases, these manifestations can be accompanied by rhabdomyolysis, myoglobinuria, and fatal renal failure. Diagnosis of McArdle disease is based on clinical diagnostic tests, together with an absence of myophosphorylase activity in skeletal muscle biopsies and genetic analysis of the myophosphorylase-encoding gene, PYGM. The recently reported association between myophosphorylase and Rac1 GTPase in a T lymphocyte cell line prompted us to study myophosphorylase expression in white blood cells (WBCs) from 20 healthy donors and 30 McArdle patients by flow cytometry using a fluorescent-labeled PYGM antibody. We found that T lymphocytes expressed myophosphorylase in healthy donors, but expression was significantly lower in McArdle patients (p<0.001). PYGM mRNA levels were also lower in white blood cells from McArdle patients. Nevertheless, in 13% of patients (who were either heterozygotes or homozygotes for the most common PYGM pathogenic mutation among Caucasians (p.R50X)), the percentage of myophosphorylase-positive white blood cells was not different compared with the control group. Our findings suggest that analysis of myophosphorylase expression in white blood cells might be a useful, less-invasive, complementary test for diagnosing McArdle disease.

  17. Diagnosis of snakebite and the importance of immunological tests in venom research.

    PubMed

    Theakston, R David G; Laing, Gavin D

    2014-05-23

    In many cases of envenoming following snake bite, the snake responsible for the accident remains unidentified; this frequently results in difficulty deciding which antivenom to administer to the systemically-envenomed victim, especially when only monospecific antivenoms are available. Normally the specific diagnosis of snake bite can be conveniently made using clinical and laboratory methods. Where clinical diagnosis depends upon the recognition of specific signs of envenoming in the patient, laboratory diagnosis is based on the changes which occur in envenomed victims including the detection of abnormalities in blood parameters, presence/absence of myoglobinuria, changes in certain enzyme levels, presence/absence of neurotoxic signs and the detection in the blood of specific venom antigens using immunologically-based techniques, such as enzyme immunoassay. It is the latter which is the main subject of this review, together with the application of techniques currently used to objectively assess the effectiveness of new and existing antivenoms, to assess first aid measures, to investigate the possible use of such methods in epidemiological studies, and to detect individual venom components. With this in mind, we have discussed in some detail how such techniques were developed and how they have helped in the treatment of envenoming particularly and in venom research in general.

  18. Methicillin-resistant Staphylococcus aureus infected gluteal compartment syndrome with rhabdomyolysis in a bodybuilder

    PubMed Central

    Woon, Colin YL; Patel, Kushal R; Goldberg, Benjamin A

    2016-01-01

    Gluteal compartment syndrome (GCS) is a rare condition. We present a case of gluteal muscle strain with hematoma formation, methicillin-resistant Staphylococcus aureus (MRSA) superinfection, leading to acute GCS, rhabdomyolysis and acute kidney injury. This combination of diagnoses has not been reported in the literature. A 36-year-old Caucasian male presented with buttock pain, swelling and fever after lifting weights. Gluteal compartment pressure was markedly elevated compared with the contralateral side. Investigations revealed elevated white blood cell, erythrocyte sedimentation rate, C-reactive protein, creatine kinase, creatinine and lactic acid. Urinalysis was consistent with myoglobinuria. Magnetic resonance imaging showed increased T2 signal in the gluteus maximus and a central hematoma. Cultures taken from the emergency debridement and fasciotomy revealed MRSA. He had repeat, debridement 2 d later, and delayed primary closure 3 d after. GCS is rare and must be suspected when patients present with pain and swelling after an inciting event. They are easily diagnosed with compartment pressure monitoring. The treatment of gluteal abscess and compartment syndrome is the same and involves rapid surgical debridement. PMID:27190761

  19. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    PubMed Central

    Scalco, Renata S; Snoeck, Marc; Quinlivan, Ros; Treves, Susan; Laforét, Pascal; Jungbluth, Heinz; Voermans, Nicol C

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild cases may remain unnoticed or undiagnosed. Exertional rhabdomyolysis is well described among athletes and military personnel, but may occur in anybody exposed to unaccustomed exercise. In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed. PMID:27900193

  20. Crush syndrome chez l’adulte et problematique de sa prise en charge a la phase aiguë

    PubMed Central

    Hemou, P.F.; Sama, H.D.; Tchétikè, P.; Potkar, T.

    2015-01-01

    Summary Crush syndrome is defined as the local and systemic response to a traumatic rhabdomyolysis caused by compartment syndrome (prolonged compression of a large muscle mass leading to ischemia). It is not usually an isolated event, and may go unnoticed in the first 24 to 48 hours of a severe polytrauma. Ignored crush syndrome can lead to acute renal failure secondary to myoglobinuria occurring in a hypovolemic patient, with acidosis and hyperkalaemia. Crush syndrome is a medical and surgical emergency, frequently occurring after disasters such as earthquakes or major explosions with collapse of buildings. The acute revascularization syndrome that can occur after decompression (either surgical, or removing the weight from the crushed body part or removing a tourniquet) can cause irreversible cardiac arrest due to acute hyperkalaemia and hypovolemia. Early fluid resuscitation (starting pre-hospital and lasting over the first 24 hours) is crucial to restore and maintain normovolemia, and a urine output of 1-2ml/kg/hour is recommended during the first 24 hours. Diuretics may help to maintain this high urine output, and preventing tubular precipitate of myoglobin in acidic urine via bicarbonate may be useful. Early nutrition targets may be obtained using early “prophylactic” haemodialysis. PMID:27777548

  1. Metabolic neuropathies and myopathies.

    PubMed

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

    Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are β-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, α-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney.

  2. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.

    PubMed Central

    Andresen, B S; Olpin, S; Poorthuis, B J; Scholte, H R; Vianey-Saban, C; Wanders, R; Ijlst, L; Morris, A; Pourfarzam, M; Bartlett, K; Baumgartner, E R; deKlerk, J B; Schroeder, L D; Corydon, T J; Lund, H; Winter, V; Bross, P; Bolund, L; Gregersen, N

    1999-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting. To examine whether these different phenotypes are due to differences in the VLCAD genotype, we investigated 58 different mutations in 55 unrelated patients representing all known clinical phenotypes and correlated the mutation type with the clinical phenotype. Our results show a clear relationship between the nature of the mutation and the severity of disease. Patients with the severe childhood phenotype have mutations that result in no residual enzyme activity, whereas patients with the milder childhood and adult phenotypes have mutations that may result in residual enzyme activity. This clear genotype-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established. PMID:9973285

  3. Enhydrina schistosa (Elapidae: Hydrophiinae) the most dangerous sea snake in Sri Lanka: three case studies of severe envenoming.

    PubMed

    Kularatne, S A M; Hettiarachchi, R; Dalpathadu, J; Mendis, A S V; Appuhamy, P D S A N; Zoysa, H D J; Maduwage, K; Weerasinghe, V S; de Silva, A

    2014-01-01

    Sea snakes are highly venomous and inhabit tropical waters of the Indian and Pacific Oceans. Enhydrina schistosa is a common species of sea snake that lives in the coastal waters, lagoons, river mouths and estuaries from the Persian Gulf through Sri Lanka and to Southeast Asia. It is considered one of the most aggressive sea snakes in Sri Lanka where fishermen and people wading are at high risk. However, sea snake bites are rarely reported. In this report, we describe three cases where E. schistosa was the offending species. These three patients presented to two hospitals on the west coast of Sri Lanka within the course of 14 months from November 2011 with different degrees of severity of envenoming. The first patient was a 26-year-old fisherman who developed severe myalgia with very high creatine kinase (CK) levels lasting longer than 7 days. The second patient was a 32-year-old fisherman who developed gross myoglobinuria, high CK levels and hyperkalaemia. Both patients recovered and their electromyographic recordings showed myopathic features. The nerve conduction and neuromuscular transmission studies were normal in both patients suggesting primary myotoxic envenoming. The third patient was a 41-year-old man who trod on a sea snake in a river mouth and developed severe myalgia seven hours later. He had severe rhabdomyolysis and died three days later due to cardiovascular collapse. In conclusion, we confirm that E. schistosa is a deadly sea snake and its bite causes severe rhabdomyolysis.

  4. Acute exercise-induced bilateral thigh compartment syndrome.

    PubMed

    Boland, Michael R; Heck, Chris

    2009-03-01

    Acute compartment syndrome of the thigh is rare due to the space's ability to accommodate large volumes of fluid and, with the exception of the lateral septum, its thin compliant linings. This article describes a case of bilateral exercise-induced severe compartment syndrome treated with anterior and posterior fasciotomies. A 29-year-old man was admitted to intensive care with myoglobinuria. His left thigh was evaluated 18 hours later for compartment syndrome. The patient reported that 14 hours prior to initial presentation, he had participated in a 1-hour session of vigorous basketball. He gradually developed bilateral moderately severe thigh pain and tea-colored urine. Physical examination revealed pain secondary to passive stretch of both knees at 20 degrees flexion, plus firm anterior and posterior compartments to palpation. A handheld pressure monitor revealed the following compartment pressures: left anterior 80 mm Hg; left posterior 75 mm Hg; right anterior 45 mm Hg; and right posterior 50 mm Hg. Bilateral emergent anterior and posterior compartment fasciotomies were performed. The patient developed a significant severe distal motor and sensory neurological deficit on the left side, which recovered to 3/5 motor strength and protective sensation. At 6-month follow-up, he ambulated with the assistance of a left ankle foot orthosis. Acute severe compartment syndrome can occur following vigorous exercise. We recommend fasciotomies after exercise-induced acute compartment syndrome rather than initial observation because of the severity of morbidity associated with undertreated compartment syndrome.

  5. [Unusual and fatal type of burn injury: hot air sauna burn].

    PubMed

    García-Tutor, E; Koljonen, V

    2007-01-01

    Sauna bathing is a popular recreational activity in Finland and is generally considered safe even for pregnant women and patients suffering from heart problems; but mixing alcohol with sauna bathing can be hazardous. In the normal Finnish recreational sauna the temperature is usually between 80 and 90 degrees C. A wide variety of burn injuries, in all age groups, are related to sauna bathing; scalds and contact burns account for over 85% while hot air, steam and flame burns for only 15%. Dehydration in patients under the influence of alcohol heightens the risk of hypotension which impairs skin blood circulation. This increased warming of the skin is an effect that is more marked on the outer and upper parts of the body exposed to hot air. Such patients require intensive care on admission: fluid replacement according to the Parkland formula, forced diuresis and immediate correction of acidosis and myoglobinuria. These patients have significant rhabdomyolysis on admission. The best predictor of survival is the creatine kinase level on the second post-injury day. CT scans are necessary to diagnose the underlying conditions of unconsciousness. The necrotic area extends to subcutaneous fat tissue and even to the underlying muscles. The level of excision is typically fascial and, in some areas, layers of the muscle must be removed. Owing to the popularity of sauna bathing throughout the world, it is important to know the extent of damage in this type of injury, in order not to underestimate the severity of such lesions.

  6. Severe and fatal mass attacks by 'killer' bees (Africanized honey bees--Apis mellifera scutellata) in Brazil: clinicopathological studies with measurement of serum venom concentrations.

    PubMed

    França, F O; Benvenuti, L A; Fan, H W; Dos Santos, D R; Hain, S H; Picchi-Martins, F R; Cardoso, J L; Kamiguti, A S; Theakston, R D; Warrell, D A

    1994-05-01

    In São Paulo State, Brazil, five males, aged between 8 and 64 years, were attacked by 'Africanized' honey bees (Apis mellifera scutellata). The estimated number of stings received by each patient ranged from > 200 to > 1000. All five were transferred to intensive care units in São Paulo City. Clinical features included intravascular haemolysis, respiratory distress with ARDS, hepatic dysfunction, rhabdomyolysis (with myoglobinaemia and myoglobinuria), hypertension and myocardial damage (perhaps explained by release of endogenous catecholamines by venom phospholipase A2 and mellitin), shock, coma, acute renal failure and bleeding. Laboratory findings included gross neutrophil leucocytosis, elevated serum enzymes [AST, ALT, LDH, CPK (predominantly CPK-MM)] and creatinine. Clotting times were slightly prolonged. Despite treatment with antihistamines, corticosteroids, bronchodilators, vasodilators, bicarbonate, mannitol and mechanical ventilation, three of the patients died between 22 and 71 h after the attacks, with histopathological features of ARDS, hepatocellular necrosis, acute tubular necrosis, focal subendocardial necrosis and disseminated intravascular coagulation. Whole bee venom and phospholipase A2 (PLA2) antigen concentrations were measured in serum and urine for the first time, using enzyme immunoassay. High venom and PLA2 concentrations were detected in serum and urine for more than 50 h after the stings in two fatal cases, in one of which the total circulating unbound whole venom was estimated at 27 mg, one hour after the attack. An antivenom should be developed to treat the increasing numbers of victims of mass attacks by Africanized 'killer' bees in USA, Middle and South America.

  7. [Isotretinoin and exercise: can the two walk together?].

    PubMed

    Dalal, Adam; Ben-Barak, Shira; Zlotogorski, Abraham; Constantini, Naama

    2014-02-01

    Since its introduction in 1982, isotretinoin has revolutionized acne treatment, targeting the underlying mechanism of the disease, with effective and long-lasting results. During the first decade of its marketing, several cases of hyperCKemia and rhabdomyolysis were linked to isotretinon therapy. A special concern was given to the possible triggering of muscle toxicity by vigorous exercise. These potential effects discouraged the prescription of isotretinoin to physically active patients or required them to abstain from exercise during treatment. Common musculoskeletal adverse effects of isotretinoin include muscle or joint pains. HyperCKemia is frequently found in patients receiving treatment for rare cases of rhabdomyolysis. Isotretinoin-associated muscle toxicity is usually detected in asymptomatic patients, even though symptoms can appear without hyperCKemia. A possible synergistic effect of isotretinoin and exercise is plausible, although supported by weak evidence and mediated by an unknown mechanism. There are only two reports of myoglobinuria and no reports of decreased renal function in exercising patient under treatment. In conclusion, we believe that current data should not deter physicians from offering isotretinoin to physically active patients nor require them to abstain from exercise. Physicians must explain to patients the possible side effects of treatment, ask them to refrain from an unusual change in their exercise regimen and advise them to avoid other triggers of rhabdomyolysis. Patients should be aware of possible signs of muscle toxicity and inform their doctors about any relevant symptoms.

  8. Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy.

    PubMed

    Spiegel, Ronen; Saada, Ann; Halvardson, Jonatan; Soiferman, Devorah; Shaag, Avraham; Edvardson, Simon; Horovitz, Yoseph; Khayat, Morad; Shalev, Stavit A; Feuk, Lars; Elpeleg, Orly

    2014-07-01

    Isolated metabolic myopathies encompass a heterogeneous group of disorders, with mitochondrial myopathies being a subgroup, with depleted skeletal muscle energy production manifesting either by recurrent episodes of myoglobinuria or progressive muscle weakness. In this study, we investigated the genetic cause of a patient from a consanguineous family who presented with adolescent onset autosomal recessive mitochondrial myopathy. Analysis of enzyme activities of the five respiratory chain complexes in our patients' skeletal muscle showed severely impaired activities of iron sulfur (Fe-S)-dependent complexes I, II and III and mitochondrial aconitase. We employed exome sequencing combined with homozygosity mapping to identify a homozygous mutation, c.1A>T, in the FDX1L gene, which encodes the mitochondrial ferredoxin 2 (Fdx2) protein. The mutation disrupts the ATG initiation translation site resulting in severe reduction of Fdx2 content in the patient muscle and fibroblasts mitochondria. Fdx2 is the second component of the Fe-S cluster biogenesis machinery, the first being IscU that is associated with isolated mitochondrial myopathy. We suggest adding genetic analysis of FDX1L in cases of mitochondrial myopathy especially when associated with reduced activity of the respiratory chain complexes I, II and III.

  9. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V).

    PubMed

    Quinlivan, Rosaline; Martinuzzi, Andrea; Schoser, Benedikt

    2014-11-12

    Background McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria rhabdomyolysis and acute renal failure. This is an update of a review first published in 2004.Objectives To review systematically the evidence from randomised controlled trials (RCTs) of pharmacological or nutritional treatments for improving exercise performance and quality of life in McArdle disease.Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE on 11 August 2014.Selection criteria We included RCTs (including cross-over studies) and quasi-RCTs. We included unblinded open trials and individual patient studies in the discussion. Interventions included any pharmacological agent or nutritional supplement. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO2) max, walking speed, muscle force or power and fatigability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase and a reduction in the frequency of myoglobinuria), subjective measures (including quality of life scores and indices of disability) and serious adverse events.Data collection and analysis Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. Two review authors independently assessed the risk of bias of relevant studies, with comments from a third author. Two authors extracted data onto a specially designed form.Main results We identified 31 studies, and 13 fulfilled the criteria for inclusion. We described trials that were not eligible for the review in the Discussion. The included studies involved a total of 85 participants, but the number in each individual trial was small; the largest treatment trial included 19 participants and the smallest study included only one participant. There was no benefit with: D

  10. Lethal carnitine palmitoyltransferase (CPT) II deficiency in newborns: A molecular-genetic study

    SciTech Connect

    Taroni, F.; Gellera, C.; Cavadini, P.

    1994-09-01

    Classically, CPT II deficiency presents in young adults with recurrent episodes of paroxysmal myoglobinuria triggered by prolonged exercise, cold, or fever. More severe forms of CPT II deficiency have recently been observed in children and newborns. Here, were present biochemical and molecular studies of lethal neonatal CPT II deficiency in a premature Haitian infant of nonconsanguineous parents. He presented at birth with severe respiratory distress, cardiac arrhythmia and heart failure. His condition worsened and he died on the 4th day of life. Postmortem examination showed hypertrophied, dilated heart, and lipid storage in liver, heart and kidney. An older sibling had died unexpectantly at 4 days of age with postmortem evidence of fatty infiltration of liver, kidney, heart and muscle. Biochemical study of cultured fibroblasts demonstrated dramatic reduction of palmitate oxidation (to < 3%) and very low residual CPT II activity ({le}15%). No CPT II protein was detected by Western blot analysis of fibroblasts. However, immunoprecitation of cells pulse-labeled with L-[{sup 35}S] methionine demonstrated normal amounts of newly synthesized CPT II, thus suggesting altered stability of the enzyme. To identify the molecular defect in his patient, individual CPT II exons were amplified by genomic PCR and directly sequenced. A missense mutation was found in exon 4, resulting in the nonconservative amino acid substitution at codon 227 (Pro227Leu). SSCP analysis of a genomic PCR fragment encompassing the mutation demonstrated that the patient was homozygous and the parents were heterozygous for this mutation. The mutation was detected neither in a large number of controls nor in other CPT II deficient patients. Finally, CPT II activity in COS-1 cells transfected with mutated CPT II cDNA was <8% than that in cells transfected with wild-type cDNA, thus demonstrating the pathogenic role of this mutation.

  11. Renal Involvement in Idiopathic Inflammatory Myopathies.

    PubMed

    Cucchiari, David; Angelini, Claudio

    2017-02-01

    Renal involvement in idiopathic inflammatory myopathies is not as uncommon as was previously thought, as it develops in about one fifth of patients. Clinical presentation includes either acute kidney injury or chronic glomerulonephritis. The former usually develops abruptly during acute phases of rhabdomyolysis: in this case, kidney injury is caused by the toxic effects that myoglobinuria has on the kidney tubules, including cast formation and iron-induced oxidative stress and the development of a third space into the injured muscles. The latter instead has an autoimmune nature, a pleomorphic histological picture, and a more indolent course, with the exception of crescentic glomerulonephritis. Accurate diagnosis and management is crucial for these patients, as timely evaluation and treatment can prevent most of the complications. In the setting of rhabdomyolysis-induced acute kidney injury, the necessity of dialysis can be avoided through aggressive hydration and alkalinization, in order to force diuresis and avoid acidosis and hyperkalemia. In immune-mediated glomerulonephritis, renal biopsy is of undoubtedly value in the diagnostic process and can add prognostic and therapeutic information. In these forms, the development of chronic kidney disease can be prevented or at least delayed by the institution or modification of immunosuppressive treatment. Moreover, the use of drugs that inhibit the renin-angiotensin-aldosterone system and some lifestyle modifications, such as smoking cessation, weight loss, and salt restriction have also value in reducing proteinuria and the progression of kidney damage. In this review, we have summarized the currently available evidence and the different case series in an attempt to provide the readers with the most complete and practical notions that are needed to handle these delicate patients.

  12. Renal uptake of myoglobin is mediated by the endocytic receptors megalin and cubilin.

    PubMed

    Gburek, Jakub; Birn, Henrik; Verroust, Pierre J; Goj, Bogusława; Jacobsen, Christian; Moestrup, Søren K; Willnow, Thomas E; Christensen, Erik I

    2003-09-01

    Nephrotoxicity of myoglobin is well recognized as playing a part in the development of acute renal failure in settings of myoglobinuria. However, the molecular mechanism of myoglobin uptake in renal proximal tubules has not been clarified. Here, we report that the endocytic receptors megalin and cubilin are involved in renal reabsorption of myoglobin. Both receptors were captured from solubilized renal brush-border membranes by affinity chromatography using myoglobin-Sepharose. Myoglobin bound to purified megalin and cubilin with Kd values of 2.0 and 3 microM, respectively, as evaluated by surface plasmon resonance analysis. Apomyoglobin bound to megalin with the same affinity, and the affinity of apomyoglobin to cubilin was reduced (Kd = 5 microM). Radioiodinated myoglobin could be displaced by apomyoglobin in inhibition studies using isolated renal brush-border membranes (Ki approximately 2 microM). Receptor-associated protein as well as antibodies directed against megalin and cubilin markedly inhibited the uptake of fluorescent-labeled myoglobin by cultured yolk sac BN-16 cells. The significance of megalin- and cubilin-mediated endocytosis for myoglobin uptake in vivo was demonstrated by use of kidney-specific megalin knockout mice. Injected myoglobin was extensively reabsorbed by megalin-expressing proximal tubular cells, whereas there was very little uptake in the megalin-deficient cells. In conclusion, this study establishes the molecular mechanism of myoglobin uptake in the renal proximal tubule involving the endocytic receptors megalin and cubilin. Identification of the receptors for tubular uptake of myoglobin may be essential for development of new therapeutic strategies for myoglobinuric acute renal failure.

  13. Ultrastructural alterations in skeletal muscle of pigs with acute monensin myotoxicosis.

    PubMed Central

    Van Vleet, J. F.; Ferrans, V. J.

    1984-01-01

    Large doses of monensin, a Na+-selective carboxylic ionophore, produce polyfocal, monophasic necrosis of skeletal muscle, with Type I fiber selectivity, in swine. For a study of the sequential ultrastructural alterations in affected skeletal muscles, 14 weanling pigs were given 40 mg monensin/kg body weight and were euthanatized 1, 2, 4, 8, and 16 days later. Myotoxicosis and myoglobinuria were apparent clinically. At necropsy, white, dry areas of necrosis were present in the muscle masses of the anterior and posterior thigh, shoulder, and loin. Two patterns of skeletal muscle necrosis were observed on Day 1, especially in Type I fibers. In fibers exhibiting the first of these patterns, the contractile material was disrupted, forming dense amorphous and filamentous clumps scattered within the persistent sheaths of external lamina (sarcolemmal tubes); the mitochondria were swollen and contained flocculent matrix densities, and the nuclei were pyknotic. Fibers showing the second pattern were uniformly dense, but their sarcoplasm was not disrupted. Sublethally injured fibers were also observed and showed focal myofibrillar lysis. On Days 2 and 4, the necrotic muscle had marked infiltration of macrophages in the interstitium and within sarcolemmal tubes. Rapid resolution of the fiber necrosis occurred by phagocytosis of the sarcoplasmic debris. Regeneration of affected muscles developed early following injury and progressed rapidly to complete restoration of the necrotic muscles without residual fibrosis. Regeneration was initiated on Day 1 by activation of satellite cells to form presumptive myoblasts; on Days 4 and 8 these cells showed evidence of fusion, forming myotubes to restore the necrotic fibers. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:6696050

  14. Post-mortem urinary myoglobin levels with reference to the causes of death.

    PubMed

    Zhu, B L; Ishida, K; Quan, L; Taniguchi, M; Oritani, S; Kamikodai, Y; Fujita, M Q; Maeda, H

    2001-01-15

    To evaluate pathophysiological significance of post-mortem urinary myoglobin levels in determining the cause of death, we investigated 210 forensic autopsy cases, partially in comparison with serum levels. Post-mortem serum myoglobin levels were extraordinary high in most cases possibly due to post-mortem change. Urinary myoglobin levels did not correlate with the serum levels, showing possible post-mortem elevation in cases of a prolonged post-mortem period over 48h. A high (>1000 ng/ml), moderate (100-1000 ng/ml), slight (50-100 ng/ml) and not significant (<50 ng/ml) elevation of urinary myoglobin were observed in 26, 43, 31 and 110 cases, respectively. Half the highly elevated cases were those with a survival time over 24h. In cases of minor muscle injury such as head trauma, elevation of urinary myoglobin level was closely related to longer survival. In acute/subacute deaths with a post-mortem interval within 48h, a significant difference was observed in relation to the blood carboxyhemoglobin (COHb) levels of fire victims: myoglobinuria over 100 ng/ml was more frequently and markedly observed in cases with COHb below 60% than over 60%, suggesting muscle damage in fatal burns. Similar elevation was observed in heat stroke victims, and also in some cases of acute and subacute death from polytrauma, asphyxiation, drowning, electricity and spontaneous cerebral bleeding, but not in myocardial infarction. Thus, it was suggested that high post-mortem urinary myoglobin levels in acute and subacute death cases may be a possible indicator of antemortem massive skeletal muscle damage as well as exertional muscle hyperactivity or convulsive disorders associated with hypoxia.

  15. Rhabdomyolysis in Critically Ill Surgical Patients

    PubMed Central

    Kuzmanovska, Biljana; Cvetkovska, Emilija; Kuzmanovski, Igor; Jankulovski, Nikola; Shosholcheva, Mirjana; Kartalov, Andrijan; Spirovska, Tatjana

    2016-01-01

    Introduction: Rhabdomyolysis is a syndrome of injury of skeletal muscles associated with myoglobinuria, muscle weakness, electrolyte imbalance and often, acute kidney injury as severe complication. The aim: of this study is to detect the incidence of rhabdomyolysis in critically ill patients in the surgical intensive care unit (ICU), and to raise awareness of this medical condition and its treatment among the clinicians. Material and methods: A retrospective review of all surgical and trauma patients admitted to surgical ICU of the University Surgical Clinic “Mother Teresa” in Skopje, Macedonia, from January 1st till December 31st 2015 was performed. Patients medical records were screened for available serum creatine kinase (CK) with levels > 200 U/l, presence of myoglobin in the serum in levels > 80 ng/ml, or if they had a clinical diagnosis of rhabdomyolysis by an attending doctor. Descriptive statistical methods were used to analyze the collected data. Results: Out of totally 1084 patients hospitalized in the ICU, 93 were diagnosed with rhabdomyolysis during the course of one year. 82(88%) patients were trauma patients, while 11(12%) were surgical non trauma patients. 7(7.5%) patients diagnosed with rhabdomyolysis developed acute kidney injury (AKI) that required dialysis. Average values of serum myoglobin levels were 230 ng/ml, with highest values of > 5000 ng/ml. Patients who developed AKI had serum myoglobin levels above 2000 ng/ml. Average values of serum CK levels were 400 U/l, with highest value of 21600 U/l. Patients who developed AKI had serum CK levels above 3000 U/l. Conclusion: Regular monitoring and early detection of elevated serum CK and myoglobin levels in critically ill surgical and trauma patients is recommended in order to recognize and treat rhabdomyolysis in timely manner and thus prevent development of AKI. PMID:27703296

  16. The Spectrum of Renal Involvement in Patients With Inflammatory Myopathies

    PubMed Central

    Couvrat-Desvergnes, Grégoire; Masseau, Agathe; Benveniste, Olivier; Bruel, Alexandra; Hervier, Baptiste; Mussini, Jean-Marie; Buob, David; Hachulla, Eric; Rémy, Philippe; Azar, Raymond; Namara, Evelyne Mac; MacGregor, Brigitte; Daniel, Laurent; Lacraz, Adeline; Broucker, Thomas De; Rouvier, Philippe; Carli, Philippe; Laville, Maurice; Dantan, Etienne; Hamidou, Mohamed; Moreau, Anne

    2014-01-01

    Abstract Data regarding the incidence and outcome of renal involvement in patients with inflammatory myopathies (IM) remain scarce. We assessed the incidence and causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in 150 patients with dermatomyositis, polymyositis, and antisynthetase syndrome followed in 3 French referral centers. Renal involvement occurred in 35 (23.3%) patients: AKI in 16 (10.7%), and CKD in 31 (20.7%) patients. The main cause of AKI was drug or myoglobinuria-induced acute tubular necrosis. Male sex, cardiovascular risk factors, cardiac involvement, and initial proteinuria >0.3 g/d were associated with the occurrence of AKI. The outcome of patients with AKI was poor: 13 (81%) progressed to CKD and 2 (12.5%) reached end-stage renal disease. In multivariate survival analysis, age at IM onset, male sex, a history of cardiovascular events, and a previous episode of AKI were associated with the risk of CKD. We also identified 14 IM patients who underwent a kidney biopsy in 10 nephrology centers. Renal pathology disclosed a wide range of renal disorders, mainly immune-complex glomerulonephritis. We identified in 5 patients a peculiar pattern of severe acute renal vascular damage consisting mainly of edematous thickening of the intima of arterioles. We found that AKI and CKD are frequent in patients with IM. Prevention of AKI is crucial in these patients, as AKI is a major contributor to their relatively high risk of CKD. A peculiar pattern of acute vascular damage is part of the spectrum of renal diseases associated with IM. PMID:24378741

  17. The spectrum of renal involvement in patients with inflammatory myopathies.

    PubMed

    Couvrat-Desvergnes, Grégoire; Masseau, Agathe; Benveniste, Olivier; Bruel, Alexandra; Hervier, Baptiste; Mussini, Jean-Marie; Buob, David; Hachulla, Eric; Rémy, Philippe; Azar, Raymond; Mac Namara, Evelyne; MacGregor, Brigitte; Daniel, Laurent; Lacraz, Adeline; De Broucker, Thomas; Rouvier, Philippe; Carli, Philippe; Laville, Maurice; Dantan, Etienne; Hamidou, Mohamed; Moreau, Anne; Fakhouri, Fadi

    2014-01-01

    Data regarding the incidence and outcome of renal involvement in patients with inflammatory myopathies (IM) remain scarce. We assessed the incidence and causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in 150 patients with dermatomyositis, polymyositis, and antisynthetase syndrome followed in 3 French referral centers. Renal involvement occurred in 35 (23.3%) patients: AKI in 16 (10.7%), and CKD in 31 (20.7%) patients. The main cause of AKI was drug or myoglobinuria-induced acute tubular necrosis. Male sex, cardiovascular risk factors, cardiac involvement, and initial proteinuria >0.3 g/d were associated with the occurrence of AKI. The outcome of patients with AKI was poor: 13 (81%) progressed to CKD and 2 (12.5%) reached end-stage renal disease. In multivariate survival analysis, age at IM onset, male sex, a history of cardiovascular events, and a previous episode of AKI were associated with the risk of CKD. We also identified 14 IM patients who underwent a kidney biopsy in 10 nephrology centers. Renal pathology disclosed a wide range of renal disorders, mainly immune-complex glomerulonephritis. We identified in 5 patients a peculiar pattern of severe acute renal vascular damage consisting mainly of edematous thickening of the intima of arterioles. We found that AKI and CKD are frequent in patients with IM. Prevention of AKI is crucial in these patients, as AKI is a major contributor to their relatively high risk of CKD. A peculiar pattern of acute vascular damage is part of the spectrum of renal diseases associated with IM.

  18. What Caused the UK's Largest Common Dolphin (Delphinus delphis) Mass Stranding Event?

    PubMed Central

    Jepson, Paul D.; Deaville, Robert; Acevedo-Whitehouse, Karina; Barnett, James; Brownlow, Andrew; Brownell Jr., Robert L.; Clare, Frances C.; Davison, Nick; Law, Robin J.; Loveridge, Jan; Macgregor, Shaheed K.; Morris, Steven; Murphy, Sinéad; Penrose, Rod; Perkins, Matthew W.; Pinn, Eunice; Seibel, Henrike; Siebert, Ursula; Sierra, Eva; Simpson, Victor; Tasker, Mark L.; Tregenza, Nick; Cunningham, Andrew A.; Fernández, Antonio

    2013-01-01

    On 9 June 2008, the UK's largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06∶30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a “two-stage process” where a group of normally pelagic dolphins entered Falmouth Bay and, after 3–4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE. PMID

  19. Spasmodic muscle cramps and weakness as presenting symptoms in Wilson disease.

    PubMed

    Rosen, John M; Kuntz, Nancy; Melin-Aldana, Hector; Bass, Lee M

    2013-10-01

    Wilson disease (WD) is an autosomal-recessive disorder of hepatic copper metabolism that has tremendous variability in its presentation. Phenotypic diversity of the disease can lead to delayed diagnosis. We describe a case of WD in a 10-year-old boy presenting with 3 months of increasingly intense, spasmodic lower extremity muscle cramps. Physical examination revealed tenderness on calf palpation and dark flat lesions over his ankles, knees, and elbows. Initial testing revealed creatine kinase of 302 IU/L (normal 24-248 IU/L), hemoglobin of 8.9 g/dL (11.5-15.5 g/dL), aspartate aminotransferase of 114 IU/L (16-52 IU/L), alanine aminotransferase of 54 IU/L (2-30 IU/L), and myoglobinuria. Extensive evaluation of his myopathy, including MRI and muscle biopsy, was negative. Additional laboratory tests revealed a prothrombin time of 21.3 seconds (11.8-15.5 seconds), total bilirubin of 1.4 mg/dL (<1 mg/dL), direct bilirubin of 0.5 mg/dL (<0.3 mg/dL), albumin of 2.1 g/dL (3.1-4.6 g/dL), a reticulocyte percentage of 4.5% (0.5%-2.5%), a negative Coombs direct antibody test, ceruloplasmin of 3 mg/dL (21-51 mg/dL), and 24-h urine copper of 393 μg/24 h (15-60 μg/24 h). Liver biopsy showed patchy advanced fibrosis, mild inflammation, positive staining for copper, and a tissue copper concentration of 768 µg/g (10-35 μg/g). Brain MRI revealed symmetric intrinsic T1 shortening within bilateral basal ganglia. Trientene therapy was initiated for WD. Symptoms and laboratory abnormalities resolved and remain normal at 21 months' follow-up. Musculoskeletal involvement in WD is uncommon and typically defined as bone demineralization, arthropathy, or hypokalemic muscle weakness. In patients with unexplained musculoskeletal symptoms and hepatic abnormalities, a diagnosis of WD should be considered and appropriate evaluation initiated.

  20. The greater black krait (Bungarus niger), a newly recognized cause of neuro-myotoxic snake bite envenoming in Bangladesh.

    PubMed

    Faiz, Abul; Ghose, Aniruddha; Ahsan, Farid; Rahman, Ridwanur; Amin, Robed; Hassan, Mahtab Uddin; Chowdhury, A Wahed; Kuch, Ulrich; Rocha, Thalita; Harris, John B; Theakston, R David G; Warrell, David A

    2010-11-01

    Prospective studies of snake bite patients in Chittagong, Bangladesh, included five cases of bites by greater black kraits (Bungarus niger), proven by examination of the snakes that had been responsible. This species was previously known only from India, Nepal, Bhutan and Burma. The index case presented with descending flaccid paralysis typical of neurotoxic envenoming by all Bungarus species, but later developed generalized rhabdomyolysis (peak serum creatine kinase concentration 29,960 units/l) with myoglobinuria and acute renal failure from which he succumbed. Among the other four patients, one died of respiratory paralysis in a peripheral hospital and three recovered after developing paralysis, requiring mechanical ventilation in one patient. One patient suffered severe generalized myalgia and odynophagia associated with a modest increase in serum creatine kinase concentration. These are the first cases of Bungarus niger envenoming to be reported from any country. Generalized rhabdomyolysis has not been previously recognized as a feature of envenoming by any terrestrial Asian elapid snake, but a review of the literature suggests that venoms of some populations of Bungarus candidus and Bungarus multicinctus in Thailand and Vietnam may also have this effect in human victims. To investigate this unexpected property of Bungarus niger venom, venom from the snake responsible for one of the human cases of neuro-myotoxic envenoming was injected into one hind limb of rats and saline into the other under buprenorphine analgesia. All animals developed paralysis of the venom-injected limb within two hours. Twenty-four hours later, the soleus muscles were compared histopathologically and cytochemically. Results indicated a predominantly pre-synaptic action (β-bungarotoxins) of Bungarus niger venom at neuromuscular junctions, causing loss of synaptophysin and the degeneration of the terminal components of the motor innervation of rat skeletal muscle. There was oedema and

  1. Calcitriol Directly Sensitizes Renal Tubular Cells to ATP-Depletion- and Iron-Mediated Attack

    PubMed Central

    Zager, Richard A.

    1999-01-01

    Vitamin Ds have been reported to have diverse effects on cell homeostasis, leading to suggestions that they have therapeutic applications extending beyond their traditional actions on the Ca2+/parathyroid/bone axis. As some of these potential indications carry an inherent risk of acute renal failure (ARF; eg, cancer chemotherapy and organ transplantation), the goal of this study was to assess whether vitamin Ds directly affect renal tubule injury responses. Cultured human proximal tubular (HK-2) cells were exposed to physiological or pharmacological doses of either calcitriol (D3) or a synthetic vitamin D2 analogue (19-nor) for 3 to 48 hours. Their impact on cell integrity (percent lactate dehydrogenase (LDH) release and tetrazolium dye MTT uptake) under basal conditions and during superimposed injuries (ATP depletion/Ca2+ ionophore or iron-mediated oxidant stress) were determined. As vitamin Ds can be anti-proliferative, cell outgrowth ([3H]thymidine uptake and crystal violet staining) was also tested. Finally, the action of D3 on in vivo ARF (glycerol-induced myoglobinuria) and isolated proximal tubule injury responses were assessed. D3 induced a rapid, dose-dependent increase in HK-2 susceptibility to both ATP-depletion/Ca2+-ionophore- and Fe-mediated attack without independently affecting cell integrity or proliferative responses. In contrast, D2 negatively affected only Fe toxicity and only after relatively prolonged exposure (48 hours). D3 dramatically potentiated in vivo ARF (two- to threefold increase in azotemia), suggesting potential in vivo relevance of the above HK-2 cell results. Proximal tubules, isolated from these glycerol-exposed mice, suggested that D3 can worsen tubule injury despite a parodoxic suppression of H2O2 production. In contrast, D3 had a mild negative impact on cellular energetics (depressed ATP/ADP ratios), and it accentuated plasma membrane phospholipid breakdown. The latter was observed in both glycerol-treated and control tubules

  2. What caused the UK's largest common dolphin (Delphinus delphis) mass stranding event?

    PubMed

    Jepson, Paul D; Deaville, Robert; Acevedo-Whitehouse, Karina; Barnett, James; Brownlow, Andrew; Brownell, Robert L; Clare, Frances C; Davison, Nick; Law, Robin J; Loveridge, Jan; Macgregor, Shaheed K; Morris, Steven; Murphy, Sinéad; Penrose, Rod; Perkins, Matthew W; Pinn, Eunice; Seibel, Henrike; Siebert, Ursula; Sierra, Eva; Simpson, Victor; Tasker, Mark L; Tregenza, Nick; Cunningham, Andrew A; Fernández, Antonio

    2013-01-01

    On 9 June 2008, the UK's largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06:30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a "two-stage process" where a group of normally pelagic dolphins entered Falmouth Bay and, after 3-4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE.