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Sample records for rhabdomyolysis

  1. [Rhabdomyolysis].

    PubMed

    Rosa, Nuno Guimarães; Silva, Gil; Teixeira, Alves; Rodrigues, Fernando; Araújo, José Augusto

    2005-01-01

    Rhabdomyolysis is a common entity that often has a multifactorial etiology. It usually affects healthy individuals, following trauma, excessive physical activity, convulsive crisis, alcohol and other drugs consumption or infections. Accumulation of intracellular calcium, activation of proteases and lipases, production of free radicals and the infiltration by inflammatory cells, are some of the mechanisms responsible for muscular necrosis. Myoglobinuric acute renal failure (ARF) is only possible in the presence of myoglobin, liberated by the muscle cells, and of hypovolemia/renal hypoperfusion. One of the most important complications of this entity is electrolyte disturbance (hyperkalemia, hypocalcemia, metabolic acidosis), that can be aggravated by the establishment of ARF. The diagnosis of rhabdomyolysis relies on the elevation of creatine kinase and on the presence of myoglobinuria. The main therapeutic goals are removal of precipitating factors, handling of biochemical complications, prevention and treatment of ARF using renal replacement techniques when necessary. Early diagnosis and treatment are of critical importance in epidemic forms of rhabdomyolysis (e. g. earthquakes) often associated with ARF. In this setting, the quick access to the dialysis equipment and human resources can be compromised and conservative measures, as an early and vigorous hydratation associated with a forced alkaline diuresis, can improve the prognosis of this complication. PMID:16584660

  2. Rhabdomyolysis updated

    PubMed Central

    Efstratiadis, G; Voulgaridou, A; Nikiforou, D; Kyventidis, A; Kourkouni, E; Vergoulas, G

    2007-01-01

    Rhabdomyolysis constitutes a common cause of acute renal failure and presents paramount interest. A large variety of causes with different pathogenetic mechanisms can involve skeletal muscles resulting in rhabdomyolysis with or without acute renal failure. Crush syndrome, one of the most common causes of rhabdomyolysis presents increased clinical interest, particularly in areas often involved by earthquakes, such as Greece and Turkey. Drug abusers are another sensitive group of young patients prone to rhabdomyolysis, which attracts the clinical interest of a variety of medical specialties. We herein review the evidence extracted from updated literature concerning the data related to pathogenetic mechanisms and pathophysiology as well as the management of this interesting syndrome. PMID:19582207

  3. 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 β-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

  4. Diagnostic Evaluation of Rhabdomyolysis

    PubMed Central

    Nance, Jessica R.; Mammen, Andrew L.

    2015-01-01

    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 following an inciting factor and may be associated with dark pigmentation of the urine. Serum creatine kinase and urine myoglobin levels are markedly elevated. The 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 disturbance, and autoimmune myopathies. Inherited predisposition to rhabdomyolysis can occur with disorders of glycogen metabolism, fatty acid beta-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. PMID:25678154

  5. [Metabolic rhabdomyolysis during statin therapy].

    PubMed

    Vergely, N; Leca, V; Antoine, J-C; Germain, N; Khalfallah, Y; Estour, B

    2009-08-01

    The occurrence of rhabdomyolysis during statin treatment for dyslipidemia is a well-known side effect. However, the differential diagnosis of rhabdomyolysis is large. We report on a patient treated with statin who presented a rhabdomyolysis. The persistence of laboratory abnormalities allowed to discover a metabolic rhabdomyolysis, namely a carnitine palmitoyltransférase II deficiency. The diagnosis of the genetic abnormality allows to modify the therapeutic care. PMID:19419805

  6. Acute rhabdomyolysis and inflammation.

    PubMed

    Hamel, Yamina; Mamoune, Asmaa; Mauvais, François-Xavier; Habarou, Florence; Lallement, Laetitia; Romero, Norma Beatriz; Ottolenghi, Chris; de Lonlay, Pascale

    2015-07-01

    Rhabdomyolysis results from the rapid breakdown of skeletal muscle fibers, which leads to leakage of potentially toxic cellular content into the systemic circulation. Acquired causes by direct injury to the sarcolemma are most frequent. The inherited causes are: i) metabolic with failure of energy production, including mitochondrial fatty acid ß-oxidation defects, LPIN1 mutations, inborn errors of glycogenolysis and glycolysis, more rarely mitochondrial respiratory chain deficiency, purine defects and peroxysomal α-methyl-acyl-CoA-racemase defect (AMACR), ii) structural causes with muscle dystrophies and myopathies, iii) calcium pump disorder with RYR1 gene mutations, iv) inflammatory causes with myositis. Irrespective of the cause of rhabdomyolysis, the pathology follows a common pathway, either by the direct injury to sarcolemma by increased intracellular calcium concentration (acquired causes) or by the failure of energy production (inherited causes), which leads to fiber necrosis. Rhabdomyolysis are frequently precipitated by febrile illness or exercise. These conditions are associated with two events, elevated temperature and high circulating levels of pro-inflammatory mediators such as cytokines and chemokines. To illustrate these points in the context of energy metabolism, protein thermolability and the potential benefits of arginine therapy, we focus on a rare cause of rhabdomyolysis, aldolase A deficiency. In addition, our studies on lipin-1 (LPIN1) deficiency raise the possibility that several diseases involved in rhabdomyolysis implicate pro-inflammatory cytokines and may even represent primarily pro-inflammatory diseases. Thus, not only thermolability of mutant proteins critical for muscle function, but also pro-inflammatory cytokines per se, may lead to metabolic decompensation and rhabdomyolysis. PMID:25778939

  7. Rhabdomyolysis: the hidden killer.

    PubMed

    Criner, Judy A; Appelt, Mavis; Coker, Chantal; Conrad, Shirley; Holliday, Jackie

    2002-06-01

    Rhabdomyolysis can strike anyone given the right circumstances. Combining vigorous exercise, drugs, and extreme heat puts one at risk. However, there are many causes for "rhabdo." With early recognition and treatment, a devastating outcome can be prevented. Education is the key! PMID:12080571

  8. 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

  9. 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 37.8°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

  10. 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

  11. 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

  12. Exertional Rhabdomyolysis in the Athlete

    PubMed Central

    Tietze, David C.; Borchers, James

    2014-01-01

    Context: Exertional rhabdomyolysis is a relatively uncommon but potentially fatal condition affecting athletes that requires prompt recognition and appropriate management. Evidence Acquisition: A search of the PubMed database from 2003 to 2013 using the term exertional rhabdomyolysis was performed. Further evaluation of the bibliographies of articles expanded the evidence. Study Design: Clinical review. Level of Evidence: Level 3. Results: Exertional rhabdomyolysis (ER) is a relatively uncommon condition with an incidence of approximately 29.9 per 100,000 patient years but can have very serious consequences of muscle ischemia, cardiac arrhythmia, and death. The athlete will have pain, weakness, and swelling in the muscles affected as well as significantly elevated levels of creatine kinase (CK). Hydration is the foundation for any athlete with ER; management can also include dialysis or surgery. Stratifying the athlete into high- or low-risk categories can determine if further workup is warranted. Conclusion: Exertional rhabdomyolysis evaluation requires a history, physical examination, and serology for definitive diagnosis. Treatment modalities should include rest and hydration. Return to play and future workup should be determined by the risk stratification of the athlete. Strength-of-Recommendation Taxonomy (SORT): C. PMID:24982707

  13. Acute kidney injury due to rhabdomyolysis.

    PubMed

    Lima, Rafael Siqueira Athayde; da Silva Junior, Geraldo Bezerra; Liborio, Alexandre Braga; Daher, Elizabeth De Francesco

    2008-09-01

    Rhabdomyolysis is a clinical and biochemical syndrome that occurs when skeletal muscle cells disrupt and release creatine phosphokinase (CK), lactate dehydrogenase (LDH), and myoglobin into the interstitial space and plasma. The main causes of rhabdomyolysis include direct muscular injury, strenuous exercise, drugs, toxins, infections, hyperthermia, seizures, meta-bolic and/or electrolyte abnormalities, and endocrinopathies. Acute kidney injury (AKI) occurs in 33-50% of patients with rhabdomyolysis. The main pathophysiological mechanisms of renal injury are renal vasoconstriction, intraluminal cast formation, and direct myoglobin toxicity. Rhabdo-myolysis can be asymptomatic, present with mild symptoms such as elevation of muscular en-zymes, or manifest as a severe syndrome with AKI and high mortality. Serum CK five times higher than the normal value usually confirms rhabdomyolysis. Early diagnosis and saline volume expansion may reduce the risk of AKI. Further studies are necessary to establish the importance of bicarbonate and mannitol in the prevention of AKI due to rhabdomyolysis. PMID:18711286

  14. Fatal rhabdomyolysis in a flame burn patient.

    PubMed

    Lazarus, D; Hudson, D A

    1997-08-01

    Rhabdomyolysis due to flame burns is not well described. A case of fatal rhabdomyolysis in an epileptic patient who sustained 65 per cent body surface area, very deep, flame burns is described. It appears as if the sustained muscle compression from the restrictive, circumferential eschar was the major factor in the aetiology of the rhabdomyolysis. Despite aggressive fluid management, the patient died of acute renal failure and adult respiratory distress syndrome. We have subsequently identified three other cases of pigmenturia occurring following burns. It would seem as if rhabdomyolysis following extensive full thickness burns may be more common than previously suggested. Fluid requirements are in excess of those proposed by traditional protocols. Rhabdomyolysis in flame burn patients indicates a poor prognosis. PMID:9426917

  15. A Case of Phenytoin-induced Rhabdomyolysis in Status Epilepticus

    PubMed Central

    Kim, Hyunjin; Jo, Sungyang; Park, Kye Won; Han, Su-Hyun; Lee, Sang-Ahm

    2016-01-01

    Phenytoin is a commonly used antiepileptic drug, especially when treating status epilepticus. Here, we present a patient who suffered from status epilepticus and developed rhabdomyolysis after being treated with phenytoin. As multiple seizures itself can induce rhabdomyolysis, it is difficult to recognize that phenytoin can be the cause of rhabdomyolysis in status epilepticus patients. Even though phenytoin is a rare cause of rhabdomyolysis, we should discern that phenytoin can be a causative drug to bring about rhabdomyolysis. PMID:27390679

  16. 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

  17. Rhabdomyolysis After Cosmetic Laser-Assisted Liposuction.

    PubMed

    Shin, Jin-yong; Chang, Hak

    2015-08-01

    A 34-year-old-female patient visited our emergency room for symptoms of disturbance of urination and shortness of breath. She was diagnosed with rhabdomyolysis with acute kidney injury after laser-assisted liposuction and required hemodialysis. Although laser-assisted liposuction is a well-used procedure, it can cause local complications, such as burns and skin irregularities, as well as systemic complications, such as infection, fever, and emboli. However, laser-assisted, liposuction-induced rhabdomyolysis has not been reported. Repetitive exercises, trauma, and crush injury are the major causes of rhabdomyolysis. In this study, a unique case of rhabdomyolysis that developed after laser-assisted liposuction is reported. PMID:26085224

  18. Rhabdomyolysis and acute renal failure after gardening.

    PubMed

    Vucicevic, Zeljko

    2015-01-01

    Acute nontraumatic exertional rhabdomyolysis may arise when the energy supply to muscle is insufficient to meet demands, particularly in physically untrained individuals. We report on a psychiatric patient who developed large bruises and hemorrhagic blisters on both hands and arms, rhabdomyolysis of both forearm muscles with a moderate compartment syndrome, and consecutive acute renal failure following excessive work in the garden. Although specifically asked, the patient denied any hard physical work or gardening, and heteroanamnestic data were not available. The diagnosis of rhabdomyolysis was easy to establish, but until reliable anamnestic data were obtained, the etiology remained uncertain. Four days after arrival, the patient recalled working hard in the garden. The etiology of rhabdomyolysis was finally reached, and the importance of anamnestic data was once more confirmed. PMID:25954536

  19. Rhabdomyolysis and Acute Renal Failure after Gardening

    PubMed Central

    Vucicevic, Zeljko

    2015-01-01

    Acute nontraumatic exertional rhabdomyolysis may arise when the energy supply to muscle is insufficient to meet demands, particularly in physically untrained individuals. We report on a psychiatric patient who developed large bruises and hemorrhagic blisters on both hands and arms, rhabdomyolysis of both forearm muscles with a moderate compartment syndrome, and consecutive acute renal failure following excessive work in the garden. Although specifically asked, the patient denied any hard physical work or gardening, and heteroanamnestic data were not available. The diagnosis of rhabdomyolysis was easy to establish, but until reliable anamnestic data were obtained, the etiology remained uncertain. Four days after arrival, the patient recalled working hard in the garden. The etiology of rhabdomyolysis was finally reached, and the importance of anamnestic data was once more confirmed. PMID:25954536

  20. Frequent rhabdomyolysis in anti-NMDA receptor encephalitis.

    PubMed

    Lim, Jung-Ah; Lee, Soon-Tae; Kim, Tae-Joon; Moon, Jangsup; Sunwoo, Jun-Sang; Byun, Jung-Ick; Jung, Keun-Hwa; Jung, Ki-Young; Chu, Kon; Lee, Sang Kun

    2016-09-15

    The aim of this study was to analyze the clinical presentation and provocation factors of rhabdomyolysis in anti-NMDAR encephalitis. Among the 16 patients with anti-NMDAR encephalitis in our institutional cohort, nine patients had elevated CK enzyme levels and clinical evidence of rhabdomyolysis. Rhabdomyolysis was more frequent after immunotherapy. The use of dopamine receptor blocker (DRB) increased the risk of rhabdomyolysis. None of the patients without rhabdomyolysis received DRBs. Rhabdomyolysis is a frequent complication in anti-NMDAR encephalitis and more common after immunotherapy and the use of DRBs increases the risk. Therefore, DRBs should be administered carefully in patients with anti-NMDAR encephalitis. PMID:27609293

  1. Isotretinoin induced rhabdomyolysis? A case report.

    PubMed

    Trauner, M A; Ruben, B S

    1999-11-01

    Isotretinoin, an effective therapy for nodulocystic acne and dissecting cellulitis of the scalp, has many known side effects. However, its association with elevated creatine kinase levels and its potential to cause rhabdomyolysis is not well established. We describe a patient with a significant elevation in creatine kinase after beginning therapy with isotretinoin for dissecting cellulitis of the scalp. The implications of isotretinoin causing rhabdomyolysis are discussed. PMID:10673455

  2. Rhabdomyolysis

    MedlinePlus

    ... Shafuddin AA, Weisbord SD, Palevsky PM, et al. Acute kidney injury. In: Taal MW, Chertow GM, Marsden PA, et al, eds. Brenner and Rector's The Kidney . 9th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 30. Read More Acute kidney failure Acute tubular necrosis Alcohol use disorder ...

  3. 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

  4. Rhabdomyolysis as a complication of canine babesiosis.

    PubMed

    Jacobson, L S; Lobetti, R G

    1996-06-01

    Rhabdomyolysis was diagnosed in two dogs with babesiosis. The first animal presented with muscle pain and caramel-coloured urine, and had markedly elevated serum myoglobin and muscle enzymes. Acute renal failure complicated the clinical picture. The second dog exhibited muscle pain and tremors, together with neurological signs and pulmonary oedema, and died soon after admission. Muscle necrosis and haemorrhage were found at necropsy. In human malaria, a disease clinically similar to canine babesiosis, rhabdomyolysis is unusual, but clinically silent muscle damage appears to be common. Likewise, biochemical evidence of muscle damage is readily found in experimental bovine babesiosis. Muscle enzymes were mildly elevated in three dogs with severe babesiosis and pigmenturia but there was no obvious muscle damage, indicating that this might also apply to canine babesiosis. The pathogenesis of infection-associated rhabdomyolysis and acute renal failure remains unclear, but inflammatory cytokines and nitric oxide could play an important role. PMID:8965483

  5. Fatal rhabdomyolysis in systemic lupus erythematosus.

    PubMed

    de Carvalho, Jozélio Freire; da Mota, Licia Maria Henrique; Bonfa, Eloisa

    2011-09-01

    The authors describe herein the sixth lupus case that evolved with rhabdomyolysis. A 36-year-old woman with systemic lupus erythematosus was admitted to our hospital with malaise, myalgia, dysphagia, fever, preserved muscle strength, leukocytosis (15,600 cells), and increased creatine kinase of 1,358 IU/L that reached 75,000 IU/L in few days. She denied the use of myotoxic drugs and alcohol. Urine 1 showed false positive for hemoglobinuria (myoglobin) without erythrocytes in the sediment, confirming the diagnosis of rhabdomyolysis. Secondary causes were excluded. She was treated with hyperhydration and alkalinization of urine. Despite treatment, the patient developed pulmonary congestion and she died. The authors also review in this article rhabdomyolysis in patients with systemic lupus erythematosus. PMID:21127876

  6. 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

  7. Rhabdomyolysis induced by excessive coffee drinking.

    PubMed

    Chiang, W-F; Liao, M-T; Cheng, C-J; Lin, S-H

    2014-08-01

    Excessive ingestion of caffeine-containing beverages is a rare cause of rhabdomyolysis. Here, we describe the case of a 44-year-old woman presented with nausea, vomiting, palpitations, and tea-colored urine 6 h after drinking a liter of black coffee containing approximately 565 mg of caffeine for mental alertness. Laboratory studies were notable for myoglobinuria and markedly elevated plasma creatine kinase (CK) level of 7315 U/L. With volume expansion and alkalization, her plasma CK level returned to normal within 5 days. Rhabdomyolysis should be considered a potential health hazard from excessive consumption of caffeine-containing products. PMID:24220878

  8. Rhabdomyolysis After Ankle Strain and Light Cycling

    PubMed Central

    Hu, James; Ng, David

    2016-01-01

    A 35-year-old female presented to the emergency room with severe upper leg and back pain, which began 3 days after low-intensity cycling and falling from a stationary bike. She developed rhabdomyolysis with a maximum serum creatine kinase level of 72,358 U/L. This case report demonstrates that rhabdomyolysis has a wide range and spectrum of causes and risk factors. Although uncommon, this condition can occur after low-intensity exercise despite absence of other significant risk factors. Thus, clinicians should maintain a high clinical suspicion when initial history, physical examination, and laboratory tests suggest this diagnosis. PMID:27540443

  9. Rhabdomyolysis After Ankle Strain and Light Cycling.

    PubMed

    Hu, James; Ng, David

    2016-09-01

    A 35-year-old female presented to the emergency room with severe upper leg and back pain, which began 3 days after low-intensity cycling and falling from a stationary bike. She developed rhabdomyolysis with a maximum serum creatine kinase level of 72,358 U/L. This case report demonstrates that rhabdomyolysis has a wide range and spectrum of causes and risk factors. Although uncommon, this condition can occur after low-intensity exercise despite absence of other significant risk factors. Thus, clinicians should maintain a high clinical suspicion when initial history, physical examination, and laboratory tests suggest this diagnosis. PMID:27540443

  10. Successful reintroduction of statin therapy after statin-associated rhabdomyolysis.

    PubMed

    Simons, Janet E; Holbrook, Anne M; Don-Wauchope, Andrew C

    2015-01-01

    The case report demonstrates the successful use of an alternative statin after a statin-related episode of rhabdomyolysis. Statin-associated rhabdomyolysis is a serious adverse event with a very low incidence and is considered the most severe of the muscle-related side effects of the statins. Rechallenge with statins is not a recommended practice after rhabdomyolysis. The patient experienced a myocardial infarct 1 y after the episode of rhabdomyolysis. He used alternative lipid-lowering therapy for 2 y. His low-density lipoprotein cholesterol was not meeting typical secondary prevention targets. An alternative statin was introduced and the patient has been followed for 4 years without recurrence of the rhabdomyolysis. This case suggests it may be time to reconsider the accepted practice of permanently avoiding statin therapy after rhabdomyolysis. PMID:26228678

  11. Methocarbamol suspension for the treatment of rhabdomyolysis in equines.

    PubMed

    Pruitt, Bobby N

    2013-01-01

    Rhabdomyolysis in equines occurs in horses due to physical overexertion or underlying pathologic myopathy. Methocarbamol is a muscle relaxant that can be used in equines to treat symptoms associated with Rhabdomyolysis. Methocarbamol is available as a solution for injection but is not commercially available as an oral suspension. This article focuses on the treatment of Tying-up caused by overexertion, and details the treatment of Rhabdomyolysis with an oral suspension that was prepared for a veterinarian by a compounding pharmacist. PMID:24459784

  12. Rhabdomyolysis in adolescent athletes: review of cases.

    PubMed

    Hummel, Kevin; Gregory, Andrew; Desai, Neerav; Diamond, Alex

    2016-05-01

    Rhabdomyolysis is a syndrome characterized by muscle pain, weakness and myoglobinuria and ranges in severity from asymptomatic to life threatening with acute kidney failure. While a common condition in adult populations, it is understudied in pediatrics and the majority of adolescent cases are likely exercise-induced, caused by strenuous exercise in athletes. Recently, in our pediatric sports medicine practice, we have seen numerous cases of late adolescent high school athletes who present with severe muscle pain and were found to have elevated creatine kinase levels. The cases review potential contributing factors including characteristics of the workout, use of supplements, caffeine, medication, and metabolic or genetic predisposition. Treatment for exercised-induced rhabdomyolysis rarely requires more than rehydration. Return to play should be progressive, individualized, and include acclimatization and monitoring of hydration status, though guidelines require further review. PMID:27031535

  13. 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…

  14. Rhabdomyolysis developing after transcatheter arterial chemoembolization for hepatocellular carcinoma.

    PubMed

    Matake, Kunishige; Tajima, Tsuyoshi; Yoshimitsu, Kengo; Irie, Hiroyuki; Aibe, Hitoshi; Sugitani, Atsushi; Honda, Hiroshi

    2009-11-01

    A 25-year-old man with hepatocellular carcinoma developed severe muscular weakness and pain 15 days after transcatheter arterial chemoembolization (TACE). The diagnosis of rhabdomyolysis was made based on myalgia localized in the bilateral upper extremities (bilateral trapezius, deltoid, biceps brachii, and teres major muscles) on magnetic resonance imaging and increased levels of muscle-derived serum enzymes. In this case, some drugs administered during the clinical course of TACE (diclofenac, famotidine, and cefotiam dihydrochloride) were suspected to be involved in the rhabdomyolysis, but the exact cause of rhabdomyolysis was not identified. The symptoms were completely improved by right trisegmentectomy of the liver following conservative treatment. PMID:19680719

  15. Hypokalemic rhabdomyolysis: an unusual presentation of Sjogren's syndrome

    PubMed Central

    Cherif, Eya; Ben Hassine, Lamia; Kechaou, Ines; Khalfallah, Narjess

    2013-01-01

    Hypokalaemic rhabdomyolysis represents a medical emergency requiring rapid diagnosis and appropriate aetiological treatment. Renal tubular acidosis is a common cause of hypokalemia which can be idiopathic or secondary to systemic disorders such as Sjogren's syndrome. It can remain asymptomatic or manifest with metabolic abnormalities including hypokalemia paralysis, hypocalcaemia and hyperchloremic metabolic acidosis. Rhabdomyolysis presenting with severe hypokalemia as the first manifestation of Sjogren's syndrome is rare. We report a case of a 59-year-old woman who presented to our department with severe weakness of all limbs. Laboratory examination demonstrated hypokalemic rhabdomyolysis caused by distal renal tubular acidosis. Investigations revealed Sjogren's syndrome as the underlying cause of the metabolic disorders. PMID:24165505

  16. 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

  17. Colchicine-Induced Rhabdomyolysis: An Autopsy Case.

    PubMed

    Arslan, Murat Nihat; Özgün, Ayşe; Daş, Taner; Kumru, Durmuş; Şam, Bülent; Koç, Sermet

    2016-06-01

    Colchicine is derived from Colchicum autumnale and Gloriosa superba and is used to treat acute gout and familial Mediterranean fever (FMF). Musculoskeletal adverse effects range from myopathy to rhabdomyolysis. An 18-year-old woman, with a 2-year history of FMF treated with colchicine, took 9 colchicine pills (4.5 mg) to relieve severe abdominal pain. On the sixth day of hospitalization, the patient's condition worsened, and she died. As this was a case of fatal poisoning, a forensic autopsy was performed, and the cause of death was determined to be complications of muscle destruction due to colchicine intoxication with the findings of myocytolysis, positive antimyoglobin antibody staining kidney tubules. Colchicine toxicity begins with gastrointestinal symptoms. Multiorgan effects follow the gastrointestinal effects. Serious outcomes of colchicine toxicity are rhabdomyolysis, bone marrow suppression, and disseminated intravascular coagulation. In chronic diseases that require lifelong treatment with medications, adverse effects can arise with long periods of use. Our patient had been treated for FMF with colchicine for 2 years but took too many colchicine pills to relieve her severe abdominal pain. Warning patients about the effects of high doses of drugs and providing information about their toxic effects and what to do "in case" of overuse could be lifesaving. PMID:27049658

  18. 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

  19. Rhabdomyolysis After Performing Blood Flow Restriction Training: A Case Report.

    PubMed

    Tabata, Shogo; Suzuki, Yukio; Azuma, Koichiro; Matsumoto, Hideo

    2016-07-01

    Tabata, S, Suzuki, Y, Azuma, K, and Matsumoto, H. Rhabdomyolysis after performing blood flow restriction training: a case report. J Strength Cond Res 30(7): 2064-2068, 2016-Rhabdomyolysis is a serious and potentially life-threatening condition related to resistance training. Despite numerous reports of low-intensity blood flow restriction (BFR) training inducing muscle hypertrophy and increasing strength, few reports of rhabdomyolysis related to BFR training have been published. Here, we report a 30-year-old obese Japanese man admitted to our hospital the day after his first BFR training session with complaints of severe muscle pain in his upper and lower extremities, high fever, and pharyngeal pain. He was diagnosed with acute rhabdomyolysis based on a serum creatine phosphokinase level of 56,475 U·L and a urine myoglobin level of >3,000 ng·ml, and with acute tonsillitis based on a white blood cell count of 17,390 and C-reactive protein level of 10.43 mg·dl. A number of factors are suspected to be related to the onset and exacerbation of rhabdomyolysis, including excessive muscular training with BFR, bacterial infection, and medication. After 10 days of hospitalization with intravenous fluids and antibacterial drugs, he recovered without complications. This case indicates that BFR training should be conducted with careful consideration of the physical condition and strength of the individual to prevent serious complications, such as rhabdomyolysis. PMID:26677831

  20. Return to physical activity after exertional rhabdomyolysis.

    PubMed

    O'Connor, Francis G; Brennan, Fred H; Campbell, William; Heled, Yuval; Deuster, Patricia

    2008-01-01

    Exertional rhabdomyolysis (ER) is a condition characterized by muscle pain, swelling, and weakness following some exertional stress, with or without concomitant heat stress. Athletes who experience ER often present to the emergency department, the training room, or the physician's office seeking guidance and care for this condition, often feeling it is simply normal delayed onset muscle soreness. The astute clinician must perform a thorough history and focused exam, in addition to ordering a serum creatine kinase (CK) and urinalysis. In this clinical setting, a CK equal to or greater than five times normal or a urine dipstick testing positive for blood with no demonstrable red blood cells upon microscopic assessment confirms the diagnosis. A urine or serum myoglobin is more definitive when expeditiously available. After treatment for ER, the provider must risk-stratify the athlete for risk of recurrence, consider further testing, and make the difficult decision on when, if, and under what conditions the athlete can safely return to play. PMID:19005354

  1. 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

  2. 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

  3. Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure.

    PubMed

    Young, Park Chi; Hae, Chung Choon; Lee, Kim Hyun; Hoon, Chung Jong

    2003-12-01

    Rhabdomyolysis is a rare complication that emerges in a variety of infectious diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and acute renal failure. On admission, an eschar, which is characteristic of tsutsugamushi infection, was found on her right flank area. Moreover, her tsutsugamushi antibody titer was 1:40960. The elevated values of serum creatinine phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to myoglobinuria are consistent with indications of rhabdomyolysis and acute renal failure due to tsutsugamushi infection. Her health improved without any residual effects after treatment with doxycyclin and hydration with normal saline. PMID:14717236

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

    PubMed

    Gautam, Parshotam L; Luthra, Neeru; Nain, Prabhdeep Singh

    2015-09-01

    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

  5. Genetic polymorphisms associated with exertional rhabdomyolysis.

    PubMed

    Deuster, Patricia A; Contreras-Sesvold, Carmen L; O'Connor, Francis G; Campbell, William W; Kenney, Kimbra; Capacchione, John F; Landau, Mark E; Muldoon, Sheila M; Rushing, Elisabeth J; Heled, Yuval

    2013-08-01

    Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER. DNA samples derived from a laboratory-based study of persons who had never experienced an episode of ER (controls) and clinical ER cases referred for testing over the past several years were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes. These included angiotensin I converting enzyme (ACE), α-actinin-3 (ACTN3), creatine kinase muscle isoform (CKMM), heat shock protein A1B (HSPA1B), interleukin 6 (IL6), myosin light chain kinase (MYLK), adenosine monophosphate deaminase 1 (AMPD1), and sickle cell trait (HbS). Population included 134 controls and 47 ER cases. The majority of ER cases were men (n = 42/47, 89.4 %); the five women with ER were Caucasian. Eighteen African Americans (56.3 %) were ER cases. Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM (odds ratio/OR = 3.1, confidence interval/CI 1.33-7.10), 3.0 times for the XX genotype of ACTN3 SNP (OR = 2.97, CI 1.30-3.37), and 5.7 times for an A allele of MYLK (OR = 21.35, CI 2.60-12.30). All persons with HbS were also ER cases. Three distinct polymorphisms were associated with ER. Further work will be required to replicate these findings and determine the mechanism(s) whereby these variants might confer susceptibility. PMID:23543093

  6. [Rhabdomyolysis in a medical student induced by body-building exercise (rhabdomyolysis following acute muscular exertion)].

    PubMed

    Arányi, J; Radó, J

    1992-08-01

    A medical student sportsman had been admitted to the hospital because of weakness and painful swelling of the muscle as well as dark urine appearing after carrying out an excessive body-building performance. On the basis of indirect evidences pigmenturia "per exclusionem" was a manifestation of urinary myoglobin excretion. The development of an "acute exertional rhabdomyolysis" was confirmed by the increased serum enzyme levels and myoglobinuria. The outcome of the illness was fortunate, as acute renal failure could be avoided. On the basis of survey of the literature it can be stated, that this presumably frequently occurring, but rarely recognized disease may have importance from clinical, sporting medicine and pathophysiological point of view. PMID:1495807

  7. [Clinico-pharmacologic explanation models of cerivastatin associated rhabdomyolysis].

    PubMed

    Zeitlinger, Markus; Müller, Markus

    2003-01-01

    Because of fatal cases of rhabdomyolysis the HMG-CoA-reductase inhibitor cerivastatin had to be withdrawn from the global market in 2001. The high frequency and severity of cerivastatin-associated rhabdomyolysis caused concerns about the safety of the entire class of HMG-CoA-reductase inhibitors (statins). Still, the frequency of deadly incidents of rhabdomyolysis with cerivastatin was 16 to 80 times higher than with other statins. This seems to be due to a combination of several pharmacokinetic and pharmacodynamic characteristics of cerivastatin. Cerivastatin shows the highest oral bioavailability within its class. Interactions with other drugs like gemfibrocil may cause further elevation of cerivastatin plasma levels, thereby leading to higher frequencies of side effects in peripheral organs. With approximately 1 pM cerivastatin shows the lowest IC50 for inhibition of HMG-CoA-reductase of all statins. The combination of high systemic drug levels and high intrinsic activity potentially leads to apoptosis and energy-depletion of skeletal-muscle cells. Therefore cerivastatin-associated fatal rhabdomyolysis seems to be based on specific pharmacokinetic and pharmacodynamic properties of cerivastatin, and is not a general characteristic of all members of this drug-class. The experiences with cerivastatin support the importance of clinical studies even about well established drugs, and underline the relevance of precise reporting of adverse events by each physician. PMID:12879633

  8. The role of myoglobin degradation in nephrotoxicity after rhabdomyolysis.

    PubMed

    Zorova, Ljubava D; Pevzner, Irina B; Chupyrkina, Anastasia A; Zorov, Savva D; Silachev, Denis N; Plotnikov, Egor Y; Zorov, Dmitry B

    2016-08-25

    The fate of myoglobin in renal cells was explored in an animal model of rhabdomyolysis known as the pathology highly related to oxidative stress resulting in impairment of renal functioning. The working hypothesis was that the proper degradation of myoglobin in rhabdomyolytic kidney can activate the reparative processes in the tissue. We found that incubation of myoglobin with kidney cells causes its accumulation in the cytoplasm. In rhabdomyolytic rats, the level of heme and free iron in cytoplasm and mitochondria of kidney cells is remarkably increased while inhibition of proteolysis results in further elevation of myoglobin content in the renal tissue. Heme oxygenase and ferritin levels were found to be increased in the kidney tissue at rhabdomyolysis and simulating conditions performed by i/v injection of myoglobin. In addition, the level of peroxidized lipids was high in rhabdomyolytic kidney and became even higher after inhibition of proteolysis by aprotinin. Elevated levels of carbonylated proteins were also observed after rhabdomyolysis, however, if prior to induction of rhabdomyolysis the injection of myoglobin was done, the level of carbonylated proteins dropped versus unprimed kidney tissue thus affording protection to the kidney against oxidative stress. Injection of myoglobin to the rat results in impairment of renal functioning and inhibition of myoglobin degradation in the rhabdomyolytic animal aggravates acute renal failure, demonstrating that degradation of myoglobin is somehow beneficial although it may result in undesired release of free iron which can participate in toxic redox cycling. PMID:27329933

  9. A Case of Occult Compartment Syndrome and Nonresolving Rhabdomyolysis

    PubMed Central

    Minnema, Brian J.; Neligan, Peter C.; Quraishi, Nasir A.; Fehlings, Michael G.

    2008-01-01

    Case report A 32-year-old African male presented with 10 hours of severe back pain. Initial computed tomography scan of the back showed no abnormality, and initial laboratory investigations were consistent with rhabdomyolysis. Despite stopping potential causative medications, aggressive intravenous hydration, and urine alkalinization, his creatinine kinase continued to steadily climb. Thirty-six hours after admission, a magnetic resonance imaging of his back was done because of new swelling over the right paraspinal muscles and loss of sensation in this region. Marked swelling of the right erector spinae muscles was observed, and right and left compartment pressure measurements were 108 and 21 mm Hg, respectively. He had urgent fasciotomy after which his rhabdomyolysis and pain recovered. Conclusion Our case highlights the need for early consideration of compartment syndrome as a possible cause of back pain in the setting of rhabdomyolysis. Rhabdomyolysis can present in the absence of late complications such as neurological and vascular compromise. PMID:18350340

  10. Two Cases of Rhabdomyolysis (Haff Disease) After Eating Carp Fish

    PubMed Central

    Louis, Joey V.; Sein, Saw; Lyon, Claudia; Apergis, George

    2016-01-01

    Unexplained rhabdomyolysis after eating fish is a rare condition caused by an unidentified toxin. Most of the incidences in the United States have been linked to consuming buffalo fish or crawfish. We present 2 cases of Haff disease in which the patients consumed grass carp as opposed to the usual suspects of buffalo fish or crawfish.

  11. Rhabdomyolysis as presenting feature of acute HIV-1 seroconversion in a pediatric patient.

    PubMed

    Gagnon, Jason; Katner, Harold; Core, S Brent; Dozier, Jean; Patel, Chintan; Davis, Chanty

    2016-04-01

    Acute rhabdomyolysis is a rare phenomenon in the emergency setting almost exclusively associated with trauma, drugs, and recent upper respiratory and gastrointestinal infection. Rare reports in the literature have highlighted adult patients presenting with rhabdomyolysis as 1 component in a constellation of symptoms in acute HIV-1 seroconversion; however, there are few reports of rhabdomyolysis as the sole presenting symptom. This case highlights the importance of investigating HIV and other sexually transmitted diseases in pediatric cases of rhabdomyolysis in the emergency care setting. PMID:26584564

  12. 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

  13. Acute-onset rhabdomyolysis secondary to sitagliptin and atorvastatin interaction

    PubMed Central

    Khan, Muhammad Waqas; Kurian, Saji; Bishnoi, Rohit

    2016-01-01

    Rhabdomyolysis is a serious medical condition in which the skeletal muscle tissue gets damaged and breaks down at rapid rates, potentially leading to death if not managed early on. Rhabdomyolysis in adults has several etiologies such as crush injuries, prolonged immobilization, strenuous exercise, hormonal or metabolic causes, infections, and drug–drug interactions. We present a case report of the interaction of two drugs that are used commonly in the general population. We here discuss a case of a 60-year-old female who presented to the hospital with complaints of generalized weakness, muscle aches, and atypical chest pain for a week after her primary care physician started her on sitagliptin while she was already on atorvastatin. After review of literature, this is the second known case of such an interaction causing acute breakdown of skeletal musculature. PMID:27199569

  14. Rhabdomyolysis Due to Severe Hypophosphatemia in Diabetic Ketoacidosis.

    PubMed

    Shah, S K; Shah, L; Bhattarai, S; Giri, M

    2015-01-01

    Rhabdomyolysis is a syndrome characterized by injury to skeletal muscle fibers with disruption and release of toxic metabolites into circulation. It is characterized by triad of muscle weakness, myalgia and dark urine and is associated with increased creatine kinase and lactate dehydrogenase. A severely malnourished 10 year old girl with severe diabetic ketoacidosis as hemr initial presentation of type 1 diabetes mellitus developed rhabdomyolysis (CK- 12,000 U/L) with non-oliguric renal failure during her initial course of hospital stay. The possible cause of her RM was attributed to severe hypophosphatemia (minimum serum phosphate, 0.8 mg/dL). Management of diabetic ketoacidosis phosphate supplementation and urinary alkalinization with diuresis improved her clinical course. She was discharged on Day 9 with Insulin. We recommend frequent monitoring of serum phosphate during early period of DKA, particularly in malnourished children, and its normalization in case of severe hypophosphatemia. PMID:26994037

  15. Synthetic cannabinoid hyperemesis resulting in rhabdomyolysis and acute renal failure.

    PubMed

    Argamany, Jacqueline R; Reveles, Kelly R; Duhon, Bryson

    2016-04-01

    Synthetic cannabinoid usage has increased in the past decade. Concurrently, emergency management of associated adverse effects due to synthetic cannabinoid usage has also risen. Reported toxicities include psychosis, seizures, cardiotoxicity, acute kidney injury, and death. While cannabis was first described as a cause of acute hyperemesis in 2004, a more recent case series also describes the association between cannabinoid hyperemesis and risk of acute renal failure. Synthetic cannabinoids have also been reported to cause acute hyperemesis and acute renal failure; however, the risk of rhabdomyolysis-induced renal failure has yet to be elucidated. In this article, we report the first known case of synthetic cannabinoid hyperemesis leading to rhabdomyolysis and acute renal failure. PMID:26422191

  16. 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

  17. Acute-onset rhabdomyolysis secondary to sitagliptin and atorvastatin interaction.

    PubMed

    Khan, Muhammad Waqas; Kurian, Saji; Bishnoi, Rohit

    2016-01-01

    Rhabdomyolysis is a serious medical condition in which the skeletal muscle tissue gets damaged and breaks down at rapid rates, potentially leading to death if not managed early on. Rhabdomyolysis in adults has several etiologies such as crush injuries, prolonged immobilization, strenuous exercise, hormonal or metabolic causes, infections, and drug-drug interactions. We present a case report of the interaction of two drugs that are used commonly in the general population. We here discuss a case of a 60-year-old female who presented to the hospital with complaints of generalized weakness, muscle aches, and atypical chest pain for a week after her primary care physician started her on sitagliptin while she was already on atorvastatin. After review of literature, this is the second known case of such an interaction causing acute breakdown of skeletal musculature. PMID:27199569

  18. Rare times rare: The hyponatremia, rhabdomyolysis, anterior compartment syndrome sequence

    PubMed Central

    Dubin, Ina; Gelber, Moshe

    2016-01-01

    Lesson Primary polydipsia occurs in up to 25% of patients with chronic psychiatric disorders (especially schizophrenia), related to the disease, its treatment or both. Urine output fails to match intake >10 L/day and water intoxication may develop. Rhabdomyolysis is a rare complication of hyponatremia, and an acute anterior compartment syndrome of the leg, an emergency, may be very rarely associated. PMID:27186379

  19. Statin-Induced Rhabdomyolysis: A Comprehensive Review of Case Reports

    PubMed Central

    Mendes, Polyana; Robles, Priscila Games

    2014-01-01

    ABSTRACT Purpose: To identify case reports of statin-induced rhabdomyolysis and summarize common predisposing factors, symptoms, diagnostic findings, functional outcomes, characteristics, treatment, and rehabilitation. Method: MEDLINE, CINAHL, SCOPUS, and PEDro databases were searched (1990–2013) for relevant case reports using the search terms “Statins,” “Rhabdomyolysis,” “Myalgia,” “Muscle damage,” “Muscle injury,” and “Myopathy.” Relevance (based on title and abstract) was assessed by one investigator; two investigators independently reviewed the relevant articles to determine inclusion in the review. Results: A total of 112 cases met the inclusion criteria. The majority were in men (70%) and people over 45 years of age (mean 64 [SD 14] years). Simvastatin was the most commonly reported statin (n=55); the majority of cases reported the use of concomitant medications such as fibrates (n=25). Weakness (n=65) and muscle pain (n=64) were the most common symptoms. In 19 cases, the patient was referred to rehabilitation, but the case reports do not include descriptions of the treatment. Conclusion: Statin-induced rhabdomyolysis was more commonly reported when statins were used in conjunction with other drugs, which potentiated its effect. Research is needed to identify the role of exercise and rehabilitation following statin-induced rhabdomyoloysis since muscle damage may be severe and may have long-term effects on muscle function. PMID:24799748

  20. 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

  1. [Rhabdomyolysis associated with dengue fever in a lupic patient].

    PubMed

    Verdolin, Louise D; Borner, Alice R; Mussi, Henrique; Gismondi, Ronaldo A; Schau, Bruno; Ramos, Ricardo C

    2014-01-01

    This report describes the case of a woman with systemic lupus erythematous (SLE) that developed rhabdomyolysis after being infected by dengue virus. There are only a few cases of SLE accompanied by rhabdomyolysis, none of them associated with dengue fever. Initially, the woman presented high fever, myalgia, muscular weakness, mild headache, polyarthralgia and thrombocytopenia reminding a lupus flare, but since the number of people infected by dengue at that time was high and the symptoms from both conditions are similar, a dengue serology was requested. After a few days, the patient developed rhabdomyolysis. She was then submitted to immunosuppressive drugs, urinary alkalization and vigorous hydration, which improved her muscle damage and inflammatory condition. The positive dengue serology was only available after the therapy above had been established. She was discharged in an asymptomatic state. This case demonstrates how alike dengue fever and a lupus flare are, warning clinicians that, especially during an epidemic, both diseases should be carefully differentiated in order to establish a correct and efficient therapy. PMID:25627228

  2. Frostbite with rhabdomyolysis and renal failure: radionuclide study. [/sup 99m/Tc

    SciTech Connect

    Rosenthall, L.; Kloiber, R.; Gagnon, R.; Damtew, B.; Lough, J.

    1981-08-01

    There is a growing list of muscle lesions exhibiting concentration of bone-seeking /sup 99m/Tc-labeled phosphate complexes; however, rhabdomyolysis due to cold injury has not been included. We performed a multiradiopharmaceutical study that yielded interesting results on a patient who sustained frostbite injury of the legs that led to rhabdomyolysis and acute renal failure.

  3. Recurrent exercise-induced rhabdomyolysis due to low intensity fitness exercise in a healthy young patient

    PubMed Central

    Karre, Premnath Reddy; Gujral, Jeetinder

    2011-01-01

    Rhabdomyolysis is an uncommon but life threatening condition that develops due to breakdown of muscle and release of intracellular components into the circulation. A 24-year-old man otherwise healthy was admitted to our hospital because of muscle aches and weakness as well as cola coloured urine developed 3 days after carrying out the low intensity exercise. Diagnosis of rhabdomyolysis was made with creatine kinase (CK) levels of 214 356 U/l. He was treated for a similar condition at age 21. A muscle biopsy was done and the findings were normal. Rhabdomyolysis can develop with low intensity exercise; thus, it be considered in healthy young people. Young people with recurrent rhabdomyolysis due to low intensity exercise, in the absence of obvious medical and physical causes, should be evaluated further to rule out uncommon metabolic diseases. Our case demonstrates that complications especially renal failure in patients with rhabdomyolysis do not correspond to CK levels. PMID:22700603

  4. 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

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

    PubMed

    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

  6. 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

  7. 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

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

    PubMed Central

    Huerta-Alardín, 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

  9. Statin-induced rhabdomyolysis in patient with renal failure and underlying undiagnosed hypothyroidism

    PubMed Central

    Ambapkar, Sachinkumar N.; Shetty, Naresh; Dwivedy, Arpita; Malve, Harshad Onkarrao

    2016-01-01

    Rhabdomyolysis is a syndrome characterized by muscle necrosis which causes the release of myoglobin into the bloodstream. The manifestations of this syndrome range from asymptomatic elevation of serum muscle enzymes to life-threatening cases associated with extremely high enzyme levels, electrolyte imbalance, and acute renal failure. Symptoms of rhabdomyolysis include dark urine, muscle weakness, and fatigue. Statins are commonly used drugs for the prevention and management of dyslipidemia. We present an interesting and critical case on statin-induced rhabdomyolysis with renal failure and previously undiagnosed idiopathic hypothyroidism. PMID:27275082

  10. Statin-induced rhabdomyolysis in patient with renal failure and underlying undiagnosed hypothyroidism.

    PubMed

    Ambapkar, Sachinkumar N; Shetty, Naresh; Dwivedy, Arpita; Malve, Harshad Onkarrao

    2016-05-01

    Rhabdomyolysis is a syndrome characterized by muscle necrosis which causes the release of myoglobin into the bloodstream. The manifestations of this syndrome range from asymptomatic elevation of serum muscle enzymes to life-threatening cases associated with extremely high enzyme levels, electrolyte imbalance, and acute renal failure. Symptoms of rhabdomyolysis include dark urine, muscle weakness, and fatigue. Statins are commonly used drugs for the prevention and management of dyslipidemia. We present an interesting and critical case on statin-induced rhabdomyolysis with renal failure and previously undiagnosed idiopathic hypothyroidism. PMID:27275082

  11. Poststernotomy Osteomyelitis Presenting with Severe Sepsis and Rhabdomyolysis

    PubMed Central

    Tan, Eugene M.; Lyle, Melissa; Cawcutt, Kelly; Temesgen, Zelalem

    2016-01-01

    A 39-year-old male, who recently underwent a composite valve graft of the aortic root and ascending aorta for bicuspid aortic valve and aortic root aneurysm, was hospitalized for severe sepsis, rhabdomyolysis (creatine kinase 29000 U/L), and severe liver dysfunction (AST > 7000 U/L, ALT 4228 U/L, and INR > 10). Cardiac magnetic resonance imaging (MRI) findings were consistent with sternal osteomyelitis with a 1.5 cm abscess at the inferior sternotomy margin, which was contiguous with pericardial thickening. Aspiration and culture of this abscess did not yield any organisms, so he was treated with vancomycin and cefepime empirically for 4 weeks. Because this patient was improving clinically on antibiotics and did not show external signs of wound infection, there was no compelling indication for sternectomy. This patient's unusual presentation with osteomyelitis and rhabdomyolysis has never been reported and is crucial for clinicians to recognize in order to prevent delays in diagnosis. PMID:27143974

  12. 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

  13. 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

  14. Severe Rhabdomyolysis Caused by Plasmodium vivax Malaria in the Brazilian Amazon

    PubMed Central

    Siqueira, André M.; Alexandre, Márcia A. A.; Mourão, Maria P. G.; Santos, Valquir S.; Nagahashi-Marie, Suely K.; Alecrim, Maria G. C.; Lacerda, Marcus V. G.

    2010-01-01

    Severe rhabdomyolysis (creatine phosphokinase = 29,400U/L) developed in a 16-year-old boy from Manaus, Brazil, after he started treatment with chloroquine for infection with Plasmodium vivax. Treatment led to myoglobinuria and acute renal failure. After hemodialysis, the patient improved and a muscle biopsy specimen showed no myophosphorylase or deaminase deficiency. This case of rhabdomyolysis associated with P. vivax infection showed no comorbidities. The pathogenesis is still unclear. Although rhabdomyolysis is generally reported as a complication of Plasmodium falciparum malaria, leading to metabolic and renal complications,1 it has been reported in a patient with P. vivax infection with myoadenylate deaminase deficiency.2 We report a case in a patient without typical muscle enzyme deficiencies in which severe rhabdomyolysis developed while the patients was being treated with chloroquine for a confirmed P. vivax infection. PMID:20682866

  15. 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

  16. 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

  17. Specific macrophage subtypes influence the progression of rhabdomyolysis-induced kidney injury.

    PubMed

    Belliere, Julie; Casemayou, Audrey; Ducasse, Laure; Zakaroff-Girard, Alexia; Martins, Frédéric; Iacovoni, Jason S; Guilbeau-Frugier, Céline; Buffin-Meyer, Bénédicte; Pipy, Bernard; Chauveau, Dominique; Schanstra, Joost P; Bascands, Jean-Loup

    2015-06-01

    Rhabdomyolysis can be life threatening if complicated by AKI. Macrophage infiltration has been observed in rat kidneys after glycerol-induced rhabdomyolysis, but the role of macrophages in rhabdomyolysis-induced AKI remains unknown. Here, in a patient diagnosed with rhabdomyolysis, we detected substantial macrophage infiltration in the kidney. In a mouse model of rhabdomyolysis-induced AKI, diverse renal macrophage phenotypes were observed depending on the stage of the disease. Two days after rhabdomyolysis, F4/80(low)CD11b(high)Ly6b(high)CD206(low) kidney macrophages were dominant, whereas by day 8, F4/80(high)CD11b(+)Ly6b(low)CD206(high) cells became the most abundant. Single-cell gene expression analyses of FACS-sorted macrophages revealed that these subpopulations were heterogeneous and that individual cells simultaneously expressed both M1 and M2 markers. Liposomal clodronate-mediated macrophage depletion significantly reduced the early infiltration of F4/80(low)CD11b(high)Ly6b(high)CD206(low) macrophages. Furthermore, transcriptionally regulated targets potentially involved in disease progression, including fibronectin, collagen III, and chemoattractants that were identified via single-cell analysis, were verified as macrophage-dependent in situ. In vitro, myoglobin treatment induced proximal tubular cells to secrete chemoattractants and macrophages to express proinflammatory markers. At day 30, liposomal clodronate-mediated macrophage depletion reduced fibrosis and improved both kidney repair and mouse survival. Seven months after rhabdomyolysis, histologic lesions were still present but were substantially reduced with prior depletion of macrophages. These results suggest an important role for macrophages in rhabdomyolysis-induced AKI progression and advocate the utility of long-term follow-up for patients with this disease. PMID:25270069

  18. Specific Macrophage Subtypes Influence the Progression of Rhabdomyolysis-Induced Kidney Injury

    PubMed Central

    Belliere, Julie; Casemayou, Audrey; Ducasse, Laure; Zakaroff-Girard, Alexia; Martins, Frédéric; Iacovoni, Jason S.; Guilbeau-Frugier, Céline; Buffin-Meyer, Bénédicte; Pipy, Bernard; Chauveau, Dominique

    2015-01-01

    Rhabdomyolysis can be life threatening if complicated by AKI. Macrophage infiltration has been observed in rat kidneys after glycerol-induced rhabdomyolysis, but the role of macrophages in rhabdomyolysis-induced AKI remains unknown. Here, in a patient diagnosed with rhabdomyolysis, we detected substantial macrophage infiltration in the kidney. In a mouse model of rhabdomyolysis-induced AKI, diverse renal macrophage phenotypes were observed depending on the stage of the disease. Two days after rhabdomyolysis, F4/80lowCD11bhighLy6bhighCD206low kidney macrophages were dominant, whereas by day 8, F4/80highCD11b+Ly6blowCD206high cells became the most abundant. Single-cell gene expression analyses of FACS-sorted macrophages revealed that these subpopulations were heterogeneous and that individual cells simultaneously expressed both M1 and M2 markers. Liposomal clodronate-mediated macrophage depletion significantly reduced the early infiltration of F4/80lowCD11bhighLy6bhighCD206low macrophages. Furthermore, transcriptionally regulated targets potentially involved in disease progression, including fibronectin, collagen III, and chemoattractants that were identified via single-cell analysis, were verified as macrophage-dependent in situ. In vitro, myoglobin treatment induced proximal tubular cells to secrete chemoattractants and macrophages to express proinflammatory markers. At day 30, liposomal clodronate-mediated macrophage depletion reduced fibrosis and improved both kidney repair and mouse survival. Seven months after rhabdomyolysis, histologic lesions were still present but were substantially reduced with prior depletion of macrophages. These results suggest an important role for macrophages in rhabdomyolysis-induced AKI progression and advocate the utility of long-term follow-up for patients with this disease. PMID:25270069

  19. Primary aldosteronism associated with severe rhabdomyolysis due to profound hypokalemia.

    PubMed

    Goto, Atsushi; Takahashi, Yoshihiko; Kishimoto, Miyako; Minowada, Shigeru; Aibe, Hitoshi; Hasuo, Kanehiro; Kajio, Hiroshi; Noda, Mitsuhiko

    2009-01-01

    A 55-year-old Japanese man was admitted to our hospital with severe weakness. Without measurement of serum electrolyte concentrations, diuretic therapy for hypertension was started 2 weeks prior to admission. Laboratory findings showed profound hypokalemia (1.4 mEq/L), and extreme elevation of the serum creatinine phosphokinase levels (15,760 IU/L), suggesting that the patient had hypokalemic paralysis and hypokalemia-induced rhabdomyolysis. Further evaluations, including adrenal venous sampling strongly suggested that he had primary aldosteronism. He was treated successfully by laparoscopic adrenalectomy. This case provides an important lesson that serum electrolyte concentrations should be measured in hypertensive patients before the administration of antihypertensive agents. PMID:19218772

  20. A case of anorexia nervosa with acute renal failure induced by rhabdomyolysis; possible involvement of hypophosphatemia or phosphate depletion.

    PubMed

    Wada, S; Nagase, T; Koike, Y; Kugai, N; Nagata, N

    1992-04-01

    A 16-year-old girl with anorexia nervosa first presented with malnutrition, liver dysfunction, and rhabdomyolysis. Administration of fluid and nutrition saved her from the initial critical state, but acute renal failure followed. Laboratory examination revealed intrinsic renal failure induced by rhabdomyolysis. Latent phosphate depletion and refeeding-induced hypophosphatemia was implicated as the cause of rhabdomyolysis; however coexisting hypotension, dehydration, and liver dysfunction may have contributed to the renal failure. The patient recovered from azotemia by hemodialysis. This is the first reported case of anorexia nervosa with acute renal failure resulting from rhabdomyolysis induced by hypophosphatemia or phosphate depletion. PMID:1633352

  1. A rare autopsy case of traumatic rhabdomyolysis associated with intermittent assault.

    PubMed

    Chiba, Fumiko; Makino, Yohsuke; Motomura, Ayumi; Inokuchi, Go; Ishii, Namiko; Torimitsu, Suguru; Hoshioka, Yumi; Abe, Hiroko; Yamaguchi, Rutsuko; Hashimoto, Mari; Sakuma, Ayaka; Nagasawa, Sayaka; Saito, Hisako; Yajima, Daisuke; Iwase, Hirotaro

    2016-05-01

    Traumatic rhabdomyolysis generally occurs after severe blunt trauma and is acute in onset, associated with severe disease, and potentially lethal. Accordingly, diagnosis of traumatic rhabdomyolysis in patients without massive subcutaneous or intramuscular hemorrhage is difficult, especially in the postmortem period, which is limited in terms of the availability of biochemical examination tools and accurate history of illness. To the best of our knowledge, there are no previous reports of death from traumatic rhabdomyolysis among individuals who did not pursue medical consultation. A previously healthy man in his early sixties had been punched and kicked several times in the previous 2months, but he had not gone to a hospital. He suddenly lost consciousness at his workplace approximately 5days after the most recent assault, and cardiopulmonary arrest occurred when the emergency service arrived. He died the same day, and a medicolegal autopsy was performed. Although several sites of minor subcutaneous and muscle hemorrhage were observed, the cause of death was unclear upon macroscopic assessment. Immunohistochemical staining revealed acute renal failure caused by rhabdomyolysis. We herein report a rare case of fatal traumatic rhabdomyolysis, seemingly associated with minor and apparently nonlethal muscle injury. PMID:27161922

  2. 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

  3. 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

  4. A Case of Mushroom Poisoning with Russula subnigricans: Development of Rhabdomyolysis, Acute Kidney Injury, Cardiogenic Shock, and Death.

    PubMed

    Cho, Jong Tae; Han, Jin Hyung

    2016-07-01

    Mushroom exposures are increasing worldwide. The incidence and fatality of mushroom poisoning are reported to be increasing. Several new syndromes in mushroom poisoning have been described. Rhabdomyolytic mushroom poisoning is one of new syndromes. Russula subnigricans mushroom can cause delayed-onset rhabdomyolysis with acute kidney injury in the severely poisoned patient. There are few reports on the toxicity of R. subnigricans. This report represents the first record of R. subnigricans poisoning with rhabdomyolysis in Korea, describing a 51-year-old man who suffered from rhabdomyolysis, acute kidney injury, severe hypocalcemia, respiratory failure, ventricular tachycardia, cardiogenic shock, and death. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown cause. Furthermore, R. subnigricans should be considered in the mushroom poisoning with rhabdomyolysis. PMID:27366018

  5. A Case of Mushroom Poisoning with Russula subnigricans: Development of Rhabdomyolysis, Acute Kidney Injury, Cardiogenic Shock, and Death

    PubMed Central

    2016-01-01

    Mushroom exposures are increasing worldwide. The incidence and fatality of mushroom poisoning are reported to be increasing. Several new syndromes in mushroom poisoning have been described. Rhabdomyolytic mushroom poisoning is one of new syndromes. Russula subnigricans mushroom can cause delayed-onset rhabdomyolysis with acute kidney injury in the severely poisoned patient. There are few reports on the toxicity of R. subnigricans. This report represents the first record of R. subnigricans poisoning with rhabdomyolysis in Korea, describing a 51-year-old man who suffered from rhabdomyolysis, acute kidney injury, severe hypocalcemia, respiratory failure, ventricular tachycardia, cardiogenic shock, and death. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown cause. Furthermore, R. subnigricans should be considered in the mushroom poisoning with rhabdomyolysis. PMID:27366018

  6. Update: Exertional rhabdomyolysis, active component, U.S. Army, Navy, Air Force, and Marine Corps, 2011-2015.

    PubMed

    2016-03-01

    Among active component members of the U.S. Army, Navy, Air Force, and Marine Corps in 2015, there were 456 incident episodes of rhabdomyolysis likely due to physical exertion or heat stress ("exertional rhabdomyolysis"). Annual rates of incident diagnoses of exertional rhabdomyolysis increased 17% between 2014 and 2015. In 2015, the highest incidence rates occurred in service members who were male; younger than 20 years of age; black, non-Hispanic; members of the Marine Corps and Army; recruit trainees; and in combat-specific occupations. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain and swelling, limited range of motion, or the excretion of dark urine (e.g., myoglobinuria) after strenuous physical activity, particularly in hot, humid weather. PMID:27030929

  7. 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

  8. Hemolytic uremic syndrome and rhabdomyolysis in a patient with succinate coenzyme Q reductase (complex II) deficiency.

    PubMed

    Micheletti, M V; Lavoratti, G; Gasperini, S; Donati, M A; Pela, I

    2011-07-01

    Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Besides diarrhea-associated HUS, due to verotoxin-producing Escherichia coli, in children HUS without prodromal diarrhea may be associated with other infectious and autoimmune diseases, genetic defects of the complement-regulator alternative-pathway, and inborn errors of vitamin B12 metabolism. Rhabdomyolysis is the dissolution of skeletal muscle due to various causes, including inborn errors of metabolism. Recurrent rhabdomyolysis and HUS have been previously described in one patient with a genetic defect of oxidative phosphorylation. We report the case of a 2-year-old boy with recurrent HUS and rhabdomyolysis in whom a succinate coenzyme Q reductase (complex II) deficiency was diagnosed. We hypothesize that defects of oxidative phosphorylation could be another etiological factor in atypical HUS. PMID:21722608

  9. 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

  10. Potential factors involved in the causation of rhabdomyolysis following status asthmaticus.

    PubMed

    Qiao, Hongmei; Cheng, Huanji; Liu, Li; Yin, Jianing

    2016-01-01

    Rhabdomyolysis is a rare but potentially fatal complication of status asthmaticus. Since the first case was reported in 1978, only a few dozen cases have been described till date. We performed a literature review with the aim to characterize the pathophysiological basis of the occurrence of rhabdomyolysis in patients with status asthmaticus. Excessive exertion of respiratory muscles, hypoxia and acidosis, electrolyte imbalance, infections, some drugs used for asthma control, use of mechanical ventilation, prolonged cardiopulmonary resuscitation, higher age of the patient and some underlying diseases or genetic factors appear to be involved in its causation. In patients with status asthmaticus, it is important to pay more attention to these factors and to closely monitor creatine kinase levels in blood so as to ensure early detection of rhabdomyolysis. PMID:27555875

  11. 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

  12. Meloxicam-induced rhabdomyolysis in the context of an acute ross river viral infection.

    PubMed

    Al Kindi, Mahmood; Limaye, Vidya; Hissaria, Pravin

    2012-01-01

    Acute rhabdomyolysis is a clinical and laboratory syndrome resulting from the breakdown of skeletal muscle, with the release of intracellular contents into the circulatory system, which can cause potentially lethal complications. Here, we present the case of a patient who developed acute rhabdomyolysis after consumption of meloxicam for jaw pain and experienced generalized myalgias in the context of an acute febrile illness with generalized urticaria. Further investigation indicated elevated muscle enzymes and acute renal failure. Serological analysis revealed that the patient was positive for Ross River virus (RRV) IgM. Genetic studies to detect CYP2C9 polymorphisms were negative. Meloxicam was discontinued. He responded to conservative measures within 2 weeks. Oral aspirin challenge was negative, suggesting a drug-specific effect of meloxicam rather than a class effect. Our case indicates a causative role for meloxicam and/or acute RRV in rhabdomyolysis. PMID:22211172

  13. Primary Sjö-gren's syndrome presenting with distal, renal tubular acidosis and rhabdomyolysis.

    PubMed

    Prakash, E B S; Fernando, M E; Sathiyasekaran, Malathi; Bhoopathy, R M; Jayanth, J J; Samuel, J

    2006-12-01

    Primary Sjögren's syndrome (PSS) is rare in India. Clinically manifest renal disease in PSS is uncommon and is usually an autoimmune tubulointerstitial nephritis presenting with distal renal tubular acidosis (dRTA) or a urinary concentrating defect. Hypokalemic paralysis due to dRTA in PSS is rare but well documented in medical literature. Rhabdomyolysis as a consequence of hypokalemia in PSS is exceptional. We report a case of PSS with dRTA and rhabdomyolysis causing prolonged respiratory failure and quadriparesis. PMID:17334013

  14. 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.

  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. Acute Rhabdomyolysis Associated with Coadministration of Levofloxacin and Simvastatin in a Patient with Normal Renal Function

    PubMed Central

    Paparoupa, Maria; Pietrzak, Sebastian; Gillissen, Adrian

    2014-01-01

    We report a rare case of severe acute rhabdomyolysis in association with coadministration of levofloxacin and simvastatin in a patient with normal renal function. A 70-year-old Caucasian male was treated due to community acquired pneumonia with levofloxacin in a dosage of 500 mg once and then twice a day. On the 8th day of hospitalization the patient presented with acute severe rhabdomyolysis requiring an intensive care support. After discontinuation of levofloxacin and concomitant medication with simvastatin 80 mg/day, clinical and laboratory effects were totally reversible. Up to now, levofloxacin has been reported to induce rhabdomyolysis mainly in patients with impaired renal function, as the medication has a predominant renal elimination. In our case renal function remained normal during the severe clinical course. According to a recent case report rhabdomyolysis was observed due to interaction of simvastatin and ciprofloxacin. To our best knowledge this is the first case of interaction between simvastatin and levofloxacin to be reported. This case emphasizes the need of close monitoring of creatine kinase in patients under more than one potentially myotoxic medication especially when patients develop muscle weakness. PMID:25140181

  17. Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis.

    PubMed

    Dlamini, N; Voermans, N C; Lillis, S; Stewart, K; Kamsteeg, E-J; Drost, G; Quinlivan, R; Snoeck, M; Norwood, F; Radunovic, A; Straub, V; Roberts, M; Vrancken, A F J E; van der Pol, W L; de Coo, R I F M; Manzur, A Y; Yau, S; Abbs, S; King, A; Lammens, M; Hopkins, P M; Mohammed, S; Treves, S; Muntoni, F; Wraige, E; Davis, M R; van Engelen, B; Jungbluth, H

    2013-07-01

    Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are a common cause of neuromuscular disease, ranging from various congenital myopathies to the malignant hyperthermia (MH) susceptibility trait without associated weakness. We sequenced RYR1 in 39 unrelated families with rhabdomyolysis and/or exertional myalgia, frequent presentations in the neuromuscular clinic that often remain unexplained despite extensive investigations. We identified 9 heterozygous RYR1 mutations/variants in 14 families, 5 of them (p.Lys1393Arg; p.Gly2434Arg; p.Thr4288_Ala4290dup; p.Ala4295Val; and p.Arg4737Gln) previously associated with MH. Index cases presented from 3 to 45 years with rhabdomyolysis, with or without exertional myalgia (n=12), or isolated exertional myalgia (n=2). Rhabdomyolysis was commonly triggered by exercise and heat and, less frequently, viral infections, alcohol and drugs. Most cases were normally strong and had no personal MH history. Inconsistent additional features included heat intolerance, and cold-induced muscle stiffness. Muscle biopsies showed mainly subtle changes. Familial RYR1 mutations were confirmed in relatives with similar or no symptoms. These findings suggest that RYR1 mutations may account for a substantial proportion of patients presenting with unexplained rhabdomyolysis and/or exertional myalgia. Associated clinico-pathological features may be subtle and require a high degree of suspicion. Additional family studies are paramount in order to identify potentially MH susceptible relatives. PMID:23628358

  18. 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

  19. Exertional rhabdomyolysis after spinning: case series and review of the literature.

    PubMed

    Ramme, Austin J; Vira, Shaleen; Alaia, Michael J; VAN DE Leuv, Jonathan; Rothberg, Robert C

    2016-06-01

    Spinning is a popular indoor stationary cycling program that uses group classes as a motivational tool. Exertional rhabdomyolysis (ER) is frequently reported in athletes and military recruits; however, infrequently it has been reported after spinning class. ER is diagnosed by clinical history, physical exam, and laboratory values. Hydration, electrolyte management, and pain control are key components to treatment of this condition. Severe cases can be complicated by acute renal failure, compartment syndrome, arrhythmia, and disseminated intravascular coagulation. We describe three cases of admission due to rhabdomyolysis after spinning. The diagnosis, admission criteria, and medical treatment of ER are presented in the context of a literature review. A retrospective review of three cases with review of the current literature. The medical and laboratory records of three patient cases were reviewed. A search of the PubMed database was used to perform a comprehensive review of exertional rhabdomyolysis. Our institution's IRB reviewed this study. We report three cases of exertional rhabdomyolysis after spinning and describe the diagnostic workup and medical management of these patients. The diagnosis of ER is made by clinical history, physical exam, and laboratory values. The disease spectrum ranges from mild to severe with the potential of serious complications in some patients. We demonstrate three cases of ER in deconditioned individuals who presented to the emergency department for evaluation. Careful medical management and patient monitoring resulted in improved patient symptomatology and eventual return to physical activity. PMID:25665750

  20. Exertional rhabdomyolysis: attrition through exercise, a case series and review of the literature.

    PubMed

    Reese, Jason M; Fisher, Scott D; Robbins, David P

    2012-01-01

    Rhabdomyolysis is a common syndrome that can range from asymptomatic to a severe life-threatening condition. It is the result of acute muscle fiber necrosis leading to cell lysis and subsequent transfer of those byproducts into the circulatory system.1-3 The most significant constituent of these byproducts is myoglobin, which has been known to cause renal failure in 10?50% of patients that develop rhabdomyolysis.4,5 In addition, the electrolytes contained within these cells are leached into the blood stream, which can lead to significant electrolyte abnormalities. The etiology of rhabdomyolysis is broad and includes inherited diseases, drugs, toxins, muscle compression or overexertion, infections, and more. This syndrome may carry a mortality rate ranging from 7?80%.3,6 We describe five patients assigned to various companies within 160th Special Operations Aviation Regiment (Airborne) that developed exertional rhabdomyolysis of the bilateral upper extremities between June 2011 and January 2012. In this case series we will describe the events leading up to the diagnosis, lack of risk factors or family history, diagnostic criteria, treatment, and future concerns related to the condition. PMID:23032321

  1. 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

  2. CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies.

    PubMed

    Scalco, Renata Siciliani; Gardiner, Alice R; Pitceathly, Robert D S; Hilton-Jones, David; Schapira, Anthony H; Turner, Chris; Parton, Matt; Desikan, Mahalekshmi; Barresi, Rita; Marsh, Julie; Manzur, Adnan Y; Childs, Anne-Marie; Feng, Lucy; Murphy, Elaine; Lamont, Phillipa J; Ravenscroft, Gianina; Wallefeld, William; Davis, Mark R; Laing, Nigel G; Holton, Janice L; Fialho, Doreen; Bushby, Kate; Hanna, Michael G; Phadke, Rahul; Jungbluth, Heinz; Houlden, Henry; Quinlivan, Ros

    2016-08-01

    Rhabdomyolysis is often due to a combination of environmental trigger(s) and genetic predisposition; however, the underlying genetic cause remains elusive in many cases. Mutations in CAV3 lead to various neuromuscular phenotypes with partial overlap, including limb girdle muscular dystrophy type 1C (LGMD1C), rippling muscle disease, distal myopathy and isolated hyperCKemia. Here we present a series of eight patients from seven families presenting with exercise intolerance and rhabdomyolysis caused by mutations in CAV3 diagnosed by next generation sequencing (NGS) (n = 6). Symptoms included myalgia (n = 7), exercise intolerance (n = 7) and episodes of rhabdomyolysis (n = 2). Percussion-induced rapid muscle contractions (PIRCs) were seen in five out of six patients examined. A previously reported heterozygous mutation in CAV3 (p.T78M) and three novel variants (p.V14I, p.F41S, p.F54V) were identified. Caveolin-3 immunolabeling in muscle was normal in 3/4 patients; however, immunoblotting showed more than 50% reduction of caveolin-3 in five patients compared with controls. This case series demonstrates that exercise intolerance, myalgia and rhabdomyolysis may be caused by CAV3 mutations and broadens the phenotypic spectrum of caveolinopathies. In our series, immunoblotting was a more sensitive method to detect reduced caveolin-3 levels than immunohistochemistry in skeletal muscle. Patients presenting with muscle pain, exercise intolerance and rhabdomyolysis should be routinely tested for PIRCs as this may be an important clinical clue for caveolinopathies, even in the absence of other "typical" features. The use of NGS may expand current knowledge concerning inherited diseases, and unexpected/atypical phenotypes may be attributed to well-known human disease genes. PMID:27312022

  3. Exercise-induced rhabdomyolysis and transient loss of deambulation as outset of partial carnitine palmityl transferase II deficiency.

    PubMed

    Rigante, Donato; Bersani, Giulia; Compagnone, Adele; Zampetti, Anna; De Nisco, Alessia; Sacco, Emanuela; Marrocco, Raffaella

    2011-06-01

    We report the case of a 13-year-old boy with an abrupt onset of leg pain and muscle weakness, incapability of deambulation and a laboratory picture of exercise-induced acute rhabdomyolysis. Intravenous hyperhydration and forced diuresis were adopted to avoid renal complications. No evidence of articular or residual muscular damage was appreciated in the short-term. The recurrence of rhabdomyolysis required a muscular biopsy showing a disturbance of fatty acid β-oxidation pathway. PMID:19855973

  4. 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

  5. [Anesthetic management of a patient with carnitine palmitoyltransferase deficiency with a history of rhabdomyolysis].

    PubMed

    Nakamura, Sayaka; Sugita, Michiko; Nakahara, Eriko; Yamamoto, Tatsuo

    2013-03-01

    Carnitine palmitoyltransferase (CPT) makes the fatty acids available through beta-oxidation. Deficiency of CPT causes difficulties of muscle cells to metabolize fatty acid. In affected patients, exercise, fast for a prolonged period, and stress, lead to exhaustion of the store of glucose in the body, and rhabdomyolysis may occur, since muscle can not utilize fatty acid as an alternative energy source. Therefore, anesthetic management of CPT deficiency needs infusion of glucose continuously, avoiding the use of the drugs that cause rhabdomyolysis and suppressing the surgical stress. A 67-year-old man, who had previous history of rhabdmyolysis during the postoperative period, and diagnosed CPT deficiency was scheduled for total gastrectomy. General anesthesia was induced with remifentanil, thiamylal and rocuronium after epidural catheter insertion. During surgery, general anesthesia was maintained with remifentanil, sevoflurane, and blood glucose was monitored frequently, with continuous glucose infusion. No complications occurred during anesthesia and perioperative course was uneventful. PMID:23544345

  6. 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

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat.

    PubMed Central

    Nath, K A; Balla, G; Vercellotti, G M; Balla, J; Jacob, H S; Levitt, M D; Rosenberg, M E

    1992-01-01

    Heme proteins such as myoglobin or hemoglobin, when released into the extracellular space, can instigate tissue toxicity. Myoglobin is directly implicated in the pathogenesis of renal failure in rhabdomyolysis. In the glycerol model of this syndrome, we demonstrate that the kidney responds to such inordinate amounts of heme proteins by inducing the heme-degradative enzyme, heme oxygenase, as well as increasing the synthesis of ferritin, the major cellular repository for iron. Prior recruitment of this response with a single preinfusion of hemoglobin prevents kidney failure and drastically reduces mortality (from 100% to 14%). Conversely, ablating this response with a competitive inhibitor of heme oxygenase exacerbates kidney dysfunction. We provide the first in vivo evidence that induction of heme oxygenase coupled to ferritin synthesis is a rapid, protective antioxidant response. Our findings suggest a therapeutic strategy for populations at a high risk for rhabdomyolysis. Images PMID:1634613

  10. [Rhabdomyolysis after radical nephrectomy in the lateral decubitus position: report of 2 cases].

    PubMed

    Shibamori, Kosuke; Yamamoto, Takanobu; Matsuki, Masahiro; Matsuda, Yohei; Kato, Shuichi; Takei, Fumiyasu; Yanase, Masahiro

    2014-10-01

    Rhabdomyolysis is a rare perioperative complication, however, potentially lead to fatal outcome. We experienced 2 cases of rhabdomyolysis after radical nephrectomy and nephroureterectomy in the lateral decubitus position. (Case 1) A 40-years old man was seen in our hospital because of asymptomatic grosshematuria. Computed tomography revealed right renal pelvic cancer, cT3N0M0. Right radical nephroureterectomy, lymph node dissection, partial cystectomy was underwent, and the operation was finished without any trouble. At the post-operative day 1, serum creatinine level was elevated to the point of 4.2 mg/dl, and serum creatine kinase was 1,945 IU/l. Continuous hemodiafiltration (CHDF) was done at intensive-care unit (ICU), and serum creatinine and creatine kinase level were decreased. At the post-operative day 1, urine myoglobin level was prominently elevated (2,943.7 ng/ml), so we diagnosed acute renal failure due to rhabdomyolysis. (Case 2) A 40-years old man was incidentally pointed out of right renal tumor that was seen as renal cell carcinoma, cT1aN0M0. Open partial nephrectomy was underwent, and there was no trouble during the operation. After recovering from anesthesia, the patient felt left thigh pain strongly. Serum creatine kinase was 888 IU/L after the operation. At the postoperative day 1, serum creatine kinase level was markedly increased (31,138 IU/L). Serum creatinine level was 1.34 mg/dl. Urine and serum myoglobin level was prominently elevated (89,000 ng/ml and 8,634 ng/ml, respectively). We diagnosed it rhabdomyolysis, and he received large amount of fluid intravenously at intensive-care unit. Serum creatine kinase was peak out at the post-operative day 3 (20,709 IU/L), and hemodialysis was not performed. PMID:25757354

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

    PubMed Central

    van Staa, Tjeerd P; Carr, Daniel F; O’Meara, 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

  12. Hypokalemic quadriparesis and rhabdomyolysis as a rare presentation of distal renal tubular acidosis.

    PubMed

    Ahmad Bhat, Manzoor; Ahmad Laway, Bashir; Mustafa, Farhat; Shafi Kuchay, Mohammad; Mubarik, Idrees; Ahmad Palla, Nazir

    2014-01-01

    Distal renal tubular acidosis is a syndrome of abnormal urine acidification and is characterized by hyperchloremic metabolic acidosis, hypokalemia, hypercalciurea, nephrocalcinosis and nephrolithiasis. Despite the presence of persistent hypokalemia, acute muscular paralysis is rarely encountered in males. Here, we will report an eighteen year old male patient who presented with flaccid quadriparesis and was subsequently found to have rhabdomyolysis, severe short stature, skeletal deformities and primary distal renal tubular acidosis. PMID:25250276

  13. A case of anorexia nervosa with acute renal failure resulting from rhabdomyolysis.

    PubMed

    Abe, K; Mezaki, T; Hirono, N; Udaka, F; Kameyama, M

    1990-01-01

    Symptoms of acute renal failure were observed in an anorexia patient who had a history of frequent vomiting. The acute renal failure might have resulted from rhabdomyolysis subsequent to a disturbance of electrolyte balance. This acute renal failure might have resulted in death if not treated. We postulate that even a mild case of anorexia nervosa should be carefully observed to prevent such possible tragedy. PMID:2330820

  14. Adult Patient with Novel H1N1 Infection Presented with Encephalitis, Rhabdomyolysis, Pneumonia and Polyneuropathy.

    PubMed

    Patel, Ketan K; Patel, Atul K; Shah, Shalin; Ranjan, Rajiv; Shah, Sudhir V

    2012-07-01

    Neurological complications of influenza are well known. Influenza A is commonly associated with neurological complications. Neurological complications especially encephalitis is described in the pediatric age group of patients with current pandemic novel H1N1 infection. We are describing a case of novel H1N1 infection presenting with multi-system involvement (encephalitis, bilateral pneumonia, severe rhabdomyolysis leading to renal failure and polyneuropathy) in adult patient. PMID:23055650

  15. Adult Patient with Novel H1N1 Infection Presented with Encephalitis, Rhabdomyolysis, Pneumonia and Polyneuropathy

    PubMed Central

    Patel, Ketan K; Patel, Atul K; Shah, Shalin; Ranjan, Rajiv; Shah, Sudhir V

    2012-01-01

    Neurological complications of influenza are well known. Influenza A is commonly associated with neurological complications. Neurological complications especially encephalitis is described in the pediatric age group of patients with current pandemic novel H1N1 infection. We are describing a case of novel H1N1 infection presenting with multi-system involvement (encephalitis, bilateral pneumonia, severe rhabdomyolysis leading to renal failure and polyneuropathy) in adult patient. PMID:23055650

  16. 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

  17. Acute Kidney Injury and Quadriparesis Due to Rosuvastatin Induced Rhabdomyolysis- A Case Report.

    PubMed

    Suthar, Kamlesh S; Vanikar, Aruna V; Trivedi, Hargovind L

    2015-05-01

    Statins as lipid lowering drugs, are safe and effective in reducing cardiovascular disease risk, but rarely produce myopathy like myalgia, myositis or rhabdomyolysis. We report the case of Rosuvastatin induced rhabdomyolytic acute renal failure and quadriparesis in a 67-year old male, a known case of type-2 diabetes mellitus and with a history of coronary angioplasty four months back. He was on antihypertensive, oral hypoglycemic and antiplatelet medications with Rosuvastatin 40mg/day. He was admitted with altered sensorium, breathlessness, vomiting, muscle weakness and decreased urine output and had raised serum creatinine, creatinine phosphokinase and myoglobin. After ruling out all other causation for rhabdomyolysis, we stopped Rosuvastatin and started supportive management and hemodialysis. Patient showed gradual recovery in renal function and quadriparesis. Patient was discharged with good urine output and on antihypertensive, hypoglycemic drug and diet restrictions for lipid control. He recovered completely and had normal renal function with well controlled lipid level on follow up of 6 months after discharge. Thus, prompt diagnosis of Rhabdomyolysis due to Rosuvastatin in absence of other aetiology and the multidisciplinary management can prevent further complication with favorable outcome. PMID:26155510

  18. Tubular von Hippel-Lindau Knockout Protects against Rhabdomyolysis-Induced AKI

    PubMed Central

    Fähling, Michael; Mathia, Susanne; Paliege, Alexander; Koesters, Robert; Mrowka, Ralf; Peters, Harm; Persson, Pontus Börje; Neumayer, Hans-Hellmut; Bachmann, Sebastian

    2013-01-01

    Renal hypoxia occurs in AKI of various etiologies, but adaptation to hypoxia, mediated by hypoxia-inducible factor (HIF), is incomplete in these conditions. Preconditional HIF activation protects against renal ischemia-reperfusion injury, yet the mechanisms involved are largely unknown, and HIF-mediated renoprotection has not been examined in other causes of AKI. Here, we show that selective activation of HIF in renal tubules, through Pax8-rtTA–based inducible knockout of von Hippel-Lindau protein (VHL-KO), protects from rhabdomyolysis-induced AKI. In this model, HIF activation correlated inversely with tubular injury. Specifically, VHL deletion attenuated the increased levels of serum creatinine/urea, caspase-3 protein, and tubular necrosis induced by rhabdomyolysis in wild-type mice. Moreover, HIF activation in nephron segments at risk for injury occurred only in VHL-KO animals. At day 1 after rhabdomyolysis, when tubular injury may be reversible, the HIF-mediated renoprotection in VHL-KO mice was associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal, as demonstrated by quantitative PCR, pathway enrichment analysis, and immunohistochemistry. In conclusion, a HIF-mediated shift toward improved energy supply may protect against acute tubular injury in various forms of AKI. PMID:23970125

  19. Acute Kidney Injury and Quadriparesis Due to Rosuvastatin Induced Rhabdomyolysis- A Case Report

    PubMed Central

    Vanikar, Aruna V.; Trivedi, Hargovind L.

    2015-01-01

    Statins as lipid lowering drugs, are safe and effective in reducing cardiovascular disease risk, but rarely produce myopathy like myalgia, myositis or rhabdomyolysis. We report the case of Rosuvastatin induced rhabdomyolytic acute renal failure and quadriparesis in a 67-year old male, a known case of type-2 diabetes mellitus and with a history of coronary angioplasty four months back. He was on antihypertensive, oral hypoglycemic and antiplatelet medications with Rosuvastatin 40mg/day. He was admitted with altered sensorium, breathlessness, vomiting, muscle weakness and decreased urine output and had raised serum creatinine, creatinine phosphokinase and myoglobin. After ruling out all other causation for rhabdomyolysis, we stopped Rosuvastatin and started supportive management and hemodialysis. Patient showed gradual recovery in renal function and quadriparesis. Patient was discharged with good urine output and on antihypertensive, hypoglycemic drug and diet restrictions for lipid control. He recovered completely and had normal renal function with well controlled lipid level on follow up of 6 months after discharge. Thus, prompt diagnosis of Rhabdomyolysis due to Rosuvastatin in absence of other aetiology and the multidisciplinary management can prevent further complication with favorable outcome. PMID:26155510

  20. Severe hypokalemia and thyrotoxic paralysis from painless thyroiditis complicated by life-threatening polymorphic ventricular tachycardia and rhabdomyolysis.

    PubMed

    Chang, Kyung Yoon; Lee, Su-Hyun; Park, Hoon Suk; Ko, Sun-Hee; Ahn, Yu-Bae; Kim, Hyung Wook

    2014-01-01

    A 61-year-old man presented with lower extremity paralysis and severe hypokalemia. His thyroid function test showed thyrotoxicosis. Despite attempts to correct his hypokalemia, he developed pulseless polymorphic ventricular tachycardia two hours later. He was successfully resuscitated after defibrillation. We performed continuous venovenous hemodiafiltration for 10 days due to acute kidney injury and rhabdomyolysis. We observed life-threatening polymorphic ventricular tachycardia requiring urgent defibrillation, as well as rhabdomyolysis requiring dialysis during the transient thyrotoxic phase of painless thyroiditis. Pay attention to the possibility of the development of life-threatening ventricular tachycardia associated with hypokalemia in the setting of thyroiditis and thyrotoxic paralysis. PMID:25130115

  1. Acute kidney injury mediated by oxidative stress in Egyptian horses with exertional rhabdomyolysis.

    PubMed

    el-Ashker, Maged R

    2011-06-01

    The present study was carried out to evaluate the role of oxidative stress in the pathophysiologic process of acute renal failure associated with exertional rhabdomyolysis (ER) in Egyptian horses. ER was tentatively diagnosed in 31 Baladi horses based on case history, physical examination findings and confirmed by elevation of plasma creatine kinase (CK) and urine myoglobin concentrations. According to severity of the condition, the diseased horses were categorized into two main groups; the first group included 18 horses with minimal clinical signs and plasma CK <60 000 IU/L; whereas, the second group included 13 horses with overt clinical signs and plasma CK >100 000 IU/L). It was found that plasma creatol (CTL) was positively correlated (p < 0.01) with plasma malondialdehyde (MDA) (r = 0.775), nitric oxide (NO) (r = 0.768), methyguanididne (MG) (r = 0.995), CK (r = 0.768), urine glucose (r = 0.778), urine protein (r = 0.767), renal failure index (RFI) (r = 0.814) and urine sodium (r = 0.799) and negatively correlated (p < 0.01) with total antioxidant capacity (TAC) (r = -0.795), superoxide dismutase (SOD) (r = -0.815), glutathione peroxidase (GSH-Px) (r = -0.675), Vitamin C (r = -0.830), urine creatinine (r = -0.800), urine/plasma creatinine ratio (r = -0.827) and urine/plasma urea ratio (r = -0.807). The correlation between these biochemical variables might suggest a possible role of oxidative stress in renal injury associated with severe rhabdomyolysis in horses. It is suggested that exaggeration of oxidative stress associated with increased muscle membrane leakage plays a key role in acute kidney injury in Baladi horses with severe rhabdomyolysis. PMID:21461642

  2. Severe Rhabdomyolysis Associated with Simvastatin and Role of Ciprofloxacin and Amlodipine Coadministration

    PubMed Central

    De Schryver, Nicolas; Wittebole, Xavier; Van den Bergh, Peter; Haufroid, Vincent; Goffin, Eric; Hantson, Philippe

    2015-01-01

    Simvastatin is among the most commonly used prescription medications for cholesterol reduction and the most common statin-related adverse drug reaction is skeletal muscle toxicity. Multiple factors have been shown to influence simvastatin-induced myopathy. In addition to age, gender, ethnicity, genetic predisposition, and dose, drug-drug interactions play a major role. This is particularly true for drugs that are extensively metabolized by cytochrome P450 (CYP)3A4. We describe a particularly severe case of rhabdomyolysis after the introduction of ciprofloxacin, a weak CYP3A4 inhibitor, in a patient who previously tolerated the simvastatin-amlodipine combination. PMID:25883814

  3. 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

  4. Hashimoto's thyroiditis presenting as Hoffman's syndrome, rhabdomyolysis and acute kidney injury

    PubMed Central

    Ahmed, Gasim Salaheldin; Zaid, Hassan Musa; Moloney, Manus

    2014-01-01

    An otherwise healthy young man presented with gradual progressive fatigue for the past 12 months disturbing his daily activities. Clinical examination revealed marked generalised muscular hypertrophy including the temporalis muscles bilaterally. Investigation revealed that the patient was grossly hypothyroid due to Hashimoto's thyroiditis with rhabdomyolysis and acute kidney injury. The finding of muscle weakness and pseudohypertrophy in association with hypothyroidism is called Hoffman’s syndrome. The patient was hydrated and thyroxine replacement initiated. On follow-up, the patient showed clinical as well as biochemical improvement. PMID:25100806

  5. 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

  6. 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. PMID:27034860

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

    PubMed Central

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

    2014-01-01

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

  8. Continuous veno-venous hemofiltration for massive rhabdomyolysis after malignant hyperthermia: report of 2 cases.

    PubMed

    Fang, Shudong; Xu, Hui; Zhu, Yesen; Jiang, Hong

    2013-01-01

    We present 2 cases of fulminant malignant hyperthermia (MH), complicated with massive rhabdomyolysis. The patients were successfully treated in the intensive care unit of our university teaching hospital, despite the lack of availability of dantrolene in our country, by early application of continuous veno-venous hemofiltration (CVVH). Both male patients developed fulminant malignant hyperthermia during anesthesia for oromaxillofacial surgery. CVVH was employed when the values of creatine phosphokinase (CPK), myoglobin (Mb), and lactate dehydrogenase (LDH) increased significantly. After emergency treatment and CVVH therapy, the values of CPK, Mb, and LDH in the blood plasma of the patients decreased significantly. The complications, including acute renal failure, disseminated intravascular coagulation, and acute respiratory distress syndrome were also treated without any obvious organ damage. Early detection and management are the keys to treat MH successfully. CVVH is a valuable therapeutic application in the initial/critical management of severe rhabdomyolysis. If these complications occur even with initial treatment with dantrolene, our experiences may be useful adjunctive treatments to consider. PMID:23506280

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

    PubMed

    Sumnu, Abdullah; 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. PMID:27034860

  10. Exertional rhabdomyolysis in an acutely detrained athlete/exercise physiology professor.

    PubMed

    Pearcey, Gregory E P; Bradbury-Squires, David J; Power, Kevin E; Behm, David G; Button, Duane C

    2013-11-01

    The authors report a case of exercise-induced (exertional) rhabdomyolysis in a male athlete/exercise physiology professor who started a high-intensity resistance training program after a period of detraining. The subject performed 1 high-intensity resistance training session that consisted of 48 total sets of push-ups (24) and chin-ups (24) with no rest between the sets. Two days after the exercise session, the subject reported "Cola colored" urine. On arriving at the hospital, test results indicated elevated myoglobin and creatine kinase (CK) levels (59 159 U/L; normal is 20-200 U/L). Treatment included intravenous hydration with sodium bicarbonate to reduce myoglobin, blood work to monitor CK levels, and acupuncture from the shoulder to hand. Three weeks posttreatment, the subject started to exercise again. This case study illustrates that unaccustomed exercise in the form of high-intensity resistance training may be harmful (ie, severe delayed onset muscle soreness or even worse, as reported in this case, rhabdomyolysis) to detrained athletes. PMID:23727696

  11. Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis

    PubMed Central

    VALBERG, S. J.; McKENZIE, E. C.; EYRICH, L. V.; SHIVERS, J.; BARNES, N. E.; FINNO, C. J.

    2016-01-01

    Summary Reasons for performing study Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. Objectives To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). Study design Prospective and retrospective histopathological description. Methods Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann–Whitney U and Fisher's exact tests. Results Centrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. Conclusions In a subset of Arabian horses with intermittent episodes of exertional

  12. [Rhabdomyolysis induced by succinylcholine chloride and sevoflurane in an elderly man].

    PubMed

    Takamatsu, F; Taoda, M; Uchihashi, Y; Satoh, T

    1996-11-01

    An 81-year-old man was scheduled for cervical lymph node biopsy. His laboratory data were within normal ranges. After induction of anesthesia with thiopental 175 mg and succinylcholine chloride (SCC) 40 mg, moderate masseter spasm was observed. Anesthesia was maintained with nitrous oxide, oxygen and sevoflurane. After the operation he had severe muscle pain and CK was elevated up to 81,400IU.l-1. The body temperature was not elevated above 37.2 degrees C during and after the operation. The skinned fiber examination, performed one month later, showed his calcium-induced-calcium-release (CICR) to be within normal ranges. We diagnosed him as rhabdomyolysis induced by coadministration of SCC and sevoflurane, especially SCC. We concluded that even in an elderly man, SCC should be administered cautiously. PMID:8953878

  13. Rhabdomyolysis and acute renal failure following use of succinylcholine and enflurane: report of a case.

    PubMed

    Lee, S C; Abe, T; Sato, T

    1987-09-01

    A case of succinylcholine and enflurane induced rhabdomyolysis and myoglobinuric acute renal failure in a mentally retarded patient is presented. The report illustrates some principles of management and the correlation of laboratory findings with the syndrome. When using general anesthesia in mentally retarded patients it is recommended that: 1) a careful personal and family past anesthetic history be taken; 2) drugs and apparatus for treatment of the crisis be available before anesthesia is induced; 3) the use of succinylcholine and potent inhalation anesthetic agents be avoided; 4) there is early diagnosis by prompt recognition of the clinical signs; and 5) that body temperature monitoring and frequent observation of vital signs during and after an operation be carried out. PMID:3476700

  14. [Carbohydrate and nitrogenous metabolism condition in the rat tissue under experimental rhabdomyolysis].

    PubMed

    Kaliman, P A; Okhrimenko, S M

    2012-01-01

    Some effects of glycerol injection on indices of the condition of the thiol-disulfide system as well as carbohydrate and nitrogen metabolism in rats in vivo were studied. A decrease was revealed in levels of non-protein SH-groups in the liver, kidney and heart, as well as of protein SH-groups in the kidney and heart of rats following glycerol injection. That might be connected with SH-group oxidation under the excessive arrival of free haem into tissues under rhabdomyolysis. A decrease in glycogen and increase in tyrosine aminotransferase activity in the liver were observed. Activation of nitrogenous metabolism following glycerol injection is indicated by the increase of aminotransferase activity in organs, and concentration of blood urea. High concentration of creatinine in the rat serum can reflect malfiltration in kidneys. PMID:22679761

  15. 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

  16. Severe rhabdomyolysis from red-bellied black snake (Pseudechis porphyriacus) envenoming despite antivenom.

    PubMed

    Lim, Adeline Y L; Singh, Puneet N; Isbister, Geoffrey K

    2016-07-01

    Envenoming by the Australian red-bellied black snake (Pseudechis porphyriacus) causes non-specific systemic symptoms, anticoagulant coagulopathy, myotoxicity and local effects. Current management for systemic envenoming includes administration of one vial of tiger snake antivenom within 6 h of the bite to prevent myotoxicity. We present a case of severe rhabdomyolysis in a 16 year old male which developed despite early administration of one vial of tiger snake antivenom. Free venom was detected after the administration of antivenom concurrent with rapidly decreasing antivenom concentrations. The case suggests that insufficient antivenom was administered and the use of larger doses of antivenom need to be explored for red-bellied black snake envenoming. PMID:27039255

  17. Statin-associated rhabdomyolysis triggered by drug-drug interaction with itraconazole.

    PubMed

    Dybro, Anne Mette; Damkier, Per; Rasmussen, Torsten Bloch; Hellfritzsch, Maja

    2016-01-01

    A 47-year-old woman had been treated with high-dose simvastatin for several years. After systemic treatment with the antifungal agent itraconazole, she developed muscle pain and highly elevated levels of creatine kinase and myoglobin. Muscle biopsy was compatible with statin-associated rhabdomyolysis, probably caused by a drug-drug interaction between simvastatin and itraconazole. The patient made full recovery. Three commonly used statins-simvastatin, atorvastatin and lovastatin-are metabolised by the liver enzyme CYP3A4. Several potent inhibitors of this enzyme are known, for example, azole antifungal agents such as itraconazole and posaconazole. If antifungal treatment is indicated in a patient using a CYP3A4-metabolised statin, we recommend (1) topical administration of the antifungal agent if possible, (2) the use of a non-CYP3A4-inhibiting antifungal drug such as terbinafine or (3) temporary discontinuation of statin treatment. PMID:27605198

  18. 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

  19. Eccentric contractions do not induce rhabdomyolysis in malignant hyperthermia susceptible mice.

    PubMed

    Corona, Benjamin T; Rouviere, Clement; Hamilton, Susan L; Ingalls, Christopher P

    2008-11-01

    Recent studies suggest a link between exercise-induced rhabdomyolysis and mutations of the ryanodine receptor (RYR1) associated with malignant hyperthermia (MH). We hypothesized that MH-susceptible mice (RYR1Y522S/wt) would exhibit greater anterior crural muscle [tibialis anterior (TA) and extensor digitorum longus (EDL) muscles] damage and strength deficits following the performance of a single or repeated bouts of eccentric contractions compared with wild-type (WT) mice. After a single injury bout, RYR1Y522S/wt mice produced more isometric torque than WT mice immediately and 3 and 7 days postinjury. Moreover, EDL muscle isometric specific force deficits were fully recovered for RYR1Y522S/wt but not WT mice 14 days postinjury. The percentage of fibers in TA muscle exhibiting signs of muscle damage 7 and 14 days postinjury were at least three times less in RYR1Y522S/wt than in WT mice. Uninjured and injured EDL muscle from RYR1Y522S/wt mice also displayed greater S-glutathionylation of RYR1 than that from WT mice. During the weekly injury bouts, torque production by RYR1Y522S/wt mice was fully recovered before the third and fourth injury bouts, whereas torque was still reduced for WT mice. Three days after multiple injury bouts, there were approximately 50% fewer fibers exhibiting signs of muscle damage in RYR1Y522S/wt than in WT TA muscle. These findings indicate that the RYR1Y522S/wt mutation protects skeletal muscle from exercise-induced muscle injury and do not support a direct association between MH susceptibility and contraction-induced rhabdomyolysis when core temperature is maintained at lower physiological temperatures during exercise. PMID:18787086

  20. [A steroid-responsive case of severe rhabdomyolysis associated with cytomegalovirus infection].

    PubMed

    Sato, Keishiro; Yoneda, Makoto; Hayashi, Koji; Nakagawa, Hiroto; Higuchi, Itsuro; Kuriyama, Masaru

    2006-05-01

    A 31-year-old man was admitted to our hospital, complaining of muscular weakness and pain in the legs one month after a common cold. On admission, neurological examinations demonstrated moderate weakness in the arms and mild weakness in the legs with decreased or diminished deep tendon reflexes, and mild dysphagia. Weakness was gradually extended to the arm, throat and respiratory muscles, requiring artificial ventilation. Laboratory examinations demonstrated increased levels of CK (upto 24,380 IU/L) and positive anti-cytomegalovirus (CMV) -IgM antibodies in the serum, and myogloburinuria. CMV was not detected in either the blood cells or muscles by PCR. There were no antibodies against viruses including Ebstein-Barr virus and HIV, in the serum. There were no autoantibodies related to collagen diseases in the serum. Systemic PET scan did not show any evidence of malignancy. Bone marrow biopsy did not show any atypical cells. Muscle MRI demonstrated mild atrophy with high intensity signals in part. Muscle biopsy demonstrated scattered necrotic and regenerated muscle fibers without inflammatory cell infiltration. The patient was therefore diagnosed as having rhabdomyolysis associated with CMV infection. After three courses of intravenously administered high dose methylprednislone over three days, muscle weakness improved gradually, and the serum CK level was normalized in two months. The patient recovered and was removed from artificial ventilation three months after the therapy. There were no sign of renal failure. Steroid therapy should be considered for the treatment of rhabdomyolysis or myopathy associated with CMV infection in order to prevent renal failure or fatal progression of the disease. PMID:16886796

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

    PubMed Central

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

    2015-01-01

    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

  2. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride

    PubMed Central

    Roe, Charles R.; Sweetman, Lawrence; Roe, Diane S.; David, France; Brunengraber, Henri

    2002-01-01

    The current dietary treatment of long-chain fatty acid oxidation defects (high carbohydrate with medium-even-chain triglycerides and reduced amounts of long-chain fats) fails, in many cases, to prevent cardiomyopathy, rhabdomyolysis, and muscle weakness. We hypothesized that the apparent defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis). We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function. We fed subjects with long-chain defects a controlled diet in which the fat component was switched from medium-even-chain triglycerides to triheptanoin. In three patients with very-long-chain acyl-CoA dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others. There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders. PMID:12122118

  3. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride.

    PubMed

    Roe, Charles R; Sweetman, Lawrence; Roe, Diane S; David, France; Brunengraber, Henri

    2002-07-01

    The current dietary treatment of long-chain fatty acid oxidation defects (high carbohydrate with medium-even-chain triglycerides and reduced amounts of long-chain fats) fails, in many cases, to prevent cardiomyopathy, rhabdomyolysis, and muscle weakness. We hypothesized that the apparent defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis). We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function. We fed subjects with long-chain defects a controlled diet in which the fat component was switched from medium-even-chain triglycerides to triheptanoin. In three patients with very-long-chain acyl-CoA dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others. There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders. PMID:12122118

  4. Rhabdomyolysis and acute renal failure following minimally invasive spine surgery: report of 5 cases.

    PubMed

    Dakwar, Elias; Rifkin, Stephen I; Volcan, Ildemaro J; Goodrich, J Allan; Uribe, Juan S

    2011-06-01

    Minimally invasive spine surgery is increasingly used to treat various spinal pathologies with the goal of minimizing destruction of the surrounding tissues. Rhabdomyolysis (RM) is a rare but known complication of spine surgery, and acute renal failure (ARF) is in turn a potential complication of severe RM. The authors report the first known case series of RM and ARF following minimally invasive lateral spine surgery. The authors retrospectively reviewed data in all consecutive patients who underwent a minimally invasive lateral transpsoas approach for interbody fusion with the subsequent development of RM and ARF at 2 institutions between 2006 and 2009. Demographic variables, patient home medications, preoperative laboratory values, and anesthetic used during the procedure were reviewed. All patient data were recorded including the operative procedure, patient positioning, postoperative hospital course, operative time, blood loss, creatine phosphokinase (CPK), creatinine, duration of hospital stay, and complications. Five of 315 consecutive patients were identified with RM and ARF after undergoing minimally invasive lateral transpsoas spine surgery. There were 4 men and 1 woman with a mean age of 66 years (range 60-71 years). The mean body mass index was 31 kg/m2 and ranged from 25 to 40 kg/m2. Nineteen interbody levels had been fused, with a range of 3-6 levels per patient. The mean operative time was 420 minutes and ranged from 315 to 600 minutes. The CPK ranged from 5000 to 56,000 U/L, with a mean of 25,861 U/L. Two of the 5 patients required temporary hemodialysis, while 3 required only aggressive fluid resuscitation. The mean duration of the hospital stay was 12 days, with a range of 3-25 days. Rhabdomyolysis is a rare but known potential complication of spine surgery. The authors describe the first case series associated with the minimally invasive lateral approach. Surgeons must be aware of the possibility of postoperative RM and ARF, particularly in

  5. CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles

    PubMed Central

    Rubio-Navarro, Alfonso; Carril, Mónica; Padro, Daniel; Guerrero-Hue, Melanie; Tarín, Carlos; Samaniego, Rafael; Cannata, Pablo; Cano, Ainhoa; Villalobos, Juan Manuel Amaro; Sevillano, Ángel Manuel; Yuste, Claudia; Gutiérrez, Eduardo; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

    2016-01-01

    Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis. PMID:27162559

  6. CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles.

    PubMed

    Rubio-Navarro, Alfonso; Carril, Mónica; Padro, Daniel; Guerrero-Hue, Melanie; Tarín, Carlos; Samaniego, Rafael; Cannata, Pablo; Cano, Ainhoa; Villalobos, Juan Manuel Amaro; Sevillano, Ángel Manuel; Yuste, Claudia; Gutiérrez, Eduardo; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

    2016-01-01

    Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis. PMID:27162559

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

    PubMed Central

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

    2016-01-01

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

  8. 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. PMID:27034948

  9. Intermittent rhabdomyolysis with adult onset associated with a mutation in the ACADVL gene.

    PubMed

    Antunes, Ana Patrícia; Nogueira, Célia; Rocha, Hugo; Vilarinho, Laura; Evangelista, Teresinha

    2013-12-01

    Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD) is an autosomal recessive disease. Most common phenotypes occur in the neonatal period or in childhood with cardiomyopathy, hepatomegaly, and hypoketogenic hypoglycemia. Juvenile/adult-onset is characterized by exercise intolerance and recurrent rhabdomyolysis triggered by prolonged exercise or fasting. This article reports a patient with the homozygous mutation c.1097G>A (p.R366H) in the ACADVL gene. In Portugal, VLCAD deficiency became part of the neonatal screening plan in 2004, and as of 2012, 8 early-onset cases have been diagnosed, giving an incidence rate of 1:97.238 per 737.902 newborns. This patient was diagnosed outside of the neonatal screening plan. Beta-oxidation defects pose a diagnostic challenge because of their transient clinical and laboratorial manifestations and the absence of morphological changes in muscle biopsy further complicate matters, especially in the late-onset forms of the disease. The adult phenotype of VLCAD deficiency is highlighted, emphasizing the need for a high suspicion index and the value of tandem mass spectrometry for the diagnosis. PMID:24263034

  10. [Antioxidant effects of L-arginine in the rat heart in experimental rhabdomyolysis].

    PubMed

    Filimonenko, V P; Nikitchenko, I V; Kaliman, P A

    2009-01-01

    The glycerol administration in a dose of 1 ml of 50% water solution/100 g b. w. was found to cause considerable accumulation of the total heme in the rat blood serum that is accompanied by an increase of TBA-reactive products and protein carbonyl derivates contents and by changes of protein level. Heme entering in the heart tissue is observed in the first hours after glycerol injection. The breaches of heart antioxidant-prooxidant balance are noted in twenty-four hours: TBA-reactive products and protein carbonyl derivates accumulation, heme oxygenase and catalase activation, superoxide dismutase activity lowering and reduction of glutathione content elevation. Pretreatment by L-arginine (0.5 h before glycerol administration) almost did not affect the blood serum changes caused by glycerol injection. However in the rat heart L-arginine administration prevents from TBA-reactive products and protein carbonyl derivates accumulation and the breaches of superoxide dismutase and catalase activities. Besides L-arginine causes the ealier heme oxygenase induction. Possible mechanisms of L-arginine protective action in the rat heart under experimental rhabdomyolysis are discussed. PMID:19877424

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

    PubMed

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

    2016-05-18

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

  12. Heritability of Recurrent Exertional Rhabdomyolysis in Standardbred and Thoroughbred Racehorses Derived From SNP Genotyping Data.

    PubMed

    Norton, Elaine M; Mickelson, James R; Binns, Matthew M; Blott, Sarah C; Caputo, Paul; Isgren, Cajsa M; McCoy, Annette M; Moore, Alison; Piercy, Richard J; Swinburne, June E; Vaudin, Mark; McCue, Molly E

    2016-11-01

    Recurrent exertional rhabdomyolysis (RER) in Thoroughbred and Standardbred racehorses is characterized by episodes of muscle rigidity and cell damage that often recur upon strenuous exercise. The objective was to evaluate the importance of genetic factors in RER by obtaining an unbiased estimate of heritability in cohorts of unrelated Thoroughbred and Standardbred racehorses. Four hundred ninety-one Thoroughbred and 196 Standardbred racehorses were genotyped with the 54K or 74K SNP genotyping arrays. Heritability was calculated from genome-wide SNP data with a mixed linear and Bayesian model, utilizing the standard genetic relationship matrix (GRM). Both the mixed linear and Bayesian models estimated heritability of RER in Thoroughbreds to be approximately 0.34 and in Standardbred racehorses to be approximately 0.45 after adjusting for disease prevalence and sex. To account for potential differences in the genetic architecture of the underlying causal variants, heritability estimates were adjusted based on linkage disequilibrium weighted kinship matrix, minor allele frequency and variant effect size, yielding heritability estimates that ranged between 0.41-0.46 (Thoroughbreds) and 0.39-0.49 (Standardbreds). In conclusion, between 34-46% and 39-49% of the variance in RER susceptibility in Thoroughbred and Standardbred racehorses, respectively, can be explained by the SNPs present on these 2 genotyping arrays, indicating that RER is moderately heritable. These data provide further rationale for the investigation of genetic mutations associated with RER susceptibility. PMID:27489252

  13. 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

  14. Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury.

    PubMed

    Boddu, Ravindra; Hull, Travis D; Bolisetty, Subhashini; Hu, Xianzhen; Moehle, Mark S; Daher, João Paulo Lima; Kamal, Ahmed Ibrahim; Joseph, Reny; George, James F; Agarwal, Anupam; Curtis, Lisa M; West, Andrew B

    2015-07-15

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson's disease, and LRRK2 is also linked to Crohn's and Hansen's disease. LRRK2 is expressed in many organs in mammals but is particularly abundant in the kidney. We find that LRRK2 protein is predominantly localized to collecting duct cells in the rat kidney, with much lower expression in other kidney cells. While genetic knockout (KO) of LRRK2 expression is well-tolerated in mice and rats, a unique age-dependent pathology develops in the kidney. The cortex and medulla of LRRK2 KO rat kidneys become darkly pigmented in early adulthood, yet aged animals display no overt signs of kidney failure. Accompanying the dark pigment we find substantial macrophage infiltration in LRRK2 KO kidneys, suggesting the presence of chronic inflammation that may predispose to kidney disease. Unexpectedly, the dark kidneys of the LRRK2 KO rats are highly resistant to rhabdomyolysis-induced acute kidney injury compared with wild-type rats. Biochemical profiling of the LRRK2 KO kidneys using immunohistochemistry, proteomic and lipidomic analyses show a massive accumulation of hemoglobin and lipofuscin in renal tubules that account for the pigmentation. The proximal tubules demonstrate a corresponding up-regulation of the cytoprotective protein heme oxygenase-1 (HO-1) which is capable of mitigating acute kidney injury. The unusual kidney pathology of LRRK2 KO rats highlights several novel physiological roles for LRRK2 and provides indirect evidence for HO-1 expression as a protective mechanism in acute kidney injury in LRRK2 deficiency. PMID:25904107

  15. 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

  16. 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

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

    PubMed Central

    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

    2016-01-01

    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

  18. An Unexpected Interaction between Sofosbuvir/Ledipasvir and Atorvastatin and Colchicine Causing Rhabdomyolysis in a Patient with Impaired Renal Function

    PubMed Central

    Andres, Jennifer

    2016-01-01

    Hepatitis C virus (HCV) infection affects roughly 170 million people worldwide. Sofosbuvir/Ledipasvir (Sof/Led) is a new once daily direct acting antiviral combination pill that was approved in October 2014 for use in patients with HCV genotype 1 infection. Coadministration of Sof/Led is studied only with rosuvastatin which shows significantly increased level of drug and is associated with increased risk of myopathy, including rhabdomyolysis. There is no mention of such HMG-CoA reductase inhibitor interaction as a class, as pravastatin did not have any clinically significant interaction with Sof/Led. Other myotoxic drugs, including colchicine are not studied. We present a case of a serious drug interaction between Sof/Led and atorvastatin, in the background of CKD and colchicine use.

  19. [Effect of L-arginine on pro- and antioxidant status of the rat vessels and lungs in experimental rhabdomyolysis].

    PubMed

    Fylymonenko, V P; Nikitchenko, I V; Kaliman, P A

    2009-01-01

    The glycerol administration was found to cause accumulation of the total heme in rat blood serum, vessels and lungs that are accompanied by increase of TBA-reactive products and protein carbonyl derivates contents. A decrease of superoxide dismutase activity and an increase of reduced glutathione in lung were observed. Heme entering the vessels and lungs is accompanied by elevation in heme oxygenase activity. Pretreatment by L-arginine (0.5 h before glycerol administration) didn't affect blood serum and vessels changes caused by glycerol injection. However, in lungs, L-arginine prevents TBA-reactive products and protein carbonyl derivates accumulation, the decrease ofsuperoxide dismutase activity and causes the ealier heme oxygenase induction. Prooxidant effects of heme in tissues studied and possible mechanisms of L-arginine protective action in lung under experimental rhabdomyolysis are discussed. PMID:20095386

  20. Heme oxygenase activity and some indices of antioxidant protection in rat liver and kidney in glycerol model of rhabdomyolysis.

    PubMed

    Kaliman, P A; Strel'chenko, E V; Nikitchenko, I V; Filimonenko, V P

    2003-01-01

    Activity of heme oxygenase, superoxide dismutase, and catalase, the content of reduced glutathione and total heme in the liver and kidneys, and serum absorption spectrum in the Soret band were studied in rats with glycerol-induced rhabdomyolysis. Glycerol increased the content of heme-containing metabolites in the serum and the total heme content in the liver and kidneys, and decreased the content of reduced glutathione and catalase activity in the examined organs. Superoxide dismutase activity increased in the liver and decreased in the kidneys. Heme oxygenase activity increased in the liver and kidneys 2 and 6 h postinjection, respectively. The effects of heme delivered to the liver and kidneys from the vascular bed on the antioxidant defense and heme oxygenase activity were studied. PMID:12717508

  1. 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

  2. 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-α (TNF-α). In addition, whole blood was used for determination of selenium, reduced glutathione (G-SH) and prostaglandin F2-α (PGF2α). 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- α, IL6 and PGF2- α 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

  3. Statin-induced myotoxicity: pharmacokinetic differences among statins and the risk of rhabdomyolysis, with particular reference to pitavastatin.

    PubMed

    Catapano, Alberico L

    2012-03-01

    3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely prescribed therapeutic class of drugs worldwide, with established clinical benefits both in terms of improving serum lipid profiles and reducing cardiovascular events and mortality. Although statins have a favorable risk-to-benefit ratio, they have the potential to cause adverse events which can result in muscular inflammation (myositis), muscle breakdown (rhabdomyolysis) and, ultimately, kidney failure. While the incidence of rhabdomyolysis is approximately 3.4 cases per 100,000 person-years with standard-dose statin therapy, the risk of developing the condition increases substantially at higher therapeutic doses. This effect may be exacerbated by prescribing statins in combination with certain other medications because drug � drug interactions increase statin exposure by interacting with enzymes that would normally be involved in their metabolism and clearance. Co-administration of drugs that inhibit the cytochrome P450 (CYP) enzymes responsible for metabolizing statins, or that interact with the organic anion-transporting polypeptides (OATPs) responsible for statin uptake into hepatocytes, substantially increases the risk of developing myotoxicity. Such effects vary among statins according to their metabolic profile. For example, pitavastatin, a novel statin approved for the treatment of hypercholesterolemia and combined (mixed) dyslipidemia, is not catabolized by CYP3A4, unlike other lipophilic statins, and may be less dependent on the OATP1B1 transporter for its uptake into hepatocytes before clearance. Such differences in drug � drug interaction profiles among available statins offer the possibility of reducing the risk of myotoxicity among high-risk patients. PMID:22022768

  4. [A case of acute renal failure in neuroleptic malignant syndrome associated with rhabdomyolysis--possible contributing role of hyperreninemia].

    PubMed

    Fujisawa, K; Maruyama, Y; Nakamura, K; Nagase, M

    1994-10-01

    A schizophrenic woman, aged 45, was admitted complaining of high fever, oliguria, blackish urine, muscle swelling and pain. She had been treated for the past 3 years with haloperidol (8 mg), levomepromazine (150 mg), chlorpromazine (75 mg), lithium carbonate (600 mg), bromocriptine mesilate (7.5 mg), etizolam (1 mg), and flunitrazepam (2 mg), Physical examination revealed her to be an obese and uncommunicatable woman with swelling and weakness of the extremities and abdominal distension without borborygmus. Urine was dark brown and (+) for protein and occult blood. Blood chemistry analysis revealed BUN 71 mg/dl, creatinine 6.8 mg/dl, CPK 143,850 IU and myoglobin 3,980 ng/ml. PRA on the 11th hospital day was 96 ng/ml/hour. This patient fulfilled the Levenson's diagnostic criteria for manifestations of neuroleptic malignant syndrome (NMS). High PRA did not decrease after cessation of the diuretics. After treatment with dantrolene sodium and 10 treatments with hemodialysis, azotemia disappeared with the start of diuresis. The PRA also decreased to the normal level. Characteristic acceleration of the central sympathetic stimuli in NMS seemed to have induced hyperreninemia, which together with rhabdomyolysis, might have contributed to the development of acute renal failure. PMID:7815749

  5. Reduction of the risk of rhabdomyolysis after bariatric surgery with lower fluid administration in the perioperative period: a cohort study.

    PubMed

    Matłok, Maciej; Major, Piotr; Małczak, Piotr; Wysocki, Michał; Hynnekleiv, Leif; Nowak, Mateusz; Karcz, Konrad; Pędziwiatr, Michał; Budzyński, Andrzej

    2016-04-13

    INTRODUCTION    Obesity is a growing worldwide problem. One of the most effective treatments is a bariatric procedure; however, surgery is associated with the risk of complications, such as staple line leakage, suture line bleeding, and rhabdomyolysis (RML). OBJECTIVES    The objective of our study was to assess the risk of RML after bariatric surgery related to intravenous fluid administration in the perioperative period. PATIENTS AND METHODS    The study involved 194 patients who underwent a bariatric surgery (laparoscopic sleeve gastrectomy or laparoscopic gastric bypass). We studied an association between the development of RML and sex, age, weight, duration of surgery, type of surgery, and the volume of intravenously administered fluids during the perioperative period. RESULTS    The median duration of surgery was 132.5 minutes. The median volume of administered fluids was 3150 ml from the introduction of anesthesia to 24 hours after surgery. Biochemical RML (creatine phosphokinase >1000 U/l) was observed in 30 patients (15.46%). RML with clinical manifestations developed in 6 patients. Multivariate logistic regression revealed an increase in the odds ratio of biochemical RML with an increase of weight on the day of surgery, operative time, and volume of intravenous fluids. A multiple regression model showed that every 500 ml of transfused fluid over the median volume increases creatine phosphokinase concentrations in the first postoperative day by 241.77 U/l over the median level, with the operative time and patient's weight remaining at median values. CONCLUSIONS    We observed an association between the administration of lower fluid volumes and a lower risk of RML. We postulate that decreasing intravenous fluid administration may reduce the risk of RML after bariatric surgery. PMID:27074693

  6. 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, TNFα 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, TNFα 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, 756–769

  7. 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

  8. Exertional rhabdomyolysis and exercise intolerance revealing dystrophinopathies.

    PubMed

    Figarella-Branger, D; Baeta Machado, A M; Putzu, G A; Malzac, P; Voelckel, M A; Pellissier, J F

    1997-07-01

    Exercise intolerance associated with myalgias, muscle cramps or myoglobinuria may be associated with a dystrophinopathy. A search for abnormal dystrophin expression (using immunohistochemistry, immunoblot and DNA analysis) was carried out in a series of 15 patients. They were selected because they presented exercise intolerance, negative biochemical tests (lipid, glycogen and mitochondrial metabolism) and abnormal immunohistochemistry with at least one anti-dystrophin antibody (anti-Dys 1, rod domain; anti-Dys 2, C terminus; anti-Dys 3, N terminus). Lack of anti-Dys 1 immunoreactivity was seen in three patients and abnormal immunoreactivity with all three anti-dystrophin antibodies in two. Immunoblot confirmed the dystrophinopathy in these five patients only, and multiplex polymerase chain reaction DNA analysis revealed a deletion in the dystrophin gene in two of these patients, affecting the proximal part of the rod domain in one and the distal part of this domain in the other. The clinical, biological and histopathological features of the five patients reported here, together with the previous cases reported in the literature, are described and reveal that exercise intolerance associated with dystrophinopathy displays characteristic clinical, biological and immunohistochemical features and defines a new dystrophinopathy phenotype. The absence of staining in the rod domain provides a secure diagnosis of this syndrome. Dystrophinopathy is one etiology of idiopathic myoglobinuria, requiring genetic counseling. PMID:9224530

  9. Acute Rhabdomyolysis Following Synthetic Cannabinoid Ingestion

    PubMed Central

    Adedinsewo, Demilade A.; Odewole, Oluwaseun; Todd, Taylor

    2016-01-01

    Context: Novel psychoactive substances, including synthetic cannabinoids, are becoming increasingly popular, with more patients being seen in the emergency room following acute ingestion. These substances have been associated with a wide range of adverse effects. However, identification of complications, clinical toxicity, and management remain challenging. Case Report: We present the case of a young African-American male who developed severe agitation and bizarre behavior following acute K2 ingestion. Laboratory studies revealed markedly elevated serum creatine phosphokinase (CPK) with normal renal function. The patient was managed with aggressive intravenous (IV) fluid hydration and treatment of underlying psychiatric illness. Conclusion: We recommend the routine evaluation of renal function and CPK levels with early initiation of IV hydration among patients who present to the emergency department following acute ingestion of synthetic cannabinoids to identify potential complications early as well as institute early supportive therapy. PMID:27500131

  10. Traumatic rhabdomyolysis from severe beating--experience of volume diuresis in 200 patients.

    PubMed

    Knottenbelt, J D

    1994-08-01

    Fluid loading with balanced salt solution (BSS) was carried out in 200 patients with extensive soft tissue injuries from severe beatings. Urinary volume and dipstick specific gravity testing were used to monitor renal function with administration of furosemide for persistent oliguria. Acute intrinsic renal failure (AIRF) occurred in 21 patients (10.5%) and five patients died (2.5%); two of hyperkalemia, two of sepsis and one of multiple organ failure. Significantly increased rates of AIRF and death were associated with injury-admission intervals of more than 12 hours, severe metabolic acidosis, low initial hemoglobin, heavy pigmenturia, and high serum creatine kinase (CK) levels. An increased serum creatinine/BUN ratio was noted in four of the five patients who died. An average of 7.5 L fluids was needed in non-AIRF patients to achieve adequate diuresis with a mean positive fluid balance of 4.7 L. No patient without pigmenturia developed AIRF. Balanced salt solution volume diuresis supplemented with furosemide as necessary appears to be safe and effective in preventing AIRF in soft tissue injuries sustained in beatings. PMID:8064919

  11. Evaluation of the severity of traumatic rhabdomyolysis using technetium-99m pyrophosphate scintigraphy.

    PubMed

    Chang, H R; Kao, C H; Lian, J D; Shu, K H; Cheng, C H; Wu, M J; Chen, C H

    2001-01-01

    A quantitative scoring method was designed to assess the extent of muscle damage. Technetium-99m pyrophosphate (99mTc-PYP) scintigraphy was performed for 9 patients experiencing crush injury in the Chichi (Taiwan) earthquake. The magnitude of muscle uptake of 99mTc-PYP was graded as follows: grade 0, less than bone radioactivity (BRA); grade 1, equal to BRA; grade 2, higher than BRA; or grade 3, greatly higher than BRA. The area of muscle injury was estimated according to the rule of nines. The sum of the muscle injury size multiplied by its corresponding grading was defined as the anterior or posterior score according to the anterior or posterior images. Each image was interpreted by two physicians and average anterior and posterior scores were calculated. The muscle score was defined as the geometric mean of the average anterior and posterior scores. Significant correlations were obtained between the muscle score and duration of time trapped (r = 0.868, p < 0.01), peak serum creatine kinase level (r = 0.866, p < 0.01), peak serum phosphorus level (r = 0.877, p < 0.01) and number of hospital days (r = 0.875, p < 0.01). A negative correlation between the muscle score and blood pH (r = -0.706, p < 0.01) was also observed. We concluded that this scoring method may be used as an adjunct for evaluating the locations of trauma and the severity of crush syndrome, and for predicting the duration of hospital stay. PMID:11423690

  12. Compartment syndrome, rhabdomyolysis and risk of acute renal failure as complications of the urological surgery.

    PubMed

    Kochiashvili, D; Sutidze, M; Tchovelidze, Ch; Rukhadze, I; Dzneladze, A

    2007-02-01

    Current knowledge related to the risk of CS when operating in these positions (Lloyd Davies and Trendelenburg tilt) is such that it can be deemed negligent to keep patients in this position (with legs higher than the heart) when not absolutely necessary. If it means repositioning and redraping, thus adding a few extra minutes to the episode and costing a small amount in additional drapes, surely this is a small price to pay for excellent perioperative care? If repositioning is impossible to execute, the head-down tilt position should be reversed every two hours, for a short period of time, to allow more natural perfusion of the lower limbs to occur. Raza et al recommend that if the anticipated procedure duration is beyond four hours, the legs should be removed from supports every two hours for a short period to prevent reperfusion injury. The use of Allen stirrups is preferred to calf supports or metal skids. Turnbull and Mills suggest that we should certainly review our use of compression stockings and intermittent compression devices when operating on patients in the Lloyd Davies position. It will be deemed negligent to misdiagnose (ie: mistake for a DVT) or delay treatment (by prolonged re-assessment) of CS postoperatively when patients have been subjected to prolonged surgery in these abnormal positions. Delayed or missed diagnosis may not only be limb-threatening (and cause a very protracted hospital stay)--it can be life-threatening. With today's current knowledge, surgeons undertaking prolonged surgery in abnormal positions must be aware of this, fortunately rare, complication. Practice guidelines within perioperative care should reflect current knowledge and ensure that risk is minimized. Patients who take legal action if they have experienced this condition may be awarded substantial costs against negligence if lack of care can be proven or diagnosis has been delayed. PMID:17404439

  13. Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.

    PubMed

    Osaki, Yoshinori; Nakagawa, Yoshimi; Miyahara, Shoko; Iwasaki, Hitoshi; Ishii, Akiko; Matsuzaka, Takashi; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Sone, Hirohito; Ohashi, Ken; Ishibashi, Shun; Yamada, Nobuhiro; Shimano, Hitoshi

    2015-10-23

    HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs. PMID:26381177

  14. The priority of Antonino D'Antona in describing rhabdomyolysis with acute kidney injury, following the Messina earthquake (December 28, 1908). Commentary.

    PubMed

    De Santo, Natale Gaspare; Bisaccia, Carmela; De Santo, Luca Salvatore

    2016-01-01

    Following the Messina-Reggio Calabria earthquake (December 28, 1908) outstanding medical reports were published by Franz von Colmers (1875-1960), Antonino D'Antona (1842-1913), and Rocco Caminiti (1868-1940). The reports of D'Antona and Caminiti were heretofore neglected. Colmers, D'Antona and Caminiti described crush-syndrome. D'Antona who cured patients in shock also described two deaths due to uraemia. This gives him a priority in the description of crush syndrome with renal injury which has been traditionally attributed to Bywaters and Beall. PMID:27033609

  15. 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.” PMID:26952148

  16. [Activity of key enzymes of heme metabolism and cytochrome P-450 content in the rat liver in experimental rhabdomyolysis and hemolytic anemia].

    PubMed

    Kaliman, P A; Inshina, N N; Strel'chenko, E V

    2003-01-01

    The 5-aminolevulinate synthase, heme oxygenase, tryptophan-2,3-dioxygenase activities, the content of total heme and cytochrome P-450 content in the rat liver and absorption spectrum of blood serum in Soret region under glycerol model of rhabdomiolisis and hemolytic anemia caused by single phenylhydrazine injection have been investigated. The glycerol injection caused a considerable accumulation of heme-containing products in the serum and the increase of the total heme content, holoenzyme, total activity and heme saturation of tryptophan-2,3-dioxygenase, as well as the increase of the 5-aminolevulinate synthase and heme oxygenase activities in the liver during the first hours of its action and the decrease of cytochrome P-450 content in 24 h. Administration of phenylhydrazine lead to the increasing of hemolysis products content in blood serum too, although it was less expressed. The phenylhydrazine injection caused the increase of activities of 5-aminolevulinate synthase, holoenzyme, total activity and heme saturation of tryptophan-2,3-dioxygenase, as well as decrease of cytochrome P-450 content in the rat liver in 2 h. The increase of the total heme content and heme oxygenase activity has been observed in 24 h. The effect of heme arrival from the blood stream, as well as a direct influence of glycerol and phenylhydrazine on the investigated parameters are discussed. PMID:14577161

  17. Methadone for Fun Sake… Kidneys Are at Stake!!!

    PubMed

    Chaudhari, Sameer; Wankhedkar, Kashmira; Popis-Matejak, Beata; Baumstein, Donald

    2016-01-01

    Acute renal failure from rhabdomyolysis is a well-established clinical entity; however, rhabdomyolysis exclusively caused by the ingestion of methadone requiring hemodialysis is very uncommon. With a similar mechanism to opiates, methadone can cause rhabdomyolysis and further consequences. Given the increasing use of methadone as a therapy for opiate dependence, clinicians prescribing this medication should be aware of this life-threatening complication. PMID:25782567

  18. Severe obstructive sleep apnea after cerivastatin therapy: a case report.

    PubMed

    Ebben, Matthew R; Sethi, Nitin K; Spielman, Arthur J

    2008-06-15

    All available 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been implicated in causing rhabdomyolysis either as monotherapy or in combination with other myotoxic drugs such as cyclosporine, colchicine and fibrates. Cerivastatin (Baycol) is a third generation statin, which has been implicated in cases of fatal rhabdomyolysis. It was voluntary withdrawn from the U.S. market by Bayer after reports of fatal rhabdomyolysis appeared in the literature. We present here a case of an 85-year-old woman who developed rhabdomyolysis and severe obstructive sleep apnea (OSA) symptoms after having been started on cerivastatin therapy for hypercholesteremia. PMID:18595439

  19. Myoglobin blood test

    MedlinePlus

    ... muscle tissue that leads to the release of muscle fiber contents into the blood ( rhabdomyolysis ) Skeletal muscle inflammation ( myositis ) Skeletal muscle ischemia (oxygen deficiency) Skeletal ...

  20. 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.

  1. Trimethoprim-Sulfamethoxazole-Induced Rhabdomyolysis; Gabapentin-Induced Hypoglycemia in Diabetic and Nondiabetic Patients; Purple Glove Syndrome After Oral Phenytoin Administration; Acute Dystonic Reaction After Methylphenidate Initiation; Serotonin Syndrome with Vilazodone Monotherapy; Cabozantinib-Associated Dermatologic Adverse Reactions.

    PubMed

    Mancano, Michael A

    2015-09-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:26715798

  2. [Acute poisoning due to oral intake of an organic solvent].

    PubMed

    Holtz, J; Nicole, A; Regamey, C

    1992-11-21

    We report a case of paint thinner intoxication by oral intake, with loss of consciousness, upper gastrointestinal injuries, renal failure, rhabdomyolysis and cervical plexus injury. The clinical picture was similar to other cases reported in the literature. PMID:1448688

  3. Myoglobin blood test

    MedlinePlus

    ... due to: Heart attack Malignant hyperthermia (very rare) Muscular dystrophy Breakdown of muscle tissue that leads to the ... chap 421. Read More Heart attack Malignant hyperthermia Muscular dystrophy Myoglobin urine test Myositis Rhabdomyolysis Update Date 2/ ...

  4. 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

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

    PubMed

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

    2012-05-01

    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

  6. Carnitine palmitoyltransferase II deficiency

    PubMed Central

    Roe, C R.; Yang, B-Z; Brunengraber, H; Roe, D S.; Wallace, M; Garritson, B K.

    2008-01-01

    Background: Carnitine palmitoyltransferase II (CPT II) deficiency is an important cause of recurrent rhabdomyolysis in children and adults. Current treatment includes dietary fat restriction, with increased carbohydrate intake and exercise restriction to avoid muscle pain and rhabdomyolysis. Methods: CPT II enzyme assay, DNA mutation analysis, quantitative analysis of acylcarnitines in blood and cultured fibroblasts, urinary organic acids, the standardized 36-item Short-Form Health Status survey (SF-36) version 2, and bioelectric impedance for body fat composition. Diet treatment with triheptanoin at 30% to 35% of total daily caloric intake was used for all patients. Results: Seven patients with CPT II deficiency were studied from 7 to 61 months on the triheptanoin (anaplerotic) diet. Five had previous episodes of rhabdomyolysis requiring hospitalizations and muscle pain on exertion prior to the diet (two younger patients had not had rhabdomyolysis). While on the diet, only two patients experienced mild muscle pain with exercise. During short periods of noncompliance, two patients experienced rhabdomyolysis with exercise. None experienced rhabdomyolysis or hospitalizations while on the diet. All patients returned to normal physical activities including strenuous sports. Exercise restriction was eliminated. Previously abnormal SF-36 physical composite scores returned to normal levels that persisted for the duration of the therapy in all five symptomatic patients. Conclusions: The triheptanoin diet seems to be an effective therapy for adult-onset carnitine palmitoyltransferase II deficiency. GLOSSARY ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATP = adenosine triphosphate; BHP = β-hydroxypentanoate; BKP = β-ketopentanoate; BKP-CoA = β-ketopentanoyl–coenzyme A; BUN = blood urea nitrogen; CAC = citric acid cycle; CoA = coenzyme A; CPK = creatine phosphokinase; CPT II = carnitine palmitoyltransferase II; LDL = low-density lipoprotein; MCT

  7. Statin myopathy.

    PubMed

    Radcliffe, Kristofer A; Campbell, William W

    2008-01-01

    Many different classes of medications can cause toxic myopathy. One of the most frequently implicated classes is the statins. Statin myotoxicity ranges from asymptomatic creatine kinase elevations or myalgias to muscle necrosis and fatal rhabdomyolysis. Statins may also cause an autoimmune myopathy requiring immunosuppressive treatment. The mechanisms of statin myotoxicity are unclear. If unrecognized in its early manifestations, complications from continued statin therapy may lead to rhabdomyolysis and death. Risk factors for myotoxicity include concomitant medication use and medical conditions, and the patient's underlying genetic constitution. We review these considerations along with the recommended evaluation and treatment for patients presenting with statin myotoxicity. PMID:18367041

  8. 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

  9. Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation.

    PubMed

    Rodgers, Bradley K; Kumar, Avinash B

    2016-01-01

    Toxic epidermal necrolysis syndrome (TEN) is a rare severe cutaneous adverse drug reaction that involves skin and mucous membranes. We describe a case of TEN presenting with stage III acute kidney injury, rhabdomyolysis, and acute respiratory failure likely triggered by allopurinol for recently diagnosed gout. Prompt diagnosis, multidisciplinary management, including aggressive resuscitation, cardiorespiratory support, intravenous immunoglobulin therapy, and daily wound care resulted in a positive outcome despite a predicted mortality greater than 60%. Although allopurinol is a known triggering agent, TEN presenting with rhabdomyolysis and acute kidney injury is rare. PMID:24832386

  10. 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

  11. [Brown urine : Myoglobin-induced renal failure after concomitant administration of simvastatin and amiodarone].

    PubMed

    Pietsch, U; Müller-Höcker, C; Filipovic, M

    2016-05-01

    Rhabdomyolysis is a rare but well-known complication of statin therapy. The risk is considerably increased when concomitant drugs are administered that inhibit metabolism and breakdown via the cytochrome CYP3A4. We report a case of myoglobin-induced acute renal failure secondary to the concomitant use of simvastatin and amiodarone. The risk of rhabdomyolysis is mainly determined by the statin dose; in the case of the concomitant use of CYP3A4 inhibitors, a maximal daily dose of 20 mg is recommended to avoid harmful drug interactions. PMID:27142363

  12. Super vasomol hair dye poisoning.

    PubMed

    Kumar, Praveen A S; Talari, Keerthi; Dutta, T K

    2012-01-01

    Hair dye poisoning is not rare but is an emerging poisoning in India. The main component of hair dye causing toxicity is paraphenylenediamine (PPD). Acute poisoning by PPD causes characteristic severe angioedema of the upper airway accompanied by a swollen, dry, hard, and protruding tongue. Systemic intoxication results in multisystem involvement and can cause rhabdomyolysis, acute renal failure (ARF). PPD consumption is an uncommon cause of ARF. There is no specific antidote for PPD and treatment is mainly supportive. We report a case of suicidal ingestion of hair dye that presented with cervicofascial edema and later developed rhabdomyolysis and ARF. Our patient improved with dialysis and symptomatic management. PMID:22736909

  13. A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel.

    PubMed

    Floyd, J S; Kaspera, R; Marciante, K D; Weiss, N S; Heckbert, S R; Lumley, T; Wiggins, K L; Tamraz, B; Kwok, P-Y; Totah, R A; Psaty, B M

    2012-05-01

    An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may cause other clinically important drug-drug interactions. Medication use in cases of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95% confidence interval (CI), 6.1-143). In a replication effort that used the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), it was found that clopidogrel was used more commonly in patients with rhabdomyolysis receiving cerivastatin (17%) than in those receiving atorvastatin (0%, OR infinity; 95% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in vitro findings suggest that clopidogrel may cause clinically important, dose-dependent drug-drug interactions with other medications metabolized by CYP2C8. PMID:22419147

  14. Management of a mixed overdose of calcium channel blockers, β-blockers and statins

    PubMed Central

    Thakrar, Reena; Shulman, Rob; Bellingan, Geoff; Singer, Mervyn

    2014-01-01

    We describe a case of extreme mixed overdose of calcium channel blockers, β-blockers and statins. The patient was successfully treated with aggressive resuscitation including cardiac pacing and multiorgan support, glucagon and high-dose insulin for toxicity related to calcium channel blockade and β-blockade, and ubiquinone for treating severe presumed statin-induced rhabdomyolysis and muscle weakness. PMID:24907219

  15. 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

  16. Acute kidney injury and dermonecrosis after Loxosceles reclusa envenomation.

    PubMed

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

    2014-07-01

    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

  17. Right bundle branch block: an uncommon cardiotoxic manifestation of hair dye poisoning-a case report.

    PubMed

    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

  18. 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…

  19. Expanding the phenotype of GMPPB mutations.

    PubMed

    Cabrera-Serrano, Macarena; Ghaoui, Roula; Ravenscroft, Gianina; Johnsen, Russell D; Davis, Mark R; Corbett, Alastair; Reddel, Stephen; Sue, Carolyn M; Liang, Christina; Waddell, Leigh B; Kaur, Simranpreet; Lek, Monkol; North, Kathryn N; MacArthur, Daniel G; Lamont, Phillipa J; Clarke, Nigel F; Laing, Nigel G

    2015-04-01

    Dystroglycanopathies are a heterogeneous group of diseases with a broad phenotypic spectrum ranging from severe disorders with congenital muscle weakness, eye and brain structural abnormalities and intellectual delay to adult-onset limb-girdle muscular dystrophies without mental retardation. Most frequently the disease onset is congenital or during childhood. The exception is FKRP mutations, in which adult onset is a common presentation. Here we report eight patients from five non-consanguineous families where next generation sequencing identified mutations in the GMPPB gene. Six patients presented as an adult or adolescent-onset limb-girdle muscular dystrophy, one presented with isolated episodes of rhabdomyolysis, and one as a congenital muscular dystrophy. This report expands the phenotypic spectrum of GMPPB mutations to include limb-girdle muscular dystrophies with adult onset with or without intellectual disability, or isolated rhabdomyolysis. PMID:25681410

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

    PubMed

    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

  1. 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

  2. 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

  3. 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

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

    PubMed

    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

  5. Monitor lizard bite-induced acute kidney injury--a case report.

    PubMed

    Vikrant, Sanjay; Verma, Balbir Singh

    2014-04-01

    Envenomations by venomous lizards are rare. Monitor lizard bite-induced acute kidney injury (AKI) is a previously unreported complication in humans. A 55-year-old female was bitten on her right leg during farming activity by a monitor lizard (Varanus bengalensis). The patient experienced severe local pain and bleeding from the wound, coagulopathy, hemolysis, rhabdomyolysis, sepsis, and AKI. Patient was treated with supportive care and peritoneal dialysis but succumbed to a sudden cardiac arrest. Post mortem kidney biopsy revealed pigment induced-acute tubular injury. AKI after monitor lizard envenomation is caused by acute tubular injury in the setting of intravascular hemolysis, rhabdomyolysis and sepsis. Coagulopathy and direct nephrotoxicity may be the other contributory factors in causing AKI. PMID:24341640

  6. Acute kidney injury after massive attack of Africanised bees.

    PubMed

    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

  7. Clinically symptomatic heterozygous carnitine palmitoyltransferase II (CPT II) deficiency.

    PubMed

    Joshi, Pushpa Raj; Deschauer, Marcus; Zierz, Stephan

    2012-12-01

    Two symptomatic patients with heterozygous carnitine palmitoyltransferase II (CPT II) deficiency are reported. Patient 1, a 21-year-old female professional tennis player, suffered from exercise-induced attacks of muscle pain, burning sensations and proximal weakness. Patient 2, a 30-year-old male amateur marathon runner developed muscle cramps and rhabdomyolysis upon extensive exercise and insolation-induced fever. In both patients, the common p.S113L mutation was found in heterozygote state. No second mutation could be found upon sequencing of all the exons of CPT2 gene including exon-intron boundaries. Biochemically, residual CPT activity in muscle homogenate upon inhibition by malonyl-CoA and Triton-X-100 was intermediate between controls and patients with mutations on both alleles. Although CPT II deficiency is an autosomal recessive disorder, the reported patients indicate that heterozygotes might also have typical attacks of myalgia, pareses or rhabdomyolysis. PMID:23184072

  8. A potentially life-threatening complication of university orientation activities

    PubMed Central

    Leung, Ling Pong

    2012-01-01

    BACKGROUND: This case report describes a university student who participated in an orientation activity and developed exertional rhabdomyolysis. METHODS: With prompt intravenous volume expansion started in the accident and emergency department, he made an uneventful recovery despite a marked elevation of creatine kinase. The riskfactors of developing exertional rhabdomyolysis were reviewed. Suggestions based on these risk factors were made to the organizers of such orientation programmes. RESULTS: He was discharged on day 6. On follow-up on day 8 after presentation at theaccident and emergency department, the CK level was 46 000 U/L and it fell to 2600 U/L in another 2 weeks. On follow-up 3 weeks after the incident, he remained well without symptoms. CONCLUSION: For the clinicians, once rhadbomyolysis is suspected or diagnosed, intravenous fluid therapy with a crystalloid should be initiated as soon as possible to prevent the occurrence of acute renal faiure. PMID:25215042

  9. [Demographics, clinical features, treatments, and outcomes of patients who were transferred to emergency facilities in Japan after consuming dangerous drugs].

    PubMed

    Kamijo, Yoshito

    2015-09-01

    We conducted a multicenter survey of patients who were transported to emergency facilities in Japan from January 2006 to December 2012 after consuming dangerous drugs. Participants were 518 patients. Harmful behavior was observed at the scene of poisoning for about 10% of patients, including violence to others, and traffic accidents. Some patients had physical complications such as rhabdomyolysis, renal dysfunction, and hepatic dysfunction. Of the 182 patients admitted to hospitals, 29 needed respirators and 21 were hospitalized for ≥ 7 days. Although most patients completely recovered, consuming dangerous drugs can result in physical complications including rhabdomyolysis, as well as physical or neuropsychiatric symptoms, which may require active interventions such as respirator use or prolonged hospitalization. PMID:26394510

  10. [DRESS syndrome induced by ciprofloxacine].

    PubMed

    Sahnoun, Rym; El Aïdli, Sihem; Zaïem, Ahmed; Lakhoua, Ghozlane; Kastalli, Sarrah; Daghfous, Riadh

    2015-04-01

    The Drug rash with hypereosinophilia and systemic symptoms (DRESS) syndrome, or hypersensitivity syndrome, is a severe drug-induced hypersensitivity syndrome. It has been exceptionally described with ciprofloxacin. We report a 47-year-old-woman who developed DRESS syndrome, 2 days after taking ciprofloxacin for a urinary infection. She had a generalized maculopapular rash, severe rhabdomyolysis, liver involvement, renal failure and hypereosinophilia. Clinical symptoms had completely resolved after ciprofloxacin withdrawal. Renal failure has decrease after short corticosteroid treatment. PMID:25680964

  11. Case Report: Elevated CPK, an indicator of idiopathic inflammatory myopathy?

    PubMed Central

    Khan, Hina N.; Jilani, Usman; Arora, Shitij

    2016-01-01

    Polymyositis is a rare disease with incidence rates at about 1 per 100,000 people annually. In this case report we will review a case of proximal muscle weakness with an elevated creatine phosphokinase that was initially misdiagnosed twice as rhabdomyolysis. Therefore, emphasizing that idiopathic inflammatory myopathy is a potential cause of myasthenia that must be considered in the differential. The case will also describe the current treatment and treatment response in polymyositis.

  12. 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

  13. Paraphenylenediamine: Blackening more than just hair.

    PubMed

    Gude, Dilip; Bansal, Dharam Pal; Ambegaonkar, Rahul; Prajapati, Jayaram

    2012-06-01

    Paraphenylenediamine is an important constituent of hair dye toxicity of which one could herald fatal complications such as rhabdomyolysis, renal failure, angioneurotic edema, and respiratory failure. We present a case of hair dye poisoning that presented with respiratory distress due to laryngeal edema and later developed trismus, subclinical tetany, apnea, and conduction abnormality on electrocardiogram. This case report highlights the need for a thorough toxicological review of the components of any ingested substance. PMID:23626641

  14. Case Report: Elevated CPK, an indicator of idiopathic inflammatory myopathy?

    PubMed

    Khan, Hina N; Jilani, Usman; Arora, Shitij

    2016-01-01

    Polymyositis is a rare disease with incidence rates at about 1 per 100,000 people annually. In this case report we will review a case of proximal muscle weakness with an elevated creatine phosphokinase that was initially misdiagnosed twice as rhabdomyolysis. Therefore, emphasizing that idiopathic inflammatory myopathy is a potential cause of myasthenia that must be considered in the differential. The case will also describe the current treatment and treatment response in polymyositis. PMID:27540467

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

    PubMed

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

    2015-01-01

    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

  17. Active safety monitoring of newly marketed medications in a distributed data network: application of a semi-automated monitoring system.

    PubMed

    Gagne, J J; Glynn, R J; Rassen, J A; Walker, A M; Daniel, G W; Sridhar, G; Schneeweiss, S

    2012-07-01

    We developed a semi-automated active monitoring system that uses sequential matched-cohort analyses to assess drug safety across a distributed network of longitudinal electronic health-care data. In a retrospective analysis, we show that the system would have identified cerivastatin-induced rhabdomyolysis. In this study, we evaluated whether the system would generate alerts for three drug-outcome pairs: rosuvastatin and rhabdomyolysis (known null association), rosuvastatin and diabetes mellitus, and telithromycin and hepatotoxicity (two examples for which alerting would be questionable). Over >5 years of monitoring, rate differences (RDs) in comparisons of rosuvastatin with atorvastatin were -0.1 cases of rhabdomyolysis per 1,000 person-years (95% confidence interval (CI): -0.4, 0.1) and -2.2 diabetes cases per 1,000 person-years (95% CI: -6.0, 1.6). The RD for hepatotoxicity comparing telithromycin with azithromycin was 0.3 cases per 1,000 person-years (95% CI: -0.5, 1.0). In a setting in which false positivity is a major concern, the system did not generate alerts for the three drug-outcome pairs. PMID:22588606

  18. Safety of statins.

    PubMed

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

    2013-07-01

    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

  19. [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

  20. Free heme pool and activity of key enzyme of heme synthesis in the rat liver under action of agents affecting reduced glutathione level.

    PubMed

    Barannik, T V; Inshina, N M; Kaliman, P A

    2005-01-01

    The decrease of GSH level in the rat liver was found to be accompanied by an increase of tryptophan 2,3-dioxygenase (TDO) heme saturation during first hours after HgCl2, phenylhydrazine (Ph) injection or rhabdomyolysis (the coefficient of correlation -0.978). The activity of the key enzyme of heme synthesis--5-aminolevulinate synthase (ALAS) was 2.5-fold increased in the first hours after Ph injection and rhabdomyolysis. Glutathione injection in vivo as well as CdCl2 caused the increase of GSH content and the inhibition of ALAS. The coefficient of correlation for GSH content and ALAS activity under the action of agents altering both these parameters (CdCl2, Ph, GSH injection and rhabdomyolysis) is 0.938. Taking into account the presence of heme regulatory motif with conserved cystein in many proteins, including ALAS and TDO (accession number in SwissProt database AAH61793 and P21643, respectively), the link between alterations of GSH content, ALAS activity and heme saturation of TDO in the rat liver could be proposed. The further experiments should be performed in order to elucidate the mechanisms of GSH level influence on free heme pool formation in the liver cells. PMID:16846079

  1. 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

  2. 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

  3. Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?

    PubMed

    Sanchis-Gomar, F; Pareja-Galeano, H; Perez-Quilis, C; Santos-Lozano, A; Fiuza-Luces, C; Garatachea, N; Lippi, G; Lucia, A

    2015-01-01

    Intensive muscular activity can trigger oxidative stress, and free radicals may hence be generated by working skeletal muscle. The role of the enzyme xanthine oxidase as a generating source of free radicals is well documented and therefore is involved in the skeletal muscle damage as well as in the potential transient cardiovascular damage induced by high-intensity physical exercise. Allopurinol is a purine hypoxanthine-based structural analog and a well-known inhibitor of xanthine oxidase. The administration of the xanthine oxidase inhibitor allopurinol may hence be regarded as promising, safe, and an economic strategy to decrease transient skeletal muscle damage (as well as heart damage, when occurring) in top-level athletes when administered before a competition or a particularly high-intensity training session. Although continuous administration of allopurinol in high-level athletes is not recommended due to its possible role in hampering training-induced adaptations, the drug might be useful in non-athletes. Exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals participating in a type of intense exercise to which they are not accustomed. This condition can cause exercise-related myoglobinuria, thus increasing the risk of acute renal failure and is also associated with sickle cell trait. In this manuscript, we have reviewed the recent evidence about the effects of allopurinol on exercise-induced muscle damage. More research is needed to determine whether allopurinol may be useful for preventing not only exertional rhabdomyolysis and acute renal damage but also skeletal muscle wasting in critical illness as well as in immobilized, bedridden, sarcopenic or cachectic patients. PMID:25181966

  4. [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

  5. Statins and myotoxicity: a therapeutic limitation.

    PubMed

    Tiwari, Atul; Bansal, Vinay; Chugh, Anita; Mookhtiar, Kasim

    2006-09-01

    Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors represent the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia implicated in the pathogenesis of coronary heart disease and atherosclerosis. However, the popular profile of statins in terms of efficacy has been maligned by its adverse events. The myotoxicity, ranging from mild myopathy to serious rhabdomyolysis, associated with HMG-CoA reductase inhibitors, during treatment of hypercholesterolaemia is of paramount importance. Rhabdomyolysis is a rare but idiosyncratic muscle wasting disorder of different etiologies. Statin-associated rhabdomyolysis causes skeletal muscle injury by self-perpetuating events leading to fatal irreversible renal damage through a series of biochemical reactions. Preferential distribution and action of statins in liver could be the key to minimise myotoxicity concerns. Hepato-specific distribution of statins is governed by various factors such as physicochemical properties, pharmacokinetic properties and selective transporter-mediated uptake in liver rather in extrahepatic cells. The interactions of statins with concomitant drugs of different classes merit attention for their safety profile. Although pharmacokinetic as well as pharmacodynamic interactions have been implicated in pathophysiology of statin-induced muscle wasting, the underlying mechanism is not clearly understood. Besides, pharmacokinetic and phramcodynamic factors, statin-associated myotoxcity may also implicate pharmacogenomic factors. The pharmacogenomics characterised by CYP polymorphism and other genetic factors is responsible for inter-individual variations to efficacy and tolerability of statins. The pathophysiological mechanisms may include statin-induced differences in cholesterol:phospholipid ratio, isoprenoid levels, small GTP binding proteins and apoptosis. However, the present understanding of pathophysiological mechanisms, does not offer a reliable

  6. Toxic Myopathies

    PubMed Central

    Pasnoor, Mamatha; Barohn, Richard J.; Dimachkie, Mazen M.

    2014-01-01

    Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, as they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features and possible underlying cellular mechanisms. PMID:25037083

  7. Search for rare liver diseases: the case of glycosylation defects mimicking Wilson Disease.

    PubMed

    Socha, Piotr; Vajro, Pietro; Lefeber, Dirk; Adamowicz, Maciej; Tanner, Stuart

    2014-09-01

    Pediatric hepatology appears to be a very specific field of paediatrics which deals mainly with rare diseases although clinical features can be commonly found - like increased activity of transaminases. Some of these rare diseases like Wilson disease are commonly looked for and recently Wilsonian like phenotypes have been described which additionally presented with abnormal glycosylation of the plasma protein transferrin. In a subgroup of those patients with specific additional clinical symptoms (cleft uvula, low blood sugar, rhabdomyolysis and dilated cardiomyopathy) phosphoglucomutase 1 deficiency was identified. We recommend screening for abnormal glycosylation of the plasma protein transferrin in children with unexplained liver injury. PMID:24972800

  8. Thermal dysregulation in Prader-Willi syndrome: a potentially fatal complication in adolescence, not just in infancy.

    PubMed

    McVea, Steven; Thompson, Andrew James; Abid, Noina; Richardson, Julie

    2016-01-01

    A 13-year-old boy with a background of Prader-Willi syndrome (PWS) was admitted to the regional paediatric intensive care unit, with community-acquired pneumonia. Despite a week of intravenous antibiotics, resolution of inflammatory markers and resolving consolidation on radiograph, he remained feverish. Fever of unknown origin investigations were negative and he was diagnosed with central thermal dysregulation secondary to hypothalamic dysfunction in PWS. Following a hyperpyrexia period, secondary rhabdomyolysis and renal failure developed. This was successfully managed with active cooling, ventilation and haemofiltration. After weaning from haemofiltration, the patient was successfully extubated to non-invasive respiratory support. PMID:27358096

  9. [Dangerous drugs: products containing synthetic chemicals].

    PubMed

    Kamijo, Yoshito

    2016-02-01

    When the patients poisoned with "dangerous drugs", that is, products containing synthetic chemicals such as synthetic cannabinoids and cathinones, are transferred to the emergency facilities, the chemicals really consumed cannot be determined there. So, supportive care may be the most important strategy for treating them. For example, those with serious consciousness disturbance should be supported with ventilator after intubation. Those with remarkable excitatory CNS or sympathetic symptoms, benzodiazepines such as diazepam and midazolam, should be administered. Those with hallucination or delusion, antipsychotics such as haloperidol or risperidone should be administered. Those with rhabdomyolysis, hypermyoglobinemia and acute kidney injury, intravenous fluids and hemodialysis should be introduced. PMID:26915246

  10. Acute renal failure in the "Comrades Marathon" runners.

    PubMed

    Seedat, Y K; Aboo, N; Naicker, S; Parsoo, I

    This study investigated the clinical and biochemical features of acute renal failure in marathon runners. Over a period of 18 years (1969-1986), 19 patients were admitted to the renal unit. The histories and biochemical data of 4 patients seen in 1986 are described. The pathophysiology of acute renal failure is multifactorial and is the combined effect of rhabdomyolysis, dehydration, hypotension, nonsteroidal anti-inflammatory drugs, and hyperuricaemia. Efforts to correct dehydration have resulted in a decrease in the incidence of acute renal failure. The use of nonsteroidal anti-inflammatory drugs is to be deprecated and efforts should be made to publicize this harmful effect. PMID:2485484

  11. The unsuspected killer: Liquefied petroleum gas overexposure in South Africa.

    PubMed

    Sampson, L W J; van der Schyff, N; Cupido, C

    2015-02-01

    A 21-year-old woman with no past medical history of note was found unconscious together with five of her family members after prolonged exposure to liquefied petroleum gas. She was admitted to the intensive care unit at Victoria Hospital, Wynberg, Cape Town, South Africa, following resuscitation for pulseless electrical activity. On examination the following was found: coma without focal neurology; shock requiring fluid resuscitation and adrenaline; probable pneumonitis or aspiration pneumonia; acute rhabdomyolysis with severe metabolic acidosis; and raised serum K+. A carboxyhaemoglobin test was unable to confirm or exclude carbon monoxide poisoning. PMID:26242505

  12. Flank pain and acute renal failure after binge drinking: a growing concern?

    PubMed

    Calviño, Jesús; Bravo, Juan; Millán, Beatriz; Gonzalez-Tabares, Lourdes

    2013-01-01

    We describe two cases of acute renal failure (ARF) after heavy alcohol intake. Remarkable features included a few days latency period after binge drinking, acute flank pain resembling pyelonephritis, lack of rhabdomyolysis or liver injury, and concomitant intake of non-steroidal anti-inflammatory drugs (NSAIDs). Renal function improved with conservative treatment, and despite NSAIDs use, hyperkalemia was not clinically significant. Since binge drinking is common in the Western population, early recognition of this syndrome may be helpful when examining a patient with flank pain and ARF of unclear etiology. PMID:23477481

  13. Invasive pulmonary aspergillosis in a patient presenting with idiopathic systemic capillary leak syndrome

    PubMed Central

    Hayama, Manabu; Shime, Nobuaki; Mio, Tadashi

    2014-01-01

    A 54-year-old man presented to our emergency department with fever and dyspnoea. He required vigorous haemodynamic support and mechanical ventilation for hypotensive distributive shock with hypoalbuminaemia, haemoconcentration, rhabdomyolysis and acute renal failure, consistent with idiopathic systemic capillary leak syndrome. Left lung consolidation and hypoxaemia were observed 6 days after admission. Sputum smear revealed the presence of acute angled branching hyphae, consistent with a diagnosis of invasive pulmonary aspergillosis. Antifungal therapy was administered and mechanical ventilation discontinued on day 66. The patient recovered and was discharged from the hospital on day 185. PMID:24859554

  14. [Pharmacovigilance update].

    PubMed

    Livio, F

    2013-01-01

    Main pharmacovigilance updates in 2012 are reviewed here. Dabigatran: elderly patients with renal failure are at higher risk of bleeding. Dual renin-angiotensin-aldosterone system blockade comprising aliskiren is harmful. Incretins: low risk of acute pancreatitis. Interaction between fusidic acid and statins: many reports of rhabdomyolysis. Interactions between boceprevir/telaprevir and antiretroviral therapies: complex, but manageable. Citalopram, ondansetron: maximum recommended doses are reduced. Atomoxetine: significant increase in blood pressure and heart rate in a fraction of exposed patients. Agomelatine: elevated liver enzymes are common. Fingolimod: bradycardia and heart blocks after first dose - stronger safety recommendations regarding use in patients with heart conditions and strengthened cardiovascular monitoring. PMID:23367709

  15. 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

  16. Therapeutic plasma exchange as treatment for propofol infusion syndrome.

    PubMed

    Levin, Phillip D; Levin, Valentin; Weissman, Charles; Sprung, Charles L; Rund, Deborah

    2015-10-01

    Propofol infusion syndrome (PRIS), a rare complication of propofol sedation, is associated with high mortality. There is no specific therapy. A 16-year-old with head injury and status epilepticus is described. Three days after seizure resolution, whilst receiving propofol, he developed severe lactic acidosis, rhabdomyolysis, and hemodynamic instability. Suspected PRIS was treated with a single session of therapeutic plasma exchange (TPE). This was associated with immediate improvement in hemodynamic status, resolution of lactic acidosis within 24 h, normalization of CPK over 10 days, and a subsequent full recovery. TPE is suggested as a novel therapy for PRIS. PMID:25619501

  17. Case Series of Synthetic Cannabinoid Intoxication from One Toxicology Center

    PubMed Central

    Katz, Kenneth D.; Leonetti, Adam L.; Bailey, Blake C.; Surmaitis, Ryan M.; Eustice, Eric R.; Kacinko, Sherri; Wheatley, Scott M.

    2016-01-01

    Synthetic cannabinoid use has risen at alarming rates. This case series describes 11 patients exposed to the synthetic cannabinoid, MAB-CHMINACA who presented to an emergency department with life-threatening toxicity including obtundation, severe agitation, seizures and death. All patients required sedatives for agitation, nine required endotracheal intubation, three experienced seizures, and one developed hyperthermia. One developed anoxic brain injury, rhabdomyolysis and died. A significant number were pediatric patients. The mainstay of treatment was aggressive sedation and respiratory support. Synthetic cannabinoids pose a major public health risk. Emergency physicians must be aware of their clinical presentation, diagnosis and treatment. PMID:27330661

  18. Death from a possible anaphylactic reaction to ecstasy.

    PubMed

    Sauvageau, Anny

    2008-02-01

    Ecstasy (3,4 methylenedioxymethamphetamine, or MDMA) is a recreational drug widely used among young people in discos or rave parties (1,2). MDMA is taken because it gives a feeling of euphoria, enhances energy and sociability, and heightens sensations and sexual arousal. However, several side effects have been described: headache, nausea, anorexia, xerostomia, insomnia, myalgia, trismus, and bruxism (2,3). More serious complications have also been reported, sometimes even leading to death: hyperthermia, disseminated intravascular coagulopathy, rhabdomyolysis, acute renal failure, liver failure, and water intoxication (2,3). We report the unusual case of a death due to an apparent allergic reaction following ecstasy ingestion. PMID:18259964

  19. MR imaging of urgent inflammatory and infectious conditions affecting the soft tissues of the musculoskeletal system.

    PubMed

    Yu, Joseph S; Habib, Paula

    2009-07-01

    Soft tissue infections and inflammatory conditions of the musculoskeletal system are a group of disorders commonly seen by emergency room physicians and radiologists. Many of these entities can either be limb- or life-threatening. Magnetic resonance imaging is currently the best imaging modality to evaluate these conditions. In this review, the characteristic imaging findings of cellulitis, abscess formation, necrotizing fasciitis, pyomyositis, diabetic ischemic infarction, acute and exertional compartment syndromes, and rhabdomyolysis will be emphasized as well as imaging factors that can help to differentiate these disorders. PMID:19132424

  20. 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

  1. Acute poisoning with Tricholoma equestre.

    PubMed

    Anand, Jacek Sein; Chwaluk, Paweł; Sut, Michał

    2009-01-01

    Four cases, including three adults and one child, suffering from acute poisoning with Tricholoma equestre were described. The patients had eaten from 100 to 400 grams of the mushroom within a few consecutive meals. After consuming about 1000 grams of Tricholoma equestre for 3-4 days, the subjects developed fatigue, muscle weakness, myalgia, and in two cases acute respiratory failure with the need of respiratorotherapy. Maximal serum CK was 48136 U/L in the adults and 306 U/L in children. Maximal serum levels of AST and ALT were 802 U/L and 446 U/L in adults and 39 U/L, and 56 U/L in a child. All routine biochemical tests were within normal range. No other causes of rhabdomyolysis such as parasitic or viral infections, immune diseases, trauma or exposure to medications were found. Patient, aged 72 yrs., who developed acute respiratory failure, died in the second day of hospitalization. In other patients all the above mentioned symptoms and biochemical abnormalities disappeared from 2 to 3 weeks of hospitalization. Physicians should be aware of the possibility of appearance of rhabdo-myolysis after repeated consumption of large quantities of Tricholoma equestre. PMID:19788144

  2. Statin-induced myopathies.

    PubMed

    Tomaszewski, Michał; Stępień, Karolina M; Tomaszewska, Joanna; Czuczwar, Stanisław J

    2011-01-01

    Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for atherosclerosis, and therefore they are frequently prescribed medications. The most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis or rhabdomyolysis. Clinical trials commonly define statin toxicity as myalgia or muscle weakness with creatine kinase (CK) levels greater than 10 times the normal upper limit. Rhabdomyolysis is the most severe adverse effect of statins, which may result in acute renal failure, disseminated intravascular coagulation and death. The exact pathophysiology of statin-induced myopathy is not fully known. Multiple pathophysiological mechanisms may contribute to statin myotoxicity. This review focuses on a number of them. The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk. Currently, the only effective treatment of statin-induced myopathy is the discontinuation of statin use in patients affected by muscle aches, pains and elevated CK levels. PMID:22001973

  3. Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

    PubMed Central

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

    2014-01-01

    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

  4. 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

  5. [A case of fatal pneumonia caused by Legionella pneumophila serogroup 6 developed after drowning in a public bath].

    PubMed

    Tokuda, H; Yahagi, N; Kasai, S; Kitamura, S; Otsuka, Y

    1997-02-01

    A 57-year-old male was admitted to our hospital because of high fever, productive cough and dyspnea. Six days prior to admission he had an episode of drowning in a public bath. On admission chest X-ray showed wide-spread pneumonia causing severe respiratory distress for which mechanical ventilatory support was started. Despite chemotherapy including erythromycin and rifampicin his condition continued to deteriorate. Chemistry showed marked elevation of CPK and findings of acute renal failure. He eventually passed away with septic shock. During the course Legionellae remained negative with culture of broncho-alveolar lavage fluid. L. pneumophila serogroup 1 (SG1) antigen in the urine was not detected, and no elevation of serum antibody titer was noted. Culture of the material obtained from the lung abscess at autopsy revealed L. pneumophila SG6 and serum antibody titer against SG6 also was found to be extremely high. With this evidence we concluded that this case of pneumonia was caused by L. pneumophila SG6. We believe this is the first reported case of the SG6 pneumonia in Japan. Another remarkable feature of this case was massive rhabdomyolysis pathologically confirmed after autopsy. Although the pathogenesis of this process has not been clarified, there are several case reports of rhabdomyolysis complicated with Legionnair's disease in the past. Therefore, we should bear in mind and pay careful attention while coping with this disease. PMID:9077075

  6. Measurement of serum myoglobin concentrations in horses by immunodiffusion.

    PubMed

    Holmgren, N; Valberg, S

    1992-06-01

    Quantitative immunodiffusion in one dimension was performed in 6-mm Duran tubes containing a 1% Nobel agar solution and various dilutions of antisera. A series of dilutions of pure myoglobin in equine sera as well as plasma from horses with rhabdomyolysis were tested. Standard curves were prepared of the migration distance of the formed precipitate from the meniscus of the gel after 3, 6, 12, and 24 hours. The clearest line of precipitate was formed with a 1:20 dilution of antisera in agar. Standard curves were nonlinear and plasma myoglobin could be detected at 2 micrograms of myoglobin/ml or greater. The test was optimal, with an error of 5.6%, when read at 24 hours at approximately 25 C. Tubes with agar could be stored for 6 months at 4 C without affecting the accuracy of the test. The specificity of myoglobin for skeletal or cardiac muscle, and its rapid clearance from serum after muscle necrosis, make it ideally suited for evaluating acute muscle damage and for testing the susceptibility of horses for rhabdomyolysis following an exercise test. PMID:1626787

  7. Inhibition of cytochrome P450 2E1 and activation of transcription factor Nrf2 are renoprotective in myoglobinuric acute kidney injury.

    PubMed

    Wang, Zhe; Shah, Sudhir V; Liu, Hua; Baliga, Radhakrishna

    2014-08-01

    Rhabdomyolysis accounts for ∼10% of acute kidney injuries. In glycerol-induced myoglobinuric acute kidney injury, we found an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear protein, a key redox-sensitive transcription factor, and Nrf2-regulated genes and proteins including upregulation of heme oxygenase-1. In in vitro studies, pretreatment of LLC-PK1 cells with an activator of Nrf2 before myoglobin exposure significantly decreased oxidant generation and cytotoxicity, whereas Nrf2 inhibition and gene silencing exacerbated the injury. Chlormethiazole, a specific CYP2E1 transcription inhibitor, prevented an increase in catalytic iron in the kidneys, decreased oxidative stress, blocked nuclear translocation of the Nrf2 protein, decreased heme oxygenase-1 upregulation, and provided functional and histological protection against acute kidney injury. CYP2E1 inhibitors and gene silencing in renal tubular epithelial cells significantly decreased reactive oxygen species generation and provided marked protection against myoglobin-induced cytotoxicity. Thus, during CYP2E1-induced oxidative stress, the transcription factor Nrf2 has a pivotal role in the early adaptive response. Inhibition of CYP2E1 coupled with the prior induction of Nrf2 may be a valuable tool to reduce CYP2E1-mediated rhabdomyolysis-induced acute kidney injury. PMID:24717297

  8. Musculoskeletal adverse drug reactions: a review of literature and data from ADR spontaneous reporting databases.

    PubMed

    Conforti, Anita; Chiamulera, Christian; Moretti, Ugo; Colcera, Sonia; Fumagalli, Guido; Leone, Roberto

    2007-01-01

    The musculoskeletal system can be a target organ for adverse drug reactions (ADRs). Drug-induced muscle, bone or connective tissue injuries may be due to, i), primary direct drug action, or, ii), undirected consequence of generalized drug-induced disease. Musculoskeletal ADRs may be only temporarily disabling, such as muscle cramps, as well as in other cases may be serious and life-threatening, such as rhabdomyolysis. In the last few years there has been an increasing awareness of musculoskeletal ADRs. Some recent drug safety issues dealt with serious or uncommon musculoskeletal reactions like rhabdomyolysis associated to statins and tendon rupture associated to fluoroquinolones. In this review, we firstly selected those drug classes having a significantly high percentage of musculoskeletal disorder reports in the WHO adverse drug reaction database, maintained by the Uppsala Monitoring Centre. Secondly, the different musculoskeletal ADRs were closely analyzed through the data obtained from an Italian interregional ADRs spontaneous reporting database. The findings on drugs associated to different musculoskeletal disorders, have been integrated with a review of the epidemiological data available in the literature. For the most involved drugs (HMG-CoA reductase inhibitors, fluoroquinolones, corticosteroids, bisphosphonates, retinoids) the underlying musculoskeletal ADR mechanisms were also reviewed and discussed. PMID:18690950

  9. Cocaine and kidney injury: a kaleidoscope of pathology

    PubMed Central

    Goel, Narender; Pullman, James M.; Coco, Maria

    2014-01-01

    Cocaine is abused worldwide as a recreational drug. It is a potent activator of the sympathetic nervous system leading to intense vasoconstriction, endothelial dysfunction, oxidative stress, platelet activation and decrease in prostaglandins E2 and prostacyclin. Cocaine can lead to widespread systemic adverse effects such as stroke, myocardial infarction, arterial dissection, vascular thrombosis and rhabdomyolysis. In human and rat kidneys, cocaine has been associated with glomerular, tubular, vascular and interstitial injury. It is not uncommon to diagnose cocaine-related acute kidney injury (AKI), malignant hypertension and chronic kidney disease. Cocaine abuse can lead to AKI by rhabdomyolysis, vasculitis, infarction, thrombotic microangiopathy and malignant hypertension. It is reported that 50–60% of people who use both cocaine and heroin are at increased risk of HIV, hepatitis and additional risk factors that can cause kidney diseases. While acute interstitial nephritis (AIN) is a known cause of AKI, an association of AIN with cocaine is unusual and seldom reported. We describe a patient with diabetes mellitus, hypertension and chronic hepatitis C, who presented with AKI. Urine toxicology was positive for cocaine and a kidney biopsy was consistent with AIN. Illicit drugs such as cocaine or contaminants may have caused AIN in this case and should be considered in the differential diagnosis of causes of AKI in a patient with substance abuse. We review the many ways that cocaine adversely impacts on kidney function. PMID:25859366

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

    PubMed

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

    2014-01-01

    Sea snakes are highly venomous and inhabit tropical waters of the Indian and Pacific Oceans. Enhydrina schistosa is a common species of sea snake that lives in the coastal waters, lagoons, river mouths and estuaries from the Persian Gulf through Sri Lanka and to Southeast Asia. It is considered one of the most aggressive sea snakes in Sri Lanka where fishermen and people wading are at high risk. However, sea snake bites are rarely reported. In this report, we describe three cases where E. schistosa was the offending species. These three patients presented to two hospitals on the west coast of Sri Lanka within the course of 14 months from November 2011 with different degrees of severity of envenoming. The first patient was a 26-year-old fisherman who developed severe myalgia with very high creatine kinase (CK) levels lasting longer than 7 days. The second patient was a 32-year-old fisherman who developed gross myoglobinuria, high CK levels and hyperkalaemia. Both patients recovered and their electromyographic recordings showed myopathic features. The nerve conduction and neuromuscular transmission studies were normal in both patients suggesting primary myotoxic envenoming. The third patient was a 41-year-old man who trod on a sea snake in a river mouth and developed severe myalgia seven hours later. He had severe rhabdomyolysis and died three days later due to cardiovascular collapse. In conclusion, we confirm that E. schistosa is a deadly sea snake and its bite causes severe rhabdomyolysis. PMID:24239658

  11. 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.

  12. Opioid overdose with gluteal compartment syndrome and acute peripheral neuropathy

    PubMed Central

    Adrish, Muhammad; Duncalf, Richard; Diaz-Fuentes, Gilda; Venkatram, Sindhaghatta

    2014-01-01

    Patient: Male, 42 Final Diagnosis: Gluteal compartment syndrome • acute peripheral nauropathy Symptoms: — Medication: — Clinical Procedure: — Specialty: Critical Care Medicine Objective: Management of emergency care Background: Heroin addiction is common, with an estimated 3.7 million Americans reporting to have used it at some point in their lives. Complications of opiate overdose include infection, rhabdomyolysis, respiratory depression and central or peripheral nervous system neurological complications. Conclusions: We present a 42-year-old male admitted after heroin use with heroin-related peripheral nervous system complication preceded by an acute gluteal compartment syndrome and severe rhabdomyolysis. Case Report: Early diagnosis and surgical intervention of the compartment syndrome can lead to full recovery while any delay in management can be devastating and can lead to permanent disability. The presence of peripheral nervous system injuries may portend a poor prognosis and can also lead to long term disability. Careful neurological evaluation for signs and symptoms of peripheral nervous system injuries is of paramount importance, as these may be absent at presentation in patients with opioid overdose. There is a potential risk of delaying a necessary treatment like fasciotomy in these patients by falsely attributing clinical symptoms to a preexisting neuropathy. Early EMG and nerve conduction studies should be considered when the etiology of underlying neurological weakness is unclear. PMID:24459539

  13. 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

  14. Tarui disease and distal glycogenoses: clinical and genetic update.

    PubMed

    Toscano, A; Musumeci, O

    2007-10-01

    Phosphofructokinase deficiency (Tarui disease) was the first disorder recognized to directly affect glycolysis. Since the discovery of the disease, in 1965, a wide range of biochemical, physiological and molecular studies have greatly contributed to our knowledge concerning not only phosphofructokinase function in normal muscle but also on the general control of glycolysis and glycogen metabolism. Studies on phosphofructokinase deficiency vastly enriched the field of glycogen storage diseases, making a relevant improvement also in the molecular genetic area. So far, more than one hundred patients have been described with prominent clinical symptoms characterized by muscle cramps, exercise intolerance, rhabdomyolysis and myoglobinuria, often associated with haemolytic anaemia and hyperuricaemia. The muscle phosphofructokinase gene is located on chromosome 12 and about 20 mutations have been described. Other glycogenoses have been recognised in the distal part of the glycolytic pathway: these are infrequent but some may induce muscle cramps, exercise intolerance and rhabdomyolysis. Phosphoglycerate Kinase, Phosphoglycerate Mutase, Lactate Dehydrogenase, beta-Enolase and Aldolase A deficiencies have been described as distal glycogenoses. From the molecular point of view, the majority of these enzyme deficiencies are sustained by "private" mutations. PMID:18421897

  15. Disaster nephrology: medical perspective.

    PubMed

    Atef-Zafarmand, Alireza; Fadem, Steve

    2003-04-01

    Disaster medicine is an extension of emergency medicine involving mass casualties and use of the best available techniques in search and rescue. To achieve the best results extensive predisaster preparedness is mandatory. Earthquakes have caused the loss of more than 1 million lives in the 20th century. Evidence-based medicine confirms that these deaths were mostly preventable based on experience in developed countries. The key to success is implementing building codes and structural reinforcement. In earthquakes as well as in collapse of buildings in bomb blasts, loss of life is either because of the direct effect of trauma or to the metabolic consequences of rhabdomyolysis and complications of its management. Hyperkalemia and infection are the commonest causes of death in victims who survive the direct effect of trauma. Acute renal failure, a grave complication of rhabdomyolysis, is mostly preventable by timely rehydration and bicarbonate therapy. Mannitol therapy can be very efficient in reducing the severity of muscle damage and its sequelae. Fasciotomy can be limb saving if it is done in the early hours, although a firm guideline is still lacking. Although each country is responsible for improving the structure of buildings and organizing an efficient disaster response, national and international organizations in developed countries should give high priority to communicating with developing countries to encourage their preparedness. PMID:12879371

  16. 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

  17. 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 6–12 h 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

  18. 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

  19. Effects of HMG-CoA reductase inhibitors on skeletal muscle: are all statins the same?

    PubMed

    Evans, Marc; Rees, Alan

    2002-01-01

    The 3-hydroxy-3-methyl coenzyme A (HMG-CoA) reductase inhibitors or statins, specifically inhibit the enzyme HMG-CoA in the liver, thereby inhibiting the rate limiting step in cholesterol biosynthesis and so reducing plasma cholesterol levels. Numerous studies have consistently demonstrated that cholesterol lowering with statin therapy reduces morbidity and mortality from coronary heart disease, whilst recent evidence has demonstrated that benefits of statin therapy may also extend into stroke prevention. Since hypercholesterolaemia is a chronic condition, the long-term safety and tolerability of these agents is an important issue. Numerous large-scale clinical trials have consistently demonstrated a positive safety and tolerability profile for statins. Hepatic, renal and muscular systems are rarely affected during statin therapy, with adverse reactions involving skeletal muscle being the most common, ranging from mild myopathy to myositis and occasionally to rhabdomyolysis and death. Postmarketing data supports the positive safety and tolerability profile of statins, with an overall adverse event frequency of less than 0.5% and a myotoxicity event rate of less than 0.1%. The recent withdrawal of cerivastatin from the world market due to deaths from rhabdomyolysis has, however, focused attention on the risk of adverse events and in particular myotoxicity associated with statins. Indeed, initial clinical trial data supports postmarketing data, demonstrating a higher incidence of myotoxicity associated with cerivastatin, particularly when used in combination with fibrates. The potential mechanisms underlying statin-induced myotoxicity are complex with no clear consensus of opinion. Candidate mechanisms include intracellular depletion of essential metabolites and destabilisation of cell membranes, resulting in increased cytotoxicity. Cytochrome P450 3A4 is the main isoenzyme involved in statin metabolism. Reduced activity of this enzyme due to either reduced

  20. 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

  1. [Prevention of coronary heart disease with statins. Which patients profit?].

    PubMed

    Adam, O; Forth, W

    2003-06-19

    Statins are generally considered as safe drugs with a very favorable cost-efficacy-ratio. Calculation of health expenses limits the prescription of statins in primary prevention to persons on high risk (i.e. 20% risk of a coronary infarction within the next 10 years). Prescription of statins in secondary prevention of atherosclerosis is mandatory. Advanced age, impairment of renal function or polypharmacotherapy increase the incidence of severe side-effects, especially myopathy and rhabdomyolysis. These patients should be given statins with lesser risk of these side-effects. Combination of statins with fibrates has attracted public concern, but may be indicated in persons with otherwise not treatable hyperlipidemia. These patients need intensive monitoring, just as patients on other drugs that are metabolized via the enzyme CYP3A4. Patients on statins should get dietary counseling, as an appropriate diet increases the effect of statins. PMID:12891851

  2. Accidental five fold overdose of propofol for induction in a 38-days-old infant undergoing emergency bilateral inguinal hernia repair

    PubMed Central

    Seyedhejazi, Mahin; Abafattash, Ghafur; Taheri, Reza

    2011-01-01

    The induction dose of propofol is higher in younger children (2.9 mg/kg for infants younger than 2 years) than in older children (2.2 mg/kg for children 6-12 years of age). A modest reduction in systolic blood pressure often accompanies bolus administration. The major concern with propofol is the potential for propofol infusion syndrome (lactic acidosis, rhabdomyolysis, cardiac and renal failure), which is generally associated with high-dose infusion for an extended period. We report a 38-days-old male infant underwent emergency bilateral inguinal hernia repair who accidentally received a five-fold dose of propofol for induction of general anesthesia. PMID:22144931

  3. Neuroleptic-induced extrapyramidal symptoms with fever. Heterogeneity of the 'neuroleptic malignant syndrome'.

    PubMed

    Levinson, D F; Simpson, G M

    1986-09-01

    From 39 reported cases of the "neuroleptic malignant syndrome," three groups were identified: those with concurrent medical problems that could cause fever that accompanied the extrapyramidal symptoms; those with medical problems less clearly related to fever; and those without other medical disorders. Dehydration, infection, pulmonary embolus, and rhabdomyolysis were the common complications of untreated extrapyramidal symptoms. Three patients died, all with medical complications. In 14 cases, no medical cause of fever was identified. Hypotheses about mechanisms for fever include psychiatric illness, disruption of dopaminergic aspects of thermoregulation, and peripheral and central effects on muscle contraction leading to excess heat production. Neuroleptic-induced rigidity should be treated vigorously, with prompt discontinuation of neuroleptic therapy and administration of dopamine agonists in severe cases with or without fever. The cases of extrapyramidal symptoms with fever are too heterogeneous to justify the assumption of a unitary and "malignant" syndrome. PMID:2875701

  4. 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

  5. Acute myocardial infarction with multiple coronary thromboses in a young addict of amphetamines and benzodiazepines.

    PubMed

    Al Shehri, Mohammed A; Youssef, Ali A

    2016-07-01

    A 35-year-old man of average build and a smoker, with a background of a psychiatric disorder, was brought by his neighbor to the emergency department after an hour of severe chest pain. Upon arrival at the hospital he had cardiac arrest, was resuscitated, and moved to the catheterization laboratory with inferior, posterior, and lateral myocardial infarction. Coronary angiography showed an unusual thrombosis in multiple coronary branches. Toxicology report showed high levels of amphetamines and benzodiazepines in the patient's original blood sample. The patient was kept under ventilation for 18 days, with difficult recovery due to severe withdrawal manifestations, ventilation acquired pneumonia, and rhabdomyolysis inducing acute renal failure. The patient regained near normal left ventricular function after baseline severe regional and global dysfunction. We postulate a relationship between the use of amphetamines, potentiated by benzodiazepines, and occurrence of acute thrombosis of multiple major coronary arteries. PMID:27358538

  6. 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

  7. 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

  8. Recommendations for anesthesia and perioperative management of patients with neuromuscular disorders.

    PubMed

    Racca, F; Mongini, T; Wolfler, A; Vianello, A; Cutrera, R; Del Sorbo, L; Capello, E C; Gregoretti, C; Massa, R; De Luca, D; Conti, G; Tegazzin, V; Toscano, A; Ranieri, V M

    2013-04-01

    Patients with neuromuscular disorders are at high risk of intraoperative and postoperative complications. General anesthesia in these patients may exacerbate respiratory and cardiovascular failure due to a marked sensitivity to several anesthetic drugs. Moreover, succinylcholine and halogenated agents can trigger life-threatening reactions, such as malignant hyperthermia, rhabdomyolysis and severe hyperkalemia. Therefore, regional anesthesia should be used whenever possible. If general anesthesia is unavoidable, special precautions must be taken. In particular, for patients at increased risk of respiratory complications (i.e., postoperative atelectasis, acute respiratory failure, nosocomial infections), noninvasive ventilation associated with aggressive airway clearance techniques can successfully treat upper airway obstruction, hypoventilation and airway secretion retention, avoiding prolonged intubation and tracheotomy. Anesthesia and perioperative management of patients with neuromuscular disorders are described in this article. To grade the strength of recommendations and the quality of evidence we adopted the GRADE approach. In case of low-quality evidence, these recommendations represent the collective opinion of the expert panel. PMID:23419334

  9. Atypical presentation of distal renal tubular acidosis in two siblings.

    PubMed

    Tasic, Velibor; Korneti, Petar; Gucev, Zoran; Hoppe, Bernd; Blau, Nenad; Cheong, Hae Il

    2008-07-01

    Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy. PMID:18386070

  10. 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

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

    PubMed

    Frydman, M; Straussberg, R; Shomrat, R; Goebel, H; Legum, C; Shiloh, Y

    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. "Idiopathic" 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. PMID:8533818

  12. The Biochemistry and Physiology of Mitochondrial Fatty Acid β-Oxidation and Its Genetic Disorders.

    PubMed

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

    2016-01-01

    Mitochondrial fatty acid β-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

  13. Renal involvement in psychological eating disorders.

    PubMed

    Li Cavoli, Gioacchino; Mulè, Giuseppe; Rotolo, Ugo

    2011-01-01

    Psychological eating disorders--anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder--are an increasing public health problem with severe clinical manifestations: hypothermia, hypotension, electrolyte imbalance, endocrine disorders and kidney failure; they are of interest to nephrologists, but pathophysiological mechanisms in determining the renal involvement are still unclear. We describe pathophysiology, histological features and clinical manifestations of the most frequent psychological eating disorders: AN and BN. Regarding AN, we analyze the recent literature, and identify 3 principal pathways towards renal involvement: chronic dehydration-hypokalemia, nephrocalcinosis and chronic rhabdomyolysis. Regarding BN, we describe the correlation between obesity and many proinflammatory cytokines, chemokines, growth factors and adipokines, having potential metabolic and hemodynamic effects on the kidney and an important role in the pathogenesis of obesity-related renal injury, independently of hypertension and diabetes. PMID:22135793

  14. Exercise collapse associated with sickle cell trait (ECAST): case report and literature review.

    PubMed

    Quattrone, Richard D; Eichner, E Randy; Beutler, Anthony; Adams, W Bruce; O'Connor, Francis G

    2015-01-01

    Sickle cell trait (SCT) has been associated with exertional collapse (ECAST) and exercise-related sudden death in athletes and military warfighters. The mechanisms underlying ECAST remain controversial in the sports medicine community. Multiple case presentations and anecdotal reports postulate the role of extraordinary exercise intensity, but other risk factors including dehydration, heat, previous exertional rhabdomyolysis, genetic cofactors, and dietary supplements have been cited as potential contributors. Others have hypothesized some of the aforementioned factors combining in a "perfect storm" to trigger ECAST with a resultant potentially fatal "metabolic crisis." This case report provides a brief review of SCT as it pertains to exercise in warfighters and athletes, identifies known and postulated risk factors associated with ECAST, and introduces the potential mechanistic role of the "double hit" as a contributor to ECAST. PMID:25757006

  15. 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

  16. Venomous bites and stings in the tropical world.

    PubMed

    Warrell, D A

    Snakes of the families Viperidae and Elapidae are responsible for the high incidence of morbidity and mortality after snake bites in countries of West Africa, the Indian subcontinent, South-East Asia, New Guinea and Latin America. Envenoming can cause local effects, notably tissue necrosis; and systemic effects, including paralysis, haemostatic disturbances, shock, increased capillary permeability, myocardial damage, rhabdomyolysis and acute renal failure. Specific hyperimmune serum (antivenom) is the mainstay of medical treatment for severe envenoming. Ancillary treatments such as assisted ventilation, repletion of circulating volume, renal dialysis and surgical debridement of necrotic tissues are needed in some cases. Scorpion stings are a common medical problem in middle and southern America, North Africa and the Middle East. Vasodilator drugs are important to counter the effects of massive catecholamine release. Bites by spiders and stings by hymenoptera and marine animals are responsible for deaths and morbidity in some tropical countries. PMID:8264466

  17. Statin therapy, myopathy and exercise--a case report.

    PubMed

    Semple, Stuart J

    2012-01-01

    In a bid to reduce the morbidity and mortality associated with coronary artery disease, statin therapy has become a cornerstone treatment for patients with dyslipideamia. Statins, or HMG-CoA reductase inhibitors, are effective in blocking hepatic synthesis of cholesterol and are generally regarded as safe. Although rare, severe adverse side effects such as rhabdomyolysis have been reported, however, the more common complaint from patients is that related to myopathy. There is also mounting evidence that exercise may exacerbate these side effects, however the mechanisms are yet to be fully defined and there is controversy regarding the role that inflammation may play in the myopathy. This paper reports a patients experience during 6 months of simvastatin therapy and provides some insight into the white cell count (inflammation) following two bouts of moderate intensity exercise before and during statin therapy. It also highlights the need for rehabilitation practitioners to be aware of the adverse effects of statins in exercising patients. PMID:22420409

  18. Emergency Endovascular Treatment of an Acute Traumatic Rupture of the Thoracic Aorta Complicated by a Distal Low-Flow Syndrome

    SciTech Connect

    Bruninx, Guy; Wery, Didier; Dubois, Eric; El Nakadi, Badih; Dueren, Eric van; Verhelst, Guy; Delcour, Christian

    1999-11-15

    We report the case of a patient who suffered major trauma following a motorcycle accident that resulted in multiple fractures, bilateral hemopneumothorax, pulmonary contusions, and an isthmic rupture of the aorta with a pseudoaneurysm compressing the descending aorta. This compression was responsible for distal hypotension and low flow, leading to acute renal insufficiency and massive rhabdomyolysis. Due to the critical clinical status of the patient, which prevented any type of open thoracic surgery, endovascular treatment was performed. An initial stent-graft permitted alleviation of the compression and the re-establishment of normal hemodynamic conditions, but its low position did not allow sufficient coverage of the rupture. A second stent-graft permitted total exclusion of the pseudoaneurysm while preserving the patency of the left subclavian artery.

  19. Role of transcranial magnetic stimulation in differentiating motor nervous tract disorders from other causes of recumbency in four horses and one donkey.

    PubMed

    Nollet, H; Vanschandevijl, K; Van Ham, L; Vanderstraeten, G; Deprez, P

    2005-11-19

    Transcranial magnetic stimulation and measurement of the magnetic motor-evoked potentials (MMEPs) in the thoracic and pelvic limbs of four recumbent horses and one recumbent donkey were used to assess the integrity of the descending motor pathways, in order to confirm or exclude a descending motor tract lesion as the cause of the recumbency. In two of the animals abnormal MMEPs were recorded; in one of the horses a lesion along the cervical spinal cord due to a fracture of the fifth cervical vertebra was diagnosed and confirmed by radiography and postmortem examination; in another horse, damage to the peripheral nerves of the left forelimb was diagnosed and confirmed postmortem when a large abscess was found to have been compressing the peripheral nerves at the level of the last cervical vertebra. In the three other animals, normal MMEPs were recorded, and laminitis, rhabdomyolysis and physitis were diagnosed as the causes of the recumbency. PMID:16299367

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

    PubMed

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

    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

  1. 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

  2. Mass envenomations by honey bees and wasps.

    PubMed Central

    Vetter, R S; Visscher, P K; Camazine, S

    1999-01-01

    Stinging events involving honey bees and wasps are rare; most deaths or clinically important incidents involve very few stings (< 10) and anaphylactic shock. However, mass stinging events can prove life-threatening via the toxic action of the venom when injected in large amounts. With the advent of the Africanized honey bee in the southwestern United States and its potential for further spread, mass envenomation incidents will increase. Here we review the literature on mass stinging events involving honey bees and wasps (i.e., yellowjackets, wasps, and hornets). Despite different venom composition in the two insect groups, both may cause systemic damage and involve hemolysis, rhabdomyolysis, and acute renal failure. Victim death may occur due to renal failure or cardiac complications. With supportive care, however, most victims should be able to survive attacks from hundreds of wasps or approximately 1000 honey bees. PMID:10344177

  3. 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

  4. Snakebite nephrotoxicity in Asia.

    PubMed

    Kanjanabuch, Talerngsak; Sitprija, Visith

    2008-07-01

    Snakebites have the highest incidence in Asia and represent an important health problem. Clinical renal manifestations include proteinuria, hematuria, pigmenturia, and renal failure. Nephropathy usually is caused by bites by snakes with hemotoxic or myotoxic venoms. These snakes are Russell's viper, saw-scaled viper, hump-nosed pit viper, green pit viper, and sea-snake. Renal pathologic changes include tubular necrosis, cortical necrosis, interstitial nephritis, glomerulonephritis, and vasculitis. Hemodynamic alterations caused by vasoactive mediators and cytokines and direct nephrotoxicity account significantly for the development of nephropathy. Hemorrhage, hypotension, disseminated intravascular coagulation, intravascular hemolysis, and rhabdomyolysis enhance renal ischemia leading to renal failure. Enzymatic activities of snake venoms account for direct nephrotoxicity. Immunologic mechanism plays a minor role. PMID:18620959

  5. Possible fatal acetaminophen intoxication with atypical clinical presentation.

    PubMed

    De-Giorgio, Fabio; Lodise, Maria; Chiarotti, Marcello; d'Aloja, Ernesto; Carbone, Arnaldo; Valerio, Luca

    2013-09-01

    Acetaminophen or paracetamol, a commonly used over-the-counter analgesic, is known to elicit severe adverse reactions when taken in overdose, chronically at therapeutic dosage or, sporadically, following single assumptions of a therapeutic dose. Damage patterns including liver damage and, rarely, acute tubular necrosis or a fixed drug exanthema. We present a case of fatal acetaminophen toxicity with postmortem blood concentration 78 μg/mL and unusual clinical features, including a visually striking and massive epidermolysis and rhabdomyolysis, disseminated intravascular coagulation and myocardial ischemia. This case is compared with the most similar previous reports in terms of organ damage, clinical presentation, and cause of death. We conclude that a number of severe patterns of adverse effects to acetaminophen are emerging that were previously greatly underestimated, thus questioning the adequacy of the clinical spectrum traditionally associated with acetaminophen intoxication and leading to the need to review this spectrum and the associated diagnostic criteria. PMID:23822653

  6. Ascending paresis as presentation of an unusual association between necrotizing autoimmune myopathy and systemic lupus erythematosus.

    PubMed

    García-Reynoso, Marco Julio; Veramendi-Espinoza, Liz Eliana; Ruiz-Garcia, Henry Jeison

    2014-01-01

    A 45 year-old man went to the emergency room due to disease duration of 15 days of insidious onset and progressive course. It began with symmetrical weakness and pain in feet and ankles that extends upward to the knees. Later, this progressed to paraparesis with Creatine phosphokinase levels of 44,270 U/L and respiratory failure that required mechanical ventilation. Electromyography and muscle biopsy of quadriceps were made. The patient responded to corticotherapy in pulses and supporting management. The presentation of ascending paresis suggested the diagnosis of Guillain-Barré syndrome. However, the degree of muscle involvement with rhabdomyolysis explains the neurological damage by itself. The biopsy revealed pathological criteria for necrotizing autoimmune myopathy (NAM), as well as other clinical and laboratory evidence. Patient disease continued and reached criteria for systemic lupus erythematosus (SLE). To our best knowledge, this is the first report of the NAM and SLE association. PMID:23906548

  7. 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

  8. Recurrent episodes of myoglobinuria, mental retardation and seizures but no hemolysis in two brothers with phosphoglycerate kinase deficiency.

    PubMed

    Coppens, Sandra; Koralkova, Pavla; Aeby, Alec; Mojzikova, Renata; Deconinck, Nicolas; Kadhim, Hazim; van Wijk, Richard

    2016-03-01

    We report two brothers with mild intellectual deficiency, exercise intolerance, rhabdomyolysis, seizures and no hemolysis. Phosphoglycerate kinase (PGK) activity was strongly decreased in their red blood cells. Subsequent molecular analysis of PGK1 revealed hemizygosity for a novel mutation c.756 + 3A > G, in intron 7. Analysis of the effect of this mutation on pre-mRNA processing demonstrated markedly decreased levels of normal PGK1 mRNA. In addition, the c.756 + 3A > G change resulted in abnormally spliced transcripts. If translated, these transcripts mostly encode for C-terminally truncated proteins. The consequences of the c.756 + 3A > G mutation is discussed, as well as the genotype-to-phenotype correlation with regard to previously described mutations (PGK Fukuroi and PGK Antwerp), which also result in C-terminal truncated proteins. PMID:26883264

  9. Brain Infarction: Rare Neurological Presentation of African Bee Stings.

    PubMed

    Alvis-Miranda, Hernando Raphael; Duarte-Valdivieso, Nancy Carolina; Alcala-Cerra, Gabriel; Moscote-Salazar, Luis Rafael

    2014-01-01

    Bee stings are commonly encountered worldwide. Various manifestations after bee sting have been described including local reactions which are common, systemic responses such as anaphylaxis, diffuse intravascular coagulation and hemolysis. We report a case of a 74-year-old man who developed neurologic deficit 5 hours after bee stings, which was confirmed to be left frontal infarction on brain CT-scan. The case does not follow the reported  pattern  of hypovolemic or anaphylactic shock, hemolysis and/or  rhabdomyolysis, despite the potentially lethal amount of venom injected. Diverse mechanisms have been proposed to give an explanation to all the clinical manifestation of both toxic and allergic reactions secondary to bee stings. Currently, the most accepted one state that victims can develop severe syndrome characterized by the release of a large amount of cytokines. PMID:27162866

  10. [Entactogenic drugs "ecstasy" (MDMA), "eve" (MDE) and other ring-substituted methamphetamine derivatives. A new class of substances among illegal designer drugs?].

    PubMed

    Gouzoulis-Mayfrank, E; Hermle, L; Kovar, K A; Sass, H

    1996-05-01

    The widely used recreational drugs 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and 3,4-methylenedioxyethamphetamine (MDE, Eve) occupy an intermediate position between stimulants and hallucinogens. Besides stimulation similar to that caused by amphetamines, they usually induce a pleasant, easily controllable emotional state with relaxation, fearlessness and feelings of happiness, but they sometimes also have stronger, hallucinogenic, effects. A number of pharmacological studies support the hypothesis that these drugs make up a distinct class of psychoactive substances, which have been designated "entactogens." On the drug scene, MDMA and MDE are considered "safe." However, this view must be corrected. Complications are rare, but potentially devastating ([long-lasting anxiety and depressive syndromes in chronic users, fatalities with hyperpyrexia, rhabdomyolysis and DIC syndrome (disseminated instravascular coagulation), possible hepatotoxicity]. Moreover, the clinical relevance of animal studies showing neurotoxic effects of MDMA on central serotonergic pathways is still not clear. PMID:9005345

  11. [A case of Legionella pneumonia with multiple organ failure].

    PubMed

    Li, Jiali; Wen, Rui; Deng, Hong; Li, Qian

    2016-06-28

    Legionella pneumonia (LP) is a rare systemic infectious disease, which is often misdiagnosed by clinicians due to the atypical symptoms. A middle-aged man who suffered from fever and dyspnea was diagnosed as community acquired pneumonia (CAP) in Changsha Central Hospital in March 2015. The treatment was unsatisfied firstly. The patients showed further symptoms of rhabdomyolysis, acute liver and renal failure, and impaired neural functions, who was diagnosed as LP with multiple organ failure based on a positive test for Legionella antibody. The patient was recovered after treated with moxifloxacin combined with azithromycin and continuous renal replacement therapy. LP should be paid attention when patient was diagnosed as CAP and failed to be treated. The satisfied outcome is achieved after application of macrolide, quinolones and comprehensive treatments. PMID:27374453

  12. 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

  13. Acute tubular nephropathy in a patient with acute HIV infection: review of the literature.

    PubMed

    Ananworanich, Jintanat; Datta, Anandita A; Fletcher, James Lk; Townamchai, Natavudh; Chomchey, Nitiya; Kroon, Eugene; Sereti, Irini; Valcour, Victor; Kim, Jerome H

    2014-01-01

    We report a 57-year old man with diabetes mellitus and hypertension who presented with acute HIV infection. Routine blood tests showed an elevated blood urea nitrogen and creatinine. Renal biopsy showed acute tubular nephropathy, which has not been reported to occur during acute HIV infection, in the absence of rhabdomyolysis or multiple organ system failure. Antiretroviral therapy was initiated. His renal failure gradually resolved without further intervention. At one year of follow-up his HIV RNA was undetectable, and his renal function was normal. The case illustrates a rare manifestation of acute HIV infection - acute renal failure - in an older man with diabetes and hypertension. In this setting acute kidney injury might mistakenly have been attributed to his chronic comorbidities, and this case supports early HIV-1 testing in the setting of a high index of suspicion. PMID:25745498

  14. Novel psychoactive substances: the pharmacology of stimulants and hallucinogens.

    PubMed

    Schifano, Fabrizio; Papanti, G Duccio; Orsolini, Laura; Corkery, John M

    2016-07-01

    There are increasing levels of concern relating to the rapidly evolving novel psychoactive substances/NPS and web markets' scenarios. The paper aims at providing an overview of the clinical pharmacological issues related to some of the most popular NPS categories, e.g. stimulants and hallucinogens. NPS intake is typically associated with the imbalance of a complex range of neurotransmitter pathways/receptors, namely: dopamine; cannabinoid/CB1; and 5-HT2A. The intake is almost invariably undetectable with standard screening tests. Hence, it may frequently occur that the acute management of NPS misusers will need to focus on decreasing levels of both self/outward-directed aggression and agitation. Benzodiazepines may be considered as first line treatment. Alternatively, propofol and/or antipsychotics can be administered. Focus will be as well on treatment of possible rhabdomyolysis and hyperthermia. Indeed, future studies should inform better tailored management/treatment strategies. PMID:26985969

  15. Propofol-Related Infusion Syndrome in Critically Ill Pediatric Patients: Coincidence, Association, or Causation?

    PubMed Central

    Timpe, Erin M.; Eichner, Samantha F.; Phelps, Stephanie J.

    2006-01-01

    Over the past two decades numerous reports have described the development of a propofol-related infusion syndrome (PRIS) in critically ill adult and pediatric patients who received continuous infusion propofol for anesthesia or sedation. The syndrome is generally characterized by progressive metabolic acidosis, hemodynamic instability and bradyarrhythmias that are refractory to aggressive pharmacological treatments. PRIS may occur with or without the presence of hepatomegaly, rhabdomyolysis or lipemia. To date, the medical literature contains accounts of 20 deaths in critically ill pediatric patients who developed features consistent with PRIS. These reports have generated considerable discussion and debate regarding the relationship, if any, between propofol and a constellation of clinical symptoms and features that have been attributed to its use in critically ill pediatric patients. This paper reviews the literature concerning PRIS, its clinical presentation, proposed mechanisms for the syndrome, and potential management should the syndrome occur. PMID:23118644

  16. A fatal outcome due to pulmonary hemorrhage following Russell’s viper bite

    PubMed Central

    Palangasinghe, Dhammika R.; Weerakkody, Ranga M.; Dalpatadu, Chamila G.; Gnanathasan, Christeine A.

    2015-01-01

    Russell’s viper (RV) envenomation causes local effects, coagulopathy, thrombosis, rhabdomyolysis, acute kidney injury, and neurological manifestations. Although coagulopathy and endothelial destruction causing local and mucosal surface bleeding is known, isolated severe pulmonary hemorrhage is not commonly reported. We report a previously healthy 18-year-old male who had bilateral severe pulmonary hemorrhages, which resulted in a fatal outcome following RV bite. This diagnosis was supported by persistent alveolar shadows, with minimum improvement despite hemodialysis without heparin, mixed acidosis and endotracheal tube bleeding. Other bleeding manifestations were absent. Polyvalent antivenom was administered in lieu of prolonged whole blood clotting time. Thrombocytopenia and mildly deranged clotting parameters were noted. Pulmonary hemorrhages were significant enough to require transfusion. This case highlights the importance of suspecting pulmonary hemorrhages in patients with alveolar shadows and desaturation following RV bite despite the absence of other bleeding manifestations in light of failure of optimum therapy including hemodialysis. PMID:25935188

  17. 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.

  18. [Desoxypipradrol - a new (already well known) designer drug].

    PubMed

    Müller, Dieter; Angerer, Verena; Kithinji, Josephine; Auwärter, Volker; Neurath, Hartmud; Liebetrau, Gesine; Just, Simone; Hermanns-Clausen, Maren

    2016-07-01

    Novel psychoactive substances (NPS) are easily accessible and the consumption has increased in recent years. New compounds as well as compounds derived from pharmaceutical research or the patent literature are provided, mostly without any declaration. As a consequence, severe adverse reactions may occur after consumption of unknown doses of these drugs, in particular after mixed intake of different psychoactive substances or co-medication. The toxic effects in such cases are not predictable. We report cases of rhabdomyolysis in patients after consumption of desoxipipradrol in combination with other NPS. Particularly in case of synergistic serotonergic effects a distinct stimulation of 5-HT2A-receptors (or 5-HT1A-receptors) should be considered which may lead to serotonergic syndrome. PMID:27359314

  19. Negative Health Implications Of Sickle Cell Trait in High Income Countries: From The Football Field To The Laboratory

    PubMed Central

    Key, Nigel S.; Connes, Philippe; Derebail, Vimal K.

    2015-01-01

    Worldwide, sickle cell trait is a highly prevalent gene carrier state. While generally a benign condition with a normal life expectancy, it is becoming increasingly clear that the sickle trait is associated with certain adverse outcomes. This article will focus on three of these outcomes, namely exertional rhabdomyolysis and sudden death, chronic renal dysfunction, and venous thromboembolism. In each case, the epidemiological evidence for the association is reviewed, together with the existing data on potential underlying mechanisms. Because newborn screening programmes for sickle cell anaemia also identify those with sickle cell trait, it is imperative that further studies determine what, if any, preventive measures can be taken to reduce the burden of these uncommon but potentially morbid complications in affected individuals. PMID:25754217

  20. Acute painful paraplegia in a 49-year-old man with allergic asthma.

    PubMed

    Sorino, Claudio; Agati, Sergio; Milani, Giuseppe; Maspero, Annarosa

    2014-01-01

    We present a case of a 49-year-old man, with a 10-year history of bronchial asthma and nasal polyposis, who developed acutely painful paraplegia and paresthesias. Laboratory data showed elevated blood creatine kinase levels and myoglobinuria, which were diagnostic for rhabdomyolysis but only partially explained the neurological deficit. Electrophysiological studies revealed a sensorimotor neuropathy of multiple mononeuritis type. The patient also had leucocytosis with marked eosinophilia and antineutrophil cytoplasmic autoantibodies. Bronchial biopsies showed inflammatory infiltrates with a prevalence of eosinophils. All these findings led us to diagnose eosinophilic granulomatosis with polyangiitis, a systemic vasculitis with almost constant respiratory tract involvement and good response to corticosteroid treatment. This can also affect other organs including the nervous system, while muscular involvement is unusual. Some diseases deserve attention in differential diagnosis. Histology can support the diagnosis which remains essentially clinical. Steroid sparing agents/immunosuppressants are suggested for extensive disease. PMID:24980994

  1. 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

  2. Relative safety profiles of high dose statin regimens

    PubMed Central

    Escobar, Carlos; Echarri, Rocio; Barrios, Vivencio

    2008-01-01

    Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses. PMID:18827903

  3. An unusual electrical burn caused by alkaline batteries.

    PubMed

    Roan, Tyng-Luen; Yeong, Eng-Kean; Tang, Yueh-Bih

    2015-02-01

    Electrical burns caused by low-voltage batteries are rarely reported. We recently encountered a male patient who suffered from a superficial second-degree burn over his left elbow and back. The total body surface area of the burn was estimated to be 6%. After interviewing the patient, the cause was suspected to be related to the explosion of a music player on the left-side of his waist, carried on his belt while he was painting a bathroom wall. Elevated creatine kinase levels and hematuria indicated rhabdomyolysis and suggested an electrical burn. Initial treatment was done in the burn intensive care unit with fluid challenge and wound care. The creatine kinase level decreased gradually and the hematuria was gone after 4 days in the intensive care unit. He was then transferred to the general ward for further wound management and discharged from our burn center after a total of 11 days without surgical intervention. PMID:25678181

  4. 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

  5. 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

  6. Disseminated Zygomycosis Due to Rhizopus schipperae after Heatstroke

    PubMed Central

    Anstead, Gregory M.; Sutton, Deanna A.; Thompson, Elizabeth H.; Weitzman, Irene; Otto, Randal A.; Ahuja, Sunil K.

    1999-01-01

    A 21-year-old woman suffered heatstroke and developed diarrhea while trekking across south Texas. The heatstroke was complicated by seizures, rhabdomyolysis, pneumonia, renal failure, and disseminated intravascular coagulation. The patient’s stool and blood cultures grew Campylobacter jejuni. The patient subsequently developed paranasal and gastrointestinal zygomycosis and required surgical debridement and a prolonged course of amphotericin B. The zygomycete cultured was Rhizopus schipperae. This is only the second isolate of R. schipperae that has been described. R. schipperae is characterized by the production of clusters of up to 10 sporangiophores arising from simple but well-developed rhizoids. These asexual reproductive propagules are produced on Czapek Dox agar but are absent on routine mycology media, where only chlamydospores are observed. Despite multiorgan failure, bacteremia, and disseminated zygomycosis, the patient survived and had a good neurological outcome. Heatstroke has not been previously described as a risk factor for the development of disseminated zygomycosis. PMID:10405417

  7. Heat-related illness in sports and exercise.

    PubMed

    Nichols, Andrew W

    2014-12-01

    Exertional heat-related illness (EHRI) is comprised of several states that afflict physically active persons when exercising during conditions of high environmental heat stress. Certain forms of EHRI may become life threatening if not treated. Exertional heat stroke (EHS), characterized by a core body temperature of >40 ° C and mental status changes, is the most severe form of EHRI. EHS must be treated immediately with rapid body cooling to reduce morbidity and mortality. Many EHRI cases are preventable by following heat acclimatization guidelines, modifying sports and exercise sessions during conditions of high environmental heat stress, maintaining adequate hydration, avoiding exertion in the heat when ill, and by educating sports medicine personnel, coaches, parents, and athletes on the early recognition and prevention of EHRI. Heat exhaustion, exercise-associated collapse, exercise-associated muscle cramps, exercise-associated hyponatremia, and exertional rhabdomyolysis are also described. PMID:25240413

  8. Statin-Associated Side Effects.

    PubMed

    Thompson, Paul D; Panza, Gregory; Zaleski, Amanda; Taylor, Beth

    2016-05-24

    Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated, but associated with various statin-associated symptoms (SAS), including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These are "statin-associated symptoms" because they are rare in clinical trials, making their causative relationship to statins unclear. SAS are, nevertheless, important because they prompt dose reduction or discontinuation of these life-saving mediations. SAMS is the most frequent SAS, and mild myalgia may affect 5% to 10% of statin users. Clinically important muscle symptoms, including rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM), are rare. Antibodies against HMG-CoA reductase apparently provoke SINAM. Good evidence links statins to DM, but evidence linking statins to other SAS is largely anecdotal. Management of SAS requires making the possible diagnosis, altering or discontinuing the statin treatment, and using alternative lipid-lowering therapy. PMID:27199064

  9. 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

  10. 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

  11. Translational insight into statin-induced muscle toxicity: from cell culture to clinical studies.

    PubMed

    Taha, Dhiaa A; De Moor, Cornelia H; Barrett, David A; Gershkovich, Pavel

    2014-08-01

    Statins are lipid-lowering drugs used widely to prevent and treat cardiovascular and coronary heart diseases. These drugs are among the most commonly prescribed medicines intended for long-term use. In general, statins are well tolerated. However, muscular adverse effects appear to be the most common obstacle that limits their use, resulting in poor patient compliance or even drug discontinuation. In addition, rare but potentially fatal cases of rhabdomyolysis have been reported with the use of these drugs, especially in the presence of certain risk factors. Previous reports have investigated statin-induced myotoxicity in vivo and in vitro using a number of cell lines, muscle tissues, and laboratory animals, in addition to randomized clinical trials, observational studies, and case reports. None of them have compared directly results from laboratory investigations with clinical observations of statin-related muscular adverse effects. To the best of our knowledge this is the first review article that combines laboratory investigation with clinical aspects of statin-induced myotoxicity. By reviewing published literature of in vivo, in vitro, and clinically relevant studies of statin myotoxicity, we aim to translate this important drug-related problem to establish a clear picture of proposed mechanisms that explain the risk factors and describe the diagnostic approaches currently used for evaluating the degree of muscle damage induced by these agents. This review provides baseline novel translational insight that can be used to enhance the safety profile, to minimize the chance of progression of these adverse effects to more severe and potentially fatal rhabdomyolysis, and to improve the overall patient compliance and adherence to long-term statin therapy. PMID:24530275

  12. 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 μg/L) and creatine kinase (219 μkat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17 g/kg (blood) and 2.81 g/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 μg/L and 57.5 μg/L, resp. (serum) and 8.15 μg/L and 602.3 μg/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

  13. 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

  14. Severe hypokalemic paralysis as a manifestation of a mitochondrial disorder.

    PubMed

    Finsterer, Josef; Lässer, Stefan

    2013-01-01

    Mitochondrial disorder (MtD) is usually a multisystem disease due to impaired mitochondrial energy production. Severe hypokalemia resulting in muscle weakness and rhabdomyolysis has not been reported as a phenotypic feature of MtD. Here we describe a 60-year-old male patient who developed myalgias followed by generalized muscle weakness a few days before admission. Symptoms were attributed to severe hypokalemia that occurred after the patient had discontinued spironolactone, a competitive antagonist of the aldosterone receptor, four months earlier on his own judgment. Spironolactone was given for 10 years to treat suspected primary hyperaldosteronism (Conn's syndrome). He presented with myopathic face, bilateral ptosis, hypertelorism, brachydactylia, weakness of the axial and limb muscles, and bilateral leg edema. Hypertelorism and brachydactylia are known as physical traits of MtD. Laboratory investigations revealed hypokalemia of 1.7 mmol/l and elevated serum levels of creatine kinase (2,772 U/l). Electrocardiogram showed sinus rhythm, left bundle-branch-block, repolarization abnormalities, and prolonged QTc (571 ms), which is associated with a propensity to ventricular arrhythmias. Diagnostic work-up revealed bilateral adenomas of the suprarenal glands. Conn's syndrome was regarded as a manifestation of MtD, since MtDs are frequently associated with endocrine abnormalities. The patient also presented with occasional double vision, ptosis, renal insufficiency, bilateral renal cysts, hypertriglyceridemia, arterial hypertension, and hypertrophic cardiomyopathy. Taken together, we have made the diagnosis of MtD. In conclusion, MtD may be associated with adrenal adenomas, which may cause severe symptomatic hypokalemia, manifesting as generalized weakness and myalgias due to rhabdomyolysis. Endocrine involvement may be a phenotypic feature of MtD. PMID:23985882

  15. 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

  16. Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

    PubMed Central

    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

  17. 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 24 h. 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

  18. 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

  19. 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

  20. The concurrent association of inflammatory polymyositis and Crohn’s ileo-colitis in a Sri Lankan man: a case report of a rare association and literature review

    PubMed Central

    2014-01-01

    Background Crohn’s disease is a relapsing, systemic inflammatory disease affecting the gastrointestinal tract with associated extraintestinal manifestations and immune disorders. Among the few cases reported, the association of Crohn’s disease with polymyositis varies in its complexity and severity. We report here the first known case of inflammatory polymyositis leading to rhabdomyolysis in a male patient diagnosed with Crohn’s ileocolitis. Case presentation A 42-year-old previously healthy man presented with acute polymyositis leading to rhabdomyolysis. The acute nature of the illness raised the suspicion of an infective, toxic, or metabolic insult, which was excluded during further investigations. Prolonged low-grade fever and raised inflammatory markers led to the suspicion of inflammatory polymyositis, which was confirmed by electromyography and muscle histology. In the absence of an infective cause, the concurrent association of prolonged diarrhea containing blood and mucous after recovery from an acute phase of myositis proved a diagnostic challenge. Ileocolonoscopy findings of extensive aphthous ulceration with skip lesions extending to the terminal ileum, and histology showing polymorph infiltration of the lamina propria, transmural involvement, and micro abscess formation was suggestive of Crohn’s disease. Sensory motor axonal peripheral neuropathy, which is another rare association of inflammatory bowel disease, was also present. Conclusion An unrecognized genetic predisposition or altered gut permeability causing disruption of the gut immune barrier triggering an immune response against skeletal muscles may have contributed to this unique association. Both polymyositis and Crohn’s ileocolitis responded well to corticosteroids and azathioprine, which is supportive of their immune pathogenesis. Myositis can be considered to be a rare extraintestinal manifestation of Crohn’s disease and can be used in the differential diagnosis of

  1. Blood lactate threshold and type II fibre predominance in patients with exertional heatstroke.

    PubMed Central

    Hsu, Y D; Lee, W H; Chang, M K; Shieh, S D; Tsao, W L

    1997-01-01

    OBJECTIVES: Severe damage to skeletal muscle is usually seen in patients with exertional heatstroke. Thirty seven young military recruits with exertional heatstroke in Taiwan from 1992 to 1995 were studied to evaluate changes in muscle pathology and blood lactate with exercise. METHODS: A biopsy sample of the vastus lateralis was taken from recruits within 10 days of the initial presentation. Results were compared with those from 15 controls matched for age and sex. During the recovery period, 90-150 days after exertional heatstroke, 29 patients participated in a constant work load test on the treadmill to assess their blood lactate threshold, and a second biopsy sample was taken. Each biopsy was examined histologically for pathology, distribution of fibre types, and fibre diameter. RESULTS: Twenty four of the 37 patients with exertional heatstroke developed rhabdomyolysis and 18 of these had type II fibre predominance in their muscle biopsy. The patients with type II fibre predominance had a higher tendency to develop rhabdomyolysis (chi 2 = 6.84, P < 0.01). The time required to reach a blood lactate threshold during a constant treadmill work load after recovery was significantly shorter in the patients with exertional heatstroke who had type II fibre predominance (P < 0.01). There was a positive correlation between the highest value of blood lactate and the percentage of type II fibres in all tested subjects (r = 0.82, P < 0.01). CONCLUSION: Patients with type II fibre predominance are more susceptible to exertional heatstroke and tend to have a higher blood lactate concentration and a shorter time to reach blood lactate threshold under a treadmill load test. Images PMID:9048720

  2. 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

  3. Cost-Effectiveness of Statins for Primary Cardiovascular Prevention in Chronic Kidney Disease

    PubMed Central

    Erickson, Kevin F.; Japa, Sohan; Owens, Douglas K.; Chertow, Glenn M.; Garber, Alan M.; Goldhaber-Fiebert, Jeremy D.

    2013-01-01

    Objectives To evaluate the cost-effectiveness of statins for primary prevention of myocardial infarction (MI) and stroke in patients with chronic kidney disease (CKD). Background Patients with CKD have an elevated risk of MI and stroke. Although HMG Co-A reductase inhibitors (“statins”) may prevent cardiovascular events in patients with non-dialysis-requiring CKD, adverse drug effects and competing risks could materially influence net effects and clinical decision-making. Methods We developed a decision-analytic model of CKD and cardiovascular disease (CVD) to determine the cost-effectiveness of low-cost generic statins for primary CVD prevention in men and women with hypertension and mild-to-moderate CKD. Outcomes included MI and stroke rates, discounted quality adjusted life years (QALYs) and lifetime costs (2010 USD), and incremental cost-effectiveness ratios. Results For 65 year-old men with moderate hypertension and mild-to-moderate CKD, statins reduced the combined rate of MI and stroke, yielded 0.10 QALYs, and increased costs by $1,800 ($18,000 per QALY gained). For patients with lower baseline cardiovascular risks, health and economic benefits were smaller; for 65 year-old women, statins yielded 0.06 QALYs and increased costs by $1,900 ($33,400 per QALY gained). Results were sensitive to rates of rhabdomyolysis and drug costs. Statins are less cost-effective when obtained at average retail prices, particularly in patients at lower CVD risk. Conclusions While statins reduce absolute CVD risk in patients with CKD, increased risk of rhabdomyolysis, and competing risks associated with progressive CKD, partly offset these gains. Low-cost generic statins appear cost-effective for primary prevention of CVD in patients with mild-to-moderate CKD and hypertension. PMID:23500327

  4. Long-Term Major Clinical Outcomes in Patients With Long Chain Fatty Acid Oxidation Disorders Before and After Transition to Triheptanoin Treatment—A Retrospective Chart Review

    PubMed Central

    Vockley, Jerry; Marsden, Deborah; McCracken, Elizabeth; DeWard, Stephanie; Barone, Amanda; Hsu, Kristen; Kakkis, Emil

    2015-01-01

    Background Long chain fatty acid oxidation disorders (LC-FAOD) are caused by defects in the metabolic pathway that converts stored long-chain fatty acids into energy, leading to a deficiency in mitochondrial energy production during times of physiologic stress and fasting. Severe and potentially life threatening clinical manifestations include rhabdomyolysis, hypoglycemia, hypotonia/weakness, cardiomyopathy and sudden death. We present the largest cohort of patients to date treated with triheptanoin, a specialized medium odd chain (C7) triglyceride, as a novel energy source for the treatment of LC-FAOD. Methods This was a retrospective, comprehensive medical record review study of data from 20 of a total 24 patients with LC-FAOD who were treated for up to 12.5 years with triheptanoin, as part of a compassionate use protocol. Clinical outcomes including hospitalization event rates, number of hospitalization days/year, and abnormal laboratory values were determined for the total period of the study before and after triheptanoin treatment, as well as for specified periods before and after initiation of triheptanoin treatment. Other events of interest were documented including rhabdomyolysis, hypoglycemia, and cardiomyopathy. Results LC-FAOD in these 20 subjects was associated with 320 hospitalizations from birth to the end date of study. The mean hospitalization days/year decreased significantly by 67% during the period after triheptanoin initiation (n=15; 5.76 vs 17.55 vs; P=0.0242) and a trend toward a 35% lower hospitalization event rate was observed in the period after triheptanoin initiation compared with the before-treatment period (n=16 subjects >6 months of age; 1.26 vs 1.94; P=0.1126). The hypoglycemia event rate per year in 9 subjects with hypoglycemia problems declined significantly by 96% (0.04 vs 0.92; P=0.0091) and related hospitalization days/year were also significantly reduced (n=9; 0.18 vs 8.42; P=0.0257). The rhabdomyolysis hospital event rate in 11

  5. Renal Failure Prevalence in Poisoned Patients

    PubMed Central

    Arefi, Mohammad; Taghaddosinejad, Fakhroddin; Salamaty, Peyman; Soroosh, Davood; Ashraf, Hami; Ebrahimi, Mohsen

    2014-01-01

    Background: Renal failure is an important adverse effect of drug poisoning. Determining the prevalence and etiology of this serious side effect could help us find appropriate strategies for the prevention of renal failure in most affected patients. Objectives: The present study is aimed to identify drugs that induce renal failure and also to find the prevalence of renal failure in patients referred to emergency departments with the chief complaint of drug poisoning, in order to plan better therapeutic strategies to minimize the mortality associated with drug poisoning induced renal failure. Patients and Methods: This cross-sectional study surveyed 1500 poisoned patients referred to the Emergency Department of Baharloo Hospital in Tehran during 2010. Demographic data including age and gender as well as clinical data including type of medication, duration of hospital stay, and presence of renal failure were recorded. Mann-Whitney U test and chi-squared statistics were used to analyze the results. Results: A total number of 435 patients were poisoned with several drugs, 118 patients were intoxicated with sedative-hypnotic drugs, 279 patients were exposed to opium, and 478 patients were administered to other drugs. The method of intoxication included oral 84.3%, injective 9%, inhalation 4.3% and finally a combination of methods 2.3%. Laboratory results revealed that 134 cases had renal failure and 242 had rhabdomyolysis. The incidence of rhabdomyolysis and renal failure increased significantly with age, and also with time of admission to the hospital. Renal failure was reported in 25.1% of patients exposed to opium, vs. 18.2% of patients poisoned with aluminum phosphide, 16.7% of those with organophosphate, 8% with multiple drugs, 6.7% with alcohol, heavy metals and acids, and 1.7% with sedative hypnotics. Conclusions: Based on the findings of this study, there is a high probability of renal failure for patients poisoned with drugs such as opium, aluminum phosphide

  6. Substrate kinetics in patients with disorders of skeletal muscle metabolism.

    PubMed

    Ørngreen, Mette Cathrine

    2016-07-01

    The main purpose of the following studies was to investigate pathophysiological mechanisms in fat and carbohydrate metabolism and effect of nutritional interventions in patients with metabolic myopathies and in patients with severe muscle wasting. Yet there is no cure for patients with skeletal muscle disorders. The group of patients is heterozygous and this thesis is focused on patients with metabolic myopathies and low muscle mass due to severe muscle wasting. Disorders of fatty acid oxidation (FAO) are, along with myophosphorylase deficiency (McArdle disease), the most common inborn errors of metabolism leading to recurrent episodes of rhabdomyolysis in adults. Prolonged exercise, fasting, and fever are the main triggering factors for rhabdomyolysis in these conditions, and can be complicated by acute renal failure. Patients with low muscle mass are in risk of loosing their functional skills and depend on a wheel chair and respiratory support. We used nutritional interventions and metabolic studies with stable isotope technique and indirect calorimetry in patients with metabolic myopathies and patients with low muscle mass to get information of the metabolism of the investigated diseases, and to gain knowledge of the biochemical pathways of intermediary metabolism in human skeletal muscle. We have shown that patients with fat metabolism disorders in skeletal muscle affecting the transporting enzyme of fat into the mitochondria (carnitine palmitoyltransferase II deficiency) and affecting the enzyme responsible for breakdown of the long-chain fatty acids (very long chain acyl-CoA dehydrogenase deficiency) have a normal fatty acid oxidation at rest, but enzyme activity is too low to increase fatty acid oxidation during exercise. Furthermore, these patients benefit from a carbohydrate rich diet. Oppositely is exercise capacity worsened by a fat-rich diet in these patients. The patients also benefit from IV glucose, however, when glucose is given orally just before

  7. 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

  8. Glucuronidation converts clopidogrel to a strong time-dependent inhibitor of CYP2C8: a phase II metabolite as a perpetrator of drug-drug interactions.

    PubMed

    Tornio, A; Filppula, A M; Kailari, O; Neuvonen, M; Nyrönen, T H; Tapaninen, T; Neuvonen, P J; Niemi, M; Backman, J T

    2014-10-01

    Cerivastatin and repaglinide are substrates of cytochrome P450 (CYP)2C8, CYP3A4, and organic anion-transporting polypeptide (OATP)1B1. A recent study revealed an increased risk of rhabdomyolysis in patients using cerivastatin with clopidogrel, warranting further studies on clopidogrel interactions. In healthy volunteers, repaglinide area under the concentration-time curve (AUC(0-∞)) was increased 5.1-fold by a 300-mg loading dose of clopidogrel and 3.9-fold by continued administration of 75 mg clopidogrel daily. In vitro, we identified clopidogrel acyl-β-D-glucuronide as a potent time-dependent inhibitor of CYP2C8. A physiologically based pharmacokinetic model indicated that inactivation of CYP2C8 by clopidogrel acyl-β-D-glucuronide leads to uninterrupted 60-85% inhibition of CYP2C8 during daily clopidogrel treatment. Computational modeling resulted in docking of clopidogrel acyl-β-D-glucuronide at the CYP2C8 active site with its thiophene moiety close to heme. The results indicate that clopidogrel is a strong CYP2C8 inhibitor via its acyl-β-D-glucuronide and imply that glucuronide metabolites should be considered potential inhibitors of CYP enzymes. PMID:24971633

  9. Induction of the C-terminal proteolytic cleavage of AβPP by statins.

    PubMed

    Descamps, Olivier; Zhang, Qiang; John, Varghese; Bredesen, Dale E

    2011-01-01

    Statins are drugs commonly used to inhibit cholesterol synthesis, with the goal of reducing vascular diseases such as myocardial infarction and stroke. Statins have also been suggested as a therapeutic option for Alzheimer's disease (AD), although their benefit in AD remains controversial. We have previously shown that the intracellular C-terminal cleavage of the amyloid-β protein precursor (AβPP) is a major contributor to the neuronal toxicity seen in AD, and that this cleavage can be induced by amyloid-β. We now report that certain brain permeable statins are also able to induce the C-terminal cleavage of AβPP and associated cell death, whereas other statins do not. This statin effect on AβPP exceeded the effects of all other FDA-approved drugs in a library composed of these compounds, suggesting that this effect on AβPP cleavage is unique to a subset of the statins. Furthermore, the greatest effect occurred with cerivastatin, which has previously been shown to be the statin associated with the greatest risk of rhabdomyolysis. These results may have implications for the choice of which statins to evaluate in AD therapeutic trials; furthermore, the results may inform statin choice in individuals who are at high risk for the development of AD, such as those with an apolipoprotein E ε4 allele. PMID:21422530

  10. 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

  11. Unmasking the Janus face of myoglobin in health and disease.

    PubMed

    Hendgen-Cotta, U B; Flögel, U; Kelm, M; Rassaf, T

    2010-08-15

    For more than 100 years, myoglobin has been among the most extensively studied proteins. Since the first comprehensive review on myoglobin function as a dioxygen store by Millikan in 1939 and the discovery of its structure 50 years ago, multiple studies have extended our understanding of its occurrence, properties and functions. Beyond the two major roles, the storage and the facilitation of dioxygen diffusion, recent physiological studies have revealed that myoglobin acts as a potent scavenger of nitric oxide (NO(*)) representing a control system that preserves mitochondrial respiration. In addition, myoglobin may also protect the heart against reactive oxygen species (ROS), and, under hypoxic conditions, deoxygenated myoglobin is able to reduce nitrite to NO(*) leading to a downregulation of the cardiac energy status and to a decreased heart injury after reoxygenation. Thus, by controlling the NO(*) bioavailability via scavenging or formation, myoglobin serves as part of a sensitive dioxygen sensory system. In this review, the physiological relevance of these recent findings are delineated for pathological states where NO(*) and ROS bioavailability are known to be critical determinants for the outcome of the disease, e.g. ischemia/reperfusion injury. Detrimental and beneficial effects of the presence of myoglobin are discussed for various states of tissue oxygen tension within the heart and skeletal muscle. Furthermore, the impact of myoglobin on parasite infection, rhabdomyolysis, hindlimb and liver ischemia, angiogenesis and tumor growth are considered. PMID:20675542

  12. Delayed Presentation of Gluteal Compartment Syndrome: The Argument for Fasciotomy

    PubMed Central

    Lawrence, John E.; Cundall-Curry, Duncan J.; Stohr, Kuldeep K.

    2016-01-01

    A male patient in his fifties presented to his local hospital with numbness and weakness of the right leg which left him unable to mobilise. He reported injecting heroin the previous morning. Following an initial diagnosis of acute limb ischaemia the patient was transferred to a tertiary centre where Computed Tomography Angiography was reported as normal. Detailed neurological examination revealed weakness in hip flexion and extension (1/5 on the Medical Research Council scale) with complete paralysis of muscle groups distal to this. Sensation to pinprick and light touch was globally reduced. Blood tests revealed acute kidney injury with raised creatinine kinase and the patient was treated for rhabdomyolysis. Orthopaedic referral was made the following day and a diagnosis of gluteal compartment syndrome (GCS) was made. Emergency fasciotomy was performed 56 hours after the onset of symptoms. There was immediate neurological improvement following decompression and the patient was rehabilitated with complete nerve recovery and function at eight-week follow-up. This is the first documented case of full functional recovery following a delayed presentation of GCS with sciatic nerve palsy. We discuss the arguments for and against fasciotomy in cases of compartment syndrome with significant delay in presentation or diagnosis. PMID:27073707

  13. 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

  14. Delayed Presentation of Acute Gluteal Compartment Syndrome

    PubMed Central

    Tasch, James J.; Misodi, Emmanuel O.

    2016-01-01

    Patient: Male, 23 Final Diagnosis: Acute gluteal compartment syndrome Symptoms: — Medication: — Clinical Procedure: Gluteal fasciotomy Specialty: Critical Care Medicine Objective: Unusual clinical course Background: Acute gluteal compartment syndrome is a rare condition that usually results from prolonged immobilization following a traumatic event, conventionally involving the presence of compounding factors such as alcohol or opioid intoxication. If delay in medical treatment is prolonged, severe rhabdomyolysis may ensue, leading to acute renal failure and potentially death. Case Report: We report the case of a 23-year-old male with a recent history of incarceration and recreational drug use, who presented with reports of severe right-sided buttock pain and profound right-sided neurological loss following a questionable history involving prolonged immobilization after a fall from a standing position. The patient required an emergent gluteal fasciotomy immediately upon admission and required temporary hemodialysis. After an extended hospital stay, he ultimately recovered with only mild deficits in muscular strength in the right lower extremity. Conclusions: This report demonstrates the importance of early recognition of gluteal compartment syndrome to prevent morbidity and mortality. Compartment syndrome presents in many unique ways, and healthcare practitioners must have a keen diagnostic sense to allow for early surgical intervention. Proper wick catheter measurements should be utilized more frequently, instead of relying on clinical symptomatology such as loss of peripheral pulses for diagnosis of compartment syndrome. PMID:27432320

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

    PubMed

    Zornetta, Irene; Caccin, Paola; Fernandez, Julián; Lomonte, Bruno; Gutierrez, José María; 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

  16. [Intoxications specific to the Aquitaine region].

    PubMed

    Bédry, 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

  17. Hypokalemic paralysis in a professional bodybuilder.

    PubMed

    Mayr, Florian B; Domanovits, Hans; Laggner, Anton N

    2012-09-01

    Severe hypokalemia is a potentially life-threatening disorder and is associated with variable degrees of skeletal muscle weakness, even to the point of paralysis. On rare occasions, diaphragmatic paralysis from hypokalemia can lead to respiratory arrest. There may also be decreased motility of smooth muscle, manifesting with ileus or urinary retention. Rarely, severe hypokalemia may result in rhabdomyolysis. Other manifestations of severe hypokalemia include alteration of cardiac tissue excitability and conduction. Hypokalemia can produce electrocardiographic changes such as U waves, T-wave flattening, and arrhythmias, especially if the patient is taking digoxin. Common causes of hypokalemia include extrarenal potassium losses (vomiting and diarrhea) and renal potassium losses (eg, hyperaldosteronism, renal tubular acidosis, severe hyperglycemia, potassium-depleting diuretics) as well as hypokalemia due to potassium shifts (eg, insulin administration, catecholamine excess, familial periodic hypokalemic paralysis, thyrotoxic hypokalemic paralysis). Although the extent of diuretic misuse in professional bodybuilding is unknown, it may be regarded as substantial. Hence, diuretics must always be considered as a cause of hypokalemic paralysis in bodybuilders. PMID:21871759

  18. Histological Changes in Skeletal Muscle During Death by Drowning: An Experimental Study.

    PubMed

    Girela-López, Eloy; Ruz-Caracuel, Ignacio; Beltrán, Cristina; Jimena, Ignacio; Leiva-Cepas, Fernando; Jiménez-Reina, Luis; Peña, José

    2016-06-01

    A diagnosis of drowning is a challenge in legal medicine as there is generally a lack of pathognomonic findings indicative of drowning. This article investigates whether the skeletal muscle undergoes structural changes during death by drowning. Eighteen Wistar rats were divided into 3 equal groups according to the cause of death: drowning, exsanguination, and cervical dislocation. Immediately after death, samples of the masseter, sternohyoid, diaphragm, anterior tibial, soleus, and extensor digitorum longus muscles were obtained and examined by light and electron microscopy.In the drowning group, all muscles except the masseter displayed scattered evidence of fiber degeneration, and modified Gomori trichrome staining revealed structural changes in the form of abnormal clumps of red material and ragged red fibers. Under the electron microscope, there was myofibrillar disruption and large masses of abnormal mitochondria. In the exsanguination group, modified Gomori trichrome staining disclosed structural changes and mitochondrial abnormalities were apparent under light microscopy; however, there was no evidence of degeneration. No alterations were observed in the cervical dislocation group.As far as we know, this is the first time that these histological findings are described in death by drowning and are consistent with rhabdomyolysis and intense anoxia of skeletal muscle. PMID:27043461

  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. 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; Lönn, 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

  1. Hydrophobic statins induce autophagy and cell death in human rhabdomyosarcoma cells by depleting geranylgeranyl diphosphate.

    PubMed

    Araki, Makoto; Maeda, Masatomo; Motojima, Kiyoto

    2012-01-15

    Statins are the most common type of medicine used to treat hypercholesterolemia; however, they are associated with a low incidence of myotoxicity such as myopathy and rhabdomyolysis. The mechanisms for the adverse effects remain to be fully elucidated for safer chronic use and drug development. The results of our earlier work suggested that hydrophobic statins induce autophagy in cultured human rhabdomyosarcoma A204 cells. In this study, we first confirmed the statin-induced autophagy by assessing other criteria, including induced expression of the autophagy-related genes, enhanced protein degradation of autophagy marker protein p62 and electron microscopic observation of induced formation of autophagosome. We next demonstrated that the extent of inhibition of HMG-CoA reductase in the cell is parallel with the ability of a statin to induce autophagy. Thus, the primary activity of statins causes autophagy in A204 cells. Considering the mechanism for the induction, we showed that statins induce autophagy by depleting cellular levels of geranylgeranyl diphosphate (GGPP) mostly through an unknown pathway that does not involve two major small G proteins, Rheb and Ras. Finally, we demonstrated that the ability of statins to induce autophagy parallels their toxicity to A204 cells and that both can be suppressed by GGPP. PMID:22094060

  2. Lipin-1 Regulates Autophagy Clearance and Intersects with Statin Drug Effects in Skeletal Muscle

    PubMed Central

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

    2014-01-01

    SUMMARY 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 mTOR abundance in lipin-1-haploinsufficent and –deficient muscle. Lipin-1 restoration in skeletal muscle prevents myonecrosis and statin toxicity in vivo, and activated protein kinase D rescues autophagic flux and lipid homeostasis 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

  3. Mechanisms and assessment of statin-related muscular adverse effects

    PubMed Central

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, 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

  4. Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells.

    PubMed

    Sacher, Julia; Weigl, Lukas; Werner, Martin; Szegedi, Csaba; Hohenegger, Martin

    2005-09-01

    The 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are widely used and well tolerated cholesterol-lowering drugs. In rare cases, side effects occur in skeletal muscle, including myositis or even rhabdomyolysis. However, the molecular mechanisms are not well understood that lead to these muscle-specific side effects. Here, we show that statins cause apoptosis in differentiated human skeletal muscle cells. The prototypical representative of statins, simvastatin, triggered sustained intracellular Ca(2+) transients, leading to calpain activation. Intracellular chelation of Ca(2+) completely abrogated cell death. Moreover, ryanodine also completely prevented the simvastatin-induced calpain activation. Nevertheless, an activation of the ryanodine receptor by simvastatin could not be observed. Downstream of the calpain activation simvastatin led to a translocation of Bax to mitochondria in a caspase 8-independent manner. Consecutive activation of caspase 9 and 3 execute apoptotic cell death that was in part reversed by the coadministration of mevalonic acid. Conversely, the simvastatin-induced activation of calpain was not prevented by mevalonic acid. These data delineate the signaling cascade that leads to muscle injury caused by statins. Our observations also have implications for improving the safety of this important medication and explain to some extent why physical exercise aggravates skeletal muscle side effects. PMID:15914674

  5. Possible mechanisms underlying statin-induced skeletal muscle toxicity in L6 fibroblasts and in rats.

    PubMed

    Itagaki, Mai; Takaguri, Akira; Kano, Seiichiro; Kaneta, Shigeru; Ichihara, Kazuo; Satoh, Kumi

    2009-01-01

    3-Hydroxy-3-methylglutaryl CoA reductase inhibitors (statins) are safe and well-tolerated therapeutic drugs. However, they occasionally induce myotoxicity such as myopathy and rhabdomyolysis. Here, we investigated the mechanism of statin-induced myotoxicity in L6 fibroblasts and in rats in vivo. L6 fibroblasts were differentiated and then treated with pravastatin, simvastatin, or fluvastatin for 72 h. Hydrophobic simvastatin and fluvastatin decreased cell viability in a dose-dependent manner via apoptosis characterized by typical nuclear fragmentation and condensation and caspase-3 activation. Both hydrophobic statins transferred RhoA localization from the cell membrane to the cytosol. These changes induced by both hydrophobic statins were completely abolished by the co-application of geranylgeranylpyrophosphate (GGPP). Y27632, a Rho-kinase inhibitor, mimicked the hydrophobic statin-induced apoptosis. Hydrophilic pravastatin did not affect the viability of the cells. Fluvastatin was continuously infused (2.08 mg/kg at an infusion rate of 0.5 mL/h) into the right internal jugular vein of the rats in vivo for 72 h. Fluvastatin infusion significantly elevated the plasma CPK level and transferred RhoA localization in the skeletal muscle from the cell membrane to the cytosol. In conclusion, RhoA dysfunction due to loss of lipid modification with GGPP is involved in the mechanisms of statin-induced skeletal muscle toxicity. PMID:19129682

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

    PubMed

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

    2015-06-01

    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 2.7 mmol/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

  7. 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

  8. 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

  9. 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

  10. 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

  11. [The combinations of statins and fibrates: pharmacokinetic and clinical implications].

    PubMed

    González Santos, Pedro

    2014-07-01

    With mixed dyslipidemia of the atherogenic dyslipidemia type, once the LDL-c objectives have been achieved through statin treatment, there is often a residual risk, for which the addition of a fibrate is recommended. The combination of statins and fibrates has been limited by the possibility of drug interactions, which mostly result in myopathy. Interactions between statins and other drugs are caused by pharmacokinetic mechanisms, mainly by changing the metabolism of statins in the CYP450 enzyme system, in the hepatic glucuronidation pathway or in the transporters responsible for statin distribution in tissues. The most significant adverse eff ect of statins is myopathy, which can also be induced by fibrates and is more frequent when the 2 drugs (statins and fibrates) are combined. This adverse eff ect manifests clinically as myalgia, muscle weakness, increased CK levels and, in its most severe form, rhabdomyolysis. This interaction mainly aff ects gemfibrozil due to its specific action on the CYP450 enzyme system and that interferes with the hepatic glucuronidation of statins by using the same isoenzymes and with organic anion transporters in the liver. When combining statins, we should use other fibric acid derivatives, preferably fenofibrate. PMID:25043540

  12. [The concurrence of light-chain deposition disease, AL-amyloidosis, and cast nephropathy in a patient with multiple myeloma].

    PubMed

    Rekhtina, I G; Zakharova, E V; Stoliarevich, E S; Sinitsina, M N; Denisova, E N

    2015-01-01

    Despite of the fact that their clinical manifestations are similar, AL-amyloidosis (AL-A) and light chain deposition disease (LCDD) are individual nosological entities in view of considerable differences in their pathogenesis and pathomorphology. The paper describes a rare case of the concurrence of LCDD and AL-A in a patient with multiple myeloma. Clinically, there was dialysis-dependent renal failure, flail leg syndrome, myocardiopathy, and rhabdomyolysis. At the disease onset, his nephrobiopsy specimen could diagnose LCDD and myeloma or cast nephropathy. The disease was characterized by an aggressive course. Despite the administration of innovative agents, the patient had a short-term remission and died from disease progression. Autopsy additionally revealed amyloid deposition in the heart and kidney. The development of AL-A in the presence of prior LCDD may reflect the progression of the tumor and the appearance of an additional subclone of plasma cells that produce amyloidogenic light chains. The uncommonness of this case is that renal amyloid was found in the tubular casts and absent in the glomeruli, which may be considered as a special form--tubular AL-amyloidosis. PMID:26281203

  13. Localization of O-GlcNAc-modified proteins in neuromuscular diseases.

    PubMed

    Nakamura, Seika; Nakano, Satoshi; Nishii, Makoto; Kaneko, Satoshi; Kusaka, Hirofumi

    2012-06-01

    O-linked N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of nucleocytoplasmic proteins that induces the attachment of N-acetylglucosamine to serine or threonine residues of a protein. In contrast to other protein glycosylations, this modification is highly reversible and, similar to phosphorylation, it plays important roles in various cell signals. Here, we immunolocalized O-GlcNAc-modified proteins in muscle biopsy specimens from 40 patients with neuromuscular diseases and controls. In normal muscle fibers, O-GlcNAc was found along plasma membranes and in nuclei. Diffuse and increased cytoplasmic staining of O-GlcNAc was detected in (1) regenerating muscle fibers in muscular dystrophy, myositis, and rhabdomyolysis; (2) a proportion of atrophic fibers in myositis, such as those found in perifascicular regions in dermatomyositis; and (3) vacuolated fibers in sporadic inclusion body myositis (s-IBM) and distal myopathy with rimmed vacuoles (DMRV). Target formations in neurogenic muscular atrophy were O-GlcNAc positive. Increase of O-GlcNAc glycosylation could be associated with the stress response, as these lesions have been shown to be positive for several stress markers. Vacuolar rims in s-IBM and DMRV were sometimes sharply lined by O-GlcNAc-positive deposits, which reflects myonuclear breakdown occurring from the disease. PMID:22718293

  14. 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

  15. Delayed Presentation of Acute Gluteal Compartment Syndrome.

    PubMed

    Tasch, James J; Misodi, Emmanuel O

    2016-01-01

    BACKGROUND Acute gluteal compartment syndrome is a rare condition that usually results from prolonged immobilization following a traumatic event, conventionally involving the presence of compounding factors such as alcohol or opioid intoxication. If delay in medical treatment is prolonged, severe rhabdomyolysis may ensue, leading to acute renal failure and potentially death. CASE REPORT We report the case of a 23-year-old male with a recent history of incarceration and recreational drug use, who presented with reports of severe right-sided buttock pain and profound right-sided neurological loss following a questionable history involving prolonged immobilization after a fall from a standing position. The patient required an emergent gluteal fasciotomy immediately upon admission and required temporary hemodialysis. After an extended hospital stay, he ultimately recovered with only mild deficits in muscular strength in the right lower extremity. CONCLUSIONS This report demonstrates the importance of early recognition of gluteal compartment syndrome to prevent morbidity and mortality. Compartment syndrome presents in many unique ways, and healthcare practitioners must have a keen diagnostic sense to allow for early surgical intervention. Proper wick catheter measurements should be utilized more frequently, instead of relying on clinical symptomatology such as loss of peripheral pulses for diagnosis of compartment syndrome. PMID:27432320

  16. Propofol Infusion Syndrome in Refractory Status Epilepticus: A Case Report and Topical Review

    PubMed Central

    Dam, Mette

    2016-01-01

    Propofol infusion syndrome (PRIS) is a fatal complication when doses of propofol administration exceed 4 mg/kg/h for more than 48 hours. Propofol overdosage is not uncommon in patients with refractory status epilepticus (RSE). We describe a case of refractory status epilepticus complicated by propofol infusion syndrome and collect from 5 databases all reports of refractory status epilepticus cases that were treated by propofol and developed the syndrome and outline whether refractory status epilepticus treatment with propofol is standardized according to international recommendations, compare it with alternative medications, and discuss how this syndrome can be treated and prevented. A total of 21 patients who developed this syndrome reported arrhythmia in all cases (100%), rhabdomyolysis in 9 cases (42%), lactic acidosis in 13 cases (62%), renal failure in 8 cases (38%), lipemia in 7 cases (33%), and elevated hepatic enzymes in 6 cases (28%). 13 patients died (66%). Propofol is still given in a dosage higher than what is internationally recommended, and new treatment modalities such as renal replacement therapy, blood exchange, and extracorporeal membrane oxygenation seem to be promising. In conclusion, propofol should be carefully titrated, the maximal infusion rate needs to be reassessed, and combination of different sedative agents may be considered. PMID:27493812

  17. 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

  18. Detection of Pharmacovigilance-Related adverse Events Using Electronic Health Records and automated Methods

    PubMed Central

    Haerian, K; Varn, D; Vaidya, S; Ena, L; Chase, HS; Friedman, C

    2013-01-01

    Electronic health records (EHRs) are an important source of data for detection of adverse drug reactions (ADRs). However, adverse events are frequently due not to medications but to the patients’ underlying conditions. Mining to detect ADRs from EHR data must account for confounders. We developed an automated method using natural-language processing (NLP) and a knowledge source to differentiate cases in which the patient’s disease is responsible for the event rather than a drug. Our method was applied to 199,920 hospitalization records, concentrating on two serious ADRs: rhabdomyolysis (n = 687) and agranulocytosis (n = 772). Our method automatically identified 75% of the cases, those with disease etiology. The sensitivity and specificity were 93.8% (confidence interval: 88.9-96.7%) and 91.8% (confidence interval: 84.0-96.2%), respectively. The method resulted in considerable saving of time: for every 1 h spent in development, there was a saving of at least 20 h in manual review. The review of the remaining 25% of the cases therefore became more feasible, allowing us to identify the medications that had caused the ADRs. PMID:22713699

  19. 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

  20. 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

  1. Lipid Metabolism Disorders, Lymphocytes Cells Death, and Renal Toxicity Induced by Very Low Levels of Deoxynivalenol and Fumonisin B1 Alone or in Combination Following 7 Days Oral Administration to Mice

    PubMed Central

    Kouadio, J. H.; Moukha, S.; Brou, K.; Gnakri, D.

    2013-01-01

    Scope: In our previous study focused on in vitro interactive effect of Fusarium mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1), we reported that these toxins tested at low level and in association could lead to additive or synergistic cytotoxic effect. The aim of the present study is to confirm those findings by in vivo study. Materials and Methods: Swiss mice were orally administered with low doses of DON (45 μg/kg bw/day), FB1 (110 μg/kg bw/day), and their mixture (DON + FB1) for 7 days. Results: As results, no death or abnormal symptoms were observed in all groups. The significant of loss of weight was observed in females group treated with FB1 and its association with DON. Serum chemistry examinations revealed that disorders in lipid metabolism, renal filtration perturb and a rhabdomyolysis. DON has been found as particular inducer of kidney cell deoxyribonucleic acid (DNA) methylation and blood lymphocytes cell death as measured by lymphocytes DNA fragmentation. Female mice were more sensitive and the mixture of DON and FB1 led to additive or more than additive effect particularly for their target kidney which showed different pattern of toxicity. Conclusion: Based on the results of this study, the no-observed-adverse effect level (NOAEL) o both DON and FB1 should be low than 45 μg/kg bw/day and 110 μg/kg bw/day, respectively in mice. PMID:24403731

  2. Statin-associated myopathy: from genetic predisposition to clinical management.

    PubMed

    Vrablik, M; Zlatohlavek, L; Stulc, T; Adamkova, V; Prusikova, M; Schwarzova, L; Hubacek, J A; Ceska, R

    2014-01-01

    Statin-associated myopathy (SAM) represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis. Its frequency ranges from 1-5 % in clinical trials to 15-20 % in everyday clinical practice. To a large extent, these variations can be explained by the definition used. Thus, we propose a scoring system to classify statin-induced myopathy according to clinical and biochemical criteria as 1) possible, 2) probable or 3) definite. The etiology of this disorder remains poorly understood. Most probably, an underlying genetic cause is necessary for overt SAM to develop. Variants in a few gene groups that encode proteins involved in: i) statin metabolism and distribution (e.g. membrane transporters and enzymes; OATP1B1, ABCA1, MRP, CYP3A4), ii) coenzyme Q10 production (e.g. COQ10A and B), iii) energy metabolism of muscle tissue (e.g. PYGM, GAA, CPT2) and several others have been proposed as candidates which can predispose to SAM. Pharmacological properties of individual statin molecules (e.g. lipophilicity, excretion pathways) and patients´ characteristics influence the likelihood of SAM development. This review summarizes current data as well as our own results. PMID:25428737

  3. 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

  4. 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

  5. Adenovirus-mediated expression of myogenic differentiation factor 1 (MyoD) in equine and human dermal fibroblasts enables their conversion to caffeine-sensitive myotubes.

    PubMed

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

    2014-03-01

    Several human and animal myopathies, such as malignant hyperthermia (MH), central core disease and equine recurrent exertional rhabdomyolysis (RER) are confirmed or thought to be associated with dysfunction of skeletal muscle calcium regulation. For some patients in whom the genetic cause is unknown, or when mutational analysis reveals genetic variants with unclear pathogenicity, defects are further studied through use of muscle histopathology and in vitro contraction tests, the latter in particular, when assessing responses to ryanodine receptor agonists, such as caffeine. However, since muscle biopsy is not always suitable, researchers have used cultured cells to model these diseases, by examining calcium regulation in myotubes derived from skin, following forced expression of muscle-specific transcription factors. Here we describe a novel adenoviral vector that we used to express equine MyoD in dermal fibroblasts. In permissive conditions, transduced equine and human fibroblasts differentiated into multinucleated myotubes. We demonstrate that these cells have a functional excitation-calcium release mechanism and, similarly to primary muscle-derived myotubes, respond in a dose-dependent manner to increasing concentrations of caffeine. MyoD-induced conversion of equine skin-derived fibroblasts offers an attractive method for evaluating calcium homeostasis defects in vitro without the need for invasive muscle biopsy. PMID:24342283

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

    PubMed

    García-Tutor, E; Koljonen, V

    2007-01-01

    Sauna bathing is a popular recreational activity in Finland and is generally considered safe even for pregnant women and patients suffering from heart problems; but mixing alcohol with sauna bathing can be hazardous. In the normal Finnish recreational sauna the temperature is usually between 80 and 90 degrees C. A wide variety of burn injuries, in all age groups, are related to sauna bathing; scalds and contact burns account for over 85% while hot air, steam and flame burns for only 15%. Dehydration in patients under the influence of alcohol heightens the risk of hypotension which impairs skin blood circulation. This increased warming of the skin is an effect that is more marked on the outer and upper parts of the body exposed to hot air. Such patients require intensive care on admission: fluid replacement according to the Parkland formula, forced diuresis and immediate correction of acidosis and myoglobinuria. These patients have significant rhabdomyolysis on admission. The best predictor of survival is the creatine kinase level on the second post-injury day. CT scans are necessary to diagnose the underlying conditions of unconsciousness. The necrotic area extends to subcutaneous fat tissue and even to the underlying muscles. The level of excision is typically fascial and, in some areas, layers of the muscle must be removed. Owing to the popularity of sauna bathing throughout the world, it is important to know the extent of damage in this type of injury, in order not to underestimate the severity of such lesions. PMID:17886710

  7. 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 [TNFα], 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 TNFα, 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

  8. [Hypokalemic paralysis: the first presentation of primary Sjögren's syndrome].

    PubMed

    Martinho, Aurélia L; Capela, Andreia; Duarte, Fernanda

    2012-01-01

    The Sjögren's syndrome is a systemic autoimmune disorder characterized by chronic inflammation of the exocrine glands with extraglandular manifestations in up to 25% patients. Renal involvement occurs in 18.4-67% of cases, with tubulointerstitial nephritis being the most frequent pathology. We present the case of a 37 year-old woman admitted because of generalized grade 2 muscle weakness which developed over a week. We detected: hypokalemia, rhabdomyolysis, urinary pH 6.5, proteinuria and metabolic acidemia. The laboratory tests suggestive of distal renal tubular acidosis with hypokalaemia led to the diagnosis of lymphoplasmocytic tubulointerstitial nephritis, which was confirmed by renal biopsy, and to a clinical suspicion of Sjögren's syndrome. Primary Sjögren's syndrome was diagnosed in this patient based on the following criteria: xerophthalmia, xerostomia, sialadenitis, positive anti-SSA and anti-SSB antibodies, and absence of criteria for lupus and rheumatoid arthritis. During hospitalization, the patient developed deep vein thrombosis. Tests showed positive antiphospholipid antibodies and the diagnosis of secondary antiphospholipid syndrome was made. She was treated with potassium, bicarbonate, steroids, ramipril and warfarin. The authors wish to highlight the extraglandular manifestations and in particular the rarity of hypokalemic paralysis as the presenting manifestation of primary Sjögren's syndrome. PMID:22985924

  9. 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. PMID:27022213

  10. 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

  11. VLCAD deficiency: Follow-up and outcome of patients diagnosed through newborn screening in Victoria.

    PubMed

    Evans, Maureen; Andresen, Brage S; Nation, Judy; Boneh, Avihu

    2016-08-01

    Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited metabolic disorder of fatty acid oxidation. Treatment practices of the disorder have changed over the past 10-15years since this disorder was included in newborn screening programs and patients were diagnosed pre-symptomatically. A genotype-phenotype correlation has been suggested but the discovery of novel mutations make this knowledge limited. Herein, we describe our experience in treating patients (n=22) diagnosed through newborn screening and mutational confirmation and followed up over a median period of 104months. We report five novel mutations. In 2013 we formalised our treatment protocol, which essentially follows a European consensus paper from 2009 and our own experience. The prescribed low natural fat diet is relaxed for patients who are asymptomatic when reaching age 5years but medium-chain triglyceride oil is recommended before and after physical activity regardless of age. Metabolic stability, growth, development and cardiac function are satisfactory in all patients. There were no episodes of encephalopathy or hypoglycaemia but three patients had episodes of muscle pain with our without rhabdomyolysis. Body composition studies showed a negative association between dietary protein intake and percent body fat. Larger patient cohort and longer follow up time are required for further elucidation of genotype-phenotype correlations and for establishing the role of dietary protein in metabolic stability and long-term healthier body composition in patients with VLCAD deficiency. PMID:27246109

  12. A benefit–risk assessment model for statins using multicriteria decision analysis based on a discrete choice experiment in Korean patients

    PubMed Central

    Byun, Ji-Hye; Kwon, Sun-Hong; Ha, Ji-Hye; Lee, Eui-Kyung

    2016-01-01

    Purpose The benefit–risk balance for drugs can alter post approval owing to additional data on efficacy or adverse events. This study developed a quantitative benefit–risk assessment (BRA) model for statins using multicriteria decision analysis with discrete choice experiments and compared a recent BRA with that at the time of approval. Patients and methods Following a systematic review of the literature, the benefit criteria within the statin BRA model were defined as a reduction in the plasma low-density lipoprotein cholesterol level and a reduction in myocardial infarction incidence; the risk criteria were hepatotoxicity (Liv) and fatal rhabdomyolysis (Rha). The scores for these criteria were estimated using mixed treatment comparison methods. Weighting was calculated from a discrete choice experiment involving 203 Korean patients. The scores and weights were integrated to produce an overall value representing the benefit–risk balance, and sensitivity analyses were conducted. Results In this BRA model, low-density lipoprotein (relative importance [RI]: 37.50%) was found to be a more important benefit criterion than myocardial infarction (RI: 35.43%), and Liv (RI: 16.28%) was a more important risk criterion than Rha (RI: 10.79%). Patients preferred atorvastatin, and the preference ranking of cerivastatin and simvastatin was switched post approval because of the emergence of additional risk information related to cerivastatin. Conclusion A quantitative statin BRA model confirmed that the preference ranking of statins changed post approval because of the identification of additional benefits or risks. PMID:27358567

  13. 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 2.7 mmol/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

  14. 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

  15. 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

  16. 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, Glória E.; Castro, Isac; Baptista, Maria A. S. F.; Cury, Patrícia 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

  17. A prospective study on treatment of hypercholesterolemia with lovastatin in renal transplant patients receiving cyclosporine.

    PubMed

    Cheung, A K; DeVault, G A; Gregory, M C

    1993-06-01

    Hypercholesterolemia occurs commonly in renal transplant recipients and may contribute to the high cardiovascular morbidity and mortality in these patients. Although an effective hypolipidemic agent, lovastatin has been associated with rhabdomyolysis and acute renal failure in patients on cyclosporin A (CsA). In this study, lovastatin was administered at 10 mg/day for 8 wk followed by 20 mg/day for 12 wk to six renal transplant recipients who were receiving CsA concomitantly. The 10-mg/day dose was effective, but an additional lipid-lowering effect was seen with the 20-mg/day dose. Both serum total cholesterol and low-density lipoprotein cholesterol levels decreased by 27% at the end of the 20 wk of lovastatin administration. Serum high-density lipoprotein cholesterol and triglyceride levels remained unchanged. No significant clinical or laboratory adverse effects were observed, including muscular symptoms, ophthalmologic abnormalities, or alterations in serum creatine kinase, urea nitrogen, creatinine, transaminases, and CsA levels. Peak and trough plasma concentrations of active lovastatin were comparable to those reported in normal subjects receiving a higher lovastatin dose without CsA. It was concluded that the administration of low-dose (10 to 20 mg/day) lovastatin to renal transplant recipients receiving concomitant CsA can be safe and effective in lowering serum cholesterol. PMID:8338920

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

    PubMed

    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 drug-drug 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-naïve 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

  19. The South African form of severe and complicated canine babesiosis: clinical advances 1994-2004.

    PubMed

    Jacobson, Linda S

    2006-05-31

    Babesia (canis) rossi infection is common in dogs in South Africa, and frequently causes severe, life-threatening disease. Acidemia, persistent hyperlactatemia, hemoconcentration, elevated creatinine, cerebral babesiosis, pulmonary edema and pancreatitis are all associated with mortality rates above 30%, compared with overall mortality of 12% in admitted cases. Although half the admitted cases are severely anemic, hemoconcentration is associated with far higher mortality. Cerebral babesiosis is uncommon, but carries a poor prognosis. The pathological mechanism has been suggested to be endothelial cell damage and necrosis, followed by segmental microvascular necrosis with perivascular edema and hemorrhage. Renal involvement in babesiosis resembles the functional renal failure of sepsis. Hypotension is common, and other cardiovascular disturbances have been documented. Cerebellar ataxia, rhabdomyolysis and pancreatitis are recently identified complications. While the previous categorization into "severe" (life-threatening anemia) and "complicated" (complications not directly attributable to anemia) disease has proved useful, the distinction is artificial and probably unnecessary. An updated approach to classification is suggested, aimed at grouping animals by severity and prognosis, and using simple measures, such as clinical collapse and abnormal breathing, as much as possible. Although inflammatory mechanisms are undoubtedly important in the pathophysiology of babesiosis, there can be little doubt that tissue hypoxia plays a major role in the disease process. PMID:16503090

  20. 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

  1. Complications associated with sickle cell trait: a brief narrative review.

    PubMed

    Tsaras, Geoffrey; Owusu-Ansah, Amma; Boateng, Freda Owusua; Amoateng-Adjepong, Yaw

    2009-06-01

    Sickle cell trait occurs in approximately 300 million people worldwide, with the highest prevalence of approximately 30% to 40% in sub-Saharan Africa. Long considered a benign carrier state with relative protection against severe malaria, sickle cell trait occasionally can be associated with significant morbidity and mortality. Sickle cell trait is exclusively associated with rare but often fatal renal medullary cancer. Current cumulative evidence is convincing for associations with hematuria, renal papillary necrosis, hyposthenuria, splenic infarction, exertional rhabdomyolysis, and exercise-related sudden death. Sickle cell trait is probably associated with complicated hyphema, venous thromboembolic events, fetal loss, neonatal deaths, and preeclampsia, and possibly associated with acute chest syndrome, asymptomatic bacteriuria, and anemia in pregnancy. There is insufficient evidence to suggest an independent association with retinopathy, cholelithiasis, priapism, leg ulcers, liver necrosis, avascular necrosis of the femoral head, and stroke. Despite these associations, the average life span of individuals with sickle cell trait is similar to that of the general population. Nonetheless, given the large number of people with sickle cell trait, it is important that physicians be aware of these associations. PMID:19393983

  2. Exercise-induced myalgia may limit the cardiovascular benefits of statins.

    PubMed

    Opie, Lionel H

    2013-12-01

    The positive health benefits of statins extend beyond the cardiovascular and include increased flow mediated dilation, decreased atrial fibrillation, modest antihypertensive effects and reduced risks of malignancies. Prominent among the statin side-effects are myalgia and muscular weakness, which may be associated with a rise in circulating creatine kinase values. In increasing severity and decreasing incidence, the statin-induced muscle related conditions are myalgia, myopathy with elevated creatine kinase (CK) levels with or without symptoms, and rhabdomyolysis. Statin use may increase CK levels without decreasing average muscle strength or exercise performance. In one large study, only about 2 % had myalgia that could be attributed to statin use. A novel current hypothesis is that statins optimize cardiac mitochondrial function but impair the vulnerable skeletal muscle by inducing different levels of reactive oxygen species (ROS) in these two sites. In an important observational study, both statins and exercise reduced the adverse outcomes of cardiovascular disease, and the effects were additive. The major unresolved problem is that either can cause muscular symptoms with elevation of blood creatine kinase levels. There is, as yet, no clearly defined outcomes based policy to deal with such symptoms from use of either statins or exercise or both. A reasonable practical approach is to assess the creatine kinase levels, and if elevated to reduce the statin dose or the intensity of exercise. PMID:23934075

  3. Non-cardiovascular effects associated with statins.

    PubMed

    Desai, Chintan S; 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

  4. RyR1 S-Nitrosylation Underlies Environmental Heat Stroke and Sudden Death in Y522S RyR1 Knock-in Mice

    PubMed Central

    Durham, William J.; Aracena-Parks, Paula; Long, Cheng; Rossi, Ann E.; Goonasekera, Sanjeewa A.; Boncompagni, Simona; Galvan, Daniel L.; Gilman, Charles P.; Baker, Mariah; Shirokova, Natalia; Protasi, Feliciano; Dirksen, Robert; Hamilton, Susan L.

    2008-01-01

    SUMMARY Mice with a malignant hyperthermia mutation (Y522S) in the ryanodine receptor (RyR1) display muscle contractures, rhabdomyolysis, and death in response to elevated environmental temperatures. We demonstrate that this mutation in RyR1 causes Ca2+ leak which drives increases generation of reactive nitrogen species (RNS). Subsequent S-nitrosylation of the mutant RyR1 increases its temperature sensitivity for activation, producing muscle contractures upon exposure to elevated temperatures. The Y522S mutation in humans is associated with central core disease. Many mitochondria in the muscle of heterozygous Y522S mice are swollen and misshapen. The mutant muscle displays decreased force production and increased mitochondrial lipid peroxidation with aging. Chronic treatment with N-acetylcysteine protects against mitochondrial oxidative damage and the decline in force generation. We propose a feed forward cyclic mechanism that increases the temperature sensitivity of RyR1 activation and underlies heat stroke and sudden death. The cycle eventually produces a myopathy with damaged mitochondria. PMID:18394989

  5. Propofol Infusion Syndrome in Refractory Status Epilepticus: A Case Report and Topical Review.

    PubMed

    Walli, Akil; Poulsen, Troels Dirch; Dam, Mette; Børglum, Jens

    2016-01-01

    Propofol infusion syndrome (PRIS) is a fatal complication when doses of propofol administration exceed 4 mg/kg/h for more than 48 hours. Propofol overdosage is not uncommon in patients with refractory status epilepticus (RSE). We describe a case of refractory status epilepticus complicated by propofol infusion syndrome and collect from 5 databases all reports of refractory status epilepticus cases that were treated by propofol and developed the syndrome and outline whether refractory status epilepticus treatment with propofol is standardized according to international recommendations, compare it with alternative medications, and discuss how this syndrome can be treated and prevented. A total of 21 patients who developed this syndrome reported arrhythmia in all cases (100%), rhabdomyolysis in 9 cases (42%), lactic acidosis in 13 cases (62%), renal failure in 8 cases (38%), lipemia in 7 cases (33%), and elevated hepatic enzymes in 6 cases (28%). 13 patients died (66%). Propofol is still given in a dosage higher than what is internationally recommended, and new treatment modalities such as renal replacement therapy, blood exchange, and extracorporeal membrane oxygenation seem to be promising. In conclusion, propofol should be carefully titrated, the maximal infusion rate needs to be reassessed, and combination of different sedative agents may be considered. PMID:27493812

  6. [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

  7. 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

  8. Biochemical Correction of Very Long–chain Acyl-CoA Dehydrogenase Deficiency Following Adeno-associated Virus Gene Therapy

    PubMed Central

    Merritt, J. Lawrence; Nguyen, Tien; Daniels, Jan; Matern, Dietrich; Schowalter, David B.

    2009-01-01

    We report the development of a gene replacement strategy for very long–chain acyl-CoA dehydrogenase (VLCAD) deficiency. VLCAD is a mitochondrial enzyme involved in fatty acid β-oxidation, a key step in energy production during times of fasting or stress. Deficiency of VLCAD classically presents as hepatic dysfunction, hypoglycemia, cardiomyopathy, rhabdomyolysis, and/or sudden death. While dietary therapy for VLCAD deficiency has proven beneficial in preventing some symptoms, a risk of metabolic catastrophic decompensation remains throughout life during times of increased energy demand. We designed a recombinant adeno-associated virus (AAV) expressing the human VLCAD gene (AAV8-hVLCAD). To demonstrate its in vivo activity, AAV8-hVLCAD was administered via the tail vein to VLCAD-knockout mice. A reduction in accumulated serum long-chain acylcarnitines and increased fasting tolerance judged on blood glucose concentrations were observed as of 11 days postinjections through >100 days. Western analysis of liver, skeletal muscle, and heart extracts using PEP1 anti-hVLCAD antibody revealed short-term hVLCAD expression in the liver and muscle and longer-term expression in heart. This demonstrates the ability of human VLCAD to correct the biochemical phenotype of VLCAD-deficient mice. PMID:19156135

  9. [Bilateral tibial compartment syndrome with crush symptoms after cannabis abuse].

    PubMed

    Huber, F X; Eckstein, H H; Allenberg, J R

    1997-08-01

    Acute compartmental syndrome (CS) is a surgical emergency. Different conditions in which high non-physiological pressure appears within a closed fascial space reduce the necessary blood perfusion. CS is caused by trauma, burns, bleeding in patients with coagulopathies arterial injuries, nephrotic syndrome or unusual physical exercise with secondary compartmental swelling. When decompression occurs too late, permanent loss of function and limb contracture may result. In the following paper we report on a case of four-compartmental syndrome in the lower legs of a patient with drug intoxication. After cannabis consumption, the patient fell asleep sitting cross-legged. During our first examination several hours later, the signs of compartmental syndrome with spontaneous pain, turgid swelling and paresis were present. Bilateral skin incision technique was used to gain entrance into the four compartments in both lower legs. Immediately after the operation, the patient showed crush syndrome with high serum creatine kinase activity 140.501 U/l and acute renal failure caused by rhabdomyolysis. Within 2 weeks of haemofiltration and dialysis, a full recovery to a normal serum creatinine level of 0.7 mg/dl was achieved. After emergency treatment and rehabilitation, the patient showed neither vascular nor neural defects. PMID:9377997

  10. A case of fulminant type 1 diabetes associated with acute renal failure.

    PubMed

    Deng, Datong; Xia, Li; Chen, Mingwei; Xu, Min; Wang, Youmin; Wang, Changjiang

    2015-01-01

    A 56-year-old man suffered from severe diabetic ketoacidosis which was complicated by acute renal failure and rhabdomyolysis. Before admission the patient had had flu-like symptoms for 5 days and had developed polyuria and polydipsia. The clinical examination on admission showed his plasma glucose level was 80.65 mmol/L while the HbA1c was 7.4%. His amylase concentration was high without any signs of pancreatitis. The islet-associated autoantibodies (GAD antibody, islet cell antibody) were absent. These data were compatible with the diagnosis of fulminant type 1 diabetes. A continuous intravenous insulin infusion therapy was given during the acute phase to control hyperglycemia and ketoacidosis. This patient remained dependent on continuous veno-venous hemofiltration (CVVHF) for 5 days, followed by regular kidney dialysis for three times, before his renal function was finally recovered. To conclude, this is a rare case of abrupt onset fulminant type 1 diabetes with the onset of acute renal failure. Hence, early detection, quick diagnosis and immediate treatment are very important. In particular, prompt CVVHF and kidney dialysis are required and useful for rescuing the renal function. PMID:26071577

  11. From a fish tank injury to hospital haemodialysis: the serious consequences of drug interactions.

    PubMed

    Hill, Fay Joanne; McCloskey, Sarah Jane; Sheerin, Neil

    2015-01-01

    We present the case of a 68-year-old man admitted to hospital with severe acute kidney injury secondary to statin-induced rhabdomyolysis. Five weeks previously, the patient started a course of clarithromycin for infection of a finger wound with Mycobacterium marinum. His current medications included simvastatin, which he continued along with clarithromycin. The severity of the acute kidney injury necessitated initial continuous venovenous haemofiltration followed by 12 haemodialysis sessions before a spontaneous improvement in renal function occurred. Statins are widely prescribed and we report this case to encourage increased vigilance in avoiding drug interactions known to increase the risk of statin-induced myopathy, including macrolide antibiotics, calcium channel antagonists and amiodarone. The authors would also like to highlight recent guidance on atorvastatin as the statin of choice in patients with chronic kidney disease, and of the need for dose adjustment in those with an estimated glomerular filtration rate less than 30 mLs/min/1.73 m². PMID:26106178

  12. [Malignant hyperthermia syndrome in the intensive care unit : Differential diagnosis and acute measures].

    PubMed

    Grander, W

    2016-06-01

    Malignant hyperthermia is a life-threatening disease caused by derangement of the autonomic nerve system and hypermetabolism of the peripheral musculature. Commonly body core temperatures of more than 40 °C will be found in this disease which is caused mostly by psychopharmacological drugs like antidepressants, neuroleptics but also antibiotics, pain killers, anti-Parkinson drugs, and volatile anesthetics. The inducers of malignant hyperthermia interact with postsynaptic receptors (serotonin, anticholinergics) or muscular intracellular structures responsible for calcium utilization (volatile anesthetics, succinylcholine). Rarely malignant hyperthermia is a consequence of mental stress or vigorous exercise and or heat. Malignant hyperthermic syndromes lead to a severe dysbalance of the autonomic nerve system accompanied by rhabdomyolysis, disseminated intravascular coagulopathy, and finally multi-organ failure. Accordingly, medical management is primarily directed to stabilize vital functions, withdrawal of the causing drug, and if possible antagonizing toxic substances. The leading symptom hyperthermia needs to be treated physically with available cooling systems. PMID:27272514

  13. Hypothesis: exertional heat stroke-induced myopathy and genetically inherited malignant hyperthermia represent the same disorder, the human stress syndrome.

    PubMed

    Zhao, Xuesheng; Song, Qing; Gao, Yan

    2014-11-01

    Exertional heat stroke is usually experienced as a result of a prolonged and intensive exercise. It is a life-threatening condition that is characterized by an increase in core body temperature and rhabdomyolysis. The associated hyperkalemia and metabolic acidosis may lead to an acute renal, cardiac, and hemostatic failure. Exactly, the same symptoms are noticed in case of the anesthesia-induced malignant hyperthermia (MH), an inherited disorder of the skeletal muscle ryanodine receptor. This receptor is a Ca(2+) channel that is activated by the volatile anesthetic agents and depolarizing muscle relaxant. The presence of MH-associated ryanodine receptor variant in the individuals who suffered from EH and improvement of the symptoms with dantrolene has frequently raised the question as to whether the two disorders actually represent one and the same disease. Nevertheless, an exact explanation of the susceptibility of the genetically predisposed MH individuals to ER remains elusive. We have attempted to review the published clinical reports to explore the possibility that ER and EH represent one and the same disorder. PMID:24948473

  14. [Exertion-related heat stroke. Lethal multiorgan failure from accidental hyperthermia in a 23 year old athlete].

    PubMed

    Dunker, M; Rehm, M; Briegel, J; Thiel, M; Schelling, G

    2001-07-01

    We report the case of a 23-year-old rower who suffered from an exertional heatstroke while trying to lose 2 kg in weight by jogging before a competition. The development of this illness was favoured by clothes that were inappropriate for the environmental conditions and which the sportsman wore intentionally to enhance sweating. The maximum core temperature was over 43 degrees C. As a consequence the comatose patient developed a fulminant multi-organ failure with the liver ceasing its function, renal failure, massive rhabdomyolysis, and disseminated intravascular coagulation. In addition, he suffered from pericardial effusion and acute pulmonary failure (ARDS). In spite of maximum intensive care with an extensive substitution of blood products, continuous hemodiafiltration, and inhalative administration of nitrous oxide the young sportsman died 48 h after his admission to the intensive care unit. This tragic course demonstrates the danger of the widespread habit of losing weight by vigorously exercising with inappropriate clothes. In this article, potential risk factors, symptomatology, therapy, and methods of preventing an exertional heatstroke are shown and discussed. PMID:11496687

  15. Ischemic preconditioning and inflammatory response syndrome after reperfusion injury: an experimental model in diabetic rats.

    PubMed

    Grigorescu, Bianca Liana; Georgescu, Anca Meda; Cioc, Adrian-Dan; Fodor, Raluca-Ştefania; Cotoi, Ovidiu Simion; Fodor, Pal; Copotoiu, Sanda Maria; Azamfirei, Leonard

    2015-01-01

    Quantification of local ischemia and inflammatory response syndrome correlated with histological changes associated with ischemia-reperfusion injury (IRI) after revascularization techniques. We included 12 adult male Wistar rats, aged eight weeks that were randomly divided into two groups. The first group acted as the control and at the second group, we induced diabetes by intraperitoneal streptozotocin administration (60 mg/kg). After eight weeks, the rats were subject to ischemic preconditioning for 10 minutes at three regular intervals. Twenty-four hours post-preconditioning, both groups were subject to ischemia for 20 minutes, followed by 30 minutes of reperfusion. Oxygen extraction was higher in Group 1, the arterio-venous CO2 gradient was higher in the control group, but not significant. The lactate production was higher in Group 1. The second group had a higher Na+ and also a significant difference in K+ values. Receptor for Advanced Glycation End (RAGE) values were higher in the second group but with no significant difference (RAGE1=0.32 ng/mL versus RAGE2=0.40 ng/mL). The muscle samples from the control group displayed significant rhabdomyolysis, damage to the nucleus, while the preconditioned group showed almost normal morphological characteristics. The lungs and kidneys were most damaged in the control group, with damage expressed as thickened alveolar septa, neutrophil infiltrates, eosinophilic precipitates in the proximal convolute tubule. Ischemic preconditioning significantly attenuates the ischemic reperfusion injury. PMID:26743274

  16. Heat stroke: a comprehensive review.

    PubMed

    Yeo, Theresa Pluth

    2004-01-01

    Heat stroke (HS) is a serious and potentially life-threatening condition defined as a core body temperature >40.6 degrees C. Two forms of HS are recognized, classic heat stroke, usually occurring in very young or elderly persons, and exertional heat stroke, more common in physically active individuals. An elevated body temperature and neurologic dysfunction are necessary but not sufficient to diagnose HS. Associated clinical manifestations such as extreme fatigue; hot dry skin or heavy perspiration; nausea; vomiting; diarrhea; disorientation to person, place, or time; dizziness; uncoordinated movements; and reddened face are frequently observed. Potential complications related to severe HS are acute renal failure, disseminated intravascular coagulation, rhabdomyolysis, acute respiratory distress syndrome, acid-base disorders, and electrolyte disturbances. Long-term neurologic sequelae (varying degrees of irreversible brain injury) occur in approximately 20% of patients. The prognosis is optimal when HS is diagnosed early and management with cooling measures and fluid resuscitation and electrolyte replacement begins promptly. The prognosis is poorest when treatment is delayed >2 hours. PMID:15461044

  17. Fatal heat stroke associated with topiramate therapy.

    PubMed

    Borron, Stephen W; Woolard, Robert; Watts, Susan

    2013-12-01

    A 40-year-old man with diabetes and seizure disorder was found at home unresponsive and "very hot to touch" by his father 40 minutes before emergency medical services arrival. His usual medications included topiramate, divalproex sodium, and rosiglitazone/metformin. Paramedics administered oxygen, intravenous fluids, and naloxone. They did not witness or report seizure activity. Upon emergency department arrival, the patient was unresponsive (Glasgow Coma Scale 3), hypotensive (94/50 mm Hg), and tachypneic (32 breaths per minute), with a heart rate of 60 beats per minute and elevated rectal temperature peaking at 43.2°C. His skin was hot and dry, without rash; physical examination was otherwise normal. Laboratory studies revealed severe metabolic acidosis with acute renal failure and rhabdomyolysis. In spite of sedation, intubation, and aggressive cooling measures, the patient had cardiac arrest and died approximately 2 hours after arrival. Serum topiramate and valproate concentrations were within therapeutic ranges at 8.8 μg/mL (therapeutic 2-12) and 97 μg/mL (therapeutic 50-100), respectively. PMID:23993866

  18. Clinical toxicology: a tropical Australian perspective.

    PubMed

    Currie, B J

    2000-02-01

    Tropical Australia has an amazing diversity of venomous fauna, from "the world's most venomous creature," the multi-tentacled (chirodropid) box jellyfish Chironex fleckeri, to aggressive spiders whose venom remains to be characterized. All genera of highly venomous Australasian elapid snakes are present, except for tiger snakes. Most notable is the taipan (Oxyuranus scutellatus), with the most efficient "snap-release" biting mechanism of any snake and venom components causing the full constellation of clinical envenoming features: coagulopathy from fibrinogen depletion (procoagulant), neurotoxicity (predominantly presynaptic neurotoxin) and rhabdomyolysis (myotoxin). Brown snakes (Pseudonaja textilis and P. nuchalis) now account for most snake bite fatalities in Australia, as a result of severe coagulopathy and a poorly defined early scenario of collapse, postulated to be caused by profound hypotension caused by transient myocardial dysfunction associated with prothrombin activation. Other venomous entities include paralyzing ticks, the blue-ringed octopus, stone fish and other marine animals with venomous spines, paralyzing cone shells, and a wide range of jellyfish including Carukia barnesi and possibly other four-tentacled (carybdeid) box jellyfish causing the Irukandji syndrome. PMID:10688264

  19. Mild uncoupling of respiration and phosphorylation as a mechanism providing nephro- and neuroprotective effects of penetrating cations of the SkQ family.

    PubMed

    Plotnikov, E Y; Silachev, D N; Jankauskas, S S; Rokitskaya, T I; Chupyrkina, A A; Pevzner, I B; Zorova, L D; Isaev, N K; Antonenko, Y N; Skulachev, V P; Zorov, D B

    2012-09-01

    It is generally accepted that mitochondrial production of reactive oxygen species is nonlinearly related to the value of the mitochondrial membrane potential with significant increment at values exceeding 150 mV. Due to this, high values of the membrane potential are highly dangerous, specifically under pathological conditions associated with oxidative stress. Mild uncoupling of oxidative phosphorylation is an approach to preventing hyperpolarization of the mitochondrial membrane. We confirmed data obtained earlier in our group that dodecylrhodamine 19 (C(12)R1) (a penetrating cation from SkQ family not possessing a plastoquinone group) has uncoupling properties, this fact making it highly potent for use in prevention of pathologies associated with oxidative stress induced by mitochondrial hyperpolarization. Further experiments showed that C(12)R1 provided nephroprotection under ischemia/reperfusion of the kidney as well as under rhabdomyolysis through diminishing of renal dysfunction manifested by elevated level of blood creatinine and urea. Similar nephroprotective properties were observed for low doses (275 nmol/kg) of the conventional uncoupler 2,4-dinitrophenol. Another penetrating cation that did not demonstrate protonophorous activity (SkQR4) had no effect on renal dysfunction. In experiments with induced ischemic stroke, C(12)R1 did not have any effect on the area of ischemic damage, but it significantly lowered neurological deficit. We conclude that beneficial effects of penetrating cation derivatives of rhodamine 19 in renal pathologies and brain ischemia may be at least partially explained by uncoupling of oxidation and phosphorylation. PMID:23157263

  20. Fever, Myositis, and Paralysis: Is This Inflammatory Myopathy or Neuroinvasive Disease?

    PubMed

    Kiran, Aneeta R; Lau, Richard A; Wu, Kim M; Wong, Andrew L; Clements, Philip J; Heinze, Emil R

    2016-01-01

    West Nile virus (WNV) is a mosquito-borne RNA Flavivirus which emerged in North America in 1999. Most patients present with a febrile illness but a few develop WNV neuroinvasive disease. Myopathy is an uncommon manifestation. We describe a case of a 42-year-old male from Los Angeles who presented with 8 days of fever and muscle pain. Initial physical exam was normal except for 4/5 muscle strength testing in his extremity proximal muscles. Laboratory revealed a creatine kinase of 45,000 and a urinalysis with large blood but no red blood cells, suggesting rhabdomyolysis. The patient's condition declined despite aggressive supportive care and hydration, and on hospital day #6 he developed severe altered mental status and progressed to complete right arm paralysis and 2/5 muscle strength in bilateral legs. EMG/NCS showed sensorimotor axonal polyneuropathy and the cerebrospinal fluid was positive for IgM and IgG WNV antibodies. The patient was diagnosed with WNV neuroinvasive disease, poliomyelitis (and encephalitis) type with myopathy/muscle involvement. He was treated supportively and his muscle and neurologic disease gradually improved. At 12-month follow-up his muscle enzymes had normalized and his weakness had improved to 5/5 strength in bilateral legs and 3/5 strength in the right arm. PMID:27119037

  1. 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

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

    PubMed

    Tóth, Anita Réka; 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

  3. Rationale and design of the cardiorespiratory fitness and hospitalization events in armed forces study in Eastern Taiwan

    PubMed Central

    Lin, Gen-Min; Li, Yi-Hwei; Lee, Chung-Jen; Shiang, Jeng-Chuan; Lin, Ko-Huan; Chen, Kai-Wen; Chen, Yu-Jung; Wu, Ching-Fen; Lin, Been-Sheng; Yu, Yun-Shun; Lin, Felicia; Su, Fung-Ying; Wang, Chih-Hung

    2016-01-01

    AIM To investigate the association between cardiorespiratory fitness and hospitalization events in a cohort of large voluntary arm forces in Taiwan. METHODS The cardiorespiratory fitness and hospitalization events in armed forces (CHIEF) is a retrospective cohort consisting of more than 4000 professional military members aged 18-50 years in Eastern Taiwan. All participants received history taking, physical examination, chest radiography, 12-lead electrocardiography, blood tests for cell counts and fasting glucose, lipid profiles, uric acid, renal function and liver function in the Hualien Armed Forces General Hospital during 2014. In addition, participants were required to undergo two indoor resistant exercise tests including 2-min push-up and 2-min sit-up, both scored by infrared sensing, and one outdoor endurance 3000-m none weight-bearing running test, the main indicator of cardiorespiratory fitness in the Military Physical Training and Testing Center in Eastern Taiwan in 2014. RESULTS Hospitalization events for cardiovascular disease, acute kidney injury, rhabdomyolysis, severe infectious disease, acute psychiatric illness, diabetes, orthopedic surgery and mortality will be identified in the National Insurance Research Database for 10 years. CONCLUSION CHIEF will be among the largest Eastern Asian armed forces cohort, in which physical status was strictly evaluated to follow up the hospitalization events for severe illness. PMID:27621774

  4. Molecular mechanisms of statin intolerance

    PubMed Central

    Franczyk, Beata; Toth, Peter P.; Rysz, Jacek; Banach, Maciej

    2016-01-01

    Statins reduce cardiovascular morbidity and mortality in primary and secondary prevention. Despite their efficacy, many persons are unable to tolerate statins due to adverse events such as hepatotoxicity and myalgia/myopathy. In the case of most patients, it seems that mild-to-moderate abnormalities in liver and muscle enzymes are not serious adverse effects and do not outweigh the benefits of coronary heart disease risk reduction. The risk for mortality or permanent organ damage ascribed to statin use is very small and limited to cases of myopathy and rhabdomyolysis. Statin-induced muscle-related adverse events comprise a highly heterogeneous clinical disorder with numerous, complex etiologies and a variety of genetic backgrounds. Every patient who presents with statin-related side effects cannot undergo the type of exhaustive molecular characterization that would include all of these mechanisms. Frequently the only solution is to either discontinue statin therapy/reduce the dose or attempt intermittent dosing strategies at a low dose. PMID:27279860

  5. Drug-Induced Nephrotoxicity and Its Biomarkers

    PubMed Central

    Kim, Sun Young; Moon, Aree

    2012-01-01

    Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefi ts with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identifi ed for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity. PMID:24130922

  6. 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

  7. Selective serotonin reuptake inhibitor drug interactions in patients receiving statins.

    PubMed

    Andrade, Chittaranjan

    2014-02-01

    Elderly patients commonly receive statin drugs for the primary or secondary prevention of cardiovascular and cerebrovascular events. Elderly patients also commonly receive antidepressant drugs, usually selective serotonin reuptake inhibitors (SSRIs), for the treatment of depression, anxiety, or other conditions. SSRIs are associated with many pharmacokinetic drug interactions related to the inhibition of the cytochrome P450 (CYP) metabolic pathways. There is concern that drugs that inhibit statin metabolism can trigger statin adverse effects, especially myopathy (which can be potentially serious, if rhabdomyolysis occurs). However, a detailed literature review of statin metabolism and of SSRI effects on CYP enzymes suggests that escitalopram, citalopram, and paroxetine are almost certain to be safe with all statins, and rosuvastatin, pitavastatin, and pravastatin are almost certain to be safe with all SSRIs. Even though other SSRI-statin combinations may theoretically be associated with risks, the magnitude of the pharmacokinetic interaction is likely to be below the threshold for clinical significance. Risk, if at all, lies in combining fluvoxamine with atorvastatin, simvastatin, or lovastatin, and even this risk can be minimized by using lower statin doses and monitoring the patient. PMID:24602259

  8. Three fatal intoxications due to methylone.

    PubMed

    Pearson, Julia M; Hargraves, Tiffanie L; Hair, Laura S; Massucci, Charles J; Frazee, C Clinton; Garg, Uttam; Pietak, B Robert

    2012-07-01

    We present three fatal intoxications of methylone, a cathinone derivative. Blood was analyzed with a routine alkaline liquid-liquid extraction and analyzed by gas chromatography coupled with a mass spectrometer (GC-MS). Methylone was identified by a full scan mass spectral comparison to an analytical standard of methylone. For a definitive and conclusive confirmation and quantitation, methylone was also derivatized with heptafluorobutyric anhydride and analyzed by GC-MS. In all three fatalities, the deceased exhibited seizure-like activity and elevated body temperatures (103.9, 105.9 and 107°F) before death. Two of the three cases also exhibited metabolic acidosis. One of the three cases had prolonged treatment and hospitalization before death with symptoms similar to sympathomimetic toxicity, including metabolic acidosis, rhabdomyolysis, acute renal failure and disseminated intravascular coagulation. The laboratory results for this patient over the 24 h period of hospitalization were significant for increased lactate, liver transaminases, creatinine, myoglobin, creatine kinase and clotting times, and decreased pH, glucose and calcium. Peripheral blood methylone concentrations in the three fatal cases were 0.84, 3.3 and 0.56 mg/L. In conlusion, peripheral blood methylone concentrations in excess of 0.5 mg/L may result in death due to its toxic properties, which can include elevated body temperature and other sympathomimetic-like symptoms. PMID:22589523

  9. 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

  10. 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

  11. Acute endosulfan poisoning: a retrospective study.

    PubMed

    Moon, Jeong Mi; Chun, Byeong Jo

    2009-05-01

    Endosulfan is a widely used insecticide that is associated with a high fatality rate in humans when ingested accidentally or with the aim of suicide. However, the literature concerning human endosulfan exposure is limited to case reports. Thus, we sought to 1) describe the clinical features of patients with acute endosulfan poisoning and 2) identify independent factors to predict patients' outcome. Fifty-two patients who presented with acute endosulfan poisoning between January 2001 and January 2007 were enrolled in this retrospective study. Sixteen (30.7%) of the 52 patients died, and 48 patients experienced seizures. Endosulfan poisoning caused the hypotension and the abnormalities on electrocardiogram at presentation. Over half of the patients developed complications, such as rhabdomyolysis, hepatic toxicity, and hypotension. These complications resolved without sequelae in the survival group. Refractory status epilepticus was the most common cause of death in this series (75.0%). Amount ingested being greater than 35 g of endosulfan was the most found to be an independent variable that predicted patient mortality. Patients with this risk factor must be treated aggressively during the early stage of endosulfan poisoning. PMID:19755461

  12. Paravertebral compartment syndrome after training causing severe back pain in an amateur rugby player: report of a rare case and review of the literature

    PubMed Central

    2013-01-01

    Background Acute compartment syndrome (CS) of the paravertebral muscles without external trauma is rarely reported in literature. Not all of clinical symptoms for CS are applicable to the paravertebral region. Case presentation A 30-year-old amateur rugby player was suffering from increasing back pain following exertional training specially targeting back muscles. He presented with hardly treatable pain of the lumbar spine, dysaesthesia of the left paravertebral lumbar region as well as elevated muscle enzymes. Magnetic resonance imaging (MRI) showed an edema of the paravertebral muscles. Compartment pressure measurement revealed increased values of 47 mmHg on the left side. Seventy-two hours after onset of back pain a fasciotomy of the superficial thoracolumbar fascia was performed. Immediately postoperatively the clinical condition improved and enzyme levels significantly decreased. The patient started with light training exercises 3 weeks after the operation. Conclusions We present a rare case of an exercise-induced compartment syndrome of the paravertebral muscles and set it in the context of existing literature comparing various treatment options and outcomes. Where there is evidence of paravertebral compartment syndrome we recommend immediate fasciotomy to prevent rhabdomyolysis and further consequential diseases. PMID:24004522

  13. 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

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

    PubMed

    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

  15. 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

  16. 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 drug–drug 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-naïve 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

  17. 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

  18. Lipids in liver transplant recipients.

    PubMed

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

    2016-03-28

    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. PMID:27022213

  19. 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

  20. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update.

    PubMed

    Schachter, Michael

    2005-02-01

    low-density lipoprotein cholesterol, followed by atorvastatin, simvastatin and pravastatin. As a class, statins are generally well tolerated and serious adverse events, including muscle toxicity leading to rhabdomyolysis, are rare. Consideration of the differences between the statins helps to provide a rational basis for their use in clinical practice. PMID:15660968

  1. Statin safety: lessons from new drug applications for marketed statins.

    PubMed

    Jacobson, Terry A

    2006-04-17

    Safety has become a central issue in the management of dyslipidemia with statins. A review of New Drug Applications (NDAs) and the US Food and Drug Administration (FDA) Web site was conducted for all 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, with a major focus on cerivastatin and rosuvastatin. The findings provide insight into the incidence of adverse events for this class of drugs and support the significant benefits of statins relative to associated risks. These data delineate the nature of statin associated liver, muscle, and renal adverse events. Although transaminase levels increase in a dose-related fashion with statins, a definitive correlation between statin therapy and hepatotoxicity is not supported by statin NDA data. Statin-induced myopathy is a relatively rare event (1 in 1,000) and rhabdomyolysis is even rarer (1 in 10,000). The cerivastatin NDA, along with its supplementary NDA, was the first to demonstrate a clear statin dose-response relation with myopathy and a threshold effect above which myotoxicity increases significantly. Proteinuria was identified as a consequence of statin therapy with data from the rosuvastatin NDA, and subsequent analysis suggests a class effect that is dose related but transient. Studies in cell culture suggest the mechanism is a pharmacologic effect on the proximal renal tubule. The available evidence suggests no clear renal toxicity with currently approved statins, because no declines in renal function or glomerular filtration rate have been documented over time. Overall, currently marketed statins have a very favorable benefit-to-risk relation with respect to liver, muscle, and renal issues. PMID:16581328

  2. Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions.

    PubMed

    Shitara, Yoshihisa; Sugiyama, Yuichi

    2006-10-01

    3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used for the treatment of hypercholesterolemia. Their efficacy in preventing cardiovascular events has been shown by a large number of clinical trials. However, myotoxic side effects, sometimes severe, including myopathy or rhabdomyolysis, are associated with the use of statins. In some cases, such toxicity is associated with pharmacokinetic alterations. In this review, the pharmacokinetic aspects and physicochemical properties of statins are reviewed in order to understand the mechanism governing their pharmacokinetic alterations. Among the statins, simvastatin, lovastatin and atorvastatin are metabolized by cytochrome P450 3A4 (CYP3A4) while fluvastatin is metabolized by CYP2C9. Cerivastatin is subjected to 2 metabolic pathways mediated by CYP2C8 and 3A4. Pravastatin, rosuvastatin and pitavastatin undergo little metabolism. Their plasma clearances are governed by the transporters involved in the hepatic uptake and biliary excretion. Also for other statins, which are orally administered as open acid forms (i.e. fluvastatin, cerivastatin and atorvastatin), hepatic uptake transporter(s) play important roles in their clearances. Based on such information, pharmacokinetic alterations of statins can be predicted following coadministration of other drugs or in patients with lowered activities in drug metabolism and/or transport. We also present a quantitative analysis of the effect of some factors on the pharmacokinetics of statins based on a physiologically based pharmacokinetic model. To avoid a pharmacokinetic alteration, we need to have information about the metabolizing enzyme(s) and transporter(s) involved in the pharmacokinetics of statins and, along with such information, model-based prediction is also useful. PMID:16714062

  3. 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

  4. Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone.

    PubMed

    Johnson, Timothy E; Zhang, Xiaohua; Bleicher, Kimberly B; Dysart, Gary; Loughlin, Amy F; Schaefer, William H; Umbenhauer, Diane R

    2004-11-01

    Statins are widely used to treat lipid disorders. These drugs are safe and well tolerated; however, in <1% of patients, myopathy and/or rhabdomyolysis can develop. To better understand the mechanism of statin-induced myopathy, we examined the ability of structurally distinct statins to induce apoptosis in an optimized rat myotube model. Compound A (a lactone) and Cerivastatin (an open acid) induced apoptosis, as measured by TUNEL and active caspase 3 staining, in a concentration- and time-dependent manner. In contrast, an epimer of Compound A (Compound B) exhibited a much weaker apoptotic response. Statin-induced apoptosis was completely prevented by mevalonate or geranylgeraniol, but not by farnesol. Zaragozic acid A, a squalene synthase inhibitor, caused no apoptosis on its own and had no effect on Compound-A-induced myotoxicity, suggesting the apoptosis was not a result of cholesterol synthesis inhibition. The geranylgeranyl transferase inhibitors GGTI-2133 and GGTI-2147 caused apoptosis in myotubes; the farnesyl transferase inhibitor FTI-277 exhibited a much weaker effect. In addition, the prenylation of rap1a, a geranylgeranylated protein, was inhibited by Compound A in myotubes at concentrations that induced apoptosis. A similar statin-induced apoptosis profile was seen in human myotube cultures but primary rat hepatocytes were about 200-fold more resistant to statin-induced apoptosis. Although the statin-induced hepatotoxicity could be attenuated with mevalonate, no effect was found with either geranylgeraniol or farnesol. In studies assessing ubiquinone levels after statin treatment in rat and human myotubes, there was no correlation between ubiquinone levels and apoptosis. Taken together, these observations suggest that statins cause apoptosis in myotube cultures in part by inhibiting the geranylgeranylation of proteins, but not by suppressing ubiquinone concentration. Furthermore, the data from primary hepatocytes suggests a cell-type differential

  5. Acetaminophen Attenuates Lipid Peroxidation in Children Undergoing Cardiopulmonary Bypass

    PubMed Central

    Simpson, Scott A.; Zaccagni, Hayden; Bichell, David P.; Christian, Karla G.; Mettler, Bret A.; Donahue, Brian S.; Roberts, L. Jackson; Pretorius, Mias

    2014-01-01

    Objective Hemolysis, occurring during cardiopulmonary bypass (CPB), is associated with lipid peroxidation and postoperative acute kidney injury (AKI). Acetaminophen (ApAP) inhibits lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated rhabdomyolysis-induced AKI. This pilot study tests the hypothesis that ApAP attenuates lipid peroxidation in children undergoing CPB. Design Single center prospective randomized double blinded study. Setting University-affiliated pediatric hospital. Patients Thirty children undergoing elective surgical correction of a congenital heart defect. Interventions Patients were randomized to ApAP (OFIRMEV® (acetaminophen) injection, Cadence Pharmaceuticals, San Diego, CA) or placebo every 6 hours for 4 doses starting before the onset of CPB. Measurement and Main Results Markers of hemolysis, lipid peroxidation (isofurans and F2-isoprostanes) and AKI were measured throughout the perioperative period. CPB was associated with a significant increase in free hemoglobin (from a pre-bypass level of 9.8±6.2 mg/dl to a peak of 201.5±42.6 mg/dl post-bypass). Plasma and urine isofuran and F2-isoprostane concentrations increased significantly during surgery. The magnitude of increase in plasma isofurans was greater than the magnitude in increase in plasma F2-isoprostanes. ApAP attenuated the increase in plasma isofurans compared to placebo (P=0.02 for effect of study drug). There was no significant effect of ApAP on plasma F2-isoprostanes or urinary makers of lipid peroxidation. ApAP did not affect postoperative creatinine, urinary neutrophil gelatinase-associated lipocalin or prevalence of AKI. Conclusion CPB in children is associated with hemolysis and lipid peroxidation. ApAP attenuated the increase in plasma isofuran concentrations. Future studies are needed to establish whether other therapies that attenuate or prevent the effects of free hemoglobin result in more effective inhibition of lipid peroxidation in patients

  6. Protection of rat skeletal muscle fibers by either L-carnitine or coenzyme Q10 against statins toxicity mediated by mitochondrial reactive oxygen generation

    PubMed Central

    La Guardia, P. G.; Alberici, L. C.; Ravagnani, F. G.; Catharino, R. R.; Vercesi, A. E.

    2013-01-01

    Mitochondrial redox imbalance has been implicated in mechanisms of aging, various degenerative diseases and drug-induced toxicity. Statins are safe and well-tolerated therapeutic drugs that occasionally induce myotoxicity such as myopathy and rhabdomyolysis. Previous studies indicate that myotoxicity caused by statins may be linked to impairment of mitochondrial functions. Here, we report that 1-h incubation of permeabilized rat soleus muscle fiber biopsies with increasing concentrations of simvastatin (1–40 μM) slowed the rates of ADP-or FCCP-stimulated respiration supported by glutamate/malate in a dose-dependent manner, but caused no changes in resting respiration rates. Simvastatin (1 μM) also inhibited the ADP-stimulated mitochondrial respiration supported by succinate by 24% but not by TMPD/ascorbate. Compatible with inhibition of respiration, 1 μM simvastatin stimulated lactate release from soleus muscle samples by 26%. Co-incubation of muscle samples with 1 mM L-carnitine, 100 μM mevalonate or 10 μM coenzyme Q10 (Co-Q10) abolished simvastatin effects on both mitochondrial glutamate/malate-supported respiration and lactate release. Simvastatin (1 μM) also caused a 2-fold increase in the rate of hydrogen peroxide generation and a decrease in Co-Q10 content by 44%. Mevalonate, Co-Q10 or L-carnitine protected against stimulation of hydrogen peroxide generation but only mevalonate prevented the decrease in Co-Q10 content. Thus, independently of Co-Q10 levels, L-carnitine prevented the toxic effects of simvastatin. This suggests that mitochondrial respiratory dysfunction induced by simvastatin, is associated with increased generation of superoxide, at the levels of complexes-I and II of the respiratory chain. In all cases the damage to these complexes, presumably at the level of 4Fe-4S clusters, is prevented by L-carnitine. PMID:23720630

  7. 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

  8. 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

  9. 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

  10. A Multi-Stage Ultra-Endurance Run over 1,200 KM Leads to a Continuous Accumulation of Total Body Water

    PubMed Central

    Knechtle, Beat; Duff, Brida; Schulze, Ingo; Kohler, Götz

    2008-01-01

    We determined whether ultra-runners in a multi-stage ultra- endurance run lose body mass, fat mass, skeletal muscle mass or total body water in a descriptive field study at the ‘Deutschlandlauf’ 2007 a 1,200 km run within 17 consecutive days with 10 male non-professional Caucasian ultra-runners (mean ± SD, 43.8 ± 6.2 years, 73.8 ± 6.0 kg body mass, 1.77 ± 0.05 m body height, BMI 23.3 ± 1.8 kg·m-2). Body mass, fat mass, skeletal muscle mass, lean body mass and percent total body water were determined using bioelectrical impedance analysis and the anthropometric method before the race and after each stage. In addition, urinary specific gravity was measured in order to quantify hydration status. Fat mass (bioelectrical impedance analysis) decreased by 3.9 kg (p < 0.05), skeletal muscle mass (anthropometric method) decreased by 2.0 kg (p < 0.05) whereas percent total body water increased by 6.1 % (p < 0.05) by the end of the race. Ultra-runners in a multi-stage ultra-endurance event over 1,200 km, with 17 consecutive stages, showed a cumulative increase in percent total body water, a decrease in skeletal muscle mass and a decrease in fat mass, depending upon the method used. We presume that the eccentric component of running leads to damage of skeletal muscle, leading to rhabdomyolysis, with impaired renal function. Key pointsUltra-runners in a multi-stage ultra-endurance run over 1,200 km in 17 consecutive stages suffered a decrease in fat mass, skeletal muscle mass and an increase in total body water, whereas overall body mass showed no change. PMID:24149903

  11. 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

  12. 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

  13. Emerging drugs of abuse: current perspectives on substituted cathinones.

    PubMed

    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

  14. 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.

  15. Neuroleptic intolerance in patients with anti-NMDAR encephalitis

    PubMed Central

    Lejuste, Florian; Thomas, Laure; Picard, Géraldine; Desestret, Virginie; Ducray, François; Rogemond, Veronique; Psimaras, Dimitri; Antoine, Jean-Christophe; Delattre, Jean-Yves; Groc, Laurent; Leboyer, Marion

    2016-01-01

    Objective: To precisely describe the initial psychiatric presentation of patients with anti-NMDA receptor (NMDAR) antibodies encephalitis (anti-NMDAR encephalitis) to identify potential clues enhancing its early diagnosis. Methods: We retrospectively studied the French Reference Centre medical records of every adult patient with anti-NMDAR encephalitis to specify the patients' initial psychiatric symptoms leading to hospitalization in a psychiatric department and the reasons underlying the diagnosis of anti-NMDAR encephalitis. Results: The medical records of 111 adult patients were reviewed. Psychiatric features were the initial presentation in 65 patients (59%). Among them, several psychiatric manifestations were observed, including visual and auditory hallucinations (n = 26, 40%), depression (n = 15, 23%), mania (n = 5, 8%), acute schizoaffective episode (n = 15, 23%), and eating disorder or addiction (n = 4; 6%). Forty-five patients (40% of total cohort) were first hospitalized in a psychiatric institution (91% women), with a median duration of stay of 9 days (range 0.25–239 days). Among them, 24 patients (53%) had associated discreet neurologic signs at the first evaluation, while 17 additional patients (38%) developed neurologic signs within a few days. Twenty-one patients (47%) were transferred to a medical unit for a suspicion of antipsychotic intolerance characterized by high temperature, muscle rigidity, mutism or coma, and biological results suggesting rhabdomyolysis. Conclusions: Several psychiatric presentations were observed in patients with anti-NMDAR encephalitis, although none was specific; however, patients, mostly women, also had discreet neurologic signs that should be carefully assessed as well as signs of antipsychotic intolerance that should raise suspicion for anti-NMDAR encephalitis. PMID:27606355

  16. 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

  17. 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

  18. Synthesis and characterization of cationic polymeric nanoparticles as simvastatin carriers for enhancing the osteogenesis of bone marrow mesenchymal stem cells.

    PubMed

    Wang, Chau-Zen; Fu, Yin-Chih; Jian, Shih-Ciang; Wang, Yan-Hsiung; Liu, Po-Len; Ho, Mei-Ling; Wang, Chih-Kuang

    2014-10-15

    Simvastatin (SIM) can increase osteoblast activity and enhance osteogenesis. However, some limitations of SIM have been noted, such as statin-associated rhabdomyolysis and its poor solubility in water. In this study, we fabricated new cationic nanoparticles (NPs) designed for the controlled release of hydrophobic SIM and endocytosis by cells with the aim of reducing the total required amount of SIM administered and enhancing the osteogenesis of bone marrow mesenchymal stem cells (BMSCs). New copolymers of bis(poly(lactic-co-glycolic acid)-phenylalanine-polyethylene glycol)-quaternary ammonium grafted diethyltriamine (bis(PLGA-phe-PEG)-qDETA; BPPD) were created using a diethyltriamine-quaternary ammonium (qDETA) moiety, hetero-bifunctional polyethylene glycol (COOH-PEG-NH2), phenylalanine (phe) and poly(lactic-co-glycolic acid) (PLGA). SIM encapsulated in BPPD NPs (SIM/BPPD) was fabricated using a water-miscible solvent. The size distributions of BPPD NPs and SIM/BPPD NPs, the encapsulation efficacy and the in vitro release profile of SIM in SIM/BPPD NPs over 6days were investigated. Based on the results of Alizarin Red S staining, alkaline phosphatase (ALP) activity assays and quantitative polymerase chain reaction (Q-PCR) results, we propose that SIM/BPPD NPs may induce osteogenesis in BMSCs by enhancing the expression of an osteogenic gene, which subsequently elevates ALP activity and mineralization, resulting in enhanced BMSC osteogenesis. These results suggest that the SIM/BPPD NPs may be used as hydrophobic drug carriers to reduce the total required amount of SIM administered and to provide an effective SIM release mechanism for enhancing BMSC osteogenesis. Surprisingly, BPPD NPs were also shown to have the ability to promote osteogenesis in BMSCs by enhancing the expression of osteogenic genes, especially osteocalcin (OC), and subsequently elevating ALP activity and mineralization. PMID:25086394

  19. Procoagulant activity in patients with sickle cell trait.

    PubMed

    Lawrie, Andrew S; Pizzey, Arnold; Trompeter, Sara; Meiselman, Herbert; Mohandas, Narla; Dumanski, Jan P; Westerman, Maxwell P

    2012-06-01

    Patients with sickle cell trait (STr) are usually considered to be asymptomatic. However, complications, including hypercoagulability, increased risk of venous thromboembolism and the exertional exercise syndrome with rhabdomyolysis and sudden death, have been described. The exact cause of these adverse events is unclear. We have investigated two patients, a set of monozygotic twins with STr, to establish their procoagulant activity status as a potential indicator of thrombotic risk. In-vivo thrombin generation was assessed by the measurement of prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT). D-dimer was used as a marker of fibrinolytic activity. The potential to generate thrombin was determined using an ex-vivo thrombin generation test (TGT). The impact of red blood cell (RBC)-derived microparticle shedding and RBC rheology were examined. TAT (>60 μg/l) and F1 + 2 (948 pmol/l) were markedly elevated in patient 2 but within the normal reference range in patient 1 (TAT = 2.5 μg/l; F1 + 2 = 138 pmol/l). D-dimer levels (0.9 mg/l FEU) were similarly elevated in both patients. TGT peak thrombin and endogenous thrombin potential (ETP) were elevated to similar degrees in both patients. Flow cytometric analysis for RBC-derived microparticles showed that both patients had elevated levels on two occasions. RBC deformability, blood viscosity and RBC aggregation were normal and similar in both patients. The results demonstrated different coagulation activity in the patients with one patient in a prothrombotic state, suggesting that there may be two levels of hypercoagulability in STr. Measurement of such differences would allow for separation of high and low-risk patients from serious complications. PMID:22343687

  20. 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

  1. 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

  2. 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

  3. 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

  4. Computed Biological Relations among Five Select Treatment-Related Organ/Tissue Toxicities.

    PubMed

    Sakellaropoulos, Theodore; Herod, Timothy J; Alexopoulos, Leonidas G; Bai, Jane P F

    2016-05-16

    Drug toxicity presents a major challenge in drug development and patient care. We set to build upon previous works regarding select drug-induced toxicities to find common patterns in the mode of action of the drugs associated with these toxicities. In particular, we focused on five disparate organ toxicities, peripheral neuropathy (PN), rhabdomyolysis (RM), Stevens-Johnson syndrome/toxic epidermal necrosis (SJS/TEN), lung injury (LI), and heart contraction-related cardiotoxicity (CT), and identified biological commonalities between and among the toxicities in terms of pharmacological targets and nearest neighbors (indirect effects) using the hyper-geometric test and a distance metric of Spearman correlation. There were 20 significant protein targets associated with two toxicities and 0 protein targets associated with three or more toxicities. Per Spearman distance, PN was closest to SJS/TEN compared to other pairs, whereas the pairs involving RM were more different than others excluding RM. The significant targets associated with RM outnumbered those associated with every one of the other four toxicities. Enrichment analysis of drug targets that are expressed in corresponding organ/tissues determined proteins that should be avoided in drug discovery. The identified biological patterns emerging from the mode of action of these drugs are statistically associated with these serious toxicities and could potentially be used as predictors for new drug candidates. The predictive power and usefulness of these biological patterns will increase with the database of these five toxicities. Furthermore, extension of our approach to all severe adverse reactions will produce useful biological commonalities for reference in drug discovery and development. PMID:27063352

  5. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide

    PubMed Central

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  6. [Mushroom poisoning--the dark side of mycetism].

    PubMed

    Flammer, René; Schenk-Jäger, Katharina M

    2009-05-01

    Most mushroom intoxications become evident within 12 hours with vomiting and diarrhea. They can be divided into incidents with a short latency (less than four hours) and incidents with a long latency (longer than four hours). As a rule of thumb amatoxin poisonings must be considered in case of symptoms appearing with a long latency (8-12-18 h), especially after consumption of non-controlled wild mushrooms. Shorter latencies do not exclude amatoxin poisoning. Large meals of mushrooms, which are rich in chitin, mixed meals and individual factors, may shorten latency and disguise amatoxin poisoning. Any vomiting and diarrhea after mushroom consumption is suspicious. Unless the mushrooms are not to be identified within 30 minutes by an expert, specific treatment for amatoxin poisoning must be started. Identification shall be achieved by macroscopic or microscopic means; and urine analysis for amatoxins are crucial. By commencing treatment before analysis, mortality rates may be as low as 5%. Current standards in amatoxin poisoning treatment can be obtained at the Swiss Toxicological Information Centre (Phone 145), where contacts to mycologists are available as well. Emergency mycologists are listed on the website www.vapko.ch. Of the 18 different syndromes we present the most common and most important in Switzerland. In an overview all of them are listed. Early gastrointestinal syndrome with its short latency of less than 4 h and indigestion with a very variable latency are the most common. Psychotropic symptoms after consumptions of fly agaric and panther cap are rare, in case of psilocybin-containing mushrooms, symptoms are frequent, but hardly ever lead to medical treatment. In case of renal failure and rhabdomyolysis of unknown origin, completing a patient's history by questioning nutritional habits might reveal causal relationship with ingestion of orellanin-containing mushrooms or tricholoma equestre respectively. Mushrooms in the backyard are attractive for

  7. Human rabies--Wisconsin, 2010.

    PubMed

    2011-09-01

    In late December 2010, a male resident of Wisconsin, aged 70 years, sought treatment for progressive right shoulder pain, tremors, abnormal behavior, and dysphagia at an emergency department (ED). He was admitted for observation and treated with benzodiazepines and haloperidol, a neuroleptic, for presumed alcohol withdrawal syndrome. The next day, he had rhabdomyolysis, fever, and rigidity, and neuroleptic malignant syndrome was diagnosed. The neuroleptic was discontinued, but the patient's clinical status worsened, with encephalopathy, respiratory failure, acute renal failure requiring hemodialysis, and episodes of cardiac arrest. With continued clinical deterioration, additional causes were considered, including rabies. On hospital day 12, rabies virus antigens and nucleic acid were detected in the nuchal skin biopsy and rabies virus nucleic acid in saliva specimens sent to CDC. A rabies virus variant associated with silver-haired bats (Lasionycteris noctivagans) was identified. The patient died on hospital day 13. His spouse reported that they had been selling firewood, and bats had been present in the woodpile; however, the man had not reported a bat bite. Two relatives and five health-care workers potentially exposed to the man's saliva received postexposure prophylaxis. This case highlights the variable presentations of rabies and the ease with which a diagnosis of rabies can be missed in a clinically challenging patient with comorbidities. Clinicians should consider rabies in the differential diagnosis for patients with progressive encephalitis or neurologic illness of unknown etiology and caregivers should take precautions to avoid exposure to body fluids. Continued public education regarding risks for rabies virus exposure during interactions with wildlife, particularly bats, is important. PMID:21881547

  8. A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER) Database and Association Analysis

    PubMed Central

    Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi

    2016-01-01

    Background Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. Methods and Findings We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. Conclusions Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported

  9. 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

  10. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide.

    PubMed

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  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. Heat stroke with multiple organ failure treated with cold hemodialysis and cold continuous hemodiafiltration: a case report.

    PubMed

    Wakino, Shu; Hori, Shingo; Mimura, Takuya; Fujishima, Seitaroh; Hayashi, Koichi; Inamoto, Hajime; Saruta, Takao; Aikawa, Naoki

    2005-10-01

    A 23-year-old comatose man was presented in the emergency room. He had been working inside a building under construction on a hot summer's day. His core body temperature was 42.1 degrees C and he was diagnosed with heat stroke. Urgent cooling procedures, including applying cold vapor to the patient's skin, a gastric lavage with cold water and an intravenous cold saline infusion, were not completely successful and his body temperature remained above 40 degrees C. Because his high temperature was refractory to conventional cooling procedures and we suspected that acute renal failure (ARF) by rhabdomyolysis would develop, we applied hemodialysis (HD) using cold dialysate (initially 30 degrees C and later 35 degrees C), followed by continuous hemodiafiltration (CHDF) with cold dialysate (35 degrees C) at a high flow rate of 18,000 mL per hour. The patient's body temperature fell below 38.0 degrees C within 3 h and was kept below 38.0 degrees C. Continuous hemodiafiltration was continued for one week. During the first week, the patient suffered from multiple organ failure (MOF) involving renal failure, as well as the failure of heart, liver, lung, and central nervous systems. Disseminated intravascular coagulation also developed. However, by virtue of cold CHDF, he almost recovered 3 weeks after the onset, except for remaining mild liver and renal dysfunction. In severe heat stroke, cold HD and high flow, cold CHDF should be a therapeutic choice for cooling and treatment of MOF. Considering mild liver and renal dysfunction still remained, this case suggested these procedures should be initiated at the very beginning of the treatment of severe heat stroke. PMID:16202019

  13. 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

  14. HMG CoA reductase inhibitor-induced myotoxicity: pravastatin and lovastatin inhibit the geranylgeranylation of low-molecular-weight proteins in neonatal rat muscle cell culture.

    PubMed

    Flint, O P; Masters, B A; Gregg, R E; Durham, S K

    1997-07-01

    In previous studies, inhibition of cholesterol synthesis by HMG CoA reductase inhibitors (HMGRI) was associated with myotoxicity in cultures of neonatal rat skeletal myotubes, and rhabdomyolysis in rats, rabbits, and humans in vivo. In vitro myotoxicity was directly related to HMGRI-induced depletion of mevalonate, farnesol, and geranylgeraniol, since supplementation with these intermediate metabolites abrogated the toxicity. Both farnesol and geranylgeraniol are required for the posttranslational modification, or isoprenylation, of essential regulatory proteins in mammalian cells. The objective of the present study was to measure changes in protein isoprenylation in cultured neonatal rat skeletal muscle cells exposed for 24 hr to increasing concentrations of pravastatin or lovastatin. Proteins were labeled with [3H]mevalonate, [3H]farnesyl pyrophosphate (FPP), or [3H]geranylgeranyl pyrophosphate (GGPP), and then separated by SDS-PAGE and quantitated by scintillation counting and densitometry of autoradiographs. Mevalonate and FPP labeling of the majority of proteins increased in a concentration-dependent manner, even at concentrations greater than 2 microM lovastatin and 25 microM pravastatin that completely inhibited cholesterol synthesis. In contrast, mevalonate and FPP labeling of three protein bands with molecular weights of 26.6, 27.7, and 28.9 kDa was markedly inhibited at concentrations higher than 1 microM lovastatin and 400 microM pravastatin, which inhibited protein synthesis and disrupted myotube morphology after longer exposures in a previous study. In contrast, these proteins were equally well labeled by GGPP at all HMGRI concentrations tested, suggesting that isoprenylation of the 26.9-, 27.8-, and 28.9-kDa proteins requires geranylgeraniol. The results of this study indicate that HMGRI-induced myotoxicity is most likely related to reduced posttranslational modification of specific regulatory proteins by geranylgeraniol. PMID:9221829

  15. Mitochondrial-targeted plastoquinone derivatives. Effect on senescence and acute age-related pathologies.

    PubMed

    Skulachev, M V; Antonenko, Y N; Anisimov, V N; Chernyak, B V; Cherepanov, D A; Chistyakov, V A; Egorov, M V; Kolosova, N G; Korshunova, G A; Lyamzaev, K G; Plotnikov, E Y; Roginsky, V A; Savchenko, A Y; Severina, I I; Severin, F F; Shkurat, T P; Tashlitsky, V N; Shidlovsky, K M; Vyssokikh, M Y; Zamyatnin, A A; Zorov, D B; Skulachev, V P

    2011-06-01

    Plastoquinone, a very effective electron carrier and antioxidant of chloroplasts, was conjugated with decyltriphenylphosphonium to obtain a cation easily penetrating through membranes. This cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H(2) from its oxidized form that appears as a result of the antioxidant activity of SkQ1H(2). SkQ1H(2) prevents oxidation of cardiolipin, a mitochondrial phospholipid that is especially sensitive to attack by reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H(2)O(2)-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (cataract, retinopathies, achromotrichia, osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of β-galactosidase, phosphorylation of H2AX histones, etc.) and (iii) lower tissue damage and save the lives of young animals after treatments resulting in kidney ischemia, rhabdomyolysis, heart attack, arrhythmia, and stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondria-mediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast "biochemical suicide" of an organism after a severe metabolic crisis. PMID:21269268

  16. 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

  17. 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 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

  18. 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

  19. 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

  20. Leptospirosis Presenting with Rapidly Progressing Acute Renal Failure and Conjugated Hyperbilirubinemia: A Case Report.

    PubMed

    Pothuri, Pallavi; Ahuja, Keerat; Kumar, Viki; Lal, Sham; Tumarinson, Taisiya; Mahmood, Khalid

    2016-01-01

    BACKGROUND Unexplained renal insufficiency combined with hepatic failure is a common problem encountered by clinicians. As with many disease processes involving multi-organ systems, reversible causes are usually not readily identifiable, and for many patients their health deteriorates rapidly. We present a rare cause of acute renal failure and hyperbilirubinemia occurring simultaneously, with leptospirosis presenting as Weil's disease. CASE REPORT A 53-year-old male presented to our clinic with complaints of anuria over the past two days. His symptoms started with dark urine, severe cramps in the thighs, and chills. The patient was a visitor to the United States from Guyana. Positive physical examination findings included mild tachycardia and hypotension, scleral icterus, and tenderness over abdomen, costovertebral angles, and thighs. The patient had a high white blood cell count, thrombocytopenia, renal/hepatic insufficiency, and an urinary tract infection (UTI). The patient was initially treated under the suspicion of acute kidney injury secondary to rhabdomyolysis and pyelonephritis. The patient continued to deteriorate with decreasing platelet counts, worsening renal function, hyperbilirubinemia, and respiratory distress, with no improvement with hemodialysis. Broad-spectrum antibiotics were administered, including doxycycline, due to a high suspicion of leptospirosis. The patient's condition drastically improved after initiation of doxycycline. On subsequent days, the patient's Leptospira antibody results were available, showing titers of more than 1:3200. Hemodialysis was discontinued as the patient started producing urine with improved kidney function. CONCLUSIONS As world travel becomes more economically feasible, we will continue to encounter foreign endemic diseases. Leptospirosis presenting as Weil's disease is a common cause of renal and hyperbilirubinemia in endemic areas. Often, as was the case for our patient where the time from presentation to acute

  1. Movement disorder emergencies in childhood.

    PubMed

    Kirkham, F J; Haywood, P; Kashyape, P; Borbone, J; Lording, A; Pryde, K; Cox, M; Keslake, J; Smith, M; Cuthbertson, L; Murugan, V; Mackie, S; Thomas, N H; Whitney, A; Forrest, K M; Parker, A; Forsyth, R; Kipps, C M

    2011-09-01

    The literature on paediatric acute-onset movement disorders is scattered. In a prospective cohort of 52 children (21 male; age range 2mo-15y), the commonest were chorea, dystonia, tremor, myoclonus, and Parkinsonism in descending order of frequency. In this series of mainly previously well children with cryptogenic acute movement disorders, three groups were recognised: (1) Psychogenic disorders (n = 12), typically >10 years of age, more likely to be female and to have tremor and myoclonus (2) Inflammatory or autoimmune disorders (n = 22), including N-methyl-d-aspartate receptor encephalitis, opsoclonus-myoclonus, Sydenham chorea, systemic lupus erythematosus, acute necrotizing encephalopathy (which may be autosomal dominant), and other encephalitides and (3) Non-inflammatory disorders (n = 18), including drug-induced movement disorder, post-pump chorea, metabolic, e.g. glutaric aciduria, and vascular disease, e.g. moyamoya. Other important non-inflammatory movement disorders, typically seen in symptomatic children with underlying aetiologies such as trauma, severe cerebral palsy, epileptic encephalopathy, Down syndrome and Rett syndrome, include dystonic posturing secondary to gastro-oesophageal reflux (Sandifer syndrome) and Paroxysmal Autonomic Instability with Dystonia (PAID) or autonomic 'storming'. Status dystonicus may present in children with known extrapyramidal disorders, such as cerebral palsy or during changes in management e.g. introduction or withdrawal of neuroleptic drugs or failure of intrathecal baclofen infusion; the main risk in terms of mortality is renal failure from rhabdomyolysis. Although the evidence base is weak, as many of the inflammatory/autoimmune conditions are treatable with steroids, immunoglobulin, plasmapheresis, or cyclophosphamide, it is important to make an early diagnosis where possible. Outcome in survivors is variable. Using illustrative case histories, this review draws attention to the practical difficulties in

  2. 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

    2016-01-01

    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

  3. Long-term effects following 4 years of randomized treatment with atorvastatin in patients with type 2 diabetes mellitus on hemodialysis.

    PubMed

    Krane, Vera; Schmidt, Kay-Renke; Gutjahr-Lengsfeld, Lena J; Mann, Johannes F E; März, Winfried; Swoboda, Florian; Wanner, Christoph

    2016-06-01

    The 4D (Die Deutsche Diabetes Dialyse) Study was a randomized, double-blind trial comparing 4 years of treatment with atorvastatin to placebo in 1255 hemodialysis patients with type 2 diabetes. The primary end point of cardiovascular events (cardiac death, myocardial infarction, and stroke) was non-significantly reduced by 8%. However, long-term effects remained uncertain. Therefore, surviving patients were invited to a follow-up survey done by questionnaire. Post-trial statin therapy was at nephrologist discretion, and outcomes were centrally adjudicated and analyzed by intention to treat and time to first event in the original treatment groups. Median overall follow-up was 11.5 years. Post-trial statin use and low-density lipoprotein cholesterol levels did not differ between groups. Statin treatment non-significantly affected the former primary outcome (relative risk, 0.91; 95% confidence interval, 0.78-1.07). The risk of all cardiac events combined and the risk of cardiac death were significantly lower in the original statin group compared to placebo (0.83, 0.70-0.97, and 0.80, 0.66-0.97). No significant effect was detected on cerebrovascular events, fatal stroke, fatal cancer, non-vascular, or all-cause death. No rhabdomyolysis was reported. Thus, after 4 years of atorvastatin treatment in diabetic hemodialysis patients, similar effects on outcomes were found after 11.5 years of follow-up as were found at the end of the original study. There was no evidence of emerging hazards in the long term, confirming current clinical practice guidelines. PMID:26924051

  4. A case of fatal caffeine poisoning.

    PubMed

    Rudolph, T; Knudsen, K

    2010-04-01

    Caffeine is a natural alkaloid methylxanthine that is found in various plants such as coffee or tea. Symptoms of a severe overdose may present with hypokalemia, hyponatremia, ventricular arrhythmias, hypertension followed by hypotension, respiratory failure, seizures, rhabdomyolysis, ventricular fibrillation and finally circulatory collapse. A 21-year-old woman called for the ambulance herself soon after the ingestion of about 10,000 mg of caffeine. At the arrival of the ambulance, the patient went into cardiac arrest almost immediately. After a total resuscitation period of 34 min including seven counter-shocks and 2 mg epinephrine, the patient was stable enough to be transferred to the hospital. The patient soon went into VF again and received two more counter-shocks and 1 mg epinephrine and finally an intravenous bolus dose of 300 mg amiodarone. The initial arterial blood gas showed pH at 6.47, lactate at 33 mmol/l and potassium level at 2.3 mmol/l. Unfortunately, no blood samples for caffeine analysis were taken. Three days after hospital admission, the patient developed myoclonus, which did not respond to medical treatment. Excessive intake of caffeine may produce arrhythmias and pronounced hypokalemia and ensuing ventricular fibrillation. In case of counter-shock-resistant VF, it can be necessary to give an early loading dose of amiodarone. Furthermore, it may be beneficial to replace the potassium as early as possible. Epinephrine and buffer solutions used during resuscitation may further decrease blood potassium levels and should be administrated cautiously. Epinephrine can be replaced by other vasopressor drugs, such as vasopressin without effects on beta-receptors. PMID:20096021

  5. Diversity and severity of adverse reactions to quinine: A systematic review.

    PubMed

    Liles, Nathan W; Page, Evaren E; Liles, Amber L; Vesely, Sara K; Raskob, Gary E; George, James N

    2016-05-01

    Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of drug-induced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immune-mediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered. PMID:26822544

  6. 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

  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. "Bath salts" and "plant food" products: the experience of one regional US poison center.

    PubMed

    Murphy, Christine M; Dulaney, Anna R; Beuhler, Michael C; Kacinko, Sherri

    2013-03-01

    included rhabdomyolysis, renal failure, excited delirium syndrome, and death. While treatments have not been empirically determined, sedation with benzodiazepines, aggressive cooling for hyperthermic patients, and use of small doses of antipsychotics for choreoathetoid movements not controlled with benzodiazepines are not likely to be harmful. PMID:22733603

  9. Hypothesizing that designer drugs containing cathinones ("bath salts") have profound neuro-inflammatory effects and dangerous neurotoxic response following human consumption.

    PubMed

    Blum, Kenneth; Foster Olive, M; Wang, Kevin K W; Febo, Marcelo; Borsten, Joan; Giordano, John; Hauser, Mary; Gold, Mark S

    2013-09-01

    Consensus in the most recent literature indicates that psychoactive "bath salts" is a relatively new drug-combination that was added to Schedule I classification in October 2011. Common ingredients include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not yet been well studied. We propose an intensive systematic investigation to determine the potential for cathinones to produce neurotoxic effects in various brain regions. In spite of a lack of evidence, for neurotoxicity there are number of horrific cases now on record that suggest intensification of research is needed. For example, a suicide by hanging had high 3,4-MDPV concentration while a driver under the influence had the highest reported methylone (MEPH) concentration. More interestingly, there have been consistent case reports indicating delayed responses, including: severe agitation with possible psychosis, suicidal ideation, rhabdomyolysis, hypertension, tachycardia, and death. In animal studies, amphetamine (AMPH), methamphetamine (METH) and cocaine release dopamine (DA), similarly to the action of cathinone and particular cathinone analogues. Two components of bath salts, MEPH and MDPV produce opposite effects at human dopamine transporter (hDAT) comparable to METH and cocaine, respectively. Moreover, it has already been found by others that MEPH is almost as potent as METH; and MDPV is much more potent than cocaine with longer lasting effects. It has been conjectured correctly that bath salts containing MDPV and MEPH (or a similar drug) might be expected both, to initially release DA and subsequently prevent its reuptake via hDAT. The null hypothesis, that cathinones do not cause neurotoxicity to dopamine nerve endings of the striatum, seems parsimonious and requires intensive investigation. Our hypothesis is that when consumed by humans, cathinones may induce neurotoxic pathways involving the neuro

  10. Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats.

    PubMed

    Schaefer, William H; Lawrence, Jeffery W; Loughlin, Amy F; Stoffregen, Dana A; Mixson, Lori A; Dean, Dennis C; Raab, Conrad E; Yu, Nathan X; Lankas, George R; Frederick, Clay B

    2004-01-01

    As a class, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors can potentially cause skeletal myopathy. One statin, cerivastatin, has recently been withdrawn from the market due to an unacceptably high incidence of rhabdomyolysis. The mechanism underlying statin-induced myopathy is unknown. This paper sought to investigate the relationship among statin-induced myopathy, mitochondrial function, and muscle ubiquinone levels. Rats were administered cerivastatin at 0.1, 0.5, and 1.0 (mg/kg)/day or dose vehicle (controls) by oral gavage for 15 days. Samples of type I-predominant skeletal muscle (soleus) and type II-predominant skeletal muscle [quadriceps and extensor digitorum longus (EDL)], and blood were collected on study days 5, 10, and 15 for morphological evaluation, clinical chemistry, mitochondrial function tests, and analysis of ubiquinone levels. No histological changes were observed in any of the animals on study days 5 or 10, but on study day 15, mid- and high-dose animals had necrosis and inflammation in type II skeletal muscle. Elevated creatine kinase (CK) levels in blood (a clinical marker of myopathy) correlated with the histopathological diagnosis of myopathy. Ultrastructural characterization of skeletal muscle revealed disruption of the sarcomere and altered mitochondria only in myofibers with degeneration, while adjacent myofibers were unaffected and had normal mitochondria. Thus, mitochondrial effects appeared not to precede myofiber degeneration. Mean coenzyme Q9 (CoQ9) levels in all dose groups were slightly decreased relative to controls in type II skeletal muscle, although the difference was not significantly different in most cases. Mitochondrial function in skeletal muscle was not affected by the changes in ubiquinone levels. The ubiquinone levels in high-dose-treated animals exhibiting myopathy were not significantly different from low-dose animals with no observable toxic effects. Furthermore, ubiquinone levels did not correlate

  11. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance.

    PubMed

    Neuvonen, Pertti J; Niemi, Mikko; Backman, Janne T

    2006-12-01

    Lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl-coenzyme A inhibitors (statins), are widely used in the treatment and prevention of atherosclerotic disease. The benefits of statins are well documented. However, lipid-lowering drugs may cause myopathy, even rhabdomyolysis, the risk of which is increased by certain interactions. Simvastatin, lovastatin, and atorvastatin are metabolized by cytochrome P450 (CYP) 3A4 (simvastatin acid is also metabolized by CYP2C8); their plasma concentrations and risk of myotoxicity are greatly increased by strong inhibitors of CYP3A4 (eg, itraconazole and ritonavir). Weak or moderately potent CYP3A4 inhibitors (eg, verapamil and diltiazem) can be used cautiously with small doses of CYP3A4-dependent statins. Cerivastatin is metabolized by CYP2C8 and CYP3A4, and fluvastatin is metabolized by CYP2C9. The exposure to fluvastatin is increased by less than 2-fold by inhibitors of CYP2C9. Pravastatin, rosuvastatin, and pitavastatin are excreted mainly unchanged, and their plasma concentrations are not significantly increased by pure CYP3A4 inhibitors. Cyclosporine (INN, ciclosporin) inhibits CYP3A4, P-glycoprotein (multidrug resistance protein 1), organic anion transporting polypeptide 1B1 (OATP1B1), and some other hepatic uptake transporters. Gemfibrozil and its glucuronide inhibit CYP2C8 and OATP1B1. These effects of cyclosporine and gemfibrozil explain the increased plasma statin concentrations and, together with pharmacodynamic factors, the increased risk of myotoxicity when coadministered with statins. Inhibitors of OATP1B1 may decrease the benefit/risk ratio of statins by interfering with their entry into hepatocytes, the site of action. Lipid-lowering drugs can be involved also in other interactions, including those between enzyme inducers and CYP3A4 substrate statins, as well as those between gemfibrozil and CYP2C8 substrate antidiabetics. Knowledge of the pharmacokinetic and pharmacodynamic properties of lipid

  12. Hyperglycemic hyperosmolar nonketotic syndrome.

    PubMed

    Venkatraman, R; Singhi, Sunit C

    2006-01-01

    Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) was infrequently diagnosed till recently. Now it is being diagnosed with increasing frequency in obese children with type 2 diabetes mellitus (T2 DM) and its incidence is likely to go up, given global increase in incidence of childhood obesity, increased insulin resistance, and T2 DM. The syndrome is characterized by severe hyperglycemia, a marked increase in serum osmolality and dehydration without accumulation of beta -hydroxybutyric or acetoacetic ketoacids. Significant ketogenesis is restrained by the ability of the pancreas to secrete small amount of insulin. Prolonged phase of osmotic diuresis leads to severe depletion of body water, which excees that of sodium, resulting in hypertonic dehydration. These children, usually obese adolescents with T2 DM, present with signs of severe dehydration and depressed mental status but continue to have increased rather than decreased urine output and are at increased risk of developing rhabdomyolysis and malignant hyperthermia. Emergency treatment is directed at restoration of the intravascular volume, followed by correction of deficits of fluid and electrolyte (Na+, K+, Ca++, Mg++, PO4++), hyperglycemia and serum hyperosmolarity, and a thorough search for conditions that may lead to this metabolic decompensation and their treatment. Use of iso-osomolar isotonic fluid (0.9% saline) until hemodynamic stabilization initially, followed by 0.45% saline with insulin infusion at the rate of 0.1 units/kg/hour, addition of 5% dextrose in fluids and reduction of insulin infusion once the blood glucose is 250 to 300 mg/dl is generally recommended. However, evidence-based guidelines about composition and tonicity of fluids and electrolyte solutions for early resuscitation and rehydration, the rate of infusion-rapid vs slow, and insulin dose-low vs normal, in treatment of HHNS in children are awaited. Careful monitoring of glucose levels and ensuring adequate hydration in patients

  13. Metabolic markers in sports medicine.

    PubMed

    Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna

    2012-01-01

    Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should

  14. Leptospirosis Presenting with Rapidly Progressing Acute Renal Failure and Conjugated Hyperbilirubinemia: A Case Report

    PubMed Central

    Pothuri, Pallavi; Ahuja, Keerat; Kumar, Viki; Lal, Sham; Tumarinson, Taisiya; Mahmood, Khalid

    2016-01-01

    Patient: Male, 53 Final Diagnosis: Leptospirosis Symptoms: — Medication: — Clinical Procedure: None Specialty: Infectious Diseases Objective: Rare disease Background: Unexplained renal insufficiency combined with hepatic failure is a common problem encountered by clinicians. As with many disease processes involving multi-organ systems, reversible causes are usually not readily identifiable, and for many patients their health deteriorates rapidly. We present a rare cause of acute renal failure and hyperbilirubinemia occurring simultaneously, with leptospirosis presenting as Weil’s disease. Case Report: A 53-year-old male presented to our clinic with complaints of anuria over the past two days. His symptoms started with dark urine, severe cramps in the thighs, and chills. The patient was a visitor to the United States from Guyana. Positive physical examination findings included mild tachycardia and hypotension, scleral icterus, and tenderness over abdomen, costovertebral angles, and thighs. The patient had a high white blood cell count, thrombocytopenia, renal/hepatic insufficiency, and an urinary tract infection (UTI). The patient was initially treated under the suspicion of acute kidney injury secondary to rhabdomyolysis and pyelonephritis. The patient continued to deteriorate with decreasing platelet counts, worsening renal function, hyperbilirubinemia, and respiratory distress, with no improvement with hemodialysis. Broad-spectrum antibiotics were administered, including doxycycline, due to a high suspicion of leptospirosis. The patient’s condition drastically improved after initiation of doxycycline. On subsequent days, the patient’s Leptospira antibody results were available, showing titers of more than 1:3200. Hemodialysis was discontinued as the patient started producing urine with improved kidney function. Conclusions: As world travel becomes more economically feasible, we will continue to encounter foreign endemic diseases. Leptospirosis

  15. 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

  16. 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

  17. What's in the Literature?

    PubMed

    Silvestri, Nicholas J; Wolfe, Gil I; Bromberg, Mark; Lacomis, David

    2016-06-01

    One of the first questions asked by patients and family members when a diagnosis of amyotrophic lateral sclerosis is made is "what about stem cells?" The term "stem cells" has attractiveness to it, with the assumption that stem cell treatment (stem nerve cells) can replace lost nerve cells. There are perhaps 2 types of stem cell trials, those that are vetted by the Food and Drug Administration and those that have no official oversight and whose results are infrequently published. The issue of the latter was discussed in the last edition of this column. The results of one of the formal stem cell trials now in the United States have been reported. Spinal muscular atrophy is a form of motor neuron disease affecting children and has a genetic cause, which has led to a feasibility study giving antisense oligonucleotides, and the results have also been reported. Biomarkers of amyotrophic lateral sclerosis are being sought, and the presence of neurofilaments is promising. Inflammatory neuropathies are an important group because they are treatable. Intravenous immune globulin is a commonly used agent, but a number of questions persist: one is efficacy among brands, another is the probability of a response, and a third is optimum dosing and taper schedules. A number of recent articles address these issues. The predictive value of single-fiber electromyography in determining which patients with ocular myasthenia will develop generalized disease, the risk of crisis after thymectomy, and 2 papers discussing new forms of congenital myasthenic syndrome are discussed. The risk of brain tumors, quality of life, and the assessment of trunk muscle strength in patients with type 1 myotonic dystrophy is reviewed. An article describing the discovery of mutations in SCN4A as a cause of congenital myopathy is discussed, as is one describing the occurrence of rhabdomyolysis in a group of patients subsequently discovered to have various forms of muscular dystrophy. Finally, articles

  18. 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

  19. [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

  20. The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy.

    PubMed

    Eng, Heather; Scialis, Renato J; Rotter, Charles J; Lin, Jian; Lazzaro, Sarah; Varma, Manthena V; Di, Li; Feng, Bo; West, Michael; Kalgutkar, Amit S

    2016-05-01

    Chronic treatment of methicillin-resistantStaphylococcus aureusstrains with the bacteriostatic agent fusidic acid (FA) is frequently associated with myopathy including rhabdomyolysis upon coadministration with statins. Because adverse effects with statins are usually the result of drug-drug interactions, we evaluated the inhibitory effects of FA against human CYP3A4 and clinically relevant drug transporters such as organic anion transporting polypeptides OATP1B1 and OATP1B3, multidrug resistant protein 1, and breast cancer resistance protein, which are involved in the oral absorption and/or systemic clearance of statins including atorvastatin, rosuvastatin, and simvastatin. FA was a weak reversible (IC50= 295 ± 1.0μM) and time-dependent (KI= 216 ± 41μM andkinact= 0.0179 ± 0.001 min(-1)) inhibitor of CYP3A4-catalyzed midazolam-1'-hydroxylase activity in human liver microsomes. FA demonstrated inhibition of multidrug resistant protein 1-mediated digoxin transport with an IC50value of 157 ± 1.0μM and was devoid of breast cancer resistance protein inhibition (IC50> 500μM). In contrast, FA showed potent inhibition of OATP1B1- and OATP1B3-specific rosuvastatin transport with IC50values of 1.59μM and 2.47μM, respectively. Furthermore, coadministration of oral rosuvastatin and FA to rats led to an approximately 19.3-fold and 24.6-fold increase in the rosuvastatin maximum plasma concentration and area under the plasma concentration-time curve, respectively, which could be potentially mediated through inhibitory effects of FA on rat Oatp1a4 (IC50= 2.26μM) and Oatp1b2 (IC50= 4.38μM) transporters, which are responsible for rosuvastatin uptake in rat liver. The potent inhibition of human OATP1B1/OATP1B3 by FA could attenuate hepatic uptake of statins, resulting in increased blood and tissue concentrations, potentially manifesting in musculoskeletal toxicity. PMID:26888941

  1. Outcome of Patients with Carbon Monoxide Poisoning at a Far-East Poison Center

    PubMed Central

    Lin, Ja-Liang; Huang, Wen-Hung; Yang, Huang-Yu; Weng, Cheng-Hao; Lin, Che-Min; Lee, Shwu-Hua; Wang, I-Kuan; Liang, Chih-Chia; Chang, Chiz-Tzung; Lin, Wey-Ran; Yen, Tzung-Hai

    2015-01-01

    Introduction Many cases of carbon monoxide poisoning in Taiwan are due to burning charcoal. Nevertheless, few reports have analyzed the mortality rate of these patients who survive to reach a hospital and die despite intensive treatment. Therefore, this study examined the clinical features, physiological markers, and outcomes after carbon monoxide poisoning and the associations between these findings. Methods We analyzed the records of 261 patients who were referred for management of carbon monoxide intoxication between 2000 and 2010. Patients were grouped according to status at discharge as alive (survivor, n = 242) or dead (non-survivor, n = 19). Demographic, clinical, laboratory, and mortality data were obtained for analysis. Results Approximately half of the cases (49.4%) attempted suicide by burning charcoal. Most of the patients were middle-aged adults (33±19 years), and were referred to our hospital in a relatively short period of time (6±10 hours). Carbon monoxide produced many serious complications after exposure: fever (26.1%), hypothermia (9.6%), respiratory failure (34.1%), shock (8.4%), myocardial infarction (8.0%), gastrointestinal upset (34.9%), hepatitis (18.4%), renal failure (25.3%), coma (18.0%) and rhabdomyolysis (21.8%). Furthermore, the non-survivors suffered greater incidences of hypothermia (P<0.001), respiratory failure (P<0.001), shock (P<0.001), hepatitis ((P=0.016), renal failure (P=0.003), coma (P<0.001) than survivors. All patients were treated with high concentration of oxygen therapy using non-rebreather mask. However, hyperbaric oxygen therapy was only used in 18.8% of the patients. In a multivariate-Cox-regression model, it was revealed that shock status was a significant predictor for mortality after carbon monoxide poisoning (OR 8.696, 95% CI 2.053-37.370, P=0.003). Finally, Kaplan-Meier analysis confirmed that patients with shock suffered greater cumulative mortality than without shock (Log-rank test, Chi-square 147.404, P<0

  2. 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; García, Hugo R Hernández; 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

  3. Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk

    PubMed Central

    Hou, Qingtao; Li, Sheyu; Li, Ling; Li, Yun; Sun, Xin; Tian, Haoming

    2015-01-01

    Abstract Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin-related myopathy risk remained controversial. This study aimed to investigate this genetic association. Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle–Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27–3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43–3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41–10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47–5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64–5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38–6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74–2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57–3.12, P = 0.52). The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of

  4. 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

    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, Sjögren'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

  5. [Sudden unexpected natural death from a viewpoint of forensic pathology].

    PubMed

    Takatsu, A

    1995-12-01

    for grasping antemortem pathophysiological state in SUND cases 1) Standardization of the degree of cardiac hypertrophy based on heart weight. In the course of our preliminary examination, we found that heart weight correlates significantly with body length and weight. Therefore, we tried to standardize the range of normotrophy, hypertrophy and hypoplasia/atrophy of the heart based on the correlation between heart weight and body type index calculated by body length and weight (Broca's index). 2) Evaluation of the clinical laboratory data in cadaveric blood. We examined 32 clinical laboratory parameters in cadaveric blood samples obtained from 192 autopsy cases. Behaviour of the laboratory parameters in cadaveric blood in relation to postmortem interval was divided into four types: increased, decreased, no particular tendency and remaining between upper and lower normal value. Parameters included in the last type, which is a useful tool for speculation of antemortem pathophysiology were T-Bil, TTT, ZTT, BUN, Cre, UA, alpha 1- and beta 2-microglobin, T-Chol, GHA1c, TP, A/G, Hb and Hct. A case was demonstrated in which values of clinical laboratory parameters in agonar stage were the same as in cadaveric blood obtained at autopsy. This indicates that caution is necessary in evaluating clinical laboratory data in agonar patients in the emergency room. 3) Diagnostic evaluation of immunohistochemical myoglobin staining in the kidney In order to evaluate the diagnostic value of myoglobin (Mb) staining in the kidney in medicolegal autopsy cases, Mb staining was carried out on the kidney sections of 141 victims, including 59 natural and 82 unnatural deaths. At the same time, Serum and Urine GFR parameters were measured and systemic histological changes were observed on some sections of each kidney. The incidence of Mb positive cases was 74.6% in unnatural, and 25.4% in natural death, indicating the importance of nontraumatic rhabdomyolysis in natural death cases. PMID:8583687

  6. When Coke Is Not Hydrating

    PubMed Central

    Talibmamury, Nibras; Alalusi, Sumer; Nadham, Omar; Omer, Abdel Rahman; Smalligan, Roger D.

    2014-01-01

    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, Sjögren’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