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Sample records for rhabdomyolysis

  1. Diagnostic evaluation of rhabdomyolysis.

    PubMed

    Nance, Jessica R; Mammen, Andrew L

    2015-06-01

    Rhabdomyolysis is characterized by severe acute muscle injury resulting in muscle pain, weakness, and/or swelling with release of myofiber contents into the bloodstream. Symptoms develop over hours to days after an inciting factor and may be associated with dark pigmentation of the urine. Serum creatine kinase and urine myoglobin levels are markedly elevated. Clinical examination, history, laboratory studies, muscle biopsy, and genetic testing are useful tools for diagnosis of rhabdomyolysis, and they can help differentiate acquired from inherited causes of rhabdomyolysis. Acquired causes include substance abuse, medication or toxic exposures, electrolyte abnormalities, endocrine disturbances, and autoimmune myopathies. Inherited predisposition to rhabdomyolysis can occur with disorders of glycogen metabolism, fatty acid ?-oxidation, and mitochondrial oxidative phosphorylation. Less common inherited causes of rhabdomyolysis include structural myopathies, channelopathies, and sickle-cell disease. This review focuses on the differentiation of acquired and inherited causes of rhabdomyolysis and proposes a practical diagnostic algorithm. Muscle Nerve 51: 793-810, 2015. PMID:25678154

  2. Rhabdomyolysis After Laparoscopic Nephrectomy

    PubMed Central

    Merriam, William G.; Trabulsi, Edouard J.; Byrne, Dolores; Gomella, Leonard

    2007-01-01

    Background and Objectives: Laparoscopic renal surgery has become a widely applied technique in recent years. The development of postoperative rhabdomyolysis is a known but rare complication of laparoscopic renal surgery. Herein, 4 cases of rhabdomyolysis and a review of the literature are presented with respect to pathogenesis, treatment, and prevention of this dire complication. Methods: A retrospective review of over 600 laparoscopic renal operations over the past 8 years was performed. All cases of postoperative rhabdomyolysis were identified. A Medline search was performed to find articles related to the development of postoperative rhabdomyolysis. Cases of rhabdomyolysis developing after laparoscopic renal surgery and common risk factors between cases were identified. Results: The incidence of postoperative rhabdomyolysis in our series is 0.67%. It is similar to the rate reported in other series. Male sex, high body mass index, prolonged operative times, and the lateral decubitus position are all risk factors in its development. Conclusion: The prevention and optimal management of postoperative rhabdomyolysis following laparoscopic renal surgery has yet to be defined. The risk factors we identified should be carefully addressed and minimized. A better understanding of the pathogenesis of rhabdomyolysis will also be a key component in its prevention. PMID:18237506

  3. Rhabdomyolysis in a recreational swimmer.

    PubMed

    Stella, J J; Shariff, A H

    2012-02-01

    Rhabdomyolysis is a clinical and biochemical syndrome resulting from skeletal muscle injury, which may ultimately lead to acute renal failure (ARF) and death. Exertional rhabdomyolysis refers to skeletal muscle injury that is usually induced by strenuous eccentric exercises in a hot and humid environment. It is usually seen in marathoners and military personnel. We present the case of a 32-year-old Malaysian man who had rhabdomyolysis and myoglobinuria without ARF after two episodes of unaccustomed swimming. He was treated conservatively, and recovered uneventfully. A brief discussion on the pathophysiology of rhabdomyolysis, the principles of management and recuperation is included. PMID:22337202

  4. Rhabdomyolysis: Pathogenesis, Diagnosis, and Treatment

    PubMed Central

    Torres, Patrick A.; Helmstetter, John A.; Kaye, Adam M.; Kaye, Alan David

    2015-01-01

    Background Rhabdomyolysis is a complex medical condition involving the rapid dissolution of damaged or injured skeletal muscle. Methods This review focuses on the epidemiology, pathophysiology, causes, presentation, diagnosis, complications, management, and anesthetic considerations related to rhabdomyolysis. Results Any form of muscle damage––and by extension any entity that causes muscle damage––can initiate rhabdomyolysis. One of the most important treatment goals when rhabdomyolysis is suspected is avoiding acute kidney injury. Conclusion All clinicians should be aware of common causes, diagnosis, and treatment options. PMID:25829882

  5. Rhabdomyolysis complicating doxylamine overdose.

    PubMed

    Mendoza, F S; Atiba, J O; Krensky, A M; Scannell, L M

    1987-11-01

    A 16-year-old male presenting with anticholinergic symptoms was found to have hematuria and oliguria. Evaluation of the patient revealed a serum creatinine of 2.2 mg/dl, myoglobinuria, and a creatine phosphokinase (CPK) level of 78, 750 IU/l with 99 percent fraction 3 isoenzyme. A toxic screen showed the presence of doxylamine, an antihistamine of the ethanolamine class, at a level of 75 times therapeutic. The patient did not have a history of trauma or seizures. The extremely high CPK level with the doxylamine overdose suggests that doxylamine may be associated with nontraumatic rhabdomyolysis. This is the first case report of rhabdomyolysis being associated with an antihistamine overdose. PMID:3665331

  6. Laxative-induced rhabdomyolysis

    PubMed Central

    Merante, Alfonso; Gareri, Pietro; Marigliano, Norma Maria; De Fazio, Salvatore; Bonacci, Elvira; Torchia, Carlo; Russo, Gaetano; Lacroce, Pasquale; Lacava, Roberto; Castagna, Alberto; De Sarro, Giovambattista; Ruotolo, Giovanni

    2010-01-01

    The present study describes a case of laxative-induced rhabdomyolysis in an elderly patient. An 87-year-old woman was hospitalized for the onset of confusion, tremors, an inability to walk, and a fever that she had been experiencing for 36 hours. She often took high dosages of lactulose and sorbitol syrup as a laxative (about 70 g/day). During her physical examination, the patient was confused, drowsy, and she presented hyposthenia in her upper and lower limbs, symmetric and diffuse moderate hyporeflexia, and her temperature was 37.8C. Laboratory tests revealed severe hyponatremia with hypokalemia, hypocalcemia, hypochloremia, and metabolic alkalosis. Moreover, rhabdomyolysis markers were found. The correction of hydroelectrolytic imbalances with saline, potassium and sodium chlorure, calcium gluconate was the first treatment. During her hospitalization the patient presented acute delirium, treated with haloperidol and prometazine chloridrate intramuscularly. She was discharged 12 days later, after resolution of symptoms, and normalized laboratory tests. Over-the-counter drugs such as laxatives are usually not considered dangerous; on the other hand, they may cause serum electrolytic imbalance and rhabdomyolysis. A careful monitoring of all the drugs taken by the elderly is one of the most important duties of a physician since drug interactions and their secondary effects may be fatal. PMID:20396636

  7. Laxative-induced rhabdomyolysis.

    PubMed

    Merante, Alfonso; Gareri, Pietro; Marigliano, Norma Maria; De Fazio, Salvatore; Bonacci, Elvira; Torchia, Carlo; Russo, Gaetano; Lacroce, Pasquale; Lacava, Roberto; Castagna, Alberto; De Sarro, Giovambattista; Ruotolo, Giovanni

    2010-01-01

    The present study describes a case of laxative-induced rhabdomyolysis in an elderly patient. An 87-year-old woman was hospitalized for the onset of confusion, tremors, an inability to walk, and a fever that she had been experiencing for 36 hours. She often took high dosages of lactulose and sorbitol syrup as a laxative (about 70 g/day). During her physical examination, the patient was confused, drowsy, and she presented hyposthenia in her upper and lower limbs, symmetric and diffuse moderate hyporeflexia, and her temperature was 37.8 degrees C. Laboratory tests revealed severe hyponatremia with hypokalemia, hypocalcemia, hypochloremia, and metabolic alkalosis. Moreover, rhabdomyolysis markers were found. The correction of hydroelectrolytic imbalances with saline, potassium and sodium chlorure, calcium gluconate was the first treatment. During her hospitalization the patient presented acute delirium, treated with haloperidol and prometazine chloridrate intramuscularly. She was discharged 12 days later, after resolution of symptoms, and normalized laboratory tests. Over-the-counter drugs such as laxatives are usually not considered dangerous; on the other hand, they may cause serum electrolytic imbalance and rhabdomyolysis. A careful monitoring of all the drugs taken by the elderly is one of the most important duties of a physician since drug interactions and their secondary effects may be fatal. PMID:20396636

  8. Rhabdomyolysis Secondary to Bee Sting

    PubMed Central

    Akdur, Okhan; Can, Serdar; Afacan, Gksu

    2013-01-01

    Insect stings belonging to Hymenoptera defined as wasps, yellow jackets, bees, or hornets by human usually result in unserious clinical pictures that go with pain. Rhabdomyolysis following a bee sting is a rare condition. This paper emphasizes rhabdomyolysis as a rare complication of this frequently observed envenomation. Rare but severe clinical results may occur due to multiple bee stings, such as intravascular hemolysis, rhabdomyolysis, acute renal insufficiency, and hepatic dysfunction. In bee stings as in our case, clinicians should be alert for rhabdomyolysis in cases with generalized body and muscle pain. Early onset alkaline diuresis and management in patients with rhabdomyolysis are vital in protecting the renal functions and preventing morbidity and mortality. PMID:23606996

  9. Myalgias and Myopathies: Rhabdomyolysis.

    PubMed

    Dawley, Courtney

    2016-01-01

    Rhabdomyolysis is the rapid breakdown of skeletal muscle with release of electrolytes, myoglobin, and other proteins into the circulation. The clinical presentation encompasses a spectrum of patients ranging from those with asymptomatic increases in creatine kinase (CK) levels to those with fulminant disease complicated by acute kidney injury (AKI), severe electrolyte abnormalities, compartment syndrome, and disseminated intravascular coagulation. A CK level at least 10 times the upper limit of normal typically is considered diagnostic, as is myoglobinuria. AKI is the most significant complication. Prompt recognition and management of rhabdomyolysis is crucial to preserving renal function. Management consists of rapidly initiating aggressive intravenous saline resuscitation to maintain a urine output of at least 300 mL/hour. Sodium bicarbonate can be used for patients who are acidotic, and mannitol can be used for those whose urine output is not at goal. Significant electrolyte abnormalities may be present and must be managed to avoid cardiac arrhythmias and arrest. Compartment syndrome can develop as an early or late finding and requires decompressive fasciotomy for definitive management. Intravenous fluids typically are continued until CK levels are lower than 1,000 U/L. PMID:26734834

  10. Hypokalemia and rhabdomyolysis.

    PubMed

    Horwitz, Henrik; Woeien, Vidar A; Petersen, Linda Wiuff; Jimenez-Solem, Espen

    2015-01-01

    The adverse drug event manager of the Capital Region of Denmark received a report of a 65-year-old male with type II diabetes and long-lasting treatment with indapamide. In addition, he had a history of a high consumption of licorice. For 2 weeks, the patient suffered from myalgia, which the general practitioner suspected to be polymyalgia rheumatica and referred him to the hospital. Initial blood samples revealed a reduced potassium concentration of 1.5 mmol/L (reference value: 6.6-4.6 mmol/L) and an elevated creatine kinase of 18,400 IU/L (reference value: 40-280 IU/L). We believe that the patient developed rhabdomyolysis due to severe hypokalemia, possibly induced by a pharmacodynamic interaction between licorice and indapamide. PMID:25969658

  11. Rhabdomyolysis: a genetic perspective.

    PubMed

    Scalco, Renata Siciliani; Gardiner, Alice R; Pitceathly, Robert Ds; Zanoteli, Edmar; Becker, Jefferson; Holton, Janice L; Houlden, Henry; Jungbluth, Heinz; Quinlivan, Ros

    2015-01-01

    Rhabdomyolysis (RM) is a clinical emergency characterized by fulminant skeletal muscle damage and release of intracellular muscle components into the blood stream leading to myoglobinuria and, in severe cases, acute renal failure. Apart from trauma, a wide range of causes have been reported including drug abuse and infections. Underlying genetic disorders are also a cause of RM and can often pose a diagnostic challenge, considering their marked heterogeneity and comparative rarity.In this paper we review the range of rare genetic defects known to be associated with RM. Each gene has been reviewed for the following: clinical phenotype, typical triggers for RM and recommended diagnostic approach. The purpose of this review is to highlight the most important features associated with specific genetic defects in order to aid the diagnosis of patients presenting with hereditary causes of recurrent RM. PMID:25929793

  12. A case of flax seed induced rhabdomyolysis.

    PubMed

    Prasad, Anushre; Kumar, Ritesh; Ramanan, Harini; Khandige, Nalini; Prabhu, Krishnananda

    2012-12-01

    Rhabdomyolysis is a clinical and a biochemical syndrome that occurs due to a skeletal muscle injury. The main cause of rhabdomyolysis is a muscle crush injury, toxins, ischaemia and metabolic disorders. Rare cases of rhabdomyolysis have been reported which had been caused by drugs and after insect stings. The breakdown products of the damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful for the kidneys and they may lead to kidney failure. The symptoms of rhabdomyolysis depend on the severity of the condition. The milder forms of rhabdomyolysis may not cause any muscle symptoms, and the diagnosis is based on abnormal blood tests. The most reliable test in the diagnosis of rhabdomyolysis is the blood level of Creatine Kinase (CK) which is released by the damaged muscles. Here in, we report an unusual case of flax seed induced rhabdomyolysis to alert the medical community about this rare complication. PMID:23373049

  13. Hair dye poisoning and rhabdomyolysis.

    PubMed

    Bokutz, Munira; Nasir, Nosheen; Mahmood, Faisal; Sajid, Sara

    2015-04-01

    Hair dye ingestion is a rare cause of toxicity in Pakistan. We are presenting the case report of a 55 year old male who presented with accidental hair dye ingestion and developed laryngeal oedema requiring emergent tracheostomy. He had also developed aspiration pneumonitis and chemical oesophagitis. However, the most alarming manifestation was rhabdomyolysis. Hair dye toxicity can be fatal if not recognized early. There is no antidote available. Rhabdomyolysis is a complication and needs to be managed aggressively in order to prevent long term morbidity. PMID:25976581

  14. Massive Rhabdomyolysis Following Cardiopulmonary Bypass

    PubMed Central

    Kim, Young Sam; Yoon, Yong Han; Kim, Joung Taek

    2014-01-01

    Here, we report a case of massive rhabdomyolysis following an uncomplicated repair of a ventricular septal defect in a five-month-old baby. Postoperatively, the patient was hemodynamically stable but metabolic acidosis continued, accompanied by fever and delayed mental recovery. The next day, he became comatose and never regained consciousness thereafter. The computed tomography of the brain revealed a diffuse brain injury. The patient followed a downhill course and eventually died on postoperative day 33. An unusually high level of creatine phosphokinase was noticed, peaking (21,880 IU/L) on postoperative day 2, suggesting severe rhabdomyolysis. The relevant literature was reviewed, and the possibility of malignant hyperthermia obscured by cardiopulmonary bypass and hypothermia was addressed. PMID:24782976

  15. Severe rhabdomyolysis after doxylamine overdose.

    PubMed

    Soto, L F; Miller, C H; Ognibere, A J

    1993-06-01

    Clinicians should be aware of the complications of rhabdomyolysis in patients who ingest doxylamine succinate and other over-the-counter antihistamines. The easy availability of these substances increases the potential not only for intentional overdose by adults but also for inadvertent ingestion by children. Prompt intervention and careful assessment of renal function, urinary output, and serum creatine kinase levels may represent the difference between an uncomplicated course and acute renal failure. PMID:8099438

  16. Nuclear medicine imaging in rhabdomyolysis

    SciTech Connect

    Cornelius, E.A.

    1982-10-01

    A case of severe rhabdomyolysis is reported in which, some seven and one-half weeks after its occurrence, a gallium scan was strongly positive, due to abscess formation in the damaged muscle. A bone scan was weakly positive in the same area, due to gallium photons. A review of the the reported cases reveals that bone scans are a very sensitive indicator of acute muscle damage and are useful to monitor its repair.

  17. Nelarabine Associated Myotoxicity and Rhabdomyolysis

    PubMed Central

    Haider, Mahnur; Rizvi, Syed Ahsan

    2015-01-01

    Nelarabine (ara-G; Arranon; compound 506U78) is an antineoplastic purine analog used for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). The drug was granted accelerated approval in October 2005 by the US Food and Drug Administration (FDA) given the efficacy (induction of complete responses) noted in 2 single-arm trials (one in pediatric setting and one in adult patient population). The main spectra of toxicities that have been reported in these clinical trials and subsequent studies are hematological and neurological. Nelarabine induced rhabdomyolysis and increased creatinine phosphokinase (CK; CPK) levels apparently have been reported and this side effect has been added as an adverse reaction in the product monograph from the drug company during postmarketing surveillance. However, the true extent and incidence of the myotoxicity from the drug are unclear. In this paper we report a grade IV CK elevation and rhabdomyolysis in a patient with T-ALL treated with nelarabine. Given the reported finding, we examined the literature further for myotoxicity, increased CK, and/or rhabdomyolysis associated with the use of the nelarabine and report our findings. PMID:25866685

  18. Risk factors for rhabdomyolysis following doxylamine overdose.

    PubMed

    Jo, Young-Il; Song, Jong-Oh; Park, Jung-Hwan; Koh, Soon-Young; Lee, Seung-Min; Seo, Tae-Ho; Lee, Jong-Ho

    2007-08-01

    The objective of this prospective study was to identify risk factors for developing rhabdomyolysis in patients with doxylamine overdose. Patients who were admitted to a university teaching hospital between July 2000 and September 2005 due to doxylamine overdose were recruited. Demographic information, clinical variables, and laboratory data were investigated. Twenty-seven (M/F 12/15, age 33.2 +/-13.1 years) patients were enrolled. Sixteen (59%) of 27 patients developed rhabdomyolysis and three (19%) of 16 patients with rhabdomyolysis also developed acute renal failure. Patients who developed rhabdomyolysis differed from those who did not in the amount of doxylamine ingested, initial serum creatitnine and arterial pH. In multivariate regression analysis, the only reliable predictor of rhabdomyolysis was the amount of doxylamine ingested (P = 0.039). The amount of doxylamine ingested (>/= 20 mg/kg) predicted the development of rhabdomyolysis with a sensitivity of 81%, a specificity of 82%, a positive predictive value of 87%, and a negative predictive value of 75%.In conclusion, rhabdomyolysis following doxylamine overdose was common, occurring in 87% of patients who ingested more than 20 mg/kg. The amount of doxylamine ingested was the only reliable predictor for developing rhabdomyolysis following doxylamine overdose. PMID:17884948

  19. Haff Disease: Rhabdomyolysis After Eating Buffalo Fish

    PubMed Central

    Herman, Linda L.; Bies, Christine

    2014-01-01

    Haff disease, rhabdomyolysis after ingesting certain types of fish, was first reported in 1924 in Europe. There have been a limited number of cases reported in the United States. We present the case of a patient who presents with symptoms of rhabdomyolysis after eating cooked buffalo fish purchased at a suburban grocery market. PMID:25247039

  20. Non-traumatic rhabdomyolysis and diabetes.

    PubMed

    Sani, M-A; Campana-Salort, E; Begu-LeCorroller, A; Baccou, M; Valro, R; Vialettes, B

    2011-06-01

    The present clinical report describes the case of a spontaneously resolving rhabdomyolysis episode in a type 1 diabetic patient, who presented with multiple risk factors of this muscle complication, including uncontrolled brittle diabetes with sequences of hyper- and hypoglycaemic episodes in the same day, caloric restriction and intensive exercise. It should be borne in mind that rhabdomyolysis is not particularly rare in diabetes and can be severe. To raise clinicians' awareness of a possible rhabdomyolysis diagnosis, the various clinical conditions that are likely to lead to this complication in diabetic patients are also reviewed here. PMID:21550832

  1. Low-Intensity Repetitive Exercise Induced Rhabdomyolysis

    PubMed Central

    Tran, Mina; Hayden, Nicholas; Garcia, Brandon; Tucci, Veronica

    2015-01-01

    Rhabdomyolysis is a rare condition caused by the proteins of damaged muscle cells entering the bloodstream and damaging the kidneys. Common symptoms of rhabdomyolysis are muscle pain and fatigue in conjunction with dark urine; kidney damage is a common symptom among these patients. We present a case of a 23-year-old woman who displayed myalgia in the upper extremities caused by low-intensity and high-repetition exercise. She was successfully diagnosed and treated for exertional rhabdomyolysis. This patient had no significant medical history that would induce this condition. We urge the emergency medical community to observe and monitor patients that complain of myalgia to ensure they are not suffering from rhabdomyolysis even in atypical cases. PMID:26693360

  2. Rhabdomyolysis

    MedlinePLUS

    ... by injury or any other condition that damages skeletal muscle. Problems that may lead to this disease include: ... A physical exam will show tender or damaged skeletal muscles. The following tests may be done: Creatine kinase ( ...

  3. Acute rhabdomyolysis associated with atypical Guillain-Barr syndrome.

    PubMed Central

    Scott, A. J.; Duncan, R.; Henderson, L.; Jamal, G. A.; Kennedy, P. G.

    1991-01-01

    We report a patient with atypical Guillain-Barr syndrome associated with acute rhabdomyolysis. Rhabdomyolysis may be the cause of elevation of creatine kinase sometimes seen in patients with Guillain-Barr syndrome. PMID:2057435

  4. A case of massive rhabdomyolysis following molindone administration.

    PubMed

    Johnson, S B; Alvarez, W A; Freinhar, J P

    1986-12-01

    Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction. PMID:3782049

  5. Increased Frequency of Rhabdomyolysis in Familial Dysautonomia

    PubMed Central

    Palma, Jose-Alberto; Roda, Ricardo; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

    2015-01-01

    Background Familial dysautonomia (FD, OMIM# 223900) is an autosomal recessive disease featured by impaired pain and temperature perception and lack of functional muscle spindles. After 3 FD patients presented with rhabdomyolysis in a short time span, we aimed to determine the frequency of rhabdomyolysis is this population. Methods and Results In a retrospective chart review of 665 FD patients, 8 patients had at least 1 episode of rhabdomyolysis. Two patients had 2 episodes. The average incidence of rhabdomyolysis in FD was 7.5 per 10,000 person-years. By comparison, the average incidence with statins has been reported to be 0.44 per 10,000 person-years. Mean maximum creatine kinase (CK) level was 32,714 64,749 U/l. Three patients had a hip magnetic resonance imaging showing gluteal hyperintensities. Conclusions Patients with FD have an increased incidence of rhabdomyolysis. We hypothesize that this may result from a combination of absent functional muscle spindles and muscle mitochondrial abnormalities. PMID:26202308

  6. Rhabdomyolysis Presenting as Orbital Apex Syndrome.

    PubMed

    Wi, Jae Min; Chi, Mijung

    2016-01-01

    Rhabdomyolysis is a condition in which striated muscle tissue breaks down rapidly and releases muscular cell constituents into extracellular fluid and the circulation. Renal symptoms, such as acute renal failure, are major complications of rhabdomyolysis. However, no previous report of rhabdomyolysis associated with orbital complication has been issued. Here, we report the first patient of rhabdomyolysis presenting as orbital apex syndrome. A 66-year-old man presented with right periorbital swelling with erythematous patches and conjunctival chemosis. In addition, swelling, redness, and vesicles were observed in both lower legs. He was found in a drunken state with the right side of his face pressed against a table. Ophthalmic examination showed right eye fixation in all directions and ischemic change of retina. Blood testing showed elevated muscle enzyme associated with muscle destruction. And computed tomography of the orbit showed swelling of right extraocular muscles and crowding of right orbital apex. Under a diagnosis of rhabdomyolysis-associated orbital apex syndrome and central retinal artery occlusion, intravenous steroid and antibiotics therapy with intraocular pressure-lowering topicals were begun. Clinical presentation, treatment course, and follow-up are discussed. PMID:26703071

  7. Mitochondrial myopathy presenting as rhabdomyolysis.

    PubMed

    Patchett, David C; Grover, Michael L

    2011-06-01

    A 37-year-old white woman presented with acute bilateral hamstring pain after hiking. She had a creatine kinase level of 11,144 U/L. Rhabdomyolysis was diagnosed and the patient was admitted for intravenous fluid hydration. The patient continued to have exercise-induced myalgias and elevations in her creatine kinase level. Rheumatologic causes were ruled out and results from electromyogram testing were nondiagnostic. A muscle biopsy revealed a mitochondrial myopathy. The 22 mitochondrial DNA and transfer RNA genes were sequenced. An A-to-G transition was found at nucleotide position 4281 in the transfer RNA isoleucine gene. The patient was placed on a regimen of riboflavin, vitamin C, and coenzyme Q10, which provided mild relief. The patient returned to the emergency department 2 more times after vigorous exercise, with creatine kinase levels as high as 2800 U/L. At last follow-up, the patient was using a fentanyl citrate transdermal patch, which enabled her to perform moderate exercise without pain. PMID:21771927

  8. Alcohol abuse-related severe acute pancreatitis with rhabdomyolysis complications

    PubMed Central

    SU, MAO-SHENG; JIANG, YING; YAN, XIAO-YUAN HU; ZHAO, QING-HUA; LIU, ZHI-WEI; ZHANG, WEN-ZHI; HE, LEI

    2013-01-01

    Non-traumatic rhabdomyolysis is a rare complication of acute pancreatitis. One of the major risk factors of both acute pancreatitis and rhabdomyolysis is alcohol abuse. However, only a few studies have reported the prognosis and association of severe acute pancreatitis (SAP) and rhabdomyolysis in alcohol abuse patients. In the present study, we report two cases presenting with SAP complicated by rhabdomyolysis following high-dose alcohol intake. The disease onset, clinical manifestations, laboratory data, diagnosis and treatment procedure of each patient were recorded, and the association with rhabdomyolysis was analyzed. Alcohol consumption was the most predominant cause of SAP and rhabdomyolysis in these patients. SAP-related rhabdomyolysis was primarily induced by the toxicity associated with pancreatic necrosis. The laboratory tests revealed that the concentration of serum creatine kinase (CK) and myoglobin increased and acute renal failure symptoms were present, which provided an exact diagnosis for SAP-induced rhabdomyolysis. Rhabdomyolysis and subsequent hypermyoglobinuria severely impaired kidney function and aggravated hypocalcemia. The therapy of early stage SAP complicated by rhabdomyolysis involved liquid resuscitation support. When first stage treatment fails, blood purification should be performed immediately. Both patients developed multiple organ failure (MOF) and succumbed to the disease. Considering the two cases presented, we conclude that alcohol-related SAP complicated by rhabdomyolysis may have a poor clinical prognosis. PMID:23251265

  9. Acute kidney injury and rhabdomyolysis due to multiple wasp stings

    PubMed Central

    Radhakrishnan, Hemachandar

    2014-01-01

    In most patients, wasp stings cause local reactions and rarely anaphylaxis. Acute kidney injury and rhabdomyolysis are unusual complications of wasp stings. We report a case of acute kidney injury and rhabdomyolysis secondary to multiple wasp stings. A 55-year-old farmer developed multi organ dysfunction with acute kidney injury and rhabdomyolysis 3 days after he had sustained multiple wasp stings. The etiology of acute kidney injury is probably both rhabdomyolysis and acute tubular necrosis. He improved completely after hemodialysis and intensive care. PMID:25097363

  10. Rhabdomyolysis, compartment syndrome and thermal injury

    PubMed Central

    Coban, Yusuf Kenan

    2014-01-01

    Rhabdomyolysis (RML) after electrical burns and crush injuries is a well-known clinical entity, but its occurrence following thermal injury has not gained so much attention. Capillary leak syndrome and following polycompartmental syndrome are devastating end results of major thermal injuries. In the current review, polycompartment syndrome within the clinical picture of systemic oedema and its relationship to RML is discussed along with its management and prevention. PMID:24834396

  11. Exertional Rhabdomyolysis: What Is It and Why Should We Care?

    ERIC Educational Resources Information Center

    Thomas, David Q.; Carlson, Kelli A.; Marzano, Amy; Garrahy, Deborah

    2012-01-01

    Exertional rhabdomyolysis gained increased attention recently when 13 football players from the University of Iowa developed this condition after an especially demanding practice session and were hospitalized. Exertional rhabdomyolysis may lead to severe kidney stress, kidney failure, and even sudden death. Anyone who does physical exercise at a

  12. Exertional Rhabdomyolysis: What Is It and Why Should We Care?

    ERIC Educational Resources Information Center

    Thomas, David Q.; Carlson, Kelli A.; Marzano, Amy; Garrahy, Deborah

    2012-01-01

    Exertional rhabdomyolysis gained increased attention recently when 13 football players from the University of Iowa developed this condition after an especially demanding practice session and were hospitalized. Exertional rhabdomyolysis may lead to severe kidney stress, kidney failure, and even sudden death. Anyone who does physical exercise at a…

  13. Typhoid Fever Complicated by Hemophagocytic Lymphohistiocytosis and Rhabdomyolysis.

    PubMed

    Non, Lemuel R; Patel, Rupa; Esmaeeli, Amir; Despotovic, Vladimir

    2015-11-01

    Hemophagocytic lymphohistiocytosis (HLH) and rhabdomyolysis are rare complications of typhoid fever from Salmonella enterica serovar Typhi. Herein, we describe the clinical features in a 21-year-old female from India who presented to the intensive care unit with fever, severe pancytopenia, and rhabdomyolysis. PMID:26324725

  14. Rhabdomyolysis: a review, with emphasis on the pediatric population.

    PubMed

    Elsayed, Essam F; Reilly, Robert F

    2010-01-01

    Rhabdomyolysis is a common clinical syndrome and accounts for 7% of all cases of acute kidney injury (AKI) in the USA. It can result from a wide variety of disorders, such as trauma, exercise, medications and infection, but in the pediatric population, infection and inherited disorders are the most common causes of rhabdomyolysis. Approximately half of patients with rhabdomyolysis present with the triad of myalgias, weakness and dark urine. The clinical suspicion, especially in the setting of trauma or drugs, is supported by elevated creatinine kinase levels and confirmed by the measurement of myoglobin levels in serum or urine. Muscle biopsy and genetic testing should be performed if rhabdomyolysis is recurrent or metabolic myopathy is suspected. Early recognition is important to prevent AKI through the use of aggressive hydration. Prevention is important in patients with inherited forms, but novel therapies may be developed with the better understanding of the pathophysiology and genetics of rhabdomyolysis. PMID:19529963

  15. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians.

    PubMed

    Huerta-Alardn, Ana L; Varon, Joseph; Marik, Paul E

    2005-04-01

    Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration. PMID:15774072

  16. Bench-to-bedside review: Rhabdomyolysis an overview for clinicians

    PubMed Central

    Huerta-Alardn, Ana L; Varon, Joseph; Marik, Paul E

    2005-01-01

    Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration. PMID:15774072

  17. Acute renal failure due to atraumatic rhabdomyolysis in coma diabeticum.

    PubMed

    Zobel, G; Ring, E; Trop, M; Trittenwein, G

    1986-01-01

    A case report of a twelve year old boy with coma diabeticum and atraumatic rhabdomyolysis is presented. At admission the patient was comatose. Hyperglycemia and hyperosmolarity were the main metabolic disorders. 32 hours after admission marked myoglobinuria due to atraumatic rhabdomyolysis led to acute renal failure. At first uremia was compensated by arteriovenous hemofiltration and later by conventional hemodialysis. During the sixth week after admission urinary output started and serum creatinine and urea levels gradually declined to normal. Special attention should be paid to atraumatic rhabdomyolysis in patients with coma diabeticum. Continuous arteriovenous hemofiltration is an effective extracorporal therapeutic technique to compensate uremia in critically ill patients. PMID:3818184

  18. Mojave rattlesnake envenomation: prolonged neurotoxicity and rhabdomyolysis.

    PubMed

    Jansen, P W; Perkin, R M; Van Stralen, D

    1992-03-01

    An 11-year-old girl presented to the emergency department with hypoventilation and shock after being bitten by a Mojave rattlesnake. Intubation was required, and she improved rapidly after fluid resuscitation and antivenom administration. She was extubated four hours after envenomation and did well. The patient subsequently developed increased weakness and cranial nerve paresis and required reintubation for respiratory failure at 30 hours after envenomation despite administration of 30 vials of antivenom. She improved after administration of additional antivenom and was extubated ten hours later. Twenty-four hours after envenomation, signs of rhabdomyolysis were noted with myoglobinuria and a creatine phosphokinase level of 96,400 units/L. Myoglobinuric renal failure was treated with mannitol, hydration, and alkalinization of the urine. The patient's renal and neurological functions improved steadily during the following three to four days. Neurotoxic and myotoxic effects of Mojave venom are known to occur but are not well documented in human beings. Recognition of potential complications from envenomation such as respiratory paralysis and rhabdomyolysis with myoglobinuric renal failure is critical. PMID:1536496

  19. Rhabdomyolysis in a young vegetarian athlete.

    PubMed

    Borrione, Paolo; Spaccamiglio, Angela; Salvo, Raffaella Antonella; Mastrone, Antonietta; Fagnani, Federica; Pigozzi, Fabio

    2009-11-01

    Rhabdomyolysis is a rare but potentially life-threatening disorder. The long list of known risk factors includes trauma, drug intoxication, alcoholism, hyperpyrexia, vascular occlusion, infections, electrolyte imbalances, heat intolerance, seizures, severe exertion, and substance abuse. Exercise-induced muscle damage is commonly experienced after physical activity, and different studies showed that the amount of protein consumed seems to affect its magnitude. In this regard, some concern has been raised about vegetarian athletes. We present a case of rhabdomyolysis that occurred in a young athlete following a poorly planned vegetarian diet. The athlete experienced progressive weakness and intermittent muscle aches particularly in the legs, malaise, episodic tachycardia, and nausea. Serum creatine kinase was markedly elevated (9952 units/liter), and a mild alteration of transaminase values was observed. The patient was hydrated intravenously and recovered fully within 5 days. The controlled introduction of a planned amount of protein in the diet allowed the athlete to carry on with his sporting activity fully without any further muscle problems. Physical exercise mainly engages the muscular system, and a balanced diet is essential to ensure the energy demands and the anabolic response. A vegetarian diet per se is not associated with detrimental effects in athletes, but an optimal protein intake should be achieved through careful planning with an emphasis on protein-rich plant foods. PMID:19661778

  20. Pheniramine Maleate-Induced Rhabdomyolysis and Aki: Is it Fatal?

    PubMed Central

    Venugopal, K; Reddy, M Mallikarjun; Bharathraj, M.Y; Jaligidad, Kadappa; Kushal, D.P

    2014-01-01

    Pheniramine maleate is an easily accessible, over-the-counterantihistaminic, which is frequently involved in overdoses. Pheniramine has antimuscarinic effect causing tachycardia, dilated pupils, urinary retention, and dry flushed skin, and decreased bowel sounds, confusion, mild increase in body temperature, cardiac arrhythmias, and seizures at lethal doses. It has not been implicated as an important cause of rhabdomyolysis and acute kidney injury (AKI). Rhabdomyolysis causing AKI is rarely reported in the literature. This case report emphasizes the occurrence of nontraumatic rhabdomyolysis in pheniramine maleate overdose which required hemodialysis. Since there is a lack of a specific antidote, treatment is mainly symptomatic and supportive. We report a fatal case of a young male with a very high dose of consumption of pheniramine maleate (4.077 g), which was complicated by seizures, respiratory depression, nontraumatic rhabdomyolysis, and AKI. Despite hemodialysis, ventilator support, and other intensive supportive care, patient could not survive and death ensued due to multiorgan dysfunction syndrome. PMID:25948974

  1. Clinical spectrum of rhabdomyolysis presented to pediatric emergency department

    PubMed Central

    2013-01-01

    Background Rhabdomyolysis is a potentially life-threatening syndrome that can develop from a variety of causes. The aim of the work is to analyze the clinical spectrum and to evaluate the prevalence of various etiologies in children, who present to the emergency department (ED) with rhabdomyolysis. Methods During a 6-year study period, we retrospectively analyzed the medical charts of patients, aged 18 years or younger, with a definite diagnosis of rhabdomyolysis and serum creatinine phosphokinase (CK) levels greater than 1000IU/L. We analyzed the clinical spectrum and evaluated the potential risk factors of acute renal failure (ARF). Results Thirty-seven patients (mean age = 10.2 5.5 years), including 26 males and 11 females, were enrolled in the study. Two of the most common presented symptoms in these 37 patients were muscle pain and muscle weakness (83.8% and 73%, respectively). Dark urine was reported in only 5.4% of the patients. The leading cause of rhabdomyolysis in the 0- to 9-year age group was presumed infection, and the leading cause in the 10- to 18-year age group was trauma and exercise. The incidence of ARF associated with rhabdomyolysis was 8.1 % and no child needed for renal replacement therapy (RRT). We did not identify any reliable predictors of ARF or need for RRT. Conclusions The classic triad of symptoms of rhabdomyolysis includes myalgia, weakness and dark urine are not always presented in children. The cause of rhabdomyolysis in younger age is different from that of teenager group. However, the prognosis of rhabdomyolysis was good with appropriate management. PMID:24004920

  2. Sertraline-Induced Rhabdomyolysis: A Case Report and Literature Review.

    PubMed

    Snyder, Mitchell; Kish, Troy

    2016-01-01

    The objective of this study is to report a case of sertraline-induced rhabdomyolysis in a female patient with a history of depression. A 25-year-old Hispanic woman with a history of depression reported to the emergency department (ED) with a chief complaint of muscle swelling and soreness and dark urine. The patient's creatine phosphokinase was 15,103 U/L. Despite treatment with IV normal saline, the patient's symptoms persisted and the creatine phosphokinase continued to rise to a peak of 16,778 U/L on day 2. The patient reported completing a strenuous, although routine, exercise the day before arriving at the ED, and her medication history was only significant for sertraline. Of note, 6 weeks before her visit to the ED, sertraline was increased from 100 mg daily to 150 mg daily. The patient's rhabdomyolysis was attributed to sertraline in conjunction with recent exercise. Selective serotonin reuptake inhibitor (SSRI)-induced rhabdomyolysis has been documented in 5 case reports. Similar to most reports, our patient presented with rhabdomyolysis in the presence of both SSRI use and exercise. Unlike the majority of previous reports, our patient was not taking other medications with documented association to rhabdomyolysis and had performed routine exercise before presenting with rhabdomyolysis. Although the mechanism of SSRI-induced rhabdomyolysis is not known, a theory posits that sertraline may have a role in muscle contraction and relaxation, leading to shorter time to contracture and longer time of contraction. The use of sertraline and other SSRIs may be associated with development of rhabdomyolysis, especially in the presence of strenuous exercise. PMID:25581857

  3. Acute renal failure in severe exertional rhabdomyolysis.

    PubMed

    Uberoi, H S; Dugal, J S; Kasthuri, A S; Kolhe, V S; Kumar, A K; Cruz, S A

    1991-09-01

    During the last 6 years, 7 healthy individuals who were reasonably well acclimatised to physical exertion came under observation with acute renal failure due to exercise induced myoglobinuria. Their mean age was 20 years, and renal failure resulted after cross country run of 10-15 km in 6 cases and long route march of 90 km in 3 days in one case. There was no evidence of effects of heat, dehydration or hypotension. Apart from myoglobinuria and significant urinary sediments, serum aldolase (mean 69.0 SL u/ml) and serum creatinine phosphokinase (mean 120.0 Sigma u/ml) were also elevated. Maximum blood urea and creatinine were 224 mg/dl and 13.9 mg/dl respectively. Hypocalcaemia was noticed in 3 cases, hyperkalaemia in 4 cases and hyperuricaemia in one case during the oliguric phase. One case had features of non-oliguric acute renal failure. All cases recovered though 4 cases required dialysis support. Kidney biopsy in 3 cases showed recovering acute tubular necrosis with eosinophilic material in tubules. Lactate studies in the convalescent period revealed normal response and repeat physical exertion of same severity after 6 months did not reproduce the syndrome. It is concluded that exertional rhabdomyolysis unassociated with heat stress is a rare entity, and with prompt diagnosis and energic management results are rewarding. PMID:1814900

  4. Exertional rhabdomyolysis after recent coxsackie B virus infection.

    PubMed

    Marinella, M A

    1998-11-01

    Acute, exertional rhabdomyolysis typically follows strenuous exercise of the eccentric type, such as that which occurs during military training or repetitive weight lifting in unconditioned individuals. Complications can be significant and include compartment syndrome and acute renal failure due to myoglobinuria, especially in the setting of volume depletion. Rhabdomyolysis may also be precipitated by viral infections, usually influenza virus. I report an unusual case of a female patient who had acute rhabdomyolysis, complicated by compartment syndrome of both legs, after beginning an exercise regimen on a treadmill. The patient reported a viral-like illness several days before and was found to have a rise in antibodies to coxsackieviruses B4 and B5. PMID:9824191

  5. Doxylamine overdose as a potential cause of rhabdomyolysis.

    PubMed

    Leybishkis, B; Fasseas, P; Ryan, K F

    2001-07-01

    Doxylamine succinate, an over-the-counter antihistamine, is commonly used as a nighttime sleep aid in the short-term management of insomnia. It is also used in combination with antitussive and decongestant agents for the temporary relief of common cold symptoms. Doxylamine is frequently involved in accidental and intentional overdoses. Rhabdomyolysis and secondary acute renal failure are rare but potentially serious complications, making early recognition and treatment essential. With the large number of nonprescription antihistamines and sleep aids available to the general public, it is important to keep in mind that overdose is a potential problem. The complications associated with overdose of these medications are just as life threatening as those associated with prescription drugs. A high index of suspicion and evaluation of rhabdomyolysis is warranted in antihistamine toxicity. We report an observation of severe rhabdomyolysis associated with doxylamine overdose. PMID:11465247

  6. Sports Induced Cardiac Arrest: A Case of Missed Rhabdomyolysis

    PubMed Central

    Gautam, Parshotam L; Nain, Prabhdeep Singh

    2015-01-01

    Exercise induced rhabdomyolysis although uncommon, is well known in strenuous and exhaustive sports like marathons, cycling and wrestlers. But it is not known in Kabaddi players. We report a case of nearly fatal rhabdomyolysis which was missed during early resuscitation in emergency room and lead to cardiac arrest due to catastrophic metabolic acidosis and severe -hyperkalemia. After high quality cardiopulmonary resuscitation and return of spontaneous rhythm, emergency resuscitative exploratory laparotomy was performed for suspected bladder injury which was negative. He had remarkable recovery over 24 h following diagnosis and aggressive supportive management including peritoneal dialysis. Heat stroke and rhabdomyolysis should be suspected early in players playing strenuous sports in tropical countries even during winter. High degree of suspicion and early aggressive general support is the key to success for unusual clinical presentation of any such clinical entity. PMID:26500986

  7. Exercise-induced rhabdomyolysis from stationary biking: a case report

    PubMed Central

    Inklebarger, J; Galanis, N; Kirkos, J; Kapetanos, G

    2010-01-01

    There are several reports concerning exercise and rabdomyolysis. There has been no report in the English literature of exercise induced rabdomyolisis from a stationary bike. A 63-year-old female recreational athlete presented to our hospital seeking treatment for lower back, leg pain and stiffness after exercising on a stationary bicycle one day prior. Blood work showed a raised CK of 38,120 U/L, a myoglobin of 5330 and an AST 495 U/L with normal urea and electrolytes. Urinalysis remained negative. She was admitted for oral and intravenous hydration and fluid balance monitoring This is a very rare case of rhabdomyolysis due to exercise. This study highlights the difficulties faced by accident and emergency teams in distinguishing delayed onset muscle soreness (DOMS) from exercise-induced rhabdomyolysis, and reinforces the concept that rhabdomyolysis can occur at any level of exercise intensity. PMID:21311638

  8. Rhabdomyolysis Secondary to Influenza A Infection: A Case Report and Review of the Literature

    PubMed Central

    Fadila, Mario F.; Wool, Kenneth J.

    2015-01-01

    Context: Rhabdomyolysis is a serious clinical syndrome that results from damage to skeletal muscles. Common causes include drugs, crush injuries, seizures, heat, exertion, and infection. Viral infections, particularly Influenza A, have been recognized as a cause of rhabdomyolysis. Case Report: Our report describes a 58-year-old male who presented with viral pneumonia secondary to Influenza A virus infection. His hospital course was complicated by acute renal failure secondary to rhabdomyolysis, which was attributed to an overwhelming viremia. We discuss the differential diagnosis of rhabdomyolysis and review the literature for cases of Influenza A-related rhabdomyolysis. We also discuss the proposed mechanisms for the condition. Conclusion: The scope of clinical manifestations of Influenza A infection extends beyond pulmonary syndromes. Rhabdomyolysis is being increasingly recognized as a complication of Influenza A infection with considerable morbidity and mortality. PMID:25839005

  9. Acute renal dysfunction in a patient presenting with rhabdomyolysis due to Hypothyroidism attributed to Hashimoto's Disease

    PubMed Central

    Nikolaidou, C; Gouridou, E; Ilonidis, G; Boudouris, G

    2010-01-01

    We describe a patient with rhabdomyolysis and acute renal dysfunction due to hypothyroidism, attributed to Hashimoto's disease. Though rhabdomyolysis could be life-threatening, it is a rare complication of hypothyroidism, especially when other precipitating factors, such as exercise, alcohol, medications or renal failure, are absent. Nevertheless, hypothyroidism can be an authentic cause of rhabdomyolysis and should always be considered when elevated creatine kinase (CK) and other muscle enzymes concentrations cannot be attributed to any major factor. PMID:21311639

  10. Rhabdomyolysis Caused by Candida parapsilosis in a Patient with Acute Myeloid Leukemia after Bone Marrow Transplantation.

    PubMed

    Kakiuchi, Seiji; Yakushijin, Kimikazu; Yamamoto, Katsuya; Tomioka, Hideo; Inui, Yumiko; Okamura, Atsuo; Kawamoto, Shinichiro; Minami, Yosuke; Murayama, Tohru; Ito, Mitsuhiro; Matsuoka, Hiroshi; Minami, Hironobu

    2015-01-01

    Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients. PMID:26278302

  11. Rhabdomyolysis due to Trimethoprim-Sulfamethoxazole Administration following a Hematopoietic Stem Cell Transplant

    PubMed Central

    Augustyn, Alexander; Lisa Alattar, Mona; Naina, Harris

    2015-01-01

    Rhabdomyolysis, a syndrome of muscle necrosis, is a life-threatening event. Here we describe the case of a patient with chronic myeloid leukemia who underwent a haploidentical stem cell transplant and subsequently developed rhabdomyolysis after beginning trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis therapy. Rechallenge with TMP/SMX resulted in a repeat episode of rhabdomyolysis and confirmed the association. Withdrawal of TMP/SMX led to sustained normalization of creatine kinase levels in the patient. A high index of suspicion is necessary to identify TMP/SMX as the cause of rhabdomyolysis in immunocompromised patients. PMID:26557399

  12. Compartment syndrome, rhabdomyolysis and risk of acute renal failure as complications of the lithotomy position.

    PubMed

    Bocca, Gianlorenzo; van Moorselaar, Jeroen A; Feitz, Wout F J; van der Staak, Frans H J M; Monnens, Leo A H

    2002-01-01

    Compartment syndrome, rhabdomyolysis and the risk of acute renal failure are potential complications of the lithotomy position. A six-year-old girl is described who developed a compartment syndrome with rhabdomyolysis after prolonged surgery in the lithotomy position. This complication occurred three times over ten years in our hospital. Rhabdomyolysis may induce acute renal failure. The pathogenesis of rhabdomyolysis--induced renal failure has not yet been elucidated. However, forced diuresis by intravenous administration of mannitol and furosemide can prevent acute renal failure. PMID:12018636

  13. Drug-Induced Rhabdomyolysis with Elevated Cardiac Troponin T

    PubMed Central

    Egholm, Gro; Pareek, Manan

    2015-01-01

    The essential role of cardiac troponin in the diagnosis of acute myocardial infarction has led to the development of high-sensitivity assays, which are able to detect very small amounts of myocardial necrosis. The high-sensitivity cardiac troponin T assay, however, is not entirely specific for myocardial injury. This case report describes a 48-year-old woman, who, two years after cardiac transplantation, presented with rhabdomyolysis. During the course of the disease, her troponin T level was elevated on repeated occasions, but other definitive evidence of myocardial injury was not found. Asymptomatic cardiac troponin T elevations during rhabdomyolysis may be due to either cardiac involvement or false positive results stemming from skeletal muscle injury. PMID:26557852

  14. Rhabdomyolysis and myoglobinuric nephrosis (capture myopathy) in a striped dolphin.

    PubMed

    Herrez, P; Sierra, E; Arbelo, M; Jaber, J R; de Los Monteros, A Espinosa; Fernndez, A

    2007-10-01

    This report describes delayed myoglobinuric capture myopathy in a striped dolphin (Stenella coeruleoalba) found stranded alive on the coast of Fuerteventura (Canary Islands, Spain). The animal was transported to Gran Canaria where it died 48 hr after stranding. The main lesions consisted of acute rhabdomyolysis affecting both cardiac and skeletal muscles, and myoglobinuric nephrosis. Using immunohistochemistry, degenerate myofibers with depletion of myoglobin, and an intracytoplasmatic immunoreaction for fibrinogen were observed. Orange-red pigmented casts in renal tubular lumens were strongly immunolabeled for myoglobin. To our knowledge, this is the first pathologic description of capture myopathy with myoglobinuric nephrosis in stranded cetaceans. Stress, exertion, trauma, and crush injury caused during the stranding, restraint, and transportation were the main causes of rhabdomyolysis in this case. PMID:17984278

  15. Rhabdomyolysis and acute kidney injury in dengue fever.

    PubMed

    Mishra, Arvind; Singh, Varun Kumar; Nanda, Satyan

    2015-01-01

    Rhabdomyolysis is a rare but potentially lethal complication of severe dengue fever. We present a case of 21-year-old man with fever, bodyache and black coloured and decreasing amount of urine. He was positive for NS1 (non-structural protein-1) antigen and IgM antibody for dengue. Platelet count was below 20 × 10(9)/L and kidney function test was deranged. Urine was positive for myoglobin. The patient was managed emergently on conservative lines and improved in 10 days. Rhabdomyolysis should always be kept in mind in a patient with severe dengue, as its early detection and prompt management can prevent further progression to acute renal failure. PMID:26174727

  16. Metabolic acidosis, rhabdomyolysis, and cardiovascular collapse after prolonged propofol infusion.

    PubMed

    Cannon, M L; Glazier, S S; Bauman, L A

    2001-12-01

    The authors present the hospital course of a 13-year-old girl with a closed head injury who received a prolonged infusion of propofol for sedation and, subsequently, died as a result of severe metabolic acidosis, rhabdomyolysis, and cardiovascular collapse. The patient had been treated for 4 days at a referring hospital for a severe closed head injury sustained in a fall from a bicycle. During treatment for elevations of intracranial pressure, she received a continuous propofol infusion (100 microg/kg/min). The patient began to exhibit severe high anion gap/low lactate metabolic acidosis, and was transferred to the pediatric intensive care unit at the authors' institution. On arrival there, the patient's Glasgow Coma Scale score was 3 and this remained unchanged during her brief stay. The severe metabolic acidosis was unresponsive to maximum therapy. Acute renal failure ensued as a result of rhabdomyolysis, and myocardial dysfunction with bizarre, wide QRS complexes developed without hyperkalemia. The patient died of myocardial collapse with severe metabolic acidosis and multisystem organ failure (involving renal, hepatic, and cardiac systems) approximately 15 hours after admission to the authors' institution. This patient represents another case of severe metabolic acidosis, rhabdomyolysis, and cardiovascular collapse observed after a prolonged propofol infusion in a pediatric patient. The authors suggest selection of other pharmacological agents for long-term sedation in pediatric patients. PMID:11765823

  17. Sturge-Weber syndrome coexisting with episodes of rhabdomyolysis

    PubMed Central

    2013-01-01

    Background Sturge-Weber syndrome is a congenital neurocutaneous disorder characterized by facial port-wine stain, leptomeningeal angioma, and neurological disorders. Sturge-Weber syndrome can coexist with other disorders in a few patients; however, muscular abnormalities have not been reported in patients with Sturge-Weber syndrome. Case presentation A Chinese girl presented with extensive port-wine stains, congenital bilateral glaucoma, and leptomeningeal angiomatosis. The neurocutaneous symptoms were consistent with the diagnostic criteria of Sturge-Weber syndrome. Meanwhile, episodes of rhabdomyolysis were supported by the recurrent symptoms as follows: exercise intolerance, hyperCKmia, elevated serum myoglobin, and renal failure. Myopathological features and high level of blood long-chain acyl-carnitine indicated that episodes of rhabdomyolysis might be caused by lipid metabolic myopathy. Causative mutations were not found in the CPT2, ACADVL, and GNAQ gene. Conclusions We report the first case that Sturge-Weber syndrome coexists with episodes of rhabdomyolysis associated with lipid metabolic myopathy. PMID:24207015

  18. FATAL RHABDOMYOLYSIS IN DENGUE HEMORRHAGIC FEVER: A CASE REPORT.

    PubMed

    Siriyakorn, Nirada; Insiripong, Somchai

    2015-01-01

    Dengue hemorrhagic fever is caused by dengue virus infection. The classical manifestations consist of fever, thrombocytopenia, and hemoconcentration. However, its unusual complications may be fatal, such as prolong shock, massive bleeding, volume overload, and unusual manifestations, for example, severe rhabdomyolysis. Here we report a case of 17-year old Thai man who was referred to our hospital because of 7-day fever with thrombocytopenia, hemoconcentration and right pleural effusion. The serology tests confirmed to be dengue infection. He developed various complications: severe hepatitis, coagulopathy, and heavy proteinuria; encephalopathy that needed a respiratory ventilator. On day 12 of fever, he had myalgia and passed dark urine. Serum creatinine and serum creatinine phosphokinase (CPK) were found abnormally high. He was diagnosed as severe rhabdomyolysis with acute kidney injury, and immediate hemodialysis was performed. He did not respond to treatment and expired within three hours. Although the mechanism of severe rhabdomyolysis in dengue fever is not clearly known, it may theoretically be proposed such as direct muscle cell injury leading to myositis by dengue virus, myotoxic cytokines which are produced in response to viral infection, dehydration or hypophosphatemia. PMID:26506741

  19. Nontraumatic rhabdomyolysis with short-term alcohol intoxication – a case report

    PubMed Central

    Papadatos, Stamatis S; Deligiannis, Georgios; Bazoukis, George; Michelongona, Paschalia; Spiliopoulou, Aikaterini; Mylonas, Stefanos; Zissis, Christos

    2015-01-01

    Key Clinical Message Alcohol-induced rhabdomyolysis is a potentially life-threatening condition due to the probability of progression to acute renal injury. Patients admitted to emergency department with acute alcohol intoxication should always undergo blood and urine tests for early recognition and treatment of rhabdomyolysis. PMID:26509002

  20. Incidence, Etiology, and Outcomes of Rhabdomyolysis in a Single Tertiary Referral Center

    PubMed Central

    Park, Jae-Seok; Seo, Min-Sook; Gil, Hyo-Wook; Yang, Jong-Oh; Lee, Eun-Young

    2013-01-01

    We have encountered numerous cases of rhabdomyolysis associated with acute pesticide intoxication; however, the cause, incidence, and treatment outcomes of rhabdomyolysis have not been studied. The current study involved 2,125 patients hospitalized with acute chemical poisoning. Based on clinical and laboratory parameters and treatment outcomes, we found that overall incidence of rhabdomyolysis in our hospital was 0.06% (93 of 143,830 patients admitted), but the incidence associated with acute pesticide intoxication was 1.8% (33 of 1,793 cases). The incidence of rhabdomyolysis after pesticide intoxication was significantly higher in men than in women (P = 0.010). The amount of pesticide ingested was significantly higher in rhabdomyolysis patients than that in those who did not develop rhabdomyolysis (mean SD, 114.1 79.5 mL vs 74.1 94.2 mL, P = 0.010). Our results show that pesticide intoxication is a frequent cause of rhabdomyolysis and is more common among men than women. The volume of pesticide ingested, and not the degree of human toxicity, is the main factor influencing the incidence of rhabdomyolysis. PMID:23960447

  1. An unexpected and devastating adverse event of dasatinib: Rhabdomyolysis

    PubMed Central

    Uz, Burak; Dolasik, Ilhan

    2015-01-01

    We, herein, describe a 52-year-old male whom developed rhabdomyolysis and acute renal failure likely related to dasatinib shortly after the administration of treatment. After withdrawal of dasatinib, the myalgia reduced, and his CK returned to normal levels within a week. On follow-up acute renal failure did resolve without requiring dialysis, but unfortunately the patient died of severe respiratory distress. We recommend that musculoskeletal symptoms should be monitorized during therapy with dasatinib, and CML patients with musculoskeletal symptoms should have CK levels checked in order to prevent this unexpected but devastating adverse event. PMID:26870658

  2. Kinetic modelling of haemodialysis removal of myoglobin in rhabdomyolysis patients.

    PubMed

    Keir, R; Evans, N D; Hutchison, C A; Vigano, M R; Stella, A; Fabbrini, P; Storr, M; Chappell, M J

    2014-05-01

    An extended two compartment model is proposed to describe the dynamics of myoglobin in rhabdomyolysis patients undergoing dialysis. Before using clinical data to estimate the model's unknown parameters, structural identifiability analysis was performed to determine the parameters uniqueness given certain clinical observations. A Taylor series expansion method was implemented which found that the model was structurally globally/uniquely identifiable for both on- and off-dialysis phases. The fitted model was then used in a predictive capacity showing that the use of Theralite high cut-off (HCO) or HCO 1100 dialyser gave a significant reduction in myoglobin renal exposure compared to standard haemodialysis (HD). PMID:24008249

  3. Rhabdomyolysis and Acute Kidney Injury due to Severe Heat Stroke.

    PubMed

    Trujillo, Mximo H; Fragachn G, Carlos

    2011-01-01

    We present a case of heat stroke (HS) and acute kidney injury (AKI) due to severe rhabdomyolysis in a 14-year-old previously healthy female patient. When she was practicing strenuous exercise she suffered acute seizures and high fever. These symptoms were followed by coma and multiple organ failure (MOF), which included AKI, encephalopathy, fulminant hepatic failure (FHF), and disseminated intravascular coagulation (DIC). The patient was managed in the ICU with renal replacement therapy, ventilatory support, and other vital supporting measures. After three weeks of ICU treatment she made a full recovery. PMID:24826326

  4. An unexpected and devastating adverse event of dasatinib: Rhabdomyolysis.

    PubMed

    Uz, Burak; Dolasik, Ilhan

    2016-01-01

    We, herein, describe a 52-year-old male whom developed rhabdomyolysis and acute renal failure likely related to dasatinib shortly after the administration of treatment. After withdrawal of dasatinib, the myalgia reduced, and his CK returned to normal levels within a week. On follow-up acute renal failure did resolve without requiring dialysis, but unfortunately the patient died of severe respiratory distress. We recommend that musculoskeletal symptoms should be monitorized during therapy with dasatinib, and CML patients with musculoskeletal symptoms should have CK levels checked in order to prevent this unexpected but devastating adverse event. PMID:26870658

  5. A Patient with Dengue Fever Presenting with Rhabdomyolysis.

    PubMed

    Nakamura, Masayuki; Ikeda, Shuntaro; Nagahara, Hiroyuki; Hitsumoto, Tatsurou; Matsui, Shogo; Kadota, Hisaki; Shimizu, Hideaki; Ohshima, Kiyotaka; Yakushiji, Naoki; Hamada, Mareomi

    2015-01-01

    A 16-year-old boy stayed in Tokyo near Yoyogi Park for extracurricular high school activities. After returning home, he experienced an episode of fever and visited our emergency outpatient unit. He initially exhibited symptoms of leukopenia, thrombocytopenia and concomitant rhabdomyolysis and after admission simultaneously developed a biphasic fever and systemic erythema. Based on the results of reverse transcription polymerase chain reaction testing, he was finally diagnosed with dengue fever. After an absence of 70 years, dengue fever has reemerged as a domestic infection. Awareness of this trend led to our diagnosis. PMID:26134201

  6. Clinical features of and risk factors for rhabdomyolysis among adult patients with dengue virus infection.

    PubMed

    Huang, Shi-Yu; Lee, Ing-Kit; Liu, Jien-Wei; Kung, Chia-Te; Wang, Lin

    2015-01-01

    Among 1,076 dengue patients, 9 patients with rhabdomyolysis and 1,067 patients without rhabdomyolysis (controls) were retrospectively analyzed. Of nine patients with rhabdomyolysis, the most commonly reported symptom other than fever was myalgia; dengue hemorrhagic fever (DHF) was found in seven cases, and acute kidney injury was found in six cases. Furthermore, one (11.1%) patient died. The median duration from hospital admission to rhabdomyolysis diagnosis was 3 days. Patients with rhabdomyolysis had higher age, proportion of men, prevalence of hypertension, frequency of myalgia, and incidences of DHF, pleural effusion, and acute kidney injury than controls. Multivariate analysis showed that hypertension (odds ratio [OR] = 14.270), myalgia (OR = 20.377), and acute kidney injury (OR = 65.547) were independent risk factors for rhabdomyolysis. Comparison of cytokine/chemokine concentrations in 101 DHF patients, including those with (N = 4) and without (N = 97) rhabdomyolysis, showed that interleukin-6 and tumor necrosis factor-α levels were significantly increased in the former. PMID:25349377

  7. Clinical Features of and Risk Factors for Rhabdomyolysis Among Adult Patients with Dengue Virus Infection

    PubMed Central

    Huang, Shi-Yu; Lee, Ing-Kit; Liu, Jien-Wei; Kung, Chia-Te; Wang, Lin

    2015-01-01

    Among 1,076 dengue patients, 9 patients with rhabdomyolysis and 1,067 patients without rhabdomyolysis (controls) were retrospectively analyzed. Of nine patients with rhabdomyolysis, the most commonly reported symptom other than fever was myalgia; dengue hemorrhagic fever (DHF) was found in seven cases, and acute kidney injury was found in six cases. Furthermore, one (11.1%) patient died. The median duration from hospital admission to rhabdomyolysis diagnosis was 3 days. Patients with rhabdomyolysis had higher age, proportion of men, prevalence of hypertension, frequency of myalgia, and incidences of DHF, pleural effusion, and acute kidney injury than controls. Multivariate analysis showed that hypertension (odds ratio [OR] = 14.270), myalgia (OR = 20.377), and acute kidney injury (OR = 65.547) were independent risk factors for rhabdomyolysis. Comparison of cytokine/chemokine concentrations in 101 DHF patients, including those with (N = 4) and without (N = 97) rhabdomyolysis, showed that interleukin-6 and tumor necrosis factor-α levels were significantly increased in the former. PMID:25349377

  8. Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats

    PubMed Central

    Shih, Chih-Chin; Hii, Hiong-Ping; Tsao, Cheng-Ming; Chen, Shiu-Jen; Ka, Shuk-Man; Liao, Mei-Hui; Wu, Chin-Chen

    2016-01-01

    Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1) used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS). Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg) accompanied by procainamide therapy (50 mg/kg). During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6) levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis. PMID:26918767

  9. Rhabdomyolysis in the Setting of Induced Hypothyroidism and Statin Therapy: A Case Report

    PubMed Central

    Jbara, Yaser; Bricker, Dean

    2015-01-01

    Mild elevation of creatine kinase (CK) is common in untreated hypothyroidism, but severe myositis and overt rhabdomyolysis are rare. Similarly, muscle pain and CK elevation are potential side effects of statin therapy, yet rhabdomyolysis is likewise rare in the absence of medication interactions adversely affecting statin metabolism. The coexistence of statin therapy and hypothyroid states may synergistically increase the risk of myopathy. We describe a case of rhabdomyolysis attributable to induced hypothyroidism in a patient on chronic statin medication who was anticipating adjuvant radioiodine (131I) therapy for a thyroid carcinoma PMID:25960964

  10. Rhabdomyolysis in a neonate due to very long chain acyl CoA dehydrogenase deficiency

    PubMed Central

    Scott Schwoerer, Jessica; Cooper, Gena; van Calcar, Sandra

    2015-01-01

    Very long chain acyl CoA dehydrogenase deficiency (VLCADD) is an inborn error in long chain fatty acid oxidation with significant variability in the severity and timing of its clinical presentation. Neonatal presentations of VLCADD have included hypoglycemia and cardiomyopathy while rhabdomyolysis is usually a later onset complication. We describe a neonate with VLCADD presenting with rhabdomyolysis prior to the return of an abnormal newborn screen. This report suggests that evaluating for rhabdomyolysis, in addition to a cardiac and hepatic work-up, is an important part of the initial evaluation of an infant with an abnormal newborn screen suggesting a diagnosis of VLCADD.

  11. Potential role of coenzyme Q10 in facilitating recovery from statin-induced rhabdomyolysis.

    PubMed

    Wang, L W; Jabbour, A; Hayward, C S; Furlong, T J; Girgis, L; Macdonald, P S; Keogh, A M

    2015-04-01

    Rhabdomyolysis is a rare, but serious complication of statin therapy, and represents the most severe end of the spectrum of statin-induced myotoxicity. We report a case where coenzyme Q10 facilitated recovery from statin-induced rhabdomyolysis and acute renal failure, which had initially persisted despite statin cessation and haemodialysis. This observation is biologically plausible due to the recognised importance of coenzyme Q10 in mitochondrial bioenergetics within myocytes, and the fact that statins inhibit farnesyl pyrophosphate production, a biochemical step crucial for coenzyme Q10 synthesis. Coenzyme Q10 is generally well tolerated, and may potentially benefit patients with statin-induced rhabdomyolysis. PMID:25827512

  12. Electroconvulsive in a Schizophrenic Patient With Neuroleptic Malignant Syndrome and Rhabdomyolysis.

    PubMed

    San Gabriel, Maria Chona P; Eddula-Changala, Bharathi; Tan, Yonghong; Longshore, Carrol T

    2015-09-01

    We present the case of a middle-aged man with a chronic history of schizoaffective disorder, depressed type, stable on a second-generation antipsychotic. Psychotic symptoms recurred contingent to medication noncompliance necessitating hospitalization. Treatment was complicated by the development of neuroleptic malignant syndrome (NMS). In addition, subsequent medication rechallenges failed because of recurrent rhabdomyolysis and atypical NMS. Electroconvulsive therapy (ECT) treatment was initiated, affording remission of psychotic symptoms and nonrecurrence of NMS and rhabdomyolysis. Our experience confirmed the efficacy of ECT treatment in providing symptom relief of psychosis complicated by recurrent episodes of NMS and atypical NMS. Likewise, it illustrated the efficacy of ECT treatment for rhabdomyolysis. PMID:25243752

  13. Rhabdomyolysis. The role of diagnostic and prognostic factors

    PubMed Central

    Keltz, Eran; Khan, Fahmi Yousef; Mann, Gideon

    2013-01-01

    Summary Rhabdomyolysis, literally meaning the breakdown of muscle tissue, is a common syndrome with many causes, acquired ones such as exertion, trauma, infections, temperature extremes, drugs, toxins, electrolyte and endocrine abnormalities, and congenital ones such as myopathies and connective tissue disorders. All results in a common pathophysiologic pathway which ends with the dispersing of muscle tissue content into the circulation. Rhabdomyolysis has characteristic clinical, laboratory and radiologic features, but does require a high index of suspicion so that the diagnosis would not be missed. The sensitivity and specificity of the various characteristics, as well as clinical guidelines, are discussed in this paper. The syndrome may present with several complications, e.g. arrhythmias, electrolyte abnormalities, acute renal injury, acidosis, volume depletion, compartment syndrome and disseminated intravascular coagulation. The prognosis is highly variable and depends on the underlying etiologies and complications, but is in general considered as good. The milestone of treatment is vigorous fluid resuscitation. Treatment options, in practice and in research, are discussed in the following pages. PMID:24596694

  14. Spinning-induced Rhabdomyolysis: Eleven Case Reports and Review of the Literature

    PubMed Central

    Kim, Daejin; Ko, Eun-Jung; Cho, HyeJeong; Park, Su Hyung; Lee, Sang Hwan; Cho, Nam-gil; Lee, So-Young; Jeong, Hye Yun

    2015-01-01

    Non-traumatic exertional rhabdomyolysis (exRML) occurs in individuals with normal muscles when the energy supplied to the muscle is insufficient. Here, we report 11 cases of spinning-induced rhabdomyolysis and review related literature. Spinning is a kind of indoor bicycle sport. The 11 patients who were diagnosed with exRML and admitted to CHA Bundang Medical Center were female and their ages ranged from 15 to 46 years. Two to three days prior to the presentation, the patients had attended a spinning class for the first time. All the patients had been otherwise healthy without any known medical illnesses. They were successfully treated without any complications, except mild non-symptomatic hypocalcemia. However, in the literature, severe complications such as compartment syndrome or acute kidney injury had been reported in relation to exRML including spinning-induced rhabdomyolysis. This spinning exercise needs prior guidelines and specific warnings to prevent exertional rhabdomyolysis. PMID:26848305

  15. Emotionally-intense situations can result in rhabdomyolysis in McArdle disease.

    PubMed

    Brady, Stefen; Godfrey, Richard; Scalco, Renata S; Quinlivan, Ros M

    2014-01-01

    Despite the majority of patients with McArdle disease reporting symptoms including fatigue, cramps and episodes of myoglobinuria from early childhood, diagnosis is often delayed by several decades. Additionally, many individuals with rhabdomyolysis remain undiagnosed. The occurrence of symptoms during exercise, particularly isometric muscle contraction such as heavy lifting, is well known in McArdle disease. However, isometric muscle contraction that occurs with emotion is not recognised as exercise and may be missed as a trigger for rhabdomyolysis, potentially leading to a delay in diagnosis. Three patients are presented here, all with symptoms from childhood including episodes of rhabdomyolysis induced by tense emotional situations without physical exertion; two patients reported recurrent episodes while watching rather than playing football. The remaining patient developed rhabdomyolysis during a heated argument. These patients' histories emphasise the risk from sustained isometric muscle contraction that occurs in emotive situations for patients with McArdle disease. PMID:25293680

  16. Spinning-induced Rhabdomyolysis: Eleven Case Reports and Review of the Literature.

    PubMed

    Kim, Daejin; Ko, Eun-Jung; Cho, HyeJeong; Park, Su Hyung; Lee, Sang Hwan; Cho, Nam-Gil; Lee, So-Young; Jeong, Hye Yun; Yang, Dong Ho

    2015-12-01

    Non-traumatic exertional rhabdomyolysis (exRML) occurs in individuals with normal muscles when the energy supplied to the muscle is insufficient. Here, we report 11 cases of spinning-induced rhabdomyolysis and review related literature. Spinning is a kind of indoor bicycle sport. The 11 patients who were diagnosed with exRML and admitted to CHA Bundang Medical Center were female and their ages ranged from 15 to 46 years. Two to three days prior to the presentation, the patients had attended a spinning class for the first time. All the patients had been otherwise healthy without any known medical illnesses. They were successfully treated without any complications, except mild non-symptomatic hypocalcemia. However, in the literature, severe complications such as compartment syndrome or acute kidney injury had been reported in relation to exRML including spinning-induced rhabdomyolysis. This spinning exercise needs prior guidelines and specific warnings to prevent exertional rhabdomyolysis. PMID:26848305

  17. Rapid onset of rhabdomyolysis after switching to a raltegravir-based antiretroviral regimen.

    PubMed

    Tsai, Wan-Jung; Lee, Susan Shin-Jung; Tsai, Hung-Chin; Sy, Cheng-Len; Chen, Jui-Kuang; Wu, Kuang-Sheng; Wang, Yung-Hsin; Chen, Yao-Shen

    2016-04-01

    Raltegravir is the first integrase inhibitor antiretroviral agent that has been demonstrated to have antiviral efficacy and safety. However, the US Food and Drug Administration has recommended use with caution in patients with risk factors for rhabdomyolysis, based on four case reports of rhabdomyolysis in patients with identifiable risk factors. We present a 32-year-old Asian man with human immunodeficiency virus (HIV), but without other underlying diseases, who developed rapid-onset, raltegravir-associated rhabdomyolysis and hyperlactatemia. Our patient lacked predisposing factors for rhabdomyolysis, and the rapid onset time of 4 days was the shortest reported. Therefore, clinicians should exercise caution when using raltegravir and closely monitor all patients for the symptoms of muscle pain and weakness. This case has been reported to the National Adverse Drug Reactions Reporting System of the Department of Health in Taiwan. PMID:23612027

  18. TASER® Electronic Control Device-Induced Rhabdomyolysis and Renal Failure: A Case Report

    PubMed Central

    Ahmad, Ibrahim

    2015-01-01

    Many law enforcement agencies around the United States are employing the use of TASER® electronic control devices (TASER® International Inc.) to subdue combative suspects. Since its inception the TASER® has had a temporal association with reports of rhabdomyolysis. Case reports have reported TASER® induced rhabdomyolysis as mild but serious cases have also been reported. Herein we present the case of a single patient who was admitted to our health network with severe rhabdomyolysis after receiving TASER® shocks and review the pertinent literature. No direct link has been established between clinically significant rhabdomyolysis and TASER® device application but this case serves as an example of a sparsely documented but serious complication that may occur in patients who are at risk for restraint by an electronic control device. PMID:26557540

  19. A case of rhabdomyolysis in the presence of multiple risk factors and dextroamphetamine use.

    PubMed

    Santoro, Jonathan D; Black, Jeanette M; Hamm, L Lee

    2013-06-01

    A 44-year-old Caucasian woman presented to the emergency room with worsening low back pain and loss of cutaneous sensation over the paraspinal muscles from T10 to S1. The patient had ingested the attention-deficit disorder medication dextroamphetamine before engaging in intense physical exercise with subsequent consumption of 3 alcoholic beverages before developing symptoms. The patient's creatine kinase levels remained elevated for 8 days with constant severe pain under standard treatment for rhabdomyolysis. Despite stabilization of pain and laboratory values at discharge, the patient continues to experience low paraspinal back pain. In patients with risk factors for rhabdomyolysis, the use of dextroamphetamine should be monitored closely. Outside our findings, there is no literature linking dextroamphetamine with rhabdomyolysis at nontoxic concentrations or with use of the supplement caffeine containing weight loss supplement, Hydroxycut. The authors believe that further research into the potential role of dextroamphetamine use in the setting of other risk factors for rhabdomyolysis is warranted. PMID:23276898

  20. TASER(®) Electronic Control Device-Induced Rhabdomyolysis and Renal Failure: A Case Report.

    PubMed

    Gleason, James Benjamin; Ahmad, Ibrahim

    2015-10-01

    Many law enforcement agencies around the United States are employing the use of TASER(®) electronic control devices (TASER(®) International Inc.) to subdue combative suspects. Since its inception the TASER(®) has had a temporal association with reports of rhabdomyolysis. Case reports have reported TASER(®) induced rhabdomyolysis as mild but serious cases have also been reported. Herein we present the case of a single patient who was admitted to our health network with severe rhabdomyolysis after receiving TASER(®) shocks and review the pertinent literature. No direct link has been established between clinically significant rhabdomyolysis and TASER(®) device application but this case serves as an example of a sparsely documented but serious complication that may occur in patients who are at risk for restraint by an electronic control device. PMID:26557540

  1. Rhabdomyolysis after tourniquet use in proximal tibial osteotomy: a case report and review of the literature.

    PubMed

    Trkmen, ?smail; Esenkaya, ?rfan; Unay, Koray; Akal, Mehmet Akif

    2015-01-01

    Rhabdomyolysis following pneumotic tourniquet use is an extremely rare complication. In this case report, we aimed to present an unusual tourniquet complication following proximal tibial osteotomy. A 55-year-old female patient was operated on for genu varum in our clinic. Postoperatively, an anuria developed, and liver and kidney function test levels increased. The patient was diagnosed with acute rhabdomyolysis, and an aggressive treatment was begun. PMID:26200417

  2. In silico prediction of rhabdomyolysis of compounds by self-organizing map and support vector machine.

    PubMed

    Hu, Xiaoying; Yan, Aixia

    2011-12-01

    Rhabdomyolysis is a potentially lethal syndrome resulting in leakage of myocyte intracellular contents into the plasma. Some drugs, such as lipid-lowering drugs and antihistamines, can cause rhabdomyolysis. In this work, a dataset containing 186 chemical compounds causing rhabdomyolysis and 117 drugs not causing rhabdomyolysis was collected. The dataset was split into a training set (containing 230 compounds) and a test set (containing 73 compounds). A Kohonen's self-organizing map (SOM) and a support vector machine (SVM) were applied to develop classification models to differentiate compounds causing and not causing rhabdomyolysis. Using the SOM method, classification accuracies of 93.3% for the training set and 84.5% for the test set were achieved; using the SVM method, classification accuracies of 95.2% for the training set and 84.9% for the test set were achieved. In addition, the extended connectivity fingerprints (ECFP_4) for all the molecules were calculated and analyzed to find the important features of molecules relating to rhabdomyolysis. PMID:21856410

  3. Risk factors for rhabdomyolysis in self-induced water intoxication (SIWI) patients.

    PubMed

    Morita, Seiji; Inokuchi, Sadaki; Yamamoto, Rie; Inoue, Shigeaki; Tamura, Kouzo; Ohama, Shiro; Nakagawa, Yoshihide; Yamamoto, Isotoshi

    2010-04-01

    Self-induced water intoxication (SIWI) patients present with various neurological and non-neurological symptoms. However, it is reported that non-neurological manifestations such as rhabdomyolysis are comparatively rare. The mechanism underlying rhabdomyolysis remains controversial. To investigate this further, we evaluated 22 SIWI patients for rhabdomyolysis. We reviewed the records of 22 patients with SIWI and evaluated their clinical characteristics. These patients were divided into the following two groups: Group A with rhabdomyolysis and Group B without it. We compared these groups to study the risk factors underlying the occurrence of rhabdomyolysis. Furthermore, we compared the complications and the duration of hospitalization between the two groups. The maximum serum sodium correction speed per hour, the increase in the serum sodium level in the initial 24 h, and the duration of hospitalization for group A were faster, higher, and longer, respectively, when compared with those in group B. Only group A patients showed complications. The rapid correction of hyponatremia may possibly trigger rhabdomyolysis in SIWI patients. PMID:18439783

  4. Differences in gene expression profiles and signaling pathways in rhabdomyolysis-induced acute kidney injury

    PubMed Central

    Geng, Xiaodong; Wang, Yuanda; Hong, Quan; Yang, Jurong; Zheng, Wei; Zhang, Gang; Cai, Guangyan; Chen, Xiangmei; Wu, Di

    2015-01-01

    Purpose: Rhabdomyolysis is a threatening syndrome because it causes the breakdown of skeletal muscle. Muscle destruction leads to the release of myoglobin, intracellular proteins, and electrolytes into the circulation. The aim of this study was to investigate the differences in gene expression profiles and signaling pathways upon rhabdomyolysis-induced acute kidney injury (AKI). Methods: In this study, we used glycerol-induced renal injury as a model of rhabdomyolysis-induced AKI. We analyzed data and relevant information from the Gene Expression Omnibus database (No: GSE44925). The gene expression data for three untreated mice were compared to data for five mice with rhabdomyolysis-induced AKI. The expression profiling of the three untreated mice and the five rhabdomyolysis-induced AKI mice was performed using microarray analysis. We examined the levels of Cyp3a13, Rela, Aldh7a1, Jun, CD14. And Cdkn1a using RT-PCR to determine the accuracy of the microarray results. Results: The microarray analysis showed that there were 1050 downregulated and 659 upregulated genes in the rhabdomyolysis-induced AKI mice compared to the control group. The interactions of all differentially expressed genes in the Signal-Net were analyzed. Cyp3a13 and Rela had the most interactions with other genes. The data showed that Rela and Aldh7a1 were the key nodes and had important positions in the Signal-Net. The genes Jun, CD14, and Cdkn1a were also significantly upregulated. The pathway analysis classified the differentially expressed genes into 71 downregulated and 48 upregulated pathways including the PI3K/Akt, MAPK, and NF-κB signaling pathways. Conclusion: The results of this study indicate that the NF-κB, MAPK, PI3K/Akt, and apoptotic pathways are regulated in rhabdomyolysis-induced AKI. PMID:26823722

  5. Severe Rhabdomyolysis without Systemic Involvement: A Rare Case of Idiopathic Eosinophilic Polymyositis

    PubMed Central

    Farooq, Ayesha; Choksi, Vivek; Chu, Andrew; Mankodi, Dhruti; Shaharyar, Sameer; O'Brien, Keith; Shankar, Uday

    2015-01-01

    Introduction. Eosinophilic polymyositis (EPM) is a rare cause of rhabdomyolysis characterized by eosinophilic infiltrates in the muscle. We describe the case of a young patient with eosinophilic polymyositis causing isolated severe rhabdomyolysis without systemic involvement. Case Presentation. A 22-year-old Haitian female with no past medical history presented with progressive generalized muscle aches without precipitating factors. Examination of the extremities revealed diffuse muscle tenderness. Laboratory findings demonstrated peripheral eosinophilia and high creatinine phosphokinase (CPK) and transaminase levels. Workup for the common causes of rhabdomyolysis were negative. Her CPK continued to rise to greater than 100,000 units/L so a muscle biopsy was performed which showed widespread eosinophilic infiltrate consistent with eosinophilic polymyositis. She was started on high dose systemic corticosteroids with improvement of her symptoms, eosinophilia, and CPK level. Discussion. This case illustrates a systematic workup of rhabdomyolysis in the presence of peripheral eosinophilia. Many differential diagnoses must be considered before establishing a diagnosis of idiopathic eosinophilic polymyositis. To our knowledge, our case of eosinophilic polymyositis is unique as it presented with severe rhabdomyolysis without another organ involvement. Clinicians should maintain a high index of suspicion for this physically debilitating disease to aid in prompt diagnosis. PMID:26229703

  6. Five factors contributing to severe rhabdomyolysis in a 21 yr old IV drug abuser: a case report

    PubMed Central

    Ganeshram, Prasanthi; Goundan, Poorani Nallam; Arthur, Preetham

    2009-01-01

    Rhabdomyolysis is a potentially life-threatening condition resulting from the release of large quantities of myocyte breakdown products into the circulation, following injury to striated muscles. There are several causes of rhabdomyolysis - traumatic and non-traumatic. We present a 21-year-old male intravenous drug abuser, who was referred to us with fever, altered sensorium and seizures. He developed severe rhabdomyolysis following a mixed meningeal infection by Streptococcus pneumoniae and Mycobacterium tuberculosis. This patients examination and investigation suggested a combination of factors leading to the severe rhabdomyolysis which proved fatal. The patients creatine phosphokinase was elevated to 167,000 U/L, following hyperpyrexia, seizures, meningitis (pneumococcal and tuberculous), pentazocine and alcohol abuse. The increase in mortality rate with the onset of rhabdomyolysis warrants immediate cessation of the insult and aggressive management. PMID:19829812

  7. BIOPSY PROVEN ACUTE TUBULAR NECROSIS DUE TO RHABDOMYOLYSIS IN A DENGUE FEVER PATIENT: A CASE REPORT AND REVIEW OF LITERATURE

    PubMed Central

    Repizo, Liliany P.; Malheiros, Denise M.; Yu, Luis; Barros, Rui T.; Burdmann, Emmanuel A.

    2014-01-01

    Renal histology results are very scarce in dengue-associated rhabdomyolysis patients developing acute kidney injury (AKI). We report a case of dengue fever-induced AKI associated to rhabdomyolysis with a renal biopsy showing acute tubular necrosis (ATN) and renal deposition of myoglobin. A 28-year-old patient who presented dengue fever (DF) complicated by severe AKI and rhabdomyolysis is described. The patient required hemodialysis for three weeks. A renal biopsy revealed ATN with positive staining for myoglobin in the renal tubuli. The patient was discharged with recovered renal function. In conclusion, this case report described a biopsy proven ATN associated to DF-induced rhabdomyolysis, in which renal deposition of myoglobin was demonstrated. We suggest that serum creatine phosphokinase should be monitored in DF patients to allow for an early diagnosis of rhabdomyolysis and the institution of renal protective measures. PMID:24553615

  8. Molecular analysis of LPIN1 in Jordanian patients with rhabdomyolysis

    PubMed Central

    Jaradat, Saied A.; Amayreh, Wajdi; Al-Qa'qa', Kefah; Krayyem, Jan

    2015-01-01

    Recessive mutations in LPIN1, which encodes a phosphatidate phosphatase enzyme, are a frequent cause of severe rhabdomyolysis in childhood. Hence, we sequenced the 19 coding exons of the gene in eight patients with recurrent hereditary myoglobinuria from four unrelated families in Jordan. The long-term goal is to facilitate molecular genetic diagnosis without the need for invasive procedures such as muscle biopsies. Three different mutations were detected, including the novel missense mutation c.2395G>C (Gly799Arg), which was found in two families. The two other mutations, c.2174G>A (Arg725His) and c.1162C>T (Arg388X), have been previously identified, and were found to cosegregate with the disease phenotype in the other two families. Intriguingly, patients homozygous for Arg725His were also homozygous for the c.1828C>T (Pro610Ser) polymorphism, and were exercise-intolerant between myoglobinuria episodes. Notably, patients homozygous for Arg388X were also homozygous for the c.2250G>C silent variant (Gly750Gly). Taken together, the data provide family-based evidence linking hereditary myoglobinuria to pathogenic variations in the C-terminal lipin domain of the enzyme. This finding highlights the functional significance of this domain in the absence of structural information. This is the first analysis of LPIN1 in myoglobinuria patients of Jordanian origin, and the fourth such analysis worldwide. PMID:26909335

  9. Molecular analysis of LPIN1 in Jordanian patients with rhabdomyolysis.

    PubMed

    Jaradat, Saied A; Amayreh, Wajdi; Al-Qa'qa', Kefah; Krayyem, Jan

    2016-02-01

    Recessive mutations in LPIN1, which encodes a phosphatidate phosphatase enzyme, are a frequent cause of severe rhabdomyolysis in childhood. Hence, we sequenced the 19 coding exons of the gene in eight patients with recurrent hereditary myoglobinuria from four unrelated families in Jordan. The long-term goal is to facilitate molecular genetic diagnosis without the need for invasive procedures such as muscle biopsies. Three different mutations were detected, including the novel missense mutation c.2395G>C (Gly799Arg), which was found in two families. The two other mutations, c.2174G>A (Arg725His) and c.1162C>T (Arg388X), have been previously identified, and were found to cosegregate with the disease phenotype in the other two families. Intriguingly, patients homozygous for Arg725His were also homozygous for the c.1828C>T (Pro610Ser) polymorphism, and were exercise-intolerant between myoglobinuria episodes. Notably, patients homozygous for Arg388X were also homozygous for the c.2250G>C silent variant (Gly750Gly). Taken together, the data provide family-based evidence linking hereditary myoglobinuria to pathogenic variations in the C-terminal lipin domain of the enzyme. This finding highlights the functional significance of this domain in the absence of structural information. This is the first analysis of LPIN1 in myoglobinuria patients of Jordanian origin, and the fourth such analysis worldwide. PMID:26909335

  10. Rhabdomyolysis and Acute Renal Impairment in a Patient with Hypothyroidism: A Case Report

    PubMed Central

    Issa, Mayada

    2014-01-01

    We report the case of a 33-year-old male with hypothyroidism who developed acute renal impairment with rhabdomyolysis after strenuous physical activity (snow shoveling). His thyroid function test confirmed marked hypothyroidism. Severe elevation of serum CK consistent with rhabdomyolysis was noted and an elevated creatinine indicated acute renal impairment. Patient's condition improved significantly after starting him on thyroid hormone replacement therapy and aggressive hydration. Acute renal impairment with rhabdomyolysis in patients with hypothyroidism is quite rare and we expect that this case report adds to the existing literature on this subject. We also emphasize that thyroid status should be evaluated in patients with unexplained acute renal impairment and presenting with the symptoms of muscle involvement. PMID:24822067

  11. Myocarditis and Rhabdomyolysis in a Healthy Young Man Caused by Salmonella Gastroenteritis

    PubMed Central

    Ajaz, Yasmeen; Roy Narayanan, Sunil

    2015-01-01

    Salmonella gastroenteritis is a common, self-limiting, foodborne disease and a rare cause of life-threatening complications especially in immunocompetent individuals. Moreover, bacterial infections of the GI tract have been rarely reported as a cause of serious complications like acute myocarditis and rhabdomyolysis. While viral infections are commonly associated with myocarditis, bacterial infections are infrequently seen with these conditions. Similarly, bacterial infections may lead to only 5% of adult rhabdomyolysis events whereas viral-induced myositis appears to be the commonest. A 28-year-old young male with no past medical problems presented with acute salmonella gastroenteritis that was complicated by myocardial injury (most likely myocarditis), rhabdomyolysis, acute renal failure, and shock. He made an uneventful complete recovery of all complications by early recognition of these rare complications and prompt institution of appropriate therapy. PMID:26124970

  12. An unusual cause of rhabdomyolysis in emergency setting: challenges of diagnosis.

    PubMed

    Petrov, Mikhail; Yatsynovich, Yan; Lionte, Catalina

    2015-01-01

    Rhabdomyolysis is a rare phenomenon that may be challenging to recognize in an emergency setting. Drugs are one of the common causes. Trimethoprim-sulfamethoxazole is a commonly used antibiotic effective in the treatment of upper and lower respiratory tract infections as well as renal, urinary, and gastrointestinal tract infections. It has variable side effects, ranging from mild symptoms of fatigue and insomnia to a potentially life-threatening Steven-Johnson syndrome and renal failure. Rhabdomyolysis is a rare complication of therapy with this drug and is commonly seen in immunocompromised patients or those with an allogenic stem cell transplant. In this article, we report a case of rhabdomyolysis in an immunocompetent patient who has undergone treatment with trimethoprim-sulfamethoxazole and a possible drug interaction with nonsteroidal anti-inflammatory drugs, with the latter acting as an aggravating factor of this complication. PMID:24997105

  13. Hypokalemia-Induced Rhabdomyolysis by Primary Aldosteronism Coexistent With Sporadic Inclusion Body Myositis

    PubMed Central

    Lee, Jong Ha; Chon, Suk

    2015-01-01

    We describes a patient with hypokalemia-induced rhabdomyolysis due to primary aldosteronism (PA), who suffered from slowly progressive muscle weakness after laparoscopic adrenalectomy, and was later diagnosed with coexisting sporadic inclusion body myositis (sIBM). A 54-year-old Asian male presented with severe muscle weakness of both lower extremities. Laboratory findings showed profound hypokalemia, and extreme elevation of the serum creatine phosphokinase levels, suggestive of hypokalemia-induced rhabdomyolysis. Further evaluation strongly suggested PA by an aldosterone-producing adenoma, which was successfully removed surgically. However, muscle weakness slowly progressed one year after the operation and a muscle biopsy demonstrated findings consistent with sIBM. This case is the first report of hypokalemia-induced rhabdomyolysis by PA coexistent with sIBM, to the best of our knowledge. PMID:26605182

  14. Rhabdomyolysis with acute renal failure triggered by the seasonal flu vaccination in a patient taking simvastatin

    PubMed Central

    Shah, S V; Reddy, K

    2010-01-01

    A man in his 70s presented with bilateral, painful legs and feeling generally unwell following the seasonal flu vaccination. The patient had a background of B cell lymphoma in partial remission. His current medications included simvastatin. Initial investigations revealed rhabdomyolysis and acute renal failure. He was admitted to critical care for renal replacement treatment. Other causes of rhabdomyolysis were excluded and expert opinion agreed that the most likely cause was the influenza vaccination with the concurrent use of simvastatin. The patient's renal function gradually normalised and after several months the patient has regained full power in his legs. PMID:22778082

  15. [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. PMID:25352283

  16. Technetium-99m pyrophosphate imaging in acute renal failure associated with nontraumatic rhabdomyolysis

    SciTech Connect

    Patel, R.; Mishkin, F.S.

    1986-10-01

    Technetium-99m pyrophosphate (Tc-PYP) imaging was performed in five patients with acute renal failure associated with nontraumatic rhabdomyolysis. Four patients had phencyclidine intoxication and one had viral pneumonia. During the acute phase, marked uptake of pyrophosphate was seen in all patients in several muscle groups, but always in the thigh adductors. The results show that phencyclidine intoxication can result in diffuse muscle uptake of Tc-PYP without overt evidence of muscle injury. Tc-PYP imaging may provide a clue to the cause of acute renal failure in patients with suspected rhabdomyolysis in whom elevations of serum creatine phosphokinase concentrations are equivocal.

  17. [Rhabdomyolysis following cerivastatin monotherapy--implications for therapy with HMG-CoA reductase inhibitors].

    PubMed

    Sparing, R; Sellhaus, B; Noth, J; Block, F

    2003-02-01

    Cerivastatine was administered as a reversible HMG-CoA reductase inhibitor (statine) to treat hypercholesterolemia until its withdrawal from the market following 52 reports of death due to drug-related rhabdomyolysis and acute renal failure. In most cases, cerivastatine was applied in combination with drugs which influenced the liver metabolism of cerivastatine via cytochromeoxidase P 450 isoenzymes. We report a well-documented case of acute rhabdomyolysis following cerivastatine monotherapy. The diagnosis was confirmed additionally by muscle biopsy.Finally,we give an overview of the current knowledge concerning therapy with HMG-CoA reductase inhibitors,1 year after the withdrawal of cerivastatine from the market. PMID:12596018

  18. Rhabdomyolysis: historical background, clinical, diagnostic and therapeutic features.

    PubMed

    Cervellin, Gianfranco; Comelli, Ivan; Lippi, Giuseppe

    2010-06-01

    Rhabdomyolysis, a term used to describe the rapid breakdown of striated muscle, is characterized by rupture and necrosis of muscle fibers. This process results in the release of cell breakdown products into the bloodstream and extracellular space. Although direct muscle injury remains the most common cause of muscle injury, additional causes include hereditary enzyme disorders, drugs, toxins, endocrinopathies, malignant hyperthermia, neuroleptic malignant syndrome, heatstroke, hypothermia, electrolyte alterations, diabetic ketoacidosis and non-ketotic hyperosmolar coma, severe hypo- or hyperthyroidism and bacterial or viral infections. The classic triad of symptoms includes muscle pain, weakness and dark urine, although more than 50% of the patients do not complain of muscle pain or weakness. Additional systemic symptoms include fever, general malaise, tachycardia, nausea and vomiting. The laboratory diagnosis is based essentially on the measurement of creatine kinase in serum or plasma. Plasma and urine myoglobin measurement might be useful in the early stages of the syndrome and for identifying a subset of patients with minor skeletal muscle injury. Patient monitoring is pivotal (the mortality rate is as high as 8%), and should be focused on preventing the detrimental consequences, that often include renal disease and coagulopathy. In the pre-hospital setting, forced hydration with 1.5-2 L of sterile saline solution should be started immediately, followed by 1.5-2 L/h. Following hospital admission, continuous hydration should be ensured, alternating the saline solution with a 5% glucose solution. In the presence of myoglobinuria, urine should be alkalinized by use of sodium bicarbonate solution. Clin Chem Lab Med 2010;48:749-56. PMID:20298139

  19. A rare case of brucine poisoning complicated by rhabdomyolysis and acute renal failure.

    PubMed

    Naik, B Sadananda; Chakrapani, M

    2009-06-01

    Brucine is the predominant alkaloid present in the bark of the tree Strychnos nux vomica and is a weaker alkaloid when compared to strychnine. However, its toxicological property is akin to strychnine. We report a rare case of brucine poisoning complicated by acute renal failure and rhabdomyolysis. A 24-year-old male presented with a history of consumption of a decoction made from the bark of the Strychnos nux vomica tree. Soon after, he developed widespread muscle spasms and convulsions, which were promptly treated. On the fifth day of admission, he developed features of rhabdomyolysis and acute renal failure. Investigations revealed elevated creatine phosphokinase levels and elevated blood urea and serum creatinine. The patient was managed with hemodialysis and recovered gradually. There are many reports of strychnine poisoning producing rhabdomyolysis and renal failure. In this case report, attention is drawn to the fact that brucine, although a weaker alkaloid, can also produce life threatening complications like rhabdomyolysis and acute renal failure. PMID:19694317

  20. Fatal theophylline poisoning with rhabdomyolysis. A potential role for dantrolene treatment.

    PubMed

    Parr, M J; Willatts, S M

    1991-07-01

    A fatal case of theophylline poisoning is described. The patient developed rhabdomyolysis, renal failure and compartment syndrome, as well as the more usual features of severe theophylline poisoning. Dantrolene appeared to be useful in controlling the hypermetabolic state associated with the overdose and may have a role in future treatment. PMID:1862895

  1. Thigh compartment syndrome complicated by sciatic nerve palsy, rhabdomyolysis, and acute renal failure.

    PubMed

    Alobaidi, Ahmad; Backdash, Mohamad Munir; El-Menyar, Ayman

    2016-02-01

    We reported a rare case of thigh compartment syndrome (TCS) complicated by sciatic nerve palsy, rhabdomyolysis, and acute renal failure in an alcoholic patient. Intensive care measures and immediate posteromedial decompressive fasciotomy were performed. These timely interventions resulted in improvement of the nerve injury and restoration of the kidney function. PMID:26862401

  2. Rhabdomyolysis-Associated Mutations in Human LPIN1 Lead to Loss of Phosphatidic Acid Phosphohydrolase Activity.

    PubMed

    Schweitzer, George G; Collier, Sara L; Chen, Zhouji; Eaton, James M; Connolly, Anne M; Bucelli, Robert C; Pestronk, Alan; Harris, Thurl E; Finck, Brian N

    2015-01-01

    Rhabdomyolysis is an acute syndrome due to extensive injury of skeletal muscle. Recurrent rhabdomyolysis is often caused by inborn errors in intermediary metabolism, and recent work has suggested that mutations in the human gene encoding lipin 1 (LPIN1) may be a common cause of recurrent rhabdomyolysis in children. Lipin 1 dephosphorylates phosphatidic acid to form diacylglycerol (phosphatidic acid phosphohydrolase; PAP) and acts as a transcriptional regulatory protein to control metabolic gene expression. Herein, a 3-year-old boy with severe recurrent rhabdomyolysis was determined to be a compound heterozygote for a novel c.1904T>C (p.Leu635Pro) substitution and a previously reported genomic deletion of exons 18-19 (E766-S838_del) in LPIN1. Western blotting with patient muscle biopsy lysates demonstrated a marked reduction in lipin 1 protein, while immunohistochemical staining for lipin 1 showed abnormal subcellular localization. We cloned cDNAs to express recombinant lipin 1 proteins harboring pathogenic mutations and showed that the E766-S838_del allele was not expressed at the RNA or protein level. Lipin 1 p.Leu635Pro was expressed, but the protein was less stable, was aggregated in the cytosol, and was targeted for proteosomal degradation. Another pathogenic single amino acid substitution, lipin 1 p.Arg725His, was well expressed and retained its transcriptional regulatory function. However, both p.Leu635Pro and p.Arg725His proteins were found to be deficient in PAP activity. Kinetic analyses demonstrated a loss of catalysis rather than diminished substrate binding. These data suggest that loss of lipin 1-mediated PAP activity may be involved in the pathogenesis of rhabdomyolysis in lipin 1 deficiency. PMID:25967228

  3. A Case of Paraspinal Muscle Rhabdomyolysis in a 22-Year-Old Male After Ingesting a Supplement Containing Higenamine.

    PubMed

    Jeter, Jonathan; DeZee, Kent J; Kennedy, Laura

    2015-07-01

    Rhabdomyolysis is a painful and potentially life-threatening injury in which muscle breaks down in response to an insult. In this case report, we describe the clinical course of a 22-year-old man who developed paraspinal muscle rhabdomyolysis and possible compartment syndrome in association with strenuous activity and the ingestion of an exercise supplement containing the stimulant higenamine. Although he did not experience any renal damage, he did experience a high level of pain acutely and for the next 4 months. A history of exercise supplement intake should increase the index of suspicion for rhabdomyolysis when a patient presents with moderate to severe muscle pain, even if the muscle group is not in a classic location for rhabdomyolysis. PMID:26126260

  4. Hypokalemia-Induced Rhabdomyolysis as a result of Distal Renal Tubular Acidosis in a Pregnant Woman: A Case Report and Literature Review

    PubMed Central

    Srisuttayasathien, Manasawee

    2015-01-01

    Rhabdomyolysis in pregnancy is a rare occurrence. The manifestation of distal renal tubular acidosis (RTA) for the first time during adulthood is uncommon. According to a review of the literature, pregnancy may predispose individuals to rhabdomyolysis due to hypokalemia. A reduction in interstitial potassium ions could decrease muscular blood flow and lead to muscle injury. This report describes the case of a pregnant woman with rhabdomyolysis induced by hypokalemia resulting from distal RTA. The patient subsequently delivered a healthy newborn. PMID:26788388

  5. Community acquired methicillin-resistant Staphylococcus aureus pneumonia leading to rhabdomyolysis: a case report

    PubMed Central

    2010-01-01

    Community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) is considered an underreported entity in India. In this case report, the authors describe a thirty-five year old immunocompetent male presenting with severe respiratory distress requiring intubation. On further work up, a CT thorax showed features consistent with necrotizing pneumonia. The morphology and sensitivity pattern of the organism found in the bronchoalveolar lavage fluid and blood culture were consistent with MRSA. The patient's stay in the hospital was complicated by acute renal failure due to rhabdomyolysis with CPK levels of 9995 U/L. The patient was started on dialysis and improved there after. This case brings to light that CA-MRSA is becoming a problem in developing nations where antibiotics are frequently used empirically with little laboratory guidance. It also is a rare reporting of rhabdomyolysis due to CA-MRSA. PMID:20205915

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

    PubMed Central

    Mamoune, Asmaa; Bahuau, Michel; Hamel, Yamina; Serre, Valrie; 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

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

    PubMed

    Mamoune, Asmaa; Bahuau, Michel; Hamel, Yamina; Serre, Valrie; 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. PMID:25392908

  8. Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone.

    PubMed

    Syed, Husnain; Som, Sumit; Khan, Nazia; Faltas, Wael

    2009-01-01

    The present report highlights the possible adverse effects of doxylamine, a common over the counter sleep aid. Doxylamine is an antihistamine that at toxic doses can cause anticholinergic effects, including seizures, rhabdomyolysis and death. The following case describes a patient with doxylamine toxicity who presented with seizure and confusion. Our patient was managed symptomatically, and remained otherwise stable throughout his hospitalisation. This case is atypical in terms of a delayed rhabdomyolysis and a false positive urine drug screen test for methadone. There is evidence that doxylamine at toxic levels can lead to false positives for methadone and phencyclidine testing using immunoassay-based urine drug screen kits. Urine drug screen testing on patients who are hospitalised is typically performed using immunoassays. However, in certain cases confirmatory secondary testing may be required. Doxylamine is prone to abuse and knowledge of the clinical presentation of its toxicity and the management of acute overdose can be life-saving. PMID:21686586

  9. Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone

    PubMed Central

    Syed, Husnain; Som, Sumit; Khan, Nazia; Faltas, Wael

    2009-01-01

    The present report highlights the possible adverse effects of doxylamine, a common over the counter sleep aid. Doxylamine is an antihistamine that at toxic doses can cause anticholinergic effects, including seizures, rhabdomyolysis and death. The following case describes a patient with doxylamine toxicity who presented with seizure and confusion. Our patient was managed symptomatically, and remained otherwise stable throughout his hospitalisation. This case is atypical in terms of a delayed rhabdomyolysis and a false positive urine drug screen test for methadone. There is evidence that doxylamine at toxic levels can lead to false positives for methadone and phencyclidine testing using immunoassay-based urine drug screen kits. Urine drug screen testing on patients who are hospitalised is typically performed using immunoassays. However, in certain cases confirmatory secondary testing may be required. Doxylamine is prone to abuse and knowledge of the clinical presentation of its toxicity and the management of acute overdose can be life-saving. PMID:21686586

  10. Rhabdomyolysis, acute renal failure, and multiple focal neuropathies after drinking alcohol soaked with centipede.

    PubMed

    Wang, I-Kuan; Hsu, Shih-Pin; Chi, Ching-Chi; Lee, Kam-Fai; Lin, Paul Yann; Chang, Hsueh-Wen; Chuang, Feng-Rong

    2004-01-01

    Many Chinese like to drink alcohol soaked with creatures for promoting health. This study reports a 49-year-old male who presented with multiple focal neuropathies of the upper limbs, coagulopathy, erythematous swelling of the bilateral upper extremities and trunk with bullous skin lesions, and rhabdomyolysis associated with acute renal failure after drinking alcohol soaked with centipede. Soaking a centipede, Scolopendra subspinipes mutilans, in 53% alcohol, produced the wine. Supportive treatment was administered, and the skin lesions and renal failure improved with subsequent neurologic deficit during the week following initial presentation. Alcohol binge or immobilization was the likely cause of neuropathy, bullous skin lesions and rhabdomyolysis in the patient. However, there is a possibility that centipede venom also contributed to the illness in this patient. PMID:15083930

  11. Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure

    PubMed Central

    Boutaud, Olivier; Moore, Kevin P.; Reeder, Brandon J.; Harry, David; Howie, Alexander J.; Wang, Shuhe; Carney, Clare K.; Masterson, Tina S.; Amin, Taneem; Wright, David W.; Wilson, Michael T.; Oates, John A.; Roberts, L. Jackson

    2010-01-01

    Hemoproteins, hemoglobin and myoglobin, once released from cells can cause severe oxidative damage as a consequence of heme redox cycling between ferric and ferryl states that generates radical species that induce lipid peroxidation. We demonstrate in vitro that acetaminophen inhibits hemoprotein-induced lipid peroxidation by reducing ferryl heme to its ferric state and quenching globin radicals. Severe muscle injury (rhabdomyolysis) is accompanied by the release of myoglobin that becomes deposited in the kidney, causing renal injury. We previously showed in a rat model of rhabdomyolysis that redox cycling between ferric and ferryl myoglobin yields radical species that cause severe oxidative damage to the kidney. In this model, acetaminophen at therapeutic plasma concentrations significantly decreased oxidant injury in the kidney, improved renal function, and reduced renal damage. These findings also provide a hypothesis for potential therapeutic applications for acetaminophen in diseases involving hemoprotein-mediated oxidative injury. PMID:20133658

  12. Alpha-sarcoglycanopathy presenting as exercise intolerance and rhabdomyolysis in two adults.

    PubMed

    Tarnopolsky, M; Hoffman, E; Giri, M; Shoffner, J; Brady, L

    2015-12-01

    Two patients with exercise-induced myalgias and rhabdomyolysis with myoglobinuria were evaluated with muscle biopsy and comprehensive myopathy next generation sequencing (NGS) gene panels. Genetic analysis revealed homozygosity for two known pathogenic SGCA mutations (R284C in Patient 1 and V247M in Patient 2). Muscle biopsy showed minimal changes with normal immunohistochemistry for ?-sarcoglycan. Western blotting showed 27% and 35% of normal ?-sarcoglycan immunoreactivity when compared to age matched controls, confirming the diagnosis of ?-sarcoglycanopathy in both patients. The sarcoglycan genes should be added to the differential diagnosis for cases that present with rhabdomyolysis, exercise intolerance, and hyperCKemia, even in the absence of muscle weakness or normal ?-sarcoglycan immunohistochemistry. Work-up of patients with these types of non-specific presentation may be best facilitated through the use of non-specific NGS myopathy panels. PMID:26453141

  13. Rhabdomyolysis in presumed viscero-cutaneous loxoscelism: report of two cases.

    PubMed

    Frana, Francisco Oscar de Siqueira; Barbaro, Katia Cristina; Abdulkader, Regina Clia Rodrigues de Moraes

    2002-01-01

    Until now, in viscero-cutaneous loxoscelism, discoloured urine has been attributed only to haemoglobinuria induced by the intravascular haemolysis caused by the venom. In this paper, 2 cases (in Brazil) of viscero-cutaneous loxoscelism with rhabdomyolysis and acute renal failure are described. Both patients presented with severe oedema, erythema and dermonecrosis at the bite site. Elevated creatine kinase levels were found in both cases (6841 and 1718 U/L) associated with severe acute renal failure (one required dialysis for 50 days). Therefore, in viscero-cutaneous loxoscelism, rhabdomyolysis secondary to intense local tissue damage can occur and should be considered as a contributing factor in acute renal failure. Creatine kinase should therefore be monitored in viscero-cutaneous loxoscelism to avoid acute renal failure and to reduce the severity of any renal damage. PMID:12174781

  14. Role of dipstick in detection of haeme pigment due to rhabdomyolysis in victims of Bam earthquake.

    PubMed

    Amini, M; Sharifi, A; Najafi, I; Eghtesadi-Araghi, P; Rasouli, M R

    2010-09-01

    Avoiding life-threatening complications of rhabdomyolysis depends on early diagnosis and prompt management. The aim of this study was to evaluate the role of urinary dipstick test in the detection of haeme pigment in patients who were at risk of acute renal failure (ARF) due to rhabdomyolysis after suffering injury in the Bam earthquake. Serum creatine phosphokinase (CPK) level was used as the gold standard for prediction of ARF. ARF developed in 8 (10%) of 79 patients studied. We found no significant differences in the sensitivity, specificity and accuracy of dipstick urine and serum CPK tests for identifying patients who were at risk of ARF. However, dipstick urine test is an easy test that can be performed quickly at an earthquake site. PMID:21218726

  15. Predictors and outcomes of increases in creatine phosphokinase concentrations or rhabdomyolysis risk during statin treatment

    PubMed Central

    van Staa, Tjeerd P; Carr, Daniel F; OMeara, Helen; McCann, Gerry; Pirmohamed, Munir

    2014-01-01

    Aim The aim was to evaluate clinical risk factors associated with myotoxicity in statin users. Methods This was a cohort study of patients prescribed a statin in UK primary care practices contributing to the Clinical Practice Research Datalink. Outcomes of interest were creatine phosphokinase (CPK) concentrations and clinical records of rhabdomyolysis. Results The cohort comprised 641 703 statin users. Simvastatin was most frequently prescribed (66.3%), followed by atorvastatin (24.4%). CPK was measured in 127 209 patients: 81.4% within normal range and 0.7% above Rhabdomyolysis was recorded in 59 patients. Patients with concomitant prescribing of CYP3A4-interacting drugs had an increased odds ratio (OR) of rhabdomyolysis compared with controls (OR 3.71, 95% CI 1.18, 11.61) and >four times ULN CPK compared with normal CPK (OR 1.28, 95% CI 1.01, 1.60). Rosuvastatin users had higher risk of >four times ULN CPK (OR 1.62, 95% CI 1.22, 2.15) as did patients with larger daily doses of other statin types. A recent clinical record of myalgia was associated with an increased OR of >four times ULN CPK (OR 1.73, 95% CI 1.37, 2.18). In patients who were rechallenged to statins and had repeat CPK measurements after >four times ULN CPK abnormalities, 54.8% of the repeat CPK values were within normal range, 32.1% between one to three times and 13.0% >four times ULN. Conclusions The frequencies of substantive CPK increases and rhabdomyolysis during statin treatment were low, with highest risks seen in those on large daily doses or interacting drugs and on rosuvastatin. CPK measurements appeared to have been done in a haphazard manner and better guidance is needed. PMID:24602118

  16. "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." PMID:10050578

  17. Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury

    PubMed Central

    Komada, Takanori; Usui, Fumitake; Kawashima, Akira; Kimura, Hiroaki; Karasawa, Tadayoshi; Inoue, Yoshiyuki; Kobayashi, Motoi; Mizushina, Yoshiko; Kasahara, Tadashi; Taniguchi, Shun’ichiro; Muto, Shigeaki; Nagata, Daisuke; Takahashi, Masafumi

    2015-01-01

    Rhabdomyolysis is one of the main causes of community-acquired acute kidney injury (AKI). Although inflammation is involved in the pathogenesis of rhabdomyolysis-induced AKI (RIAKI), little is known about the mechanism that triggers inflammation during RIAKI. Recent evidence has indicated that sterile inflammation triggered by tissue injury can be mediated through multiprotein complexes called the inflammasomes. Therefore, we investigated the role of NLRP3 inflammasomes in the pathogenesis of RIAKI using a glycerol-induced murine rhabdomyolysis model. Inflammasome-related molecules were upregulated in the kidney of RIAKI. Renal tubular injury and dysfunction preceded leukocyte infiltration into the kidney during the early phase of RIAKI, and they were markedly attenuated in mice deficient in NLRP3, ASC, caspase-1, and interleukin (IL)-1β compared with those in wild-type mice. No difference in leukocyte infiltration was observed between wild-type and NLRP3-deficient mice. Furthermore, NLRP3 deficiency strikingly suppressed the expression of renal injury markers and inflammatory cytokines and apoptosis of renal tubular cells. These results demonstrated that NLRP3 inflammasomes contribute to inflammation, apoptosis, and tissue injury during the early phase of RIAKI and provide new insights into the mechanism underlying the pathogenesis of RIAKI. PMID:26045078

  18. A Substrate Pharmacophore for the Human Organic Cation/Carnitine Transporter Identifies Compounds Associated with Rhabdomyolysis

    PubMed Central

    Ekins, Sean; Diao, Lei; Polli, James E.

    2012-01-01

    The human Organic Cation/Carnitine Transporter (hOCTN2), is a high affinity cation/carnitine transporter expressed widely in human tissues and is physiologically important for the homeostasis of L-carnitine. The objective of this study was to elucidate the substrate requirements of this transporter via computational modelling based on published in vitro data. Nine published substrates of hOCTN2 were used to create a common features pharmacophore that was validated by mapping other known OCTN2 substrates. The pharmacophore was used to search a drug database and retrieved molecules that were then used as search queries in PubMed for instances of a side effect (rhabdomyolysis) associated with interference with L-carnitine transport. The substrate pharmacophore was comprised of two hydrogen bond acceptors, a positive ionizable feature and ten excluded volumes. The substrate pharmacophore also mapped 6 out of 7 known substrate molecules used as a test set. After searching a database of ~800 known drugs, thirty drugs were predicted to map to the substrate pharmacophore with L-carnitine shape restriction. At least 16 of these molecules had case reports documenting an association with rhabdomyolysis and represent a set for prioritizing for future testing as OCTN2 substrates or inhibitors. This computational OCTN2 substrate pharmacophore derived from published data partially overlaps a previous OCTN2 inhibitor pharmacophore and is also able to select compounds that demonstrate rhabdomyolysis, further confirming the possible linkage between this side effect and hOCTN2. PMID:22339151

  19. Two Cases of Rhabdomyolysis After Training With Electromyostimulation by 2 Young Male Professional Soccer Players.

    PubMed

    Kstner, Andreas; Braun, Markus; Meyer, Tim

    2015-11-01

    We report 2 cases of enormously elevated creatine kinase (CK) activity after training with electromyostimulation (EMS) by 2 young male professional soccer players. In one of them, a single training session with EMS caused exercise-induced rhabdomyolysis with a maximal CK activity of 240?000 U/L. These cases illustrate that unaccustomed EMS exercise may be harmful and can cause rhabdomyolysis even in highly trained athletes and even after 1 single session. Thus, EMS has to be conducted carefully especially by individuals who are known to frequently show notable increases in CK activity even after modest training stimuli. We suggest that EMS should not be applied as sole training stimulus and should not be conducted by strength training beginners. Furthermore, we recommend controlling plasma CK activity and urine color for beginners with EMS when they report strong muscle ache. Athletes with signs of rhabdomyolysis after EMS should be brought to hospital for monitoring of renal function and possible further treatment. PMID:25353720

  20. Rhabdomyolysis after midazolam administration in a cirrhotic patient treated with atorvastatin

    PubMed Central

    Gigante, Antonietta; Giraldi, Gianluca Di Lazzaro; Gasperini, Maria Ludovica; Barbano, Biagio; Liberatori, Marta; Sardo, Liborio; Mario, Francesca Di; Giorgi, Antonella; Rossi-Fanelli, Filippo; Amoroso, Antonio

    2014-01-01

    The administration of statins in patients with liver disease is not an absolute contraindication. Hepatotoxicity is a rare and often dose-related event and in the literature there are only a few described cases of fatal rhabdomyolysis in patients with chronic liver disease after statin administration. During treatment with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, the factors responsible for myopathy may either be related to the patient, or due to interactions with other medications that are metabolic substrates of the same isozymes and therefore able to increase blood statin concentration. The most important side effects consist of increased transaminase levels, abdominal pain or muscle weakness, increased serum levels of creatine kinase and rhabdomyolysis. In this article we report a case of fatal rhabdomyolysis with acute renal failure after gastric endoscopy, where midazolam was used as a sedation agent in a patient with chronic liver disease treated with a high dose of atorvastatin. Therefore, we suggest paying particular attention to the potential risks of associating atorvastatin and midazolam in patients with chronic liver disease who need to undergo gastric endoscopy. PMID:25133049

  1. Bilateral gluteal compartment syndrome complicated by rhabdomyolysis and acute kidney injury in a patient with alcohol intoxication

    PubMed Central

    Young Cho, Jae; Lee, Jae-Won; Jung Cho, Eun; Kim, Myung-Gyu; Jo, Sang Kyung; Yong Cho, Won; Kyu Kim, Hyoung

    2012-01-01

    Bilateral gluteal compartment syndrome is a rare clinical entity that can be complicated by rhabdomyolysis or acute kidney injury (AKI). We report the a case of a 30-year-old woman without any comorbid diseases who was diagnosed with bilateral gluteal compartment syndrome complicated by rhabdomyolysis and dialysis-requiring AKI, which was caused by prolonged immobilization under the influence of alcohol. Although the patients renal function recovered fully after 5 sessions of hemodialysis, sciatic neuropathy caused by gluteal compartment syndrome led to permanent foot drop.

  2. Exertional rhabdomyolysis in quarter horses and thoroughbreds: one syndrome, multiple aetiologies.

    PubMed

    Valberg, S J; Mickelson, J R; Gallant, E M; MacLeay, J M; Lentz, L; de la Corte, F

    1999-07-01

    The purpose of this study was to determine if chronic exertional rhabdomyolysis (ER) in Quarter Horses and Thoroughbreds represents one or several distinct myopathies. Eighteen Quarter Horses and 18 Thoroughbreds with ER were selected from cases presented to the Veterinary Hospital on the basis of a history of ER, assessment of muscle histopathology, and serum CK activity before and 4 h post exercise. In addition, 2 of 3 of the following parameters were evaluated: muscle glycogen concentrations, thyroid hormones (T3, T4), fractional excretion (FE) of sodium, potassium and chloride. The CK response to training, the metabolic response to a near maximal standardised exercise test (SET), blood glucose concentrations after an i.v. glucose challenge and a skeletal muscle in vitro caffeine contracture test were performed on 5 of the Quarter Horses, selected because of polysaccharide storage myopathy (PSSM), and 5 of the Thoroughbreds. Serum T3 and T4 were all within normal limits. Low FE of sodium and potassium were seen in < 20% of Quarter Horses and Thoroughbreds. Four hours post exercise, CK was increased in 77% of Quarter Horses and 72% of Thoroughbreds with ER. Muscle glycogen concentrations in Quarter Horses with ER were significantly higher than in normal Quarter Horses and Thoroughbreds with ER. No Thoroughbreds, but 15/18 Quarter Horses with ER had abnormal polysaccharide accumulation in muscle biopsies consistent with a diagnosis of PSSM. PSSM Quarter Horses had higher CK activity during training than Thoroughbreds and higher glycogen utilisation with the SET. PSSM Quarter Horses also had significantly enhanced glucose clearance compared to normal Quarter Horses and Thoroughbreds with ER. Thoroughbreds with ER had significantly lower thresholds for caffeine-induced contracture than normal horses and PSSM Quarter Horses. It was concluded that there are multiple causes for exertional rhabdomyolysis. In Quarter Horses, rhabdomyolysis is commonly due to a glycogen storage disorder, PSSM, and is readily expressed in untrained horses. In Thoroughbreds, ER is commonly due to an underlying abnormality of muscle contraction. Rhabdomyolysis in Thoroughbreds, however, is only expressed intermittently when key stressors are present. PMID:10659313

  3. [Rhabdomyolysis and myopathy as the only manifestations of severe hypothyroidism secondary to Hashimoto's thyroiditis].

    PubMed

    Brito, Juan P; Domecq, Juan P; Prutsky, Gabriela; Mlaga, Germn; Young, Larry; Kargi, Atil Y

    2013-03-01

    Hashimoto's thyroiditis is the most frequent cause of hypothyroidism. In the regions with no iodine deficiency, it is more frequent in women and oftentimes has a familial association. The symptoms and signs of hypothyroidism are systemic and depend on the duration and intensity of the thyroid hormone deficiency. Neuromuscular manifestations are seldom the only symptoms and signs present. We present the case of a young patient with severe myopathy, where rhabdomyolysis was the sole manifestation of severe hypothyroidism secondary to Hashimoto's thyroiditis. PMID:23612826

  4. Running a risk? Sport supplement toxicity with ephedrine in an amateur marathon runner, with subsequent rhabdomyolysis

    PubMed Central

    Rhidian, Rhys

    2011-01-01

    A 36-year-old man presented to the emergency department acutely unwell after being found collapsed while running a halfmarathon. He presented with a reduced Glasgow coma score, was tachycardic, agitated, hypoxic and profusely sweating. He had taken a ‘supplement’ given to him prior to the race by a friend, as he was concerned about not finishing. This contained both caffeine and a large dose of ephedrine (60 mg in total). After initial resuscitation he was intubated, and was transferred to critical care. He subsequently developed rhabdomyolysis, requiring haemofiltration. PMID:22669965

  5. Herbal-drug interaction induced rhabdomyolysis in a liposarcoma patient receiving trabectedin

    PubMed Central

    2013-01-01

    Background Rhabdomyolysis is an uncommon side effect of trabectedin which is used for the second line therapy of metastatic sarcoma after anthracycline and ifosfamide failure. This side effect may be due to pharmacokinetic interactions caused by shared mechanisms of metabolism involving the cytochrome P450 (CYP) system in the liver. Here, for the first time in literature, we describe the unexpected onset of heavy toxicity, including rhabdomyolysis, after the fourth course of trabectedin in a patient with retroperitoneal liposarcoma who at the same time was taking an alternative herbal medicine suspected of triggering this adverse event. Case presentation This is the case of a 56 year old Caucasian man affected by a relapsed de-differentiated liposarcoma who, after the fourth cycle of second-line chemotherapy with trabectedin, complained of sudden weakness, difficulty walking and diffuse muscle pain necessitating complete bed rest. Upon admission to our ward the patient showed grade (G) 4 pancytopenia and a marked increase in liver lytic enzymes, serum levels of myoglobin, creatine phosphokinase (CPK) and lactate dehydrogenase. No cardiac or kidney function injuries were present. Based on these clinical and laboratory features, our conclusive diagnosis was of rhabdomyolysis induced by trabectedin. The patient did not report any trauma or muscular overexertion and no co-morbidities were present. He had not received any drugs during treatment with trabectedin, but upon further questioning the patient informed us he had been taking a folk medicine preparation of chokeberry (Aronia melanocarpa) daily during the last course of trabectedin and in the 2 subsequent weeks. One week after hospitalization and cessation of intake of chokeberry extract, CPK and other markers of myolysis slowly returned to standard range, and the patient noted a progressive recovery of muscle strength. The patient was discharged on day 14 when a blood transfusion and parenteral hydration gradually lowered general toxicity. Progressive mobilization of the patient was obtained as well as a complete normalization of the laboratory findings. Conclusions The level of evidence of drug interaction leading to the adverse event observed in our patient was 2 (probable). Thus our case underlines the importance of understanding rare treatment-related toxicities such as trabectedin-induced rhabdomyolysis and the possible role of the drug-drug interactions in the pathogenesis of this rare side effect. Furthermore, this report draws attention to a potential problem of particular concern, that of nutritional supplements and complementary and alternative drug interactions. These are not widely recognized and can cause treatment failure. PMID:23899130

  6. MANAGEMENT OF ACUTE RENAL FAILURE WITH DELAYED HYPERCALCEMIA SECONDARY TO SARCOCYSTIS NEURONA-INDUCED MYOSITIS AND RHABDOMYOLYSIS IN A CALIFORNIA SEA LION (ZALOPHUS CALIFORNIANUS).

    PubMed

    Alexander, Amy B; Hanley, Christopher S; Duncan, Mary C; Ulmer, Kyle; Padilla, Luis R

    2015-09-01

    A 3-yr-old captive-born California sea lion (Zalophus californianus) developed Sarcocystis neurona-induced myositis and rhabdomyolysis that led to acute renal failure. The sea lion was successfully managed with fluid therapy, antiprotozoals, antibiotics, anti-inflammatories, antiemetics, gastroprotectants, and diuretics, but developed severe delayed hypercalcemia, a syndrome identified in humans after traumatic or exertion-induced rhabdomyolysis. Treatment with calcitonin was added to the management, and the individual recovered fully. The case emphasizes that animals with rhabdomyolysis-induced renal failure risk developing delayed hypercalcemia, which may be life threatening, and calcium levels should be closely monitored past the resolution of renal failure. PMID:26352981

  7. Drug-induced hyperthermia and rhabdomyolysis during the perioperative period: report of three patients.

    PubMed

    Vorrakitpokatorn, Puthipanee; Limsakul, Aticha

    2002-09-01

    Drug-induced hyperthermia is one condition that anesthesiologists may meet even though it is uncommon, it is life threatening. We report 3 cases of patients at Siriraj Hospital, Mahidol University who developed drug-induced hyperthermia and rhabdomyolysis from different mechanisms. In two of them, the diagnosis was suspected malignant hyperthermia. Rigidity, hyperthermia and tachyarrhythmia developed just after inhalation induction (halothane and sevoflurane) and intubation with succinylcholine. The other case was the result of amphetamine abuse. He also had received both succinylcholine and inhalation agent (isoflurane) but no obvious signs or symptoms were detected during anesthesia. He developed a gradual increase in fever over 13 hours post operation and complained of muscle pain (with leg muscle cramps). All of them showed a marked increase in muscle enzymes and had rhabdomyolysis. As a result of early detection and early manangement, these three patients survived without any permanent damage to vital organs. We conclude that Thai anesthesiologists should be more aware and alert to drug-induced hyperthermia especially as nowadays many teenagers abuse stimulant drugs and "triggering" drugs as antidepressant or serotonin reuptake inhibitors are prescribed more frequently. Early detection and management will decrease morbidity and mortality. PMID:12452225

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

    PubMed

    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

  9. Review of exertional rhabdomyolysis and a case in a rhesus monkey (Macaca mulatta).

    PubMed

    Reuter, J D; Dysko, R C; Chrisp, C E

    1998-12-01

    This is the first confirmed report of exertional rhabdomyolysis in a non-human primate. The monkey was singly housed and presented with anorexia and reluctance to move. There was no external evidence of trauma. Clinicopathologic findings included mild azotemia, marked elevation in serum creatine phosphokinase (CPK), alanine aminotransferase, aspartate aminotransferase, and myoglobinuria. Two days post-incident, the peripheral skeletal muscle had marked multifocal myonecrosis and fibrillar disruption without an inflammatory reaction. Treatment included diuresis and pain relief, and urinary output was monitored. The monkey recovered over the next two weeks. The major significance of skeletal muscle damage is the potential of released myoglobin to cause acute renal failure in the presence of other co-factors such as hypovolemia, acidosis, or ischemia. CPK levels can be highly variable and are inconsistent with the degree of muscle damage; however, CPK is thought to be the most sensitive enzyme marker for muscle necrosis. Because of the potential life-threatening sequelae, exertional rhabdomyolysis should be included as a differential diagnosis when similar clinical and pathological signs are observed. PMID:10203011

  10. A Case of Primary Hypoparathyroidism Presenting with Acute Kidney Injury Secondary to Rhabdomyolysis

    PubMed Central

    Aydin, Zeki; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Cebeci, Egemen; Ozturk, Savas; Kazancioglu, Rumeyza

    2016-01-01

    Hypoparathyroidism is the most common cause of symmetric calcification of the basal ganglia. Herein, a case of primary hypoparathyroidism with severe tetany, rhabdomyolysis, and acute kidney injury is presented. A 26-year-old male was admitted to the emergency clinic with leg pain and cramps, nausea, vomiting, and decreased amount of urine. He had been treated for epilepsy for the last 10 years. He was admitted to the emergency department for leg pain, cramping in the hands and legs, and agitation multiple times within the last six months. He was prescribed antidepressant and antipsychotic medications. He had a blood pressure of 150/90 mmHg, diffuse abdominal tenderness, and abdominal muscle rigidity on physical examination. Pathological laboratory findings were as follows: creatinine, 7.5 mg/dL, calcium, 3.7 mg/dL, alanine transaminase, 4349 U/L, aspartate transaminase, 5237 U/L, creatine phosphokinase, 262.000 U/L, and parathyroid hormone, 0 pg/mL. There were bilateral symmetrical calcifications in basal ganglia and the cerebellum on computerized tomography. He was diagnosed as primary hypoparathyroidism and acute kidney injury secondary to severe rhabdomyolysis. Brain calcifications, although rare, should be considered in dealing with patients with neurological symptoms, symmetrical cranial calcifications, and calcium metabolism abnormalities.

  11. Hydroxycut weight loss dietary supplements: a contributing factor in the development of exertional rhabdomyolysis in three U.S. Army soldiers.

    PubMed

    Carol, Melinda L

    2013-09-01

    Exertional rhabdomyolysis is an enigmatic syndrome with multiple risk factors and a wide spectrum of clinical outcomes. Dietary supplements containing caffeine may potentiate the rhabdomyolysis cascade, and present an area of attainable prevention. Presented are three cases of soldiers using the weight loss supplement brand, Hydroxycut; patient education regarding caffeine and supplement safety may shield against morbidity and delayed soldier readiness associated with overcaffeination. PMID:24005555

  12. Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report.

    PubMed

    Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja

    2008-01-01

    We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment. PMID:24179353

  13. Severe Hypercalcemia Complicating Recovery of Acute Kidney Injury due to Rhabdomyolysis

    PubMed Central

    Hechanova, Lisa Aimee; Sadjadi, Seyed-Ali

    2014-01-01

    Patient: Male, 23 Final Diagnosis: Rabdomyolysis Symptoms: Cardiac arrest cardiac arrhythmia hypercalcemia Medication: Clinical Procedure: Specialty: Objective: Unusual clinical course Background: Rhabdomyolysis is frequently complicated by multiple electrolyte abnormalities, including hyperkalemia, hyperphosphatemia, and hypo/hypercalcemia. Hypercalcemia can be severe and life-threatening. Case Report: A 23-year-old white male suffered severe trauma to his lower extremities after a motor vehicle accident, leading to severe muscle damage, cardiac arrhythmia, cardiac arrest, and oliguric acute kidney injury (AKI), requiring hemodialysis treatment. As expected, he was hypocalcemic during the oliguric phase but during the diuretic phase he developed severe symptomatic hypercalcemia requiring hemodialysis treatment in spite of volume replacement and administration of pamidronate. Hypercalcemia reached a peak of 17.1 mg/dL, corrected for serum albumin and urine output was as high as 11.9 liters daily. Hypercalcemia lasted for 3 weeks and then it returned back to normal levels. Plasma levels of 25-OH and 125(OH)2 vitamin D were low, intact parathyroid hormone level was appropriately suppressed, and 24-hour urine calcium was 1194 mg (normal up to 350 mg/daily). Mobilization of calcium from calcium phosphate deposits in the injured muscles seems to be the main reason for hypercalcemia and hypercalciuria in rhabdomyolysis-induced AKI. Conclusions: Hypercalcemia is not uncommon during the recovery phase of ATN. Unattended, it can cause severe morbidity and even mortality. Fluid administration, pamidronate, and calcium-free dialysis are some methods used to correct severe hypercalcemia. Over time, hypercalcemia improves in almost all cases. PMID:25218143

  14. Rhabdomyolysis After Cooked Seafood Consumption (Haff Disease) in the United States vs China

    PubMed Central

    Diaz, James H.

    2015-01-01

    Background Haff disease is a syndrome of myalgia and rhabdomyolysis that occurs after eating cooked seafood. Methods For this descriptive analytical article, a literature search identified the scientific articles on Haff disease and/or rhabdomyolysis after eating cooked seafood in the United States and China. Analysis of those articles focused on identifying the seafood vectors of Haff disease, describing the most commonly recurring clinical and laboratory manifestations of Haff disease, and comparing the Haff disease toxidrome with other similar seafood-borne toxidromes. Statistically significant differences were determined using unpaired t tests and Fisher exact tests. Results Twenty-nine confirmed cases of Haff disease were identified in the United States, and 60 cases were identified in China during 1984-2014. Most of the US cases followed consumption of buffalo fish, and most of the Chinese cases followed consumption of freshwater pomfret. However, Haff disease also followed consumption of the same species of boiled crayfish (Procambarus clarkii) in the United States (n=9) and China (n=6). US patients with crayfish-transmitted Haff disease reported significantly more nausea with and without vomiting, chest pain, body and back pain, dyspnea, and diaphoresis than the Chinese patients and were more frequently misdiagnosed as having myocardial infarctions. Conclusion The bioaccumulation of a new, heat-stable freshwater and/or brackish/saltwater algal toxin, similar to palytoxin but primarily myotoxic and not neurotoxic, is suspected of causing Haff disease. At present, only the rapid identification of the seafood vectors of Haff disease will limit disease outbreaks and prevent further cases. PMID:26130980

  15. Acquired multiple acyl-CoA dehydrogenase deficiency and marked selenium deficiency causing severe rhabdomyolysis in a horse.

    PubMed

    Gomez, Diego E; Valberg, Stephanie J; Magdesian, K Gary; Hanna, Paul E; Lofstedt, Jeanne

    2015-11-01

    This report describes a case of severe rhabdomyolysis in a pregnant mare associated with histopathologic and biochemical features of both selenium deficiency and acquired multiple acyl-CoA dehydrogenase deficiency (MADD) due to seasonal pasture myopathy (SPM). This case highlights the importance of assessing plasma selenium levels in horses with clinical signs of pasture myopathy as this deficiency may be a contributing or exacerbating factor. PMID:26538673

  16. Comparison of lactated Ringer's solution and 0.9% saline in the treatment of rhabdomyolysis induced by doxylamine intoxication

    PubMed Central

    Cho, Young Soon; Lim, Hoon; Kim, Seung Ho

    2007-01-01

    Objective To compare the effectiveness and side effects of lactated Ringer's solution (LR) and 0.9% saline (NS) in the treatment of rhabdomyolysis induced by doxylamine intoxication. Methods In this 15?month?long prospective randomised single?blind study, after excluding 8 patients among 97 doxylamine?intoxicated patients, 28 (31%) patients were found to have developed rhabdomyolysis and were randomly allocated to NS group (n?=?15) or LR group (n?=?13). Results After 12?h of aggressive hydration (400?ml/h), urine/serum pH was found to be significantly higher in the LR group, and serum Na+/Cl? levels to be significantly higher in the NS group. There were no significant differences in serum K+ level and in the time taken for creatine kinase normalisation. The amount of sodium bicarbonate administered and the frequency administration of diuretics was significantly higher in the NS group. Unlike the NS group, the LR group needed little supplemental sodium bicarbonate and did not develop metabolic acidosis. Conclusion LR is more useful than NS in the treatment of rhabdomyolysis induced by doxylamine intoxication. PMID:17384382

  17. Exertional Rhabdomyolysis in a Collegiate American Football Player After Preventive Cold-Water Immersion: A Case Report

    PubMed Central

    Kahanov, Leamor; Eberman, Lindsey E.; Wasik, Mitchell; Alvey, Thurman

    2012-01-01

    Objective: To describe a case of exertional rhabdomyolysis in a collegiate American football player after preventive cold-water immersion. Background: A healthy man (19 years old) participated in full-contact football practice followed by conditioning (2.5 hours). After practice, he entered a coach-mandated post-practice cold-water immersion and had no signs of heat illness before developing leg cramps, for which he presented to the athletic training staff. After 10 minutes of repeated stretching, massage, and replacement of electrolyte-filled fluids, he was transported to the emergency room. Laboratory tests indicated a creatine kinase (CK) level of 2545 IU/L (normal range, 45260 IU/L), CK-myoglobin fraction of 8.5 ng/mL (normal < 6.7 ng/mL), and CK-myoglobin relative index of 30% (normal range, 25% 30%). Myoglobin was measured at 499 ng/mL (normal = 80 ng/mL). The attending physician treated the athlete with intravenous fluids. Differential Diagnosis: Exercise-associated muscle cramps, dehydration, exertional rhabdomyolysis. Treatment: The patient was treated with rest and rehydration. One week after the incident, he began biking and swimming. Eighteen days later, the patient continued to demonstrate elevated CK levels (527 IU/L) but described no other symptoms and was allowed to return to football practice as tolerated. Two months after the incident, his CK level remained high (1900 IU/L). Uniqueness: The athlete demonstrated no signs of heat illness upon entering the cold-water immersion but experienced severe leg cramping after immersion, resulting in a diagnosis of exertional rhabdomyolysis. Previously described cases have not linked cold-water immersion with the pathogenesis of rhabdomyolysis. Conclusions: In this football player, CK levels appeared to be a poor indicator of rhabdomyolysis. Our patient demonstrated no other signs of the illness weeks after the incident, yet his elevated CK levels persisted. Cold-water immersion immediately after exercise should be monitored by the athletic training staff and may not be appropriate to prevent muscle damage, given the lack of supporting evidence. PMID:22488291

  18. Rhabdomyolysis as a presenting manifestation of very long-chain acyl-coenzyme a dehydrogenase deficiency.

    PubMed

    Oliveira, Sara Freitas; Pinho, Liliana; Rocha, Hugo; Nogueira, Clia; Vilarinho, Laura; Dinis, Maria Jos; Silva, Conceio

    2013-08-01

    Very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency (MIM 201475) is a rare inherited disorder with three forms of clinical presentation: a severe early-onset form; an intermediate form with childhood onset; and an adult-onset form, of mild severity. During adolescence and adulthood, exercise intolerance, myalgia and recurrent episodes of rhabdomyolysis are the main clinical features. The authors present a case of a 13-year old female, with severe myalgia and dark urine after prolonged exercise. Analytical evaluation showed marked elevation plasma creatine kinase and myoglobin. The increased levels of tetradecenoyl carnitine in patient's dried blood spot suggested a VLCAD deficiency, which was confirmed by molecular study. Family history is remarkable for first grade consanguinity of parents and a 19-year old brother with records of repeated similar episodes after moderate intensity physical efforts which was subsequently also diagnosed with VLCAD deficiency. This is one of the first cases of late-onset of disease diagnosed in Portugal. PMID:24765510

  19. Transportation stress and the incidence of exertional rhabdomyolysis in emus (Dromaius novaehollandiae).

    PubMed

    Menon, Deepa G; Bennett, Darin C; Schaefer, Allan L; Cheng, Kimberly M

    2014-02-01

    Many emu farms are located in areas lacking processing facilities that can handle these birds. Thus, long-distance shipping of birds to an abattoir is necessary. Two experiments were conducted, wherein emus were transported in a modified horse trailer for 6 h to an abattoir. Changes in the indices of stress and metabolic homeostasis (hematology, serum biochemistry, enzymes, and body temperature and weight) were used to evaluate the physiological response to transport. The activities of enzymes alanine aminotransferase, aspartate aminotransferase, and creatine kinase increased significantly (P < 0.001) from pretransport to slaughter, indicating muscle cell wall damages. The body temperature of emus was significantly (P < 0.001) increased from 37.0 to 39.6°C after transport in experiment 1 and from 37.2 to 38.9°C in experiment 2. Transport resulted in significant weight loss in both experiments (P < 0.001; 2.1 ± 0.2 kg vs. 0.6 ± 0.2 kg) and posttransport resting at lairage led to slight regaining (P < 0.01) of BW. Oral administration of supplements before and after transport was effective in protecting against muscle damage and faster recovery of BW losses during lairage. The clinical findings were suggestive of the incidence of exertional rhabdomyolysis and thus underlined the need for careful handling and improved transport conditions of emus. PMID:24570448

  20. Rhabdomyolysis following Cardiac Surgery: A Prospective, Descriptive, Single-Center Study

    PubMed Central

    Ewila, Hesham; Aboulnaga, Sameh; Tuli, Alejandro Kohn; Singh, Rajvir

    2016-01-01

    Purpose. Rhabdomyolysis (RML) following cardiac surgery and its relationship with acute kidney injury (AKI) require investigation. Patients and Methods. All patients undergoing cardiac surgery in our hospital were enrolled in this prospective study during a 1-year period. To investigate the occurrence of RML and its association with AKI, all patients in the study underwent serial assessment of serum creatine kinase (CK) and myoglobin levels. Serial renal function, prior statin treatment, and outcome variables were recorded. Results. In total, 201 patients were included in the study: 185 men and 16 women with a mean age of 52.0 ± 12.4 years. According to the presence of RML (CK of ≥2,500 U/L), the patients were divided into Group I (RML present in 17 patients) and Group II (RML absent in 184 patients). Seven patients in Group I had AKI (41%) where 34 patients in group II had AKI (18.4%), P = 0.025. We observed a significantly longer duration of ventilation, length of stay in the ICU, and hospitalization in Group I (P < 0.001 for all observations). Conclusions. An early elevation of serum CK above 2500 U/L postoperatively in high-risk cardiac surgery could be used to diagnose RML that may predict the concomitance of early AKI.

  1. Rhabdomyolysis After Out-of-Water Exercise in an Elite Adolescent Water Polo Player Carrying the IL-6 174C Allele Single-Nucleotide Polymorphism.

    PubMed

    Eliakim, Alon; Ben Zaken, Sigal; Meckel, Yoav; Yamin, Chen; Dror, Nitzan; Nemet, Dan

    2015-12-01

    Eliakim, A, Ben Zaken, S, Meckel, Y, Yamin, C, Dror, N, and Nemet, D. Rhabdomyolysis after out-of-water exercise in an elite adolescent water polo player carrying the IL-6 174C allele single-nucleotide polymorphism. J Strength Cond Res 29(12): 3506-3508, 2015-We present an adolescent elite water polo player who despite a genetic predisposition to develop exercise-induced severe muscle damage due to carrying the IL-6 174C allele single-nucleotide polymorphism, developed acute rhabdomyolysis only after a vigorous out-of-water training, suggesting that water polo training may be more suitable for genetically predisposed athletes. PMID:25970495

  2. Refractory status epilepticus, serious rhabdomyolysis, acute liver injury, and pancytopenia after a massive intake of ethyl methanesulfonate: a case report

    PubMed Central

    Yamazaki, Hiroyuki; Tajima, Shogo; Takeuchi, Takahiro

    2015-01-01

    Ethyl methanesulfonate is a mutagenic, alkylating agent and considered harmful to humans at levels greater than a certain threshold; however, the toxicity at high doses remains unclear. We report a case of a Japanese man who presented with status epilepticus, rhabdomyolysis, pancytopenia, and hair loss after accidental ingestion of a massive amount of ethyl methanesulfonate. The patient completely recovered with critical care, including multiple antiepileptic drugs, renal replacement therapy, blood transfusion, granulocyte colony-stimulating factor therapy, and antibacterial/fungal prophylaxis. The case indicates that ethyl methanesulfonate causes neurotoxicity, hepatotoxicity, hematotoxicity, and renal toxicity, which can be successfully treated with appropriate palliative therapies. PMID:26629236

  3. Successful management of a dog that had severe rhabdomyolysis with myocardial and respiratory failure.

    PubMed

    Wells, Raegan J; Sedacca, Cassidy D; Aman, Anna M; Hackett, Timothy B; Twedt, David C; Shelton, G Diane

    2009-04-15

    CASE DESCRIPTION - A 6-year-old castrated male Llewelyn Setter was evaluated because of an acute onset of myalgia and respiratory distress. CLINICAL FINDINGS - Physical examination revealed a stiff stilted gait, swollen muscles that appeared to cause signs of pain, panting, and ptyalism. The dog had a decrease in palpebral reflexes bilaterally and a decrease in myotatic reflexes in all 4 limbs. The panniculus reflex was considered normal, and all other cranial nerve reflexes were intact. Serum biochemical analysis revealed markedly high cardiac troponin-I concentration and creatine kinase and aspartate aminotransferase activities. Urinalysis revealed myoglobinuria. Results for thoracic and abdominal radiography, blood pressure measurement, and an ECG were within anticipated limits. Echocardiographic findings were consistent with secondary systolic myocardial failure. Arterial blood gas analysis confirmed hypoxemia and hypoventilation. The dog had negative results when tested for infectious diseases. Examination of skeletal muscle biopsy specimens identified necrotizing myopathy. TREATMENT AND OUTCOME - Treatment included ventilatory support; IV administration of an electrolyte solution supplemented with potassium chloride; administration of dantrolene; vasopressor administration; parenteral administration of nutrients; use of multimodal analgesics; administration of clindamycin, furosemide, mannitol, and enrofloxacin; and dietary supplementation with L-carnitine and coenzyme Q(10). Other medical interventions were not required, and the dog made a rapid and complete recovery. CLINICAL RELEVANCE - Necrotizing myopathy resulting in rhabdomyolysis and myoglobinuria can lead to life-threatening physical and biochemical abnormalities. Making a correct diagnosis is essential, and patients require intensive supportive care. The prognosis can be excellent for recovery, provided there is no secondary organ dysfunction. PMID:19366338

  4. Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency.

    PubMed

    Diekman, E F; Visser, G; Schmitz, J P J; Nievelstein, R A J; de Sain-van der Velden, M; Wardrop, M; Van der Pol, W L; Houten, S M; van Riel, N A W; Takken, T; Jeneson, J A L

    2016-01-01

    Rhabdomyolysis is common in very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and other metabolic myopathies, but its pathogenic basis is poorly understood. Here, we show that prolonged bicycling exercise against a standardized moderate workload in VLCADD patients is associated with threefold bigger changes in phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations in quadriceps muscle and twofold lower changes in plasma acetyl-carnitine levels than in healthy subjects. This result is consistent with the hypothesis that muscle ATP homeostasis during exercise is compromised in VLCADD. However, the measured rates of PCr and Pi recovery post-exercise showed that the mitochondrial capacity for ATP synthesis in VLCADD muscle was normal. Mathematical modeling of oxidative ATP metabolism in muscle composed of three different fiber types indicated that the observed altered energy balance during submaximal exercise in VLCADD patients may be explained by a slow-to-fast shift in quadriceps fiber-type composition corresponding to 30% of the slow-twitch fiber-type pool in healthy quadriceps muscle. This study demonstrates for the first time that quadriceps energy balance during exercise in VLCADD patients is altered but not because of failing mitochondrial function. Our findings provide new clues to understanding the risk of rhabdomyolysis following exercise in human VLCADD. PMID:26881790

  5. Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations.

    PubMed

    Lalani, Seema R; Liu, Pengfei; Rosenfeld, Jill A; Watkin, Levi B; Chiang, Theodore; Leduc, Magalie S; Zhu, Wenmiao; Ding, Yan; Pan, Shujuan; Vetrini, Francesco; Miyake, Christina Y; Shinawi, Marwan; Gambin, Tomasz; Eldomery, Mohammad K; Akdemir, Zeynep Hande Coban; Emrick, Lisa; Wilnai, Yael; Schelley, Susan; Koenig, Mary Kay; Memon, Nada; Farach, Laura S; Coe, Bradley P; Azamian, Mahshid; Hernandez, Patricia; Zapata, Gladys; Jhangiani, Shalini N; Muzny, Donna M; Lotze, Timothy; Clark, Gary; Wilfong, Angus; Northrup, Hope; Adesina, Adekunle; Bacino, Carlos A; Scaglia, Fernando; Bonnen, Penelope E; Crosson, Jane; Duis, Jessica; Maegawa, Gustavo H B; Coman, David; Inwood, Anita; McGill, Jim; Boerwinkle, Eric; Graham, Brett; Beaudet, Art; Eng, Christine M; Hanchard, Neil A; Xia, Fan; Orange, Jordan S; Gibbs, Richard A; Lupski, James R; Yang, Yaping

    2016-02-01

    The underlying genetic etiology of rhabdomyolysis remains elusive in a significant fraction of individuals presenting with recurrent metabolic crises and muscle weakness. Using exome sequencing, we identified bi-allelic mutations in TANGO2 encoding transport and Golgi organization 2 homolog (Drosophila) in 12 subjects with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. A recurrent homozygous c.460G>A (p.Gly154Arg) mutation was found in four unrelated individuals of Hispanic/Latino origin, and a homozygous ?34 kb deletion affecting exons 3-9 was observed in two families of European ancestry. One individual of mixed Hispanic/European descent was found to be compound heterozygous for c.460G>A (p.Gly154Arg) and the deletion of exons 3-9. Additionally, a homozygous exons 4-6 deletion was identified in a consanguineous Middle Eastern Arab family. No homozygotes have been reported for these changes in control databases. Fibroblasts derived from a subject with the recurrent c.460G>A (p.Gly154Arg) mutation showed evidence of increased endoplasmic reticulum stress and a reduction in Golgi volume density in comparison to control. Our results show that the c.460G>A (p.Gly154Arg) mutation and the exons 3-9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations. PMID:26805781

  6. Investigation of selected biochemical indicators of Equine Rhabdomyolysis in Arabian horses: pro-inflammatory cytokines and oxidative stress markers.

    PubMed

    El-Deeb, Wael Mohamed; El-Bahr, Sabry M

    2010-12-01

    A total of 30 horses were divided into two groups, one served as a control whereas other was rhabdomyolysis diseased horses. After blood collection, the resulted sera were used for estimation of the activities of creatin kinase (CK), aspartate transaminase (AST), lactate dehydrogenase (LDH), lactic acid, triacylglycerol (TAG), glucose, total protein, albumin, globulin, urea, creatinine, Triiodothyronine (T(3)), calcium, sodium, potassium, phosphorus, chloride, vitamin E, interleukin-6 (IL-6) and tumor necrosis-? (TNF-?). In addition, whole blood was used for determination of selenium, reduced glutathione (G-SH) and prostaglandin F2-? (PGF2?). The erythrocyte hemolysates were used for the determination of the activities of super oxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), nitric oxide (NO) and malondialdehyde (MDA). The present findings revealed a significant (p???0.05) increase in the values of CK, AST, LDH, glucose, lactate, TAG, urea, creatinine, phosphorus, MDA, TNF- ?, IL6 and PGF2- ? in diseased horses when compared with the control. Furthermore, the values of calcium, SOD, CAT, TAC, NO and GSH in diseased horses were significantly (p???0.05) lower than the control. The other examined parameters were not statistically significant. In conclusion, the examined pro-inflammatory cytokines were useful biomarkers for the diagnosis of Equine rhabdomyolysis (ER) in Arabian horses beside the old examined biomarkers. In the future, efforts should be made to confirm this in other breed. If this could be achieved, it would open up new perspectives in research fields dealing with ER. PMID:20830520

  7. Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency

    PubMed Central

    Diekman, E. F.; Visser, G.; Schmitz, J. P. J.; Nievelstein, R. A. J.; de Sain-van der Velden, M.; Wardrop, M.; Van der Pol, W. L.; Houten, S. M.; van Riel, N. A. W.; Takken, T.; Jeneson, J. A. L.

    2016-01-01

    Rhabdomyolysis is common in very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and other metabolic myopathies, but its pathogenic basis is poorly understood. Here, we show that prolonged bicycling exercise against a standardized moderate workload in VLCADD patients is associated with threefold bigger changes in phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations in quadriceps muscle and twofold lower changes in plasma acetyl-carnitine levels than in healthy subjects. This result is consistent with the hypothesis that muscle ATP homeostasis during exercise is compromised in VLCADD. However, the measured rates of PCr and Pi recovery post-exercise showed that the mitochondrial capacity for ATP synthesis in VLCADD muscle was normal. Mathematical modeling of oxidative ATP metabolism in muscle composed of three different fiber types indicated that the observed altered energy balance during submaximal exercise in VLCADD patients may be explained by a slow-to-fast shift in quadriceps fiber-type composition corresponding to 30% of the slow-twitch fiber-type pool in healthy quadriceps muscle. This study demonstrates for the first time that quadriceps energy balance during exercise in VLCADD patients is altered but not because of failing mitochondrial function. Our findings provide new clues to understanding the risk of rhabdomyolysis following exercise in human VLCADD. PMID:26881790

  8. Kinin B2 receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis

    PubMed Central

    Gattai, Pedro Paulo; Mafra, Fernando Francisco Pazello; Wasinski, Frederick; Almeida, Sandro Soares; Cenedeze, Marcos Antnio; Malheiros, Denise Maria Avancini Costa; Bacurau, Reury Frank Pereira; Barros, Carlos Castilho; Cmara, Niels Olsen Saraiva; Araujo, Ronaldo Carvalho

    2014-01-01

    AIM: To investigate a potential protective role of the kinin B2 receptor in a glycerol-induced rhabdomyolysis mouse model. METHODS: We separated 28 C57Bl/6 male mice into 4 groups: untreated WT animals, untreated B2 knockout mice, glycerol-treated WT and glycerol-treated B2 knockout mice. Glycerol-treated animals received one intramuscular injections of glycerol solution (50% v/v, 7 mL/kg). After 48 h, urine and blood samples were collected to measure creatinine and urea levels. Additionally, kidney samples were extracted for histological evaluation, and the mRNA expression levels of kinin B1 and B2 receptors and inflammatory mediators were measured by real-time polymerase chain reaction. RESULTS: Serum creatinine and urea levels showed differences between untreated wild-type and glycerol-treated wild-type mice (0.66 0.04 vs 2.61 0.53 mg/dL, P < 0.01; and 33.51 2.08 vs 330.2 77.7 mg/dL, P < 0.005), and between untreated B2 knockout mice and glycerol-treated knockout mice (0.56 0.03 vs 2.23 0.87 mg/dL, P < 0.05; and 42.49 3.2 vs 327.2 58.4 mg/dL, P < 0.01), but there was no difference between the glycerol-treated wild-type and glycerol-treated knockout mice. Glycerol was able to induce a striking increase in kinin B2 receptor expression (> 30 times, 31.34 8.9) in kidney. Animals injected with glycerol had a higher degree of tubular injury than untreated animals. Wild-type and knockout mice treated with glycerol intramuscularly present kidney injury, with impairment in renal function. However, B2 knockout mice treated with glycerol did not show a different phenotype regarding kidney injury markers, when compared to the wild-type glycerol-treated group. CONCLUSION: We conclude that the kinin B2 receptor does not have a protective role in renal injury. PMID:25332899

  9. Severe Legionnaires' Disease Complicated by Rhabdomyolysis and Clinically Resistant to Moxifloxacin in a Splenectomised Patient: Too Much of a Coincidence?

    PubMed Central

    Koufakis, Theocharis; Gabranis, Ioannis; Chatzopoulou, Marianneta; Margaritis, Anastasios; Tsiakalou, Maria

    2015-01-01

    We here report a case of Legionnaires' disease in a splenectomised patient, complicated by rhabdomyolysis and acute renal failure and characterized by a poor clinical response to moxifloxacin. Splenectomy is not included among the factors, typically associated with higher risk or mortality in patients with Legionellosis. However, our report is consistent with previous case reports describing severe Legionella infections in asplenic subjects. The possibility that functional or anatomic asplenia may be a factor predisposing to severe clinical course or poor response to therapy in patients with Legionella infection cannot be excluded, deserving further investigation in the future. More studies are required in order to clarify the underlying pathophysiological mechanisms that connect asplenia, immunological response to Legionella, and pathogen's resistance to antibiotics. PMID:26682076

  10. Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids

    PubMed Central

    Zhao, Aiyu; Tan, Maybel; Maung, Aung; Salifu, Moro; Mallappallil, Mary

    2015-01-01

    The use of synthetic cannabinoids (SCBs) is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI) requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs) in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73%) as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK) level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity. PMID:26550500

  11. Full recovery after severe serotonin syndrome, severe rhabdomyolysis, multi-organ failure and disseminated intravascular coagulopathy from MDMA.

    PubMed

    Davies, O; Batajoo-Shrestha, B; Sosa-Popoteur, J; Olibrice, M

    2014-01-01

    3, 4-methylenedioxymethamphetamine (MDMA), popularly known as "ecstasy" is a synthetic, psychoactive drug used recreationally for its euphoric and "energy increasing" effects. MDMA has been linked to several severe adverse effects including the development of serotonin syndrome and sudden death. Individuals of Asian descent have been shown to have a predisposition for these severe adverse effects. We present a case of a young Asian-American male who following MDMA ingestion presented with severe rhabdomyolysis (CK 130,350 U/L), multiple organ failure and severe serotonin syndrome with one of the highest recorded temperatures '108.9F (42.7C)' in a survivor of severe serotonin syndrome. The patient initially received supportive care including ventilatory support; he eventually needed hemodialysis, but went on to make a full recovery within 3 weeks. This case shows and emphasizes the importance of 'aggressive' supportive care on patient prognosis particularly for patients on the extreme end of the serotonin syndrome. PMID:24373952

  12. Acute Kidney Injury and Rhabdomyolysis After Protobothrops flavoviridis Bite: A Retrospective Survey of 86 Patients in a Tertiary Care Center.

    PubMed

    Nishimura, Hiroaki; Enokida, Hideki; Kawahira, Shuichirou; Kagara, Ichiro; Hayami, Hiroshi; Nakagawa, Masayuki

    2016-02-01

    Acute kidney injury (AKI) is the main cause of death for victims of hematoxic snakebites. A few studies have described improvement in AKI rates in snakebite cases, but the reasons for the improvement have not been investigated. Eighty-six patients with Protobothrops flavoviridis bites admitted to a single center from January 2003 through March 2014 were included in the study. Clinical variables, including age, sex, blood pressure (BP), and serum creatinine (S-Cre), on admission were compared between patients with and without AKI. One patient died of disseminated intravascular coagulation following AKI (mortality rate 1.1%). Six patients developed AKI with rhabdomyolysis. Systolic BP, S-Cre, serum creatine kinase, white blood cell count, and platelet count differed significantly between the AKI and non-AKI groups (P = 0.01). Three of the six patients were physically challenged to a degree that made it difficult for them to move or communicate, and these difficulties likely exacerbated the severity of snakebite complications. Our study demonstrated that the risk of snakebite-induced AKI for physically challenged patients was high. To further reduce mortality due to snakebite-induced AKI, we need to make it possible for physically challenged patients to receive first aid sooner. PMID:26643529

  13. A heterozygous missense mutation in adolescent-onset very long-chain acyl-CoA dehydrogenase deficiency with exercise-induced rhabdomyolysis.

    PubMed

    Hisahara, Shin; Matsushita, Takashi; Furuyama, Hiroyasu; Tajima, Go; Shigematsu, Yosuke; Imai, Tomihiro; Shimohama, Shun

    2015-01-01

    Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is characterized by impaired mitochondrial ?-oxidation of fatty acids. The fatty acid oxidation plays a significant role in energy production especially in skeletal muscle. VLCAD is one of four acyl-CoA dehydrogenases with different-chain length specificity and catalyzes the initial step in mitochondrial ?-oxidation of fatty acids. While the clinical phenotypes in neonates and infants are described as severe, adolescent-onset or adult-onset VLCAD deficiency has a more benign course with only skeletal muscle involvement. These myopathic phenotypes are characterized by episodic muscle weakness and rhabdomyolysis triggered by fasting and strenuous exercise. We report a male teenager who manifested repeated episodes of rhabdomyolysis immediately after exertional exercise. Rhabdomyolysis was diagnosed based on the marked elevation of serum creatine kinase and myoglobinuria. Acylcarnitine analysis by tandem mass spectrometry (MS/MS) revealed elevation of serum tetradecenoylcarnitine (C14:1-AC), which represents an abnormal acylcarnitine profile associated with the mitochondrial ?-oxidation defect. High performance liquid chromatographic analysis showed decreased production of 2-hexadecenoyl-CoA (C16:1) from palmitoyl-CoA (C16:0), indicating the defect of VLCAD activity. Direct sequencing of the acyl-CoA dehydrogenase, very long-chain gene (ACADVL) that codes VLCAD revealed a heterozygous mutation (c.1242G>C) in exon 12 (E414D), which is a novel mutation in myopathic-type VLCAD deficiency. Because VLCAD functions as a homodimer, we assume that this heterozygous mutation may exhibit dominant-negative effect. This patient remains asymptomatic thereafter by avoiding exertional exercise. The findings of reduction of enzyme activity and clinical features associated with this novel missense mutation of VLCAD are discussed. PMID:25843429

  14. Selenium Inhibits Renal Oxidation and Inflammation But Not Acute Kidney Injury in an Animal Model of Rhabdomyolysis

    PubMed Central

    Shanu, Anu; Groebler, Ludwig; Kim, Hyun Bo; Wood, Sarah; Weekley, Claire M.; Aitken, Jade B.; Harris, Hugh H.

    2013-01-01

    Abstract Acute kidney injury (AKI) is a manifestation of rhabdomyolysis (RM). Extracellular myoglobin accumulating in the kidney after RM promotes oxidative damage, which is implicated in AKI. Aim: To test whether selenium (Se) supplementation diminishes AKI and improves renal function. Results: Dietary selenite increased Se in the renal cortex, as demonstrated by X-ray fluorescence microscopy. Experimental RM-stimulated AKI as judged by increased urinary protein/creatinine, clusterin, and kidney injury molecule-1 (KIM-1), decreased creatinine clearance (CCr), increased plasma urea, and damage to renal tubules. Concentrations of cholesterylester (hydro)peroxides and F2-isoprostanes increased in plasma and renal tissues after RM, while aortic and renal cyclic guanidine monophosphate (cGMP; marker of nitric oxide (NO) bioavailability) decreased. Renal superoxide dismutase-1, phospho-P65, TNF? gene, MCP-1 protein, and the 3-chloro-tyrosine/tyrosine ratio (Cl-Tyr/Tyr; marker of neutrophil activation) all increased after RM. Dietary Se significantly decreased renal lipid oxidation, phospho-P65, TNF? gene expression, MCP-1 and Cl-Tyr/Tyr, improved NO bioavailability in aorta but not in the renal microvasculature, and inhibited proteinuria. However, CCr, plasma urea and creatinine, urinary clusterin, and histopathological assessment of AKI remained unchanged. Except for the Se++ group, renal angiotensin-receptor-1/2 gene/protein expression increased after RM with parallel increases in MEK1/2 inhibitor-sensitive MAPkinase (ERK) activity. Innovation: We employed synchrotron radiation to identify Se distribution in kidneys, in addition to assessing reno-protection after RM. Conclusion: Se treatment has some potential as a therapeutic for AKI as it inhibits oxidative damage and inflammation and decreases proteinuria, albeit histopathological changes to the kidney and some plasma and urinary markers of AKI remain unaffected after RM. Antioxid Redox Signal. 18, 756769. PMID:22937747

  15. Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury.

    PubMed

    Nishida, Kento; Watanabe, Hiroshi; Ogaki, Shigeru; Kodama, Azusa; Tanaka, Ryota; Imafuku, Tadashi; Ishima, Yu; Chuang, Victor Tuan Giam; Toyoda, Masao; Kondoh, Masumi; Wu, Qiong; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

    2015-01-01

    Rhabdomyolysis-associated acute kidney injury (AKI) is a serious life-threatening condition. As such, more effective strategies are needed for its prevention. Thioredoxin-1 (Trx), a redox-active and macrophage migration inhibitory factor (MIF) modulating protein, has a short retention time in the blood. We examined the renoprotective effect of long acting Trx that was genetically fused with human serum albumin (HSA-Trx) against glycerol-induced AKI. An intravenous HSA-Trx pre-treatment attenuated the glycerol-induced decline in renal function, compared to a PBS, HSA or Trx alone. HSA-Trx caused a reduction in the tubular injuries and in the number of apoptosis-positive tubular cells. Renal superoxide, 8-hydroxy deoxyguanosine, nitrotyrosine and the plasma Cys34-cysteinylated albumin were clearly suppressed by the HSA-Trx treatment. Prior to decreasing TNF-? and IL-6, HSA-Trx suppressed an increase of plasma MIF level. In LLC-PK1 cells, HSA-Trx decreased the level of reactive oxygen species and lactate dehydrogenase release induced by myoglobin. HSA-Trx treatment resulted in a threefold increase in the survival of lethal glycerol-treated mice. The post-administration of HSA-Trx at 1 and 3?hr after glycerol injection exerted a significant renoprotective effect. These results suggest HSA-Trx has potential for use in the treatment of rhabdomyolysis-associated AKI via its extended effects of modulating oxidative stress and MIF. PMID:26412311

  16. Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury

    PubMed Central

    Nishida, Kento; Watanabe, Hiroshi; Ogaki, Shigeru; Kodama, Azusa; Tanaka, Ryota; Imafuku, Tadashi; Ishima, Yu; Giam Chuang, Victor Tuan; Toyoda, Masao; Kondoh, Masumi; Wu, Qiong; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

    2015-01-01

    Rhabdomyolysis-associated acute kidney injury (AKI) is a serious life-threatening condition. As such, more effective strategies are needed for its prevention. Thioredoxin-1 (Trx), a redox-active and macrophage migration inhibitory factor (MIF) modulating protein, has a short retention time in the blood. We examined the renoprotective effect of long acting Trx that was genetically fused with human serum albumin (HSA-Trx) against glycerol-induced AKI. An intravenous HSA-Trx pre-treatment attenuated the glycerol-induced decline in renal function, compared to a PBS, HSA or Trx alone. HSA-Trx caused a reduction in the tubular injuries and in the number of apoptosis-positive tubular cells. Renal superoxide, 8-hydroxy deoxyguanosine, nitrotyrosine and the plasma Cys34-cysteinylated albumin were clearly suppressed by the HSA-Trx treatment. Prior to decreasing TNF-α and IL-6, HSA-Trx suppressed an increase of plasma MIF level. In LLC-PK1 cells, HSA-Trx decreased the level of reactive oxygen species and lactate dehydrogenase release induced by myoglobin. HSA-Trx treatment resulted in a threefold increase in the survival of lethal glycerol-treated mice. The post-administration of HSA-Trx at 1 and 3 hr after glycerol injection exerted a significant renoprotective effect. These results suggest HSA-Trx has potential for use in the treatment of rhabdomyolysis-associated AKI via its extended effects of modulating oxidative stress and MIF. PMID:26412311

  17. Penehyclidine Hydrochloride Pretreatment Ameliorates Rhabdomyolysis-Induced AKI by Activating the Nrf2/HO-1 Pathway and Allevi-ating Endoplasmic Reticulum Stress in Rats

    PubMed Central

    Zhao, Wei; Huang, XuDong; Zhang, LiXia; Yang, XinJun; Wang, LiHui; Chen, YunShuang; Wang, JingHua; Wu, GuangLi

    2016-01-01

    Acute kidney injury (AKI) is one of the most severe complications of rhabdomyolysis (RM). The underlying mechanisms and potential preventions need to be investigated. Penehyclidine hydrochloride (PHC) was reported to ameliorate renal ischemia-reperfusion injury, but the effect of PHC on RM-reduced AKI is unknown. In this study, we established a rat model of RM-induced AKI using an intramuscular glycerol injection in the hind limbs. Rats were pretreated with PHC before the glycerol injection, and the heme oxygenase-1 (HO-1) inhibitor ZnPP was introduced to evaluate the effect of HO-1 on RM-induced AKI. PHC pretreatment ameliorated the pathological renal injury and renal dysfunction, and decreased the renal apoptosis rate in RM-induced AKI. PHC significantly up-regulated HO-1 expression, increased HO-1 enzymatic activity and decreased the accumulation of myoglobin in renal tissues. This effect was partly inhibited by ZnPP. PHC pretreatment also effectively up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) and down-regulated glucose regulated protein 78 (GRP78) and caspase-12 at both the gene and protein levels. These results suggest that the protective effects of PHC pretreatment on RM-induced AKI occur at least in part through activating the Nrf2/HO-1 pathway and alleviating endoplasmic reticulum stress (ERS) in rat renal tissues. PMID:26987113

  18. Extensive extraosseous localization of bone imaging agent in a patient with renal failure and rhabdomyolysis accompanied by combined hypercalcemia and hyperphosphatemia

    SciTech Connect

    Shih, W.J.; Flueck, J.; O'Connor, W.; Domstad, P.A.

    1989-03-01

    Four sequential Tc-99m pyrophosphate (PYP) imaging studies were performed in a 28-year-old man with high fever and exudate pharyngitis associated with renal failure. Radiotracer localization in the left ventricle (LV), lungs, kidneys, and skeletal muscles were seen in two, initial imaging studies. In the second and third imaging studies, area of increase in activity was seen in the left-sided bowel. In studies done two months later (in the third study), the radioactivity in the skeletal muscles was no longer seen. Studies obtained nine months (in the fourth study) after the first imaging showed less radiotracer localization in the LV, lungs, and kidneys as compared to that seen in the initial study. Myocardial necrosis and microcalcification were proved by LV biopsy. The exact mechanism of extraosseous bone-imaging agent localization is unknown. However, this phenomenon may be related to renal failure, rhabdomyolysis, hypercalcemia, hyperphosphatemia, or elevated parathyroid hormone. The Tc-99m PYP imaging study is useful and sensitive in the detection of extraosseous tissue calcification and monitoring of the disease process.

  19. A baby with symmetrical hand injuries and rhabdomyolysis following nonfatal electrocution by an unusual mechanism.

    PubMed

    Hon, Kam Lun; Tse, Wing Lim; Cheung, Hon Ming; Yip, Sung Tat; Cheung, Kam Lau; Wong, William

    2014-11-01

    Childhood electrical injuries are rare in the city of Hong Kong. We report the case of a 21-month boy with severe electrical injuries of both hands and explored underlying mechanism for the incident. Meticulous orthopedic repair and reconstruction ensures satisfactory cosmetic and functional outcomes. Our case concurs with the literature that young children may be predisposed to this mode of incident with their curious exploring hands. Despite regulations on electrical home safety standards, extension power boards can still pose a dangerous risk for severe morbidity in the household with young children. Prevention strategies often involve commonsense approach in home safety measures such as (1) use proper fuses in electrical boxes, (2) do not overload outlets, (3) use insulated and grounded electrical cords, (4) keep electrical cords away from a child's reach, and (5) cover electrical outlets so children will not stick items in the outlet. PMID:24560958

  20. Critical illness in energy metabolism genetic disorder: rhabdomyolysis, acute kidney injury, respiratory arrest.

    PubMed

    Giuliani, E; Coppi, F; Bertolotti, V; Gorlato, G; Zavatta, M; Barbieri, A

    2013-11-01

    In very long-chain acylCoA dehydrogenase deficiency (VLCAD), the activity of this enzyme is either reduced or absent with the inability to use long-chain fatty acids as energy substrates. A 25-year old male with VLCAD was admitted to the Emergency Department of Policlinico Teaching Hospital (Modena, Italy)for generalized weakness and oliguria, after a period of physical and mental stress and inadequate compliance to a long-chain fatty acid free diet. Laboratory tests were compatible with acute kidney injury. Seventy-two hours after admission, the subject had an episode of chest pain with elevated markers of myocardial necrosis. The rapid deterioration of muscular strength and the subsequent worsening respiratory failure necessitated ventilator support within the local Medical Intensive Care Unit. There, the patient showed a prompt normalization of respiratory parameters and a steady improvement of renal function. An inadequate compliance to lifestyle and dietary restriction in VLCAD may trigger severe and potentially lethal crisis. The in-hospital management of these patients calls for early intensive care admission as their conditions may deteriorate without warning. PMID:25014867

  1. Isolated left upper extremity myositis and severe rhabdomyolysis in an adult with H1N1 Influenza, a case report with literature review

    PubMed Central

    Agrawal, Abhinav; Razjouyan, Hadie; Atluri, Paavani; Patel, Apoorva; Eng, Margaret

    2014-01-01

    Acute viral myositis is a fairly rare condition and usually seen in recovery phase of illness, especially in pediatric or geriatric population. Influenza type A, specifically H1N1 may present with generalized myositis and mild elevation of creatinine kinase in addition to usual manifestations. We would like to discuss an atypical presentation of Type A Influenza (H1N1) in a middle aged male who was never immunized for influenza, presenting with fever, vomiting, anuria and acute severe left upper extremity pain. The most interesting presentation in our patient was that, it was limited to a single extremity, unlike generalized presentation, which was previously reported, acute renal failure warranting renal replacement therapy. This case serves as a reminder for clinicians about atypical manifestations of H1N1 and its threatening metabolic complications. Hence the practitioners should be aware of this rare but possible presentation of certain strains of influenza virus. It also accentuates the importance of being immunized, reminding us of the Old but Golden Adage “Prevention is better than Cure.”

  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. Genetics Home Reference: Brody myopathy

    MedlinePLUS

    ... with understanding Brody myopathy? autosomal ; autosomal recessive ; breakdown ; calcium ; cell ; contraction ; enzyme ; gene ; inherited ; ions ; muscle cells ; mutation ; myoglobin ; myoglobinuria ; prevalence ; protein ; recessive ; rhabdomyolysis ; ...

  4. Genetics Home Reference: Freeman-Sheldon syndrome

    MedlinePLUS

    ... palate ; philtrum ; prevalence ; protein ; ptosis ; recessive ; respiratory ; rhabdomyolysis ; scoliosis ; skeletal muscle ; strabismus ; surgery ; syndrome You may find definitions for these and ...

  5. Haff disease associated with the ingestion of the freshwater fish Mylossoma duriventre (pacu-manteiga)

    PubMed Central

    Tolesani Jnior, Oswaldo; Roderjan, Christian Nejm; do Carmo Neto, Edgard; Ponte, Micheli Mikaeli; Seabra, Mariana Cristina Pelli; Knibel, Marcos Freitas

    2013-01-01

    Haff disease associated rhabdomyolysis is correlated with the ingestion of certain freshwater fish and shellfish and is caused by an unidentified toxin. We report the case of a patient who experienced rhabdomyolysis approximately 2 hours after ingestion of the freshwater fish Mylossoma duriventre (pacu-manteiga) approximately 3 years after an outbreak had been reported in Manaus, Brazilian Amazon. PMID:24553518

  6. Genetics Home Reference: Glycogen storage disease type V

    MedlinePLUS

    ... glycogen into a simpler sugar called glucose-1-phosphate. Additional steps convert glucose-1-phosphate into glucose, a simple sugar that is the ... glucose ; glycogen ; inherited ; kidney ; muscle cells ; myoglobin ; myoglobinuria ; phosphate ; prevalence ; protein ; recessive ; rhabdomyolysis ; simple sugar ; syndrome ; tissue ...

  7. CPK isoenzymes test

    MedlinePLUS

    ... enzyme found mainly in the heart, brain, and skeletal muscle. ... also called CPK-MM) is found mostly in skeletal muscle ... for a long time ( rhabdomyolysis ) Muscular dystrophy Myositis (skeletal ... Receiving many intramuscular injections Recent nerve and ...

  8. Myoglobin Test

    MedlinePLUS

    ... those who have had extensive damage to their skeletal muscles (rhabdomyolysis). Blood levels of myoglobin can rise very ... ordered when there has been extensive injury to skeletal muscle, resulting in the rapid breakdown of muscle, and ...

  9. An overdose of ecstasy. A role for dantrolene.

    PubMed

    Singarajah, C; Lavies, N G

    1992-08-01

    An overdose of the semisynthetic, hallucinogenic amphetamine 3,4-methylenedioxymethamphetamine resulted in convulsions, hyperthermia, hyperkalaemia and rhabdomyolysis. The patient's management, which included the use of dantrolene, is discussed. PMID:1355634

  10. Phenotype standardization for statin-induced myotoxicity.

    PubMed

    Alfirevic, A; Neely, D; Armitage, J; Chinoy, H; Cooper, R G; Laaksonen, R; Carr, D F; Bloch, K M; Fahy, J; Hanson, A; Yue, Q-Y; Wadelius, M; Maitland-van Der Zee, A H; Voora, D; Psaty, B M; Palmer, C N A; Pirmohamed, M

    2014-10-01

    Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy. PMID:24897241

  11. Phenotype Standardization for Statin-Induced Myotoxicity

    PubMed Central

    Alfirevic, A; Neely, D; Armitage, J; Chinoy, H; Cooper, R G; Laaksonen, R; Carr, D F; Bloch, K M; Fahy, J; Hanson, A; Yue, Q-Y; Wadelius, M; Maitland-van Der Zee, A H; Voora, D; Psaty, B M; Palmer, C N A; Pirmohamed, M

    2014-01-01

    Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy. PMID:24897241

  12. Stroke intracerebral multiple infarcts: Rare neurological presentation of honey bee bite

    PubMed Central

    Jain, Jyoti; Banait, Shashank; Srivastava, Ajit Kumar; Lodhe, Rahul

    2012-01-01

    Honey-bee bites which require urgent hospitalization is very rare. It is mainly seen as occupational hazards in farmers, tree dwellers and honey collectors. Common clinical presentation includes minor localized reactions in form of swelling and redness sometimes anaphylactic reaction. Infrequent major complications reported from different studies include rhabdomyolysis, acute renal failure (ARF), acute pulmonary edema, intravascular coagulation, encephalopathy and very rarely cerebral haemorrhage. Stroke due to multiple intra- cerebral infarcts along with rhabdomyolysis in patient of honey-bee bite is rare neurological complication. We report a case of 70 year man with honey-bee bite and multiple intracerebral infarcts presented as stroke, and rhabdomyolysis and ARF. When a patient presented with honey-bee bite, one should suspect serious complications. Despite advances in the understanding of pathophysiology its complications remains enigmatic and in some instances may be multifactorial. Various therapeutic interventions if started early after diagnosis reduces the possible consequences as potential reversibility of the illness. PMID:22566738

  13. Repeated Topical Application of para-Phenylenediamine Induces Renal Histopathological Changes in Rats

    PubMed Central

    Bharali, Manuj Kr.; Basumatary, Rajeev; Rahman, Taibur; Dutta, Karabi

    2012-01-01

    Hemolytic anemia and rhabdomyolysis have been often reported to be an adverse effect of drug- and chemical-induced toxicity both in experimental and real-life scenario. para-Phenylenediamine (PPD) is a derivative of para-nitroaniline and has been found as an ingredient of almost all hair dye formulations in varying concentrations from 2% to 4% w/v. Earlier studies have reported that the accidental oral ingestion of PPD in humans can lead to acute renal failure because of rhabdomyolysis. In the present investigation, we have tested the chronic topical application of PPD and its effect on the renal histology of Sprague-Dawley rats. The experiment provides clear evidence that topically applied PPD induces hemolytic anemia as evident from the decrease in the total RBC count, packed cell volume, and hemoglobin content apart from rhabdomyolysis which subsequently causes acute renal failure in rats. PMID:22778510

  14. Acute pancreatitis and acute renal failure complicating doxylamine succinate intoxication.

    PubMed

    Lee, Yang Deok; Lee, Soo Teik

    2002-06-01

    Doxylamine succinate is an antihistaminic drugwith additional hypnotic, anticholinergic and local anesthetic effects first described in 1948. In Korea and many other countries, it is a common-over-the counter medication frequently involved in overdoses. Clinical symtomatology of doxylamine succinate overdose includes somnolence, coma, seizures, mydriasis, tachycardia, psychosis, and rhabdomyolysis. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. We report a case of acute renal failure and acute pancreatitis complicating a doxylamine succinate intoxication. PMID:12046971

  15. Six-Digit CPK and Mildly Affected Renal Function in McArdle Disease

    PubMed Central

    Mcinnes, Andrew D.; DeGroote, Richard J.

    2014-01-01

    A previously healthy, white 12-year-old girl presented with diffuse body aches and poor perfusion. She developed severe respiratory failure and marked rhabdomyolysis and was mechanically ventilated. Although her CPK peaked at 500,000?IU/L, her renal function was mildly affected and her creatinine did not exceed the 0.8?mg/dL. The rhabdomyolysis was gradually resolved following aggressive fluid hydration. The patient did not require dialysis and made a complete recovery. Genetic studies revealed the diagnosis of McArdle disease. PMID:25371840

  16. Partial muscle carnitine palmitoyltransferase-A deficiency

    SciTech Connect

    Ross, N.S.; Hoppel, C.L.

    1987-01-02

    After initiation of ibuprofen therapy, a 45-year-old woman developed muscle weakness and tenderness with rhabdomyolysis, culminating in respiratory failure. A muscle biopsy specimen showed a vacuolar myopathy, and markedly decreased muscle carnitine content and carnitine palmitoyltransferase activity. Following recovery, muscle carnitine content was normal but carnitine palmitoyltransferase activity was still abnormally low. The ratio of palmitoyl-coenzyme A plus carnitine to palmitoylcarnitine oxidation by muscle mitochondria isolated from the patient was markedly decreased. The authors conclude that transiently decreased muscle carnitine content interacted with partial deficiency of carnitine palmitoyltransferase-A to produce rhabdomyolysis and respiratory failure and that ibuprofen may have precipitated the clinical event.

  17. Hypokalemic myopathy in a patient with gluten-sensitive enteropathy and dermatitis herpetiformis Duhring: A case report

    PubMed Central

    Barta, Zsolt; Miltenyi, Zsofia; Toth, Laszlo; Illes, Arpad

    2005-01-01

    The case of a 22-year-old patient with symptomatic hypokalemia caused by rhabdomyolysis is presented as a rarely reported complication of gluten-sensitive enteropathy (GSE) and dermatitis herpetiformis Duhring. The patients myopathy ceased on potassium supplementation and her other complaints resolved while on gluten-free diet. Recovery was otherwise uneventful with a rapid decline in serum CPK level. At the time of her last follow-up a few months later, she was free of symptoms and CPK remained stable. Patients with GSE may present with hypokalemia in association with diarrhea and emesis, and if potassium loss is rapid, rhabdomyolysis may occur. PMID:15801003

  18. Haff disease associated with eating buffalo fish--United States, 1997.

    PubMed

    1998-12-25

    Haff disease is a syndrome of unexplained rhabdomyolysis following consumption of certain types of fish; it is caused by an unidentified toxin. Rhabdomyolysis is a clinical syndrome caused by injury to skeletal muscle that results in release of muscle cell contents into the circulation. In 1997, six cases of Haff disease were identified in the United States (four in California and two in Missouri) among persons who ate buffalo fish (Ictiobus cyprinellus), a bottom-feeding species found mostly in the Mississippi River or its tributaries. This report summarizes the investigation of these cases. PMID:9883771

  19. Right Bundle Branch Block: An Uncommon Cardiotoxic Manifestation of Hair Dye Poisoning-A Case Report

    PubMed Central

    Balasubramanian, Deepak; Subramanian, Saravanan; Thangaraju, Pugazhenthan; Shanmugam, Kani

    2014-01-01

    Hair dye poisoning has been rising in incidence in the recent years. Apart from the commoner manifestations of upper airway edema, rhabdomyolysis and acute renal failure, cardiac toxicity, convulsions and sudden cardiac death are relatively rare complications. We discuss a case of hair dye poisoning manifesting as oropharyngeal edema along with cardiac complication. The patient survived. PMID:24596762

  20. Yellow jacket envenomation-related acute renal failure.

    PubMed

    Viswanathan, Stalin; Prabhu, Chaitanya; Arulneyam, Jayanthi; Remalayam, Bhavith; Adil, Mohammed

    2011-06-01

    We report a 58-year-old man with multiple yellow jacket stings who developed urticaria, renal failure, quadriparesis, rhabdomyolysis in succession. Investigations revealed renal and hepatic dysfunction, proteinuria, demyelinating polyradiculoneuropathy, acute tubular necrosis and glomerulonephritis. He improved with methylprednisolone, antihypertensives and two sessions of haemodialysis. PMID:25984147

  1. Massive asymptomatic creatine kinase elevation in youth during antipsychotic drug treatment: case reports and critical review of the literature.

    PubMed

    Masi, Gabriele; Milone, Annarita; Viglione, Valentina; Mancini, Alice; Pisano, Simone

    2014-12-01

    A massive asymptomatic creatine kinase elevation (MACKE) has been described during antipsychotic exposure in adult psychotic patients without signs of neuroleptic malignant syndrome (NMS), or other most frequent reasons for high creatine kinase (CK) serum level (intramuscular injections, restraints, intense physical activity, dystonic reactions). In this article, we review this clinical condition, and report three cases of MACKE in nonpsychotic, drug-nave youth during treatment with second generation antipsychotics. The diagnosis of MACKE should be considered after ruling out other possible common reasons of CK increase. The finding of MACKE should indicate a need for weekly monitoring of the CK level only when there are reasons to believe elevated CK is toxic or harmful. Further investigations are recommended when signs and symptoms raise a suspicion of NMS or rhabdomyolysis, including flu-like syndrome, fever, weakness, alteration of consciousness, muscle rigidity, tachycardia, hyper-/hypotension, and dark urine. A drug discontinuation should be considered when possible signs of NMS or rhabdomyolysis are suspected, or in cases of very high and persisting CK levels. Empirical evidence indicates that there is not a "safe" antipsychotic medication; therefore, a switch to another antipsychotic with a different profile is not necessarily a safe option. The spontaneously remitting or intermittent course suggests that the "true" MACKE should be kept distinct from both rhabdomyolysis and NMS. Raising awareness with MACKE may reduce the need for unnecessary diagnosis of NMS or rhabdomyolysis, which may otherwise lead to an unnecessary discontinuation of an effective therapeutic agent. PMID:25387323

  2. Clinical Manifestation and a New "ISCU" Mutation in Iron-Sulphur Cluster Deficiency Myopathy

    ERIC Educational Resources Information Center

    Kollberg, Gittan; Tulinius, Mar; Melberg, Atle; Darin, Niklas; Andersen, Oluf; Holmgren, Daniel; Oldfors, Anders; Holme, Elisabeth

    2009-01-01

    Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The…

  3. Cerebellar syndrome following neuroleptic induced heat stroke.

    PubMed Central

    Lefkowitz, D; Ford, C S; Rich, C; Biller, J; McHenry, L C

    1983-01-01

    We report a patient in whom extreme hyperthermia, rhabdomyolysis, acute renal failure and a residual pancerebellar syndrome occurred while taking a combination of perphenazine and amitriptyline. We postulate that impaired thermoregulation due to psychotropic drugs was responsible for the development of heat stroke and that the cerebellar syndrome resulted directly from the elevated temperature. PMID:6842224

  4. Acute kidney injury and dermonecrosis after Loxosceles reclusa envenomation

    PubMed Central

    Nag, A.; Datta, J.; Das, A.; Agarwal, A. K.; Sinha, D.; Mondal, S.; Ete, T.; Chakraborty, A.; Ghosh, S.

    2014-01-01

    Spiders of the Loxosceles species can cause dermonecrosis and acute kidney injury (AKI). Hemolysis, rhabdomyolysis and direct toxin-mediated renal damage have been postulated. There are very few reports of Loxoscelism from India. We report a case of AKI, hemolysis and a gravitational pattern of ulceration following the bite of the brown recluse spider (Loxosceles spp). PMID:25097339

  5. A case of crush syndrome induced by the kneeling seiza position.

    PubMed

    Tsuji, Tomoatsu; Inoue, Shigeaki; Yamagiwa, Takeshi; Morita, Seiji; Inokuchi, Sadaki

    2014-12-01

    Crush syndrome results in a characteristic syndrome of rhabdomyolysis with myoglobinuric acute renal failure. The most commonly described crush injury is that which affects victims of natural disasters such as earthquakes. Here, we report a rare case of crush syndrome that was induced by the kneeling seiza position. PMID:25504202

  6. Clinical Manifestation and a New "ISCU" Mutation in Iron-Sulphur Cluster Deficiency Myopathy

    ERIC Educational Resources Information Center

    Kollberg, Gittan; Tulinius, Mar; Melberg, Atle; Darin, Niklas; Andersen, Oluf; Holmgren, Daniel; Oldfors, Anders; Holme, Elisabeth

    2009-01-01

    Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The

  7. Bilateral supernumerary kidneys: how much is too much?

    PubMed Central

    Patel, Ruchir; Singh, Hanish; Willens, David; Drake, Sean

    2014-01-01

    A middle aged African-American woman with a stable history of carnitine palmitoyl transferase II (CPT II) deficiency presented with myalgias for 1 week. Physical examination and laboratory findings were consistent with severe sepsis secondary to pyelonephritis leading to rhabdomyolysis. Subsequent CT of the abdomen revealed bilateral supernumerary kidneys with non-obstructive calculi within the supernumerary kidneys. Abnormal ureteral development of the supernumerary kidneys likely led to an increased risk for urinary tract infections (UTIs) and renal calculi resulting in pyelonephritis. The stress of this infection overwhelmed the muscle CPT II enzyme load, putting her in a state of rhabdomyolysis. In addition to fluids and antibiotics, she was provided a diet rich in carbohydrates and low in fats so as to limit long-chain fatty acid oxidation. Supernumerary nephrectomy was not considered during this admission. During follow-up, she developed obstructive ureteral calculi requiring placement of a right-sided ureteral stent. PMID:24692375

  8. Acute kidney injury after massive attack of Africanised bees

    PubMed Central

    Bridi, Ramaiane A; Balbi, Andre Luis; Neves, Precil M; Ponce, Daniela

    2014-01-01

    Acute kidney injury (AKI) is a well-documented complication of massive attack by Africanised bees and can be observed 48–72 h after the accident. We report a case of Africanised bees attack followed by severe and lethal AKI. A 56-year-old man was admitted to emergency department after a massive attack of Africanised bees (>1000 bee stings). He was unconscious, presenting with hypotension and tachycardia. Mechanical ventilation, volume expansion and care for anaphylaxis were instituted. The patient was transferred to the intensive care unit (ICU) and after 48 h he developed rhabdomyolysis, oliguria, increased creatinine levels, hyperkalaemia and refractory acidosis. A diagnosis of AKI secondary to rhabdomyolysis and shock was made. The patient was treated with a prolonged course of haemodialysis. However, he progressed to refractory shock and died 5 days after admission. PMID:24618864

  9. Mutations in LPIN1 Cause Recurrent Acute Myoglobinuria in Childhood

    PubMed Central

    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

    2008-01-01

    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. PMID:18817903

  10. [Muscle crush injury and crush syndrome].

    PubMed

    Reingardien?, Dagmara; Jodi?nien?, Liucija; Laauskas, Robertas

    2010-01-01

    Crush injury is defined as compression of extremities or other parts of the body that causes muscle breakdown (traumatic rhabdomyolysis). Systemic consequences of crush injuries are as follows: rhabdomyolysis, electrolyte and acid-base abnormalities, hypovolemia, and acute renal failure. Crush injuries are important injuries in disaster situations: earthquakes, hurricanes, mining and road traffic accidents, war, collapse of buildings, etc. In this review article, there are discussed about epidemiology of crush syndrome, risk factors, pathophysiology (mechanisms of muscle cell injury, release of substances from injured muscles, other consequences of reperfusion), clinical features, differential diagnosis, investigations, complications (acute renal failure, hypovolemic shock, hyperkalemia, infection, compartment syndrome), approach to treatment (adequate rehydration, a forced mannitol-alkaline diuresis, intravenous fluids, management of hyperkalemia, wound care, hyperbaric oxygen, etc.), prognosis, the mortality rate and prevention (timely support may reduce morbidity and mortality). PMID:20944453

  11. No carnitine palmitoyltransferase deficiency in skeletal muscle in 18 malignant hyperthermia susceptible individuals.

    PubMed

    Wieser, Thomas; Kraft, Birgit; Kress, Hans Georg

    2008-06-01

    Malignant hyperthermia is a rare, potentially life threatening pharmacogenetic disorder triggered by volatile anaesthetics and depolarizing muscle relaxants. The clinical picture comprises rhabdomyolysis, metabolic and respiratory acidosis, and hyperthermia. Carnitine palmitoyltransferase II deficiency is a metabolic myopathy affecting the transport of fatty acids into the mitochondria, leading to impaired energy supply under stressful conditions resulting in muscle weakness and rhabdomyolysis. It was postulated in a previous study that some patients with the MH phenotype have a carnitine palmitoyltransferase deficiency. To investigate a potential association, we tested 18 individuals with proven MH susceptibility for impairment of carnitine palmitoyltransferase enzyme activity in muscle. Enzyme activity was normal in all individuals tested indicating no impairment of the CPT system in this sample of malignant hyperthermia susceptible individuals. Thus our data do not support the hypothesis that susceptibility to malignant hyperthermia has an effect on the carnitine palmitoyltransferase enzyme system. PMID:18430572

  12. 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. PMID:18817903

  13. Toxic Effects of Rhamnus alaternus: A Rare Case Report

    PubMed Central

    Ben Ghezala, H.; Chaouali, N.; Gana, I.; Snouda, S.; Nouioui, A.; Belwaer, I.; Ouali, J.; Kaddour, M.; Masri, W.; Ben Salah, D.; Amira, D.; Ghorbal, H.; Hedhili, A.

    2015-01-01

    In Tunisia, there are about 478 species of plants commonly used in folk medicine. Medicinal plants and herbal remedies used are responsible for 2% of intoxications listed by Tunisian National Poison Center. Most cases are related to confusion between edible plants and toxic plants lookalikes or to an excessive consumption of therapeutic plants. We report the case of a 58-year-old man admitted to the Emergency Department of the Regional Hospital of Zaghouan (Tunisia), with renal failure and rhabdomyolysis. The patient reported having daily consumption of a homemade tea based on Mediterranean Buckthorn roots, during the last 6 months to treat type 2 diabetes. The aim of this work was to establish an association between the consumption of the herbal remedy and the occurrence of both renal failure and rhabdomyolysis. No similar cases have been reported in recent literature. PMID:26229696

  14. Inhibition of xanthine oxidase to prevent statin-induced myalgia and rhabdomiolysis.

    PubMed

    Alis, Rafael; Sanchis-Gomar, Fabian; Risso-Ballester, Jennifer; Perez-Quilis, Carme; Cortell-Ballester, Jose; Romagnoli, Marco; Blesa, Jose R; Emanuele, Enzo

    2015-03-01

    Although statins remain the cornerstone of lipid-lowering therapy for reducing the burden of atherosclerotic vascular disease, their administration has been associated with muscle-related adverse effects, including myalgia and rhabdomyolysis. Such adverse events are probably due to reduced antioxidant defenses associated with fewer intermediate metabolites in the cholesterol synthesis pathway. We hypothesize that the concomitant inhibition of xanthine oxidase via coadministration of allopurinol with statins could diminish reactive oxygen species (ROS)-related muscle damage, which would have in turn have positive effects on both the incidence of muscle-related adverse events and cardiovascular outcomes. Accordingly, inhibition of xanthine oxidase has been previously shown to be effective for reducing biomarkers of muscle damage following exercise in professional athletes. Because of the widespread statin utilization and increasing trends in their therapeutic use in atherosclerotic vascular diseases, the proposed strategy could have important clinical implications for reducing statin-induced myalgia and rhabdomyolysis. PMID:25568951

  15. Electric injury, Part II: Specific injuries.

    PubMed

    Fish, R M

    2000-01-01

    Electric injury can cause disruption of cardiac rhythm and breathing, burns, fractures, dislocations, rhabdomyolysis, eye and ear injury, oral and gastrointestinal injury, vascular damage, disseminated intravascular coagulation, peripheral and spinal cord injury, and Reflex Sympathetic Dystrophy. Secondary trauma from falls, fires, flying debris, and inhalation injury can complicate the clinical picture. Diagnostic and treatment considerations for electric injuries are described in this article, which is the second part of a three-part series on electric injuries. PMID:10645833

  16. Carbon monoxide poisoning and nonoliguric acute renal failure.

    PubMed Central

    Bessoudo, R.; Gray, J.

    1978-01-01

    Carbon monoxide poisoning in a 37-year-old man was complicated by neurologic damage, skin changes, muscle necrosis and nonoliguric renal failure. The relation between nontraumatic rhabdomyolysis and acute renal failure in carbon monoxide poisoning is reviewed. Recognition of the acute renal failure in such cases is important, for this complication can be fatal; the prognosis is excellent, however, if proper medical management is provided. PMID:679099

  17. Two Cases of Leptospirosis in French Travelers Returning From Koh Samui, Thailand.

    PubMed

    Christen, Jacques-Robert; Savini, Hlne; Pierrou, Candice; Boisnault, Gilles; Fournier, Pierre-Edouard; Kraemer, Philippe; Simon, Fabrice

    2015-11-01

    We report the first two cases of leptospirosis in French travelers returning from Koh Samui, a famous tourist island in Thailand, in September 2014 and March 2015. The first patient developed a severe form of the disease including hemodynamic instability, interstitial pneumonia, rhabdomyolysis with renal impairment, and deep thrombocytopenia. The second patient had a milder disease, with severe muscle pain, jaundice, and renal impairment. The two patients reported bathing in fresh water in Namuang waterfall. PMID:26412478

  18. Anesthetic agents in patients with very long-chain acyl-coenzyme A dehydrogenase deficiency: a literature review.

    PubMed

    Redshaw, Charlotte; Stewart, Catherine

    2014-11-01

    Very long-chain acyl-coenzyme A dehydrongenase deficiency (VLCADD) is a rare disorder of fatty acid metabolism that renders sufferers susceptible to hypoglycemia, liver failure, cardiomyopathy, and rhabdomyolysis. The literature about the management of these patients is hugely conflicting, suggesting that both propofol and volatile anesthesia should be avoided. We have reviewed the literature and have concluded that the source papers do not support the statements that volatile anesthetic agents are unsafe. The reports on rhabdomyolysis secondary to anesthesia appear to be due to inadequate supply of carbohydrate not volatile agents. Catabolism must be avoided with minimal fasting, glucose infusions based on age and weight, and attenuation of emotional and physical stress. General anesthesia appears to be protective of stress-induced catabolism and may offer benefits in children and anxious patients over regional anesthesia. Propofol has not been demonstrated to be harmful in VLCADD but is presented in an emulsion containing very long-chain fatty acids which can cause organ lipidosis and itself can inhibit mitochondrial fatty acid metabolism. It is therefore not recommended. Suxamethonium-induced myalgia may mimic symptoms of rhabdomyolysis and cause raised CK therefore should be avoided. Opioids, NSAIDS, regional anesthesia, and local anesthetic techniques have all been used without complication. PMID:25069536

  19. The nature and prevalence of injury during CrossFit training.

    PubMed

    Hak, Paul Taro; Hodzovic, Emil; Hickey, Ben

    2013-11-22

    CrossFit is a constantly varied, high intensity, functional movement strength and conditioning program which has seen a huge growth in popularity around the world since its inception twelve years ago. There has been much criticism as to the potential injuries associated with CrossFit training including rhabdomyolysis and musculoskeletal injuries. However to date no evidence exists in the literature to the injures and rates sustained. The purpose of this study was to determine the injury rates and profiles of CrossFit athletes sustained during routine CrossFit training. An online questionnaire was distributed amongst international CrossFit online forums. Data collected included general demographics, training programs, injury profiles and supplement use. A total of 132 responses were collected with 97 (73.5%) having sustained an injury during CrossFit training. A total of 186 injuries were reported with 9 (7.0%) requiring surgical intervention. An injury rate of 3.1 per 1000 hours trained was calculated. No incidences of rhabdomyolysis were reported. Injury rates with CrossFit training are similar to that reported in the literature for sports such as Olympic weight-lifting, power-lifting and gymnastics and lower than competitive contact sports such as rugby union and rugby league. Shoulder and spine injuries predominate with no incidences of rhabdomyolysis obtained. To our knowledge this is the first paper in the literature detailing the injury rates and profiles with CrossFit participation. PMID:24276294

  20. [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. PMID:24716429

  1. Coagulopathy in patients who experience snakebite

    PubMed Central

    Kim, Jae Seok; Yang, Jae Won; Kim, Min Soo; Han, Seung Tae; Kim, Bi Ro; Shin, Myung Sang; Lee, Jong In; Han, Byoung Geun

    2008-01-01

    Background/Aims Coagulopathy is a common complication of snakebite, but there is little information on the clinical importance of coagulopathy. We analyzed the characteristics of coagulopathy after envenomation. Methods Ninety-eight patients who experienced snakebite were enrolled in this study. We divided all the patients into three groups by the ISTH DIC scoring system: the normal, simple coagulopathy and DIC groups. The coagulopathy group included both the simple coagulopathy and DIC groups. We then conducted a case-control study. Results There was a significant decrease in the Hct, protein, albumin, ALP and cholesterol levels in the coagulopathy group, and only the cholesterol level was deceased in the DIC group (p<0.05). Leukocytosis and rhabdomyolysis were significantly associated with coagulopathy, and hemolysis and rhabdomyolysis were associated with DIC (p<0.05). The presence of rhabdomyolysis was considered a risk factor for coagulopathy (p<0.05). These conditions continued for up to six to seven days after the snakebite. Conclusions Evaluation of coagulopathy with using these characteristics is helpful to properly manage the patients who experience snakebite. PMID:18646512

  2. Safety of statins

    PubMed Central

    Maji, Debasish; Shaikh, Shehla; Solanki, Dharmesh; Gaurav, Kumar

    2013-01-01

    Statins are an established class of drugs with proven efficacy in cardiovascular risk reduction. The concern over statin safety was first raised with the revelation of myopathy and rhabdomyolysis with the use of now withdrawn cerivastatin. Enhanced understanding of the mechanisms behind adverse effects of statins including an insight into the pharmacokinetic properties have minimised fear of statin use among clinicians. Studies reveal that occurrence of myopathy and rhabdomyolysis are rare 1/100000 patient-years. The risk of myopathy/rhabdomyolysis varies between statins due to varying pharmacokinetic profiles. This explains the differing abilities of statins to adverse effects and drug interaction potentials that precipitate adverse effects. Higher dose of rosuvastatin (80 mg/day) was associated with proteinuria and hematuria while lower doses were devoid of such effects. Awareness of drugs interacting with statins and knowledge of certain combinations such as statin and fibrates together with monitoring of altered creatine kinase activity may greatly minimise associated adverse effects. Statins also asymptomatically raise levels of hepatic transaminases but are not correlated with hepatotoxicity. Statins are safe and well tolerated including more recent potent statins such as, rosuvastatin. The benefits of intensive statin use in cardiovascular risk reduction greatly outweigh risks. The present review discusses underlying causes of statin-associated adverse effects including management in high risk groups. PMID:23961479

  3. Can Gas Replace Protein Function? CO Abrogates the Oxidative Toxicity of Myoglobin

    PubMed Central

    Shaklai, Mati; Shaklai, Nurith

    2014-01-01

    Outside their cellular environments, hemoglobin (Hb) and myoglobin (Mb) are known to wreak oxidative damage. Using haptoglobin (Hp) and hemopexin (Hx) the body defends itself against cell-free Hb, yet mechanisms of protection against oxidative harm from Mb are unclear. Mb may be implicated in oxidative damage both within the myocyte and in circulation following rhabdomyolysis. Data from the literature correlate rhabdomyolysis with the induction of Heme Oxygenase-1 (HO-1), suggesting that either the enzyme or its reaction products are involved in oxidative protection. We hypothesized that carbon monoxide (CO), a product, might attenuate Mb damage, especially since CO is a specific ligand for heme iron. Low density lipoprotein (LDL) was chosen as a substrate in circulation and myosin (My) as a myocyte component. Using oxidation targets, LDL and My, the study compared the antioxidant potential of CO in Mb-mediated oxidation with the antioxidant potential of Hp in Hb-mediated oxidation. The main cause of LDL oxidation by Hb was found to be hemin which readily transfers from Hb to LDL. Hp prevented heme transfer by sequestering hemin within the Hp-Hb complex. Hemin barely transferred from Mb to LDL, and oxidation appeared to stem from heme iron redox in the intact Mb. My underwent oxidative crosslinking by Mb both in air and under N2. These reactions were fully arrested by CO. The data are interpreted to suit several circumstances, some physiological, such as high muscle activity, and some pathological, such as rhabdomyolysis, ischemia/reperfusion and skeletal muscle disuse atrophy. It appear that CO from HO-1 attenuates damage by temporarily binding to deoxy-Mb, until free oxygen exchanges with CO to restore the equilibrium. PMID:25111140

  4. The investigation and management of metabolic myopathies.

    PubMed

    Olpin, Simon Edward; Murphy, Elaine; Kirk, Richard James; Taylor, Robert William; Quinlivan, Rosaline

    2015-06-01

    Metabolic myopathies (MM) are rare inherited primary muscle disorders that are mainly due to abnormalities of muscle energy metabolism resulting in skeletal muscle dysfunction. These diseases include disorders of fatty acid oxidation, glyco(geno)lytic muscle disorders and mitochondrial respiratory chain (MRC) disease. Clinically these disorders present with a range of symptoms including infantile hypotonia, myalgia/exercise tolerance, chronic or acute muscle weakness, cramps/spasms/stiffness or episodic acute rhabdomyolysis. The precipitant may be fasting, infection, general anaesthesia, heat/cold or most commonly, exercise. However, the differential diagnosis includes a wide range of both acquired and inherited conditions and these include exposure to drugs/toxins, inflammatory myopathies, dystrophies and channelopathies. Streamlining of existing diagnostic protocols has now become a realistic prospect given the availability of second-generation sequencing. A diagnostic pathway using a 'rhabdomyolysis' gene panel at an early stage of the diagnostic process is proposed. Following detailed clinical evaluation and first-line investigations, some patients will be identified as candidates for McArdle disease/glycogen storage disease type V or MRC disease and these will be referred directly to the specialised services. However, for the majority of patients, second-line investigation is best undertaken through next-generation sequencing using a 'rhabdomyolysis' gene panel. Following molecular analysis and careful evaluation of the findings, some patients will receive a clear diagnosis. Further functional or specific targeted testing may be required in other patients to evaluate the significance of uncertain/equivocal findings. For patients with no clear diagnosis, further investigations will be required through a specialist centre. PMID:25878327

  5. Three novel mutations in the carnitine-acylcarnitine translocase (CACT) gene in patients with CACT deficiency and in healthy individuals.

    PubMed

    Fukushima, Takao; Kaneoka, Hidetoshi; Yasuno, Tetsuhiko; Sasaguri, Yukari; Tokuyasu, Tomoko; Tokoro, Kuniko; Fukao, Toshiyuki; Saito, Takao

    2013-12-01

    Carnitine-acylcarnitine translocase (CACT) and carnitine palmitoyltransferase II (CPT2) are key enzymes for transporting long-chain fatty acids into mitochondria. Deficiencies of these enzymes, which are clinically characterized by life-threatening non-ketotic hypoglycemia and rhabdomyolysis, cannot be distinguished by acylcarnitine analysis performed using tandem mass spectrometry. We had previously reported the CPT2 genetic structure and its role in CPT2 deficiency. Here, we analyzed the CACT gene in 2 patients diagnosed clinically with CACT deficiency, 18 patients with non-traumatic rhabdomyolysis and 58 healthy individuals, all of whom were confirmed to have normal CPT2 genotypes. To facilitate CACT genotyping, we used heat-denaturing high-performance liquid chromatography (DHPLC), which helped identify five distinct patterns. The abnormal heteroduplex fragments were subjected to CACT-specific DNA sequencing. We found that one patient with CACT deficiency, Case 1, carried c.576G>A and c.199-10t>g mutations, whereas Case 2 was heterozygous for c.106-2a>t and c.576G>A. We also found that one patient with non-traumatic rhabdomyolysis and one healthy individual were heterozygous for c.804delG and the synonymous mutation c.516T>C, respectively. In summary, c.576G>A, c.106-2a>t and c.516T>C are novel CACT gene mutations. Among the five mutations identified, three were responsible for CACT deficiency. We have also demonstrated the successful screening of CACT mutations by DHPLC. PMID:24088670

  6. Gluteal Compartment Syndrome following bariatric surgery: A rare but important complication

    PubMed Central

    Pereira, Bernadette; Heath, Dugal

    2015-01-01

    Gluteal Compartment Syndrome is a rare condition caused by excessive pressure within the gluteal compartments which leads to a number of potentially serious sequelae including rhabdomyolysis, nerve damage, renal failure and death. As bariatric patients are heavy and during prolonged bariatric procedures lie in one position for extended periods of time, they are especially susceptible to developing this complication. It is therefore essential that bariatric surgeons are aware of this complication and how to minimise the chances of it occurring and how to diagnose it. We describe a case of Gluteal Compartment Syndrome in a patient following a gastric bypass and review the aetiology, pathophysiology, treatment and prevention of this complication. PMID:25750728

  7. [Snake bite in a 53-year-old female tourist].

    PubMed

    Bertheau, S; Aghdassi, A; Otto, M; Hegenscheid, K; Runge, S; Lerch, M M; Simon, P

    2015-02-01

    Snake bites are rare events in Germany and are not life-threatening with usually only mild clinical symptoms. The most widespread venomous snake is the common European adder (Vipera berus). Here we present the case of a 53-year-old woman who was bitten by a common adder. Although the patient was initially in stable condition she developed edematous swelling of the complete lower limb, subcutaneous bleeding, and rhabdomyolysis. The aim of this report is to raise awareness that even in a central European country like Germany snake bites with a life-threatening course can occur and need immediate attention and medical care. PMID:25617003

  8. Anesthetic management of a patient with Weaver syndrome undergoing emergency evacuation of extra-dural hematoma: A case report and review of the literature

    PubMed Central

    Khokhar, RS; Hajnour, MSM; Aqil, M; Al-Saeed, AH; Qureshi, S

    2016-01-01

    Weaver syndrome is a rare disorder of unknown etiology characterized by skeletal overgrowth, distinctive craniofacial and digital abnormalities and advanced bone age. In general, craniofacial abnormalities that cause difficulty with tracheal intubation may improve, worsen, or remain unchanged as craniofacial structures mature. Furthermore, there is an estimated risk in these children of ≤1.09% of rhabdomyolysis or malignant hyperpyrexia. We report a case of a boy with Weaver syndrome who underwent emergency evacuation of extra-dural hematoma under general anesthesia. PMID:26955318

  9. Deep brain stimulation for medically refractory life-threatening status dystonicus in children.

    PubMed

    Walcott, Brian P; Nahed, Brian V; Kahle, Kristopher T; Duhaime, Ann-Christine; Sharma, Nutan; Eskandar, Emad N

    2012-01-01

    Generalized dystonic syndromes may escalate into persistent episodes of generalized dystonia known as status dystonicus that can be life-threatening due to dystonia-induced rhabdomyolysis and/or respiratory compromise. Treatment of these conditions usually entails parenteral infusion of antispasmodic agents and sedatives and occasionally necessitates a medically induced coma for symptom control. The authors report a series of 3 children who presented with medically intractable, life-threatening status dystonicus and were successfully treated with bilateral pallidal deep brain stimulation. Bilateral globus pallidus internus stimulation appears to be effective in the urgent treatment of medically refractory and life-threatening movement disorders. PMID:22208329

  10. [A fatal overdose of venlafaxine.

    PubMed

    Pedersen, Julie Steen; Munck, Lars Kristian

    2014-02-24

    An 18-year-old woman ingested 22 g of venlafaxine with suicidal attempt. At admittance two hours after ingestion she had serotonine syndrome, repeated seizures and hypotension. After eight hours malignant arrythmias culminated in cardiac arrest, which was successfully resuscitated. Progressive liver and cardiac failure lead to fatal outcome after 48 hours. It is discussed whether early lipid infusion should be given in case of ingestion of high doses of venlafaxine, before myoclonia, seizures, hypotension, rhabdomyolysis and liver failure developed, since these can only be treated symptomatically. PMID:25350413

  11. Adam (MDMA) and Eve (MDEA) misuse: an immunohistochemical study on three fatal cases.

    PubMed

    Fineschi, V; Centini, F; Mazzeo, E; Turillazzi, E

    1999-09-30

    Three fatal cases of MDMA/MDEA misuse have been examined. These referred to white males between 19 and 20 years of age, in which post-mortem toxicology showed the presence of MDMA (in one case), MDEA (in one case) and both (in one case). The clinical data were analysed and the histopathological findings were studied following immunohistochemical investigations. A complete immunohistochemical study has made it possible to demonstrate rhabdomyolysis and myoglobinuria with alterations of the organs typical of a DIC. Clinical, histopathological and toxicological data suggest that severe or fatal complications following ecstasy ingestion could be related to idiosyncratic response. PMID:10533279

  12. Acute kidney injury with pigment nephropathy following spider bite: a rarely reported entity in India.

    PubMed

    Golay, Vishal; Desai, Atul; Hossain, Aref; Roychowdhary, Arpita; Pandey, Rajendra

    2013-01-01

    Acute kidney injury (AKI) can be seen in tropical regions following bites of various venomous animals and insects. Renal failure is seen most commonly following the bite of spiders of the Loxosceles spp. Dermonecrosis, systemic inflammatory response, hemolysis, rhabdomyolysis, and direct venom-related effects are postulated as causes of AKI. We report a documented case of AKI with pigment nephropathy following the bite of a brown spider from a tropical region which is known to have many venomous animals but has no previous reports of AKI following spider bite. Whether this is due to absence of toxic spider species or underreporting needs to be determined. PMID:23438217

  13. Which statin should be used together with colchicine? Clinical experience in three patients with nephrotic syndrome due to AA type amyloidosis.

    PubMed

    Sahin, Garip; Korkmaz, Cengiz; Yalcin, Ahmet U?ur

    2008-01-01

    Colchicine and statins are well known drugs that cause myopathy and neuropathy. Co-administration of certain drugs with statins may increase myotoxic effect, causing myopathy and varying degrees of rhabdomyolysis. Therefore, it is very crucial to know which statin should be used during a combination therapy including colchicine and other drugs. We present three cases with AA amyloidosis secondary to familial Mediterranean fever, who developed neuromyopathy while receiving the combination of colchicine and statin. We also briefly discussed the different metabolic pathways of statins and colchicine when used together. PMID:17703308

  14. 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 necrosis of extrafusal muscle fibres in envenomed rat soleus muscles confirming the myotoxic effect of Bungarus niger venom, attributable to phospholipases A₂. This study has demonstrated that Bungarus niger is widely distributed in Bangladesh and confirms the risk of fatal neuro-myotoxic envenoming, especially as no specific antivenom is currently manufactured. The unexpected finding of rhabdomyolysis should prompt further investigation of the venom components responsible. The practical implications of having to treat patients with rhabdomyolysis and consequent acute renal failure, in addition to the more familiar respiratory failure associated with krait bite envenoming, should not be underestimated in a country that is poorly equipped to deal with such emergencies. PMID:20855420

  15. Acute kidney injury in hereditary renal hypouricaemia --a case report and review of literature.

    PubMed

    Sural, Saubhik; Chakraborty, Sutirtha

    2013-08-01

    A young male patient was admitted to our hospital with history of dysuria, recurrent vomiting, severe muscle pain and weakness which was induced by a session of rigorous exercise for the first time in the local gymnasium. He was subsequently diagnosed with exercise-induced acute kidney injury and rhabdomyolysis and managed accordingly. Later on during follow-up he was found to have extreme hypouricaemia (serum uric acid 0.2 mg/dl) and was subsequently diagnosed with renal hypouricaemia. Biochemical investigations on other family members of the patient revealed hereditary renal hypouricaemia in the family. PMID:24783397

  16. Rosuvastatin safety: lessons from the FDA review and post-approval surveillance.

    PubMed

    Davidson, Michael H

    2004-11-01

    Rosuvastatin is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Although highly efficacious, this new statin has generated considerable controversy regarding its safety. Rosuvastatin was approved for clinical use based on the largest pre-approval database for all statins prior to commercial use. In this database, rosuvastatin had a similar safety profile to other approved statins up to the highest approval dose of 40 mg. As with all statins, there is a marked increase in adverse effects when the dose is titrated from 40 to 80 mg, and rosuvastatin demonstrates a similar dose/toxicity relationship. In the pre-approval data trials on 80 mg, there was a 1.0% (n = 16) incidence of myopathy and 7 patients developed rhabdomyolysis. However the rhabdomyolysis, but the incidence rate, when corrected for prescription utilisation, is similar to other statins following initial approval. PMID:15500414

  17. How electroshock weapons kill!

    NASA Astrophysics Data System (ADS)

    Lundquist, Marjorie

    2010-03-01

    Growing numbers of law enforcement officers now carry an electroshock weapon (ESW). Over 500 U.S. deaths have followed ESW use in the past 26 years; over 450 of these deaths followed use of an electromuscular disruptor in the past 9 years. Most training courses teach that ESWs are safe; that they can kill only by the direct effect of electric current on the heart; and that a death following use of an ESW always has some other cause. All these teachings are false! The last was disproved by Lundquist.^1 Williams^2 ruled out direct electrical effects as a cause of almost all the 213 deaths he studied, leaving disruption of normal physiological processes as the only alternative explanation. Careful study of all such deaths identifies 4 different ways that death has or could have been brought about by the ESW: kidney failure following rhabdomyolysis [rare]; cardiac arrest from hyperkalemia following rhabdomyolysis [undocumented]; lactic acid-induced ventricular fibrillation [conclusive proof impossible]; and [most common] anoxia from so much lactic acid in the circulating blood that it acts as an oxygen scavenger, continuously depleting the blood of oxygen until most of the lactate has been metabolized. ^1M. Lundquist, BAPS 54(1) K1.270(2009). ^2Howard E. Williams, Taser Electronic Control Devices and Sudden In-Custody Death, 2008.

  18. Case report: severe heat stroke with multiple organ dysfunction a novel intravascular treatment approach

    PubMed Central

    Broessner, Gregor; Beer, Ronny; Franz, Gerhard; Lackner, Peter; Engelhardt, Klaus; Brenneis, Christian; Pfausler, Bettina; Schmutzhard, Erich

    2005-01-01

    Introduction We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia. Methods A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia. Results Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard and CoolLine) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke. Conclusion In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result. PMID:16285034

  19. Perils and pitfalls of long-term effects of proton pump inhibitors.

    PubMed

    Wilhelm, Sheila M; Rjater, Ryan G; Kale-Pradhan, Pramodini B

    2013-07-01

    This review summarizes the literature regarding long-term adverse effects of proton pump inhibitors (PPIs). A PubMed search (1966 to February 2013) for English language studies was conducted using key terms PPI: omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole, pneumonia, Clostridium difficile, osteoporosis, risk of fractures, thrombocytopenia, rhabdomyolysis, anemia, iron deficiency, hypomagnesemia, vitamin B?? and nephritis. The risk of pneumonia was increased 27-39% in short-term use of PPIs in three meta-analyses. C. difficile infections were also associated with the use of PPIs (odds ratio: 2.15; 95% CI: 1.81-2.55; p < 0.00001). This effect appears to be dose related. The US FDA has recently issued a warning regarding fractures and the impaired magnesium absorption associated with the use of PPI. Thrombocytopenia, iron deficiency, vitamin B12 deficiency, rhabdomyolysis and acute interstitial nephritis have also been reported with the use of PPIs. There is mounting evidence that PPIs are associated with serious adverse effects. Practitioners should be vigilant and counsel patients accordingly. PMID:23927671

  20. In vivo regulation of the heme oxygenase-1 gene in humanized transgenic mice

    PubMed Central

    Kim, Junghyun; Zarjou, Abolfazl; Traylor, Amie M.; Bolisetty, Subhashini; Jaimes, Edgar A.; Hull, Travis D.; George, James F.; Mikhail, Fady M.; Agarwal, Anupam

    2012-01-01

    Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation producing equimolar amounts of carbon monoxide, iron, and biliverdin. Induction of HO-1 is a beneficial response to tissue injury in diverse animal models of diseases including acute kidney injury. In vitro analysis has shown that the human HO-1 gene is transcriptionally regulated by changes in chromatin conformation but whether such control occurs in vivo is not known. To enable such analysis, we generated transgenic mice, harboring an 87-kb bacterial artificial chromosome expressing human HO-1 mRNA and protein and bred these mice with HO-1 knockout mice to generate humanized BAC transgenic mice. This successfully rescued the phenotype of the knockout mice including reduced birth rates, tissue iron overload, splenomegaly, anemia, leukocytosis, dendritic cell abnormalities and survival after acute kidney injury induced by rhabdomyolysis or cisplatin nephrotoxicity. Transcription factors such as USF1/2, JunB, Sp1, and CTCF were found to associate with regulatory regions of the human HO-1 gene in the kidney following rhabdomyolysis. Chromosome Conformation Capture and ChIP-loop assays confirmed this in the formation of chromatin looping in vivo. Thus, these bacterial artificial chromosome humanized HO-1 mice are a valuable model to study the human HO-1 gene providing insight to the in vivo architecture of the gene in acute kidney injury and other diseases. PMID:22495295

  1. Novel Inhibitors of Human Organic Cation/Carnitine Transporter (hOCTN2) via Computational Modeling and In Vitro Testing

    PubMed Central

    Diao, Lei; Ekins, Sean; Polli, James E.

    2010-01-01

    Purpose The objective was to elucidate the inhibition requirements of the human Organic Cation/Carnitine Transporter (hOCTN2). Methods Twenty-seven drugs were screened initially for their potential to inhibit uptake of L-carnitine into a stably transfected hOCTN2-MDCK cell monolayer. A HipHop common features pharmacophore was developed and used to search a drug database. Fifty-three drugs, including some not predicted to be inhibitors, were selected and screened in vitro. Results A common features pharmacophore was derived from initial screening data and consisted of three hydrophobic features and a positive ionizable feature. Among the 33 tested drugs that were predicted to map to the pharmacophore, 27 inhibited hOCTN2 in vitro (40% or less L-carnitine uptake from 2.5μM L-carnitine solution in presence of 500 μM drug, compared to L-carnitine uptake without drug present). Hence, the pharmacophore accurately prioritized compounds for testing. Ki measurements showed low micromolar inhibitors belonged to diverse therapeutic classes of drugs, including many not previously known to inhibit hOCTN2. Compounds were more likely to cause rhabdomyolysis if the Cmax/Ki ratio was higher than 0.0025. Conclusion A combined pharmacophore and in vitro approach found new, structurally diverse inhibitors for hOCTN2 that may possibly cause clinical significant toxicity such as rhabdomyolysis. PMID:19437106

  2. 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. PMID:26056768

  3. Sickle cell trait.

    PubMed

    Eichner, E Randy

    2007-08-01

    Sickle cell trait can pose a grave risk for some athletes. In the past few years, exertional sickling has killed nine athletes, including five college football players in training. Exercise-physiology research shows how and why sickle red cells can accumulate in the bloodstream during intense exercise bouts. Sickle cells can "logjam" blood vessels and lead to collapse from ischemic rhabdomyolysis. Diverse clinical and metabolic problems from explosive rhabdomyolysis can threaten life. Sickling can begin in 2-3 minutes of any all-out exertion, or during sustained intense exertion--and can reach grave levels very soon thereafter if the athlete struggles on or is urged on by coaches despite warning signs. Heat, dehydration, altitude, and asthma can increase the risk for and worsen sickling. This exertional sickling syndrome, however, is unique and in the field can be distinguished from heat illnesses. Sickling collapse is a medical emergency. Fortunately, screening and precautions can prevent sickling collapse and enable sickle-trait athletes to thrive in their sports. PMID:17923725

  4. Uremic toxins enhance statin-induced cytotoxicity in differentiated human rhabdomyosarcoma cells.

    PubMed

    Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi

    2014-09-01

    The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins-hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate-on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins. PMID:25192420

  5. Animal toxins and the kidney.

    PubMed

    Sitprija, Visith

    2008-11-01

    Envenomation or poisoning by toxins from animals poses an important health hazard in the tropics. Animal toxins are complex mixtures of proteins, peptides, enzymes and chemicals. These toxins exert their effects through modulation of ion channels and receptors, and via direct enzyme action. Depolarization or hyperpolarization of ion channels--caused by most marine toxins, and some snake and insect venoms--results in neuromuscular symptoms that can be associated with hemodynamic changes. Toxin enzymes, especially proteases and phospholipase A2, initiate inflammatory processes that involve the generation of proinflammatory cytokines and vasoactive mediators, resulting in systemic and renal hemodynamic alterations. Toxin enzymes also have direct effects on erythrocytes, myocytes, blood coagulation factors, vascular endothelium and epithelial cells. As a result, disseminated intravascular coagulation, bleeding diathesis, intravascular hemolysis and rhabdomyolysis are common after exposure to animal toxins. The renal manifestations of animal toxin envenomation, which are usually acute, result mainly from these enzymatic effects. All renal structures can be affected by animal toxins, and tubular necrosis is common. Acute kidney injury is attributed to decreased renal blood flow (associated with intravascular hemolysis or rhabdomyolysis), disseminated intravascular coagulation or direct tubular toxicity. Immunologic mechanisms have a minor role in the pathophysiology of nephropathy caused by animal toxins. PMID:18813235

  6. Loin to groin pain: The importance of a differential diagnosis

    PubMed Central

    Smith, Alexander E.P.; Bhatti, Ibrahim N.; Hester, Thomas; Ritchie, James F.S.

    2015-01-01

    Introduction Ureteric colic frequently presents as loin to groin pain and accounts for a significant proportion of emergency urological admissions. However, a number of differential diagnoses should be considered in a systematic approach when assessing patients. Presentation of case We report a case of a 30 year old man admitted with severe unilateral loin to groin pain following lumbar specific weightlifting exercises. After a significant delay due to initial mis-diagnosis he was diagnosed with acute paravertebral lumbar compartment syndrome (PVCS) and managed conservatively. Discussion Exertional PVCS is a rare and potentially life threatening condition arising following lumbar specific exercise that has only been recorded a handful of times previously. Patients typically present with intractable lumbar pain and rhabdomyolysis 612h following exercise. Due to initial diagnostic delay our case was managed conservatively with fluid resuscitation and monitoring of renal function. Conclusion Assessment of patients with loin pain requires a systematic approach. PVCS is a rare cause of lumbar back and loin pain but one that should be considered, particularly in active young males. Early diagnosis is key to prevent the potential sequalae of untreated rhabdomyolysis. There is currently no consensus on management option for PVCS with only a few cases being reported in the literature. We describe successful management with supportive non operative treatment. PMID:26453939

  7. Dengue-associated neuromuscular complications.

    PubMed

    Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Jain, Amita; Malhotra, Kiran Preet

    2015-01-01

    Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evolving course; benign nature; excellent response to potassium; and, often leads to diagnostic confusion with other dengue-associated neuromuscular disorders. Rhabdomyolysis is the most severe form of muscle involvement and may be life-threatening. Guillain-Barrι syndrome is another frequent neuromuscular dengue-associated complication. Dengue-associated Guillain-Barrι syndrome responds very well to intravenous immunoglobulins. Predominant spinal gray matter involvement has been reported in a patient presenting with areflexic paraparesis. Mononeuropathies often manifest with paralysis of the diaphragm due to phrenic nerve dysfunction. Brachial plexopathy, in the form of neuralgic amyotrophy, has been described much more frequently than lumbo-sacral plexopathy. Early recognition of these neuromuscular complications is needed for successful treatment and to prevent further disabilities. PMID:26238884

  8. Combination of lipid metabolism alterations and their sensitivity to inflammatory cytokines in human lipin-1-deficient myoblasts.

    PubMed

    Michot, Caroline; Mamoune, Asmaa; Vamecq, Joseph; Viou, Mai Thao; Hsieh, Lu-Sheng; Testet, Eric; Lainé, Jeanne; Hubert, Laurence; Dessein, Anne-Frédérique; Fontaine, Monique; Ottolenghi, Chris; Fouillen, Laetitia; Nadra, Karim; Blanc, Etienne; Bastin, Jean; Candon, Sophie; Pende, Mario; Munnich, Arnold; Smahi, Asma; Djouadi, Fatima; Carman, George M; Romero, Norma; de Keyzer, Yves; de Lonlay, Pascale

    2013-12-01

    Lipin-1 deficiency is associated with massive rhabdomyolysis episodes in humans, precipitated by febrile illnesses. Despite well-known roles of lipin-1 in lipid biosynthesis and transcriptional regulation, the pathogenic mechanisms leading to rhabdomyolysis remain unknown. Here we show that primary myoblasts from lipin-1-deficient patients exhibit a dramatic decrease in LPIN1 expression and phosphatidic acid phosphatase 1 activity, and a significant accumulation of lipid droplets (LD). The expression levels of LPIN1-target genes [peroxisome proliferator-activated receptors delta and alpha (PPARδ, PPARα), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), acyl-coenzyme A dehydrogenase, very long (ACADVL), carnitine palmitoyltransferase IB and 2 (CPT1B and CPT2)] were not affected while lipin-2 protein level, a closely related member of the family, was increased. Microarray analysis of patients' myotubes identified 19 down-regulated and 51 up-regulated genes, indicating pleiotropic effects of lipin-1 deficiency. Special attention was paid to the up-regulated ACACB (acetyl-CoA carboxylase beta), a key enzyme in the fatty acid synthesis/oxidation balance. We demonstrated that overexpression of ACACB was associated with free fatty acid accumulation in patients' myoblasts whereas malonyl-carnitine (as a measure of malonyl-CoA) and CPT1 activity were in the normal range in basal conditions accordingly to the normal daily activity reported by the patients. Remarkably ACACB invalidation in patients' myoblasts decreased LD number and size while LPIN1 invalidation in controls induced LD accumulation. Further, pro-inflammatory treatments tumor necrosis factor alpha+Interleukin-1beta(TNF1α+IL-1ß) designed to mimic febrile illness, resulted in increased malonyl-carnitine levels, reduced CPT1 activity and enhanced LD accumulation, a phenomenon reversed by dexamethasone and TNFα or IL-1ß inhibitors. Our data suggest that the pathogenic mechanism of rhabdomyolysis in lipin-1-deficient patients combines the predisposing constitutive impairment of lipid metabolism and its exacerbation by pro-inflammatory cytokines. PMID:23928362

  9. Malignant hypertension-associated thrombotic microangiopathy following cocaine use.

    PubMed

    Lamia, Rais; El Ati, Zohra; Fatma, Lilia Ben; Zouaghi, Karim; Smaoui, Wided; Rania, Khedher; Krid, Madiha; Hmida, Fathi Ben; Bji, Soumaya; Moussa, Fatma Ben

    2016-01-01

    Cocaine is one of the most commonly used illicit drugs with distribution and consumption throughout the world. Acute renal failure associated with rhabdomyolysis, direct vasoconstriction and hemodynamic alteration is well described in patients with cocaine intoxication. Cocaine use is associated with high blood pressure and may rarely induce malignant hypertension associated with thrombotic microangiopathy. We report the case of a patient who developed malignant hypertension associated with thrombotic microangiopathy after chronic consumption of cocaine. A kidney biopsy revealed thrombotic microangiopathy with fibrinoid necrosis of arterioles and glomerular tufts. He required dialysis sessions. Cocaine-mediated endothelial injury and platelet activation may play important pathogenetic roles in cocaine abusers who develop malignant hypertension associated with thrombotic microangiopathy. Clinicians need to be aware of this rare feature of cocaine intoxication. PMID:26787585

  10. Multiple organ dysfunction syndrome, an unusual complication of heroin intoxication: a case report and review of literature

    PubMed Central

    Feng, Gang; Luo, Qiancheng; Guo, Enwei; Yao, Yulan; Yang, Feng; Zhang, Bingyu; Li, Longxuan

    2015-01-01

    Multiple organ dysfunction syndrome (MODS) has rarely been described in patients with heroin intoxication. Here, we report a rare case of MODS involving six organs, due to heroin intoxication. The patient was a 32-year-old Chinese man with severe heroin intoxication complicated by acute pulmonary edema and respiratory insufficiency, shock, myocardial damage and cardiac insufficiency, rhabdomyolysis and acute renal insufficiency, acute liver injury and hepatic insufficiency, toxic leukoencephalopathy, and hypoglycemia. He managed to survive and was discharged after 10 weeks of intensive care. The possible pathogenesis and therapeutic measures of MODS induced by heroin intoxication and some suggestions for preventing and treating severe complications of heroin intoxication, based on clinical evidence and the pertinent literature, are discussed in this report. PMID:26617935

  11. [Hypokalemia without arterial hypertension by licorice poisoning].

    PubMed

    Luchon, L; Meyrier, A; Paillard, F

    1993-01-01

    We report a case of chronic intoxication with glycyrrhizinic acid, at a dosage of 1000 to 1500 mg per month over a period of 11 months, in a former alcoholic. This intoxication was revealed by profound hypokalaemia and rhabdomyolysis. However, blood pressure remained constantly normal. Analysis of the literature shows that liquorice intoxication, which blocks renal 11 beta-hydroxysteroid dehydrogenase evolves more frequently as isolated hypokalaemia than as a picture of pseudo-primary hyperaldosteronism accompanied with hypertension. Hypokalaemia with urinary potassium wasting and without hypertension should therefore lead to considering liquorice intoxication, which can be confirmed by disclosing shut-off of the renin-angiotensin-aldosterone axis, and by the increase of the urinary ratio of [cortisol metabolites (5 alpha tetrahydrocortisol + 5 beta tetrahydrocortisol)]/[cortisone metabolite (5 beta tetrahydrocortisol)] together with increase of urinary free cortisol excretion. PMID:8232712

  12. Duchenne muscular dystrophy and idiopathic hyperCKemia segregating in a family

    SciTech Connect

    Frydman, M.; Straussberg, R.; Shomrat, R.; Legum, C.

    1995-09-11

    A 7-month-old boy with gross motor delay and failure to thrive presented with rhabdomyolysis following an acute asthmatic episode. During hospitalization an electrocardiographic conversion to a Wolff-Parkinson-White type 1 (WPW) pattern took place. Duchenne muscular dystrophy (DMD) was suspected based on elevated creatine kinase (CK) serum levels, muscle biopsy, and family history. The diagnosis was confirmed by molecular analysis, which documented a deletion corresponding to cDNA probe 1-2a in the dystrophin gene, in the propositus and in an affected male cousin of his mother. {open_quotes}Idiopathic{close_quotes} hyperCKemia was found in the propositus, his father, and 5 of his relatives. We suggest that the unusually early and severe manifestations of DMD in this patient may be related to the coincidental inheritance of the maternal DMD gene and of a paternal gene, causing hyperCKemia. 13 refs., 3 figs., 1 tab.

  13. Cardiovascular collapse after myocardial infarction due to centipede bite.

    PubMed

    Üreyen, Çağin Mustafa; Arslan, Şakir; Baş, Cem Yunus

    2015-07-01

    Centipede bites have been reported to cause localized and/or systemic symptoms including local pain, erythema and edema, nausea and vomiting, palpitations, headache, lymphadenopathy, and rhabdomyolysis. However, acute myocardial infarction due to centipede envenomation is reported in only three cases in English medical literature.We present a case of 31-year-old male bitten by a golden colored centipede leading to myocardial infarction and cardiopulmonary arrest which is seen very rarely. The patient was admitted to emergency department with a swollen and painful right foot. However, typical chest pain became the major complaint and cardiopulmonary arrest developed while electrocardiography was being obtained. The patient was resuscitated successfully for 5 min and acute infero-posterolateral myocardial infarction was detected on electrocardiography. PMID:25994876

  14. [Fatal Lyell's syndrome caused by griseofulvin].

    PubMed

    Mion, G; Le Gulluche, Y; Carsin, H; Verdon, R; Paulet, R

    1990-01-01

    A case of toxic epidermolysis (TE) with a fatal outcome is reported. It occurred after administration of 500 mg griseofulvin twice daily in a 19-year-old female patient. She developed the first skin lesions on the sixth day of treatment. All the body surface was involved, except for the scalp. Several complications arose in the course of the disease, thrombocytopaenia, lymphocytopaenia, rhabdomyolysis, and non cardiogenic pulmonary oedema. Death occurred as a result of multiple organ failure following septic shock associated with adult respiratory distress syndrome. The pathogenesis of these complications and the major therapeutic difficulties encountered are discussed. The involvement of griseofulvin in TE has only been reported once before. The arguments in favour of its involvement in the present case are discussed. PMID:2196842

  15. Hereditary skeletal muscle diseases in the horse. A review.

    PubMed

    Nollet, H; Deprez, P

    2005-06-01

    Since riders nowadays are expecting the highest level of performance from their horses, muscular disorders therefore represent a major problem for the equine athlete. A lot of research has been done to identify muscular disorders and their etiopathogenesis. Both acquired and inherited forms of muscle diseases have been described. In this review only the latter forms will be mentioned. Major signs of all muscle disorders are muscular stiffness, cramping or pain, muscular fasciculations, muscular atrophy and exercise intolerance. Muscle biopsies can help to identify the cause of rhabdomyolysis or muscular atrophy. However, especially in hereditary muscular diseases, a lot of questions are still to be answered. Increasing knowledge of the etiopathogenesis and newer diagnostic tests may lead to a more accurate diagnosis of the individual diseases in future. PMID:16022342

  16. Dangerous reef aquaristics: Palytoxin of a brown encrusting anemone causes toxic corneal reactions.

    PubMed

    Ruiz, Yasmin; Fuchs, Joan; Beuschel, Ralf; Tschopp, Markus; Goldblum, David

    2015-11-01

    Although frequently observed in domestic saltwater aquariums, literature on exposure to palytoxin (PTX) of encrusting anemones (Zoanthidea) kept in aquariums is rare. Handling these animals for propagation purposes or during cleaning work can lead to dermal, ocular or respiratory contact with the PTX generated by some Zoanthids. The present study describes a case of ocular exposure to liquid from a Zoanthid, which led to corneal ulcers. The patient also suffered from systemic symptoms of dyspnea and shivering and a suspected rhabdomyolysis, which required monitoring in the Intensive Care Unit. After symptomatic treatment provided insufficient results, the corneal ulcers improved with an amniotic membrane transplantation. A review of the literature regarding ocular exposures to this diverse order of Hexacorallia reveals that severe and systemic symptoms can develop with minimal contact. PMID:26365918

  17. Exercise, free radicals and oxidative stress.

    PubMed

    Cooper, C E; Vollaard, N B; Choueiri, T; Wilson, M T

    2002-04-01

    This article reviews the role of free radicals in causing oxidative stress during exercise. High intensity exercise induces oxidative stress and although there is no evidence that this affects sporting performance in the short term, it may have longer term health consequences. The mechanisms of exercise-induced oxidative stress are not well understood. Mitochondria are sometimes considered to be the main source of free radicals, but in vitro studies suggest they may play a more minor role than was first thought. There is a growing acceptance of the importance of haem proteins in inducing oxidative stress. The release of metmyoglobin from damaged muscle is known to cause renal failure in exercise rhabdomyolysis. Furthermore, levels of methaemoglobin increase during high intensity exercise, while levels of antioxidants, such as reduced glutathione, decrease. We suggest that the free-radical-mediated damage caused by the interaction of metmyoglobin and methaemoglobin with peroxides may be an important source of oxidative stress during exercise. PMID:12023865

  18. Malignant hyperthermia.

    PubMed

    Bandschapp, Oliver; Girard, Thierry

    2012-01-01

    Malignant hyperthermia (MH) is a subclinical myopathy, usually triggered by volatile anaesthetics and depolarising muscle relaxants. Clinical symptoms are variable, and the condition is sometimes difficult to identify. Nevertheless, rapid recognition and specific as well as symptomatic treatment are crucial to avoid a lethal outcome. Molecular genetic investigations have confirmed the skeletal muscle type ryanodine receptor to be the major MH locus with more than 70% of MH families carrying a mutation in this gene. There is no screening method to test for MH, as current tests are invasive (open muscle biopsy) or restricted to MH families with known MH-associated mutations (molecular genetic testing). The prevalence of the MH trait is unknown, because the clinical penetrance after contact with triggering agents is very variable. More recently, MH mutations have been associated with rhabdomyolysis following statin therapy or with non-pharmacological triggering, such as exertional heat stroke. PMID:22851008

  19. Excited delirium: Consideration of selected medical and psychiatric issues

    PubMed Central

    Samuel, Edith; Williams, Robert B; Ferrell, Richard B

    2009-01-01

    Excited delirium, sometimes referred to as agitated or excited delirium, is the label assigned to the state of acute behavioral disinhibition manifested in a cluster of behaviors that may include bizarreness, aggressiveness, agitation, ranting, hyperactivity, paranoia, panic, violence, public disturbance, surprising physical strength, profuse sweating due to hyperthermia, respiratory arrest, and death. Excited delirium is reported to result from substance intoxication, psychiatric illness, alcohol withdrawal, head trauma, or a combination of these. This communication reviews the history of the origins of excited delirium, selected research related to its causes, symptoms, management, and the links noted between it and selected medical and psychiatric conditions. Excited delirium involves behavioral and physical symptoms that are also observed in medical and psychiatric conditions such as rhabdomyolysis, neuroleptic malignant syndrome, and catatonia. A useful contribution of this communication is that it links the state of excited delirium to conditions for which there are known and effective medical and psychiatric interventions. PMID:19557101

  20. Unusual Case of Acute Renal Failure Following Multiple Wasp Stings

    PubMed Central

    Rachaiah, Niranjan M; Jayappagowda, Lokesh A; Siddabyrappa, Harsha B; Bharath, Venkatesh K

    2012-01-01

    The wasp stings usually cause local reactions and rarely anaphylaxis. However the multiple wasp stings may cause multisystem involvement. We report a case of acute renal failure (ARF) following multiple wasp stings. A middle aged healthy gentleman presented with pain and swelling of the upper part of the body following multiple wasp stings. After 2 days, he developed progressive decrease in urine output with high colored urine. Physical examination revealed the edematous and tender affected part. On investigating, it was found to have sequential elevations in renal function tests. The markers of muscle injury were grossly elevated and liver enzymes were deranged. These findings suggest multisystem involvement predominantly ARF secondary to rhabdomyolysis. With the initiation of the intense hemodialysis, all the above parameters became normal. Timely intervention of multiple wasp stings causing ARF with multiorgan involvement by hemodialysis not only prevents mortality but also other complications. PMID:22408758

  1. Update on toxic myopathies.

    PubMed

    Mastaglia, F L; Needham, M

    2012-02-01

    The toxic myopathies are a clinically and pathologically diverse group of disorders that can be caused by a variety of therapeutic agents used in clinical practice, as well as various venoms and other biological toxins. The most important iatrogenic causes are the statin and fibrate cholesterol-lowering agents that can cause a severe necrotizing myopathy and acute rhabdomyolysis and myoglobinuria. The current update focuses on the mechanisms of statin myotoxicity and the importance of genetic predisposing factors for statin myopathy, as well as the recently described form of necrotizing autoimmune myopathy, which is associated with antibodies to the 3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme and is responsive to aggressive immunotherapy. Mitochondrial myopathies associated with antiretroviral agents and the pyrimidine nucleoside analogue clevudine, and recent reports of myopathies caused by ingestion of red yeast rice and toxic species of mushrooms are also discussed. PMID:21968786

  2. Perioperative management of the morbidly obese adolescent with heart failure undergoing bariatric surgery.

    PubMed

    Maxwell, Bryan G; Ingrande, Jerry; Rosenthal, David N; Ramamoorthy, Chandra

    2012-05-01

    The incidence and prevalence of adolescent obesity and adolescent heart failure are increasing, and anesthesiologists increasingly will encounter patients with both conditions. A greater understanding of the physiologic challenges of adolescent heart failure as they relate to the perioperative stressors of anesthesia and bariatric surgery is necessary to successfully manage the perioperative risks faced by this growing subpopulation. Here, we present a representative case of a morbidly obese adolescent with heart failure who underwent a laparoscopic bariatric operation and review the limited available literature on perioperative management in this age group. Specifically, we review evidence and offer recommendations related to preoperative evaluation, venous thromboembolism prophylaxis, positioning, induction, airway management, monitoring, anesthetic maintenance, ventilator management, and adverse effects of the pneumoperitoneum, rhabdomyolysis, and postoperative care. PMID:22385267

  3. Scintigraphic evaluation of muscle damage following extreme exercise: concise communication

    SciTech Connect

    Matin, P.; Lang, G.; Carretta, R.; Simon, G.

    1983-04-01

    Total body Tc-99m pyrophosphate scintigraphy was performed on 11 ''ultramarathon'' runners to assess the ability of nuclear medicine techniques to evaluate skeletal-muscle injury due to exercise. We found increased muscle radionuclide concentration in 90% of the runners. The pattern of muscle uptake correlated with the regions of maximum pain. The detection of exercise-induced rhabdomyolysis appeared to be best when scintigraphy was performed within 48 hr after the race, and to be almost undetectable after about a week. It was possible to differentiate muscle injury from joint and osseous abnormalities such as bone infarct or stress fracture. Although 77% of the runners had elevated serum creatine kinase MB activity, cardiac scintigraphy showed no evidence of myocardial injury.

  4. Propofol Infusion Syndrome in Adults: A Clinical Update

    PubMed Central

    Mirrakhimov, Aibek E.; Voore, Prakruthi; Halytskyy, Oleksandr; Khan, Maliha; Ali, Alaa M.

    2015-01-01

    Propofol infusion syndrome is a rare but extremely dangerous complication of propofol administration. Certain risk factors for the development of propofol infusion syndrome are described, such as appropriate propofol doses and durations of administration, carbohydrate depletion, severe illness, and concomitant administration of catecholamines and glucocorticosteroids. The pathophysiology of this condition includes impairment of mitochondrial beta-oxidation of fatty acids, disruption of the electron transport chain, and blockage of beta-adrenoreceptors and cardiac calcium channels. The disease commonly presents as an otherwise unexplained high anion gap metabolic acidosis, rhabdomyolysis, hyperkalemia, acute kidney injury, elevated liver enzymes, and cardiac dysfunction. Management of overt propofol infusion syndrome requires immediate discontinuation of propofol infusion and supportive management, including hemodialysis, hemodynamic support, and extracorporeal membrane oxygenation in refractory cases. However, we must emphasize that given the high mortality of propofol infusion syndrome, the best management is prevention. Clinicians should consider alternative sedative regimes to prolonged propofol infusions and remain within recommended maximal dose limits. PMID:25954513

  5. Total intravenous anesthesia for aortic aneurysm replacement surgery in a patient with limb-girdle dystrophy.

    PubMed

    Lpez lvarez, A; Romn Fernndez, A; Vilanova Vzquez, V; Corujeira Rivera, M C; Aren Gonzlez, I; Valio Hortas, C

    2014-01-01

    We report the anesthetic management with total intravenous anesthesia of a 61-year-old male diagnosed with limb-girdle muscular dystrophy admitted for replacement of ascending aorta due to an aortic aneurysm. Limb-girdle muscular dystrophy belongs to a genetically heterogeneous group of muscular dystrophies involving shoulder and hip girdles. Although the risk of malignant hyperthermia does not seem to be increased in these patients compared with the general population, the exposure to inhaled anesthetics and succinylcholine should probably be avoided because these patients have a predisposition to hyperkalemia and rhabdomyolysis. We chose to use total intravenous anesthesia with propofol, remifentanil and muscle relaxants to reduce oxygen consumption, and later to reduce the doses of propofol and remifentanil. The combination of a carefully planned anesthetic strategy, anesthetic depth, and neuromuscular blockade monitoring is explained. PMID:24035539

  6. Dystrophinopathies.

    PubMed

    Brandsema, John F; Darras, Basil T

    2015-08-01

    The dystrophinopathies fall along a spectrum of muscular dystrophy phenotypes, with variable involvement of skeletal and cardiac muscle. The diagnosis of dystrophinopathy should be suspected in any patient with a highly elevated creatine kinase level beyond the context of rhabdomyolysis secondary to toxic or metabolic myopathy. Genetic testing for dystrophinopathy is highly sensitive and specific, and identifying a proband will often lead to implications for several relatives at risk for cardiomyopathy, weakness, or anesthetic reactions. Management of the dystrophinopathies is focused primarily on supportive care, although steroid therapy has changed the natural history of Duchenne muscular dystrophy and it is now standard-of-care internationally. An exciting and ongoing area of investigation of the dystrophinopathies is focused on the potential for altering gene expression, as a way of improving muscle health and slowing the rate of muscle degeneration. PMID:26502761

  7. Management of Crush Syndrome Casualties after Disasters

    PubMed Central

    Sever, Mehmet Sukru; Vanholder, Raymond

    2011-01-01

    After direct impact of the trauma, crush syndrome is the second most frequent cause of death after mass disasters. However, since crush syndrome is quite rare in daily practice, mistakes are frequent in the treatment of these cases. This paper summarizes the etiopathogenesis of traumatic rhabdomyolysis and of crush syndrome-based acute kidney injury. The clinical and laboratory features, prophylaxis, and treatment of crush cases are described as well. The importance of early and energetic fluid resuscitation is underlined for prophylaxis of acute kidney injury. Since there is chaos, and an overwhelming number of victims, logistic drawbacks create a specific problem in the treatment of crush victims after mass disasters. Potential solutions for logistic hurdles and disaster preparedness scenarios have also been provided in this review article. PMID:23908797

  8. Propofol infusion syndrome in adults: a clinical update.

    PubMed

    Mirrakhimov, Aibek E; Voore, Prakruthi; Halytskyy, Oleksandr; Khan, Maliha; Ali, Alaa M

    2015-01-01

    Propofol infusion syndrome is a rare but extremely dangerous complication of propofol administration. Certain risk factors for the development of propofol infusion syndrome are described, such as appropriate propofol doses and durations of administration, carbohydrate depletion, severe illness, and concomitant administration of catecholamines and glucocorticosteroids. The pathophysiology of this condition includes impairment of mitochondrial beta-oxidation of fatty acids, disruption of the electron transport chain, and blockage of beta-adrenoreceptors and cardiac calcium channels. The disease commonly presents as an otherwise unexplained high anion gap metabolic acidosis, rhabdomyolysis, hyperkalemia, acute kidney injury, elevated liver enzymes, and cardiac dysfunction. Management of overt propofol infusion syndrome requires immediate discontinuation of propofol infusion and supportive management, including hemodialysis, hemodynamic support, and extracorporeal membrane oxygenation in refractory cases. However, we must emphasize that given the high mortality of propofol infusion syndrome, the best management is prevention. Clinicians should consider alternative sedative regimes to prolonged propofol infusions and remain within recommended maximal dose limits. PMID:25954513

  9. Amphetamine toxicity.

    PubMed

    White, Suzanne R

    2002-02-01

    Amphetamine abuse is widespread and associated with significant health risk. The most commonly encountered amphetamines are methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy), and the ephedra alkaloids. Although each of these harbors unique toxicity, they similarly impact the cardiovascular and neurological systems in overdose. Other serious complications associated with amphetamine abuse include severe hyperpyrexia and hyponatremia. Secondary conditions such as rhabdomyolysis, disseminated intravascular coagulation (DIC), gastrointestinal (GI) bleeding, hepatic necrosis, and renal failure are common, especially in those with hyperthermia. Chronic abuse poses risk of vasculitis, neuropsychiatric abnormalities, and cardiomyopathy. In addition, there is a growing body of evidence that even recreational abuse of methamphetamine and MDMA may produce long-lasting damage to dopaminergic and serotonergic neurons. Management principles include adequate sedation, aggressive cooling, and the use of titratable agents in the management of cardiovascular abnormalities. PMID:16088595

  10. Clinical Significance of Ryanodine Receptor 1 Gene (RYR1) Variants: Proceedings of the 2013 MHAUS Scientific Conference

    PubMed Central

    Riazi, Sheila; Kraeva, Natalia; Muldoon, Sheila M.; Dowling, James; Ho, Clara; Petre, Maria-Alexandra; Parness, Jerome; Dirksen, Robert T.; Rosenberg, Henry

    2014-01-01

    The Malignant Hyperthermia Association of the United States (MHAUS) and the Department of Anesthesia at the University of Toronto sponsored a Scientific Conference on November 12, 2013 in Toronto, Canada. The multidisciplinary group of experts, including clinicians, geneticists and physiologists involved in research related to malignant hyperthermia (MH), shared new insights into the pathophysiology of type-1 ryanodine receptor gene (RYR1)-linked diseases, as well as the relationship between MH and awake MH conditions, such as exertional rhabdomyolysis (ER) and exertional heat illness (EHI). In addition, the molecular genetics of MH, and clinical issues related to the diagnosis and management of RYR1-linked disorders, were presented. The conference also honored Dr. David H. MacLennan for his contributions to our understanding of the genetics, pathogenesis and treatment of MH and other RYR1-related myopathies. This report represents a summary of the proceedings of this conference. PMID:25189431

  11. Acute kidney injury: A rare cause.

    PubMed

    Mendonca, Satish; Barki, Satish; Mishra, Mayank; Kumar, R S V; Gupta, Devika; Gupta, Pooja

    2015-09-01

    We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering. PMID:26354573

  12. Sickle cell trait in sports.

    PubMed

    Eichner, E Randy

    2010-01-01

    Sickle cell trait (SCT) can pose a grave risk for some athletes. In the past decade in NCAA Division I football, no deaths have occurred from the play or practice of the game, but 16 deaths have occurred from conditioning for the game, and 10 (63%) of these deaths are tied to SCT, an excess of up to 21-fold. Research shows how and why, during intense exercise bouts, sickle cells can accumulate and "logjam" blood vessels, causing explosive rhabdomyolysis that can kill. Sickling can begin in 2 to 5 min of all-out exertion and can reach grave levels soon thereafter if the athlete struggles on or is urged on by coaches despite warning signs. Sickling collapse is an intensity syndrome that differs from other common causes of collapse. Tailored precautions can prevent sickling collapse and enable athletes with SCT to thrive. Irrationally intense conditioning for a game puts the lives of healthy athletes with SCT at risk. PMID:21068567

  13. Toxicological Profiles of Poisonous, Edible, and Medicinal Mushrooms

    PubMed Central

    Jo, Woo-Sik; Hossain, Md. Akil

    2014-01-01

    Mushrooms are a recognized component of the human diet, with versatile medicinal properties. Some mushrooms are popular worldwide for their nutritional and therapeutic properties. However, some species are dangerous because they cause toxicity. There are many reports explaining the medicinal and/or toxic effects of these fungal species. Cases of serious human poisoning generally caused by the improper identification of toxic mushroom species are reported every year. Different substances responsible for the fatal signs and symptoms of mushroom toxicity have been identified from various poisonous mushrooms. Toxicity studies of mushroom species have demonstrated that mushroom poisoning can cause adverse effects such as liver failure, bradycardia, chest pain, seizures, gastroenteritis, intestinal fibrosis, renal failure, erythromelalgia, and rhabdomyolysis. Correct categorization and better understanding are essential for the safe and healthy consumption of mushrooms as functional foods as well as for their medicinal use. PMID:25346597

  14. A rare case of pyomyositis due to swine flu

    PubMed Central

    Runia, AJ; Schasfoort, A; Kerver, AJH; van der Ham, AC

    2011-01-01

    Pyomyositis is a bacterial infectious disease of the large skeletal muscles, mostly seen in tropical regions. A case with such a multitude of abscesses has never been described in the western world, nor following an H1N1 infection. We report of a 31 year old man who presented himself with complaints of muscle pain and fever. His complaints were attributed to a proven H1N1 infection. However, despite proper therapy his condition worsened. He had developed multiple abscesses in both arms and legs. After surgical and radiologic drainage and antibiotic treatment our patient healed without any symptoms. Pyomositis is related with immuno-compromisation. Our patient might have been immunocompromised due to the H1N1 infection. Rhabdomyolysis following influenza has been described before, however a relation with H1N1 never was. Imaging studies help detect and confirm the diagnosis. When missed, serious complications may arise. PMID:24950578

  15. Morphologic changes in intercostal muscle tissue associated with a viper (Agkistrodon halys blomhoffi) bite.

    PubMed

    Sakuma, N; Kamei, T; Okamura, H; Ishihara, T; Matayoshi, Y

    1996-01-01

    This study examined a 73-year-old woman who had been bitten in the right thumb by a viper (Agkistrodon halys blomhoffi). She suffered acute renal failure and respiratory failure after the bite. On the 20th day, respiratory failure persisted, although she had recovered from renal failure. Intercostal muscles were obtained by biopsy on the 40th day after the bite. Specimens were observed with enzyme-histochemical and electron microscopic techniques. The size of muscle fibers varied. Most of the smaller muscle fibers were enzyme-histochemically type 2C fibers. This was considered to be the regenerative stage of acute rhabdomyolysis. Ultrastructurally, two opposite types of changes, degeneration and regeneration, were mixed in the same areas. Muscle fibers might be continuously degenerated, and the regenerative fibers might also be degenerated. This study suggests that some slow allergic reactions to snake venom might bear some relation to the degenerative changes. PMID:8727068

  16. [A severe form of heat stroke in a long-distance runner].

    PubMed

    Lepape, A; Sarron, C; Grozel, J M; Perdrix, J P; Banssillon, V

    1986-01-01

    A case of a severe heat stroke is reported in a 30 yr old white man while running a long-distance race. At the time of admission, moderate hyperthermia (40 degrees C) and coma were two major symptoms found at physical examination. Within 24 h, the clinical picture evolved to multiple organ failure with marked rhabdomyolysis, acute renal failure with hyperkalaemia and lactic acidosis. At this time, were also found a consumptive coagulopathy and acute hepatic failure. After numerous complications, most of them infectious, the patient was discharged after four months in ICU and admitted in a physical rehabilitation department. Muscle biopsy performed three years after the heat stroke showed an abnormal reactivity to caffeine, but a normal reaction to halothane. The relationship between malignant hyperthermia and heat stroke remains uncertain. PMID:3777573

  17. Red alert: labile heme is an alarmin.

    PubMed

    Soares, Miguel P; Bozza, Marcelo T

    2016-02-01

    Alarmins are a heterogeneous group of endogenous molecules that signal cellular damage when sensed extracellularly. Heme is an endogenous molecule that acts as a prosthetic group of hemoproteins, such as hemoglobin and myoglobin. When released from damaged red blood cells or muscle cells, oxidized hemoglobin and myoglobin release their prosthetic heme groups, respectively. This generates labile heme, which is sensed by pattern recognition receptors (PRR) expressed by innate immune cells and possibly regulatory T cells (TREG). The ensuing adaptive response, which alerts for the occurrence of red blood cell or muscle cell damage, regulates the pathologic outcome of hemolysis or rhabdomyolysis, respectively. In conclusion, we propose that labile heme is an alarmin. PMID:26741528

  18. Chinese Herbal Medicine on Dyslipidemia: Progress and Perspective

    PubMed Central

    Guo, Ming; Liu, Yue; Gao, Zhu-Ye; Shi, Da-zhuo

    2014-01-01

    Dyslipidemia is an independent risk factor of cardiovascular diseases. The statins are a milestone in the primary and second prevention of cardiovascular diseases and significantly improved its prognosis. Along with the long-term treatment with statins in combination with other hypolipidemic drugs or alone, its safety has attracted a particular attention in clinic, such as the elevation of transaminase and rhabdomyolysis, which have raised an idea of developing the other types of lipid-lowering agents from botanic materials. Traditional Chinese medicine (TCM) has been used in clinical practice for more than 2000 years in China and showed some beneficial effects for human health and many diseases. Recently, many studies demonstrated a favorable effect of TCM for treating dyslipidemia; however, its mechanism remains unclear or totally unknown. The progress and perspective of studies on dyslipidemia with single Chinese herb and its monomers or effective extracts during the past 10 years are discussed in the present review. PMID:24688589

  19. Fatal propofol infusion syndrome in association with ketogenic diet.

    PubMed

    Baumeister, F A M; Oberhoffer, R; Liebhaber, G M; Kunkel, J; Eberhardt, J; Holthausen, H; Peters, J

    2004-08-01

    Propofol is used for the treatment of refractory status epilepticus. When given as a long-term infusion propofol may cause a rare but frequently fatal complication, the propofol infusion syndrome. The hallmarks are metabolic acidosis, lipemia, rhabdomyolysis and myocardial failure. Propofol infusion syndrome is caused by impaired fatty acid oxidation. Beside anticonvulsants the ketogenic diet, a high-fat, low-carbohydrate, adequate-protein diet, is an effective treatment for difficult-to-control seizures. We report a 10-year-old boy with catastrophic epilepsy, who developed fatal propofol infusion syndrome when a ketogenic diet was initiated. Substances like propofol which impair fatty acid oxidation may pose an increased risk if combined with ketogenic diet. PMID:15328567

  20. How MDMA's pharmacology and pharmacokinetics drive desired effects and harms.

    PubMed

    Michael White, C

    2014-03-01

    3,4-Methylenedioxymethamphetamine (MDMA) is an agent of abuse that has been used by over 16 million Americans. Increased energy, elevated mood, bonding with others, and psychedelic effects are desired effects while liver damage, extended depressed mood, sexual assault, rhabdomyolysis, serotonin syndrome, multiorgan failure, cardiovascular events, arrhythmias, and death are possible adverse effects. These desirable and adverse effects of MDMA are extensions of its fascinating pharmacologic and pharmacokinetic profile. In addition to methamphatemine like effects, MDMA also has mescaline like effects and increases the release of cortisol, oxytocin, and antidiuretic hormone. The desirable effects of MDMA are accentuated by the rave or electronic dance music scene where warm temperatures, vigorous dancing, loud music, and light shows accentuate some of the responses. However, the same environment increases the risk of certain harms. Knowledge of the constellation of these factors is needed for education, prevention of harm, and treatment. PMID:24431106

  1. Peripheral neuropathy and statins.

    PubMed

    2007-12-01

    (1) Statins are cholesterol-lowering drugs extensively used in cardiovascular prevention. Their most well-known adverse effect is muscle damage, including rhabdomyolysis. (2) Several cases of peripheral polyneuropathy attributed to a statin have been published or reported by pharmacovigilance centres. (3) They included sensory or sensorimotor polyneuropathy with signs of sensory impairment, and a decrease or sometimes a suppression of osteotendinous reflexes. Some patients also had a marked reduction in muscle strength in the affected limb(s). Renal failure and diabetes appear to increase the risk of this adverse effect. (4) Epidemiological studies and clinical trials have shown that this adverse effect is rare, affecting only about one patient in 10 000 treated for one year. (5) After ruling out other possible causes of peripheral neuropathy, statin withdrawal often leads to clinical improvement. PMID:18092417

  2. Neuromuscular complications of statins.

    PubMed

    Ahn, Sung C

    2008-02-01

    Statins, 3-hydroxy-3-methlglutaryl coenzyme A reductase inhibitors, are commonly prescribed for patients who have hyperlipidemia. Statins were first approved in 1987. Statin therapy is well documented to reduce serum low-density lipoprotein levels, incidence of cardiovascular events, and mortality. Although statin therapy is well tolerated, serious adverse affects have been reported, including neuromuscular and hepatic complications. Myopathy is particularly concerning because of the potential for rhabdomyolysis and death. Recently, peripheral neuropathy also has been identified as a possible complication. The incidence of neuromuscular complications is expected to increase with the increased number of people using statin therapy. Clinicians should be aware of the potential neuromuscular complications. This article reviews epidemiology, possible mechanisms, risk factors, and management of statin-associated neuromuscular complications. PMID:18194749

  3. Are statins really wonder drugs?

    PubMed

    Grover, Harpreet Singh; Luthra, Shailly; Maroo, Shruti

    2014-12-01

    Statins [3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase], are wonder drugs that have reshaped the treatment of hypercholesterolemia and associated cardiovascular diseases. However, evidence from various studies indicates existence of many statin-induced side effects such as myopathies, rhabdomyolysis, hepatotoxicity, peripheral neuropathy, impaired myocardial contractility, diabetes, autoimmune diseases, and erectile dysfunction (ED). Physician awareness of these side effects is reported to be very low even for the adverse effects (AEs) most widely reported by patients. This can lead to incorrect treatment decisions, compromised patient care, and an increase in patient morbidity. Therefore, the aim of this article is to highlight the AEs of statin therapy as well as rational management of these complications to further improve safety of these excellent drugs. PMID:24231094

  4. The Biochemistry and Physiology of Mitochondrial Fatty Acid ?-Oxidation and Its Genetic Disorders.

    PubMed

    Houten, Sander M; Violante, Sara; Ventura, Fatima V; Wanders, Ronald J A

    2016-02-10

    Mitochondrial fatty acid ?-oxidation (FAO) is the major pathway for the degradation of fatty acids and is essential for maintaining energy homeostasis in the human body. Fatty acids are a crucial energy source in the postabsorptive and fasted states when glucose supply is limiting. But even when glucose is abundantly available, FAO is a main energy source for the heart, skeletal muscle, and kidney. A series of enzymes, transporters, and other facilitating proteins are involved in FAO. Recessively inherited defects are known for most of the genes encoding these proteins. The clinical presentation of these disorders may include hypoketotic hypoglycemia, (cardio)myopathy, arrhythmia, and rhabdomyolysis and illustrates the importance of FAO during fasting and in hepatic and (cardio)muscular function. In this review, we present the current state of knowledge on the biochemistry and physiological functions of FAO and discuss the pathophysiological processes associated with FAO disorders. PMID:26474213

  5. Does hypokalemia contribute to acute kidney injury in chronic laxative abuse?

    PubMed Central

    Lee, Eun-Young; Yoon, Hyaejin; Yi, Joo-Hark; Jung, Woon-Yong; Han, Sang-Woong; Kim, Ho-Jung

    2015-01-01

    Prolonged hypokalemia from chronic laxative abuse is recognized as the cause of chronic tubulointerstitial disease, known as hypokalemic nephropathy, but it is not clear whether it contributes to acute kidney injury (AKI). A 42-year-old woman with a history of chronic kidney disease as a result of chronic laxative abuse from a purging type of anorexia nervosa (AN-P), developed an anuric AKI requiring hemodialysis and a mild AKI 2 months later. Both episodes of AKI involved severe to moderate hypokalemia (1.2 and 2.7mmol/L, respectively), volume depletion, and mild rhabdomyolysis. The histologic findings of the first AKI revealed the remnants of acute tubular necrosis with advanced chronic tubulointerstitial nephritis and ischemic glomerular injury. Along with these observations, the intertwined relationship among precipitants of recurrent AKI in AN-P is discussed, and then we postulate a contributory role of hypokalemia involved in the pathophysiology of the renal ischemia-induced AKI. PMID:26484031

  6. Bilateral knee and intermittent elbow pain in a competitive archer/hunter: phosphodiesterase-5-inhibitor-statin interaction?

    PubMed

    Pujalte, George G A; Acosta, Lillybeth

    2014-09-01

    A 59-year-old white hunter and archer presented to the sports medicine clinic with bilateral knee and left elbow pain. Various treatments for presumed musculoskeletal diagnoses did not help. When reviewing his medications, the patient concluded that the only new one before the appearance of his symptoms was tadalafil. He stopped taking it, and his pain resolved immediately thereafter. On review, it was noted that the patient was also on pravastatin. There have been a few previous reports of myopathy and rhabdomyolysis with the concomitant use of a phosphodiesterase-5 inhibitor (PDE5I), such as tadalafil and a statin. We report a case where such processes may have been occurring and may have resolved shortly after discontinuing concomitant use, in turn resulting in decreased pain. Clinicians may need to be aware of the possibility of such symptoms and processes occurring in patients taking both a statin and a PDE5I. PMID:24231931

  7. Sickle cell trait testing and athletic participation: a solution in search of a problem?

    PubMed

    Thompson, Alexis A

    2013-01-01

    Carriers of a single sickle cell gene mutation generally enjoy normal lifespans without serious health consequences related to their sickle cell status, but under extreme conditions such as severe dehydration and high-intensity physical activity, complications such as exertional rhabdomyolysis, splenic infarction, and papillary necrosis can occur. Recently, the National Collegiate Athletic Association (NCAA) adopted a policy that requires sickle cell solubility testing for all incoming student athletes. However, the American Society of Hematology (ASH) and other physician organizations oppose this policy. What is the basis for this controversy and how have new findings moved the field forward? I discuss herein the epidemiology, genetics, and clinical studies of sickle cell trait; review the implications of current policies regarding sickle cell trait screening and interventions for the student athlete; and examine additional areas where more information is needed. PMID:24319243

  8. Newborn screening and renal disease: where we have been; where we are now; where we are going.

    PubMed

    Merritt, J Lawrence; Askenazi, David; Hahn, Si Houn

    2012-09-01

    Newborn screening (NBS) has rapidly changed since its origins in the 1960s. Beginning with a single condition, then a handful in the 1990 s, NBS has expanded in the past decade to allow the detection of many disorders of amino-acid, organic-acid, and fatty-acid metabolism. These conditions often present with recurrent acute attacks of metabolic acidosis, hypoglycemia, liver failure, and hyperammonemia that may be prevented with initiation of early treatment. Renal disease is an important component of these disorders and is a frequent source of morbidity. Hemodialysis is often required for hyperammonemia in the organic acidemias and urea-cycle disorders. Rhabdomyolysis with renal failure is a frequent complication in fatty-acid oxidation disorders. Newer screening methods are under investigation to detect lysosomal storage diseases, primary immunodeficiencies, and primary renal disorders. These advances will present many challenges to nephrologists and pediatricians with respect to closely monitoring and caring for children with such disorders. PMID:21947256

  9. Bi-allelic Truncating Mutations in TANGO2 Cause Infancy-Onset Recurrent Metabolic Crises with Encephalocardiomyopathy.

    PubMed

    Kremer, Laura S; Distelmaier, Felix; Alhaddad, Bader; Hempel, Maja; Iuso, Arcangela; Kpper, Clemens; Mhlhausen, Chris; Kovacs-Nagy, Reka; Satanovskij, Robin; Graf, Elisabeth; Berutti, Riccardo; Eckstein, Gertrud; Durbin, Richard; Sauer, Sascha; Hoffmann, Georg F; Strom, Tim M; Santer, Ren; Meitinger, Thomas; Klopstock, Thomas; Prokisch, Holger; Haack, Tobias B

    2016-02-01

    Molecular diagnosis of mitochondrial disorders is challenging because of extreme clinical and genetic heterogeneity. By exome sequencing, we identified three different bi-allelic truncating mutations in TANGO2 in three unrelated individuals with infancy-onset episodic metabolic crises characterized by encephalopathy, hypoglycemia, rhabdomyolysis, arrhythmias, and laboratory findings suggestive of a defect in mitochondrial fatty acid oxidation. Over the course of the disease, all individuals developed global brain atrophy with cognitive impairment and pyramidal signs. TANGO2 (transport and Golgi organization 2) encodes a protein with a putative function in redistribution of Golgi membranes into the endoplasmic reticulum in Drosophila and a mitochondrial localization has been confirmed in mice. Investigation of palmitate-dependent respiration in mutant fibroblasts showed evidence of a functional defect in mitochondrial ?-oxidation. Our results establish TANGO2 deficiency as a clinically recognizable cause of pediatric disease with multi-organ involvement. PMID:26805782

  10. Clinical and genetic features of anoctaminopathy in Saudi Arabia

    PubMed Central

    Bohlega, Saeed; Monies, Dorothy M.; Abulaban, Ahmad A.; Murad, Hatem N.; Alhindi, Hindi N.; Meyer, Brian F.

    2015-01-01

    Objectives: Characterization of the phenotypic, pathological, radiological, and genetic findings in 2 Saudi Arabian families with anoctaminopathies, and limb girdle muscular dystrophy type 2L (LGMD2L). Methods: Over a 2-year period from December 2010 to January 2013, the clinical presentations were analyzed and all genes responsible for limb girdle muscular dystrophy (LGMD) were screened in families seen at King Faisal Specialist Hospital and Research Centre, a tertiary care hospital in Riyadh, Saudi Arabia. Out of 66 families with LGMD, we identified 2 families (3.1%) with anoctaminopathy, ANO5 muscular dystrophy. Results: In the first case, a man presented with asymmetrical calves muscles weakness and atrophy, which was first noted at age 39. The creatinine kinase (CK) level was >20x normal, muscle biopsy showed necrotizing myopathic changes, and an MRI of the legs showed fatty-tissue replacement to muscle tissue with volume loss involving the gastrocnemius and soleus muscles in an asymmetrical fashion. Minimal disease progression was noted over 18 years of follow up. Exercise induced recurrent rhabdomyolysis was noted over the last 2 years. A novel ANO5 gene mutation (Arg58Trp) was found. In the second family, a male presented at the age of 41 with asymptomatic hyperCkemia and intermittent dyspnea. Over 10 years follow up, he became disabled with muscle cramps, rhabdomyolysis, myoglobinurea, and difficulty ambulating. Muscle biopsy showed necrotizing myopathy and perivascular and interstitial amyloid deposit in skeletal muscle. A homozygous deletion of 11.9 Kb encompassing exon 13 to exon 17 was found in the ANO5 gene. Full cardiac investigations were normal in both patients. Conclusion: The prevalence of LGMD2L is approximately 3.1% in a Saudi Arabian native LGMD cohort. Slowly progressive, late onset, and asymmetrical weakness was the salient features in these 2 families. The genetic findings were novel and will add to the spectrum of ANO5 known mutations. PMID:25864073

  11. Calcium homeostasis in myogenic differentiation factor 1 (MyoD)-transformed, virally-transduced, skin-derived equine myotubes.

    PubMed

    Fernandez-Fuente, Marta; Terracciano, Cesare M; Martin-Duque, Pilar; Brown, Susan C; Vassaux, Georges; Piercy, Richard J

    2014-01-01

    Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells' calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans. PMID:25148524

  12. A past Haff disease outbreak associated with eating freshwater pomfret in South China

    PubMed Central

    2013-01-01

    Background Haff disease is unexplained rhabdomyolysis caused by consumption of fishery products in the previous 24h. It was first identified in Europe in 1924 but the condition is extremely rare in China. Here we describe a past outbreak of acute food borne muscle poisoning that occurred in Guangdong Province (South China) in 2009. Methods The first full outbreak of Haff disease reported in Jiangsu Province (East China) in 2010, indicated that the incidence of the disease may be increasing in China. We, therefore first retrospectively reviewed epidemiologic, trace-back, environmental studies, and laboratory analyses, including oral toxicity testing to ascertain risk and chemical analysis to identify toxin(s), from the 2009 Guangdong outbreak. Then we compared data from the 2009 outbreak with data from all other Haff disease outbreaks that were available. Results Clinical symptoms and laboratory findings indicated that the 2009 Guangdong outbreak disease was consistent with rhabdomyolysis. Epidemiologic, trace-back, environmental studies and laboratory analyses implied that the disease was caused by freshwater Pomfrets consumed prior to the onset of symptoms. We also identified common factors between the 2009 Guangdong outbreak and previous Haff disease outbreaks reported around the world, while as with other similar outbreaks, the exact etiological factor(s) of the disease remains unknown. Conclusions The 2009 Guangdong outbreak of muscle poisoning was retrospectively identified as an outbreak of Haff disease. This comprised the highest number of cases reported in China thus far. Food borne diseases emerging in this unusual form and the irregular pattern of outbreaks present an ongoing public health risk, highlighting the need for improved surveillance and diagnostic methodology. PMID:23642345

  13. [The effect of a p-phenylenediamine containing hair dye on the Ca2+ mobilization in the chemically skinned skeletal muscle of the rat].

    PubMed

    Yabe, K

    1992-04-01

    In order to clarify the mechanism of a p-phenylenediamine (PPD)-related occurrence of rhabdomyolysis, the pharmacological effects of PPD, a main component of hair dyes, on the function of the contractile proteins and the sarcoplasmic reticulum (SR) have been investigated in single skeletal muscle fibers of the rat by using the skinned fiber method. The results of our findings are enumerated below 1) A positive contraction of the skinned fibers by the PPD, and a complete suppression of the contraction by Mg2+, and a negative contraction by caffeine while under conditions with 50 mM of PPD were noted, suggesting that the contraction of the muscle by PPD is caused by the release of Ca2+ from the SR. 2) PPD inhibited the Ca2+ uptake by the SR in a concentration-dependent manner. 3) PPD greatly accelerated Ca2+ leakage from the SR, and the number of Ca2+ remnants 3 minutes after the administration of 50 mM of PPD amounted to only 3%. 4) The calcium-induced calcium release (CICR) was accelerated in areas with a low Ca2+ concentration, and the amount of Ca2+ released at a pCa of 7.5 showed an increase of up to 63% on PPD administration of 50 mM. 5) PPD did not influence the Ca2+ sensitivity of the contractile system. It thus has been speculated that PPD can bring about rhabdomyolysis by promoting the CICR and leakage of Ca2+ from the SR, this being followed by an increase in the Ca2+ concentration and by consequent changes that develop in the muscle, such as continuous contraction, an irreversible change in the muscle's structure and/or a hypermetabolic change. PMID:1619810

  14. Multi-drug intoxication fatality involving atorvastatin: A case report.

    PubMed

    Cibickova, Lubica; Caran, Tomas; Dobias, Martin; Ondra, Peter; Vorisek, Viktor; Cibicek, Norbert

    2015-12-01

    Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein. Standard measures (gastric lavage, activated charcoal, mechanical ventilation, massive doses of vasopressors, volume expansion, diuretics and alkalinization) failed to provide sufficient drug elimination and hemodynamic support and the sufferer deceased on the fourth day. Dramatic elevations of serum myoglobin (34,020?g/L) and creatine kinase (219?kat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17g/kg (blood) and 2.81g/kg (urine). Thin layer chromatography and gas chromatography of gastric content and urine verified verapamil, moxonidin and urapidil fragment (diacerein method was unavailable). Atorvastatin and trandolapril concentrations (LC-MS(n)) equaled 277.7?g/L and 57.5?g/L, resp. (serum) and 8.15?g/L and 602.3?g/L, resp. (urine). Histology confirmed precipitates of myoglobin with acute necrosis of proximal renal tubules in association with striated muscle rhabdomyolysis and myocardial dystrophy. Cardiogenic-distributive shock in conjunction with acute renal failure due to the combined self-poisoning with vasoactive agents and atorvastatin were determined to be this decedent's immediate cause of death. The manner of death was assigned to be suicidal. PMID:26508377

  15. Nephrotoxic Effects of Common and Emerging Drugs of Abuse

    PubMed Central

    Pendergraft, William F.; Herlitz, Leal C.; Thornley-Brown, Denyse; Rosner, Mitchell

    2014-01-01

    The kidneys can be injured in diverse ways by many drugs, both legal and illegal. Novel associations and descriptions of nephrotoxic effects of common and emerging drugs of abuse have appeared over the past several years. Anabolic androgenic steroids, illicitly used by athletes and others for decades to increase muscle mass and decrease body fat, are emerging as podocyte toxins given recent descriptions of severe forms of FSGS in long-term abusers. Synthetic cannabinoids, a new group of compounds with marijuana-like effects, recently became popular as recreational drugs and have been associated with an atypical form of AKI. 3,4-Methylenedioxymethamphetamine, commonly known as ecstasy, is a widely used synthetic recreational drug with mood-enhancing properties and a constellation of toxicities that can result in death. These toxic effects include hyperthermia, hypotonic hyponatremia due to its arginine vasopressin secretagogue–like effects, rhabdomyolysis, and cardiovascular collapse. Cocaine, a serotonin-norepinephrine-dopamine reuptake inhibitor that serves as an illegal stimulant, appetite suppressant, and anesthetic, also causes vasoconstriction and rhabdomyolysis. Recent adulteration of much of the world’s supply of cocaine with levamisole, an antihelminthic agent with attributes similar to but distinct from those of cocaine, appears to have spawned a new type of ANCA-associated systemic vasculitis. This review discusses the nephrotoxic effects of these common and emerging drugs of abuse, of which both community and health care providers should become aware given their widespread abuse. Future investigation into pathogenetic mechanisms associated with these drugs is critical and may provide a window into ways to lessen and even prevent the nephrotoxic effects of these drugs of abuse and perhaps allow a deeper understanding of the nephrotoxicities themselves. PMID:25035273

  16. Extreme Conditioning Programs: Potential Benefits and Potential Risks.

    PubMed

    Knapik, Joseph J

    2015-01-01

    CrossFit, Insanity, Gym Jones, and P90X are examples of extreme conditioning programs (ECPs). ECPs typically involve high-volume and high-intensity physical activities with short rest periods between movements and use of multiple joint exercises. Data on changes in fitness with ECPs are limited to CrossFit investigations that demonstrated improvements in muscle strength, muscular endurance, aerobic fitness, and body composition. However, no study has directly compared CrossFit or other ECPs to other more traditional forms of aerobic and resistance training within the same investigation. These direct comparisons are needed to more adequately evaluate the effectiveness of ECPs. Until these studies emerge, the comparisons with available literature suggest that improvements in CrossFit, in terms of muscular endurance (push-ups, sit-ups), strength, and aerobic capacity, appear to be similar to those seen in more traditional training programs. Investigations of injuries in ECPs are limited to two observational studies that suggest that the overall injury rate is similar to that seen in other exercise programs. Several cases of rhabdomyolysis and cervical carotid artery dissections have been reported during CrossFit training. The symptoms, diagnosis, and treatment of these are reviewed here. Until more data on ECPs emerge, physical training should be aligned with US Army doctrine. If ECPs are included in exercise programs, trainers should (1) have appropriate training certifications, (2) inspect exercise equipment regularly to assure safety, (3) introduce ECPs to new participants, (4) ensure medical clearance of Soldiers with special health problems before participation in ECPs, (4) tailor ECPs to the individual Soldier, (5) adjust rest periods to optimize recovery and reduce fatigue, (6) monitor Soldiers for signs of overtraining, rhabdomyolysis, and other problems, and (7) coordinate exercise programs with other unit training activities to eliminate redundant activities and minimize the risk of overuse injuries. PMID:26360365

  17. Statin-Associated Muscular and Renal Adverse Events: Data Mining of the Public Version of the FDA Adverse Event Reporting System

    PubMed Central

    Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

    2011-01-01

    Objective Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. Methods After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Results Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Conclusions Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events. PMID:22205938

  18. Wasp sting-induced acute kidney injury

    PubMed Central

    Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Sakthirajan, Ramanathan; Shankar, Palaniselvam; Gopalakrishnan, Natarajan; Balasubramaniyan, Thoppalan

    2016-01-01

    Background Wasp stings are a common form of envenomation in tropical countries, especially in farmers. The aim of this study was to document the clinical presentation, treatment and outcomes of patients with acute kidney injury (AKI) due to multiple wasp stings in a tertiary care hospital. Methods We conducted a retrospective observational study of patients with multiple wasp stings and AKI at the Department of Nephrology between July 2011 and August 2015. The clinical features, laboratory data, treatment details and outcomes were noted. Results A total of 11 patients were included. All were from rural areas. All of them were males with age ranging from 21 to 70 years, mean age 45 ± 23 years. Six had oliguria and two had hypotension. All 11 patients had evidence of rhabdomyolysis and three also had hemolysis. Ten patients required hemodialysis with a mean number of hemodialysis sessions of 8.7 ± 2.8. Renal biopsy carried out on four patients, showed acute interstitial nephritis (AIN) in one patient, acute tubular necrosis (ATN) in two patients, and one patient had both AIN and ATN. The two patients with AIN were given steroids, while all other patients were managed with supportive measures. One patient died within 48 h of presentation due to shock. At a mean follow-up of 24 months, one had progressed to chronic kidney disease and the remaining nine had normal renal function. Conclusions Wasp sting is an occupational hazard. AKI was most commonly due to rhabdomyolysis. Early renal biopsy is indicated in those patients who do not respond to supportive measures. Timely dialysis and steroid in the case of AIN improves renal survival. PMID:26985369

  19. Nephrotoxic effects of common and emerging drugs of abuse.

    PubMed

    Pendergraft, William F; Herlitz, Leal C; Thornley-Brown, Denyse; Rosner, Mitchell; Niles, John L

    2014-11-01

    The kidneys can be injured in diverse ways by many drugs, both legal and illegal. Novel associations and descriptions of nephrotoxic effects of common and emerging drugs of abuse have appeared over the past several years. Anabolic androgenic steroids, illicitly used by athletes and others for decades to increase muscle mass and decrease body fat, are emerging as podocyte toxins given recent descriptions of severe forms of FSGS in long-term abusers. Synthetic cannabinoids, a new group of compounds with marijuana-like effects, recently became popular as recreational drugs and have been associated with an atypical form of AKI. 3,4-Methylenedioxymethamphetamine, commonly known as ecstasy, is a widely used synthetic recreational drug with mood-enhancing properties and a constellation of toxicities that can result in death. These toxic effects include hyperthermia, hypotonic hyponatremia due to its arginine vasopressin secretagogue-like effects, rhabdomyolysis, and cardiovascular collapse. Cocaine, a serotonin-norepinephrine-dopamine reuptake inhibitor that serves as an illegal stimulant, appetite suppressant, and anesthetic, also causes vasoconstriction and rhabdomyolysis. Recent adulteration of much of the world's supply of cocaine with levamisole, an antihelminthic agent with attributes similar to but distinct from those of cocaine, appears to have spawned a new type of ANCA-associated systemic vasculitis. This review discusses the nephrotoxic effects of these common and emerging drugs of abuse, of which both community and health care providers should become aware given their widespread abuse. Future investigation into pathogenetic mechanisms associated with these drugs is critical and may provide a window into ways to lessen and even prevent the nephrotoxic effects of these drugs of abuse and perhaps allow a deeper understanding of the nephrotoxicities themselves. PMID:25035273

  20. Evaluation of exertion and capture stress in serum of wild dugongs (Dugong dugon).

    PubMed

    Lanyon, Janet M; Sneath, Helen L; Long, Trevor

    2012-03-01

    Seven hundred fifty-one dugongs (Dugong dugon) were pursued, captured, and handled for up to 20 min for population sampling. Fifty of these dugongs were then removed from the water for up to 55 min for comprehensive medical examination. Fifty whole blood and separated serum samples were analyzed for potassium, sodium, chloride, creatinine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea, creatinine, glucose, anion gap, and total blood CO2. Serum biochemical variables of the dugong were compared with those obtained in previous studies of the related West Indian manatee, a mammal that does not appear to experience capture myopathy based on available data. Differences between these species included higher blood sodium and chloride in dugongs, which may reflect differences in salt balance and renal function, and higher blood lactate and CO2. Some biochemical analytes such as CK and AST, which may be indicative of rhabdomyolysis associated with capture stress myopathy (a potentially fatal condition for which dugongs have been thought to be highly susceptible) were high compared with levels previously measured in wild West Indian manatees (Trichechus latirostris). One of the 50 dugongs had marked elevations of CK and AST but showed no other clinical indications of rhabdomyolysis associated with capture myopathy such as hyperthermia. Rather, generally high levels of lactate, CK, and AST most probably reflect metabolic acidosis resulting from the exertion involved in the pursuit prior to capture. Earlier observations suggesting that dugongs were probably susceptible to capture stress myopathy (based on high serum potassium levels) were not supported by this study. Capture and handling methods currently used on dugongs in this research program do not appear to result in acute capture stress. PMID:22448507

  1. Don't be Half-Educated About Haff Disease in Louisiana.

    PubMed

    Diaz, James

    2015-01-01

    Cases of Haff disease, a syndrome of severe myalgia and rhabdomyolysis, have been reported after eating cooked fish in Europe and the US. A retrospective review of US cases was conducted to identify seafood vectors, describe presenting manifestations, and compare the Haff disease toxidrome with other seafood-borne toxidromes. Internet search engines were queried to identify all US reports of Haff disease. The case definition of Haff disease required cooked seafood ingestion history within 24 hours and markedly elevated serum creatine kinase (CK) with CK-muscle/brain (MB) fraction < 5 percent. Twenty-six cases of Haff disease were reported in the US over 30 years, 1984-2014, with spring-summer occurrences. The mean age of cases was 54.8 years without gender difference. Most cases (58 percent) followed consumption of cooked buffalo fish, Ictiobus cyprinellus, (n = 15); other cases followed consumption of boiled crayfish in Louisiana (n = 9) and baked salmon in North Carolina (n = 2). California and Louisiana accounted for most cases (n = 18, p = 0.012). Following mean incubation periods of eight hours; the most common presenting manifestations included vomiting, myalgia, muscle rigidity, chest pain mimicking myocardial infarction, diaphoresis, dyspnea, and brown urine indicating myoglobinuria. Most patients recovered within 2-5 days. Haff disease may follow the consumption of freshwater buffalo fish, freshwater crayfish, and saltwater Atlantic salmon. The bioconcentration of a new, unidentified heat-stable, freshwater and/or brackish/saltwater algal myotoxin in seafood, similar to palytoxin, is suspected of causing Haff disease. Experimental animals fed toxic buffalo fish developed rhabdomyolysis with myoglobinuria. PMID:25978748

  2. Benefit versus risk in statin treatment.

    PubMed

    Guyton, John R

    2006-04-17

    The Statin Safety Assessment Conference of the National Lipid Association (NLA), reported in this supplement to The American Journal of Cardiology, provides a comprehensive evaluation of old and new experience on adverse events associated with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins. To place these in context, one can express both the risk of side effects and the benefits for cardiovascular disease in terms of events per person-year of statin treatment. The mortality risk from fatal rhabdomyolysis is approximately 0.3 per 100,000 person-years, and the risks of nonfatal rhabdomyolysis and of putative statin-attributable peripheral neuropathy are approximately 3 and 12 events, respectively, per 100,000 person-years. Reports of acute liver failure and acute or chronic kidney disease give lower rate estimates that, even when corrected for underreporting, are approximately equal to the background rates of these conditions in the general population, lending scant support for statin-attributable etiology. In contrast, the benefit of statin use is to avert several hundred deaths and several hundred cases each of heart and brain infarction per 100,000 person-years in appropriately treated high-risk patients. Although population estimates such as these are useful, they must be translated repeatedly to individual patient-provider encounters, where clinical skill and art must combine with scientific evidence. The continued publication of individual case reports and small randomized trials among groups of patients with potential side effects should be encouraged. Statins should not be used in situations where minimal benefit is expected, as safety data and risk-benefit analysis must be meshed with guidelines that help the clinician decide whom to treat and how aggressively to treat. PMID:16581337

  3. Protective effects of L-carnitine on myoglobinuric acute renal failure in rats.

    PubMed

    Aydogdu, Nurettin; Atmaca, Gulizar; Yalcin, Omer; Taskiran, Recep; Tastekin, Ebru; Kaymak, Kadir

    2006-01-01

    1. Muscle injury (rhabdomyolysis) is one of the causes of acute renal failure (ARF). Iron, free radicals and nitric oxide (NO) play a critical role in the pathogenesis of glycerol-induced myoglobinuric ARF. L-Carnitine is an anti-oxidant and prevents the accumulation of end-products of lipid peroxidation. Therefore, the aim of the present study was to investigate the effects of L-carnitine on myoglobinuric ARF induced by intramuscular (i.m.) hypertonic glycerol injection. 2. Sprague-Dawley rats were divided into three groups. Rats in group 1 (n = 8) were given saline, whereas those in groups 2 (n = 10) and 3 (n = 10) were injected with glycerol (10 mL/kg, i.m.). Concomitant with and 24 h after glycerol injection, L-carnitine (200 mg/kg, i.p.) was administered to group 3 rats. Forty-eight hours after glycerol injection, blood samples and kidney tissues were taken from anaesthetised rats. 3. Plasma creatine kinase (CK) activity, urea, creatinine and NO levels, as well as kidney tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme activity and malondialdehyde (MDA) and glutathione (GSH) levels, were determined. In the kidney tissue, histopathological changes and iron accumulation in the tubular epithelium were also investigated. 4. Glycerol treatment caused severe ARF: a marked renal oxidative stress, significantly increased CK activity, urea and creatinine levels and decreased plasma NO levels. Histopathological findings in group 2 rats confirmed that there was renal impairment by cast formation and tubular necrosis and a marked increase in iron accumulation in the tubular epithelium. All these factors were significantly improved by L-carnitine supplementation. 5. These results may indicate that L-carnitine treatment protects against functional, biochemical and morphological damage and iron accumulation in glycerol-induced myoglobinuric ARF in rats. In this model, the protective effect of L-carnitine treatment may provide a new insight into the treatment of rhabdomyolysis-related ARF. PMID:16445710

  4. Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4

    PubMed Central

    Li, Daniel Q.; Kim, Richard; McArthur, Eric; Fleet, Jamie L.; Bailey, David G.; Juurlink, David; Shariff, Salimah Z.; Gomes, Tara; Mamdani, Muhammad; Gandhi, Sonja; Dixon, Stephanie; Garg, Amit X.

    2015-01-01

    Background: The cytochrome P450 3A4 (CYP3A4) inhibitor clarithromycin may also inhibit liver-specific organic anion–transporting polypeptides (OATP1B1 and OATP1B3). We studied whether concurrent use of clarithromycin and a statin not metabolized by CYP3A4 was associated with an increased frequency of serious adverse events. Methods: Using large health care databases, we studied a population-based cohort of older adults (mean age 74 years) who were taking a statin not metabolized by CYP3A4 (rosuvastatin [76% of prescriptions], pravastatin [21%] or fluvastatin [3%]) between 2002 and 2013 and were newly prescribed clarithromycin (n = 51 523) or azithromycin (n = 52 518), the latter an antibiotic that inhibits neither CYP3A4 nor OATP1B1 and OATP1B3. Outcomes were hospital admission with a diagnostic code for rhabdomyolysis, acute kidney injury or hyperkalemia, and all-cause mortality. All outcomes were assessed within 30 days after co-prescription. Results: Compared with the control group, patients co-prescribed clarithromycin and a statin not metabolized by CYP3A4 were at increased risk of hospital admission with acute kidney injury (adjusted relative risk [RR] 1.65, 95% confidence interval [CI] 1.31 to 2.09), admission with hyperkalemia (adjusted RR 2.17, 95% CI 1.22 to 3.86) and all-cause mortality (adjusted RR 1.43, 95% CI 1.15 to 1.76). The adjusted RR for admission with rhabdomyolysis was 2.27 (95% CI 0.86 to 5.96). The absolute increase in risk for each outcome was small and likely below 1%, even after we considered the insensitivity of some hospital database codes. Interpretation: Among older adults taking a statin not metabolized by CYP3A4, co-prescription of clarithromycin versus azithromycin was associated with a modest but statistically significant increase in the 30-day absolute risk of adverse outcomes. PMID:25534598

  5. Malignant hyperthermia

    PubMed Central

    Rosenberg, Henry; Davis, Mark; James, Danielle; Pollock, Neil; Stowell, Kathryn

    2007-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%. PMID:17456235

  6. Attenuation of Skeletal Muscle and Renal Injury to the Lower Limb following Ischemia-Reperfusion Using mPTP Inhibitor NIM-811

    PubMed Central

    Garbaisz, David; Turoczi, Zsolt; Aranyi, Peter; Fulop, Andras; Rosero, Oliver; Hermesz, Edit; Ferencz, Agnes; Lotz, Gabor; Harsanyi, Laszlo; Szijarto, Attila

    2014-01-01

    Introduction Operation on the infrarenal aorta and large arteries of the lower extremities may cause rhabdomyolysis of the skeletal muscle, which in turn may induce remote kidney injury. NIM-811 (N-metyl-4-isoleucine-cyclosporine) is a mitochondria specific drug, which can prevent ischemic-reperfusion (IR) injury, by inhibiting mitochondrial permeability transition pores (mPTP). Objectives Our aim was to reduce damages in the skeletal muscle and the kidney after IR of the lower limb with NIM-811. Materials and methods Wistar rats underwent 180 minutes of bilateral lower limb ischemia and 240 minutes of reperfusion. Four animal groups were formed called Sham (receiving vehicle and sham surgery), NIM-Sham (receiving NIM-811 and sham surgery), IR (receiving vehicle and surgery), and NIM-IR (receiving NIM-811 and surgery). Serum, urine and histological samples were taken at the end of reperfusion. NADH-tetrazolium staining, muscle Wet/Dry (W/D) ratio calculations, laser Doppler-flowmetry (LDF) and mean arterial pressure (MAP) monitoring were performed. Renal peroxynitrite concentration, serum TNF-α and IL-6 levels were measured. Results Less significant histopathological changes were observable in the NIM-IR group as compared with the IR group. Serum K+ and necroenzyme levels were significantly lower in the NIM-IR group than in the IR group (LDH: p<0.001; CK: p<0.001; K+: p = 0.017). Muscle mitochondrial viability proved to be significantly higher (p = 0.001) and renal function parameters were significantly better (creatinine: p = 0.016; FENa: p<0.001) in the NIM-IR group in comparison to the IR group. Serum TNF-α and IL-6 levels were significantly lower (TNF-α: p = 0.003, IL-6: p = 0.040) as well as W/D ratio and peroxynitrite concentration were significantly lower (p = 0.014; p<0.001) in the NIM-IR group than in the IR group. Conclusion NIM-811 could have the potential of reducing rhabdomyolysis and impairment of the kidney after lower limb IR injury. PMID:24968303

  7. Abacavir-induced fulminant hepatic failure in a HIV/HCV co-infected patient.

    PubMed

    Haas, Christopher; Ziccardi, Mary Rodriguez; Borgman, Jody

    2015-01-01

    Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen. PMID:26670894

  8. Troponin elevation after black widow spider envenomation.

    PubMed

    Bush, Sean P; Davy, J Veeran

    2015-09-01

    Black widow spider envenomation generally results in self-limiting pain that can be treated in the emergency department (ED) with analgesics and benzodiazepines, usually with no further intervention. Occasionally, a patient has to be admitted or treated with antivenom for refractory pain or a venom-induced complication. We present the case of an 84-year-old man who presented to our ED with chest pain and dyspnea after being bitten on the foot by a western black widow spider (Lactrodectus hesperus). His initial cardiac troponin I (cTnI) was elevated at 0.07 ng/ml and continued to rise to a peak of 0.17 ng/ml. He also had rhabdomyolysis, another uncommon complication of black widow envenomation. An elevated cTnI generally signifies myocardial injury and is rarely seen after black widow envenomation. We discuss the possible etiologies for an elevated cardiac biomarker, in this context, and review potentially serious complications of widow spider envenomation presenting with chest symptoms and an elevated cardiac biomarker. PMID:26206067

  9. A generalised sensation of coldness following introduction of rosuvastatin therapy.

    PubMed

    Huynh, Niem Tu; Huot, Philippe

    2014-01-01

    Rosuvastatin is the most potent 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor commercially available to lower low-density lipoprotein cholesterol. Rosuvastatin has been associated with several adverse effects, including rhabdomyolysis and arthralgias. Here, we report an unusual adverse effect occurring on treatment with rosuvastatin, a 'continuous sensation of coldness'. A 60-year-old man began experiencing this peculiar feeling shortly after introduction of rosuvastatin treatment. The gentleman had to wear extra pair of socks and cover himself with blankets while reading, even during summer with surrounding temperature above 30C. The abnormal sensation persisted for the 26?months during which he was treated with rosuvastatin, and disappeared within a week after discontinuing treatment. Physical examination, including thorough neurological examination, was entirely normal, as were haematological and biochemical parameters. While the pathophysiology of this phenomenon remains unknown, we hope that this case will encourage others to report similar symptomatology, perhaps enabling to gain more insight on the condition. PMID:25301422

  10. Myocardium and striated muscle damage caused by licit or illicit drugs.

    PubMed

    Tth, Anita Rka; Varga, Tibor

    2009-04-01

    Illicit and central nervous system active licit drug consumption related deaths are mainly the consequences of either unintentional or intentional overdose. According to the data in the relevant literature occurrences of different organ damages are also observable and this can play a role in death, as well. Organ damages may appear simultaneously with overdosing or can be extended in time, which may lead to proving the cause of death and establishing the relationships with previous medication difficult. The most frequent damage observed is rhabdomyolysis syndrome, which has been mainly described after cocaine or opium consumption. Authors present four cases from the autopsy documentation of the period between 2003 and 2008 at the Institute of Forensic Medicine, University of Szeged, Hungary in which illicit drug consumption or neuroleptic licit drug medication resulted in development of myocardium and striated muscle damage. The dominant clinical symptoms were hyperthermia, renal and circulatory failure. The laboratory tests showed renal and liver insufficiency; in addition the CK and CK-MB level increase suggested damage in striated muscles. The focal myocardium and striated muscle damage could be assessed as the cause of death in one case, but microscopic investigation proved the presence of damage in each. PMID:19342269

  11. Lipids in liver transplant recipients

    PubMed Central

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-01-01

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation.

  12. Case report: fatal poisoning with Colchicum autumnale

    PubMed Central

    Brvar, Miran; Ploj, Tom; Kozelj, Gordana; Mozina, Martin; Noc, Marko; Bunc, Matjaz

    2004-01-01

    Introduction Colchicum autumnale, commonly known as the autumn crocus, contains alkaloid colchicine with antimitotic properties. Case report A 76-year-old man with a history of alcoholic liver disease and renal insufficiency, who mistakenly ingested Colchicum autumnale instead of wild garlic (Aliium ursinum), presented with nausea, vomiting and diarrhea 12 hours after ingestion. On admission the patient had laboratory signs of dehydration. On the second day the patient became somnolent and developed respiratory insufficiency. The echocardiogram showed heart dilatation with diffuse hypokinesia with positive troponin I. The respiratory insufficiency was further deteriorated by pneumonia, confirmed by chest X-ray and later on by autopsy. Laboratory tests also revealed rhabdomyolysis, coagulopathy and deterioration of renal function and hepatic function. The toxicological analysis disclosed colchicine in the patient's urine (6 ?g/l) and serum (9 ?g/l) on the second day. Therapy was supportive with hydration, vasopressors, mechanical ventilation and antibiotics. On the third day the patient died due to asystolic cardiac arrest. Discussion and conclusion Colchicine poisoning should be considered in patients with gastroenterocolitis after a meal of wild plants. Management includes only intensive support therapy. A more severe clinical presentation should be expected in patients with pre-existing liver and renal diseases. The main reasons for death are cardiovascular collapse, respiratory failure and leukopenia with infection. PMID:14975056

  13. Long-term efficacy and safety of raltegravir in the management of HIV infection

    PubMed Central

    Liedtke, Michelle D; Tomlin, C Ryan; Lockhart, Staci M; Miller, Misty M; Rathbun, R Chris

    2014-01-01

    Raltegravir is an integrase strand-transfer inhibitor approved for the treatment of HIV infection. It was the first medication in a novel class of antiretroviral agents to be approved for use in the United States in 2007. Raltegravir exhibits potent activity against wild-type HIV-1, but resistance development has been noted through three different pathways. It is metabolized primarily through uridine diphosphate glucuronosyltransferase 1A1 and has a single inactive glucuronide metabolite. Raltegravir is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes and exhibits low potential for drugdrug interactions; however, strong uridine diphosphate glucuronosyltransferase 1A1 inhibitors or inducers can alter the pharmacokinetics of raltegravir. It is well tolerated, and the most commonly reported adverse effects include headache, nausea, and diarrhea. Serious adverse effects with raltegravir are rare but include rhabdomyolysis and severe skin and hypersensitivity reactions. It has been approved for use in both treatment-nave and treatment-experienced patients and is a preferred first-line agent in both United States and European HIV treatment guidelines. Although initial approval was granted on 48-week data, 5-year clinical data have recently been published. This article reviews the data supporting long-term efficacy and safety of raltegravir in the treatment of HIV infection. PMID:24672249

  14. Muscular damage during telbivudine treatment in a chronic hepatitis B patient.

    PubMed

    Caroleo, Benedetto; Galasso, Olimpio; Staltari, Orietta; Giofrè, Chiara; De Sarro, Giovambattista; Guadagnino, Vincenzo; Gallelli, Luca

    2011-04-01

    Muscle tissue damage might be related to metabolic and mechanical factors. Certain drugs have been associated with increased blood levels of creatin phospho kinase (CPK) and myoglobin that are biochemical markers of musculoskeletal damage. An increase of CPK plasma levels might suggest severe rhabdomyolysis with possible resulting renal failure. Telbivudine is an antiviral drug indicated for the treatment of chronic hepatitis B (CHB) in adult patients. An increase in CPK plasma levels has been recently described in some telbivudine-treated CHB patients without muscle-skeletal symptoms. In this paper we report a CHB patient that developed a severe increase of CPK plasma levels during telbivudine-treatment. Pharmacological evaluation, using the Naranjo probability scale, indicated a probable relationship between telbivudine and CPK increase, so telbivudine was discontinued and replaced with entecavir with a complete resolution of laboratory findings. In conclusion, telbivudine treatment can induce muscular damage in the absence of skeletal injury, therefore we suggest to closely monitor the muscular function of the patients treated with this drug in order to prevent possible major complications. PMID:23738248

  15. Biomarkers of multiorgan injury in a preclinical model of exertional heat stroke.

    PubMed

    King, Michelle A; Leon, Lisa R; Mustico, Danielle L; Haines, Joel M; Clanton, Thomas L

    2015-05-15

    It is likely that the pathophysiology of exertional heat stroke (EHS) differs from passive heat stroke (PHS), but this has been difficult to verify experimentally. C57Bl/6 mice were instrumented with temperature transponders and underwent 3 wk of training using voluntary and forced running wheels. An EHS group was exposed to environmental temperatures (Tenv) of 37.5, 38.5, or 39.5°C at either 30, 50, or 90% relative humidities (RH) while exercising on a forced running wheel. Results were compared with sham-matched exercise controls (EXC) and naïve controls (NC). In EHS, mice exercised in heat until they reached limiting neurological symptoms (loss of consciousness). The symptom-limited maximum core temperatures achieved were between 42.1 and 42.5°C at 50% RH. All mice that were followed for 4 days survived. Additional groups were killed at 0.5, 3, 24, and 96 h, post-EHS or -EXC. Histopathology revealed extensive damage in all regions of the small intestine, liver, and kidney. Plasma creatine kinase, blood urea nitrogen, alanine transaminase, and intestinal fatty acid binding protein-2 were significantly elevated compared with matched EXC and NC, suggesting multiple organ injury to striated muscle, kidney, liver, and intestine, respectively. EHS mice were hypoglycemic immediately following EHS but exhibited sustained hyperglycemia through 4 days. The results demonstrate unique features of survivable EHS in the mouse that included loss of consciousness, extensive organ injury, and rhabdomyolysis. PMID:25814640

  16. Asystolic Cardiac Arrest of Unknown Duration in Profound Hypothermia and Polysubstance Overdose: A Case Report of Complete Recovery

    PubMed Central

    Lubana, Sandeep Singh; Genin, Dennis Iilya; Singh, Navdeep; De La Cruz, Angel

    2015-01-01

    Patient: Male, 20 Final Diagnosis: Asystolic cardiac arrest in profound hypothermia and poly-substance overdose Symptoms: Cardiac arrest cardiac arrhythmia Medication: Clinical Procedure: Endotracheal intubation hemodialysis Specialty: Critical Care Medicine Objective: Unusual clinical course Background: Opioid addiction and overdose is a serious problem worldwide. Fatal overdoses from opioids are responsible for numerous deaths and are increasing, especially if taken in combination with other psychoactive substances. Combined with environmental exposure, opioid overdose can cause profound hypothermia. Opioid abuse and other drugs of abuse impair thermoregulation, leading to severe hypothermia. Both drug overdose and severe hypothermia can cause cardiac arrest. Case Report: We report a case of 20-year-old man with history of polysubstance abuse presenting with severe hypothermia and asystole of unknown duration with return of spontaneous circulation (ROSC) achieved after 28 minutes of cardiopulmonary resuscitation (CPR). Urine toxicology was positive for cocaine, heroin, and benzodiazepine, along with positive blood alcohol level. The patient was rewarmed using non-invasive techniques. Hospital course was complicated by acute renal failure (ARF), severe rhabdomyolysis, severe hyperkalemia, ST-elevation myocardial infarction (STEMI), shock liver, coagulopathy, and aspiration pneumonia. Conclusions: Survival with full cardiovascular and neurologic recovery after a cardiac arrest caused by drug overdose in the setting of severe hypothermia is still possible, even if the cardiac arrest is of unknown or prolonged duration. Patients with severe hypothermia experiencing cardiac arrest/hemodynamic instability can be rewarmed using non-invasive methods and may not necessarily need invasive rewarming techniques. PMID:26054008

  17. Acute cerebellar dysfunction with neuromuscular manifestations after scorpionism presumably caused by Tityus obscurus in Santarém, Pará / Brazil.

    PubMed

    Torrez, Pasesa P Q; Quiroga, Mariana M M; Abati, Paulo A M; Mascheretti, Melissa; Costa, Walter Silva; Campos, Luciana P; França, Francisco O S

    2015-03-01

    Scorpionism is a public health problem in many tropical countries, especially in North Africa, South India, Latin America and the Middle East. In Brazil, patients with severe scorpion envenoming have mainly cardiovascular events, including acute heart failure, acute respiratory distress syndrome and shock, death is rare. We described 58 accidents presumably caused by Tityus obscurus in Brazilian Amazonia. Patients reported a sensation of "electric shocks" which could last hours. The vast majority of patients presented a clinical picture compatible with acute cerebellar dysfunction, beginning minutes and lasting up to 2 days after the accident. They presented cerebellar ataxia, dysdiadochokinesia, dysmetry, dysarthria, dyslalia, nausea and vomiting. Besides, some patients presented myoclonus and fasciculation which can also be attributed to cerebellar dysfunction or maybe the result of direct action on skeletal muscle. Two patients had evidence of intense rhabdomyolysis and acute kidney injury. The clinical picture in this scorpion envenoming is mainly characterized by an acute dysfunction of cerebellar activities and abnormal neuromuscular manifestations and in some cases muscle injury which are not described in any other region of the world. This work presents clinical, epidemiologic, laboratory and treatment aspects of this unmatched scorpion envenoming in the state of Pará, northern Brazil. PMID:25549940

  18. Statin safety: an appraisal from the adverse event reporting system.

    PubMed

    Davidson, Michael H; Clark, John A; Glass, Lucas M; Kanumalla, Anju

    2006-04-17

    The adverse event (AE) profiles of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) agents are of great interest, in particular the most recently approved statin, rosuvastatin. The forwarding of reports of AEs has been shown to be influenced by several reporting biases, including secular trend, the new drug reporting effect, product withdrawals, and publicity. Comparative assessments that use AE reporting rates are difficult to interpret under these circumstances, because such effects can themselves lead to marked increases in AE reporting. Consequently, many comparative reporting rate analyses are best carried out in conjunction with other metrics that put reporting burden into context, such as report proportion. All-AE reporting rates showed a temporal profile that resembled those of other statins when marketing cycle and secular trend were taken into account. A before-and-after cerivastatin withdrawal comparison showed a substantial increase in the reporting of AEs of interest for the statin class overall. Report proportion analyses indicated that the burden of rosuvastatin-associated AEs was similar to that for other statin agents. Analyses of monthly reporting rates showed that the reporting of rosuvastatin-associated rhabdomyolysis and renal failure have increased following AE-specific mass media publicity. Postrosuvastatin AE reporting patterns were comparable to those seen with other statins and did not resemble cerivastatin. PMID:16581327

  19. Muscle strength, motor performance, cardiac and muscle biomarkers in detection of muscle side effects during and after acute lymphoblastic leukemia treatment in children.

    PubMed

    Akyay, Arzu; Olcay, Lale; Sezer, Nebahat; Atay Snmez, i?dem

    2014-11-01

    Muscle side effects have not been frequently assessed in childhood acute lymphoblastic leukemia (ALL) patients. Our objective was to determine the early and late muscle side effects during childhood ALL treatment. To this end, we examined the early muscle side effects in 15 newly diagnosed "therapy patients" (group I), and the late side effects in 18 ALL survivors "off therapy patients" (group II). Muscle side effects were assessed by measuring hand grip strength (HGS), the "timed up and go" (TUG) test, creatine phosphokinase, myoglobin, plasma electrolytes, cardiac troponin I before and after induction chemotherapy in group I. The same parameters and cranial radiotherapy dose were examined in group II at a single timepoint. Cumulative doses of chemotherapy were calculated, and echocardiograms were obtained for each group. As a result, we found that the HGS and TUG measures of group I at the end of induction were poorer than measures of the first admission, control subjects, and group II. Low HGS measures had been normalized over time, but the TUG measures remained poor. Overt rhabdomyolysis and pyomyositis were not detected in any of the patients. These results suggested that muscle side effect monitoring might be helpful in the follow-up of children with ALL. PMID:25330012

  20. Acute multiple focal neuropathies and delayed postanoxic encephalopathy after alcohol intoxication

    PubMed Central

    Wang, Wei-Che; Yang, Hsiu-Chun; Chen, Yao-Jen

    2015-01-01

    Acute-onset alcohol-associated neuropathy is only occasionally reported, and delayed postanoxic encephalopathy is rare. Here, we report a male who developed acute multiple focal neuropathies and later delayed postanoxic encephalopathy after alcohol intoxication. He had hypoxia and rhabdomyolysis, presenting with acute renal failure initially, and cardiopulmonary support, including mechanical ventilation, led to improvement of the patient at the acute stage. He suffered from bilateral hand numbness and mild weakness of the right lower limb thereafter. Nerve-conduction study revealed no pickup of compound muscle action potential or sensory nerve action potential in the bilateral ulnar nerve, but showed attenuated amplitude of compound muscle action potential in the right femoral nerve. Multiple focal neuropathies were suspected, and he received outpatient rehabilitation after being discharged. However, the patient developed gradual onset of weakness in four limbs and cognitive impairment 23 days after the hypoxia event. Brain computed tomography showed low attenuation over bilateral globus pallidus, and brain magnetic resonance imaging disclosed diffuse increased signal intensity on T2-weighted images and fluid-attenuated inversion recovery in bilateral white matter. He was admitted again under the impression of delayed postanoxic brain injury. Supportive treatment and active rehabilitation were given. He had gradual improvement in motor and functional status after rehabilitation. He could walk with festinating gait under supervision, and needed only minimal assistance in performing activities of daily living approximately 1 year later. PMID:26229472

  1. Increased inflammation and decreased insulin sensitivity indicate metabolic disturbances in zoo-managed compared to free-ranging black rhinoceros (Diceros bicornis).

    PubMed

    Schook, Mandi W; Wildt, David E; Raghanti, Mary Ann; Wolfe, Barbara A; Dennis, Patricia M

    2015-01-01

    Black rhinoceros (rhinos) living in zoos express a host of unusual disease syndromes that are associated with increased morbidity and mortality, including hemolytic anemia, rhabdomyolysis, hepatopathy and ulcerative skin disease, hypophosphatemia and iron overload. We hypothesized that iron overload is a consequence and indicator of disturbances related to inflammation and insulin/glucose metabolism. The objectives of this study were to: (1) generate the first baseline information on biomarkers of inflammation (tumor necrosis factor alpha [TNF?], serum amyloid A [SAA]), insulin sensitivity (insulin, glucose and proxy calculations of insulin sensitivity), phosphate and iron stores (ferritin) using banked serum from free-ranging black rhinos; and (2) then compare serum biomarkers between zoo-managed (n=86 individuals) and free-ranging (n=120) animals. Enzyme immunoassays were validated for serum and then biomarker levels analyzed using mixed models while controlling for sex, age and year of sample collection. Concentrations of TNF?, SAA, insulin and insulin-to glucose ratio were higher (P<0.05) in black rhinos managed in ex situ conditions compared to free-living counterparts. Findings indicate that the captive environment is contributing to increased inflammation and decreased insulin sensitivity in this endangered species. PMID:25980685

  2. Changes in urine composition after trauma facilitate bacterial growth

    PubMed Central

    2012-01-01

    Background Critically ill patients including trauma patients are at high risk of urinary tract infection (UTI). The composition of urine in trauma patients may be modified due to inflammation, systemic stress, rhabdomyolysis, life support treatment and/or urinary catheter insertion. Methods Prospective, single-centre, observational study conducted in patients with severe trauma and without a history of UTIs or recent antibiotic treatment. The 24-hour urine samples were collected on the first and the fifth days and the growth of Escherichia coli in urine from patients and healthy volunteers was compared. Biochemical and hormonal modifications in urine that could potentially influence bacterial growth were explored. Results Growth of E. coli in urine from trauma patients was significantly higher on days 1 and 5 than in urine of healthy volunteers. Several significant modifications of urine composition could explain these findings. On days 1 and 5, trauma patients had an increase in glycosuria, in urine iron concentration, and in the concentrations of several amino acids compared to healthy volunteers. On day 1, the urinary osmotic pressure was significantly lower than for healthy volunteers. Conclusion We showed that urine of trauma patients facilitated growth of E. coli when compared to urine from healthy volunteers. This effect was present in the first 24 hours and until at least the fifth day after trauma. This phenomenon may be involved in the pathophysiology of UTIs in trauma patients. Further studies are required to define the exact causes of such modifications. PMID:23194649

  3. Anesthetic- and heat-induced sudden death in calsequestrin-1-knockout mice.

    PubMed

    Dainese, Marco; Quarta, Marco; Lyfenko, Alla D; Paolini, Cecilia; Canato, Marta; Reggiani, Carlo; Dirksen, Robert T; Protasi, Feliciano

    2009-06-01

    Calsequestrin-1 (CASQ1) is a moderate-affinity, high-capacity Ca(2+)-binding protein in the sarcoplasmic reticulum (SR) terminal cisternae of skeletal muscle. CASQ1 functions as both a Ca(2+)-binding protein and a luminal regulator of ryanodine receptor (RYR1)-mediated Ca(2+) release. Mice lacking skeletal CASQ1 are viable but exhibit reduced levels of releasable Ca(2+) and altered contractile properties. Here we report that CASQ1-null mice exhibit increased spontaneous mortality and susceptibility to heat- and anesthetic-induced sudden death. Exposure of CASQ1-null mice to either 2% halothane or heat stress triggers lethal episodes characterized by whole-body contractures, elevated core temperature, and severe rhabdomyolysis, which are prevented by prior dantrolene administration. The characteristics of these events are remarkably similar to analogous episodes observed in humans with malignant hyperthermia (MH) and animal models of MH and environmental heat stroke (EHS). In vitro studies indicate that CASQ1-null muscle exhibits increased contractile sensitivity to temperature and caffeine, temperature-dependent increases in resting Ca(2+), and an increase in the magnitude of depolarization-induced Ca(2+) release. These results demonstrate that CASQ1 deficiency alters proper control of RYR1 function and suggest CASQ1 as a potential candidate gene for linkage analysis in families with MH/EHS where mutations in the RYR1 gene are excluded. PMID:19237502

  4. Pharmacokinetics and metabolism of dantrolene in horses.

    PubMed

    DiMaio Knych, H K; Arthur, R M; Taylor, A; Moeller, B C; Stanley, S D

    2011-06-01

    Dantrolene is a skeletal muscle relaxant used commonly in performance horses to prevent exertional rhabdomyolysis. The goal of the study reported here was to begin to characterize cytochrome P450-mediated metabolism of dantrolene in the horse and describe the pharmacokinetics of the compound, formulated as a capsule or a compounded paste formulation, following oral administration. Dantrolene is rapidly metabolized to 5-hydroxydantrolene both in vivo and in vitro. Preliminary work with equine liver microsomes suggest that two enzymes are responsible for the metabolism of dantrolene, as evidenced by two distinct K(m) values, one at high and one at low substrate concentrations. For the pharmacokinetic portion of the study, a randomized, balanced 2-way crossover design was employed wherein eight healthy horses received a single oral dose of either capsules or paste followed by a 4 week washout period prior to administration of the second formulation to the same horse. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 96 h postdrug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry and data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentrations were 28.9 21.6 and 37.8 12.8 ng/mL for capsules and paste, respectively and occurred at 3.8 h for both formulations. Dantrolene and its major metabolite were both below the limit of detection in both plasma and urine by 168 h postadministration. PMID:21492188

  5. Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose.

    PubMed

    Wu, Ming-Ling; Deng, Jou-Fang

    2011-01-01

    Both moclobemide and fluoxetine are used in the treatment of depression, and have been shown to produce fewer side effects than conventional tricyclic antidepressants. A combination of moclobemide and fluoxetine has been used in refractory depression, however there is potential for severe serotonin toxicity. We describe a lethal case of serotonin toxicity in a 36 year-old woman after she ingested multiple drugs, including moclobemide 4500 mg, fluoxetine 200 mg, propranolol 300 mg and several benzodiazepines. The clinical features included coma, mydriasis, hyperthermia, tremor, hyperreflexia, rhabdomyolysis, renal failure and respiratory insufficiency. Eventually, the patient died of disseminated intravascular coagulation and circulatory collapse at 22.5 h postingestion. Toxicological analysis of the patient's blood confirmed high levels of moclobemide 150 μg/mL (therapeutic 1-3 μg/mL), fluoxetine 3750 ng/mL (therapeutic 47-469 ng/mL) and several benzodiazepines. In conclusion, a combination of moclobemide and fluoxetine should be avoided in depressed patients with high suicidal tendencies. Moreover, early recognition and aggressive intervention are the mainstays in the management of potentially life-threatening serotonin toxicity. PMID:22196068

  6. Malignant hyperthermia.

    PubMed Central

    Ben Abraham, R.; Adnet, P.; Glauber, V.; Perel, A.

    1998-01-01

    Malignant hyperthermia is a rare autosomal dominant trait that predisposes affected individuals to great danger when exposed to certain anaesthetic triggering agents (such as potent volatile anaesthetics and succinylcholine). A sudden hypermetabolic reaction in skeletal muscle leading to hyperthermia and massive rhabdomyolysis can occur. The ultimate treatment is dantrolene sodium a nonspecific muscle relaxant. Certain precautions should be taken before anaesthesia of patients known to be susceptible to malignant hyperthermia. These include the prohibition of the use of triggering agents, monitoring of central body temperature and expired CO2, and immediate availability of dantrolene. In addition, careful cleansing of the anaesthesia machine of vapours of halogenated agents is recommended. If these measures are taken, the chances of an MH episode are greatly reduced. When malignant hyperthermia-does occur in the operating room, prompt recognition and treatment usually prevent a potentially fatal outcome. The most reliable test to establish susceptibility to malignant hyperthermia is currently the in vitro caffeine-halothane contracture test. It is hoped that in the future a genetic test will be available. PMID:9538480

  7. RYR1-related congenital myopathy with fatigable weakness, responding to pyridostigimine.

    PubMed

    Illingworth, M A; Main, M; Pitt, M; Feng, L; Sewry, C A; Gunny, R; Vorstman, E; Beeson, D; Manzur, A; Muntoni, F; Robb, S A

    2014-08-01

    The spectrum of RYR1 mutation associated disease encompasses congenital myopathies, exercise induced rhabdomyolysis, malignant hyperthermia susceptibility and King-Denborough syndrome. We report the clinical phenotype of two siblings who presented in infancy with hypotonia and striking fatigable ptosis. Their response to pyridostigimine was striking, but genetic screening for congenital myasthenic syndromes was negative, prompting further evaluation. Muscle MRI was abnormal with a selective pattern of involvement evocative of RYR1-related myopathy. This directed sequencing of the RYR1 gene, which revealed two heterozygous c.6721C>T (p.Arg2241X) nonsense mutations and novel c.8888T>C (p.Leu2963Pro) mutations in both siblings. These cases broaden the RYR1-related disease spectrum to include a myasthenic-like phenotype, including partial response to pyridostigimine. RYR1-related myopathy should be considered in the presence of fatigable weakness especially if muscle imaging demonstrates structural abnormalities. Single fibre electromyography can also be helpful in cases like this. PMID:24951453

  8. Risk identification and possible countermeasures for muscle adverse effects during statin therapy.

    PubMed

    Magni, Paolo; Macchi, Chiara; Morlotti, Beatrice; Sirtori, Cesare R; Ruscica, Massimiliano

    2015-03-01

    The use of statins for cardiovascular disease prevention is clearly supported by clinical evidence. However, in January 2014 the U.S. Food and Drug Administration released an advice on statin risk reporting that "statin benefit is indisputable, but they need to be taken with care and knowledge of their side effects". Among them the by far most common complication is myopathy, ranging from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. This class side effect appears to be dose dependent, with more lipophilic statin (i.e., simvastatin) carrying a higher overall risk. Hence, to minimize statin-associated myopathy, clinicians should take into consideration a series of factors that potentially increase this risk (i.e., drug-drug interactions, female gender, advanced age, diabetes mellitus, hypothyroidism and vitamin D deficiency). Whenever it is appropriate to stop statin treatment, the recommendations are to stay off statin until resolution of symptoms or normalization of creatine kinase values. Afterwards, clinicians have several options to treat dyslipidemia, including the use of a lower dose of the same statin, intermittent non-daily dosing of statin, initiation of a different statin, alone or in combination with nonstatin lipid-lowering agents, and substitution with red yeast rice. PMID:25640999

  9. Proximal Tibia Medial Biplanar Retrotubercle Open Wedge Osteotomy for Varus Knees with Medial Gonarthrosis

    PubMed Central

    Trkmen, ?smail; Esenkaya, ?rfan; nay, Koray; Trkmensoy, Fatih; zkut, Af?ar Timuin

    2014-01-01

    Objectives: The purpose of this study is to evaluate the early results of proximal tibia medial biplanar retrotubercle open wedge osteotomy for varus gonarthrosis and compare the results with the literatre. Methods: The results of proximal tibia medial biplanar retrotubercle open wedge osteotomy for 23 knees of 22 patients with medial gonarthrosis were evaluated clinically and radiologically. Results: Twenty of the patients were female and two were male. Mean age of the patients was 56.24; mean boy mass index was 31.95 and preoperative HSS (Hospital for Special Surgery) score was 68.7. Mean tibiofemoral axis was 186.39 and mean Insall-Salvatti index value was 1.04 preoperatively. Mean follow up period was 30.19 months. Mean HSS score was 86.48, femorotibial anatomic axis angle was 175 and Insall-Salvati index value 1.06 during the last follow-up. The improvement of the HSS score and the femorotibial anatomic axis angle was statistically significant. However, the change in Insall Salvati index values was statistically insignificant. Nonfatal pulmonary embolus in 1 patient, and deep vein thrombosis that occured one year after the procedure in 1 patient, rhabdomyolysis in 1 patient and loss of correction (relapse) in 1 patient were encountered as complications. Conclusion: Our results show that proximal tibia medial biplanar retrotubercle open wedge osteotomy improves the frontal and sagittal plane deformities without changing the patellar tendon length. Hence, possible patellofemoral problems are prevented and the clinical results are improved.

  10. Clinical and public health assessment of benefits and risks of statins in primary prevention of coronary events: Resolved and unresolved issues

    PubMed Central

    Moride, Yola; Hegele, Robert A; Langer, Anatoly; McPherson, Ruth; Miller, David B; Rinfret, Stéphane

    2008-01-01

    Peer-reviewed, evidence-based recommendations for statin use in primary prevention of cardiovascular events are limited. A narrative review of published randomized controlled trials and meta-analyses was conducted to critically appraise the benefits and risks of statins in primary prevention. Statins effectively reduce plasma concentrations of low-density lipoprotein cholesterol, and reduce the risk of cardiovascular events and death. The greatest benefits are observed in high-risk subjects, such as patients with diabetes or hypertension. Serious cardiovascular events should not be included among serious adverse events because they are efficacy outcomes and are dependent on the baseline risk of patients. Rates of specific serious adverse events, such as cancer and rhabdomyolysis, seem to be similar between the statin and control arms of the clinical trials examined. Thus, the benefits of statins in primary prevention outweigh the risks, particularly among high-risk patients. However, the benefit-risk ratio would likely be optimized through interventions designed to increase persistence and adherence in a real-life setting. PMID:18401470

  11. Management of heatstroke and heat exhaustion.

    PubMed

    Glazer, James L

    2005-06-01

    Heat exhaustion and heatstroke are part of a continuum of heat-related illness. Both are common and preventable conditions affecting diverse patients. Recent research has identified a cascade of inflammatory pathologic events that begins with mild heat exhaustion and, if uninterrupted, can lead eventually to multiorgan failure and death. Heat exhaustion is characterized by nonspecific symptoms such as malaise, headache, and nausea. Treatment involves monitoring the patient in a cool, shady environment and ensuring adequate hydration. Untreated heat exhaustion can progress to heatstroke, a much more serious illness involving central nervous system dysfunction such as delirium and coma. Other systemic effects, including rhabdomyolysis, hepatic failure, arrhythmias, disseminated intravascular coagulation, and even death, are not uncommon. Prompt recognition and immediate cooling through evaporation or full-body ice-water immersion are crucial. Physicians also must monitor electrolyte abnormalities, be alert to signs of renal or hepatic failure, and replace fluids in patients with heatstroke. Most experts believe that physicians and public health officials should focus greater attention on prevention. Programs involving identification of vulnerable individuals, dissemination of information about dangerous heat waves, and use of heat shelters may help prevent heat-related illness. These preventive measures, when paired with astute recognition of the early signs of heat-related illness, can allow physicians in the ambulatory setting to avert much of the morbidity and mortality associated with heat exhaustion and heatstroke. PMID:15952443

  12. Accidental carbon monoxide poisoning presenting without a history of exposure: A case report

    PubMed Central

    Bennetto, Luke; Powter, Louise; Scolding, Neil J

    2008-01-01

    Introduction Carbon monoxide poisoning is easy to diagnose when there is a history of exposure. When the exposure history is absent, or delayed, the diagnosis is more difficult and relies on recognising the importance of multi-system disease. We present a case of accidental carbon monoxide poisoning. Case presentation A middle-aged man, who lived alone in his mobile home was found by friends in a confused, incontinent state. Initial signs included respiratory failure, cardiac ischaemia, hypotension, encephalopathy and a rash, whilst subsequent features included rhabdomyolysis, renal failure, amnesia, dysarthria, parkinsonism, peripheral neuropathy, supranuclear gaze palsy and cerebral haemorrhage. Despite numerous investigations including magnetic resonance cerebral imaging, lumbar puncture, skin biopsy, muscle biopsy and electroencephalogram a diagnosis remained elusive. Several weeks after admission, diagnostic breakthrough was achieved when the gradual resolution of the patient's amnesia, encephalopathy and dysarthria allowed an accurate history to be taken for the first time. The patient's last recollection was turning on his gas heating for the first time since the spring. A gas heating engineer found the patient's gas boiler to be in a dangerous state of disrepair and it was immediately decommissioned. Conclusion This case highlights several important issues: the bewildering myriad of clinical features of carbon monoxide poisoning, the importance of making the diagnosis even at a late stage and preventing the patient's return to a potentially fatal toxic environment, and the paramount importance of the history in the diagnostic method. PMID:18430228

  13. Poisoning with over-the-counter doxylamine preparations: an evaluation of 109 cases.

    PubMed

    Kppel, C; Tenczer, J; Ibe, K

    1987-09-01

    One hundred and nine cases of monointoxication with doxylamine were evaluated with respect to age distribution, amount ingested, plasma level, and clinical symptomatology. The age of 60% of the patients ranged between 16 and 30 years. In about 60% of the cases 10 to 40 times a single therapeutic dose (25 mg) was ingested. Doxylamine plasma concentrations exceeded the maximum plasma level after a therapeutic dose by a factor of 10 to 40 in two-thirds of cases. The most frequent symptoms included impaired consciousness, seizures, tachycardia, mydriasis and a 'psychosis' similar to that in catatonic stupor. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. No symptoms were observed in 39% of the patients. No correlation was found between the amount ingested or doxylamine plasma level and the clinical symptomatology. Primary detoxication included gastric lavage, administration of activated charcoal and sodium sulfate. Regarding the high frequency of doxylamine overdose and its possible complications the question arises as to whether doxylamine-containing preparations should be subjected to prescription. PMID:3679242

  14. Envenomations by Bothrops and Crotalus snakes induce the release of mitochondrial alarmins.

    PubMed

    Zornetta, Irene; Caccin, Paola; Fernandez, Julin; Lomonte, Bruno; Gutierrez, Jos Mara; Montecucco, Cesare

    2012-01-01

    Skeletal muscle necrosis is a common manifestation of viperid snakebite envenomations. Venoms from snakes of the genus Bothrops, such as that of B. asper, induce muscle tissue damage at the site of venom injection, provoking severe local pathology which often results in permanent sequelae. In contrast, the venom of the South American rattlesnake Crotalus durissus terrificus, induces a clinical picture of systemic myotoxicity, i.e., rhabdomyolysis, together with neurotoxicity. It is known that molecules released from damaged muscle might act as 'danger' signals. These are known as 'alarmins', and contribute to the inflammatory reaction by activating the innate immune system. Here we show that the venoms of B. asper and C. d. terrificus release the mitochondrial markers mtDNA (from the matrix) and cytochrome c (Cyt c) from the intermembrane space, from ex vivo mouse tibialis anterior muscles. Cyt c was released to a similar extent by the two venoms whereas B. asper venom induced the release of higher amounts of mtDNA, thus reflecting hitherto some differences in their pathological action on muscle mitochondria. At variance, injection of these venoms in mice resulted in a different time-course of mtDNA release, with B. asper venom inducing an early onset increment in plasma levels and C. d. terrificus venom provoking a delayed release. We suggest that the release of mitochondrial 'alarmins' might contribute to the local and systemic inflammatory events characteristic of snakebite envenomations. PMID:22363828

  15. Rare complications of pediatric diabetic ketoacidosis

    PubMed Central

    Bialo, Shara R; Agrawal, Sungeeta; Boney, Charlotte M; Quintos, Jose Bernardo

    2015-01-01

    The incidence of type 1 diabetes (T1D) among youth is steadily increasing across the world. Up to a third of pediatric patients with T1D present with diabetic ketoacidosis, a diagnosis that continues to be the leading cause of death in this population. Cerebral edema is the most common rare complication of diabetic ketoacidosis in children. Accordingly, treatment and outcome measures of cerebral edema are vastly researched and the pathophysiology is recently the subject of much debate. Nevertheless, cerebral edema is not the only sequela of diabetic ketoacidosis that warrants close monitoring. The medical literature details various other complications in children with diabetic ketoacidosis, including hypercoagulability leading to stroke and deep vein thrombosis, rhabdomyolysis, pulmonary and gastrointestinal complications, and long-term memory dysfunction. We review the pathophysiology, reported cases, management, and outcomes of each of these rare complications in children. As the incidence of T1D continues to rise, practitioners will care for an increasing number of pediatric patients with diabetic ketoacidosis and should be aware of the various systems that may be affected in both the acute and chronic setting. PMID:25685287

  16. Mortality due to a retained circle hook in a longfin mako shark Isurus paucus (Guitart-Manday).

    PubMed

    Adams, D H; Borucinska, J D; Maillett, K; Whitburn, K; Sander, T E

    2015-07-01

    A female longfin mako shark Isurus paucus (Guitart-Manday, 1966) was found moribund on the Atlantic Ocean beach near Canaveral National Seashore, Florida; the shark died shortly after stranding. Macroscopic lesions included a partially healed bite mark on the left pectoral fin, a clefted snout, pericardial effusion and a pericardial mass surrounding a 12/0 circle fishing hook. The heart, pericardial mass, gills, ovary, oviduct, shell gland, epigonal organ, liver, kidney and intrarenal and interrenal glands were processed for histopathology and examined by brightfield microscopy. Microscopic examination revealed chronic proliferative and pyogranulomatous pericarditis and myocarditis with rhabdomyolysis, fibrosis and thrombosis; scant bacteria and multifocal granular deposits of iron were found intralesionally. In addition, acute, multifocal infarcts within the epigonal organ and gill filaments were found in association with emboli formed by necrocellular material. The ovary had high numbers of atretic follicles, and the liver had diffuse, severe hepatocellular degeneration, multifocal spongiosis and moderate numbers of melanomacrophage cells. This report provides evidence of direct mortality due to systemic lesions associated with retained fishing gear in a prohibited shark species. Due to the large numbers of sharks released from both recreational and commercial fisheries worldwide, impact of delayed post-release mortality on shark populations is an important consideration. PMID:24974904

  17. Proximal myopathy with focal depletion of mitochondria and megaconial congenital muscular dystrophy are allelic conditions caused by mutations in CHKB.

    PubMed

    Brady, L; Giri, M; Provias, J; Hoffman, E; Tarnopolsky, M

    2016-02-01

    We recently evaluated two of the original three patients (siblings) diagnosed with Proximal Myopathy with Focal Depletion of Mitochondria. The condition was named for the distinctive pattern of enlarged mitochondria around the periphery of muscle fibres with a complete absence in the middle. These siblings, aged 37 and 40, are cognitively normal with mild non-progressive muscle weakness and a susceptibility to rhabdomyolysis. Both were shown to be compound heterozygotes for novel mutations (c.263C>T?+?c.950T>A) in CHKB, the gene currently associated with Megaconial Congenital Muscular Dystrophy. Individuals with this condition have early-onset muscle weakness and profound intellectual disability but share the same unique pattern on muscle biopsy as was noted in Proximal Myopathy with Focal Depletion of Mitochondria; focal depletion of mitochondria was surrounded by abnormally large "megaconial" mitochondria. Thus the phenotypic spectrum of CHKB mutations ranges from a congenital muscular dystrophy with intellectual disability to a later-onset non-progressive muscular weakness with normal cognition. PMID:26782016

  18. Molecular mechanisms of crystal-related kidney inflammation and injury. Implications for cholesterol embolism, crystalline nephropathies and kidney stone disease.

    PubMed

    Mulay, Shrikant R; Evan, Andrew; Anders, Hans-Joachim

    2014-03-01

    Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. While decades of research have focused on the molecular mechanisms of solute supersaturation and crystal formation, the pathomechanisms of crystal-induced renal inflammation remain largely unknown. The recent discovery of the intracellular NLRP3 inflammasome as a pattern recognition platform that translates crystal uptake into innate immune activation via secretion of IL-1? and IL-18 revised the pathogenesis of gout, silicosis, asbestosis, atherosclerosis and other crystal-related disorders. As a proof of concept, the NLRP3 inflammasome was now shown to trigger inflammation and acute kidney injury (AKI) in oxalate nephropathy. It seems likely that this and potentially other innate immunity mechanisms drive crystalline nephropathies (CNs) that are associated with crystals of calcium phosphate, uric acid, cysteine, adenine, certain drugs or contrast media, and potentially of myoglobin during rhabdomyolysis and of light chains in myeloma. Here, we discuss the proven and potential mechanisms of renal inflammation and kidney injury in crystal-related kidney disorders. In addition, we list topics for further research in that field. This perspective may also provide novel therapeutic options that can help to avoid progressive tissue remodeling and chronic kidney disease in patients with kidney stone disease or other CNs. PMID:24163269

  19. Pathophysiologic changes due to TASER devices versus excited delirium: potential relevance to deaths-in-custody?

    PubMed

    Jauchem, James R

    2011-05-01

    The syndrome of excited delirium has been implicated in some deaths-in-custody which also involved the use of electronic control devices (ECDs) (including those manufactured by TASER International) on subjects. This review is an update on recent studies of pathophysiologic changes related to these two separate but parallel topics: a) first, the use of ECDs during law-enforcement activities; and b) second, the occurrence of excited delirium during such activities. This is a narrative review of elements that may be of use in generating hypotheses relating to potential similarities or differences between the two topics. Differences between changes in most factors due to excited delirium versus those of ECD applications were not readily apparent in most cases. These factors include: direct and indirect effects on the cardiovascular system, respiration, rhabdomyolysis and muscle enzymes, hyperkalemia, acidosis, hyperglycemia, and increased hematocrit. One factor that may exhibit consistent differences, however, is increased body temperature, which is often evident during excited delirium (versus a lack of increase temperature during ECD exposures). Thus, on the basis of this review, a more detailed delineation of this factor could be a major focus for future forensic investigations of deaths-in-custody involving either excited delirium or ECD exposures. PMID:21550562

  20. Methadone-Induced Delayed Posthypoxic Encephalopathy: Clinical, Radiological, and Pathological Findings

    PubMed Central

    Mittal, Manoj; Wang, Yunxia; Reeves, Alan; Newell, Kathy

    2010-01-01

    Objective. To describe the clinical, radiological and pathological findings in a patient with methadone-induced delayed posthypoxic encephalopathy (DPHE). Case Report. A Thirty-eight-year-old man was found unconscious for an unknown duration after methadone and diazepam ingestion. His initial vitals were temperature 104 degree Fahrenheit, heart rate 148/minute, respiratory rate 50/minute, and blood pressure 107/72?mmhg. He developed renal failure, rhabdomyolysis, and elevated liver enzymes which resolved completely in 6 days. After 2 weeks from discharge he had progressive deterioration of his cognitive, behavioral and neurological function. Brain MRI showed diffuse abnormal T2 signal in the corona radiata, centrum semiovale, and subcortical white matter throughout all lobes. Extensive work up was negative for any metabolic, infectious or autoimmune disorder. Brain biopsy showed significant axonal injury in the white matter. He was treated successfully with combination of steroids and antioxidants. Follow up at 2 year showed no residual deficits. Conclusion. Our observation suggests that patients on methadone therapy should be monitored for any neurological or psychiatric symptoms, and in suspected cases MRI brain may help to make the diagnosis of DPHE. A trial of steroids and antioxidants may be considered in these patients. PMID:21209817

  1. Acute liver damage and ecstasy ingestion.

    PubMed Central

    Ellis, A J; Wendon, J A; Portmann, B; Williams, R

    1996-01-01

    Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted but subsequently died, histological examination showing widespread microvesicular fatty change. Four patients presented with acute liver failure without hyperthermia. All four fulfilled criteria for transplantation, one died before a donor organ became available, and two died within one month post-transplantation of overwhelming sepsis. Histological examination showed submassive lobular collapse. Two patients presented with abdominal pain and jaundice and recovered over a period of three weeks; histological examination showed a lobular hepatitis with cholestasis. Patients developing jaundice or with evidence of hepatic failure particularly encephalopathy and prolongation of the international normalised ratio, or both, whether or not preceded by hyperthermia, should be referred to a specialised liver unit as liver transplantation probably provides the only chance of recovery. Images Figure 1 Figure 2 Figure 3 PMID:8675102

  2. Intrauterine fetal death caused by pit viper venom poisoning in early pregnancy.

    PubMed

    Nasu, Kaei; Ueda, Tami; Miyakawa, Isao

    2004-01-01

    Poisonous snakebite is a rare complication of pregnancy. It has been suggested that snakebite poisoning during pregnancy may cause fetal loss. We report a case of intrauterine fetal death after a poisonous snakebite in the first trimester of pregnancy. A 29-year-old pregnant Japanese woman was admitted to hospital after being bitten by a pit viper on her right heel. The patient was at 10 weeks of gestation. In response to the bite, her right leg became extremely swollen, and paralysis of the right oculomotor nerve was observed. Intravenous administration of cepharanthine, ulinastatin, hydrocortisone sodium succinate, gabexate mesylate and antibiotics was started. Laboratory data suggested the presence of rhabdomyolysis. One week after admission, although she improved clinically and symptomatically, transvaginal ultrasonography revealed intrauterine fetal death. No vaginal bleeding was observed. A dilatation and curettage was performed. The patient made an uneventful recovery and was discharged from hospital 17 days after the snakebite. Consistent with other reports, in the first trimester intrauterine fetal death may especially occur when the mother has systemic symptoms, although its mechanism remains unclear. PMID:14691344

  3. Postoperative hyperkalemia.

    PubMed

    Ayach, Taha; Nappo, Robert W; Paugh-Miller, Jennifer L; Ross, Edward A

    2015-03-01

    Hyperkalemia occurs frequently in hospitalized patients and is of particular concern for those who have undergone surgery, with postoperative care provided by clinicians of many disciplines. This review describes the normal physiology and how multiple perioperative factors can disrupt potassium homeostasis and lead to severe elevations in plasma potassium concentration. The pathophysiologic basis of diverse causes of hyperkalemia was used to broadly classify etiologies into those with altered potassium distribution (e.g. increased potassium release from cells or other transcellular shifts), reduced urinary excretion (e.g. reduced sodium delivery, volume depletion, and hypoaldosteronism), or an exogenous potassium load (e.g. blood transfusions). Surgical conditions of particular concern involve: rhabdomyolysis from malpositioning, trauma or medications; bariatric surgery; vascular procedures with tissue ischemia; acidosis; hypovolemia; and volume or blood product resuscitation. Certain acute conditions and chronic co-morbidities present particular risk. These include chronic kidney disease, diabetes mellitus, many outpatient preoperative medications (e.g. beta blockers, salt substitutes), and inpatient agents (e.g. succinylcholine, hyperosmolar volume expanders). Clinicians need to be aware of these pathophysiologic mechanisms for developing perioperative hyperkalemia as many of the risks can be minimized or avoided. PMID:25698564

  4. A genome-wide scan for tying-up syndrome in Japanese Thoroughbreds.

    PubMed

    Tozaki, T; Hirota, K; Sugita, S; Ishida, N; Miyake, T; Oki, H; Hasegawa, T

    2010-12-01

    Tying-up syndrome, also known as recurrent exertional rhabdomyolysis in Thoroughbreds, is a common muscle disorder for racehorses. In this study, we performed a multipoint linkage analysis using LOKI based on the Bayesian Markov chain Monte Carlo method using 5 half-sib families (51 affected and 277 nonaffected horses in total), and a genome-wide association study (GWAS) using microsatellites (144 affected and 144 nonaffected horses) to map candidate regions for tying-up syndrome in Japanese Thoroughbreds. The linkage analysis identified one strong L-score (82.45) between the loci UCDEQ411 and COR058 (24.9-27.9 Mb) on ECA12. The GWAS identified two suggestive genomic regions on ECA12 (24.9-27.8 Mb) and ECA20 (29.3-33.5 Mb). Based on both results, the genomic region between UCDEQ411 and TKY499 (24.9-27.8 Mb) on ECA12 was the most significant and was considered as a candidate region for tying-up syndrome in Japanese Thoroughbreds. PMID:21070280

  5. Synthetic cannabinoids: the multi-organ failure and metabolic derangements associated with getting high

    PubMed Central

    Sherpa, Dolkar; Paudel, Bishow M.; Subedi, Bishnu H.; Chow, Robert Dobbin

    2015-01-01

    Synthetic cannabinoids (SC), though not detected with routine urine toxicology screening, can cause severe metabolic derangements and widespread deleterious effects in multiple organ systems. The diversity of effects is related to the wide distribution of cannabinoid receptors in multiple organ systems. Both cannabinoid-receptor-mediated and non-receptor-mediated effects can result in severe cardiovascular, renal, and neurologic manifestations. We report the case of a 45-year-old African American male with ST-elevation myocardial infarction, subarachnoid hemorrhage, reversible cardiomyopathy, acute rhabdomyolysis, and severe metabolic derangement associated with the use of K2, an SC. Though each of these complications has been independently associated with SCs, the combination of these effects in a single patient has not been heretofore reported. This case demonstrates the range and severity of complications associated with the recreational use of SCs. Though now banned in the United States, use of systemic cannabinoids is still prevalent, especially among adolescents. Clinicians should be aware of their continued use and the potential for harm. To prevent delay in diagnosis, tests to screen for these substances should be made more readily available. PMID:26333853

  6. Treatment compliance and severe adverse events limit the use of tyrosine kinase inhibitors in refractory thyroid cancer

    PubMed Central

    Chrisoulidou, Alexandra; Mandanas, Stylianos; Margaritidou, Efterpi; Mathiopoulou, Lemonia; Boudina, Maria; Georgopoulos, Konstantinos; Pazaitou-Panayiotou, Kalliopi

    2015-01-01

    Objective The aim of the present study was to assess patient compliance with tyrosine kinase inhibitor (TKI) treatment used for refractory and progressive thyroid cancer, in addition to the efficacy and serious adverse events associated with these agents. Methods We retrospectively analyzed data from adult patients with metastatic differentiated or medullary thyroid cancer unresponsive to conventional treatment and treated with TKIs. Patients received treatment until disease progression or onset of serious adverse events, or until they expressed an intention to stop treatment. Results Twenty-four patients received TKIs. The median duration of treatment was four (range: 119) cycles. The most frequent adverse events were fatigue, nausea, diarrhea, hypertension, and stomatitis, and the most severe were nasal bleeding, diarrhea, heart failure, rhabdomyolysis, renal failure, QT prolongation, neutropenia, and severe fatigue. Dose reduction was required in eight patients, while five decided to terminate TKI therapy because adverse events impaired their everyday activities. During therapy, two patients showed a partial response and three showed stable disease. The lungs were the metastatic sites favoring a response to treatment. Conclusion Patient selection and meticulous pretreatment education are necessary in order to ensure adherence with TKI therapy. If adverse events appear, dose reduction or temporary treatment interruption may be offered because some adverse events resolve with continuation of treatment. In the event of serious adverse events, treatment discontinuation is necessary. PMID:26366098

  7. DELAYED URIC ACID ACCUMULATION IN PLASMA PROVIDES ADDITIONAL ANTI-OXIDANT PROTECTION AGAINST IRON-TRIGGERED OXIDATIVE STRESS AFTER A WINGATE TEST

    PubMed Central

    Souza-Junior, TP; Lorenço-Lima, L; Ganini, D; Vardaris, CV; Polotow, TG

    2014-01-01

    Reactive oxygen species are produced during anaerobic exercise mostly by Fe ions released into plasma and endothelial/muscle xanthine oxidase activation that generates uric acid (UA) as the endpoint metabolite. Paradoxically, UA is considered a major antioxidant by virtue of being able to chelate pro-oxidative iron ions. This work aimed to evaluate the relationship between UA and plasma markers of oxidative stress following the exhaustive Wingate test. Plasma samples of 17 male undergraduate students were collected before, 5 and 60 min after maximal anaerobic effort for the measurement of total iron, haem iron, UA, ferric-reducing antioxidant activity in plasma (FRAP), and malondialdehyde (MDA, biomarker of lipoperoxidation). Iron and FRAP showed similar kinetics in plasma, demonstrating an adequate pro-/antioxidant balance immediately after exercise and during the recovery period (5–60 min). Slight variations of haem iron concentrations did not support a relevant contribution of rhabdomyolysis or haemolysis for iron overload following exercise. UA concentration did not vary immediately after exercise but rather increased 29% during the recovery period. Unaltered MDA levels were concomitantly measured. We propose that delayed UA accumulation in plasma is an auxiliary antioxidant response to post-exercise (iron-mediated) oxidative stress, and the high correlation between total UA and FRAP in plasma (R-Square = 0.636; p = 0.00582) supports this hypothesis. PMID:25435669

  8. Difficulties in localization and treatment of insulinomas in type 1 multiple endocrine adenomatosis (MEA).

    PubMed

    Winocour, P H; Moriarty, K J; Hales, C N; Adams, J; Reeve, R; Wynick, D; Allison, D; Bloom, S R; Anderson, D C

    1992-03-01

    A 15 year old girl with a family history of type 1 multiple endocrine adenomatosis presented with reversible neurological disturbances, hypoglycaemia and hyperinsulinaemia. Initial radiology was normal, but portal venous sampling suggested an insulinoma in the tail of the pancreas which was removed with conservation of the spleen. Hypoglycaemia persisted despite high doses of diazoxide and intravenous dextrose. A second laparotomy revealed a pancreatic endocrine tumour and sub-total pancreatectomy was performed. Histology revealed islet cell microadenomatosis. Hypoglycaemia persisted despite treatment with somatostatin analogues and 40% intravenous dextrose was required to maintain normoglycaemia. A possible lesion near the splenic hilum on computed tomographic scan was reported as a splenunculus although further peripheral, hepatic and portal venous sampling suggested hepatic or systemic lesions. A positron emission scan and selective visceral angiography suggested a lesion in the left upper quadrant. Acute lactic acidosis, rhabdomyolysis and renal failure supervened. Post mortem revealed the putative 'splenunculus' to be a residual insulinoma, whilst the splenic vein was thrombosed, accounting in part for discrepant venous sampling data. Hyperinsulinaemia in type 1 multiple endocrine adenomatosis may require more aggressive surgical and hormonal intervention than when dealing with solitary insulinomas. Insulinomas may mimic developmental abnormalities on computed tomographic scanning. PMID:1350344

  9. Negative evidence for stachydrine or Galeopsis ladanum L. seeds as the causal agents of coturnism after quail meat ingestion.

    PubMed

    Uriarte-Pueyo, Inigo; Goicoechea, Mara; Gil, Ana Gloria; Lpez de Cerain, Adela; Lpez de Munain, Adolfo; Calvo, Mara Isabel

    2009-11-25

    Quail poisoning is known to produce an acute myoglobinuric syndrome called coturnism. The cause of this syndrome is still unknown, although it has been postulated that Galeopsis ladanum L. seeds, in particular lipidic compounds or stachydrine, are responsible for this toxicity. Thus, we aimed to study the implication of this plant in coturnism in order to explore the physiopathology of the disease, especially with regard to stachydrine and lipidic compounds extracted from seeds. For this purpose, Wistar rats were fed with G. ladanum seed extracts or with quail meat. However, the rhabdomyolysis outbreak could not be reproduced in any case. Therefore, in view of our results and experimental conditions, seeds of G. ladanum and stachydrine do not appear to be the responsible agents of the myopathic outbreak. This conclusion is supported by the following facts: direct administration of extracts of seeds of G. ladanum or stachydrine produces no myotoxicity in rats; G. ladanum seeds are not toxic to quails and meat from quails fed G. ladanum seeds is not toxic to rats. PMID:19860419

  10. [Intoxications specific to the Aquitaine region].

    PubMed

    Bdry, R; Gromb, S

    2009-07-01

    Some intoxications are more specifically linked to the Aquitaine region than to other regions of France, due to environmental circumstances (fauna, flora, climate) or traditional activities (gastronomy). Three types of intoxications are particular in this area. Pine processionary caterpillar envenomations (Thaumetopoea pityocampa), a Southern Europe pinewood parasite, are frequently encountered in the Landes' forest. They are responsible of ocular and/or skin lesions with urticaria or contact dermatitis, seldom associated with immediate IgE hypersensitivity. According to the south Atlantic coastal region geology and the marine streams, venomous marine animals are mainly located in Charente-Maritime for jellyfish, in Gironde and in Landes for weeverfish and in Atlantic Pyrenees for sea anemone. Usually not dangerous, first-aid workers treat most cases of these envenomations. Some endemic mushrooms (Tricholoma auratum) which grow on the dunes of the Atlantic coastal region, are usually considered as very good comestibles, but were recently responsible for serious intoxications: T.auratum was responsible of several cases of rhabdomyolysis, without neurological involvement, nor renal or hepatic lesion. Three deaths were notified. Animal studies confirmed the responsibility of the mushrooms. PMID:19375827

  11. The frequency of agitation due to inappropriate use of naltrexone in addicts

    PubMed Central

    Siadat, Sima; Eizadi-Mood, Nastaran; Sabzghabaee, Ali Mohammad; Gheshlaghi, Farzad; Yaraghi, Ahmad

    2014-01-01

    Background: There is a high tendency among specialists to treat the addicts with naltrexone; withdrawal symptoms are frequent after taking naltrexone along with opioids. This study investigated the frequency of agitation due to inappropriate use of naltrexone in addicts. Materials and Methods: This was a cross-sectional study, conducted in Noor and Aliasghar hospitals in Isfahan city. The study population included the addicts who were agitated as a result of naltrexone abuse. Scores of patients with agitation were measured with Richmond Agitation Sedation Scale (RASS). Patient outcomes including recovery without complications, recovery with complications (rhabdomyolysis), and mortality were recorded. Results: All the patients with agitation caused by naltrexone abuse during 1 year were 40 people, of whom nine were excluded due to their comorbid diseases (diabetes or cardiovascular disease). Among the remaining 31 patients, 30 were male. The patients mean age was 29.93 (5.24) years. The most common symptoms observed besides agitation was midriasis (41.9%), and vomiting (41.9%), A 38.8% of the patients scored 3 or 4, and, 61.2% scored 1 or 2 for agitation. The mean time for patients restlessness scores to reach zero was 9.30 (3.71) h (min: 3 h, max: 18 h). All the patients in both groups were discharged with recovery without complication. Conclusion: Considering the high prevalence of agitation in the poisoning emergency department due to inappropriate use of naltrexone, more accurate planning for administration of naltrexone in addicts seems necessary. PMID:25590027

  12. SUBSTRATE OXIDATION & CARDIAC PERFORMANCE DURING EXERCISE IN DISORDERS OF LONG CHAIN FATTY ACID OXIDATION

    PubMed Central

    Behrend, Annie M; Harding, Cary O; Shoemaker, James D; Matern, Dietrich; Sahn, David J; Elliot, Diane L; Gillingham, Melanie B

    2011-01-01

    Background The use of long-chain fatty acids (LCFAs) for energy is inhibited in inherited disorders of long-chain fatty acid oxidation (FAO). Increased energy demands during exercise can lead to cardiomyopathy and rhabdomyolysis. Medium-chain triglycerides (MCTs) bypass the block in long-chain FAO and may provide an alternative energy substrate to exercising muscle. Objectives To determine the influence of isocaloric MCT versus carbohydrate (CHO) supplementation prior to exercise on substrate oxidation and cardiac workload in participants with carnitine palmitoyltransferase 2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD) and long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiencies. Design Eleven subjects completed two 45-minute, moderate intensity, treadmill exercise studies in a randomized crossover design. An isocaloric oral dose of CHO or MCT-oil was administered prior to exercise; hemodynamic and metabolic indices were assessed during exertion. Results When exercise was pretreated with MCT, respiratory exchange ratio (RER), steady state heart rate and generation of glycolytic intermediates significantly decreased while circulating ketone bodies significantly increased. Conclusions MCT supplementation prior to exercise increases the oxidation of medium chain fats, decreases the oxidation of glucose and acutely lowers cardiac workload during exercise for the same amount of work performed when compared with CHO pre-supplementation. We propose that MCT may expand the usable energy supply, particularly in the form of ketone bodies, and improve the oxidative capacity of the heart in this population. PMID:22030098

  13. Peripheral nerve blocks as the sole anesthetic technique in a patient with severe Duchenne muscular dystrophy.

    PubMed

    Bang, Seung Uk; Kim, Yee Suk; Kwon, Woo Jin; Lee, Sang Mook; Kim, Soo Hyang

    2016-04-01

    General anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are associated with high risks of complications, including rhabdomyolysis, malignant hyperthermia, hemodynamic instability, and postoperative mechanical ventilation. Here, we describe peripheral nerve blocks as a safe approach to anesthesia in a patient with severe Duchenne muscular dystrophy who was scheduled to undergo surgery. A 22-year-old male patient was scheduled to undergo reduction and internal fixation of a left distal femur fracture. He had been diagnosed with Duchenne muscular dystrophy at 5 years of age, and had no locomotive capability except for that of the finger flexors and toe extensors. He had developed symptoms associated with dyspnea 5 years before and required intermittent ventilation. We blocked the femoral nerve, lateral femoral cutaneous nerve, and parasacral plexus under ultrasound on the left leg. The patient underwent a successful operation using peripheral nerve blocks with no complications. In conclusion general anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are unsafe approaches to anesthesia because of hemodynamic instability and respiratory depression. Peripheral nerve blocks are the best way to reduce the risks of critical complications, and are a safe and feasible approach to anesthesia in patients with severe Duchenne muscular dystrophy. PMID:26721827

  14. Grapefruit Juice and Statins.

    PubMed

    Lee, Jonathan W; Morris, Joan K; Wald, Nicholas J

    2016-01-01

    We determined the validity of current medical advice to avoid grapefruit juice consumption while taking 3 widely used statins. A daily glass of grapefruit juice increases blood levels of simvastatin and lovastatin by about 260% if taken at the same time (about 90% if taken 12 hours apart), and atorvastatin by about 80% (whenever taken). Simvastatin 40 mg, lovastatin 40 mg, and atorvastatin 10 mg daily reduce low-density lipoprotein (LDL) cholesterol levels in a 60-year-old man with an LDL cholesterol of 4.8 mmol/L by 37%, reducing ischemic heart disease risk by 61%. When simvastatin or lovastatin are taken at the same time as grapefruit juice, the estimated reduction in LDL cholesterol is 48%, and in heart disease is 70%. If the juice is taken 12 hours before these statins, the reductions are, respectively, 43% and 66%, and for atorvastatin, 42% and 66%. The increased rhabdomyolysis risk from grapefruit juice consumption due to the increased effective statin dose is minimal compared with the greater effect in preventing heart disease. Grapefruit juice should not be contraindicated in people taking statins. PMID:26299317

  15. Methamphetamine abuse.

    PubMed

    Winslow, Bradford T; Voorhees, Kenton I; Pehl, Katherine A

    2007-10-15

    Methamphetamine is a stimulant commonly abused in many parts of the United States. Most methamphetamine users are white men 18 to 25 years of age, but the highest usage rates have been found in native Hawaiians, persons of more than one race, Native Americans, and men who have sex with men. Methamphetamine use produces a rapid, pleasurable rush followed by euphoria, heightened attention, and increased energy. Possible adverse effects include myocardial infarction, stroke, seizures, rhabdomyolysis, cardiomyopathy, psychosis, and death. Chronic methamphetamine use is associated with neurologic and psychiatric symptoms and changes in physical appearance. High-risk sexual activity and transmission of human immunodeficiency virus are also associated with methamphetamine use. Use of methamphetamine in women who are pregnant can cause placental abruption, intrauterine growth retardation, and preterm birth, and there can be adverse consequences in children exposed to the drug. Treatment of methamphetamine intoxication is primarily supportive. Treatment of methamphetamine abuse is behavioral; cognitive behavior therapy, contingency management, and the Matrix Model may be effective. Pharmacologic treatments are under investigation. PMID:17990840

  16. Lipin-1 regulates autophagy clearance and intersects with statin drug effects in skeletal muscle.

    PubMed

    Zhang, Peixiang; Verity, M Anthony; Reue, Karen

    2014-08-01

    LPIN1 encodes lipin-1, a phosphatidic acid phosphatase (PAP) enzyme that catalyzes the dephosphorylation of phosphatidic acid to form diacylglycerol. Homozygous LPIN1 gene mutations cause severe rhabdomyolysis, and heterozygous LPIN1 missense mutations may promote statin-induced myopathy. We demonstrate that lipin-1-related myopathy in the mouse is associated with a blockade in autophagic flux and accumulation of aberrant mitochondria. Lipin-1 PAP activity is required for maturation of autolysosomes, through its activation of the protein kinase D (PKD)-Vps34 phosphatidylinositol 3-kinase signaling cascade. Statin treatment also reduces PKD activation and autophagic flux, which are compounded by diminished mammalian target of rapamycin (mTOR) abundance in lipin-1-haploinsufficent and -deficient muscle. Lipin-1 restoration in skeletal muscle prevents myonecrosis and statin toxicity in vivo, and activated PKD rescues autophagic flux in lipin-1-deficient cells. Our findings identify lipin-1 PAP activity as a component of the macroautophagy pathway and define the basis for lipin-1-related myopathies. PMID:24930972

  17. Disorders of muscle lipid metabolism: diagnostic and therapeutic challenges.

    PubMed

    Laforêt, Pascal; Vianey-Saban, Christine

    2010-11-01

    Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid β-oxidation. Three main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan's anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin. PMID:20691590

  18. A porphyrin-PEG polymer with rapid renal clearance.

    PubMed

    Huang, Haoyuan; Hernandez, Reinier; Geng, Jumin; Sun, Haotian; Song, Wentao; Chen, Feng; Graves, Stephen A; Nickles, Robert J; Cheng, Chong; Cai, Weibo; Lovell, Jonathan F

    2016-01-01

    Tetracarboxylic porphyrins and polyethylene glycol (PEG) diamines were crosslinked in conditions that gave rise to a water-soluble porphyrin polyamide. Using PEG linkers 2 kDa or larger prevented fluorescence self-quenching. This networked porphyrin mesh was retained during dialysis with membranes with a 100 kDa pore size, yet passed through the membrane when centrifugal filtration was applied. Following intravenous administration, the porphyrin mesh, but not the free porphyrin, was rapidly cleared via renal excretion. The process could be monitored by fluorescence analysis of collected urine, with minimal background due to the large Stokes shift of the porphyrin (230 nm separating excitation and emission peaks). In a rhabdomyolysis mouse model of renal failure, porphyrin mesh urinary clearance was significantly impaired. This led to slower accumulation in the bladder, which could be visualized non-invasively via fluorescence imaging. Without further modification, the porphyrin mesh was chelated with (64)Cu for dynamic whole body positron emission tomography imaging of renal clearance. Together, these data show that small porphyrin-PEG polymers can serve as effective multimodal markers of renal function. PMID:26517562

  19. Serotonin syndrome after sertraline overdose in a child: a case report.

    PubMed

    Grenha, Joana; Garrido, Ana; Brito, Hernani; Oliveira, Maria Jos; Santos, Ftima

    2013-01-01

    Serotonin syndrome is a potentially life-threatening drug effect. It may be misdiagnosed because it has mostly been reported in adults. Case Report. An 8-year-old girl with behavioral problems and medicated with risperidone and sertraline was admitted in the emergency department after she had taken voluntarily 1500?mg of sertraline (50?mg/kg). At admission, she had marked agitation, visual hallucinations, diaphoresis, flushing, and tremor. She had fever and periods of hypertension. She also showed generalized rigidity and involuntary movements. She was treated with fluids and iv diazepam, midazolam, clemastine, and biperiden. As the patient presented a severe insomnia and a progressive rhabdomyolysis, she was transferred to pediatric intensive care unit (ICU), where she was under treatment with cyproheptadine, mechanical ventilation, and muscular paralysis for 11 days. She was discharged from hospital a few days later with no neurological sequelae. Conclusions. Serotonin syndrome is still not well recognized by physicians. In our patient, the diagnosis was made early due to the history of overdose with serotonin reuptake inhibitors and the triad of mental, neurological, and autonomic signs. Parents must be educated to prevent children from having free access to drugs, avoiding self-medication or overdose. PMID:24455378

  20. Serotonin Syndrome after Sertraline Overdose in a Child: A Case Report

    PubMed Central

    Garrido, Ana; Brito, Hernani; Oliveira, Maria Jos; Santos, Ftima

    2013-01-01

    Serotonin syndrome is a potentially life-threatening drug effect. It may be misdiagnosed because it has mostly been reported in adults. Case Report. An 8-year-old girl with behavioral problems and medicated with risperidone and sertraline was admitted in the emergency department after she had taken voluntarily 1500?mg of sertraline (50?mg/kg). At admission, she had marked agitation, visual hallucinations, diaphoresis, flushing, and tremor. She had fever and periods of hypertension. She also showed generalized rigidity and involuntary movements. She was treated with fluids and iv diazepam, midazolam, clemastine, and biperiden. As the patient presented a severe insomnia and a progressive rhabdomyolysis, she was transferred to pediatric intensive care unit (ICU), where she was under treatment with cyproheptadine, mechanical ventilation, and muscular paralysis for 11 days. She was discharged from hospital a few days later with no neurological sequelae. Conclusions. Serotonin syndrome is still not well recognized by physicians. In our patient, the diagnosis was made early due to the history of overdose with serotonin reuptake inhibitors and the triad of mental, neurological, and autonomic signs. Parents must be educated to prevent children from having free access to drugs, avoiding self-medication or overdose. PMID:24455378

  1. Neuropsychiatric adverse events associated with statins: epidemiology, pathophysiology, prevention and management.

    PubMed

    Tuccori, Marco; Montagnani, Sabrina; Mantarro, Stefania; Capogrosso-Sansone, Alice; Ruggiero, Elisa; Saporiti, Alessandra; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado

    2014-03-01

    Statins, or 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, such as lovastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, rosuvastatin and pitavastatin, are cholesterol-lowering drugs used in clinical practice to prevent coronary heart disease. These drugs are generally well tolerated and have been rarely associated with severe adverse effects (e.g. rhabdomyolysis). Over the years, case series and data from national registries of spontaneous adverse drug reaction reports have demonstrated the occurrence of neuropsychiatric reactions associated with statin treatment. They include behavioural alterations (severe irritability, homicidal impulses, threats to others, road rage, depression and violence, paranoia, alienation, antisocial behaviour); cognitive and memory impairments; sleep disturbance (frequent awakenings, shorter sleep duration, early morning awakenings, nightmares, sleepwalking, night terrors); and sexual dysfunction (impotence and decreased libido). Studies designed to investigate specific neuropsychiatric endpoints have yielded conflicting results. Several mechanisms, mainly related to inhibition of cholesterol biosynthesis, have been proposed to explain the detrimental effects of statins on the central nervous system. Approaches to prevent and manage such adverse effects may include drug discontinuation and introduction of dietary restrictions; maintenance of statin treatment for some weeks with close patient monitoring; switching to a different statin; dose reduction; use of ω-3 fatty acids or coenzyme Q10 supplements; and treatment with psychotropic drugs. The available information suggests that neuropsychiatric effects associated with statins are rare events that likely occur in sensitive patients. Additional data are required, and further clinical studies are needed. PMID:24435290

  2. Measurement of 3,4-MDMA and related amines in diagnostic and forensic laboratories.

    PubMed

    Skrinska, Victor A; Gock, Susan B

    2005-01-01

    The phenylalkylamine derivatives, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam), 3,4-methylenedioxyethamphetamine (MDEA, MDE, Eve), and 3,4-methylenedioxyamphetamine (MDA), are psychostimulants with hallucinogenic properties. MDA is also a metabolite of both MDMA and MDEA. These drugs are ring-substituted amphetamine derivatives that produce hallucinogenic, entactogenic ('love drug'), and stimulating effects. MDMA was initially developed as an appetite suppressant, however, its use as a therapeutic drug has been very limited. Because of its effects as a hallucinogenic psychostimulant with relatively low toxicity, it has emerged over the last two decades as a common recreational psychostimulant or 'club drug' at 'raves'. MDMA, MDEA, and MDA are often referred to as 'rave' or 'designer' drugs. They are produced in clandestine laboratories and have an increasing presence on the illicit drug market worldwide. Significant adverse health effects have been reported that include: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, and disseminated intravascular coagulation. A number of fatal outcomes associated with severe MDMA intoxication have been reported. PMID:15916245

  3. 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

    Frana, 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 So 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 So 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. PMID:7938407

  4. Hypophosphatemia

    PubMed Central

    Knochel, James P.

    1981-01-01

    Hypophosphatemia is a common laboratory abnormality that occurs in a wide variety of disorders. When severe and prolonged, it may be associated with rhabdomyolysis, brain dysfunction, myocardial failure and certain defects of erythrocyte function and structure. Other disorders ascribed to hypophosphatemia, including platelet dysfunction and thrombocytopenia, liver dysfunction, renal tubular defects, peripheral neuropathy, metabolic acidosis and leukocyte dysfunction are less well documented. In quantitative terms, the most severe phosphate deficiency is seen in patients who consume a phosphate-deficient diet in conjunction with large amounts of phosphate-binding antacids, in persons with severe, chronic alcoholism and in patients with wasting illnesses who are refed with substances containing an inadequate amount of phosphate. When severe hypophosphatemia occurs in such a setting, the clinical effects appear to be much more pronounced. While there have been some advances in our understanding of the pathophysiology of phosphate depletion and hypophosphatemia, much remains to be learned. Treatment of hypophosphatemia is controversial; however, there is little question that it is indicated in alcoholic patients and those with severe phosphate deficiency. PMID:7010790

  5. Proteasome inhibition and oxidative reactions disrupt cellular homeostasis during heme stress.

    PubMed

    Vallelian, F; Deuel, J W; Opitz, L; Schaer, C A; Puglia, M; Lnn, M; Engelsberger, W; Schauer, S; Karnaukhova, E; Spahn, D R; Stocker, R; Buehler, P W; Schaer, D J

    2015-04-01

    Dual control of cellular heme levels by extracellular scavenger proteins and degradation by heme oxygenases is essential in diseases associated with increased heme release. During severe hemolysis or rhabdomyolysis, uncontrolled heme exposure can cause acute kidney injury and endothelial cell damage. The toxicity of heme was primarily attributed to its pro-oxidant effects; however additional mechanisms of heme toxicity have not been studied systematically. In addition to redox reactivity, heme may adversely alter cellular functions by binding to essential proteins and impairing their function. We studied inducible heme oxygenase (Hmox1)-deficient mouse embryo fibroblast cell lines as a model to systematically explore adaptive and disruptive responses that were triggered by intracellular heme levels exceeding the homeostatic range. We extensively characterized the proteome phenotype of the cellular heme stress responses by quantitative mass spectrometry of stable isotope-labeled cells that covered more than 2000 individual proteins. The most significant signals specific to heme toxicity were consistent with oxidative stress and impaired protein degradation by the proteasome. This ultimately led to an activation of the response to unfolded proteins. These observations were explained mechanistically by demonstrating binding of heme to the proteasome that was linked to impaired proteasome function. Oxidative heme reactions and proteasome inhibition could be differentiated as synergistic activities of the porphyrin. Based on the present data a novel model of cellular heme toxicity is proposed, whereby proteasome inhibition by heme sustains a cycle of oxidative stress, protein modification, accumulation of damaged proteins and cell death. PMID:25301065

  6. Pathological findings in 165 patients explored for malignant hyperthermia susceptibility.

    PubMed

    Figarella-Branger, D; Kozak-Ribbens, G; Rodet, L; Aubert, M; Borsarelli, J; Cozzone, P J; Pellissier, J F

    1993-01-01

    The pathological findings in 165 patients explored for malignant hyperthermia (MH) susceptibility are reported. The first group of 120 subjects were patients investigated for MH. These patients had suffered an attack of MH under anaesthetic or were members of families in which a subject had died of MH. In vitro contracture tests revealed 25 malignant hyperthermia susceptible (MHS) subjects, with positive contracture tests for halothane and caffeine, 5 malignant hyperthermia subjects with reaction to caffeine only (MHC), 3 malignant hyperthermia subjects with reaction to halothane only (MHH) and 87 malignant hyperthermia negative (MHN) subjects with normal contracture tests. The second group of 45 subjects had exertional heat stroke. In vitro contracture tests performed at least 3 months after the exertional heat stroke revealed 11 MHS, 6 MHC, 2 MHH subjects and 26 MHN. In both groups, whatever the in vitro contracture test results, pathological findings were heterogeneous and revealed various changes: rhabdomyolysis, mitochondrial myopathy, denervation, type II atrophy, AMPase deficiency, non-specific findings or normal features. Central core myopathy was only observed in the first subgroup and was the only disease significantly associated with MH. In contrast to previous reports, this study demonstrates the absence of a specific malignant hyperthermia or exertional heat stroke myopathy. Furthermore, the discovery of MHS subjects among the EHS group of patients highlights the need for systematic exploration of all these patients. PMID:8186710

  7. Envenomations by Bothrops and Crotalus Snakes Induce the Release of Mitochondrial Alarmins

    PubMed Central

    Zornetta, Irene; Caccin, Paola; Fernandez, Julin; Lomonte, Bruno; Gutierrez, Jos Mara; Montecucco, Cesare

    2012-01-01

    Skeletal muscle necrosis is a common manifestation of viperid snakebite envenomations. Venoms from snakes of the genus Bothrops, such as that of B. asper, induce muscle tissue damage at the site of venom injection, provoking severe local pathology which often results in permanent sequelae. In contrast, the venom of the South American rattlesnake Crotalus durissus terrificus, induces a clinical picture of systemic myotoxicity, i.e., rhabdomyolysis, together with neurotoxicity. It is known that molecules released from damaged muscle might act as danger signals. These are known as alarmins, and contribute to the inflammatory reaction by activating the innate immune system. Here we show that the venoms of B. asper and C. d. terrificus release the mitochondrial markers mtDNA (from the matrix) and cytochrome c (Cyt c) from the intermembrane space, from ex vivo mouse tibialis anterior muscles. Cyt c was released to a similar extent by the two venoms whereas B. asper venom induced the release of higher amounts of mtDNA, thus reflecting hitherto some differences in their pathological action on muscle mitochondria. At variance, injection of these venoms in mice resulted in a different time-course of mtDNA release, with B. asper venom inducing an early onset increment in plasma levels and C. d. terrificus venom provoking a delayed release. We suggest that the release of mitochondrial alarmins might contribute to the local and systemic inflammatory events characteristic of snakebite envenomations. PMID:22363828

  8. [Synthetic cannabinoids: spread, addiction biology & current perspective of personal health hazard].

    PubMed

    Bonnet, U; Mahler, H

    2015-04-01

    Among the new psychoactive substances (NPS), most frequently synthetic cannabinoids (SCBs) have been found in Europe. These are sold as active compounds in e.?g. so-called "herbal blends". When inhaled or ingested, besides intoxication symptoms, as they occur with heavy cannabis use (e.?g., tachycardia, myocardial infarction, confusion, hallucinations, panic attacks, and paranoia), harmful effects (severe agitation, coma, catatonic stupor, hypertension, cardiac arrhythmia, dyspnoea, seizures, myoclonus, rhabdomyolysis, hyperthermia, diaphoresis, acute kidney injury, vomiting, headache, and hypokalemia) arise, which are mostly unusual about cannabis use. In addition, the first cases of addiction and death related to SCBs have been reported. Taking into account the newest literature and using an algorithm with two main criteria (addiction potential, toxicity), the authors made a first attempt to rank the personal health hazard of SCBs in comparison to that of other psychoactive drugs. Accordingly, the relative health hazard of SCBs is found to be somewhat higher than that of cannabis and lower than that of synthetic cathinones ("bath salts"). However, the toxicity of SCBs, is significantly greater than the toxicity of cannabis, thus being similar to that of synthetic cathinones and benzodiazepines. The addiction potential appears to be lower than that of synthetic cathinones, benzodiazepines, or cannabis. Due to the fluctuation of substances and the availability in internet resources, legislation is facing a serious "hare-hedgehog" problem to control the manufacture, trade and possession of SCBs. PMID:25893495

  9. Normal results of post-race thallium-201 myocardial perfusion imaging in marathon runners with elevated serum MB creatine kinase levels

    SciTech Connect

    Siegel, A.J.; Silverman, L.M.; Holman, B.L.

    1985-10-01

    Elevated cardiac enzyme values in asymptomatic marathon runners after competition can arise from skeletal muscle through exertional rhabdomyolysis, silent injury to the myocardium, or a combined tissue source. Peak post-race levels of the MB isoenzyme of creatine kinase are similar to values in patients with acute myocardial infarction. Previously reported normal results of infarct-avid myocardial scintigraphy with technetium 99m pyrophosphate in runners after competition suggest a non-cardiac source but cannot exclude silent injury to the myocardium. Therefore, thallium 201 myocardial perfusion imaging was performed in runners immediately after competition together with determination of sequential cardiac enzyme levels. Among 15 runners tested, the average peak in serum MB creatine kinase 24 hours after the race was 128 IU/liter with a cumulative MB creatine kinase release of 117 IU/liter; these values are comparable to those in patients with acute transmural myocardial infarction. Thallium 201 myocardial scintigraphic results were normal in five runners randomly selected from those who volunteered for determination of sequential blood levels. It is concluded that elevations of serum MB creatine kinase in marathon runners arise from a skeletal muscle source and that thallium 201 myocardial scintigraphy is useful to assess runners for myocardial injury when clinical questions arise.

  10. Loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury.

    PubMed

    de Souza, A L; Malaque, C M; Sztajnbok, J; Romano, C C; Duarte, A J; Seguro, A C

    2008-01-01

    Herein, we describe a confirmed case of Loxosceles spider bite that illustrates the critical complications seen in loxoscelism, including skin necrosis, rhabdomyolysis, hemolysis, coagulopathy, acute kidney failure, and electrolyte disorders. Upon initial assessment, laboratory studies revealed the following: the white blood cell count was 29,400 WBCs/mm(3), hemoglobin was 9.2g/dL, and the platelet count was 218,000 cells/mm(3). Coagulation studies revealed the following: international normalized ratio, 1.83; activated partial-thromboplastin time, 62 s; D-dimer, 600 ng/mL (normal range <500 ng/mL); free protein S, 37% (normal range=64-114%); protein C, negative; and antithrombin III, negative. Various serum levels were abnormal: urea, 110 mg/dL; creatinine, 3.1mg/dL; indirect bilirubin, 3.8 mg/dL; creatine kinase, 1631 U/L; lactate dehydrogenase, 6591 U/L; potassium 6.2 mmol/L. Urine tests were positive for hemoglobin and bilirubin. In addition, concentrations of interleukin-6 and tumor necrosis factor-alpha were notably elevated in the serum. In conclusion, physicians must be alert to the possibility of loxoscelism when a patient presents with the clinical and laboratory findings described above, especially if the patient resides in an endemic area. Advances in our understanding of multiple pathways and mediators that orchestrate the response to Loxosceles venom might reveal new possibilities for the management of loxoscelism. PMID:17928022

  11. Complications and outcomes of brown recluse spider bites in children.

    PubMed

    Hubbard, Jonathan J; James, Laura P

    2011-03-01

    Brown recluse spider bites may cause severe local and systemic morbidity, but data regarding morbidity in children are limited. This study reviewed inpatient medical records (n = 26; 10 years) with a discharge diagnosis of "spider bite" from a tertiary pediatric hospital. The majority (85%) of children had an inflammatory response accompanying necrosis, usually with signs of secondary cellulitis (77%). Hemolytic anemia (50%), rhabdomyolysis (27%), and acute renal failure (12%) were the most prevalent systemic effects. Hemolytic anemia was bimodal in distribution relative to the time-of-onset of the bite (early, 2.2 0.4; late, 6.9 1.5 days postbite, respectively; P = .004). Although no fatalities occurred in the population, 65% of children had major morbidity, including wound complications requiring surgical care and acute orbital compartment syndrome. The findings emphasize the importance of anticipatory patient/family education for outpatients and careful monitoring for systemic morbidity in inpatients. Timely and appropriate supportive care should yield favorable outcomes in most cases. PMID:21307081

  12. 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. PMID:23622366

  13. [Malignant neuroleptic syndrome associated with amisulpride].

    PubMed

    Harter, C; Obier, C; Druschky, K-F; Eikelmann, B

    2008-01-01

    Malignant neuroleptic syndrome (MNS) is a rare side effect of antipsychotic medications but means a serious and life-threatening complication. The risk of MNS seems to be lower for second generation antipsychotics (SGA). We report the 9-month history of a 42-year-old female patient whose antipsychotic medication was switched to 800 mg per day of amisulpride. Two weeks after discharge she suffered muscular pain, stiffness, weakness of the legs, rigor, and fever. After attending our outpatient department and being diagnosed, she was transferred to the neurological intensive unit, where the creatine kinase (CK) level was measured at 160,000 U/l. Furthermore extensive rhabdomyolysis accompanied by a compartment syndrome was seen. Surgical intervention was necessary for the latter. The patient was then retransferred to the psychiatric department after treatment with lorazepam and withdrawal of antipsychotic medications. In addition a therapy with valproate sodium was conducted. Long-term high levels of CK and abnormalities in the electromyogram led to the hypothesis of myopathy as a possible risk factor, but a final diagnostic classification was not feasible. This report describes the appearance of a MNS as a consequence of SGA therapy, discusses risk factors and therapy options, and shows the 9-month course. PMID:17924089

  14. Illnesses and deaths among persons attending an electronic dance-music festival - New York City, 2013.

    PubMed

    Ridpath, Alison; Driver, Cynthia R; Nolan, Michelle L; Karpati, Adam; Kass, Daniel; Paone, Denise; Jakubowski, Andrea; Hoffman, Robert S; Nelson, Lewis S; Kunins, Hillary V

    2014-12-19

    Outdoor electronic dance-music festivals (EDMFs) are typically summer events where attendees can dance for hours in hot temperatures. EDMFs have received increased media attention because of their growing popularity and reports of illness among attendees associated with recreational drug use. MDMA (3,4-methylenedioxymethamphetamine) is one of the drugs often used at EDMFs. MDMA causes euphoria and mental stimulation but also can cause serious adverse effects, including hyperthermia, seizures, hyponatremia, rhabdomyolysis, and multiorgan failure. In this report, MDMA and other synthetic drugs commonly used at dance festivals are referred to as "synthetic club drugs." On September 1, 2013, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) received reports of two deaths of attendees at an EDMF (festival A) held August 31-September 1 in NYC. DOHMH conducted an investigation to identify and characterize adverse events resulting in emergency department (ED) visits among festival A attendees and to determine what drugs were associated with these adverse events. The investigation identified 22 cases of adverse events; nine cases were severe, including two deaths. Twenty-one (95%) of the 22 patients had used drugs or alcohol. Of 17 patients with toxicology testing, MDMA and other compounds were identified, most frequently methylone, in 11 patients. Public health messages and strategies regarding adverse health events might reduce illnesses and deaths at EDMFs. PMID:25522087

  15. HMG-CoA-reductase inhibitors and neuropathy: reports to the Netherlands Pharmacovigilance Centre.

    PubMed

    de Langen, J J; van Puijenbroek, E P

    2006-10-01

    The number of patients taking HMG-CoA-reductase inhibitors for hypercholesterolaemia is growing rapidly. Treatment with HMG-CoA-reductase inhibitors significantly reduces the risk of cardiovascular morbidity and mortality, but may rarely cause serious adverse drug reactions (ADRs). The most serious ADRs of HMG-CoA-reductase inhibitors are musculoskeletal symptoms including myopathy and myositis, (life-threatening) rhabdomyolysis and liver failure. Furthermore, peripheral neuropathy might also occur, especially after long-term use of HMG-CoA-reductase inhibitors. Because of the severity and the relative rarity of HMG-CoA-reductase-induced neuropathy, the Netherlands Pharmacovigilance Centre Lareb has analysed its database of reported ADRs for reports concerning neuropathy associated with the use of HMG-CoA-reductase inhibitors. Until June 2005, Lareb received 17 reports of neuropathy, peripheral neuropathy and polyneuropathy and in addition two reports of aggravation of existing polyneuropathy associated with the use of HMG-CoA-reductase inhibitors. The associations neuropathy, peripheral neuropathy and polyneuropathy and the use of hMg-CoA-reductase inhibitors are statistically significantly more often reported to Lareb. The average time to onset supports conclusions of previous studies and case reports that especially long-term exposure increases the risk for peripheral neuropathy. Considering the increasing number of patients taking HMG-CoA-reductase inhibitors, health care professionals should be aware of the possible role of these drugs in neuropathy. PMID:17057271

  16. Adverse effects of statins - mechanisms and consequences.

    PubMed

    Be?towski, Jerzy; Wjcicka, Grazyna; Jamroz-Wi?niewska, Anna

    2009-09-01

    Statins inhibit 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis, which converts HMG-CoA to mevalonate. Statins lower plasma low-density lipoprotein (LDL) cholesterol by causing intracellular cholesterol depletion and upregulating the expression of LDL receptors. Apart from cholesterol, mevalonate is also the substrate for the synthesis of nonsteroid isoprenoids including farnesylpyrophosphate, geranylgeranylpyrophosphate (both attached to small GTP-binding proteins by protein prenyltransferases), coenzyme Q, dolichol, isopentenyladenosine, etc. Depletion of these isoprenoids results in so called "pleiotropic" effects of statins which are independent of cholesterol lowering. Although statins are generally well-tolerated, adverse effects may occur in some patients. These effects result from impaired protein prenylation, deficiency of coenzyme Q involved in mitochondrial electron transport and antioxidant protection, abnormal protein glycosylation due to dolichol shortage, or deficiency of selenoproteins. Myopathy is the most frequent side effect of statins and in some cases may have a form of severe rhabdomyolysis. Less common adverse effects include hepatotoxicity, peripheral neuropathy, impaired myocardial contractility and autoimmune diseases. The risk of these unfavorable effects is largely outweighed by great reduction of cardiovascular events in statin users. However, due to increasing number of patients taking statins, monitoring for any side effects, intense research to recognize their mechanisms and to identify susceptible patients, as well as rational management of these complications are mandatory to further improve safety of these excellent drugs. PMID:19534648

  17. [Fibrate and statine myopathy].

    PubMed

    Finsterer, J

    2003-02-01

    Fibrates and statines are useful in preventing arteriosclerosis and thromboembolic events. However, they should be administered with caution. The risk of fibrate/statine myopathy, the most common side effect of fibrate/statine therapy, increases with dosage, combination of a fibrate with a statine,hypothyroidism, renal insufficiency, and intake of cytochrome P450 inhibitors. In case of clinical signs of a fibrate/statine myopathy such as proximal myalgias, stiffness,weakness, and dark urine, appropriate investigations should be initiated. If they establish the diagnosis of fibrate/statine myopathy, lipid lowering drugs should be immediately withdrawn. If rhabdomyolysis is present, prompt and adequate therapy is required. Though muscle abnormalities are rare side effects, fibrate/statine therapy should be regularly monitored with regard to clinical and laboratory alterations. The new "superstatines" rosuvastatine and pitavastatine reduce serum cholesterol more effectively than the established statines, but it is not known if they also have fewer muscular side effects than established statines. PMID:12596012

  18. The Lightning Heart: A Case Report and Brief Review of the Cardiovascular Complications of Lightning Injury

    PubMed Central

    McIntyre, William F; Simpson, Christopher S; Redfearn, Damian P; Abdollah, Hoshiar; Baranchuk, Adrian

    2010-01-01

    Lightning strike is a rare natural phenomenon, which carries a risk of dramatic medical complications to multiple organ systems and a high risk of fatality. The known complications include but are not limited to: myocardial infarction, arrhythmia, cardiac contusion, stroke, cutaneous burns, respiratory disorders, neurological disorders, acute kidney injury and death. We report a case of a healthy young man who suffered a lightning injury and discuss the cardiovascular complications of lightning injury, ranging from ECG changes to death. The patient in our case, a 27-year old previously healthy male, developed a syndrome of rhabdomyolysis and symptomatic cardiogenic pulmonary edema. Electrocardiographic findings included transient T-wave inversions, late transition shift and long QT. His clinical condition improved with supportive measures. Early recognition of lightning injury syndromes and anticipation of complications may help us improve outcomes for these patients. Evaluation of patients having experienced a lightning injury should include a minimum of a detailed history and physical examination, 12-lead ECG and drawing of baseline troponins. Prolonged electrocardiographical monitoring (for monitoring of ventricular arrhythmias) and assessment for signs and symptoms of hemodynamic compromise may be warranted. PMID:20930961

  19. AIDS-related myopathy.

    PubMed

    Sheikh, Rafiq A.; Yasmeen, Shagufta; Munn, Robert; Ruebner, Boris H.; Ellis, William G.

    1999-09-01

    Infection with the human immunodeficiency virus (HIV) is often associated with the acquired immunodeficiency syndrome (AIDS), and wasting is one of the defining clinical features of AIDS. Muscular weakness due to myopathy may develop at any stage of HIV infection. We report two illustrative cases of HIV-associated myopathies. One was due to inflammatory myosits most likely directly related to the HIV infection, and the other was most likely the result of mitochondrial damage due to zidovudine, a nucleoside analogue commonly used in treating HIV infection. Biopsies from both patients showed alterations of myofiber structures, of varying severity, culminating in necrosis, lipid droplets, and lymphoplasmocytic inflammatory response. The zidovudine-treated patient also showed distinctive mitochondrial changes, predominantly enlargement, variation in shape and size, and disorganization of the cristae. These two types of HIV-associated inflammatory myopathies are reviewed, along with other HIV-associated myopathies, including HIV wasting syndrome, nemaline rod myopathy, pyomyositis, rhabdomyolysis, cardiomyopathy, and other miscellaneous myopathies associated with HIV infection. PMID:11810429

  20. Rapidly reversible multiorgan failure after ingestion of Molly (pure 3,4-methylenedioxymethamphetamine): a case report

    PubMed Central

    2014-01-01

    Introduction Molly is a street name for pure 3,4-methylenedioxymethamphetamine, an amphetamine derivative which acts by enhancing the release of neurotransmitters such as serotonin, dopamine and norepinephrine. This produces euphoria, increased sensory awareness and central stimulation that make it a popular club drug. Nevertheless, it is also associated with serious side effects. We report an unusual case of rapid multiorgan failure after ingestion of Molly. Unlike previously described patterns of 3,4-methylenedioxymethamphetamine-related organ failure, our case does not appear to be related to hyperthermia, rhabdomyolysis or hyponatremia. Case presentation A 24-year-old Hispanic man presented to our hospital with an episode of seizure and subsequently developed acute kidney injury, respiratory failure requiring mechanical ventilation and congestive heart failure after ingestion of Molly. He rapidly recovered with supportive care and was discharged home. Conclusions The spectrum of complications associated with 3,4-methylenedioxymethamphetamine is wide and patient presentation may vary. Moreover, there appears to be multiple mechanisms involved in organ failure. Drug toxicity should be suspected while evaluating a patient with multisystem organ failure of unclear etiology. Treatment is generally supportive sometimes requiring mechanical ventilation and hemodialysis. Nevertheless, complete reversal of organ failure can be expected. PMID:24942782

  1. [Drug interactions with antilipemics].

    PubMed

    Becquemont, Laurent

    2003-01-01

    The HMG-CoA reductase inhibitors (statins) and fibrates have been associated with myotoxicity, which, in some cases, has been fatal. Rhabdomyolysis is frequently observed during drug interactions with elevated plasma concentrations. Statins have a low oral bioavailability because of their intense first-pass extraction. Cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of atorvastatin and simvastatin which present the highest risk of drug interactions with CYP3A4 inhibitors, such as macrolides, antifungal agents, protease inhibitors, calcium channel blockers, amiodarone, and grapefruit juice. Fluvastatin has a low potential for drug interactions due to its CYP2C9-dependant metabolism. Pravastatin liver extraction does not involve CYPs and presents a low potential for drug interactions. Fibrates have a high oral bioavailability (approximately 100%), and this minimises the risk of drug interactions. However, fibrates alter the pharmacokinetics of some drugs, possibly via CYP2C9 and UDP-glucuronyltransferase (UGT) inhibition. Only three cholesterol-reducing agents have demonstrated their ability to reduce the incidence of cardiovascular death in long-term follow-up randomised trials among patients with atherosclerosis. Simvastatin exhibits the highest potential for drug interactions, pravastatin and gemfibrozil the lowest. PMID:12822205

  2. Mechanisms and assessment of statin-related muscular adverse effects

    PubMed Central

    Mohammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mrike, Klaus

    2014-01-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

  3. Prostatic surgery associated acute kidney injury

    PubMed Central

    Costalonga, Elerson Carlos; Costa e Silva, Verônica Torres; Caires, Renato; Hung, James; Yu, Luis; Burdmann, Emmanuel A

    2014-01-01

    Acute kidney injury (AKI) is associated with extended hospital stays, high risks of in-hospital and long-term mortality, and increased risk of incident and progressive chronic kidney disease. Patients with urological diseases are a high-risk group for AKI owing to the coexistence of obstructive uropathy, older age, and preexistent chronic kidney disease. Nonetheless, precise data on the incidence and outcomes of postoperative AKI in urological procedures are lacking. Benign prostatic hyperplasia and prostate cancer are common diagnoses in older men and are frequently treated with surgical procedures. Whereas severe AKI after prostate surgery in general appears to be unusual, AKI associated with transurethral resection of the prostate (TURP) syndrome and with rhabdomyolysis (RM) after radical prostatectomy have been frequently described. The purpose of this review is to discuss the current knowledge regarding the epidemiology, risk factors, outcomes, prevention, and treatment of AKI associated with prostatic surgery. The mechanisms of TURP syndrome and RM following prostatic surgeries will be emphasized. PMID:25374813

  4. Myalgias and Myopathies: Drug-Induced Myalgias and Myopathies.

    PubMed

    Holder, Kathryn

    2016-01-01

    Drugs can cause myalgias and myopathies through a variety of mechanisms. Most drug-induced myopathies are potentially reversible if recognized early. Prescribers should be familiar with common drug-induced myopathies and drug-drug interactions. Clinical presentations can be subacute or acute, ranging from benign muscle pain with mild elevations of serum creatine kinase to fulminant rhabdomyolysis with high creatine kinase levels and potentially life-threatening acute kidney injury. Myalgias and proximal muscle weakness are typical symptoms; onset can be weeks to months after drug exposure. Endocrine disorders and inflammatory etiologies should be excluded because their management may differ from that of drug-induced myopathies. Statin drugs are prescribed widely, and statin-induced myopathy is one of the most commonly recognized and studied myopathies. Risk factors include dose and type of statin prescribed, older age, female sex, genetic predisposition, and concomitant use of other drugs metabolized by the cytochrome P450 system. Glucocorticoids, immunologic drugs, and antimicrobials, as well as other drugs and alcohol, can cause myopathies. Management typically involves discontinuing the drug and switching to an alternative drug or considering an alternative dosing schedule. Referral to a neuromuscular subspecialist is warranted if symptoms persist. PMID:26734833

  5. Loxosceles gaucho Venom-Induced Acute Kidney Injury In Vivo and In Vitro Studies

    PubMed Central

    Lucato, Rui V.; Abdulkader, Regina C. R. M.; Barbaro, Katia C.; Mendes, Glria E.; Castro, Isac; Baptista, Maria A. S. F.; Cury, Patrcia M.; Malheiros, Denise M. C.; Schor, Nestor; Yu, Luis; Burdmann, Emmanuel A.

    2011-01-01

    Background Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. Methodology/Principal Findings In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. Conclusions/Significance Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite. PMID:21655312

  6. Bacterial, Fungal, Parasitic, and Viral Myositis

    PubMed Central

    Crum-Cianflone, Nancy F.

    2008-01-01

    Infectious myositis may be caused by a broad range of bacterial, fungal, parasitic, and viral agents. Infectious myositis is overall uncommon given the relative resistance of the musculature to infection. For example, inciting events, including trauma, surgery, or the presence of foreign bodies or devitalized tissue, are often present in cases of bacterial myositis. Bacterial causes are categorized by clinical presentation, anatomic location, and causative organisms into the categories of pyomyositis, psoas abscess, Staphylococcus aureus myositis, group A streptococcal necrotizing myositis, group B streptococcal myositis, clostridial gas gangrene, and nonclostridial myositis. Fungal myositis is rare and usually occurs among immunocompromised hosts. Parasitic myositis is most commonly a result of trichinosis or cystericercosis, but other protozoa or helminths may be involved. A parasitic cause of myositis is suggested by the travel history and presence of eosinophilia. Viruses may cause diffuse muscle involvement with clinical manifestations, such as benign acute myositis (most commonly due to influenza virus), pleurodynia (coxsackievirus B), acute rhabdomyolysis, or an immune-mediated polymyositis. The diagnosis of myositis is suggested by the clinical picture and radiologic imaging, and the etiologic agent is confirmed by microbiologic or serologic testing. Therapy is based on the clinical presentation and the underlying pathogen. PMID:18625683

  7. Mitochondrial dysfunction by synthetic ligands of peroxisome proliferator activated receptors (PPARs).

    PubMed

    Scatena, Roberto; Martorana, Giuseppe E; Bottoni, Patrizia; Giardina, Bruno

    2004-08-01

    PPARs are a class of nuclear receptors involved in lipid and glucidic metabolism, immune regulation and cell differentiation. This spectrum of biological activities stimulated pharmacological research to synthetize different molecules with PPARs binding activity with beneficial therapeutic effects. As a matter of fact, some synthetic PPAR-ligands have been already employed in pharmacotherapy: PPAR-alpha ligands, such as fibrates, are used in hyperlipidemias and thiazolidinediones, mainly PPAR-gamma ligands, are employed as insulin sensitizers. However, both classes of drugs showed pharmacotoxicological profiles which cannot be fully ascribed to activation of their specific receptors and which are causing a growing incidence of dramatic side effects (rhabdomyolysis, acute liver failure, heart failure, etc.). A re-evaluation of the biological activities of PPAR synthetic ligands, in particular of the mitochondrial dysfunction based on a rotenone-like Complex I partial inhibition and of its consequent metabolic adaptations, seems to explain some of the pathophysiologic aspects of PPARs allowing a better definition of the therapeutic properties of the so-called PPAR-ligands. PMID:15545227

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

    PubMed

    Garca-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. PMID:17886710

  9. Proteasome inhibition and oxidative reactions disrupt cellular homeostasis during heme stress

    PubMed Central

    Vallelian, F; Deuel, J W; Opitz, L; Schaer, C A; Puglia, M; Lnn, M; Engelsberger, W; Schauer, S; Karnaukhova, E; Spahn, D R; Stocker, R; Buehler, P W; Schaer, D J

    2015-01-01

    Dual control of cellular heme levels by extracellular scavenger proteins and degradation by heme oxygenases is essential in diseases associated with increased heme release. During severe hemolysis or rhabdomyolysis, uncontrolled heme exposure can cause acute kidney injury and endothelial cell damage. The toxicity of heme was primarily attributed to its pro-oxidant effects; however additional mechanisms of heme toxicity have not been studied systematically. In addition to redox reactivity, heme may adversely alter cellular functions by binding to essential proteins and impairing their function. We studied inducible heme oxygenase (Hmox1)-deficient mouse embryo fibroblast cell lines as a model to systematically explore adaptive and disruptive responses that were triggered by intracellular heme levels exceeding the homeostatic range. We extensively characterized the proteome phenotype of the cellular heme stress responses by quantitative mass spectrometry of stable isotope-labeled cells that covered more than 2000 individual proteins. The most significant signals specific to heme toxicity were consistent with oxidative stress and impaired protein degradation by the proteasome. This ultimately led to an activation of the response to unfolded proteins. These observations were explained mechanistically by demonstrating binding of heme to the proteasome that was linked to impaired proteasome function. Oxidative heme reactions and proteasome inhibition could be differentiated as synergistic activities of the porphyrin. Based on the present data a novel model of cellular heme toxicity is proposed, whereby proteasome inhibition by heme sustains a cycle of oxidative stress, protein modification, accumulation of damaged proteins and cell death. PMID:25301065

  10. Omacor and omega-3 fatty acids for treatment of coronary artery disease and the pleiotropic effects.

    PubMed

    Kar, Subrata

    2014-01-01

    Omega-3 polyunsaturated fatty acids are found in fish oil and they have been shown to mitigate the risk of cardiovascular disease. Omega-3 fatty acids are essential fatty acids because they cannot be synthesized de novo and must be consumed from dietary sources such as marine fish. It reduces fatal and nonfatal myocardial infarction, stroke, coronary artery disease, sudden cardiac death, and all-cause mortality. It also has beneficial effects in mortality reduction after a myocardial infarction. Omacor is a highly potent form of Omega-3 fatty acids that lowers plasma triglycerides. In patients with severe hypertriglyceridemia who are refractory to statins, it helps augment triglyceride reduction. Omacor also increases high-density lipoprotein and decreases low-density lipoprotein levels. It is well tolerated with minimal adverse effects and no known interactions causing rhabdomyolysis. In high doses, Omacor has pronounced cardiovascular benefits with improvement of triglycerides and various lipid parameters. Omega-3 fatty acids have also been shown to have beneficial effects on arrhythmias, inflammation, and heart failure. It may also decrease platelet aggregation and induce vasodilation. Omega-3 fatty acids also reduce atherosclerotic plaque formation and stabilize plaques preventing plaque rupture leading to acute coronary syndrome. Moreover, omega-3 fatty acids may have antioxidant properties that improve endothelial function and may contribute to its antiatherosclerotic benefits. In this review, we sought to provide the current literature on the use of omega-3 fatty acids and the potent formulation Omacor in the treatment of coronary artery disease. PMID:21975796

  11. Non-cardiovascular effects associated with statins

    PubMed Central

    Martin, Seth S; Blumenthal, Roger S

    2014-01-01

    Statins form the pharmacologic cornerstone of the primary and secondary prevention of atherosclerotic cardiovascular disease. In addition to beneficial cardiovascular effects, statins seem to have multiple non-cardiovascular effects. Although early concerns about statin induced hepatotoxicity and cancer have subsided owing to reassuring evidence, two of the most common concerns that clinicians have are myopathy and diabetes. Randomized controlled trials suggest that statins are associated with a modest increase in the risk of myositis but not the risk of myalgia. Severe myopathy (rhabdomyolysis) is rare and often linked to a statin regimen that is no longer recommended (simvastatin 80 mg). Randomized controlled trials and meta-analyses suggest an increase in the risk of diabetes with statins, particularly with higher intensity regimens in people with two or more components of the metabolic syndrome. Other non-cardiovascular effects covered in this review are contrast induced nephropathy, cognition, cataracts, erectile dysfunction, and venous thromboembolism. Currently, systematic reviews and clinical practice guidelines indicate that the cardiovascular benefits of statins generally outweigh non-cardiovascular harms in patients above a certain threshold of cardiovascular risk. Literature is also accumulating on the potential non-cardiovascular benefits of statins, which could lead to novel applications of this class of drug in the future. PMID:25035309

  12. Safety of statins: an update

    PubMed Central

    Hu, Miao; Cheung, Bernard M.Y.

    2012-01-01

    Statins are widely used and have been proven to be effective in the prevention of atherosclerotic vascular disease events, primarily by reducing plasma low-density lipoprotein cholesterol concentrations. Although statins are generally well tolerated and present an excellent safety profile, adverse effects from muscle toxicity and liver enzyme abnormalities may occur in some patients. Myopathy and rhabdomyolysis are rare with statin monotherapy at the approved dose ranges, but the risk increases with use of higher doses, interacting drugs and genetic predisposition. Asymptomatic increases in liver transaminases with statin treatment do not seem to be associated with an increased risk of liver disease. Therefore, statin treatment can be safely used in patients with mild to moderately abnormal liver tests that are potentially attributable to nonalcoholic fatty liver disease and can improve liver tests and reduce cardiovascular morbidity in this group of patients. The risks of other unfavorable effects such as the slightly increased risk of new-onset diabetes and potentially increased risk of haemorrhagic stroke are much smaller than the cardiovascular benefits with the use of statins. PMID:25083232

  13. Status spasticus and psoas muscle edema due to anti-GAD antibody associated stiff-man syndrome

    PubMed Central

    Maramattom, Boby Varkey

    2015-01-01

    Severe muscle rigidity and spasms are uncommon causes of Intensive Care Unit (ICU) admissions. Stiff-man syndrome (SMS) is a rare disorder characterized by continuous muscle spasms, axial muscle rigidity, “tin soldier gait,” and continuous motor unit activity on electromyography. There are three clinical variants of SMS; stiff-limb syndrome, classical SMS, and paraneoplastic encephalomyelitis with rigidity and myoclonus. Three types of antibodies have been associated with SMS; however, anti-glutamic acid decarboxylase (GAD) antibodies are the most frequent and are seen in the idiopathic type of SMS. The spasms of SMS can be very disabling and severe enough to cause muscle ruptures and skeletal fractures. We present a case of anti-GAD positive SMS with “status spasticus” causing bilateral psoas myoedema and rhabdomyolysis due to repeated axial muscle jerking in a 64-year-old man and discuss the differential diagnosis of a “jerking patient in the ICU.” PMID:26321813

  14. A pharmacovigilance program from laboratory signals for the detection and reporting of serious adverse drug reactions in hospitalized patients.

    PubMed

    Ramirez, E; Carcas, A J; Borobia, A M; Lei, S H; Piana, E; Fudio, S; Frias, J

    2010-01-01

    The detection and reporting of serious adverse drug reactions (SADRs) have become important components of monitoring and evaluation activities performed in hospitals. We present the implementation of a prospective pharmacovigilance program based on automatic laboratory signals (ALSs) at a hospital. We also report the general findings after the first year of operation of the program, which involved ALSs that indicate various SADRs: agranulocytosis, aplastic anemia, liver injury, thrombocytopenia, hyponatremia, and rhabdomyolysis. The number of hospitalizations during the year was 54,525, and 1,732 patients experienced at least one ALS. The review of electronic medical records (EMRs) showed that no alternative cause (i.e., no non-SADR explanation) for the ALS was identified in 520 (30%) of the patients. After the individual ALS-patient evaluation, a total of 110 SADRs (6.35% of those identified after reviewing EMRs and 21.15% of those requiring individual patient evaluations) were identified. In other words, in order to identify a single SADR, we had to review the electronic records of approximately 16 patients and personally visit 5 patients. PMID:19890254

  15. [Pharmacokinetics characteristics of dexamethasone in Crush syndrome model rats].

    PubMed

    Murata, Isamu; Otsuka, Akio; Hara, Chihiro; Motohashi, Risa; Kouno, Shiho; Inoue, Yutaka; Kanamoto, Ikuo

    2015-01-01

    Crush syndrome (CS) is characterized by ischemia/reperfusion-induced rhabdomyolysis and subsequent systemic inflammation and has a high mortality rate, even when treated with conventional therapy. In previous studies, we demonstrated that treatment of rats with acute lethal CS using dexamethasone (DEX) had therapeutic effects in laboratory findings and improved the clinical course of CS. However, because the application of DEX in CS therapy is unknown, evaluation of the pharmacokinetic parameters of DEX was considered essential to support its clinical use. Here, we investigated the pharmacokinetic characteristics of DEX in a rat model of CS. Anesthetized rats were subjected to bilateral hind limb compression using rubber tourniquets for 5 h, followed by reperfusion for 0 to 24 h. Rats were divided randomly into 4 groups: saline-treated sham (S) and CS groups and 5.0 mg/kg DEX-treated S (S-DEX) and CS (CS-DEX) groups. Blood and tissue samples were collected for HPLC analysis. In the CS-DEX group, the pharmacokinetic parameters of the area under the concentration-time curve, mean residence time, and distribution volume levels increased significantly compared to the S-DEX group, whereas total body clearance, elimination rate constant, and renal clearance levels decreased significantly. Moreover, decrease of muscle tissue DEX concentration and of CYP3A activity were observed in the CS-DEX group. These results show the pharmacokinetic characteristics of DEX in the rat CS model and support the potential use of DEX in disaster medical care. PMID:25747231

  16. Integration of biosensors and drug delivery technologies for early detection and chronic management of illness.

    PubMed

    Ngoepe, Mpho; Choonara, Yahya E; Tyagi, Charu; Tomar, Lomas Kumar; du Toit, Lisa C; Kumar, Pradeep; Ndesendo, Valence M K; Pillay, Viness

    2013-01-01

    Recent advances in biosensor design and sensing efficacy need to be amalgamated with research in responsive drug delivery systems for building superior health or illness regimes and ensuring good patient compliance. A variety of illnesses require continuous monitoring in order to have efficient illness intervention. Physicochemical changes in the body can signify the occurrence of an illness before it manifests. Even with the usage of sensors that allow diagnosis and prognosis of the illness, medical intervention still has its downfalls. Late detection of illness can reduce the efficacy of therapeutics. Furthermore, the conventional modes of treatment can cause side-effects such as tissue damage (chemotherapy and rhabdomyolysis) and induce other forms of illness (hepatotoxicity). The use of drug delivery systems enables the lowering of side-effects with subsequent improvement in patient compliance. Chronic illnesses require continuous monitoring and medical intervention for efficient treatment to be achieved. Therefore, designing a responsive system that will reciprocate to the physicochemical changes may offer superior therapeutic activity. In this respect, integration of biosensors and drug delivery is a proficient approach and requires designing an implantable system that has a closed loop system. This offers regulation of the changes by means of releasing a therapeutic agent whenever illness biomarkers prevail. Proper selection of biomarkers is vital as this is key for diagnosis and a stimulation factor for responsive drug delivery. By detecting an illness before it manifests by means of biomarkers levels, therapeutic dosing would relate to the severity of such changes. In this review various biosensors and drug delivery systems are discussed in order to assess the challenges and future perspectives of integrating biosensors and drug delivery systems for detection and management of chronic illness. PMID:23771157

  17. Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats.

    PubMed

    Feng, Yuan; Wang, Changyuan; Liu, Qi; Meng, Qiang; Huo, Xiaokui; Liu, Zhihao; Sun, Pengyuan; Yang, Xiaobo; Sun, Huijun; Qin, Jianhua; Liu, Kexin

    2016-01-01

    A patient with rheumatoid arthritis developed rhabdomyolysis while undergoing treatment with mizoribine concomitantly with bezafibrate. The symptoms rapidly disappeared and laboratory test results normalized when she discontinued the two drugs. The purpose of the present study was to elucidate the transporter-mediated molecular pharmacokinetic mechanisms of drug-drug interactions between bezafibrate and mizoribine. Comparing bezafibrate-mizoribine group with bezafibrate group, the Tmax and Cmax of bezafibrate were essentially unchanged in rats. The AUC of bezafibrate was significantly increased and t1/2β was prolonged markedly with an obviously reduction in plasma clearance and cumulative urinary excretion. The changes were similar to oral studies following intravenous co-administration. In rat kidney slices, the uptake of bezafibrate was markedly inhibited by p-aminohippurate, benzylpenicillin and probenecid but not by tetraethyl ammonium. Mizoribine not only decreased the uptake of bezafibrate, but also inhibited the uptake of p-aminohippurate and benzylpenicillin. The uptakes of bezafibrate and mizoribine were significantly higher compared to vector-HEK293 cells. The uptakes of bezafibrate and mizoribine in highest concentration were increased 1.63 and 1.46 folds in hOAT1-transfected cells, 1.43 and 1.24 folds in hOAT3-transfected cells, respectively. The Km values of bezafibrate uptake by hOAT1/3hOAT1-/hOAT3-HEK293 K293 cells were increased 1.68 fold in hOAT1-HEK293 cell and 2.12 fold in hOAT3-HEK293 cell in the presence of mizoribine with no change of Vmax. It indicated that mizoribine could inhibit the uptake of bezafibrate by hOAT1/3-HEK293 cells in a competitive way. In conclusion, OAT1 and OAT3 are the target transporters of drug-drug interactions between bezafibrate and mizoribine in pharmacokinetic aspects. PMID:26474691

  18. SLCO1B1 Polymorphisms and Statin-Induced Myopathy

    PubMed Central

    Stewart, Alison

    2013-01-01

    Statin drugs are highly effective in lowering blood concentrations of LDL-cholesterol, with concomitant reduction in risk of major cardiovascular events. Although statins are generally regarded as safe and well-tolerated, some users develop muscle symptoms that are mostly mild but in rare cases can lead to life-threatening rhabdomyolysis. The SEARCH genome-wide association study, which has been independently replicated, found a significant association between the rs4149056 (c.521T>C) single-nucleotide polymorphism (SNP) in the SLCO1B1 gene, and myopathy in individuals taking 80 mg simvastatin per day, with an odds ratio of 4.5 per rs4149056 C allele. The purpose of this paper is to assemble evidence relating to the analytical validity, clinical validity and clinical utility of using SLCO1B1 rs4149056 genotyping to inform choice and dose of statin treatment, with the aim of minimising statin-induced myopathy and increasing adherence to therapy. Genotyping assays for the rs4149056 SNP appear to be robust and accurate, though direct evidence for the performance of array-based platforms in genotyping individual SNPs was not found. Using data from the SEARCH study, calculated values for the clinical sensitivity, specificity, positive- and negative-predictive values of a test for the C allele to predict definite or incipient myopathy during 5 years of 80 mg/day simvastatin use were 70.4%, 73.7%, 4.1% and 99.4% respectively. There is a need for studies comparing the clinical validity of SLCO1B1 rs4149056 genotyping with risk scores for myopathy based on other factors such as racial background, statin type and dose, gender, body mass index, co-medications and co-morbidities. No direct evidence was found for clinical utility of statin prescription guided by SLCO1B1 genotype. PMID:24459608

  19. Sympathomimetic syndrome, choreoathetosis, and acute kidney injury following "bath salts" injection.

    PubMed

    Sutamtewagul, Grerk; Sood, Vineeta; Nugent, Kenneth

    2014-01-01

    "Bath salts" is a well known street drug which can cause several cardiovascular and neuropsychiatric symptoms. However, only one case of acute kidney injury has been reported in the literature. We present a case with sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury following the use of bath salts. A 37-year-old man with past medical history of hypertension and depression was brought to the emergency center with body shaking. Three days before admission he injected 3 doses of bath salts intravenously and felt eye pain with blurry vision followed by a metallic taste, strange smells, profuse sweating, and body shaking. At presentation he had a sympathomimetic syndrome including high blood pressure, tachycardia, tachypnea, and hyperhydrosis with choreoathetotic movements. Laboratory testing revealed leukocytosis and acute kidney injury with a BUN of 95 mg/ dL and a creatinine of 15.2 mg/dL. Creatine kinase was 4,457 IU/dL. Urine drug screen is negative for amphetamine, cannabinoids, and cocaine; blood alcohol level was zero. During his ICU stay he became disoriented and agitated. Supportive treatment with 7.2 liters of intravenous fluid over 3 days, haloperidol, and lorazepam gradually improved his symptoms and his renal failure. Bath salts contain 3,4-methylenedioxypyrovalerone, a psychoactive norepinephrine and dopamine reuptake inhibitor. Choreoathetosis in this patient could be explained through dopaminergic effect of bath salts or uremic encephalopathy. The mechanism for acute kidney injury from bath salts may involve direct drug effects though norepinephrine and dopamine-induced vasoconstriction (renal ischemia), rhabdomyolysis, hyperthermia, and/or volume contraction. PMID:24356039

  20. Clinical Features of Severe Wasp Sting Patients with Dominantly Toxic Reaction: Analysis of 1091 Cases

    PubMed Central

    Ding, Fengfei; Xie, Minjie; Lv, Jiagao; Yao, Jihua; Pan, Dengji; Sun, Qian; Liu, Chenchen; Chen, Tie; Li, Shusheng; Wang, Wei

    2013-01-01

    Background Massive wasp stings have been greatly underestimated and have not been systematically studied. The aim of this study was to identify the clinical features and treatment strategies of severe wasp stings. Methods and Findings A multicenter retrospective study was undertaken in 35 hospitals and medical centers including 12 tertiary care hospitals and 23 secondary care hospitals in the Hubei Province, China. The detailed clinical data of 1091 hospitalized wasp sting patients were investigated. Over three-fourths (76.9%) of the cases had 10 or more stings and the in-hospital mortality of patients was 5.1%. Forty-eight patients died of organ injury following toxic reactions to the stings, whereas six died from anaphylactic shock. The in-hospital mortality in patients with >10 stings was higher than that of ≤10 stings (5.2% vs. 1.0%, p = 0.02). Acute kidney injury (AKI) was seen in 21.0% patients and most patients required blood purification therapy. Rhabdomyolysis was seen in 24.1% patients, hemolysis in 19.2% patients, liver injury in 30.1% patients, and coagulopathy in 22.5% patients. Regression analysis revealed that high creatinine level, shock, oliguria, and anemia were risk factors for death. Blood purification therapy was beneficial for patients with ≥20 stings and delayed hospital admission of patients (≥4 hours after sting). Conclusions In China, most patients with multiple wasp stings presented with toxic reactions and multiple organ dysfunction caused by the venom rather than an anaphylactic reaction. AKI is the prominent clinical manifestation of wasp stings with toxic reaction. High creatinine levels, shock, oliguria, and anemia were risk factors for death. PMID:24391743

  1. Hemolysis as a rare but potentially life-threatening complication of hemodialysis: a case report

    PubMed Central

    2014-01-01

    Background The burden of end-stage renal disease (ESRD) in the United States has increased dramatically over the past 30 years with almost 613,000 patients receiving renal replacement therapy in 2011. That same year, more than 112,000 new patients initiated dialysis with 92% of them receiving hemodialysis (HD). These patients experience significant morbidity and mortality with very frequent emergency room visits. Acute hemolysis associated with HD is a rare complication; however, if it’s not recognized early and managed adequately, it can be associated with life-threatening complications such as hyperkalemia and even myocardial infarction. Case presentation 66-year-old African-American female with a history of ESRD secondary to hypertension developed a blood infiltration on the arterial side of her arteriovenous fistula followed by sudden onset of diffuse abdominal pain with nausea and vomiting during her regular HD treatment. She was referred to the emergency department where she was found to have shortness of breath with improved gastrointestinal symptoms. Her initial work-up revealed a severe anemia with a hematocrit of 10%. Further work-up revealed massive hemolysis, likely mechanical in nature and believed to be induced by malpositioning of her HD needle in the fistula. Her hospital course was complicated by rhabdomyolysis and acute myocardial infarction thought to be secondary to supply–demand ischemia in the setting of her profound anemia. Within a week, she eventually had a full recovery. Conclusion It is extremely important for physicians and particularly emergency department physicians to be aware of this potentially life-threatening complication of HD and have a high index of suspicion in the setting of acute anemia with hemolysis in this population. PMID:25065406

  2. Inborn errors of cytoplasmic triglyceride metabolism.

    PubMed

    Wu, Jiang Wei; Yang, Hao; Wang, Shu Pei; Soni, Krishnakant G; Brunel-Guitton, Catherine; Mitchell, Grant A

    2015-01-01

    Triglyceride (TG) synthesis, storage, and degradation together constitute cytoplasmic TG metabolism (CTGM). CTGM is mostly studied in adipocytes, where starting from glycerol-3-phosphate and fatty acyl (FA)-coenzyme A (CoA), TGs are synthesized then stored in cytoplasmic lipid droplets. TG hydrolysis proceeds sequentially, producing FAs and glycerol. Several reactions of CTGM can be catalyzed by more than one enzyme, creating great potential for complex tissue-specific physiology. In adipose tissue, CTGM provides FA as a systemic energy source during fasting and is related to obesity. Inborn errors and mouse models have demonstrated the importance of CTGM for non-adipose tissues, including skeletal muscle, myocardium and liver, because steatosis and dysfunction can occur. We discuss known inborn errors of CTGM, including deficiencies of: AGPAT2 (a form of generalized lipodystrophy), LPIN1 (childhood rhabdomyolysis), LPIN2 (an inflammatory condition, Majeed syndrome, described elsewhere in this issue), DGAT1 (protein loosing enteropathy), perilipin 1 (partial lipodystrophy), CGI-58 (gene ABHD5, neutral lipid storage disease (NLSD) with ichthyosis and "Jordan's anomaly" of vacuolated polymorphonuclear leukocytes), adipose triglyceride lipase (ATGL, gene PNPLA2, NLSD with myopathy, cardiomyopathy and Jordan's anomaly), hormone-sensitive lipase (HSL, gene LIPE, hypertriglyceridemia, and insulin resistance). Two inborn errors of glycerol metabolism are known: glycerol kinase (GK, causing pseudohypertriglyceridemia) and glycerol-3-phosphate dehydrogenase (GPD1, childhood hepatic steatosis). Mouse models often resemble human phenotypes but may diverge markedly. Inborn errors have been described for less than one-third of CTGM enzymes, and new phenotypes may yet be identified. PMID:25300978

  3. Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro

    PubMed Central

    de Luna, Noem; Brull, Astrid; Guiu, Josep Maria; Lucia, Alejandro; Martin, Miguel Angel; Arenas, Joaquin; Mart, Ramon; Andreu, Antoni L.; Pins, Toms

    2015-01-01

    ABSTRACT McArdle disease, also termed glycogen storage disease type V, is a disorder of skeletal muscle carbohydrate metabolism caused by inherited deficiency of the muscle-specific isoform of glycogen phosphorylase (GP-MM). It is an autosomic recessive disorder that is caused by mutations in the PYGM gene and typically presents with exercise intolerance, i.e. episodes of early exertional fatigue frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL) and brain (GP-BB) isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is the main GP isoform found in human and rat foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in McArdle mice that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal muscle from individuals with McArdle disease. We treated mouse primary skeletal muscle cultures in vitro with sodium valproate (VPA), a histone deacetylase inhibitor. After VPA treatment, myotubes expressed GP-BB and a dose-dependent decrease in glycogen accumulation was also observed. Thus, this in vitro model could be useful for high-throughput screening of new drugs to treat this disease. The immortalization of these primary skeletal muscle cultures could provide a never-ending source of cells for this experimental model. Furthermore, VPA could be considered as a gene-expression modulator, allowing compensatory expression of GP-BB and decreased glycogen accumulation in skeletal muscle of individuals with McArdle disease. PMID:25762569

  4. The determinants of transverse tubular volume in resting skeletal muscle.

    PubMed

    Sim, Jingwei; Fraser, James A

    2014-12-15

    The transverse tubular (t)-system of skeletal muscle couples sarcolemmal electrical excitation with contraction deep within the fibre. Exercise, pathology and the composition of the extracellular fluid (ECF) can alter t-system volume (t-volume). T-volume changes are thought to contribute to fatigue, rhabdomyolysis and disruption of excitation-contraction coupling. However, mechanisms that underlie t-volume changes are poorly understood. A multicompartment, history-independent computer model of rat skeletal muscle was developed to define the minimum conditions for t-volume stability. It was found that the t-system tends to swell due to net ionic fluxes from the ECF across the access resistance. However, a stable t-volume is possible when this is offset by a net efflux from the t-system to the cell and thence to the ECF, forming a net ion cycle ECF?t-system?sarcoplasm?ECF that ultimately depends on Na(+)/K(+)-ATPase activity. Membrane properties that maximize this circuit flux decrease t-volume, including PNa(t) > PNa(s), PK(t) < PK(s) and N(t) < N(s) [P, permeability; N, Na(+)/K(+)-ATPase density; (t), t-system membrane; (s), sarcolemma]. Hydrostatic pressures, fixed charges and/or osmoles in the t-system can influence the magnitude of t-volume changes that result from alterations in this circuit flux. Using a parameter set derived from literature values where possible, this novel theory of t-volume was tested against data from previous experiments where t-volume was measured during manipulations of ECF composition. Predicted t-volume changes correlated satisfactorily. The present work provides a robust, unifying theoretical framework for understanding the determinants of t-volume. PMID:25384782

  5. Lessons from calsequestrin-1 ablation in vivo: much more than a Ca(2+) buffer after all.

    PubMed

    Protasi, Feliciano; Paolini, Cecilia; Canato, Marta; Reggiani, Carlo; Quarta, Marco

    2011-12-01

    Calsequestrin type-1 (CASQ1), the main sarcoplasmic reticulum (SR) Ca(2+) binding protein, plays a dual role in skeletal fibers: a) it provides a large pool of rapidly-releasable Ca(2+) during excitation-contraction (EC) coupling; and b) it modulates the activity of ryanodine receptors (RYRs), the SR Ca(2+) release channels. We have generated a mouse lacking CASQ1 in order to further characterize the role of CASQ1 in skeletal muscle. Contrary to initial expectations, CASQ1 ablation is compatible with normal motor activity, in spite of moderate muscle atrophy. However, CASQ1 deficiency results in profound remodeling of the EC coupling apparatus: shrinkage of junctional SR lumen; proliferation of SR/transverse-tubule contacts; and increased density of RYRs. While force development during a twitch is preserved, it is nevertheless characterized by a prolonged time course, likely reflecting impaired Ca(2+) re-uptake by the SR. Finally, lack of CASQ1 also results in increased rate of SR Ca(2+) depletion and inability of muscle to sustain tension during a prolonged tetani. All modifications are more pronounced (or only found) in fast-twitch extensor digitorum longus muscle compared to slow-twitch soleus muscle, likely because the latter expresses higher amounts of calsequestrin type-2 (CASQ2). Surprisingly, male CASQ1-null mice also exhibit a marked increased rate of spontaneous mortality suggestive of a stress-induced phenotype. Consistent with this idea, CASQ1-null mice exhibit an increased susceptibility to undergo a hypermetabolic syndrome characterized by whole body contractures, rhabdomyolysis, hyperthermia and sudden death in response to halothane- and heat-exposure, a phenotype remarkably similar to human malignant hyperthermia and environmental heat-stroke. The latter findings validate the CASQ1 gene as a candidate for linkage analysis in human muscle disorders. PMID:22130610

  6. Inhibition of prenyltransferase activity by statins in both liver and muscle cell lines is not causative of cytotoxicity.

    PubMed

    Gee, Rowena H; Spinks, Jenny N; Malia, Jason M; Johnston, Jonathan D; Plant, Nick J; Plant, Kathryn E

    2015-03-01

    As inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, statins are an important first-line treatment for hypercholesterolemia. However, a recognized side-effect of statin therapy is myopathy, which in severe cases can present as potentially fatal rhabdomyolysis. This represents an important impediment to successful statin therapy, and despite decades of research the molecular mechanisms underlying this side-effect remain unclear. Current evidence supports a role for reduced levels of mevalonate pathway intermediates, with the most accepted hypothesis being a reduction in isoprenoids formation, leading to faulty post-translational modifications of membrane-associated proteins. We have undertaken a comprehensive analysis of the impact of nine statins on two human cell lines; Huh7 hepatoma and RD rhabdomyosarcoma. In both cell lines, concentration-dependent inhibition of prenylation was observed for cerivastatin and simvastatin, which could be rescued with the pathway intermediate mevalonate; in general, muscle cells were more sensitive to this effect, as measured by the levels of unprenylated Rap1A, a marker for prenylation by geranylgeranyl transferase I. Concentration-dependent toxicity was observed in both cell lines, with muscle cells again being more sensitive. Importantly, there was no correlation between inhibition of prenylation and cell toxicity, suggesting they are not causally linked. The lack of a causal relationship was confirmed by the absence of cytotoxicity in all cell lines following exposure to specific inhibitors of geranylgeranyl transferases I and II, and farnesyl transferase. As such, we provide strong evidence against the commonly accepted hypothesis linking inhibition of prenylation and statin-mediated toxicity, with the two processes likely to be simultaneous but independent. PMID:25578243

  7. The role of microRNAs in equine medicine: a review.

    PubMed

    van der Kolk, J H; Pacholewska, A; Gerber, V

    2015-06-01

    The search for new markers of diseases in human as well as veterinary medicine is ongoing. Recently, microRNAs (miRNAs or miRs) have emerged as potential new biomarkers. MiRNAs are short sequences of RNA (?22 nucleotides) that regulate gene expression via their target messenger RNA (mRNA). Circulating miRNAs in blood can be used as novel diagnostic markers for diseases due to their evolutionary conservation and stability. As a consequence of their systemic and manifold effects on the gene expression in various target organs, the concept that miRNAs could function as hormones has been suggested. This review summarizes the biogenesis, maturation, and stability of miRNAs and discusses their use as potential biomarkers in equine medicine. To date, over 700 equine miRNAs are identified with distinct subsets of miRNAs differentially expressed in a tissue-specific manner. A physiological involvement of various miRNAs in the regulation of cell survival, steroidogenesis, and differentiation during follicle selection and ovulation in the monovular equine ovary has been demonstrated. Furthermore, miRNAs might be used as novel diagnostic markers for myopathies such as polysaccharide storage myopathy and recurrent exertional rhabdomyolysis as well as osteochondrosis. Preliminary data indicate that miRNAs in blood might play important roles in equine glucose metabolism pathway. Of note, breed differences have been reported regarding the normal equine miRNA signature. For disease prevention, it is of utmost importance to identify disease-associated biomarkers which help detect diseases before symptoms appear. As such, circulating miRNAs represent promising novel diagnostic markers in equine medicine. PMID:25695624

  8. Emerging drugs of abuse: current perspectives on substituted cathinones.

    PubMed

    Paillet-Loilier, Magalie; Cesbron, Alexandre; Le Boisselier, Reynald; Bourgine, Joanna; Debruyne, Danile

    2014-01-01

    Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines. PMID:24966713

  9. Preventive effects of hyperbaric oxygen treatment on glycerol-induced myoglobinuric acute renal failure in rats.

    PubMed

    Ayvaz, Suleyman; Aksu, Burhan; Kanter, Mehmet; Uzun, Hafize; Erboga, Mustafa; Colak, Alkin; Basaran, Umit Nusret; Pul, Mehmet

    2012-04-01

    Myoglobinuric acute renal failure (ARF) is a uremic syndrome caused by traumatic or non-traumatic skeletal muscle breakdown and intracellular elements that are released into the bloodstream. We hypothesized that hyperbaric oxygen (HBO) therapy could be beneficial in the treatment of myoglobinuric ARF caused by rhabdomyolysis. A total of 32 rats were used in the study. The rats were divided into four groups: control, control+hyperbaric oxygen (control+HBO), ARF, and ARF+hyperbaric oxygen (ARF+HBO). Glycerol (8 ml/kg) was injected into the hind legs of each of the rats in ARF and ARF+HBO groups. 2.5 atmospheric absolute HBO was applied to the rats in the control+HBO and ARF+HBO groups for 90 min on two consecutive days. Plasma urea, creatinine, sodium, potassium, calcium, aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, creatinine kinase and urine creatinine and sodium were examined. Creatinine clearance and fractional sodium excretion could then be calculated. Superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) levels were assessed in renal tissue. Tissue samples were evaluated by Hematoxylin-eosin, PCNA and TUNEL staining histopathologically. MDA levels were found to be significantly decreased whereas SOD and CAT were twofold higher in the ARF+HBO group compared to the ARF group. Renal function tests were ameliorated by HBO therapy. Semiquantitative evaluation of histopathological findings indicated that necrosis and cast formation was decreased by HBO therapy and TUNEL staining showed that apoptosis was inhibited. PCNA staining showed that HBO therapy did not increase regeneration. Ultimately, we conclude that, in accordance with our hypothesis, HBO could be beneficial in the treatment of myoglobinuric ARF. PMID:22311626

  10. Demographic, pathologic, and toxicological profiles of 127 decedents testing positive for ephedrine alkaloids.

    PubMed

    Blechman, Keith M; Karch, Steven B; Stephens, Boyd G

    2004-01-01

    The relative toxicity of ephedra-containing dietary supplements is disputed. In order to ascertain the magnitude of the problem, we reviewed all autopsies in our Medical Examiner's jurisdiction, from 1994 to 2001, where ephedrine or any its isomers (E+) were detected. Toxicology testing results were tabulated and anatomic findings in E+ cases were compared to those in a control group of drug-free trauma victims. Of 127 E+ cases identified, 33 were due to trauma. Decedents were mostly male (80.3%) and mostly Caucasian (59%). Blood ephedrine concentrations were <0.49 mg/l in 50% of the cases, range 0.07-11.73 mg/l in trauma victims, and 0.02-12.35 mg/l in non-trauma cases. Norephedrine (NE) was present in the blood of 22.8% (mean of 1.81 mg/l, S.D.=3.14 mg/l) and in the urine of 36.2% (mean of 15.6 mg/l, S.D.=21.50mg/l). Pseudoephedrine (PE) was present in the blood of 6.3% (8/127). More than 88% (113/127) of the decedents also tested positive for other drugs, the most common being cocaine (or its metabolites) and morphine. The most frequent pathologic diagnoses were hepatic steatosis (27/127) and nephrosclerosis (22/127). Left ventricular hypertrophy was common, and coronary artery disease (CAD) detected in nearly one third of the cases. The most common findings in E+ deaths are those generally associated with chronic stimulant abuse, and abuse of other drugs was common in those with CAD. There were no cases of heat stroke or rhabdomyolysis. In most cases, norephedrine was not detected, suggesting it plays no role in ephedrine toxicity. PMID:14687775

  11. Hair dye poisoning--an emerging problem in the tropics: an experience from a tertiary care hospital in South India.

    PubMed

    Chrispal, Anugrah; Begum, Anisa; Ramya, I; Zachariah, Anand

    2010-04-01

    Super-Vasmol, a cheap, freely-available hair dye is emerging as a major cause of suicidal poisoning in India. It contains potential toxins including paraphenylene diamine, resorcinol, sodium ethylenediaminetetraacetic acid and propylene glycol which can result in multiorgan dysfunction. A retrospective study was conducted over 3.5 years (January 2006-July 2009) of 13 consecutive patients with Super-Vasmol poisoning admitted to a tertiary care, referral hospital in South India. A chart review including records of clinical presentations, laboratory findings and treatment details was carried out. Eleven of the patients were women and the mean age was 27.2 years. The predominant clinical features were cervico-facial oedema and pain, cola-coloured urine and oliguria. Laboratory investigations revealed elevated hepatic transaminases (100%), leucocytosis (92.3%), elevated creatinine phosphokinase (92.3%), metabolic acidosis (84.6%), hypocalcaemia (61.5%), hyperphosphataemia (46.2%) and renal failure (38.5%). Eight of the patients were discharged with complete recovery. Trends towards a poor outcome were evident among the following patients: late presentation at our centre; when no gastric lavage was done at the primary-care centre; those requiring tracheostomy/intubation at the primary centre; presentation with a low Glasgow Coma Score or seizures; established renal failure; and those who subsequently require dialysis, mechanical ventilation or intensive care. Hair dye poisoning classically presents with cervico-facial oedema, severe rhabdomyolysis and renal failure. Early therapy with tracheostomy and aggressive forced diuresis are essential in order to prevent the high mortality associated with this toxin. It is imperative to raise public awareness of the potential toxicity of the dye as well as to educate physicians about the need for aggressive and early treatment. PMID:20305106

  12. A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products.

    PubMed

    Stolbach, Andrew; Paziana, Karolina; Heverling, Harry; Pham, Paul

    2015-09-01

    For many patients today, HIV has become a chronic disease. For those patients who have access to and adhere to lifelong antiretroviral (ARV) therapy, the potential for drug-drug interactions has become a real and life-threatening concern. It is known that most ARV drug interactions occur through the cytochrome P450 (CYP) pathway. Medications for comorbid medical conditions, holistic supplements, and illicit drugs can be affected by CYP inhibitors and inducers and have the potential to cause harm and toxicity. Protease inhibitors (PIs) tend to inhibit CYP3A4, while most non-nucleoside reverse transcriptase inhibitors (NNRTIs) tend to induce the enzyme. As such, failure to adjust the dose of co-administered medications, such as statins and steroids, may lead to serious complications including rhabdomyolysis and hypercortisolism, respectively. Similarly, gastric acid blockers can decrease several ARV absorption, and warfarin doses may need to be adjusted to maintain therapeutic concentrations. Illicit drugs such as methylenedioxymethamphetamine (MDMA, "ecstasy") in combination with PIs lead to increased toxicity, while the concomitant administration of sedative drugs such as midazolam and alprazolam in patients taking PIs can result in prolonged sedation, delayed recovery, and increased length of stay. Even supplements like St. John's Wort can alter PI concentrations. In theory, any drug that is metabolized by CYP has potential for a pharmacokinetic drug-drug interaction with all PIs, cobicistat, and most NNRTIs. When adding a new medication to an ARV regimen, use of a drug-drug interaction software and/or consultation with a clinical pharmacist/pharmacologist or HIV specialist is recommended. PMID:26036354

  13. Emerging drugs of abuse: current perspectives on substituted cathinones

    PubMed Central

    Paillet-Loilier, Magalie; Cesbron, Alexandre; Le Boisselier, Reynald; Bourgine, Joanna; Debruyne, Danièle

    2014-01-01

    Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines. PMID:24966713

  14. Major diet-drug interactions affecting the kinetic characteristics and hypolipidaemic properties of statins.

    PubMed

    Vaquero, M P; Sánchez Muniz, F J; Jiménez Redondo, S; Prats Oliván, P; Higueras, F J; Bastida, S

    2010-01-01

    Concomitant administration of statins with food may alter statin pharmacokinetics or pharmacodynamics, increasing the risk of adverse reactions such as myopathy or rhabdomyolysis or reducing their pharmacological action. This paper reviews major interactions between statins and dietary compounds. Consumption of pectin or oat bran together with Lovastatin reduces absorption of the drug, while alcohol intake does not appear to affect the efficacy and safety of Fluvastatin treatment. Grapefruit juice components inhibit cytochrome P-4503A4, reducing the presystemic metabolism of drugs such as Simvastatin, Lovastatin and Atorvastatin. Follow-up studies on the therapeutic effect of statins in patients consuming a Mediterranean-style diet are necessary to assure the correct prescription because the oil-statin and minor oil compound-statin possible interactions have been only briefly studied. Preliminary study suggests that olive oil can increase the hypolipaemiant effect of Simvastatin with respect sunflower oil. The consumption of polyunsaturated rich oils, throughout the cytochrome P- 450 activation could decrease the half-life of some statins and therefore their hypolipaemic effects. The statins and n-3 fatty acids combined therapy gives rise to pharmacodinamic interaction that improves the lipid profile and leads greater cardioprotection. Although statins are more effective in high endogenous cholesterol production subjects and plant sterols are more effective in high cholesterol absorption efficacy subjects, plant esterols-statins combined therapy generates very positive complementary effects. This review ends suggesting possible diet-stain interactions that require further investigations (e.g. types of olive oils, fruit juices other than grapefruit, fibre or consumption of alcoholic beverages rich in polyphenols or ethanol). PMID:20449528

  15. Malignant hyperthermia: a review.

    PubMed

    Rosenberg, Henry; Pollock, Neil; Schiemann, Anja; Bulger, Terasa; Stowell, Kathryn

    2015-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:10,000 to 1: 250,000 anesthetics. However, the prevalence of the genetic abnormalities may be as great as one in 400 individuals. MH affects humans, certain pig breeds, dogs and horses. The classic signs of MH include hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, hyperkalaemia, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. In humans the syndrome is inherited in an autosomal dominant pattern, while in pigs it is autosomal recessive. Uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation leads to the pathophysiologic changes. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the RYR1 gene located on chromosome 19q13.1, and at least 34 are causal for MH. Less than 1% of variants have been found in CACNA1S but not all of these are causal. Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. Elucidation of the genetic changes has led to the introduction of DNA testing for susceptibility to MH. Dantrolene sodium is a specific antagonist and should be available wherever general anesthesia is administered. Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the mortality decreasing from 80% thirty years ago to <5% in 2006. PMID:26238698

  16. Case series: toxicity from 25B-NBOMe - a cluster of N-bomb cases.

    PubMed

    Gee, Paul; Schep, Leo J; Jensen, Berit P; Moore, Grant; Barrington, Stuart

    2016-02-01

    Background A new class of hallucinogens called NBOMes has emerged. This class includes analogues 25I-NBOMe, 25C-NBOMe and 25B-NBOMe. Case reports and judicial seizures indicate that 25I-NBOMe and 25C-NBOMe are more prevalently abused. There have been a few confirmed reports of 25B-NBOMe use or toxicity. Report Observational case series. This report describes a series of 10 patients who suffered adverse effects from 25B-NBOMe. Hallucinations and violent agitation predominate along with serotonergic/stimulant signs such as mydriasis, tachycardia, hypertension and hyperthermia. The majority (7/10) required sedation with benzodiazepines. Analytical method 25B-NBOMe concentrations in plasma and urine were quantified in all patients using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Peak plasma levels were measured between 0.7-10.1 ng/ml. Discussion The NBOMes are desired by users because of their hallucinogenic and stimulant effects. They are often sold as LSD or synthetic LSD. Reported cases of 25B- NBOMe toxicity are reviewed and compared to our series. Seizures and one pharmacological death have been described but neither were observed in our series. Based on our experience with cases of mild to moderate toxicity, we suggest that management should be supportive and focused on preventing further (self) harm. High doses of benzodiazepines may be required to control agitation. Patients who develop significant hyperthermia need to be actively managed. Conclusions Effects from 25B-NBOMe in our series were similar to previous individual case reports. The clinical features were also similar to effects from other analogues in the class (25I-NBOMe, 25C-NBOMe). Violent agitation frequently present along with signs of serotonergic stimulation. Hyperthermia, rhabdomyolysis and kidney injury were also observed. PMID:26621342

  17. Statin Safety in Chinese: A Population-Based Study of Older Adults

    PubMed Central

    Li, Daniel Q.; Kim, Richard B.; McArthur, Eric; Fleet, Jamie L.; Hegele, Robert A.; Shah, Baiju R.; Weir, Matthew A.; Molnar, Amber O.; Dixon, Stephanie; Tu, Jack V.; Anand, Sonia; Garg, Amit X.

    2016-01-01

    Background Compared to Caucasians, Chinese achieve a higher blood concentration of statin for a given dose. It remains unknown whether this translates to increased risk of serious statin-associated adverse events amongst Chinese patients. Methods We conducted a population-based retrospective cohort study of older adults (mean age, 74 years) newly prescribed a statin in Ontario, Canada between 2002 and 2013, where 19,033 Chinese (assessed through a validated surname algorithm) were matched (1:3) by propensity score to 57,099 non-Chinese. This study used linked healthcare databases. Findings The follow-up observation period (mean 1.1, maximum 10.8 years) was similar between groups, as were the reasons for censoring the observation period (end of follow-up, death, or statin discontinuation). Forty-seven percent (47%) of Chinese were initiated on a higher than recommended statin dose. Compared to non-Chinese, Chinese ethnicity did not associate with any of the four serious statin-associated adverse events assessed in this study [rhabdomyolysis hazard ratio (HR) 0.61 (95% CI 0.28 to 1.34), incident diabetes HR 1.02 (95% CI 0.80 to 1.30), acute kidney injury HR 0.90 (95% CI 0.72 to 1.13), or all-cause mortality HR 0.88 (95% CI 0.74 to 1.05)]. Similar results were observed in subgroups defined by statin type and dose. Conclusions We observed no higher risk of serious statin toxicity in Chinese than matched non-Chinese older adults with similar indicators of baseline health. Regulatory agencies should review available data, including findings from our study, to decide if a change in their statin dosing recommendations for people of Chinese ethnicity is warranted. PMID:26954681

  18. Importance of early identification of methylenedioxymethamphetamine ('ecstasy') ingestion in victims of motor vehicle accidents.

    PubMed

    Weinbroum, Avi A

    2003-03-01

    The blood of motor vehicle accident victims is routinely screened upon their arrival at the emergency services mainly for alcohol, unless the suspicion of a specific compound arises. Two young men who sustained severe internal and orthopaedic injuries after a motor vehicle accident are described. The conscious patient denied their having used stupefacients, but toxicological analysis upon arrival at the operating room detected methylenedioxymethamphetamine, the metabolite methylenedioxyamphetamine and methamphetamine in their blood and urine specimens. Methylenedioxymethamphetamine concentrations in the clotted blood and in the urine ranged between 0.9-1.15 and 55-70 mg/l, respectively. Methylenedioxyamphetamine concentrations for both patients were less than 0.2 mg/l in the blood and 2.0-3.0 mg/l in the urine. Each had a blood methamphetamine concentration greater than 250 ng/ml. There was no trace of alcohol. Three days after their arrival at the hospital, acute liver insufficiency and mild rhabdomyolysis (serum glutamate-pyruvate transaminase/serum glutamic-oxaloacetic transaminase 1245/218 mU/ml, creatine phosphokinase 48 000 U/ml, respectively) were diagnosed in both patients. Appropriate treatment was administered in an intensive care area and both were discharged home several weeks later without sequelae. These findings suggest that in this era of the widespread abuse of 'ecstasy', concentrations of methylenedioxymethamphetamine, methylenedioxyamphetamine or metamphetamine should be sought routinely in motor vehicle accident victims admitted to emergency services with an altered state of consciousness so that the early monitoring of the potential development of organ pathology can be implemented. PMID:12637856

  19. Effect of Coenzyme Q10 Supplementation in Statin-Treated Obese Rats.

    PubMed

    Choi, Hye-Kyung; Won, Eun-Kyung; Choung, Se-Young

    2016-03-01

    Statins, HMG-CoA reductase inhibitors, are known to cause serious muscle injuries (e.g. myopathy, myositis and rhabdomyolysis), and these adverse effects can be rescued by co-administration of coenzyme Q10 (CoQ10) with statins. The goal of the current research is to assess the efficacy of combined treatment of CoQ10 with Atorvastatin for hyperlipidemia induced by high-fat diet in SD rats. 4-week-old Sprague-Dawley male rats were fed normal diet or high-fat diet for 6 weeks. Then, rats were treated with either Statin or Statin with various dosages of CoQ10 (30, 90 or 270 mg/kg/day, p.o.) for another 6 weeks. Compared to Statin onlytreatment, CoQ10 supplementation significantlyreduced creatine kinase and aspartate aminotransferase levels in serum which are markers for myopathy. Moreover, CoQ10 supplementation with Statin further reduced total fat, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol. In contrast, the levels of high-density lipoprotein-cholesterol and CoQ10 were increased in the CoQ10 co-treated group. These results indicate that CoQ10 treatment not only reduces the side effects of Statin, but also has an anti-obesity effect. Therefore an intake of supplementary CoQ10 is helpful for solving problem of obese metabolism, so the multiple prescription of CoQ10 makes us think a possibility that can be solved in being contiguous to the obesity problem, a sort of disease of the obese metabolism. PMID:26797109

  20. Clinical and Pathological Findings of a Fatal Systemic Capillary Leak Syndrome (Clarkson Disease)

    PubMed Central

    Zancanaro, Andrea; Serafini, Francesco; Fantin, Giuseppe; Murer, Bruno; Cicardi, Marco; Bonanni, Luca; Dalla Vestra, Michele; Scanferlato, Mauro; Mazzanti, Giovanni; Presotto, Fabio

    2015-01-01

    Abstract Systemic capillary leak syndrome (SCLS) is a rare disorder with episodes of hypotension, hypoalbuminemia, and hemoconcentration. During attacks endothelial hyperpermeability results in leakage of plasma proteins into the interstitial space. Attacks vary in severity and may be lethal. A 49-year-old previously healthy man was admitted to hospital for hypovolemic shock, anasarca with pleuropericardial effusion, muscle fatigue, and oliguria occurring after a flu-like syndrome. Laboratory data showed an increase in hematocrit (65%), leucocytes (24.590 μ/L), creatinine (2.5 mg/dL), creatine phosphokinase (10.000 U/L), and a decrease in serum albumin (17 g/L) without proteinuria. Immunoglobulins of class G/λ monoclonal gammopathy were detected (1.3 g/L). The initial suspicions addressed to a protein-loosing syndrome or to an effort-related rhabdomyolysis. Initial therapy was based on steroids, albumin, and high molecular weight plasma expanders (hydroxyethyl starch). Because of high hematocrit, phlebotomy was also performed. The patient had complete clinical remission and a diagnosis of SCLS was finally made. He received prophylactic therapy with verapamil and theophylline that was self-stopped for intolerance (hypotension and tachycardia). He had a new crisis 2 days after a physical effort, and was admitted in intensive care unit. The patient died for severe hypovolemic shock with multiorgan failure and sudden cardiac arrest 15 hours after hospital admission. Postmortem investigation revealed massive interstitial edema of main organs with myocardial hyperacute ischemia. Studies on SCLS are limited for the rarity of the disease and its unpredictable course. Both prophylactic and acute crisis treatments are empirical and optimal management of severe attacks is still lacking. PMID:25738482

  1. Quantitative Structure Activity Relationship for Inhibition of Human Organic Cation/Carnitine Transporter (OCTN2)

    PubMed Central

    Diao, Lei; Ekins, Sean; Polli, James E.

    2010-01-01

    Organic cation/carnitine transporter (OCTN2; SLC22A5) is an important transporter for L-carnitine homeostasis, but can be inhibited by drugs, which may cause L-carnitine deficiency and possibly other OCTN2-mediated drug-drug interactions. One objective was to develop a quantitative structure–activity relationship (QSAR) of OCTN2 inhibitors, in order to predict and identify other potential OCTN2 inhibitors and infer potential clinical interactions. A second objective was to assess two high renal clearance drugs that interact with OCTN2 in vitro (cetirizine and cephaloridine) for possible OCTN2-mediated drug-drug interactions. Using previously generated in vitro data of 22 drugs, a 3D quantitative pharmacophore model and a Bayesian machine learning model were developed. The four pharmacophore features include two hydrophobic groups, one hydrogen-bond acceptor, and one positive ionizable center. The Bayesian machine learning model was developed using simple interpretable descriptors and function class fingerprints of maximum diameter 6 (FCFP_6). An external test set of 27 molecules, including 15 newly identified OCTN2 inhibitors, and a literature test set of 22 molecules were used to validate both models. The computational models afforded good capability to identify structurally diverse OCTN2 inhibitors, providing a valuable tool to predict new inhibitors efficiently. Inhibition results confirmed our previously observed association between rhabdomyolysis and Cmax/Ki ratio. The two high renal clearance drugs cetirizine and cephaloridine were found not to be OCTN2 substrates and their diminished elimination by other drugs is concluded not to be mediated by OCTN2. PMID:20831193

  2. Differential Mortality of Male Spectacled Eiders (Somateria fischeri) and King Eiders (Somateria spectabilis) Subsequent to Anesthesia with Propofol, Bupivacaine, and Ketoprofen

    USGS Publications Warehouse

    Mulcahy, D.M.; Tuomi, P.; Larsen, R.S.

    2003-01-01

    Twenty free-ranging spectacled eiders (Somateria fischeri; 10 male, 10 female), 11 free-ranging king eiders (Somateria spectabilis; 6 male, 5 female), and 20 female common eiders (Somateria mollissima) were anesthetized with propofol, bupivacaine, and ketoprofen for the surgical implantation of satellite transmitters. Propofol was given to induce and maintain anesthesia (mean total dose, 26.2-45.6 mg/kg IV), bupivacaine (2-10 mg/kg SC) was infused into the incision site for local analgesia, and ketoprofen (2-5 mg/kg IM) was given at the time of surgery for postoperative analgesia. Four of 10 male spectacled eiders and 5 of 6 male king eiders died within 1-4 days after surgery. None of the female spectacled or common eiders and only 1 of the 5 female king eiders died during the same postoperative period. Histopathologic findings in 2 dead male king eiders were severe renal tubular necrosis, acute rhabdomyolysis, and mild visceral gout. Necropsy findings in 3 other dead male king eiders were consistent with visceral gout. We suspect that the perioperative use of ketoprofen caused lethal renal damage in the male eiders. Male eiders may be more susceptible to renal damage than females because of behavioral differences during their short stay on land in mating season. The combination of propofol, bupivacaine, and ketoprofen should not be used to anesthetize free-ranging male eiders, and nonsteroidal anti-inflammatory drugs should not be used perioperatively in any bird that may be predisposed to renal insufficiency.

  3. Hyperglycemic hyperosmolar syndrome at the onset of type 2 diabetes mellitus in an adolescent male.

    PubMed

    Tsai, Sarah L; Hadjiyannakis, Stasia; Nakhla, Meranda

    2012-01-01

    Hyperglycemic hyperosmolar state (HHS) is rare in the paediatric population. The diagnosis and management of HHS presents a challenge in paediatric patients who may present with a mixed picture of HHS and diabetic ketoacidosis (DKA).A 15-year-old obese African American male was brought to the emergency department following a two-day history of feeling unwell. The patient was obtunded, hypotensive and tachypneic. Initial investigations revealed the following: pH 6.97 (normal 7.35 to 7.41), HCO(3) (-) 5 mEq/L (normal 20 mEq/L to 25 mEq/L), glucose 90.9 mmol/L (normal 3.4 mmol/L to 6.3 mmol/L), serum osmolality 454 mOsm/kg (normal 275 mOsm/kg to 295 mOsm/kg), Na(+) 141 mEq/L (normal 135 mEq/L to 145 mEq/L), corrected Na(+) 165 mEq/L, K(+) 8.4 mEq/L (normal 3.5 mEq/L to 5.0 mEq/L), urinalysis revealed 1+ ketones and 4+ glucose. The patient's clinical course was complicated by severe hyperkalemia, acute renal failure, refractory status epilepticus, rhabdomyolysis, pancreatitis and hypertension.The present case emphasizes the complexity of managing patients with a mixed DKA/HHS presentation and associated morbidities. It is very important to disseminate and implement screening guidelines for type 2 diabetes mellitus, so as to prevent this potentially devastating complication. PMID:23277751

  4. In vivo evidence suggesting reciprocal renal hypoxia-inducible factor-1 upregulation and signal transducer and activator of transcription 3 activation in response to hypoxic and non-hypoxic stimuli.

    PubMed

    Nechemia-Arbely, Yael; Khamaisi, Mogher; Rosenberger, Christian; Koesters, Robert; Shina, Ahuva; Geva, Carmit; Shriki, Anat; Klaus, Stephen; Rosen, Seymour; Rose-John, Stefan; Galun, Eithan; Axelrod, Jonathan H; Heyman, Samuel N

    2013-04-01

    In vitro studies suggest that combined activation of hypoxia-inducible factor (HIF) and signal transducer and activator of transcription 3 (STAT3) promotes the hypoxia response. However, their interrelationship in vivo remains poorly defined. The present study investigated the possible relationship between HIF-1 upregulation and STAT3 activation in the rodent kidney in vivo. Activation of HIF-1 and STAT3 was analysed by immunohistochemical staining and western blot analysis in: (i) models of hypoxia-associated kidney injury induced by radiocontrast media or rhabdomyolysis; (ii) following activation of STAT3 by the interleukin (IL)-6-soluble IL-6 receptor complex; or (iii) following HIF-1α stabilization using hypoxic and non-hypoxic stimuli (mimosine, FG-4497, CO, CoCl(2)) and in targeted von Hippel-Lindau-knockout mice. Western blot analysis and immunostaining revealed marked induction of both transcription factors under all conditions tested, suggesting that in vivo STAT3 can trigger HIF and vice versa. Colocalization of HIF-1α and phosphorylated STAT3 was detected in some, but not all, renal cell types, suggesting that in some cells a paracrine mechanism may be responsible for the reciprocal activation of the two transcription factors. Nevertheless, in several cell types spatial concordance was observed under the majority of conditions tested, suggesting that HIF-1 and STAT3 may act as cotranscription factors. These in vivo studies suggest that, in response to renal hypoxic-stress, upregulation of HIF-1 and activation of STAT3 may be both reciprocal and cell type dependent. PMID:23384058

  5. Integration of Biosensors and Drug Delivery Technologies for Early Detection and Chronic Management of Illness

    PubMed Central

    Ngoepe, Mpho; Choonara, Yahya E.; Tyagi, Charu; Tomar, Lomas Kumar; du Toit, Lisa C.; Kumar, Pradeep; Ndesendo, Valence M. K.; Pillay, Viness

    2013-01-01

    Recent advances in biosensor design and sensing efficacy need to be amalgamated with research in responsive drug delivery systems for building superior health or illness regimes and ensuring good patient compliance. A variety of illnesses require continuous monitoring in order to have efficient illness intervention. Physicochemical changes in the body can signify the occurrence of an illness before it manifests. Even with the usage of sensors that allow diagnosis and prognosis of the illness, medical intervention still has its downfalls. Late detection of illness can reduce the efficacy of therapeutics. Furthermore, the conventional modes of treatment can cause side-effects such as tissue damage (chemotherapy and rhabdomyolysis) and induce other forms of illness (hepatotoxicity). The use of drug delivery systems enables the lowering of side-effects with subsequent improvement in patient compliance. Chronic illnesses require continuous monitoring and medical intervention for efficient treatment to be achieved. Therefore, designing a responsive system that will reciprocate to the physicochemical changes may offer superior therapeutic activity. In this respect, integration of biosensors and drug delivery is a proficient approach and requires designing an implantable system that has a closed loop system. This offers regulation of the changes by means of releasing a therapeutic agent whenever illness biomarkers prevail. Proper selection of biomarkers is vital as this is key for diagnosis and a stimulation factor for responsive drug delivery. By detecting an illness before it manifests by means of biomarkers levels, therapeutic dosing would relate to the severity of such changes. In this review various biosensors and drug delivery systems are discussed in order to assess the challenges and future perspectives of integrating biosensors and drug delivery systems for detection and management of chronic illness. PMID:23771157

  6. Sitagliptin/Simvastatin: a first combination tablet to treat type 2 diabetes and hypercholesterolemia – a review of its characteristics

    PubMed Central

    Ramadan, Wijdan H; Kabbara, Wissam K

    2015-01-01

    Background The purpose of this study was to review the current literature and information on the combination product Juvisync™ (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011. Methods PubMed (2001–2014) was searched for primary and review articles on sitagliptin, simvastatin, or the combination product. Drug manufacturing data and product labeling were also used. Studies of simvastatin, sitagliptin, or the combination were screened and analyzed to include relevant and recent papers. Selected English language trials were limited to those with human subjects and included both safety and efficacy outcomes. Results When compared with glipizide as add-on therapy to metformin, sitagliptin was noninferior but had lower rates of hypoglycemia and weight gain. In addition, when compared with insulin glargine, sitagliptin was less effective in decreasing glycosylated hemoglobin, but was associated with significantly lower rates of hypoglycemia. Further, trials have shown a beneficial effect of using statins in patients with diabetes mellitus with regard to decreasing cardiovascular risk, regardless of baseline lipid levels or the presence of a cardiac disease. Both medications have also demonstrated an acceptable side effect profile. However, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of myopathy and rhabdomyolysis. Conclusion Juvisync should be used in patients requiring both sitagliptin and simvastatin. Both agents have shown good efficacy and acceptable safety profiles. Sitagliptin is a good option for diabetic patients to improve glycemic control with a lower risk of hypoglycemia and weight gain. PMID:25709467

  7. The determinants of transverse tubular volume in resting skeletal muscle

    PubMed Central

    Sim, Jingwei; Fraser, James A

    2014-01-01

    The transverse tubular (t)-system of skeletal muscle couples sarcolemmal electrical excitation with contraction deep within the fibre. Exercise, pathology and the composition of the extracellular fluid (ECF) can alter t-system volume (t-volume). T-volume changes are thought to contribute to fatigue, rhabdomyolysis and disruption of excitationcontraction coupling. However, mechanisms that underlie t-volume changes are poorly understood. A multicompartment, history-independent computer model of rat skeletal muscle was developed to define the minimum conditions for t-volume stability. It was found that the t-system tends to swell due to net ionic fluxes from the ECF across the access resistance. However, a stable t-volume is possible when this is offset by a net efflux from the t-system to the cell and thence to the ECF, forming a net ion cycle ECF?t-system?sarcoplasm?ECF that ultimately depends on Na+/K+-ATPase activity. Membrane properties that maximize this circuit flux decrease t-volume, including PNa(t) > PNa(s), PK(t) < PK(s) and N(t) < N(s) [P, permeability; N, Na+/K+-ATPase density; (t), t-system membrane; (s), sarcolemma]. Hydrostatic pressures, fixed charges and/or osmoles in the t-system can influence the magnitude of t-volume changes that result from alterations in this circuit flux. Using a parameter set derived from literature values where possible, this novel theory of t-volume was tested against data from previous experiments where t-volume was measured during manipulations of ECF composition. Predicted t-volume changes correlated satisfactorily. The present work provides a robust, unifying theoretical framework for understanding the determinants of t-volume. PMID:25384782

  8. Acute methoxetamine and amphetamine poisoning with fatal outcome: a case report.

    PubMed

    Wiergowski, Marek; Anand, Jacek Sein; Krzyżanowski, Maciej; Jankowski, Zbigniew

    2014-08-01

    Methoxetamine (MXE) is a psychoactive substance distributed mostly via the Internet and is not liable to legal regulation in Poland. MXE has a toxicity profile similar to that of ketamine but longer-lasting effects. The paper describes a case of acute poisoning that resulted from recreational use of MXE and amphetamine and ended in death. In mid-July 2012, a 31-year old man was admitted to the clinical toxicology unit in Gdańsk because of poisoning with an unknown psychoactive substance. The patient was transported to the emergency department (ED) at 5:15 a.m. in a very poor general condition, in a deep coma, with acute respiratory failure, hyperthermia (> 39°C) and generalized seizures. Laboratory tests showed marked leukocytosis, signs of massive rhabdomyolysis, hepatic failure and beginning of acute renal failure. Despite intensive therapy, the patient died 4 weeks after the poisoning in the course of multi-organ dysfunction syndrome. Chemical and toxicological studies of serum and urine samples collected on the poisoning day at 1:40 p.m. confirmed that amphetamine and MXE had been taken earlier that day. Concentration of amphetamine in the serum (0.06 μg/ml) was within the non-toxic range, while MXE (0.32 μg/ml) was within the toxic range of concentrations. Amphetamine was also detected in the patient's hair, which suggested a possibility of its use within the last dozen weeks or so. The serious clinical course of intoxication and co-existence of amphetamine and MXE in the patient's blood and urine suggest the possibility of adverse interactions between them. PMID:25060403

  9. Fatal water intoxication and cardiac arrest in runners during marathons: prevention and treatment based on validated clinical paradigms.

    PubMed

    Siegel, Arthur J

    2015-10-01

    Cerebral edema due to exercise-associated hyponatremia and cardiac arrest due to atherosclerotic heart disease cause rare marathon-related fatalities in young female and middle-aged male runners, respectively. Studies in asymptomatic middle-aged male physician-runners during races identified inflammation due to skeletal muscle injury after glycogen depletion as the shared underlying cause. Nonosmotic secretion of arginine vasopressin as a neuroendocrine stress response to rhabdomyolysis mediates hyponatremia as a variant of the syndrome of inappropriate antidiuretic hormone secretion. Fatal hyponatremic encephalopathy in young female runners was curtailed using emergent infusion of intravenous hypertonic (3%) saline to reverse cerebral edema on the basis of this paradigm. This treatment was arrived at through a consensus process within the medical community. An increasing frequency of cardiac arrest and sudden death has been identified in middle-aged male runners in 2 studies since the year 2000. Same-aged asymptomatic male physician-runners showed post-race elevations in interleukin-6 and C-reactive protein, biomarkers that predict acute cardiac events in healthy persons. Hypercoagulability with invivo platelet activation and release of cardiac troponin and N-terminal pro-brain natriuretic peptide were also observed post-race in these same subjects. High short-term risk for atherothrombosis during races as shown by stratification of biomarkers in asymptomatic men may render nonobstructive coronary atherosclerotic plaques vulnerable to rupture. Pre-race aspirin use in this high-risk subgroup is prudent according to conclusive evidence for preventing first acute myocardial infarctions in same-aged healthy male physicians. On the basis of validated clinical paradigms, taking a low-dose aspirin before a marathon and drinking to thirst during the race may avert preventable deaths in susceptible runners. PMID:25910792

  10. Perioperative Intravenous Acetaminophen Attenuates Lipid Peroxidation in Adults Undergoing Cardiopulmonary Bypass: A Randomized Clinical Trial

    PubMed Central

    Billings IV, Frederic T.; Petracek, Michael R.; Roberts II, L. Jackson; Pretorius, Mias

    2015-01-01

    Background Cardiopulmonary bypass (CPB) lyses erythrocytes and induces lipid peroxidation, indicated by increasing plasma concentrations of free hemoglobin, F2-isoprostanes, and isofurans. Acetaminophen attenuates hemeprotein-mediated lipid peroxidation, reduces plasma and urine concentrations of F2-isoprostanes, and preserves kidney function in an animal model of rhabdomyolysis. Acetaminophen also attenuates plasma concentrations of isofurans in children undergoing CPB. The effect of acetaminophen on lipid peroxidation in adults has not been studied. This was a pilot study designed to test the hypothesis that acetaminophen attenuates lipid peroxidation in adults undergoing CPB and to generate data for a clinical trial aimed to reduce acute kidney injury following cardiac surgery. Methods and Results In a prospective double-blind placebo-controlled clinical trial, sixty adult patients were randomized to receive intravenous acetaminophen or placebo starting prior to initiation of CPB and for every 6 hours for 4 doses. Acetaminophen concentrations measured 30 min into CPB and post-CPB were 11.9±0.6 μg/mL (78.9±3.9 μM) and 8.7±0.3 μg/mL (57.6±2.0 μM), respectively. Plasma free hemoglobin increased more than 15-fold during CPB, and haptoglobin decreased 73%, indicating hemolysis. Plasma and urinary markers of lipid peroxidation also increased during CPB but returned to baseline by the first postoperative day. Acetaminophen reduced plasma isofuran concentrations over the duration of the study (P = 0.05), and the intraoperative plasma isofuran concentrations that corresponded to peak hemolysis were attenuated in those subjects randomized to acetaminophen (P = 0.03). Perioperative acetaminophen did not affect plasma concentrations of F2-isoprostanes or urinary markers of lipid peroxidation. Conclusions Intravenous acetaminophen attenuates the increase in intraoperative plasma isofuran concentrations that occurs during CPB, while urinary markers were unaffected. Trial Registration ClinicalTrials.gov NCT01366976 PMID:25705899

  11. Statin safety: a systematic review.

    PubMed

    Law, Malcolm; Rudnicka, Alicja R

    2006-04-17

    A systematic review of cohort studies, randomized trials, voluntary notifications to national regulatory authorities, and published case reports was undertaken to assess the incidence and characteristics of adverse effects in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins. For statins other than cerivastatin, the incidence of rhabdomyolysis in 2 cohort studies was 3.4 (1.6 to 6.5) per 100,000 person-years, an estimate supported by data from 20 randomized controlled trials. Case fatality was 10%. Incidence was about 10 times greater when gemfibrozil was used in combination with statins. Incidence was higher (4.2 per 100,000 person-years) with lovastatin, simvastatin, or atorvastatin (which are oxidized by cytochrome P450 3A4 [CYP3A4], which is inhibited by many drugs) than pravastatin or fluvastatin (which are not oxidized by CYP3A4). In persons taking simvastatin, lovastatin, or atorvastatin, 60% of cases involved drugs known to inhibit CYP3A4 (especially erythromycin and azole antifungals), and 19% involved fibrates, principally gemfibrozil. The incidence of myopathy in patients treated with statins, estimated from cohort studies supported by randomized trials, was 11 per 100,000 person-years. For liver disease, randomized trials reported fewer hepatobiliary disorders in patients allocated statins than in those allocated placebo. The notification rate of liver failure to regulatory authorities was about 1 per million person-years of statin use. Randomized trials show no excess of renal disease or proteinuria in statin-allocated participants, and the decline in glomerular filtration rate was smaller with statins than with placebo. Evidence from 4 cohort studies and case reports suggests that statins cause peripheral neuropathy, but the attributable risk is small (12 per 100,000 person-years). No change in cognitive function was found in randomized trials of statins in elderly patients. PMID:16581329

  12. Statin adverse effects : a review of the literature and evidence for a mitochondrial mechanism.

    PubMed

    Golomb, Beatrice A; Evans, Marcella A

    2008-01-01

    HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like all medications, have potential for adverse effects (AEs). Here we review the statin AE literature, first focusing on muscle AEs as the most reported problem both in the literature and by patients. Evidence regarding the statin muscle AE mechanism, dose effect, drug interactions, and genetic predisposition is examined. We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials (RCTs), muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 3A4 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence supports a mitochondrial foundation for muscle AEs associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many nonmuscle statin AEs. Evidence from RCTs and studies of other designs indicates existence of additional statin-associated AEs, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients. Awareness and vigilance for AEs should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity. PMID:19159124

  13. Muscle- and skeletal-related side-effects of statins: tip of the iceberg?

    PubMed

    Auer, Johann; Sinzinger, Helmut; Franklin, Barry; Berent, Robert

    2016-01-01

    The clinical spectrum of muscle- and skeletal-related side-effects of statins includes varied myalgias and weakness, an asymptomatic increase in the concentration of creatine kinase and other biochemical parameters, myositis and rhabdomyolysis. Currently, there is no consensus on the definition of 'statin myopathy'. Evidence suggests that deleterious effects may also be associated with the volume or dosage of structured exercise and/or the intensity of physical activity. Moreover, non-muscle adverse effects on the joints and tendons are often overlooked and underemphasized. The incidence of myopathy associated with statin treatment typically ranges between 1.5% and 10%. Few data are available regarding the prevalence of muscle- related symptoms associated with different statins and the distribution of affected muscles. Furthermore, discrepancies between clinical trials and daily practice may emanate, in part, because of inconsistent definitions or exclusion criteria.The pathophysiology of statin-related myopathy is incompletely understood. A dose-dependent and proapoptotic effect, direct effects on mitochondria, drug interactions and genetic factors, or combinations thereof, may be involved. Recently, a rare immune-mediated myopathy triggered by statin use has been described. With the increasing number of patients treated with statins and with more patients being prescribed high doses of potent statins to achieve low-density lipoprotein targets, muscle-related side-effects will become more prevalent. Currently, the only effective treatment is the discontinuation of statin use. Further research is needed to develop alternative LDL-lowering drugs when statins are not well tolerated and to establish additional effective strategies to manage lipids and lipoproteins. PMID:25230981

  14. Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism

    PubMed Central

    Golomb, Beatrice A.; Evans, Marcella A.

    2009-01-01

    HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like all medications have potential for adverse effects (AEs). Here we review the statin AE literature, first focusing on muscle AEs as the most reported problem both in the literature and by patients. Evidence regarding the statin muscle AE mechanism, dose effect, drug interactions, and genetic predisposition is examined. We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials (RCTs), muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 (CYP)3A4 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence supports a mitochondrial foundation for muscle AEs associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many non-muscle statin AEs. Evidence from RCTs and studies of other designs indicates existence of additional statin-associated AEs, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients. Awareness and vigilance for AEs should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity. PMID:19159124

  15. Effect of Coenzyme Q10 Supplementation in Statin-Treated Obese Rats

    PubMed Central

    Choi, Hye-Kyung; Won, Eun-Kyung; Choung, Se-Young

    2016-01-01

    Statins, HMG-CoA reductase inhibitors, are known to cause serious muscle injuries (e.g. myopathy, myositis and rhabdomyolysis), and these adverse effects can be rescued by co-administration of coenzyme Q10 (CoQ10) with statins. The goal of the current research is to assess the efficacy of combined treatment of CoQ10 with Atorvastatin for hyperlipidemia induced by high-fat diet in SD rats. 4-week-old Sprague-Dawley male rats were fed normal diet or high-fat diet for 6 weeks. Then, rats were treated with either Statin or Statin with various dosages of CoQ10 (30, 90 or 270 mg/kg/day, p.o.) for another 6 weeks. Compared to Statin only-treatment, CoQ10 supplementation significantly reduced creatine kinase and aspartate aminotransferase levels in serum which are markers for myopathy. Moreover, CoQ10 supplementation with Statin further reduced total fat, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol. In contrast, the levels of high-density lipoprotein-cholesterol and CoQ10 were increased in the CoQ10 co-treated group. These results indicate that CoQ10 treatment not only reduces the side effects of Statin, but also has an anti-obesity effect. Therefore an intake of supplementary CoQ10 is helpful for solving problem of obese metabolism, so the multiple prescription of CoQ10 makes us think a possibility that can be solved in being contiguous to the obesity problem, a sort of disease of the obese metabolism. PMID:26797109

  16. Dengue-associated kidney disease

    PubMed Central

    J Lizarraga, Karlo; Nayer, Ali

    2014-01-01

    Context: A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue is considered a major global health threat by the World Health Organization. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: An RNA virus from the genus Flavivirus, dengue virus is transmitted by Aedes aegypti,the yellow fever mosquito. Dengue is asymptomatic in as many as one half of infected individuals. Dengue fever is an acute febrile illness accompanied by constitutional symptoms. Dengue hemorrhagic fever and dengue shock syndrome are the severe forms of dengue infection.Dengue infection has been associated with a variety of renal disorders. Acute renal failure is a potential complication of severe dengue infection and is typically associated with hypotension, rhabdomyolysis, or hemolysis. Acute renal failure complicates severe dengue infection in 2-5% of the cases and carries a high mortality rate. Proteinuria has been detected in as high as 74% of patients with severe dengue infection. Hematuria has been reported in up to 12.5% of patients. Various types of glomerulonephritis have been reported during or shortly after dengue infection in humans and mouse models of dengue infection. Mesangial proliferation and immune complex deposition are the dominant histologic features of dengue-associated glomerulonephritis. On a rare occasion, dengue infection is associated with systemic autoimmune disorders involving the kidneys. Conclusions: In the vast majority of cases, dengue infection and associated renal disorders are self-limited. PMID:24772398

  17. [Severe accidental hypothermia in an elderly woman].

    PubMed

    Knobel, B; Mikhlin, A

    2001-11-01

    Profound hypothermia (core temperature of less than 28 degrees C) is a life threatening state and a medical emergency associated with a high mortality rate. The prognosis depends on underlying diseases, advanced or very early age, the duration prior to treatment, the degree of hemodynamic deterioration, and especially, the methods of treatment, including active external or internal rewarming. This is a case study of an 80-year-old female patient with severe accidental hypothermia (core temperature 27 degrees C). She was found in her home lying immobile on the cold floor after a fall. The patient was in a profound coma with cardiocirculatory collapse, and the medical staff treating her was inclined to pronounce her deceased. On her arrival at the hospital, she was resuscitated, put on a respirator and actively warmed. Very severe metabolic disorders were found, including a marked metabolic acidosis composed of diabetic ketoacidosis (she had suffered from insulin treated type 2 diabetes mellitus) and lactic acidosis with a very high anion gap (42) and a hyperosmotic state (blood glucose 1202 mg/dl). There were pathognomonic electrocardiographic abnormalities, J-wave of Osborn and prolonged repolarization. Slow atrial fibrillation with a ventricular response of 30 bpm followed by a nodal rhythm of 12 bpm and reversible cardiac arrest were recorded. The pulse and blood pressure were unobtainable. Despite the successful resuscitation and hemodynamic and cognitive improvement, rhabdomyolysis (CKP 6580 u/L), renal failure and hepatic damage developed. She was extubated and treated with intravenous fluids containing dopamine, bicarbonate, insulin and antibiotics. Her medical condition gradually improved, and she was discharged clear minded, functioning very well and independent. Renal and liver tests returned eventually to normal limits. Progressive bradycardia, hypotension and death due to ventricular fibrillation or asystole commonly occur during severe hypothermia. Respiratory and metabolic, sometimes lactic, acidosis, lethargy and coma, hypercoagulopathy, hyperosmolar state, acute pancreatitis and renal and hepatic failure are frequent complications of hypothermia. Underlying predisposing causes of hypothermia are diabetic ketoacidosis, cerebrovascular disease, mental retardation, hypothyroidism, pituitary and adrenal insufficiency, malnutrition, acute alcoholism, liver damage, hypoglycemia, sepsis, hypothalamic dysfunction, sepsis and polypharmacy, and especially, the use of sedative and narcotic drugs. Our case demonstrates once again that CPR once begun should continue until the successful rewarming because "no one is dead until warm and dead". PMID:11759373

  18. Marked protection against acute renal and hepatic injury after nitrited myoglobin + tin protoporphyrin administration.

    PubMed

    Zager, Richard A

    2015-11-01

    The phenomenon known as renal "ischemic preconditioning," whereby an initial ischemic insult induces resistance against subsequent kidney damage, has been well established in the experimental literature. However, a clinically applicable way to safely recapitulate this state has not been defined. We hypothesized that a unique combination of agents (nitrited myoglobin [N-Mgb] + tin protoporphyrin [SnPP]) can achieve these ends safely and synergistically, increasing cytoprotective proteins (eg, heme oxygenase 1 [HO-1], interleukin 10 [IL-10], and haptoglobin) in kidney cells. To test this hypothesis, CD-1 mice received 1 mg of N-Mgb and 1 ?mol of SnPP, either alone or in combination. Renal cortical HO-1, haptoglobin, and IL-10 gene expressions (messenger RNA [mRNA], protein levels) were determined 4 and 18 hours later. Cytoresistance to 3 forms of acute kidney injury (AKI; glycerol-induced rhabdomyolysis, maleate nephrotoxicity, and postischemic AKI progression to chronic kidney disease [CKD]) was assessed. To ascertain whether cytoresistance might emerge in extrarenal organs, hepatic HO-1, IL-10, and haptoglobin levels were also measured, and resistance to 25 minutes of hepatic ischemia-reperfusion injury and hepatotoxicity (intraperitoneal glycerol injection) was sought. N-Mgb + SnPP induced additive or synergistic increases in renal HO-1, haptoglobin, and IL-10 mRNA and protein levels (up to 20-fold) without inducing any apparent renal or extrarenal damage. After 18 hours of post-treatment, marked or complete protection against glycerol-induced AKI, maleate-induced AKI, and postischemic AKI progression to CKD had emerged. Combined N-Mgb + SnPP was more protective than either agent alone (assessed in glycerol model). N-Mgb + SnPP also upregulated cytoprotective pathways in liver and induced marked protection against both hepatic ischemia-reperfusion and toxic liver damage. In conclusion, we posit that "preconditioning" with combined administration of N-Mgb + SnPP represents a promising approach for protecting against diverse forms of renal and nonrenal (hepatic) forms of tissue damage. PMID:26117289

  19. Acidosis, lactate, electrolytes, muscle enzymes, and other factors in the blood of Sus scrofa following repeated TASER exposures.

    PubMed

    Jauchem, James R; Sherry, Clifford J; Fines, David A; Cook, Michael C

    2006-08-10

    Repeated exposure to electro-muscular incapacitating devices could result in repetitive, sustained muscle contraction, with little or no muscle recovery period. Therefore, rhabdomyolysis and other physiological responses, including acidosis, hyperkalaemia, and altered levels of muscle enzymes in the blood, would be likely to occur. Experiments were performed to investigate effects of repeated exposures of TASER International's Advanced TASER X26 on muscle contraction and resultant changes in blood factors in an anaesthetized swine model. A total of 10 animals were used. Six swine were exposed for 5 s, followed by a 5-s period of no exposure, repeatedly for 3 min. (In five of the animals, after a 1-h delay, a second 3-min exposure period was added.) The remaining four animals were used for an additional pilot study. All four limbs of each animal exhibited contraction even though the electrodes were positioned in areas at some distances from the limbs. The degree of muscle contraction generated during the second exposure period was significantly lower than that in the first exposure series. This finding was consistent with previous studies showing that prolonged activity in skeletal muscle will eventually result in a decline of force production. There were some similarities in blood sample changes in the current experiments with previous studies of muscular exercise. Thus problems concerning biological effects of repeated TASER exposures may be related, not directly to the "electric output" per se, but rather to the resulting contraction of muscles (and related interruption of respiration) and subsequent sequelae. Transient increases in hematocrit, potassium, and sodium were consistent with previous reports in the literature dealing with studies of muscle stimulation or exercise. It is doubtful that these short-term elevations would have any serious health consequences in a healthy individual. Blood pH was significantly decreased for 1h following exposure, but subsequently returned toward a normal level. Leg muscle contractions and decreases in respiration each appeared to contribute to the acidosis. Lactate was highly elevated, with a slow return (time course greater than 1 h) to baseline. Other investigators have reported profound metabolic acidosis during restraint-associated cardiac arrest. Since restraint often occurs immediately after TASER exposure, this issue should be considered in further development of deployment concepts. On the basis of the results of the current studies, the repeated use of electro-muscular incapacitating devices in a short period of time is, at least, feasible, with the caveat that some medical monitoring of subjects may be required (to observe factors such as lactate and acidosis). PMID:16289999

  20. Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR)

    PubMed Central

    Clearfield, Michael B; Amerena, John; Bassand, Jean-Pierre; Garca, Hugo R Hernndez; Miller, Sam S; Sosef, Froukje FM; Palmer, Michael K; Bryzinski, Brian S

    2006-01-01

    Background Many patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C) goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg) and atorvastatin (20 mg) in high-risk patients with hypercholesterolemia. Methods A total of 996 patients with hypercholesterolemia (LDL-C ? 3.4 and < 5.7 mmol/L [130 and 220 mg/dL]) and coronary heart disease (CHD), atherosclerosis, or a CHD-risk equivalent were randomized to once-daily rosuvastatin 10 mg or atorvastatin 20 mg. The primary endpoint was the percentage change from baseline in LDL-C levels at 6 weeks. Secondary endpoints included LDL-C goal achievement (National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] goal < 100 mg/dL; 2003 European goal < 2.5 mmol/L for patients with atherosclerotic disease, type 2 diabetes, or at high risk of cardiovascular events, as assessed by a Systematic COronary Risk Evaluation (SCORE) risk ? 5% or 3.0 mmol/L for all other patients), changes in other lipids and lipoproteins, cost-effectiveness, and safety. Results Rosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p < 0.05). Significantly more patients achieved NCEP ATP III and 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 20 mg (68.8% vs. 62.5%, p < 0.05; 68.0% vs. 63.3%, p < 0.05, respectively). High-density lipoprotein cholesterol was increased significantly with rosuvastatin 10 mg versus atorvastatin 20 mg (6.4% vs. 3.1%, p < 0.001). Lipid ratios and levels of apolipoprotein A-I also improved more with rosuvastatin 10 mg than with atorvastatin 20 mg. The use of rosuvastatin 10 mg was also cost-effective compared with atorvastatin 20 mg in both a US and a UK setting. Both treatments were well tolerated, with a similar incidence of adverse events (rosuvastatin 10 mg, 27.5%; atorvastatin 20 mg, 26.1%). No cases of rhabdomyolysis, liver, or renal insufficiency were recorded. Conclusion In high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated. PMID:17184550

  1. Labelling and 'Dear Doctor' letters: are they noncommittal?

    PubMed

    van Grootheest, A C Kees; Edwards, I Ralph

    2002-01-01

    Over the past few years, a number of drugs have been withdrawn for safety reasons, either by drug approval authorities, or by the manufacturer. A recent example is the withdrawal of cerivastatin in connection with rhabdomyolysis. Several other drugs have also been taken off the market as a security measure, not because the nature of the risk involved was unknown but because the risk had proved apparently uncontainable. It seems that the inclusion of a warning or contraindication in the Summary of Product Characteristics (SPC) or sending a 'Dear Doctor' letter is insufficient to ensure compliant prescription behaviour. There appears to be a discrepancy between the careful use of evidence underpinning the SPC content and formal warnings and changes to the SPC and the effect they have on the prescription and dispensing of the drugs involved. This results in undue loss or damage for both the manufacturer and the patient. There are no easy solutions to tackle this problem; the ineffectiveness of labelling and 'Dear Doctor' letters has ramifications for the whole regulatory/ industrial/educational complex. We discuss briefly four possible strategies for improving the current situation, with the emphasis on the place the prescriber has in this process. The first strategy is education-based. Clinicians need to know about the comparative merits of the effectiveness and risk of drugs, as well as how they work pharmacologically, toxicologically, and what interactions they have with each other. The second strategy involves improving the information available for clinicians. Frequently, physicians do not consult the SPC for verification, leaving aside whether they have taken notice of the contents of the official SPC in the first place. It is recommended that the accessibility of SPCs is enhanced for doctors and pharmacists, drawing attention specifically to any changes. There needs to be a single body of information that covers every drug. The third strategy involves communication. There is much to be done in this area both in terms of follow-up and understanding of health professional's behaviour and how to empower best practise. The final strategy involves professional freedom. It goes without saying that doctors who issue off-label prescriptions may need to justify their actions. Deviating from the SPC should always be a considered decision and health professionals need to be aware of the additional responsibilities associated with such a decision. The dispensing pharmacist can play an important role in the implementation of warnings and contraindications. PMID:12452731

  2. Deaths from exposure to paramethoxymethamphetamine in Alberta and British Columbia, Canada: a case series

    PubMed Central

    Yarema, Mark C.; Jones, Graham R.; Martz, Walter; Purssell, Roy A.; MacDonald, Judy C.; Wishart, Ian; Durigon, Monica; Tzemis, Despina; Buxton, Jane A.

    2015-01-01

    Background Paramethoxymethamphetamine (PMMA) is a ring-substituted amphetamine similar in structure to 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”), but substantially more toxic. We describe the clinical features of fatal exposures in the provinces of Alberta and British Columbia, Canada. Methods We conducted a retrospective case series on deaths in Alberta and BC between June 2011 and April 2012 for which forensic toxicologic analysis was positive for PMMA and the drug was implicated as the primary toxic agent. Data collected included patient demographics, exposure history, clinical features, investigations, therapy provided and postmortem toxicologic findings. Results A total of 27 PMMA-associated deaths (20 in Alberta, 7 in BC) were reported in the 11-month period. The median age was 24 (range 14–52) years, and 22 (81%) were male. Ten patients were pronounced dead at the scene, and 17 died in hospital. The median time from exposure to death was 17 (range 5–264) hours. The median first-recorded vital signs (and ranges) were: heart rate 160 (86–201) beats/min, blood pressure 89/43 (69/30–162/83) mm Hg, respiratory rate 40 (26–48) breaths/min, oxygen saturation 81% (68%–100%) and temperature 39.4°C (34–43.8°C). Sixteen of the 17 people who died in hospital presented with clinical features consistent with serotonin syndrome. End-organ dysfunction included hepatic (30%) and acute kidney injury (85%), rhabdomyolysis (54%), coagulopathy (61%) and cardiac ischemia (15%). Other drugs identified on toxicologic analysis were MDMA (n = 27), cocaine or its metabolite benzoylecgonine (n = 14) and methamphetamine (n = 12). Interpretation Exposure to PMMA was characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. In addition to PMMA, multiple synthetic amphetamines were present on toxicologic analysis. When evaluating patients suspected of exposure to sympathomimetic drugs of abuse, clinicians must anticipate multiple clinical effects from the increased release of dopamine, serotonin, norepinephrine and other neurotransmitters. PMID:25844375

  3. Clinical manifestations and prognostic features of acute methamphetamine intoxication.

    PubMed

    Lan, K C; Lin, Y F; Yu, F C; Lin, C S; Chu, P

    1998-08-01

    The prevalence of amphetamine abuse and the frequency of emergency department visits for amphetamine intoxication have increased dramatically worldwide. In this study, we retrospectively investigated the relationship between the prognostic features and clinical manifestations among patients admitted to the emergency department of a university hospital for acute methamphetamine intoxication during a 6-year period. Data collected included gender, age, route of abuse, time between drug exposure and arrival at the emergency department, estimated dose, signs and symptoms, laboratory values, and complications. Emergency therapy and cooling procedures were also recorded. After excluding 26 patients with multiple-drug intoxication, 18 patients (male-to-female ratio, 11:7) were include in the analysis. The mean age was 25.6 years. Thirteen patients survived and five died. Patients who died often presented with coma (80% vs 0%, p = 0.002), shock (60% vs 8%, p = 0.044), convulsions (100% vs 23%, p = 0.007), oliguria (80% vs 0%, p = 0.002), and high body temperature (41.4 +/- 0.5 degrees C vs 39.4 +/- 2.1 degrees C, p = 0.005). Furthermore, patients who died had significantly higher concentrations of blood urea nitrogen (8.7 +/- 2.1 vs 5.6 +/- 2.0 mmol/L, p = 0.01) and serum creatinine (212 +/- 71 vs 115 +/- 27 mumol/L, p = 0.033), and lower values of arterial pH (7.12 +/- 0.12 vs 7.34 +/- 0.10, p = 0.03), than those who survived. In the fatality group, the most common complication was rhabdomyolysis with acute renal failure (5 of 5); multiple organ failure resembling that from heatstroke was the leading cause of death from acute methamphetamine intoxication. In conclusion, the adverse prognostic features in patients with acute methamphetamine intoxication include coma, shock, convulsion, oliguria, and high core temperature. Acidosis, volume depletion, and ischemic renal damage were potential risk factors for development of acute renal failure in these patients. PMID:9747062

  4. Interactions between grapefruit juice and cardiovascular drugs.

    PubMed

    Bailey, David G; Dresser, George K

    2004-01-01

    Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by commercial grapefruit juice given as a single normal amount (e.g. 200-300 mL) or by whole fresh fruit segments. As a result, presystemic metabolism is reduced and oral drug bioavailability increased. Enhanced oral drug bioavailability can occur 24 hours after juice consumption. Inhibition of P-glycoprotein (P-gp) is a possible mechanism that increases oral drug bioavailability by reducing intestinal and/or hepatic efflux transport. Recently, inhibition of organic anion transporting polypeptides by grapefruit juice was observed in vitro; intestinal uptake transport appeared decreased as oral drug bioavailability was reduced. Numerous medications used in the prevention or treatment of coronary artery disease and its complications have been observed or are predicted to interact with grapefruit juice. Such interactions may increase the risk of rhabdomyolysis when dyslipidemia is treated with the HMG-CoA reductase inhibitors atorvastatin, lovastatin, or simvastatin. Potential alternative agents are pravastatin, fluvastatin, or rosuvastatin. Such interactions might also cause excessive vasodilatation when hypertension is managed with the dihydropyridines felodipine, nicardipine, nifedipine, nisoldipine, or nitrendipine. An alternative agent could be amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1 receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit juice interacting with the antidiabetic agent repaglinide may cause hypoglycemia, and interaction with the appetite suppressant sibutramine may cause elevated BP and HR. In angina pectoris, administration of grapefruit juice could result in atrioventricular conduction disorders with verapamil or attenuated antiplatelet activity with clopidrogel. Grapefruit juice may enhance drug toxicity for antiarrhythmic agents such as amiodarone, quinidine, disopyramide, or propafenone, and for the congestive heart failure drug, carvediol. Some drugs for the treatment of peripheral or central vascular disease also have the potential to interact with grapefruit juice. Interaction with sildenafil, tadalafil, or vardenafil for erectile dysfunction, may cause serious systemic vasodilatation especially when combined with a nitrate. Interaction between ergotamine for migraine and grapefruit juice may cause gangrene or stroke. In stroke, interaction with nimodipine may cause systemic hypotension. If a drug has low inherent oral bioavailability from presystemic metabolism by CYP3A4 or efflux transport by P-gp and the potential to produce serious overdose toxicity, avoidance of grapefruit juice entirely during pharmacotherapy appears mandatory. Although altered drug response is variable among individuals, the outcome is difficult to predict and avoiding the combination will guarantee toxicity is prevented. The elderly are at particular risk, as they are often prescribed medications and frequently consume grapefruit juice. PMID:15449971

  5. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups.

    PubMed

    Love, L A; Leff, R L; Fraser, D D; Targoff, I N; Dalakas, M; Plotz, P H; Miller, F W

    1991-11-01

    The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy. PMID:1659647

  6. Quantification of Na+,K+ pumps and their transport rate in skeletal muscle: Functional significance

    PubMed Central

    2013-01-01

    During excitation, muscle cells gain Na+ and lose K+, leading to a rise in extracellular K+ ([K+]o), depolarization, and loss of excitability. Recent studies support the idea that these events are important causes of muscle fatigue and that full use of the Na+,K+-ATPase (also known as the Na+,K+ pump) is often essential for adequate clearance of extracellular K+. As a result of their electrogenic action, Na+,K+ pumps also help reverse depolarization arising during excitation, hyperkalemia, and anoxia, or from cell damage resulting from exercise, rhabdomyolysis, or muscle diseases. The ability to evaluate Na+,K+-pump function and the capacity of the Na+,K+ pumps to fill these needs require quantification of the total content of Na+,K+ pumps in skeletal muscle. Inhibition of Na+,K+-pump activity, or a decrease in their content, reduces muscle contractility. Conversely, stimulation of the Na+,K+-pump transport rate or increasing the content of Na+,K+ pumps enhances muscle excitability and contractility. Measurements of [3H]ouabain binding to skeletal muscle in vivo or in vitro have enabled the reproducible quantification of the total content of Na+,K+ pumps in molar units in various animal species, and in both healthy people and individuals with various diseases. In contrast, measurements of 3-O-methylfluorescein phosphatase activity associated with the Na+,K+-ATPase may show inconsistent results. Measurements of Na+ and K+ fluxes in intact isolated muscles show that, after Na+ loading or intense excitation, all the Na+,K+ pumps are functional, allowing calculation of the maximum Na+,K+-pumping capacity, expressed in molar units/g muscle/min. The activity and content of Na+,K+ pumps are regulated by exercise, inactivity, K+ deficiency, fasting, age, and several hormones and pharmaceuticals. Studies on the α-subunit isoforms of the Na+,K+-ATPase have detected a relative increase in their number in response to exercise and the glucocorticoid dexamethasone but have not involved their quantification in molar units. Determination of ATPase activity in homogenates and plasma membranes obtained from muscle has shown ouabain-suppressible stimulatory effects of Na+ and K+. PMID:24081980

  7. Incidence, Characteristics and Risk Factors of Acute Kidney Injury among Dengue Patients: A Retrospective Analysis

    PubMed Central

    Mallhi, Tauqeer Hussain; Khan, Amer Hayat; Adnan, Azreen Syazril; Sarriff, Azmi; Khan, Yusra Habib; Jummaat, Fauziah

    2015-01-01

    Background Dengue induced acute kidney injury (AKI) imposes heavy burden of illness in terms of morbidity and mortality. A retrospective study was conducted to investigate incidence, characteristics, risk factors and clinical outcomes of AKI among dengue patients. Methodology A total 667 dengue patients (2008–2013) were retrospectively evaluated and were stratified into AKI and non-AKI groups by using AKIN criteria. Two groups were compared by using appropriate statistical methods. Results There were 95 patients (14.2%) who had AKI, with AKIN-I, AKIN-II and AKIN-III in 76.8%, 16.8% and 6.4% patients, respectively. Significant differences (P<0.05) in demographics and clinico-laboratory characteristics were observed between patients with and without AKI. Presence of dengue hemorrhagic fever [OR (95% CI): 8.0 (3.64–17.59), P<0.001], rhabdomyolysis [OR (95% CI): 7.9 (3.04–20.49)], multiple organ dysfunction [OR (95% CI): 34.6 (14.14–84.73), P<0.001], diabetes mellitus [OR (95% CI): 4.7 (1.12–19.86), P = 0.034], late hospitalization [OR (95% CI): 2.1 (1.12–19.86), P = 0.033] and use of nephrotoxic drugs [OR (95% CI): 2.9 (1.12–19.86), P = 0.006] were associated with AKI. Longer hospital stay (>3 days) was also observed among AKI patients (OR = 1.3, P = 0.044). Additionally, 48.4% AKI patients had renal insufficiencies at discharge that were signicantly associated with severe dengue, secondary infection and diabetes mellitus. Overall mortality was 1.2% and all fatal cases had AKI. Conclusions The incidence of AKI is high at 14.2% among dengue patients, and those with AKI portended significant morbidity, mortality, longer hospital stay and poor renal outcomes. Our findings suggest that AKI in dengue is likely to increase healthcare burden that underscores the need of clinicians’ alertness to this highly morbid and potentially fatal complication for optimal prevention and management. PMID:26421839

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

    PubMed

    Quinlivan, Rosaline; Martinuzzi, Andrea; Schoser, Benedikt

    2014-01-01

    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-ribose,glucagon, verapamil, vitamin B6, branched chain amino acids, dantrolene sodium, and high-dose creatine. Minimal subjective benefit was found with low dose creatine and ramipril only for patients with a polymorphism known as the D/Dangiotens in converting enzyme(ACE) phenotype. A carbohydrate-rich diet resulted in better exercise performance compared with a protein-rich diet. Two studies of oral sucrose given at different times and in different amounts before exercise showed an improvement in exercise performance. Four studies reported adverse effects. Oral ribose caused diarrhoea and symptoms suggestive of hypoglycaemia including light-headedness and hunger. In one study, branched chain amino acids caused a deterioration of functional outcomes. Dantrolene was reported to cause a number of adverse effects including tiredness, somnolence, dizziness and muscle weakness. Low dose creatine (60 mg/kg/day) did not cause side-effects but high-dose creatine (150 mg/kg/day) worsened the symptoms of myalgia.Authors' conclusions Although there was low quality evidence of improvement in some parameters with creatine, oral sucrose, ramipril and a carbohydrate rich diet, none was sufficiently strong to indicate significant clinical benefit. PMID:25391139

  9. When Coke Is Not Hydrating

    PubMed Central

    Talibmamury, Nibras; Alalusi, Sumer; Nadham, Omar; Omer, Abdel Rahman; Smalligan, Roger D.

    2014-01-01

    A 47-year-old African American man was admitted with 4 days of back pain, nausea and vomiting, and low urine output. There was no history of fever, dysuria, frequency, hesitancy, viral symptoms, trauma, rash, or constipation. Despite his past medical history of hypertension, diabetes mellitus, and hyperlipidemia he denied taking any medications for 18 months, including nonsteroidal anti-inflammatory drugs, acetaminophen, or antacids. He denied smoking and alcohol but admitted to cocaine use. No significant FH. Physical examination results were as follows: BP 235/125 mm Hg, heart rate 90 beats/min, temperature 98F, O2 saturation normal; lungs and heart normal, abdomen soft but bilateral costovertebral angle tenderness. Neurological examination was normal. Laboratory tests yielded the following results: creatinine (Cr) 10.5 mg/dL (1.2 mg/dL in 2010), blood urea nitrogen 63 mg/dL, glucose 151 mg/dL, Ca 9.4 mg/dL, PO4 6.1 mg/dL, Hgb 15 g/dL, white blood cells (WBC) 9100, platelets 167 000, amylase/lipase normal, aspartate aminotransferase/alanine aminotransferase (AST/ALT) normal, bilirubin 1.4 mg/dL, alkaline phosphatase 39 IU/L, creatine phosphokinase 127 g/L. Hepatic panel, C- and P-ANCA (cytoplasmic and perinuclearantineutrophil cytoplasm antibodies, respectively), anti-GBM (antiglomerular basement membrane), antimyeloperoxidase, antinuclear antibody, and Helicobacter pylori were all negative. C3, C4 normal, urinalysis: 2+ blood, no white blood cells or eosinophils, no casts, no albumin, negative for nitrate/leukocyte esterase and bacteria. Imaging: chest radiograph, abdominal radiograph, computed tomography of the abdomen, electrocardiography, and transthoracic echocardiography were all normal. Course. The patients urine output declined from 700 to 400 cm3/d and the on third day he required hemodialysis with Cr 14 mg/dL. Renal biopsy showed typical findings of interstitial nephritis. The patient was dialyzed for 10 days and responded to steroids and went home with an improving Cr of 3.5 mg/dL, back to baseline of 1.5 in 8 weeks. Discussion. Internists encounter patients with acute kidney injury (AKI) on a daily basis, most of which can be explained by prerenal azotemia, acute tubular necrosis (ATN), obstruction, or rhabdomyolysis among other etiologies. Cocaine is only rarely implicated as an etiology of AKI and if it is, usually the injury is due to ATN or pigment effects. Acute interstitial nephritis (AIN) caused by cocaine, on the other hand, has only been described in a handful of cases. AIN is a renal lesion that causes a decline in creatinine clearance and is characterized by an inflammatory infiltrate in the kidney interstitium and is most often associated with drug therapy. AIN can also be seen in autoimmune disorders like systemic lupus erythematosus, Sjgrens syndrome, or sarcoidosis; or with infections remote to the kidney like Legionella, leptospirosis, and streptococcal disease. Our case was very similar to the other reported cases of AIN due to cocaine in that all have occurred in middle-aged African American males and all have responded to steroids. This case reminds clinicians to consider AIN in patients with AKI and a history of cocaine abuse. PMID:26425622

  10. When Coke Is Not Hydrating: Cocaine-Induced Acute Interstitial Nephritis.

    PubMed

    Bahaa Aldeen, Mohammed; Talibmamury, Nibras; Alalusi, Sumer; Nadham, Omar; Omer, Abdel Rahman; Smalligan, Roger D

    2014-01-01

    A 47-year-old African American man was admitted with 4 days of back pain, nausea and vomiting, and low urine output. There was no history of fever, dysuria, frequency, hesitancy, viral symptoms, trauma, rash, or constipation. Despite his past medical history of hypertension, diabetes mellitus, and hyperlipidemia he denied taking any medications for 18 months, including nonsteroidal anti-inflammatory drugs, acetaminophen, or antacids. He denied smoking and alcohol but admitted to cocaine use. No significant FH. Physical examination results were as follows: BP 235/125 mm Hg, heart rate 90 beats/min, temperature 98F, O2 saturation normal; lungs and heart normal, abdomen soft but bilateral costovertebral angle tenderness. Neurological examination was normal. Laboratory tests yielded the following results: creatinine (Cr) 10.5 mg/dL (1.2 mg/dL in 2010), blood urea nitrogen 63 mg/dL, glucose 151 mg/dL, Ca 9.4 mg/dL, PO4 6.1 mg/dL, Hgb 15 g/dL, white blood cells (WBC) 9100, platelets 167 000, amylase/lipase normal, aspartate aminotransferase/alanine aminotransferase (AST/ALT) normal, bilirubin 1.4 mg/dL, alkaline phosphatase 39 IU/L, creatine phosphokinase 127 g/L. Hepatic panel, C- and P-ANCA (cytoplasmic- and perinuclear-antineutrophil cytoplasm antibodies, respectively), anti-GBM (anti-glomerular basement membrane), antimyeloperoxidase, antinuclear antibody, and Helicobacter pylori were all negative. C3, C4 normal, urinalysis: 2+ blood, no white blood cells or eosinophils, no casts, no albumin, negative for nitrate/leukocyte esterase and bacteria. Imaging: chest radiograph, abdominal radiograph, computed tomography of the abdomen, electrocardiography, and transthoracic echocardiography were all normal. Course. The patient's urine output declined from 700 to 400 cm(3)/d and the on third day he required hemodialysis with Cr 14 mg/dL. Renal biopsy showed typical findings of interstitial nephritis. The patient was dialyzed for 10 days and responded to steroids and went home with an improving Cr of 3.5 mg/dL, back to baseline of 1.5 in 8 weeks. Discussion. Internists encounter patients with acute kidney injury (AKI) on a daily basis, most of which can be explained by prerenal azotemia, acute tubular necrosis (ATN), obstruction, or rhabdomyolysis among other etiologies. Cocaine is only rarely implicated as an etiology of AKI and if it is, usually the injury is due to ATN or pigment effects. Acute interstitial nephritis (AIN) caused by cocaine, on the other hand, has only been described in a handful of cases. AIN is a renal lesion that causes a decline in creatinine clearance and is characterized by an inflammatory infiltrate in the kidney interstitium and is most often associated with drug therapy. AIN can also be seen in autoimmune disorders like systemic lupus erythematosus, Sjgren's syndrome, or sarcoidosis; or with infections remote to the kidney like Legionella, leptospirosis, and streptococcal disease. Our case was very similar to the other reported cases of AIN due to cocaine in that all have occurred in middle-aged African American males and all have responded to steroids. This case reminds clinicians to consider AIN in patients with AKI and a history of cocaine abuse. PMID:26425622

  11. Are all statins the same? Focus on the efficacy and tolerability of pitavastatin.

    PubMed

    da Silva, Pedro Marques

    2011-01-01

    Pitavastatin is the newest member of the HMG-CoA reductase inhibitor family and is approved as adjunctive therapy to diet to reduce elevated levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (Apo) B, and triglycerides and to increase levels of high-density lipoprotein (HDL) cholesterol in adult patients with primary hyperlipidemia or mixed dyslipidemia. Pitavastatin undergoes minimal metabolism by cytochrome P450 (CYP) enzymes and, therefore, has a low propensity for drug-drug interactions with drugs metabolized by CYP enzymes or the CYP3A4 substrate grapefruit juice. In clinical trials, pitavastatin potently and consistently reduced serum levels of total, LDL, and non-HDL cholesterol, and triglycerides in patients with primary hypercholesterolemia where diet and other non-pharmacological measures were inadequate. Mean reductions from baseline in serum total and LDL cholesterol and triglyceride levels were 21-32%, 30-45%, and 10-30%, respectively. Moreover, a consistent trend towards increased HDL cholesterol levels of 3-10% was seen. Long-term extension studies show that the beneficial effects of pitavastatin are maintained for up to 2 years. Pitavastatin produces reductions from baseline in serum total and LDL cholesterol levels to a similar extent to those seen with the potent agent atorvastatin and to a greater extent than those seen with simvastatin or pravastatin. In the majority of other studies comparing pitavastatin and atorvastatin, no significant differences in the favorable effects on lipid parameters were seen, although pitavastatin was consistently associated with trends towards increased HDL cholesterol levels. Pitavastatin also produces beneficial effects on lipids in patients with type 2 diabetes mellitus and metabolic syndrome without deleterious effects on markers of glucose metabolism, such as fasting blood glucose levels or proportion of glycosylated hemoglobin. Pitavastatin appears to exert a number of beneficial effects on patients at risk of cardiovascular events independent of lipid lowering. In the JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) study, pitavastatin was non-inferior to atorvastatin at reducing plaque volume in patients with ACS undergoing percutaneous coronary intervention. Further beneficial effects, including favorable effects on the size and composition of atherosclerotic plaques, improvements in cardiovascular function, and improvements in markers of inflammation, oxidative stress, and renal function, have been demonstrated in a number of small studies. Pitavastatin is generally well tolerated in hyperlipidemic patients with or without type 2 diabetes, with the most common treatment-related adverse events being musculoskeletal or gastrointestinal in nature. Increases in plasma creatine kinase levels were seen in <5% of pitavastatin recipients and the incidence of myopathy or rhabdomyolysis was extremely low. In summary, pitavastatin, the latest addition to the statin family, produces potent and consistent beneficial effects on lipids, is well tolerated, and has a favorable pharmacokinetic profile. The combination of a potent decrease in total and LDL cholesterol levels and increase in HDL cholesterol levels suggest that pitavastatin may produce substantial cardiovascular protection. PMID:21446776

  12. AB063. 63 cases of DCD experience in renal transplant recipients

    PubMed Central

    Sun, Xu

    2015-01-01

    Objective To retrospectively analyze the clinical data of patients with ESRD undergoing cardiac death organ donation free (DCD) renal transplant, summarize the recovery condition after renal transplantation and the influence of DCD donor to recipient and graft postoperative. Methods There were 32 donors in 63 cases of DCD renal transplantation, including 28 men and four women. Their ages ranged from 3-62 years old, and the average age was 33.5 years. The donors included 28 cases of traumatic brain injury, two cases of cerebral tumor, one case of cerebral vascular accident, five children donors, 16 with preoperative abnormal creatinine (sCr).The 63 recipients included 43 men and 20 women. Their ages ranged from 25-49 years old. The average age was 33.5 years. Recipients were 23 cases of chronic glomerulonephritis original disease, 18 cases of chronic renal insufficiency, and the nine cases of high blood pressure, six cases of nephrotic syndrome, seven other cases. The recipients blood type were 13 type A, 30 type B, 20 type O. HLA antigen matching included four cases of five antigen mismatches, 18 cases of four antigen mismatches, 31 cases of three antigen mismatches, two antigen mismatches 11 cases. Minimized or avoided the use of strong contraction of norepinephrine renal artery vasoactive drugs during donor maintenance. Indicators for kidney assessment: clinical data including age, blood pressure, heart rate, urine output, creatinine, primary disease, past history kidney disease, dying time, vasoactive drug use, B-renal morphology and blood flow in B-ultrasound; the warm ischemia time and cold ischemic time of donor renal; color, shape and texture of donor renal; the kidney quality by application life-port renal perfusion assessment instrument; donor kidney biopsy. ARI DCD donor kidney transplant acceptance criteria: no history of chronic kidney disease, negative biopsy, no chronic structural lesions (alternative), age <50 years, occurred during or after the trauma ICU to maintain, obvious inducement, abdominal ultrasound examination without morphological abnormalities, vascular tree clear, common causes: prehospital hypovolemic shock, boosting drugs during ICU, traumatic brain injury lead to lower blood pressure perfusion, rhabdomyolysis myoglobin casts. Caution or waive the standard for kidney: die because of drowning, suffocation longer time; active infection without treatment; ICU treatment time for more than one week; dying more than 1 hour, warm ischemia time over 30 min; appearance gray, and after heparin infusion cannot be restored; life-port continuous perfusion RI >0.6, continuous infusion flow rate <50 mL/min; renal transplant biopsy shows a wide range of micro-thrombosis. The adoption of immunosuppressive regimen was ATG + TAC + MMF + Pre. Results Forty-seven cases donors had normal sCr, 19 cases had delayed graft function (DGF) after transplantation, accounting for 40.4%. Ten cases dialyzed postoperative, accounting for 21.3%, who had an average of dialysis three times. The sCr recovery the normal time was 10.7 days. There were 16 donors had abnormal sCr (sCr at 184-504 umol/between L). All had DGF postoperative, accounting for 100%. And 11 cases dialyzed postoperative, accounting for 68.7%, an average of 6.7 times. The time of sCr returned to normal was 28.9 days after surgery. There were a total of 63 cases of DCD renal transplantation, including 35 cases of DGF, accounted for 55.6%. And 21 cases, accounting for 33.3%, should do hemodialysis postoperative. Seven cases suffered from acute rejection, 11 cases had different degree of the infection in different parts, one case died, and three cases had renal allograft loss. Conclusions Of the 63 cases of DCD renal transplantation in our hospital, through the follow up of 312 months, 94.7% of recipients transplanted kidney maintain good function in the short term. Living donor restrictions, death row organs have been banned, DCD is now an important part of the organ sources in China. Facing the organ shortage, DCD is a very po