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Sample records for rhabdomyolysis

  1. 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

  2. Exertional Rhabdomyolysis after Spinning

    PubMed Central

    Jeong, Youjin; Oh, Eun-Jung; Ahn, Ah-Leum; Choi, Jae-Kyung; Cho, Dong-Yung

    2016-01-01

    Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24–48 hours after attending a spinning class at a local gymnasium. Paired with key laboratory findings, her symptoms were suggestive of rhabdomyolysis. She required hospital admission to sustain renal function through fluid resuscitation therapy and fluid balance monitoring. Because exertional rhabdomyolysis may occur in any unfit but otherwise healthy individual who indulges in stationary cycling, the potential health risks of this activity must be considered. PMID:27900075

  3. When exercise causes exertional rhabdomyolysis.

    PubMed

    Furman, Janet

    2015-04-01

    Exertional rhabdomyolysis is a clinical condition caused by intense, repetitive exercise or a sudden increase in exercise in an untrained person, although rhabdomyolysis can occur in trained athletes. In many cases, the presentation of early, uncomplicated rhabdomyolysis is subtle, but serious complications such as renal failure, compartment syndrome, and dysrhythmias may arise if severe exertional rhabdomyolysis is undiagnosed or untreated. Management is further complicated by the lack of concrete management guidelines for treating rhabdomyolysis and returning patients to activity.

  4. Assessing acquired rhabdomyolysis in adults.

    PubMed

    Kruger, Danielle; Han, Joseph

    2017-01-01

    The presentation of patients with rhabdomyolysis is variable and can range in severity from asymptomatic serum elevations of creatine kinase to life-threatening electrolyte disturbances and acute kidney injury. Clinicians must have a high suspicion for rhabdomyolysis and be familiar with the risk factors for developing this condition. This article focuses on prompt recognition and evidence-based approaches to diagnose and treat rhabdomyolysis.

  5. 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

  6. Rhabdomyolysis case based on hypothyroidism

    PubMed Central

    Katipoglu, Bilal; Acehan, Fatih; Meteris, Ayşenur; Yılmaz, Nisbet

    2016-01-01

    Summary Hypothyroidism is a wide clinical spectrum disorder and only a few cases in literature show this. Rhabdomyolysis and acute renal impairment can be seen concurrently in a hypothyroid state. We report a case of severe hypothyroidism with poor drug compliance leading to rhabdomyolysis and acute kidney injury. Learning points: Hypothyroidism is a rare cause of acute kidney injury. In this case report, we studied a rare occurrence of acute renal impairment due to hypothyroidism with poor drug compliance, which induced rhabdomyolysis. Our report emphasized that thyroid status should be evaluated in patients with unexplained acute renal impairment or presenting with the symptoms of muscle involvement. PMID:27855234

  7. Rhabdomyolysis from Statins: What's the Risk?

    MedlinePlus

    ... complications. With Francisco Lopez-Jimenez, M.D. References Miller ML. Causes of rhabdomyolysis. http://www.uptodate.com/home. Accessed Oct. 19, 2015. Miller ML. Clinical manifestations and diagnosis of rhabdomyolysis. http:// ...

  8. Rhabdomyolysis associated with kava ingestion.

    PubMed

    Bodkin, Ryan; Schneider, Sandra; Rekkerth, Donna; Spillane, Linda; Kamali, Michael

    2012-05-01

    We report a case of rhabdomyolysis temporally related to the ingestion of a large amount of kava. Kava is a naturally occurring plant used in the United States and elsewhere in the world for its sedative properties. A previous case report also related rhabdomyolysis to the ingestion of kava. It is not clear whether this is an action of the kava itself, perhaps, due to its action on voltage ion channels or, perhaps, due to an adulterant in the product. Our patient developed peak creatine phosphokinase levels in excess of 30 000 U/L but had no significant renal damage.

  9. 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.

  10. 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

  11. Severe rhabdomyolysis after doxylamine overdose.

    PubMed

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

    1993-06-01

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

  12. Haff Disease: Rhabdomyolysis After Eating Buffalo Fish

    PubMed Central

    Herman, Linda L.; Bies, Christine

    2014-01-01

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

  13. Acute rhabdomyolysis caused by Spirulina (Arthrospira platensis).

    PubMed

    Mazokopakis, Elias E; Karefilakis, Christos M; Tsartsalis, Athanasios N; Milkas, Anastasios N; Ganotakis, Emmanuel S

    2008-06-01

    Rhabdomyolysis is a potentially life-threatening disorder that occurs as a primary disease or as a complication of a broad spectrum of other diseases. We report the first case of acute rhabdomyolysis after ingestion of Spirulina (Arthrospira platensis), a plantonic blue-green alga, as a dietary supplement.

  14. Risk factors for rhabdomyolysis following doxylamine overdose.

    PubMed

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

    2007-08-01

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

  15. White collar rhabdomyolysis with acute kidney injury

    PubMed Central

    Bhakthavatsalam, R. K.; Venu, G.; Raju, P. Krishnam; Madhusudan, H. C.

    2016-01-01

    Rhabdomyolysis is a clinical syndrome resulting from the disintegration of muscle cell and spillage of toxic intracellular contents into circulation. Strenuous, unaccustomed exercise leads to exertional rhabdomyolysis and cause AKI. We report a 26-year-old female who developed white collar rhabdomyolysis with AKI after performing sit-ups (Super Yoga Brain) for 108 times in temple. She was managed with hemodialysis and supporting therapy. She made a full recovery after 4 weeks. Awareness of this condition and early diagnosis is highlighted. PMID:27942178

  16. [Rhabdomyolysis in a bodybuilder using anabolic steroids].

    PubMed

    Hageloch, W; Appell, H J; Weicker, H

    1988-09-01

    The clinical course and the laboratory findings of a massive rhabdomyolysis in a male bodybuilder is presented. Particularly spectacular are the light- and electron-microscopical pictures of the histological findings. The acute renal failure as the most important and major life-threatening complication of the rhabdomyolysis is considered and the successful therapeutic procedure is described. The probability of a causal relation between anabolic steroids and rhabdomyolysis is discussed as well as the resulting consequences for the care of athletes in sports medicine.

  17. Low-Intensity Repetitive Exercise Induced Rhabdomyolysis.

    PubMed

    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.

  18. Hyponatraemia associated rhabdomyolysis following water intoxication

    PubMed Central

    Katsarou, Alexia; Singh, Suveer

    2010-01-01

    A young man with bipolar disorder was admitted in a coma. Cerebral oedema secondary to severe hyponatraemia was implicated. This was due to self-induced water intoxication. He developed rhabdomyolysis, a massive creatine kinase (out of proportion to longstanding antipsychotic medication) and acute renal failure. In the intensive care unit, hyponatraemia was corrected, and following appropriate fluid resuscitation, with forced alkaline diuresis, the rhabdomyolysis and renal function normalised, averting renal support. While a full recovery ensued, the persisting risk factors for hyponatraemia, that is polydipsia, and its association with rhabdomyolysis, increased the chances of a recurrence. Closely supervised regulation of his water intake, and monitoring of antipsychotic efficacy (for biochemical homeostatsis) are essential for secondary prevention. Rhabdomyolysis is a rare complication of hyponatraemia. When associated with psychogenic polydipsia, the acute and chronic management are challenging. Vaptans, which are aquaretics, that preferentially prevent renal tubular water reabsorption, may be beneficial in this situation. PMID:22778200

  19. Hyponatraemia associated rhabdomyolysis following water intoxication.

    PubMed

    Katsarou, Alexia; Singh, Suveer

    2010-09-09

    A young man with bipolar disorder was admitted in a coma. Cerebral oedema secondary to severe hyponatraemia was implicated. This was due to self-induced water intoxication. He developed rhabdomyolysis, a massive creatine kinase (out of proportion to longstanding antipsychotic medication) and acute renal failure. In the intensive care unit, hyponatraemia was corrected, and following appropriate fluid resuscitation, with forced alkaline diuresis, the rhabdomyolysis and renal function normalised, averting renal support. While a full recovery ensued, the persisting risk factors for hyponatraemia, that is polydipsia, and its association with rhabdomyolysis, increased the chances of a recurrence. Closely supervised regulation of his water intake, and monitoring of antipsychotic efficacy (for biochemical homeostatsis) are essential for secondary prevention. Rhabdomyolysis is a rare complication of hyponatraemia. When associated with psychogenic polydipsia, the acute and chronic management are challenging. Vaptans, which are aquaretics, that preferentially prevent renal tubular water reabsorption, may be beneficial in this situation.

  20. 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

  1. 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.

  2. Proton Pump Inhibitors and Risk of Rhabdomyolysis.

    PubMed

    Duncan, Scott J; Howden, Colin W

    2017-01-01

    Proton pump inhibitors (PPIs) have been associated with a variety of adverse events, although the level of evidence for many of these is weak at best. Recently, one national regulatory authority has mandated a change to the labeling of one PPI based on reports of possible associated rhabdomyolysis. Thus, in this review we summarize the available evidence linking PPI use with rhabdomyolysis. The level of evidence is insufficient to establish a causal relationship and is largely based on sporadic case reports. In general, patients with suspected PPI-associated rhabdomyolysis have not been re-challenged with a PPI after recovery. The mechanism whereby PPIs might have been associated with rhabdomyolysis is unclear but possibly related to interaction with concomitantly administered drugs such as HMG-CoA reductase inhibitors (statins). For patients with rhabdomyolysis, a careful search must be made for possible etiological factors. In patients who recover from an episode of possible PPI-related rhabdomyolysis but do not have a genuine requirement for PPI treatment, the PPI should not be re-introduced. For those with a definite indication for ongoing PPI treatment, the PPI can be re-introduced but should preferably not be administered with a statin.

  3. Automated Fluid Management for Treatment of Rhabdomyolysis

    PubMed Central

    Beilstein, Christian M.; Prowle, John R.

    2016-01-01

    Purpose. Fluid therapy aimed at increasing urine output is a commonly employed strategy to prevent acute kidney injury (AKI) in critically ill patients with rhabdomyolysis. Automated fluid management has the potential to optimise urine output while avoiding fluid accumulation in rhabdomyolysis patients. Methods. In a single centre clinical service evaluation we compared a convenience sample of critically ill adults with rhabdomyolysis treated with automated fluid management using the RenalGuard® device to patients managed with manual fluid adjustment following our standard rhabdomyolysis protocol. Primary outcome was number of hours with urine output >2 mL/kg during first 48 h of therapy. Results. Eight patients treated with RenalGuard were compared to 28 patients treated with manual fluid management. Number of hours of target urine output was greater in the RenalGuard versus the Standard group (176/312 (56.4%) versus 534/1305 (40.9%); p < 0.01). Urine output was significantly higher in the first 24 h in the RenalGuard group (median (IQR) 4033 mL (3682–7363) versus 2913 mL (2263–4188 mL); p < 0.01). Fluid balance, electrolyte, diuretics, and bicarbonate use were comparable between groups. Conclusions. Automated fluid management resulted in a higher urine output more quickly in the treatment of rhabdomyolysis. Further research is needed to analyse the effect of diuresis-matched hydration for the prevention of AKI in rhabdomyolysis. PMID:28003911

  4. Rhabdomyolysis

    MedlinePlus

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

  5. Rhabdomyolysis in Critically Ill Surgical Patients

    PubMed Central

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

    2016-01-01

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

  6. 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

  7. Abiraterone-induced rhabdomyolysis: A case report.

    PubMed

    Moore, Donald C; Moore, Andrew

    2017-03-01

    Abiraterone is an inhibitor of androgen biosynthesis indicated for the treatment of metastatic castration-resistant prostate cancer. Common side effects include diarrhea, edema, hypokalemia, hypertension, and liver function test abnormalities. We report a case of rhabdomyolysis developing in association with the use of abiraterone. Following discontinuation of abiraterone, creatine kinase concentrations decreased gradually throughout the duration of the hospitalization.

  8. [Rhabdomyolysis from gabapentin: a case report].

    PubMed

    Falconi, Daniela; Tattoli, Fabio; Brunetti, Carlo; De Prisco, Ornella; Gherzi, Maurizio; Marazzi, Federico; Marengo, Marita; Serra, Ilaria; Tamagnone, Michela; Formica, Marco

    2015-01-01

    Gabapentin (GBP) is a drug with different indications.Is not metabolized and is excreted by the kidney. The common side effects are: arthralgia, myalgia, fatigue, dizziness and ataxia. Rhabdomyolysis is an extremely rare side effect. This latter, that can be caused by trauma, strenuous exercise, infections, drugs and toxins, is a syndrome characterized by loss of skeletal muscle resulting in the release of myocyte components in the circulation. Following a case of rhabdomyolysis caused by GBP in patient with chronic renal failure (CRF). A 65-year-old diabetic men, in peritoneal dialysis (PD), affected by ischemic and hypokinetic cardiomyopathy, sensorimotor neuropathy. The patient reported: weakness, diffuse myalgias, hypotension. He had been taking GBP for three days, after the failure of therapies with tricyclic antidepressants, opioids and NSAIDs. Laboratory tests confirmed the increase of the indices of muscle necrosis.The immediate withdrawal of the drug in association with CAPD dialysis treatment, led to improvement of the clinical and biochemical parameters. During the last 10 years, 3 cases of rhabdomyolysis referred to the assumption of GBP have been reported. The use of PD for treatment of acute renal failure, has been significantly reduced over the years. The effectiveness of the purification method is much lower than the one with the continuous extracorporeal treatments. In conclusion, GBP may be associated with rhabdomyolysis. Since GBP toxicity in CRF patients is often overlooked, a better awareness of this phenomenon and a thorough follow-up of laboratory tests to detect any possible early adverse reaction is suggested.

  9. The syndrome of rhabdomyolysis: complications and treatment.

    PubMed

    Chatzizisis, Yiannis S; Misirli, Gesthimani; Hatzitolios, Apostolos I; Giannoglou, George D

    2008-12-01

    Rhabdomyolysis is a syndrome of skeletal muscle cell damage that leads to the release of toxic intracellular material into the systemic circulation. The pathogenesis of rhabdomyolysis is based on an increase in free ionized calcium in the cytoplasm. Its main complications include (a) acute renal failure, which is triggered by renal vasoconstriction and ischemia, (b) myoglobin cast formation in the distal convoluted tubules, and (c) direct renal toxic effect of myoglobin on the epithelial cells of proximal convoluted tubules. Other major complications include electrolyte disorders, such as hyperkalemia, which may cause cardiac arrhythmias, metabolic acidosis, hyperphosphatemia, early hypocalcemia, and late hypercalcemia. Compartmental syndrome and disseminated intravascular coagulopathy may also emerge. The management of myoglobinuric acute renal failure includes aggressive fluid administration to restore the hypovolemia and urine alkalization. The concomitant electrolyte and metabolic disorders should also be treated appropriately; hemodialysis should be considered when life-threatening hyperkalemia and metabolic acidosis exist. In the case of compartmental syndrome, it is important to monitor the intra-compartmental pressure and to perform fasciotomy, if required. When diagnosed early and if the appropriate treatment is initiated promptly, the complications of rhabdomyolysis are preventable and the syndrome has a good prognosis.

  10. A case of dermatomyositis with rhabdomyolysis, rescued by intravenous immunoglobulin.

    PubMed

    Mizoguchi, Fumitaka; Takada, Kazuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Kohsaka, Hitoshi; Miyasaka, Nobuyuki

    2015-07-01

    We describe a case of severe dermatomyositis (DM) complicated by rhabdomyolysis, acute tubular necrosis, and hemophagocytosis. The case failed to respond to corticosteroids, but showed rapid and significant improvement after the addition of intravenous immunoglobulin (IVIG). While the prognosis of DM is poor when it is complicated by rhabdomyolysis, the early administration of IVIG has the potential to be the cornerstone of its management.

  11. Ischemic neuropathy and rhabdomyolysis as presenting symptoms of postpartum cardiomyopathy.

    PubMed

    Helmich, Rick C G; van Laarhoven, Hanneke W M; Schoonderwaldt, Hennie C; Janssen, Mirian C H

    2009-05-01

    Rhabdomyolysis and peripheral neuropathy are two distinct disease entities which are rarely encountered in combination. We present a woman with rhabdomyolysis and peripheral neuropathy 3 weeks postpartum. Her symptoms were caused by bilateral femoral artery thrombosis due to postpartum cardiomyopathy (PPCM). This demonstrates that PPCM may present with predominantly non-cardial symptoms and underscores the importance of rapidly recognizing this disorder.

  12. Typhoid Fever Complicated by Hemophagocytic Lymphohistiocytosis and Rhabdomyolysis.

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. Cowfish (Umisuzume, Lactoria diaphana) poisoning with rhabdomyolysis.

    PubMed

    Shinzato, Takeaki; Furusu, Akira; Nishino, Tomoya; Abe, Katsushige; Kanda, Tetsuro; Maeda, Takahiro; Kohno, Shigeru

    2008-01-01

    A 40-year-old man developed weakness and myalgia of the shoulders and brachia nine hours after eating a cowfish (Umisuzume, Lactoria diaphana). A clinical symptom showed rhabdomyolysis and serum creatine phosphokinase was elevated to 180,000 IU/L on day 3. Cardiopulmonary arrest and acute renal failure developed after 59 hours and hemodiafiltration was performed. Cerebral death was diagnosed on day 9 and the patient died on day 16. The case has the characteristic clinical course of palytoxin poisoning, which has also been reported as blue humphead parrotfish poisoning from other kinds of fish.

  16. Bariatric surgery, a risk factor for rhabdomyolysis.

    PubMed

    García-García, M L; Campillo-Soto, A; Martín-Lorenzo, J G; Torralba-Martínez, J A; Lirón-Ruiz, R; Aguayo-Albasini, J L

    2013-11-01

    Rhabdomyolysis has been increasingly recognized as a complication of bariatric surgery. We report a case of this complication and its consequences, in a patient who had undergone bariatric surgery, with a very high creatine kinase (CK) concentration, and whose renal function failed. Obesity causes a range of effects on all major organ systems. Knowledge of these effects and issues specific to the intensive care unit care of bariatric patients can help to predict and manage this underestimated complication in this population in which early diagnosis can alter the outcome.

  17. 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

  18. Rhabdomyolysis following severe hypokalemia caused by familial hypokalemic periodic paralysis

    PubMed Central

    Jung, Young-Lee; Kang, Jae-Young

    2017-01-01

    Rhabdomyolysis continues to appear with increasing frequency and represents a medical emergency requiring rapid appropriate treatment. One of the unusual causes of nontraumatic rhabdomyolysis is hypokalemic periodic paralysis without secondary causes. Primary hypokalemic periodic paralysis is a rare genetic disease characterized by episodic attacks of muscle weakness due to decreases in serum potassium. A 30-year-old woman who had 3 episodic attacks of hypokalemic periodic paralysis was admitted in emergency room with sudden onset symmetrical muscle weakness. After several hours, she started to complain myalgia and severe ache in both calves without any changes. Laboratory test showed markedly elevated creatine phosphokinase, lactic dehydrogenase levels with hypokalemia, rhabdomyolysis resulting from hypokalemia was diagnosed. Here, we report an unusual case of rhabdomyolysis caused by severe hypokalemia, which was suggested a result of familial hypokalemic periodic paralysis. PMID:28255549

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

    PubMed Central

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

    2014-01-01

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

  20. [Acute rhabdomyolysis after spinal anesthesia for knee arthroscopy].

    PubMed

    Bouché, P M; Chavagnac, B; Cognet, V; Banssillon, V

    2001-08-01

    We report an observation of acute rhabdomyolysis of gluteus maximum muscles occurring in a non-obese patient installed in supine position that underwent knee arthroscopy under spinal anaesthesia. The patient had insulin-dependent diabetes melitus with documented microangiopathy. The interest of this observation resides in the occurrence of the syndrome after a short period of time (one hour) of installation in the supine position in a patient that did not have any of the generally described risk factors of rhabdomyolysis.

  1. 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.

  2. Severe Fever with Thrombocytopenia Syndrome Presenting with Rhabdomyolysis

    PubMed Central

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

    2017-01-01

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

  3. Rhabdomyolysis and acute kidney injury after acupuncture sessions.

    PubMed

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

    2014-05-01

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

  4. 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.

  5. Rhabdomyolysis associated with antimicrobial drug-resistant Mycoplasma pneumoniae.

    PubMed

    Oishi, Tomohiro; Narita, Mitsuo; Ohya, Hitomi; Yamanaka, Takayuki; Aizawa, Yuta; Matsuo, Mai; Matsunaga, Masamichi; Tsukano, Shinya; Taguchi, Testuo

    2012-05-01

    We describe a case of rhabdomyolysis in a patient infected with antimicrobial drug-resistant Mycoplasma pneumoniae The patient's acute-phase serum levels of interleukin-18 and tumor necrosis factor-α were high, which suggests a pathogenic role for M. pneumoniae. In an era of increasing antimicrobial drug resistance, a system for rapidly identifying resistant M. pneumoniae would be beneficial.

  6. 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. PMID:27635408

  7. Bone scintigraphy of severe hypercalcemia following simvastatin induced rhabdomyolysis

    PubMed Central

    Mirza, Zubair B.; Hu, Sophia; Amorosa, Louis F.

    2016-01-01

    Summary Simvastatin induced rhabdomyolysis with renal failure is a well reported clinical entity with hyperkalemia recognized as a life threatening risk. The risk of delayed hypercalcemia during the recovery of renal function is not well appreciated as this varies in severity and can be caused by multiple mechanisms. We present a patient with high dose simvastatin induced rhabdomyolysis leading to late onset of severe hypercalcemia due to calcium phosphate deposition in muscles diagnosed by distinctive bone scintigraphy. A 60-year-old Asian male was admitted to the hospital for profound weakness one week following the initiation of simvastatin 80 mg daily post myocardial infarction. His clinical course was complicated by contrast nephropathy. One week later, he developed progressive weakness in all his extremities and inability to raise his head and eat. Simvastatin was discontinued at this point. CPK elevation to greater than 425,000 U was found, consistent with rhabdomyolysis. He became oliguric requiring hemodialysis. Muscle biopsy showed severe muscle necrosis and type 2 fiber atrophy. One month later, he developed hypercalcemia with suppressed intact PTH and 1, 25(OH) D levels. Whole body bone scintigraphy showed calcium phosphate deposition throughout his musculature. His calcium levels normalized in 1 week on hemodialysis. This patient’s experience illustrates the marked risk of delayed severe hypercalcemia from rhabdomyolysis due to dissolution of myocellular calcium phosphate deposits. It also provides an opportunity to review the different mechanisms of hypercalcemia especially in statin induced rhabdomyolysis. Recognition of this phenomenon is critical for appropriate follow up and treatment of such patients. PMID:28228795

  8. Rhabdomyolysis in a Hospitalized 16-Year-Old Boy: A Rarely Reported Underlying Cause

    PubMed Central

    Singh, Rishika; Pejka, Sherry

    2016-01-01

    Rhabdomyolysis can occur because of multiple causes and account for 7% of all cases of acute kidney injury annually in the United States. Identification of specific cause can be difficult in many cases where multiple factors could potentially cause rhabdomyolysis. We present a case of 16-year-old male who had seizures and was given levetiracetam that resulted in rhabdomyolysis. This side effect has been rarely reported previously and like in our case diagnosis may be delayed. PMID:27895953

  9. Acute renal failure in a patient with Sheehan syndrome and rhabdomyolysis.

    PubMed

    Soltani, Parvin; Rezvanfar, Mohammad Reza; Pirasteh, Shadi

    2008-01-01

    We report a case of acute renal failure related to rhabdomyolysis in a patient with Sheehan syndrome, while other diseases that could cause rhabdomyolysis were excluded. The patient's kidney function completely recovered with 3 sessions of intermittent hemodialysis. After thyroxine replacement therapy, musculoskeletal symptoms disappeared and creatine kinase concentrations decreased. Steroid replacement therapy was also administered. The present case suggests that rhabdomyolysis could occur in a patient with Sheehan syndrome without other precipitating factors.

  10. 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

  11. 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

  12. [Labile iron pool formation in rat's blood under rhabdomyolysis].

    PubMed

    Shandrenko, S H

    2012-01-01

    The labile nonheme iron pool formation in blood under glycerol induced rhabdomyolysis in rats has been investigated. This iron is not included in transferrin, thereby it is redox-active. Rhabdomyolysis was caused by intramuscular injection of 50% glycerol in a dose of 10 ml/kg. In the first day it has been registered that the blood plasma free heme content increased 10 times and the liver heme-oxigenase activity increased 6 times. Plasma redox-active iron pool formation has been registered by EPR method. Such iron was absent in the control group. This iron pool content in the interval from the 1st to the 6st day was more than 2 mg/l and significantly higher than the transferrin iron level. The plasma iron pool unshielded by transferrin may be one of oxidative stress causes.

  13. Rhabdomyolysis and Autoimmune Variant Stiff-Person Syndrome

    PubMed Central

    Gangadhara, Shreyas; Gangadhara, Suhas; Gandhy, Chetan; Robertson, Derrick

    2016-01-01

    Stiff-person syndrome (SPS) is a rare neurologic disorder characterized by waxing and waning muscular rigidity, stiffness and spasms. Three subtypes have been described: paraneoplastic, autoimmune and idiopathic. Rhabdomyolysis has been described in the paraneoplastic variant, but to our knowledge no case has been reported involving the autoimmune variant. We report a case report of a 50-year-old man with history of SPS who presented with recurrent episodes of severe limb and back spasms. He was hospitalized on two separate occasions for uncontrollable spasms associated with renal failure and creatinine phosphokinase elevations of 55,000 and 22,000 U/L respectively. Laboratory tests were otherwise unremarkable. The acute renal failure resolved during both admissions with supportive management. Rhabdomyolysis has the potential to be fatal and early diagnosis is essential. It should be considered in patients who have SPS and are experiencing an exacerbation of their neurologic condition. PMID:28028432

  14. Exertional rhabdomyolysis and heat stroke: Beware of volatile anesthetic sedation

    PubMed Central

    Heytens, Karel; De Bleecker, Jan; Verbrugghe, Walter; Baets, Jonathan; Heytens, Luc

    2017-01-01

    In view of the enormous popularity of mass sporting events such as half-marathons, the number of patients with exertional rhabdomyolysis or exercise-induced heat stroke admitted to intensive care units (ICUs) has increased over the last decade. Because these patients have been reported to be at risk for malignant hyperthermia during general anesthesia, the intensive care community should bear in mind that the same risk of life-threatening rhabdomyolysis is present when these patients are admitted to an ICU, and volatile anesthetic sedation is chosen as the sedative technique. As illustrated by the three case studies we elaborate upon, a thorough diagnostic work-up is needed to clarify the subsequent risk of strenuous exercise, and the anesthetic exposure to volatile agents in these patients and their families. Other contraindications for the use of volatile intensive care sedation consist of known malignant hyperthermia susceptibility, congenital myopathies, Duchenne muscular dystrophy, and intracranial hypertension. PMID:28224104

  15. Rhabdomyolysis and Autoimmune Variant Stiff-Person Syndrome.

    PubMed

    Gangadhara, Shreyas; Gangadhara, Suhas; Gandhy, Chetan; Robertson, Derrick

    2016-10-24

    Stiff-person syndrome (SPS) is a rare neurologic disorder characterized by waxing and waning muscular rigidity, stiffness and spasms. Three subtypes have been described: paraneoplastic, autoimmune and idiopathic. Rhabdomyolysis has been described in the paraneoplastic variant, but to our knowledge no case has been reported involving the autoimmune variant. We report a case report of a 50-year-old man with history of SPS who presented with recurrent episodes of severe limb and back spasms. He was hospitalized on two separate occasions for uncontrollable spasms associated with renal failure and creatinine phosphokinase elevations of 55,000 and 22,000 U/L respectively. Laboratory tests were otherwise unremarkable. The acute renal failure resolved during both admissions with supportive management. Rhabdomyolysis has the potential to be fatal and early diagnosis is essential. It should be considered in patients who have SPS and are experiencing an exacerbation of their neurologic condition.

  16. 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

  17. [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.

  18. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration

    PubMed Central

    Jeon, Dae-Hong; Kim, Yire; Kim, Min Jeong; Cho, Hyun Seop; Bae, Eun Jin; Chang, Se-Ho; Park, Dong Jun

    2016-01-01

    Abstract Background: Proton pump inhibitors are usually safe, although serious adverse effects can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous esomeprozole administration. Methods: A 45-year-old Korean male visited our emergency room because of persistent lower chest discomfort that started 10 hours before. He had been diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic agents 1 month earlier. He continued to take medications for coronary heart disease. There was no abnormality on an electrocardiogram or in cardiac enzymes. Initial laboratory findings did not show abnormalities for muscle enzymes. Esomeprozole 40 mg was administrated intravenously for the control of his ambiguous chest discomfort. Then, 12 hours later, he complained of abrupt severe right buttock pain. An area of tender muscle swelling 8 cm in diameter was seen on his right buttock area. Creatine kinase and lactate dehydrogenase were elevated to 40,538 and 1326 U/L, respectively. A bone scan using 20 mCi of 99mTc-hydroxymethylene diphosphonate was compatible with rhabdomyolysis. Results: His muscular symptoms, signs, and laboratory findings improved markedly with conservative management, including hydration and urine alkalinization. He is being followed in the outpatient department with no evidence of recurrence. Conclusion: We should keep in mind that single-dose intravenous administration of esomeprazole can induce rhabdomyolysis. PMID:27442680

  19. Renal failure, laminitis, and colitis following severe rhabdomyolysis in a draft horse-cross with polysaccharide storage myopathy.

    PubMed

    Sprayberry, K A; Madigan, J; LeCouteur, R A; Valentine, B A

    1998-08-01

    A Thoroughbred-Percheron crossbred gelding developed a fulminant cascade of sequelae following a severe episode of rhabdomyolysis. Complications may occur with rhabdomyolysis of any etiology. In warmblood horses with Percheron bloodlines, rhabdomyolysis may be secondary to polysaccharide storage disease, and aggressive therapy should be undertaken promptly to avoid the complications.

  20. Isoniazid-induced seizures with secondary rhabdomyolysis and associated acute renal failure in a dog.

    PubMed

    Haburjak, J J; Spangler, W L

    2002-04-01

    Isoniazid-induced seizures resulted in rhabdomyolysis and associated acute renal tubular necrosis in a dog. Rhabdomyolysis and myoglobinuric renal failure, although recognised in the dog, are reported infrequently as a consequence of seizures. The clinical presentation of isoniazid toxicity in a dog is described.

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

    PubMed

    Karre, Premnath Reddy; Gujral, Jeetinder

    2011-04-01

    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.

  2. A Patient with Dengue Fever Presenting with Rhabdomyolysis.

    PubMed

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

    2015-01-01

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

  3. [Myopathy and rhabdomyolysis after treatment with simvastatin, amlodipine, and roxithromycin].

    PubMed

    Skovbølling, Sara Lyngby; Lindelof, Mette

    2014-10-06

    This is a case report of a 71-year-old male with known diabetes, hypertension and diabetic nephropaty who over the course of one year developed an unrecognized myopathy due to concomitant treatment with high-dose simvastatin and amlodipin. Due to rhabdomyolysis he was after seven days of treatment with roxithromycin admitted to hospital with loss of the ability to walk. We wish to raise awareness of the potentially severe side effects of simvastatin and to emphasize that these can be limited by increased attention to patients with risk factors and to interactions with other drugs.

  4. Reversal of drug-induced rhabdomyolysis on bone scan.

    PubMed

    Abrams, Joseph; Tiu, Serafin

    2011-08-01

    A 75-year-old man with prostate cancer was referred for metastatic workup. A Tc-99m methylene diphosphonate bone scan was performed which revealed diffusely increased radiopharmaceutical uptake in the muscles of the arms and thighs. The patient was taking simvastatin 80 mg per day and gemfibrozil 600 mg twice a day for high cholesterol. The patient reported myalgias, and laboratory evaluation was consistent with rhabdomyolysis. After discontinuation of the anticholesterol medications, the clinical and laboratory evaluations normalized. Bone scan performed 1 year later demonstrated complete resolution of muscle uptake.

  5. Postoperative rhabdomyolysis following robotic renal and adrenal surgery: a cautionary tale of compounding risk factors.

    PubMed

    Terry, Russell S; Gerke, Travis; Mason, James B; Sorensen, Matthew D; Joseph, Jason P; Dahm, Philipp; Su, Li-Ming

    2015-09-01

    This study aimed at reviewing a contemporary series of patients who underwent robotic renal and adrenal surgery by a single surgeon at a tertiary referral academic medical center over a 6-year period, specifically focusing on the unique and serious complication of post-operative rhabdomyolysis of the dependent lower extremity. The cases of 315 consecutive patients who underwent robotic upper tract surgery over a 6-year period from August 2008 to June 2014 using a standardized patient positioning were reviewed and analyzed for patient characteristics and surgical variables that may be associated with the development of post-operative rhabdomyolysis. The incidence of post-operative rhabdomyolysis in our series was 3/315 (0.95%). All three affected patients had undergone robotic nephroureterectomy. Those patients who developed rhabdomyolysis had significantly higher mean Body Mass Index, Charlson Comorbidity Index, and median length of stay than those who did not. The mean OR time in the rhabdomyolysis group was noted to be 52 min longer than the non-rhabdomyolysis group, though this value did not reach statistical significance. Given the trends of increasing obesity in the United States and abroad as well as the continued rise in robotic upper tract urologic surgeries, urologists need to be increasingly vigilant for recognizing the risk factors and early treatment of the unique complication of post-operative rhabdomyolysis.

  6. On the mechanisms underlying poisoning-induced rhabdomyolysis and acute renal failure.

    PubMed

    Talaie, Haleh; Emam-Hadi, Mohammad; Panahandeh, Reyhaneh; Hassanian-Moghaddam, Hosein; Abdollahi, Mohammad

    2008-01-01

    ABSTRACT The clinical syndrome of rhabdomyolysis is caused by injury of skeletal muscles resulting in release of intracellular muscle constituents. Drug poisoning is one of the causes of severe rhabdomyolysis. Severe electrolyte disorders and acute renal failure may occur in rhabdomyolysis, leading to life-threatening situations. Early initiation of renal replacement therapy can help improve outcome. In the present retrospective study, medical records of 181 patients suspected of rhabdomyolysis from Loghman-Hakim Hospital in the period of 2004 to 2005 were reviewed. A creatinine phosphokinase (CPK) value of greater than five times normal (>/=975 IU/L) was the basis for confirmation of a rhabdomyolysis diagnosis. An increased serum creatinine level of more than 30% was the basis for acute renal failure diagnosis. Out of 156 patients, 100 were male with an age range of 13 to 78 years. One hundred and two (92%) patients had CPK >975 U/L, and 36 patients (28.6%) had a 30% or more increase in their creatinine level during their admission days. Mean fluid intake was the same in patients with renal failure and those without renal failure. In 8.3% of the cases, multiple drug poisoning was observed. The most common compound overdose associated with rhabdomyolysis was opium. It is concluded that fluid therapy alone is not adequate in the management of acute renal failure in rhabdomyolysis. Therefore, other etiological factors are involved that remain to be elucidated by further studies.

  7. 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

  8. 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

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

    PubMed

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

    2015-04-01

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

  10. Fatal Rhabdomyolysis Caused by Morganella morganii in a Patient with Multiple Myeloma

    PubMed Central

    Imataki, Osamu; Uemura, Makiko

    2017-01-01

    A 64-year-old Japanese man with multiple myeloma was admitted to our institute due to fever and hypotension. He had received multiple courses of chemotherapy just before his febrile episode. Blood culturing detected Morganella morganii. At the time of the diagnosis, his laboratory findings revealed massive rhabdomyolysis with a significantly increased creatinine kinase level (CK; 3,582 U/L); 98.8% of which corresponded to the CK-MB isotype. We diagnosed the patient with sepsis caused by M. morganii, complicated with severe rhabdomyolysis. He died of multi-organ failure 2 days later. Clinicians should closely observe patients with possible systemic infection-associated rhabdomyolysis. PMID:28154285

  11. 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

  12. Is dilution important: Factitious Total Creatine Kinase in case of Rhabdomyolysis?

    PubMed Central

    Dinakaran, Asha; Ray, Lopamudra

    2016-01-01

    Factitious test reports may result in incorrect diagnosis and incorrect management. Such incorrect diagnosis can be prevented by a vigilant biochemist. We report a case of Rhabdomyolysis presenting with extremely low total Creatine Kinase (CK) levels which was factitious. Running the sample in dilution resulted in a very high value of total CK which could have been missed if the sample was not run in dilution and the diagnosis of Rhabdomyolysis could have been missed. PMID:27891332

  13. Is dilution important: Factitious Total Creatine Kinase in case of Rhabdomyolysis?

    PubMed

    Nanda, Sunil Kumar; Dinakaran, Asha; Ray, Lopamudra

    2016-10-01

    Factitious test reports may result in incorrect diagnosis and incorrect management. Such incorrect diagnosis can be prevented by a vigilant biochemist. We report a case of Rhabdomyolysis presenting with extremely low total Creatine Kinase (CK) levels which was factitious. Running the sample in dilution resulted in a very high value of total CK which could have been missed if the sample was not run in dilution and the diagnosis of Rhabdomyolysis could have been missed.

  14. Melting muscles: novel H1N1 influenza A associated rhabdomyolysis.

    PubMed

    D'Silva, Dimple; Hewagama, Saliya; Doherty, Richard; Korman, Tony M; Buttery, Jim

    2009-12-01

    We report the first case of myositis and rhabdomyolysis after infection with novel influenza A (H1N1/09) virus. The case demonstrates the novel virus' capacity for causing significant disease. Myositis and the possibility of rhabdomyolysis should be considered in any individual presenting with influenza-like symptoms in which severe myalgia or muscle weakness is apparent. It is likely that we will see severe clinical manifestations of infection with this novel influenza virus in the coming respiratory virus season.

  15. Recurrent rhabdomyolysis secondary to hyponatremia in a patient with primary psychogenic polydipsia

    PubMed Central

    Aguiar, Diana Tavares; Monteiro, Catarina; Coutinho, Paula

    2015-01-01

    Rhabdomyolysis is characterized by the destruction of skeletal muscle tissue, and its main causes are trauma, toxic substances and electrolyte disturbances. Among the latter is hyponatremia-induced rhabdomyolysis, a rare condition that occurs mainly in patients with psychogenic polydipsia. Psycogenic polydipsia mostly affects patients with schizophrenia, coursing with hyponatremia in almost 25% of the cases. It is also in this context that rhabdomyolysis secondary to hyponatremia occurs most often. In this article, the case of a 49-year-old male with a history of schizophrenia, medicated with clozapine, and brought to the emergency room in a state of coma and seizures is described. Severe hypoosmolar hyponatremia with cerebral edema was found on a computed tomography examination, and a subsequent diagnosis of hyponatremia secondary to psychogenic polydipsia was made. Hyponatremia correction therapy was started, and the patient was admitted to the intensive care unit. After the hyponatremia correction, the patient presented with analytical worsening, showing marked rhabdomyolysis with a creatine phosphokinase level of 44.058UI/L on day 3 of hospitalization. The condition showed a subsequent progressive improvement with therapy, with no occurrence of kidney damage. This case stresses the need for monitoring rhabdomyolysis markers in severe hyponatremia, illustrating the condition of rhabdomyolysis secondary to hyponatremia induced by psychogenic polydipsia, which should be considered in patients undergoing treatment with neuroleptics. PMID:25909317

  16. Severe rhabdomyolysis following massive ingestion of oolong tea: caffeine intoxication with coexisting hyponatremia.

    PubMed

    Kamijo, Y; Soma, K; Asari, Y; Ohwada, T

    1999-12-01

    A 36-y-o patient with schizophrenia, who had consumed gradually increasing quantities of oolong tea that eventually reached 15 L each day, became delirious and was admitted to a psychiatric hospital. After abstinence from oolong tea his delirium resolved. He was transferred to our hospital when he was discovered to have acute renal failure with hyponatremia (118 mEq/L) and severe rhabdomyolysis (creatine phosphokinase, 227,200 IU/L). On admission rhabdomyolysis had begun to improve despite a worsening of the hyponatremia (113 mEq/L). With aggressive supportive therapy, including hypertonic saline administration and hemodialysis, the patient fully recovered without detectable sequelae. The clinical course suggests that caffeine, which is present in oolong tea, was mainly responsible for the rhabdomyolysis as well as the delirium, although severe hyponatremia has been reported to cause rhabdomyolysis on rare occasions. We hypothesize that caffeine toxicity injured the muscle cells, which were fragile due to the potassium depletion induced by the coexisting hyponatremia, to result in unusually severe rhabdomyolysis. The possibility of severe rhabdomyolysis should be considered in a patient with water intoxication due to massive ingestion of caffeine-containing beverages.

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

    PubMed

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

    2010-04-01

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

  18. The Use of Coupled Plasma Filtration Adsorption in Traumatic Rhabdomyolysis

    PubMed Central

    Renda, Silvia; Giglio, Anna Maria; Scozzafava, Anna Maria; Tiburzi, Simona Paola; Casella, Patrizia; Iannelli, Fabrizio; Verre, Mario

    2017-01-01

    Severe musculoskeletal injuries induce the release of sarcoplasmic elements such as muscle enzymes, potassium, and myoglobin in the systemic circulation. The circulating myoglobin damages the glomerulus and renal tubules. Conventional haemodialysis is not able to remove myoglobin, due to its high molecular weight (17,8 kilodaltons [kDa]). We treated four traumatic rhabdomyolysis patients with Coupled Plasma Filtration Adsorption (CPFA) in order to remove myoglobin followed by 14 hours of Continuous Veno-Venous Hemofiltration (CVVH). During the treatment, all patients showed clinical improvement with a decrease in muscular (creatine kinase [CK] and myoglobin) and renal (creatinine and potassium) damage indices. One patient, in spite of full renal recovery, died of cerebral haemorrhage on the 26th day of hospital stay.

  19. Massive honey bee envenomation-induced rhabdomyolysis in an adolescent.

    PubMed

    Betten, David P; Richardson, William H; Tong, Tri C; Clark, Richard F

    2006-01-01

    Massive envenomations by honey bees are capable of causing multiorgan dysfunction as a result of the direct toxic effects of the large venom load received. Although all varieties of honey bee have the potential for these attacks, the Africanized honey bee (Apis mellifera scutellata) is the most commonly implicated subspecies. In the United States, the Africanized strain is found primarily in the southwestern states and is known for its highly defensive behavior if disturbed. Mechanisms behind the multiorgan dysfunction produced by these mass envenomations are not clearly understood. We present a case of a 13-year-old male who was stung by approximately 700 honey bees and developed progressive upper-body swelling and systemic manifestations of mass envenomation including rhabdomyolysis, renal insufficiency, and a transient transaminase elevation.

  20. Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon

    PubMed Central

    Valero, Marjorie; Salinero, Juan José; Lara, Beatriz; Gallo-Salazar, César; Areces, Francisco

    2017-01-01

    Purpose Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A). Methods Using Williams and Folland’s model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK <400 U·L-1) vs. marathoners with a high CK response (n = 31; serum CK ≥400 U·L-1). Results At the end of the race, low CK responders had lower serum CK (290±65 vs. 733±405 U·L-1; P<0.01) and myoglobin concentrations (443±328 vs. 1009±971 ng·mL-1, P<0.01) than high CK responders. Although the groups were similar in age, anthropometric characteristics, running experience and training habits, total genotype score was higher in low CK responders than in high CK responders (5.2±1.4 vs. 4.4±1.7 point, P = 0.02). Conclusion Marathoners with a lower CK response after the race had a more favorable polygenic profile than runners with high serum CK concentrations. This might suggest a significant role of genetic polymorphisms in the levels of exertional muscle damage and rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise. PMID:28257486

  1. 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

  2. A Rare Case of Acute Renal Failure Secondary to Rhabdomyolysis Probably Induced by Donepezil

    PubMed Central

    Sahin, Osman Zikrullah; Ayaz, Teslime; Yuce, Suleyman; Sumer, Fatih

    2014-01-01

    Introduction. Acute renal failure (ARF) develops in 33% of the patients with rhabdomyolysis. The main etiologic factors are alcoholism, trauma, exercise overexertion, and drugs. In this report we present a rare case of ARF secondary to probably donepezil-induced rhabdomyolysis. Case Presentation. An 84-year-old male patient was admitted to the emergency department with a complaint of generalized weakness and reduced consciousness for two days. He had a history of Alzheimer's disease for one year and he had taken donepezil 5 mg daily for two months. The patient's physical examination revealed apathy, loss of cooperation, and decreased muscle strength. Laboratory studies revealed the following: urea: 128 mg/dL; Creatinine 6.06 mg/dL; creatine kinase: 3613 mg/dL. Donepezil was discontinued and the patient's renal function tests improved gradually. Conclusion. Rhabdomyolysis-induced acute renal failure may develop secondary to donepezil therapy. PMID:24864216

  3. A rare case of acute renal failure secondary to rhabdomyolysis probably induced by donepezil.

    PubMed

    Sahin, Osman Zikrullah; Ayaz, Teslime; Yuce, Suleyman; Sumer, Fatih; Sahin, Serap Baydur

    2014-01-01

    Introduction. Acute renal failure (ARF) develops in 33% of the patients with rhabdomyolysis. The main etiologic factors are alcoholism, trauma, exercise overexertion, and drugs. In this report we present a rare case of ARF secondary to probably donepezil-induced rhabdomyolysis. Case Presentation. An 84-year-old male patient was admitted to the emergency department with a complaint of generalized weakness and reduced consciousness for two days. He had a history of Alzheimer's disease for one year and he had taken donepezil 5 mg daily for two months. The patient's physical examination revealed apathy, loss of cooperation, and decreased muscle strength. Laboratory studies revealed the following: urea: 128 mg/dL; Creatinine 6.06 mg/dL; creatine kinase: 3613 mg/dL. Donepezil was discontinued and the patient's renal function tests improved gradually. Conclusion. Rhabdomyolysis-induced acute renal failure may develop secondary to donepezil therapy.

  4. [Rhabdomyolysis and anuric kidney failure induced by the treatment with a gemfibrozil-cerivastatin combination].

    PubMed

    Sirvent, A E; Cabezuelo, J B; Enríquez, R; Amorós, F; González, C; Reyes, A

    2001-01-01

    A 67-year-old man treated with gemfibrozil for a year development rhabdomyolysis and anuric renal failure after addition of cerivastatin. The clinical features and serological studies ruled out other causes of rhabdomyolysis. Drugs were stopped and hemodialysis was carried on for 14 days until diuresis occurred. The renal function improved steadily to a serum creatinine of 1.2 mg/dl two months later. On the basis of its pharmacokinetic profile cerivastatin appears to have less interactions than other statins. There are only two reports of rhabdomyolysis and acute renal failure due to fibrates and cerivastatin combination. This patient shows the potential risk of a fibrates-cerivastatin combination. When this association is required it is necessary to avoid other nephrotoxic and myopathic factors and to monitor CK levels closely.

  5. [A case of rhabdomyolysis caused by saw palmetto of healthy foods].

    PubMed

    Hanaka, Minako; Yoshii, Chiharu; Yatera, Kazuhiro; Ito, Chiyo; Chojin, Yasuo; Nagata, Shuya; Yamasaki, Kei; Nishida, Chinatsu; Kawanami, Toshinori; Kawanami, Yukiko; Ishimoto, Hiroshi; Mukae, Hiroshi

    2012-06-01

    An 82-year-old man visited our hospital when he developed a fever of over 38 degrees C after having consumed 5 types of health foods. He had previously been treated for chronic obstructive pulmonary disease, hypertension and hyperuricemia. Blood examination on admission revealed renal dysfunction, marked elevation of C-reactive protein, and an elevated level of serum creatine kinase. According to the laboratory data and his clinical history, rhabdomyolysis complicated by acute renal failure was suspected, but his condition improved and his fever was reduced with fluid infusion. As a drug lymphocyte stimulation test was positive for only saw palmetto in the 5 health foods, we diagnosed the case as rhabdomyolysis induced by saw palmetto. We believe that this is the first case of a health food being the cause of rhabdomyolysis.

  6. 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.

  7. 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.

  8. [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.

  9. Rhabdomyolysis and myocardial damage induced by palytoxin, a toxin of blue humphead parrotfish.

    PubMed

    Okano, H; Masuoka, H; Kamei, S; Seko, T; Koyabu, S; Tsuneoka, K; Tamai, T; Ueda, K; Nakazawa, S; Sugawa, M; Suzuki, H; Watanabe, M; Yatani, R; Nakano, T

    1998-03-01

    A 55-year-old man had rhabdomyolysis and myocardial damage induced by palytoxin. Weakness and myalgia of four extremities occurred five hours after eating a fish. Rhabdomyolysis developed and the serum creatine phosphokinase (CK) was elevated to 40,000 IU/l on the 3rd day. Gastric lavage with activated charcoal and forced mannitol-alkaline diuresis therapy were performed. The patient recovered with no complication such as renal failure. In this case, palytoxin was suggested to induce myocardial damage which was demonstrated by an elevation of the myosin light chain level and a change in electrocardiogram.

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

    PubMed

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

    2008-05-01

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

  11. [Renoprotective effects of statins under the conditions of acute renal failure, caused by rhabdomyolysis].

    PubMed

    Zamorskiĭ, I I; Zeleniuk, V G

    2014-01-01

    The experiment on white rats was targeted at the examination of influence of statins (atorvastatin, lovastatin, simvastatin) under the conditions of acute renal failure, caused by rhabdomyolysis. Renoprotective effects of statins were demonstrated by reduction of hyperazotemia and proteinuria and improvement of renal excretory function, which correlated with antioxidant properties of drugs.

  12. A Case of Fulminant Varicella Infection with Purpura Fulminans, Hepatitis, and Rhabdomyolysis

    PubMed Central

    Karadag, A S; Bilgili, S G; Calka, O; Çeçen, İ; Akbayram, S

    2012-01-01

    Varicella zoster virus causes varicella which is a common disease. Generally it is self-limiting, and treatment is often unnecessary, but severe or life-threatening complications are rarely seen. We report a case of fulminant varicella complicating with purpura fulminans, hepatitis, and probable rhabdomyolysis in a previously healthy child. PMID:23248376

  13. A remarkable case of rhabdomyolysis associated with ingestion of energy drink ‘neon volt’

    PubMed Central

    Iyer, Praneet S.; Yelisetti, Rishitha; Miriyala, Varun; Siddiqui, Waqas; Kaji, Anand

    2016-01-01

    Rhabdomyolysis is defined as a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation. We present a case of a 35-year-old male who exercised for 2 h after ingesting energy drink and subsequently presented with rhabdomyolysis. After excluding common and uncommon causes of rhabdomyolysis, we reached the conclusion that the likely cause was the ingestion of energy drink ‘NEON VOLT’ in a setting of mild dehydration. Increasing physical activity and intense exercise is becoming a trend in many countries, due to its many health-related benefits such as prevention of obesity. This renewed focus toward optimal fitness has spawned many supplements that aid in improvement of the performance, muscle growth, and recovery. Energy drinks predominantly contain caffeine that is often combined with other supplements to form what manufacturers have termed an ‘energy blend’. Studies have shown that excessive caffeine intake from energy drinks can cause arrhythmias, hypertension, dehydration, sleeplessness, nervousness, and in rare instances, rhabdomyolysis. As per Drug Abuse Warning Network report, there is a sharp increase in the number of emergency department visits involving energy drinks from 1,128 visits in 2005 to 16,053 and 13,114 visits in 2008 and 2009, respectively. Due to emergence of energy drink abuse as a national health problem, Food and Drug Administration has launched a dietary supplement adverse event reporting system for surveillance of any adverse events linked to these agents. PMID:27802855

  14. Successful switch to olanzapine after rhabdomyolysis caused by water intoxication and clozapine use.

    PubMed

    Tényi, T; Vörös, V

    2006-07-01

    We report on a case of rhabdomyolysis induced by the correction of hyponatremia after psychogenic polydipsia and clozapine use, where the switch to a high dose of olanzapine resulted in the non-recurrence of rhabdomyolysis. The 46-year-old patient with the diagnosis of schizophrenia paranoid type, who had been on clozapine treatment for the previous 4 years, was admitted with the symptoms of generalized seizure and vomiting, and as severe hyponatremia was proved, its correction with the parallel use of clozapine treatment was done. CK concentrations increased to 48 120 U/L without any symptom of neuroleptic malignant syndrome. To prevent acute renal insufficiency, high-volume alkaline diuresis was initiated and clozapine was tapered and stopped. On the day 12 of treatment, olanzapine was started and was elevated to 30 mg/day. CK concentration began to fall returning to the normal concentration on day 20. Six months after the switch to olanzapine no recurrence of rhabdomyolysis was detected; clinical and laboratory findings were normal. We suggest that after a benzodiazepine-type antipychotic-induced rhabdomyolysis, a switch to another atypical antipsychotic can be a cautious clinical strategy.

  15. A remarkable case of rhabdomyolysis associated with ingestion of energy drink 'neon volt'.

    PubMed

    Iyer, Praneet S; Yelisetti, Rishitha; Miriyala, Varun; Siddiqui, Waqas; Kaji, Anand

    2016-01-01

    Rhabdomyolysis is defined as a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation. We present a case of a 35-year-old male who exercised for 2 h after ingesting energy drink and subsequently presented with rhabdomyolysis. After excluding common and uncommon causes of rhabdomyolysis, we reached the conclusion that the likely cause was the ingestion of energy drink 'NEON VOLT' in a setting of mild dehydration. Increasing physical activity and intense exercise is becoming a trend in many countries, due to its many health-related benefits such as prevention of obesity. This renewed focus toward optimal fitness has spawned many supplements that aid in improvement of the performance, muscle growth, and recovery. Energy drinks predominantly contain caffeine that is often combined with other supplements to form what manufacturers have termed an 'energy blend'. Studies have shown that excessive caffeine intake from energy drinks can cause arrhythmias, hypertension, dehydration, sleeplessness, nervousness, and in rare instances, rhabdomyolysis. As per Drug Abuse Warning Network report, there is a sharp increase in the number of emergency department visits involving energy drinks from 1,128 visits in 2005 to 16,053 and 13,114 visits in 2008 and 2009, respectively. Due to emergence of energy drink abuse as a national health problem, Food and Drug Administration has launched a dietary supplement adverse event reporting system for surveillance of any adverse events linked to these agents.

  16. 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.

  17. Statin-induced rhabdomyolysis: a comprehensive review of case reports.

    PubMed

    Mendes, Polyana; Robles, Priscila Games; Mathur, Sunita

    2014-01-01

    Objectif : Trouver des rapports de cas portant sur la rhabdomyolyse provoquée par les statines et résumer les facteurs prédisposants communs, les symptômes, les résultats diagnostiques, les résultats fonctionnels, les caractéristiques, le traitement et la réadaptation. Méthodes : On a cherché dans les bases de données MEDLINE, CINAHL, SCOPUS et PEDro (1990–2013) des rapports de cas pertinents en utilisant les termes de recherche Statins, Rhabdomyolysis, Myalgia, Muscle damage, Muscle injury et Myopathy. Un chercheur en a évalué la pertinence (en fonction du titre et du résumé) et deux autres ont revu indépendamment les articles pertinents pour déterminer s'il fallait les inclure dans la recherche. Résultats : Au total, 112 cas répondaient aux critères d'inclusion. La majorité des cas portaient sur des hommes (70 %) et les plus de 45 ans (âge moyen de 64 [ET 14] ans). La simvastatine a été la statine incriminée le plus souvent dans les rapports (n=55), la majorité des cas signalant l'utilisation simultanée de médicaments comme des fibrates (n=25). La faiblesse (n=65) et les douleurs musculaires (n=64) étaient les symptômes les plus courants. Dans 19 cas, le patient a été aiguillé vers la réadaptation, mais les rapports ne décrivent pas le traitement. Conclusion : On a signalé une rhabdomyolyse causée par les statines plus souvent lorsqu'elles étaient conjuguées à d'autres médicaments, ce qui en a accentué l'effet. Des recherches s'imposent pour déterminer le rôle de l'exercice et de la réadaptation à la suite d'une rhabdomyoloyse causée par les statines puisque les dommages musculaires peuvent être graves et qu'elles peuvent avoir des effets à long terme sur la fonction musculaire.

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

    PubMed

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

    2014-11-01

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

  19. Glutaric aciduria type II presenting as myopathy and rhabdomyolysis in a teenager.

    PubMed

    Prasad, Manish; Hussain, Shanawaz

    2015-01-01

    Late-onset glutaric aciduria type II has been described recently as a rare but treatable cause of proximal myopathy in teenagers and adults. It is an autosomal recessive disease affecting fatty acid, amino acid, and choline metabolism. This is usually a result of 2 defective flavoproteins: either electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone oxidoreductase (ETF:QO). We present a 14-year-old boy with a background of autistic spectrum disorder who presented with severe muscle weakness and significant rhabdomyolysis. Before the onset of muscle weakness, he was very active but was completely bedridden at presentation. Diagnosis was established quickly by urine organic acid and plasma acylcarnitine analysis. He has shown significant improvement after starting oral riboflavin supplementation and is now fully mobile. This case highlights that late-onset glutaric aciduria type II is an important differential diagnosis to consider in teenagers presenting with proximal myopathy and rhabdomyolysis and it may not be associated with hypoglycemia.

  20. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed Central

    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

  4. Natural history of potassium-deficiency myopathy in the dog: role of adrenocorticosteroid in rhabdomyolysis.

    PubMed

    Patterson, R E; Haut, M J; Montgomery, C A; Lowensohn, H S; McQuilken, C T; Djuh, Y Y; Huott, A; Olsson, R A

    1983-10-01

    Potassium deficiency occurs in several conditions and is reported to cause muscle weakness and rhabdomyolysis. The mechanisms by which potassium deficiency cause muscle disease remain unknown, but the primary purpose of the present study was to determine whether abnormal muscle glycogen metabolism causes muscle weakness, as suggested by previous work. We monitored the natural history of potassium deficiency in two groups of dogs, one of which also received deoxycorticosterone acetate (DOCA), an agent commonly used in other studies to accelerate potassium loss. Group I dogs on potassium-free diet alone showed a 41% decrease in muscle potassium, no change in serum CO2, creatine kinase (CK), or muscle phosphorylase activity and only mild histopathologic abnormalities before death, after 198 +/- 42 days on the diet (mean +/- S.D.). In contrast, group II dogs on the same diet plus DOCA developed clinically similar severe weakness and died more rapidly than group I, 37 +/- 7 days (p less than 0.03). DOCA dogs showed a more rapid decrease in muscle potassium to the same level as group I, a 37% increase in serum CO2, an increase in serum CK to 1060 to 2775 IU/ml, a 23% decrease in muscle phosphorylase activity, and severe muscle histopathology, including rhabdomyolysis. Neither group showed any change in body weight, electromyogram (EMG), muscle glycogen concentration, glycogen synthetase activity, serum or muscle magnesium or phosphorus, or serum T3 or T4. In conclusion, dietary potassium deficiency in dogs causes severe weakness and death without causing rhabdomyolysis or abnormal muscle glycogen metabolism. Adding DOCA to the potassium-free diet creates a different model characterized by rapid clinical deterioration and rhabdomyolysis.

  5. Mycoplasma pneumonia associated with rhabdomyolysis and the Guillain-Barre syndrome.

    PubMed

    Gupta, R; Gupta, A; Goyal, V; Guleria, R; Kumar, A

    2005-01-01

    A 25-year-old housewife who presented with Mycoplasma pneumonia who developed acute respiratory distress syndrome (ARDS) and required assisted ventilation. During her hospital stay, she developed acute renal failure because of rhabdomyolysis and was put on haemodialysis. She also had difficulty in weaning from ventilator because of acute motor-sensory axonal neuropathy (AMSAN) variant of the Guillain-Barre syndrome. The patient was treated with antibiotics and corticosteroids. The patient recovered from both the complications gradually.

  6. Determination of muscle mitochondrial respiratory capacity in Standardbred racehorses as an aid to predicting exertional rhabdomyolysis.

    PubMed

    Houben, Rosa; Leleu, Claire; Fraipont, Audrey; Serteyn, Didier; Votion, Dominique-M

    2015-09-01

    This prospective cohort study evaluated the potential of high-resolution respirometry applied to permeabilized muscle fibers for fitness evaluation in French Standardbred racehorses. Fitness evaluation by means of respirometric parameters did not correlate with racing performance registered over the following racing season. However, altered mitochondrial energy metabolism was associated with higher risk of developing exertional rhabdomyolysis, a common cause of exercise intolerance in racehorses. These data represent a first step towards establishing reference values for muscle OXPHOS capacity in this breed.

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

    PubMed

    Haas, D C; Bohnker, B K

    1999-02-01

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

  8. 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

  9. Deceased donor kidney transplantation from donors with acute renal failure due to rhabdomyolysis.

    PubMed

    Mekeel, K L; Moss, A A; Mulligan, D C; Chakkera, H A; Hamawi, K; Mazur, M J; Heilman, R L; Reddy, K S

    2009-07-01

    With the current shortage of solid organs for transplant, the transplant community continues to look for ways to increase the number of organ donors, including extending the criteria for donation. In rhabdomyolysis, the byproducts of skeletal muscle breakdown leak into the circulation resulting in acute renal failure in up to 30% of patients. In nonbrain dead patients, this condition is reversible and most patients recover full renal function. Seven potential donors had rhabdomyolysis with acute renal failure as evidenced by the presence of urine hemoglobin, plasma creatinine kinase levels of greater than five times the normal and elevated creatinine. One donor required dialysis. At our institution, 10 kidneys were transplanted from the seven donors. Two grafts had immediate function, five grafts experienced slow graft function and three grafts had delayed graft function requiring hemodialysis. At a mean of 8.7 months posttransplant (2.4-25.2 months), all patients have good graft function, are off dialysis and have a mean creatinine of 1.3 (0.7-1.8). In conclusion, our experience suggests that rhabdomyolysis with acute renal failure should not be a contraindication for donation, although recipients may experience slow or delayed graft function.

  10. 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

  11. A cola-induced hypokalemic rhabdomyolysis with electromyographic evaluation: A case report

    PubMed Central

    Ferrazzoli, Davide; Sabetta, Annarita; Palamara, Grazia; Caremani, Luca; Capobianco, Marina; Balbi, Pietro; Frazzitta, Giuseppe

    2017-01-01

    Objective: To report a rare case of hypokalemic rhabdomyolysis induced by the heavy and prolonged ingestion of cola-based beverages, and its uneventful recovery after kalemia normalization. Methods: We report a 38-year-old Caucasian male presented in our emergency room with a recent and progressive weakness of the lower limbs proximal muscles. Results: A dietary history revealed a prolonged ingestion of cola-based beverages. Blood tests showed severe hypokalemia and marked increase in serum creatine phosphokinase. The analysis of cerebrospinal fluid resulted normal. Electromyography was suggestive for a myopathy. The clinical, laboratory and neurophysiological data were evocative for a cola-induced hypokalemic rhabdomyolysis. After kalemia normalization, the improvements of the electromyographic findings paralleled the clinical recovery. Conclusion: Chronic consumption of large amount of cola-based soft drinks may result in severe symptomatic hypokalemia, eventually leading in turn to myopathy. To our knowledge, this is the first description of the electromyographic findings of the cola-induced hypokalemic rhabdomyolysis. An early diagnosis and a prompt treatment appear to be crucial for a benign clinical course. PMID:28321307

  12. Lymphoma in Danon disease with chronic rhabdomyolysis treated with EPOCH-R

    PubMed Central

    Porpaczy, Edit; Mayerhoefer, Marius; Salzer-Muhar, Ulrike; Jaeger, Ulrich

    2016-01-01

    Abstract Rare disorders often represent a challenge for clinicians and require close collaboration of an interdisciplinary team. We present the complex case of a 22-year-old male with Danon disease and late-onset of posttransplant lymphoproliferative disorder after heart transplantation. The critical aspects of his condition were: pre-existing rhabdomyolysis; infiltration of muscle and gut with lymphoma; advanced clinical stage with bulky disease; nonresponsiveness to the reduction of immunosuppression and rituximab monotherapy; expected cardiotoxicity of anthracyclines. Therefore, the patient was treated with the EPOCH-R protocol, which includes continuous administration of doxorubicin over 4 days, instead of R-CHOP, in which the anthracycline is given in a short single infusion. Complete remission was achieved after the third cycle; rhabdomyolysis did not increase and heart function was not affected. The patient received a total of 6 cycles and is still in metabolic complete remission. We conclude that patients with Danon disease can be treated with anthracycline-containing chemotherapy and that continuous infusion of EPOCH-R does not exacerbate pre-existing rhabdomyolysis. PMID:27442649

  13. Sickle Cell Trait, Rhabdomyolysis, and Mortality among U.S. Army Soldiers

    PubMed Central

    Nelson, D. Alan; Deuster, Patricia A.; Carter, Robert; Hill, Owen T.; Wolcott, Vickee L.; Kurina, Lianne M.

    2016-01-01

    Background Studies have suggested that sickle cell trait elevates the risks of exertional rhabdomyolysis and death. We conducted a study of sickle cell trait in relation to these outcomes, controlling for known risk factors for exertional rhabdomyolysis, in a large population of active persons who had undergone laboratory tests for hemoglobin AS (HbAS) and who were subject to exertional-injury precautions. Methods We used Cox proportional-hazards models to test whether the risks of exertional rhabdomyolysis and death varied according to sickle cell trait status among 47,944 black soldiers who had undergone testing for HbAS and who were on active duty in the U.S. Army between January 2011 and December 2014. We used the Stanford Military Data Repository, which contains comprehensive medical and administrative data on all active-duty soldiers. Results There was no significant difference in the risk of death among soldiers with sickle cell trait, as compared with those without the trait (hazard ratio, 0.99; 95% confidence interval [CI], 0.46 to 2.13; P = 0.97), but the trait was associated with a significantly higher adjusted risk of exertional rhabdomyolysis (hazard ratio, 1.54; 95% CI, 1.12 to 2.12; P = 0.008). This effect was similar in magnitude to that associated with tobacco use, as compared with no use (hazard ratio, 1.54; 95% CI, 1.23 to 1.94; P<0.001), and to that associated with having a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30.0 or more, as compared with a BMI of less than 25.0 (hazard ratio, 1.39; 95% CI, 1.04 to 1.86; P = 0.03). The effect was less than that associated with recent use of a statin, as compared with no use (hazard ratio, 2.89; 95% CI, 1.51 to 5.55; P = 0.001), or an antipsychotic agent (hazard ratio, 3.02; 95% CI, 1.34 to 6.82; P = 0.008). Conclusions Sickle cell trait was not associated with a higher risk of death than absence of the trait, but it was associated with a significantly

  14. Statin-associated rhabdomyolysis with acute renal failure complicated by intradialytic NSTEMI: a review of lipid management considerations.

    PubMed

    Kar, Subrata; Chockalingam, Anand

    2013-01-01

    Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are associated with myopathy, myalgias, myositis, and rhabdomyolysis. Rhabdoymyolysis is a rare complication and may cause acute renal failure, which may be fatal. In such cases, alternative therapies should be considered. In this review, we attempted to elucidate the lipid management options in patients with rhabdomyolysis and coronary artery disease. We also describe a case report of a patient who developed rhabdomyolysis from dual antilipid therapy followed by acute renal failure and non-ST elevation myocardial infarction. Such a complex case has not been reported in the literature, and lipid management options may include niacin, omega 3-fatty acids, or bile acid sequestrants. Once alternative therapies are initiated, monitoring a patient closely with evaluation for associated adverse events should be performed.

  15. 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.

  16. Acute Abdominal Aorta Thrombosis and Ischemic Rhabdomyolysis Secondary to Severe Alcohol Intoxication

    PubMed Central

    Abbas, Syed Farhat; Farooq, Madeeha; Rasheed, Amna; Ali, Furqan

    2016-01-01

    Acute alcohol intoxication is a common cause of emergency visits worldwide. Although moderate alcohol consumption is protective against coronary artery disease, binge drinking is associated with adverse cardiovascular and neurological outcomes and may even cause sudden death. Although, few past accounts of venous thrombosis with alcohol binge drinking are available, arterial thrombosis with the condition has never been reported in the literature. We present the unusual case of a young Afghan male, who presented to us with painful, tender and swollen legs three days after a heavy alcohol binge on a Saturday night. He was diagnosed as a case of acute limb ischemia secondary to massive abdominal aorta and bilateral femoral artery thrombosis. He also had acute renal failure secondary to rhabdomyolysis. Cardiac workup revealed new onset paroxysmal atrial fibrillation and a large thrombus in the left ventricular cavity. His blood ethanol level was high. He was treated by a multidisciplinary team; urgent surgical thrombectomy for thrombotic complications, intravenous fluid hydration and later renal replacement therapy for acute renal failure. To the best of our knowledge, such a constellation of clinical features in association with severe acute alcohol intoxication has not been reported in the literature. We believe, the procoagulant nature of high blood ethanol levels and the onset of atrial fibrillation after the heavy alcohol binge, known as the holiday heart syndrome, precipitated the thrombotic events leading to rhabdomyolysis and acute renal failure. Through this case, we conclude that a very heavy alcohol binge may cause thrombotic occlusion of the abdominal aorta and femoral arteries resulting in ischemic rhabdomyolysis and acute renal failure. A high index of suspicion must be kept, especially for a patient presenting with tender, swollen lower limbs and acute renal failure after an alcohol binge. PMID:28083449

  17. Rhabdomyolysis-induced compartment syndrome secondary to atorvastatin and strenuous exercise.

    PubMed

    Dunphy, Louise; Morhij, Rossel; Tucker, Sarah

    2017-03-16

    A 50-year-old male UK resident with a history of hypertension and hypercholesterolaemia presented to the emergency department with a 48-hour history of sudden onset bilateral thigh swelling and pain unrelieved by regular analgesia. 3 days prior to presentation, he performed a vigorous workout in the gym. His medications included ramipril 5 mg once daily and atorvastatin 20 mg at night time. He was a non-smoker and did not consume alcohol. He reported no known drug allergies. Physical examination confirmed bilateral swollen thighs, with no overlying skin changes, clinically suggestive of compartment syndrome. His creatine kinase was >50 000 IU with normal renal and liver function tests. Further investigation with MRI-identified prominent swelling of the vastus intermedius and medialis muscles, more marked on the left, with extensive diffuse short tau inversion recovery (STIR) signal hyperintensity and isointensity on T1 sequences, suggestive of rhabdomyolysis. He underwent bilateral fasciotomies of his thighs and aggressive intravenous fluid resuscitation with close monitoring of his electrolytes. Intraoperatively his muscle was healthy, with no evidence of haematoma or necrosis. His medication atorvastatin was stopped due to his rhabdomyolysis. 48 hours later, he returned to theatre and review of his fasciotomy wounds was unremarkable. 4 days later, he was discharged uneventfully. His postoperative recovery was complicated by a serous discharge from his left medial thigh wound. Further investigation with an ultrasound confirmed a 4×1×1cm multiloculated collection within the superficial tissue directly underlying the wound. An aspirate was performed and cultures revealed no growth. He remains under review in the department of plastic surgery. This case report discusses the aetiological spectrum, clinical presentation, pathophysiology, differential diagnosis, investigations, management and complications of rhabdomyolysis.

  18. [Legionnaires' disease complicated by rhabdomyolysis and acute renal failure: about a case].

    PubMed

    Bac, Arnaud; Ramadan, Ahmed Sabry; Youatou, Pierre; Mols, Pierre; Cerf, Dominique; Ngatchou, William

    2016-01-01

    Legionnaires' disease is a bacterial disease of the respiratory system caused by a gram-negative germ whose clinical manifestation can be benign limiting to flu-like syndrome or can be more severe being characterized by pneumonia which may be complicated by multisystem disease that can lead to death. We report the case of a 48 year-old patient with rhabdomyolysis complicated by acute renal failure following Legionella pneumophila pneumonia. We here highlight the pathophysiological aspects and treatment of this rare complication during Legionella infection.

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

    PubMed

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

    1999-07-01

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

  20. A series of cases of rhabdomyolysis after ingestion of Tricholoma equestre

    PubMed Central

    Gabija, Laubner; Gabija, Mikulevičienė

    2016-01-01

    Tricholoma equestre (hereinafter – T. equestre) is a common edible fungus that is considered to be toxic under certain conditions. Here, we report four cases of acute poisoning caused by T. equestre, including one lethal outcome in Lithuania between 2004 and 2013. In the severe case, fatigue, nausea without vomiting and muscle pain, profuse sweating without fever, and respiratory insufficiency occurred. Laboratory tests showed an elevation of creatine kinase (CK), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Although clinical findings and laboratory tests support evidence of rhabdomyolysis, no renal insufficiency was observed. Significance of T. equestre in cardiac changes is feasible but remains unclear. PMID:28356809

  1. [Distal renal tubular acidosis with rhabdomyolysis as the presenting form in 4 pregnant women].

    PubMed

    Carminati, G; Chena, A; Orlando, J M; Russo, S; Salomón, S; Carena, J A

    2001-01-01

    We describe four pregnant patients with distal renal tubular acidosis (type I) (DRTA) whose initial presentation was rhabdomyolysis (RML) secondary to severe hypokalemia. We draw attention to the unusual presentation of DRTA during pregnancy, the low frequency of DRTA in adult patients and RML as initial manifestation. In one case the DRTA was secondary to Sjögren Syndrome and the etiology was unknown in the rest of the cases. We discuss the potential pathogenic mechanisms to explain hypokalemic RML and the various causes of DRTA in adult patients.

  2. Improving effect of ethyl eicosapentanoate on statin-induced rhabdomyolysis in Eisai hyperbilirubinemic rats.

    PubMed

    Naba, Hiroyasu; Kakinuma, Chihaya; Ohnishi, Shuhei; Ogihara, Takuo

    2006-02-03

    The effect of ethyl eicosapentanoate (EPA-E) on statin-induced rhabdomyolysis was investigated by co-administration of EPA-E and pravastatin (PV), as a typical statin, to Eisai hyperbilirubinemic rats (EHBR). It was confirmed that the plasma PV concentration was not affected by simultaneous administration of EPA-E, and there was no cumulative increase of PV during prolonged co-administration of EPA-E and PV. Muscular degeneration was prominent (incidence 5/5; average grade 3.5 (range 2-4)) in EHBR treated with PV alone at 200 mg/kg/day for 14 days, but co-administration of EPA-E at doses of 100, 300, and 1000 mg/kg/day decreased the average grades to 1.4 (range 0.3-3.0), 0.5 (0.2-1.0), and 0.6 (0.0-1.7), respectively. Creatine phosphokinase (CPK) and myoglobin levels in plasma were well correlated with the grade of skeletal muscle degeneration. Thus, EPA-E appears to reduce the severity of statin-induced rhabdomyolysis.

  3. 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

  4. Paliperidone Inducing Concomitantly Syndrome of Inappropriate Antidiuretic Hormone, Neuroleptic Malignant Syndrome, and Rhabdomyolysis.

    PubMed

    Kaur, Jaspinder; Kumar, Dileep; Alfishawy, Mostafa; Lopez, Ricardo; Sachmechi, Issac

    2016-01-01

    Paliperidone, an active metabolite of risperidone, is a new atypical antipsychotic agent. Syndrome of inappropriate antidiuretic hormone (SIADH), neuroleptic malignant syndrome (NMS), and rhabdomyolysis are the uncommon side effects of psychotropic drugs. We report a case of 35-year-old male with schizoaffective disorder who was admitted for acute-on-chronic exacerbation of his psychotic disorder for which intramuscular paliperidone 234 mg injection was given. Two days later, the patient developed hyponatremic seizures secondary to SIADH which was treated with hypertonic saline. On the third day, he developed high grade fever and severe muscle rigidity with raised creatine phosphokinase (CPK) and liver enzymes levels. He was treated with dantrolene 100 mg, bromocriptine 2.5 mg, and lorazepam 2 mg. Our patient required management of the three rare conditions following treatment with paliperidone. This case highlights the need for health care providers to be aware of the rare, potentially life threatening but preventable hyponatremia, NMS, and rhabdomyolysis as a possible adverse effect of paliperidone.

  5. Paliperidone Inducing Concomitantly Syndrome of Inappropriate Antidiuretic Hormone, Neuroleptic Malignant Syndrome, and Rhabdomyolysis

    PubMed Central

    Lopez, Ricardo

    2016-01-01

    Paliperidone, an active metabolite of risperidone, is a new atypical antipsychotic agent. Syndrome of inappropriate antidiuretic hormone (SIADH), neuroleptic malignant syndrome (NMS), and rhabdomyolysis are the uncommon side effects of psychotropic drugs. We report a case of 35-year-old male with schizoaffective disorder who was admitted for acute-on-chronic exacerbation of his psychotic disorder for which intramuscular paliperidone 234 mg injection was given. Two days later, the patient developed hyponatremic seizures secondary to SIADH which was treated with hypertonic saline. On the third day, he developed high grade fever and severe muscle rigidity with raised creatine phosphokinase (CPK) and liver enzymes levels. He was treated with dantrolene 100 mg, bromocriptine 2.5 mg, and lorazepam 2 mg. Our patient required management of the three rare conditions following treatment with paliperidone. This case highlights the need for health care providers to be aware of the rare, potentially life threatening but preventable hyponatremia, NMS, and rhabdomyolysis as a possible adverse effect of paliperidone. PMID:27721999

  6. Late-onset Sheehan’s syndrome presenting with rhabdomyolysis and hyponatremia: a case report

    PubMed Central

    2013-01-01

    Introduction Hyponatremia associated with rhabdomyolysis is a rare event and a correct diagnostic approach is required to rule out this or other diseases as a primary cause and to avoid other complications resulting from a lack of appropriate treatment. Case presentation A 64-year-old Caucasian woman presented to our facility with worsening fatigue, slurred speech, nausea and vomiting, and high serum levels of creatine kinase and myoglobin together with hyponatremia. Normal arterial blood gas analysis results, normal serum potassium levels, increased urine sodium levels, urine specific gravity of >1003N/m3 and low urine volume suggested an endocrine etiology. Her low cortisol and thyroid hormone serum levels suggested a pituitary disorder. A magnetic resonance imaging study showed atrophy of her pituitary gland. A more detailed study of our patient’s obstetric history revealed a post-partum hemorrhage 30 years earlier. She was diagnosed as having late-onset Sheehan’s syndrome and treated with hormone replacement therapy, which normalized her clinical picture. Conclusions This case report shows that, in hyponatremia-associated rhabdomyolysis, an endocrinological origin should always be considered. This should include Sheehan’s syndrome as it can occur with late onset. PMID:24083446

  7. 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.

  8. 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

  9. Acute rhabdomyolysis of the soleus muscle induced by a lightning strike: magnetic resonance and scintigraphic findings.

    PubMed

    Watanabe, Naofumi; Inaoka, Tsutomu; Shuke, Noriyuki; Takahashi, Koji; Aburano, Tamio; Chisato, Naoyuki; Nochi, Hitoshi; Go, Kazutomo

    2007-07-01

    Among natural disasters, a lightning strike is a rare but potentially life-threatening phenomenon. If victims survive a cardiac arrest due to instantaneous passage of an exceptionally high voltage electric charge through the whole body, they may be afflicted with various complications such as muscle necrosis resulting in acute renal failure. In this article, we report a case of a 54-year-old man with acute rhabdomyolysis of the left soleus muscle associated with a lightning strike. T2-weighted and short-tau inversion recovery MR images showed a high signal intensity in the left soleus muscle. A whole-body bone scintigram showed abnormal uptakes in the left soleus muscle and the dorsal aspect of the left foot. MR and scintigraphic evaluations were very useful in depicting the site and extent of muscle damage. Since the patient showed a surprisingly high level of serum creatine kinase, the added information was very valuable for determining the patient's management.

  10. Sickle Cell Trait Complicated by Acute Rhabdomyolysis in Military Personnel: A Case Report.

    PubMed

    Harrison, Joshua M; Wuerdeman, Marc F

    2015-08-01

    Sickle cell trait, a trait known to be protective against falciparum malaria, is prevalent in the African American community. Unlike true sickle cell disease, sickle cell trait is currently not a disqualifying condition for military service. In the case below, we describe an occurrence, from Logar Provence, Afghanistan (2,072 m above mean sea level), of exertional acute rhabdomyolysis in an American service member known to be a sickle cell trait carrier. The case serves to educate Military Medical providers and Commanders alike, to the increased risk certain training and work environments have on sickle cell trait Service members; it raises the question of what duty limitations, if any, sickle cell carriers should have.

  11. [Drug interaction caused by communication problems. Rhabdomyolysis due to a combination of itraconazole and simvastatin].

    PubMed

    Tiessen, Renger G; Lagerwey, Hendrik Jan G; Jager, Gea J; Sprenger, Herman G

    2010-01-01

    A 58-year-old man, who spoke very little Dutch, had various symptoms and used several drugs including simvastatin. He was prescribed itraconazole for onychomycosis. Simvastatin was concurrently replaced with pravastatin to prevent drug interactions. However, the interaction still occurred when the pravastatin ran out, and the patient resumed taking simvastatin on his own initiative. Myalgia and muscle weakness developed after one week. The general practitioner found a strongly elevated creatine kinase level in the blood. The patient required hospitalisation for severe rhabdomyolysis. He was treated with an infusion of an ample quantity of physiological saline solution and made a full recovery. Due to the elevated risk of toxic interactions, doctors should beware of communication problems in complex patients and avoid new prescriptions not strictly required.

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

    PubMed

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

    2008-01-01

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

  13. Forty Years Abuse of Baking Soda, Rhabdomyolysis, Glomerulonephritis, Hypertension Leading to Renal Failure: A Case Report

    PubMed Central

    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

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

    PubMed Central

    Diaz, James H.

    2015-01-01

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

  15. Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury.

    PubMed

    Shi, Yingfeng; Xu, Liuqing; Tang, Jinhua; Fang, Lu; Ma, Shuchen; Ma, Xiaoyan; Nie, Jing; Pi, Xiaoling; Qiu, Andong; Zhuang, Shougang; Liu, Na

    2017-03-01

    Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment.

  16. Recurrent aborted sudden cardiac death with seizures and rhabdomyolysis due to bulimia-induced hypokalemia: report of one case.

    PubMed

    Finsterer, Josef; Stöllberger, Claudia

    2014-06-01

    Recurrent vomiting due to bulimia associated with abuse of furosemide and laxatives causing severe hypokalemia may result in recurrent aborted sudden cardiac death (SCD) and seizures. We report a 25-year-old female with a history of bulimia associated with abuse of furosemide and laxatives since the age of 15 years, migraine since puberty, renal abscesses at age 20 y, and rhabdomyolysis of unknown cause at age 24 y. She experienced aborted SCD due to severe hypokalemia with symptomatic seizures at 21 and 25 years of age. Bulimia patients additionally taking laxatives or furosemide are at particular risk of SCD and rhabdomyolysis and require periodic determination of electrolytes, potassium substitution, and adequate psychiatric therapy and surveillance.

  17. 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

  18. Ventilator-associated pneumonia caused by OXA-48-producing Escherichia coli complicated by ciprofloxacin-associated rhabdomyolysis.

    PubMed

    Grisold, Andrea J; Hoenigl, Martin; Ovcina, Ismar; Valentin, Thomas; Fruhwald, Sonja

    2013-12-01

    We report the emergence of OXA-48 carbapenemase-producing Escherichia coli in Austria causing ventilator-associated pneumonia in a traveler returning from Egypt. Depending on resistance testing, quinolones may remain a therapeutic option for infections caused by these multiple resistant pathogens, as this class of drugs has a favorable safety and tolerability profile when compared to the alternatives. In this patient, however, the clinical course was dramatically complicated by the development of ciprofloxacin-associated rhabdomyolysis.

  19. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia: A Case Report.

    PubMed

    Mody, Mayur D; Ravindranathan, Deepak; Gill, Harpaul S; Kota, Vamsi K

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.

  20. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

    PubMed Central

    Mody, Mayur D.; Ravindranathan, Deepak; Gill, Harpaul S.; Kota, Vamsi K.

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia. PMID:28203579

  1. Venlafaxine-associated serotonin syndrome causing severe rhabdomyolysis and acute renal failure in a patient with idiopathic Parkinson disease.

    PubMed

    Rajapakse, Senaka; Abeynaike, Lakshan; Wickramarathne, Thanushi

    2010-10-01

    A 43-year-old male patient with idiopathic Parkinson disease, on dopaminergic therapy, was admitted with confusion and agitation, diaphoresis, and hyperkinesia after the commencement of the serotonin-noradrenaline reuptake inhibitor venlafaxine 2 weeks prior for depression. He was found to have severe rhabdomyolysis and developed acute renal failure. The most likely diagnosis was serotonin syndrome induced by venlafaxine, although neuroleptic malignant syndrome was also considered. The differential diagnosis, atypical features in this presentation, and possible mechanisms are discussed.

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

    PubMed

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

    2015-11-01

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

  3. 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

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

    PubMed Central

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

    2007-01-01

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

  5. Heme oxygenase-1 induction contributes to renoprotection by G-CSF during rhabdomyolysis-associated acute kidney injury.

    PubMed

    Wei, Qingqing; Hill, William D; Su, Yunchao; Huang, Shuang; Dong, Zheng

    2011-07-01

    Granulocyte colony-stimulating factor (G-CSF) is renoprotective during acute kidney injury (AKI) induced by ischemia and cisplatin nephrotoxicity; however, the underlying mechanism is not entirely clear. Rhabdomyolysis is another important clinical cause of AKI, due to the release of nephrotoxins (e.g., heme) from disrupted muscles. The current study has determined the effects of G-CSF on rhabdomyolysis-associated AKI using in vivo and in vitro models. In C57BL/6 mice, intramuscular injection of glycerol induced AKI, which was partially prevented by G-CSF pretreatment. Consistently, glycerol-induced renal tissue damage was ameliorated by G-CSF. In addition, animal survival following the glycerol injection was improved from ∼30 to ∼70% by G-CSF. In cultured renal tubular cells, hemin-induced apoptosis was also suppressed by G-CSF. Interestingly, G-CSF induced heme oxygenase-1 (HO-1, a critical enzyme for heme/hemin degradation and detoxification) in both cultured tubular cells and mouse kidneys. Blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) could largely diminish the protective effects of G-CSF. Together, these results demonstrated the renoprotective effects of G-CSF in rhabdomyolysis-associated AKI. Notably, G-CSF may directly protect against tubular cell injury under the disease condition by inducing HO-1.

  6. 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

  7. Non-cardiogenic pulmonary edema, rhabdomyolysis and myocardial injury following heroin inhalation: a case report

    PubMed Central

    Bazoukis, G; Spiliopoulou, A; Mourouzis, K; Grigoropoulou, P; Yalouris, A

    2016-01-01

    Background: Heroin use by non-injecting routes of administration (snorting, swallowing, “chasing the dragon”) is considered to be safer but is not risk-free for fatal overdose or serious side effects. We report the case of an adolescent who was transferred unconscious to the emergency department after heroin inhalation. Description of the case: A 17-year-old male was transferred to the emergency department unconscious (Glasgow coma scale: 6/15) after heroin inhalation. He was treated with non-rebreather mask and intravenous infusion of naloxone with gradual improvement of consciousness and arterial blood gasses. The chest computed tomography showed signs of acute respiratory distress syndrome. Laboratory exams on the second day of hospitalization showed elevated creatine kinase (CK) and troponin-I levels while his electrocardiography (ECG) showed J-point elevation in V1, V2, and V3 precordial leads. On the second day of hospitalization the pulmonary infiltrates were not present in his chest X-ray while on the eighth day, troponin-I and CK levels were normalized without dynamic ECG changes and the patient was discharged uneventfully. Conclusion: Heroin inhalation may cause severe complications, such as non-cardiogenic pulmonary edema, rhabdomyolysis or myocardial injury. Hippokratia 2016, 20(1): 84-87 PMID:27895451

  8. Recurrent rhabdomyolysis due to muscle β-enolase deficiency: very rare or underestimated?

    PubMed

    Musumeci, Olimpia; Brady, Stefen; Rodolico, Carmelo; Ciranni, Annamaria; Montagnese, Federica; Aguennouz, M'hammed; Kirk, Richard; Allen, Elizabeth; Godfrey, Richard; Romeo, Sara; Murphy, Elaine; Rahman, Shamima; Quinlivan, Ros; Toscano, Antonio

    2014-12-01

    Muscle β-enolase deficiency is a very rare inherited metabolic myopathy caused by an enzymatic defect of distal glycolysis. So far, the condition has been described in only one patient with mutations in ENO3 in a compound heterozygous state who presented with exercise intolerance, post-exercise myalgia and mild hyperCKemia but no pigmenturia. We describe two men, one Italian and one Turkish, with consanguineous parents, who complained of several episodes of intense myalgia, cramps, generalized muscle tenderness and dark urine. No other family members reported similar symptoms. In both cases, there was a very mild rise in lactate during a forearm exercise test. Muscle biopsy showed minimal changes with no lipid or glycogen accumulation. Biochemical studies on muscle tissue demonstrated a marked reduction of muscle β-enolase activity (20 and 10% of residual activity, respectively). Molecular genetic analysis of ENO3 gene revealed two novel homozygous missense mutations, (p.Asn151Ser and p.Glu187Lys). Both mutations segregated as expected in the two families. Although quite rare, muscle β-enolase deficiency should be considered in the differential diagnosis of patients presenting with recurrent rhabdomyolysis. It may present also with a more severe phenotype than previously thought.

  9. Fatal endocarditis with methicilin-sensible Staphylococcus aureus and major complications: rhabdomyolysis, pericarditis, and intracerebral hematoma

    PubMed Central

    Georgescu, Anca Meda; Azamfirei, Leonard; Szalman, Krisztina; Szekely, Edit

    2016-01-01

    Abstract Background: Over the last decades Staphylococcus aureus (SA) has become the dominant etiology of native valve infective endocarditis, with the community-acquired methicillin-sensible Staphylococcus aureus (CA-MSSA) strains being the prevailing type. Case: We report here a case of extremely severe CA-MSSA aortic valve acute endocarditis associated with persistent Staphylococcus aureus bacteremia (SAB) in a previously healthy man and include a literature review. The patient developed severe and rare complications (purpura, purulent pericarditis, intracerebral hematoma, and rhabdomyolysis) through systemic embolism; they required drainage of pericardial empyema and cerebral hematoma, the latter eventually caused a fatal outcome. The strains recovered from sequential blood culture sets and pericardial fluid were MSSA negative for genes encoding for staphylococcal toxic shock syndrome toxin (TSST)-1 and Panton–Valentine leukocidin. C, G, and I enterotoxin genes were detected. Conclusions: This case with unusually severe evolution underlines the limited ability of vancomycin to control some MSSA infections, possibly due to potential involvement of SA virulence factors, hence the importance of clinical vigilance for community SAB cases. PMID:27741135

  10. 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

  11. Genetic mapping of recurrent exertional rhabdomyolysis in a population of North American Thoroughbreds

    PubMed Central

    Fritz, K.L.; McCue, M.E.; Valberg, S.J.; Rendahl, A.K.; Mickelson, J.R.

    2013-01-01

    Summary Recurrent exertional rhabdomyolysis is a heritable disorder that results in painful skeletal muscle cramping with exercise in up to 10% of all Thoroughbred racehorses. Here we report a genome-wide association study with 48,282 SNPs analyzed among 48 case and 37 control Thoroughbreds. The most significant SNPs spanned approximately 13 Mb on ECA16, and the p-value of the most significant SNP after correcting for population structure was 8.0 × 10−6. This region on ECA16 was further evaluated by genotyping 247 SNPs in both the initial population and a second population of 34 case and 98 control Thoroughbreds. Several SNPs across the 13 Mb region on ECA16 showed significance when each population was analyzed separately; however, the exact positions of the most significant SNPs within this region on ECA16 varied between populations. This variability in location may be attributed to lack of power due to insufficient sample sizes within each population individually, or to the relative distribution of long conserved haplotypes, which are characteristic of the Thoroughbred breed. Future genome-wide association studies with additional horses would likely improve the power to resolve casual loci located on ECA16 and increase the likelihood of detecting any additional loci on other chromosomes contributing to disease susceptibility. PMID:22497487

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

    PubMed

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

    2014-02-01

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

  13. 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.

  14. Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma.

    PubMed

    Shirai, Takushi; Sano, Tasuku; Kamijo, Fuminao; Saito, Nana; Miyake, Tomomi; Kodaira, Minori; Katoh, Nagaaki; Nishie, Kenichi; Okuyama, Ryuhei; Uhara, Hisashi

    2016-01-01

    We reported an 81-year-old woman with metastatic melanoma, in whom myasthenia gravis and rhabdomyolysis developed after nivolumab monotherapy. The first symptom of myasthenia gravis was dyspnea. Ultrasonography detected hypokinesis of the bilateral diaphragm suggesting myasthenia gravis, although there was no abnormal finding of the lungs in computed tomography images. Acetylcholine receptor binding antibodies were low-titer positive in the preserved serum before administration of nivolumab, strongly suggesting that the myasthenia gravis was a nivolumab-related immune adverse event. Despite the remarkable clinical benefits of immune checkpoint inhibitors for patients with advanced melanoma, it is important to recognize unexpected immune-related adverse events.

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

    PubMed Central

    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.

    2015-01-01

    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

  16. Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis.

    PubMed

    McKenzie, E C; Eyrich, L V; Payton, M E; Valberg, S J

    2016-10-01

    A previous report suggests a substantial incidence of exertional rhabdomyolysis (ER) in Arabian horses performing endurance racing. This study compared formalin histopathology and clinical and metabolic responses to a standardised field exercise test (SET) between Arabians with and without ER. Arabian horses with (n = 10; age 15.4 ± 5.6 years) and without (n = 9; 12.9 ± 6.1 years) prior ER were stall-rested for 24-48 h, after which paired ER and control horses were fitted with a telemetric ECG and performed a 47 min submaximal SET. Plasma glucose, lactate, electrolyte and total protein concentrations and packed cell volume were measured before and immediately after exercise. Blood and percutaneous gluteal muscle samples were also obtained before and 3 h after exercise for measurement of plasma creatine kinase (CK) activity and muscle glycogen concentration, respectively. Histopathologic analysis of formalin-fixed pre-exercise muscle sections was performed. Data were analyzed by ANOVA and non-parametric tests (P <0.05). No horses displayed clinical signs of ER during exercise, and plasma CK increased similarly in ER and control Arabians. Muscle glycogen, heart rate, and remaining plasma variables did not differ between horses with ER and control horses. Horses with ER had more internalised nuclei in mature myofibers, more aggregates of cytoplasmic glycogen and desmin, and higher myopathic scores than control horses. Although many horses with ER had histopathologic evidence of chronic myopathy, muscle glycogen concentrations and metabolic exercise responses were normal. Results did not support a consistent metabolic myopathy or a glycogen storage disorder in Arabians with ER.

  17. Is rhabdomyolysis an anaesthetic complication in patients undergoing robot-assisted radical prostatectomy?

    PubMed Central

    Karaoren, Gulsah; Bakan, Nurten; Kucuk, Eyüp Veli; Gumus, Eyup

    2017-01-01

    BACKGROUND: In patients undergoing robot-assisted radical prostatectomy (RARP), pneumoperitoneum, intraoperative fluid restriction and prolonged Trendelenburg position may cause rhabdomyolysis (RM) due to hypoperfusion in gluteal muscles and lower extremities. In this study, it was aimed to assess effects of body mass index (BMI), comorbidities, intra-operative positioning, fluid restriction and length of surgery on the development of RM in RARP patients during the perioperative period. SUBJECTS AND METHODS: The study included 52 American Society of Anesthesiologists I–II patients aged 50–80 years with BMI >25 kg/m2, who underwent RARP. Fluid therapy with normal saline (1 ml/kg/h) and 6% hydroxyethyl starch 200/05 (1 ml/kg/h) was given during the surgery. Charlson comorbidity index (CCI), operation time (OT) and Trendelenburg time (TT) were recorded. Blood samples for creatine phosphokinase (CPK), blood urea nitrogen, creatinine (Cr), aspartate aminotransferase (AST), alanine transferase (ALT), lactate dehydrogenase (LDH), creatinine kinase-MB, cardiac troponin I and arterial blood gases were drawn at baseline and on 6, 12, 24 and 48 h. RM was defined by serum CPK level exceeding 5000 IU/L. RESULTS: Seven patients met predefined criteria for RM. There were positive correlations among serum CPK and Cr, AST, ALT and LDH levels. However, there was no significant difference in BMI, OT and TT between patients with or without RM (P > 0.05). CCI scores were higher in patients with RM than those without (3.00 ± 0.58 vs. 2.07 ± 0.62; P < 0.01). No renal impairment was detected among patients with RM at the post-operative period. CONCLUSIONS: It was found that comorbid conditions are more important in the development of RM during RARP rather than BMI, OT or TT. Patients with higher comorbidity are at risk for RM development and that this should be kept in mind at follow-up and when informing patients. PMID:27251811

  18. 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

  19. 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

  20. 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.

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

    PubMed

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

    2015-12-01

    We present an adolescent elite water polo player who despite a genetic predisposition to develop exercise-induced severe muscle damage due to carrying the IL-6 174C allele single-nucleotide polymorphism, developed acute rhabdomyolysis only after a vigorous out-of-water training, suggesting that water polo training may be more suitable for genetically predisposed athletes.

  2. 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. PMID:27635145

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

    PubMed Central

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

    2015-01-01

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

  4. 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

  5. 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.

  6. Rhabdomyolysis: a case study exploring the possible side effect of lipid lowering medication by a HIV positive patient taking a protease inhibitor.

    PubMed

    De Carvalho, Diana; Citro, Mark; Tibbles, Anthony

    2008-12-01

    This case study explores the incidence of rhabdomyolysis in a HIV positive patient that was taking a lipid lowering drug and a protease inhibitor concurrently while under chiropractic treatment for generalized muscular soreness. Dyslipidemia is a very common problem both in the general and HIV population, with many patients being prescribed lipid lowering drugs. While extremely rare, adverse effects of lipid lowering drugs have been documented to include myopathy such as rhabdomyolysis. It is imperative that chiropractors are aware of the possible adverse side effect of lipid lowering drug therapy in their patients complaining of musculoskeletal pain. It is even more important that chiropractors treating the HIV population are aware of the potential interactions between these medications and protease inhibitors to cause myopathy.

  7. OATP1B1-related drug–drug and drug–gene interactions as potential risk factors for cerivastatin-induced rhabdomyolysis

    PubMed Central

    Tamraz, Bani; Fukushima, Hisayo; Wolfe, Alan R.; Kaspera, Rüdiger; Totah, Rheem A.; Floyd, James S.; Ma, Benjamin; Chu, Catherine; Marciante, Kristin D.; Heckbert, Susan R.; Psaty, Bruce M.; Kroetz, Deanna L.; Kwok, Pui-Yan

    2014-01-01

    Objective Genetic variation in drug metabolizing enzymes and membrane transporters as well as concomitant drug therapy can modulate the beneficial and the deleterious effects of drugs. We investigated whether patients exhibiting rhabdomyolysis who were taking cerivastatin possess functional genetic variants in SLCO1B1 and whether they were on concomitant medications that inhibit OATP1B1, resulting in accumulation of cerivastatin. Methods This study had three components: (a) resequencing the SLCO1B1 gene in 122 patients who developed rhabdomyolysis while on cerivastatin; (b) functional evaluation of the identified SLCO1B1 nonsynonymous variants and haplotypes in in-vitro HEK293/FRT cells stably transfected with pcDNA5/FRT empty vector, SLCO1B1 reference, variants, and haplotypes; and (c) in-vitro screening of 15 drugs commonly used among the rhabdomyolysis cases for inhibition of OATP1B1-mediated uptake of cerivastatin in HEK293/FRT cells stably transfected with reference SLCO1B1. Results The resequencing of the SLCO1B1 gene identified 54 variants. In-vitro functional analysis of SLCO1B1 nonsynonymous variants and haplotypes showed that the V174A, R57Q, and P155T variants, a novel frameshift insertion, OATP1B1*14 and OATP1B1*15 haplotype were associated with a significant reduction (P<0.001) in cerivastatin uptake (32, 18, 72, 3.4, 2.1 and 5.7% of reference, respectively). Furthermore, clopidogrel and seven other drugs were shown to inhibit OATP1B1-mediated uptake of cerivastatin. Conclusion Reduced function of OATP1B1 related to genetic variation and drug–drug interactions likely contributed to cerivastatin-induced rhabdomyolysis. Although cerivastatin is no longer in clinical use, these findings may translate to related statins and other substrates of OATP1B1. PMID:23652407

  8. Severe Rhabdomyolysis as Complication of Interaction between Atorvastatin and Fusidic Acid in a Patient in Lifelong Antibiotic Prophylaxis: A Dangerous Combination.

    PubMed

    Nandy, Anirban; Gaïni, Shahin

    2016-01-01

    Atorvastatin and HMG-CoA reductase inhibitors are the most frequently used medication in the world due to very few adverse toxic side effects. One potentially life threatening adverse effect is caused by clinically significant statin induced rhabdomyolysis, either independently or in combination with fusidic acid. The patient in our case who previously had cardiac insufficiency, atrial fibrillation, and thoracic aorta aneurysm and was treated with insertion of an endovascular metallic stent in the aorta is presented in the report. He had an inoperable aortitis with an infected stent and para-aortic abscesses with no identified microorganism. The patient responded well to empirical antibiotic treatment with combination therapy of fusidic acid and moxifloxacin. This treatment was planned as a lifelong prophylactic treatment. The patient had been treated with atorvastatin for several years. He developed severe rhabdomyolysis when he was started on fusidic acid and moxifloxacin. The patient made a fast recovery after termination of treatment with atorvastatin and fusidic acid. We here report a life threatening complication of rhabdomyolysis that physicians must be aware of. This can happen either in atorvastatin monotherapy or as a complication of pharmacokinetic interaction between atorvastatin and fusidic acid.

  9. Severe Rhabdomyolysis as Complication of Interaction between Atorvastatin and Fusidic Acid in a Patient in Lifelong Antibiotic Prophylaxis: A Dangerous Combination

    PubMed Central

    2016-01-01

    Atorvastatin and HMG-CoA reductase inhibitors are the most frequently used medication in the world due to very few adverse toxic side effects. One potentially life threatening adverse effect is caused by clinically significant statin induced rhabdomyolysis, either independently or in combination with fusidic acid. The patient in our case who previously had cardiac insufficiency, atrial fibrillation, and thoracic aorta aneurysm and was treated with insertion of an endovascular metallic stent in the aorta is presented in the report. He had an inoperable aortitis with an infected stent and para-aortic abscesses with no identified microorganism. The patient responded well to empirical antibiotic treatment with combination therapy of fusidic acid and moxifloxacin. This treatment was planned as a lifelong prophylactic treatment. The patient had been treated with atorvastatin for several years. He developed severe rhabdomyolysis when he was started on fusidic acid and moxifloxacin. The patient made a fast recovery after termination of treatment with atorvastatin and fusidic acid. We here report a life threatening complication of rhabdomyolysis that physicians must be aware of. This can happen either in atorvastatin monotherapy or as a complication of pharmacokinetic interaction between atorvastatin and fusidic acid. PMID:28115938

  10. Management of Severe Rhabdomyolysis and Exercise-Associated Hyponatremia in a Female with Anorexia Nervosa and Excessive Compulsive Exercising

    PubMed Central

    2016-01-01

    This case report describes the management of a 49-year-old female with restricting-type anorexia nervosa and excessive compulsive exercising associated with rhabdomyolysis, high levels of serum creatine kinase (CK) (3,238 U/L), and marked hyponatremia (Na+: 123 mEq/L) in the absence of purging behaviours or psychogenic polydipsia; it is the first case report to describe exercise-associated hyponatremia in a patient with anorexia nervosa. The patient, who presented with a body mass index (BMI) of 13.4 kg/m2, was successfully treated by means of an adapted inpatient version of an enhanced form of cognitive behavioural therapy (CBT-E). Within a few days, careful water restriction, solute refeeding, and the specific cognitive behavioural strategies and procedures used to address the patient's excessive compulsive exercising and undereating produced a marked reduction in CK levels, which normalised within one week. Exercise-associated hyponatremia also gradually improved, with serum sodium levels returning to normal within two weeks. The patient thereby avoided severe complications such as cerebral or pulmonary oedema or acute renal failure and was discharged after 20 weeks of treatment with a BMI of 19.0 kg/m2 and improved eating disorder psychopathology. PMID:27721832

  11. Systemic rhabdomyolysis induced by venom of freshwater stingrays Plesiotrygon iwamae and Potamotrygon motoro (Chondrichthyes-Potamotrygonidae) from the Amazon Basin.

    PubMed

    Lameiras, Juliana Luiza Varjão; da Costa, Oscar Tadeu Ferreira; Moroni, Fábio Tonissi; Araújo, José de Ribamar; Caranhas, Sandra Maria Evangelista; Marques, Carlos Melquiades Almeida; Dos-Santos, Maria Cristina; Duncan, Wallice Luiz Paxiúba

    2014-01-01

    Injuries caused by freshwater stingrays are characterized by intense pain and pathological changes at the lesion site, including oedema, erythema and, in most cases, necrosis. In this study, the systemic myotoxic activity induced by mucus extracts from the dorsal region and stinger of the stingrays Plesiotrygon iwamae and Potamotrygon motoro was described, analysed and quantified. Twenty-four hours after injection of 400 μg of the extracts into the gastrocnemius muscle of mice, the following effects were observed: coagulative necrosis of the muscle tissue, muscle fibre regeneration and the presence of inflammatory infiltrates, including neutrophils, macrophages, and a reduced number of eosinophils and lymphocytes. These changes were also observed, although to a lesser extent, in the gastrocnemius muscles of the contralateral limbs, demonstrating that the extracts from the two species could induce systemic rhabdomyolysis. Based on morphometric analysis, it was observed that the stinger extract of P. motoro was more potent in inducing local and systemic myotoxic activity, followed by the dorsal extract from P. motoro and stinger and dorsal extracts from P. iwamae, which induced similar effects.

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

    PubMed Central

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

    2016-01-01

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

  13. Exercise-Induced Rhabdomyolysis and Stress-Induced Malignant Hyperthermia Events, Association with Malignant Hyperthermia Susceptibility, and RYR1 Gene Sequence Variations

    PubMed Central

    2013-01-01

    Exertional rhabdomyolysis (ER) and stress-induced malignant hyperthermia (MH) events are syndromes that primarily afflict military recruits in basic training and athletes. Events similar to those occurring in ER and in stress-induced MH events are triggered after exposure to anesthetic agents in MH-susceptible (MHS) patients. MH is an autosomal dominant hypermetabolic condition that occurs in genetically predisposed subjects during general anesthesia, induced by commonly used volatile anesthetics and/or the neuromuscular blocking agent succinylcholine. Triggering agents cause an altered intracellular calcium regulation. Mutations in RYR1 gene have been found in about 70% of MH families. The RYR1 gene encodes the skeletal muscle calcium release channel of the sarcoplasmic reticulum, commonly known as ryanodine receptor type 1 (RYR1). The present work reviews the documented cases of ER or of stress-induced MH events in which RYR1 sequence variations, associated or possibly associated to MHS status, have been identified. PMID:23476141

  14. 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

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

    PubMed

    Navarrete, Norberto; Aldana, Norberto Navarrete

    2013-01-01

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

  16. Association of Rhabdomyolysis with Renal Outcomes and Mortality in Burn Patients

    DTIC Science & Technology

    2013-05-01

    estimates of rates of AKI in the burn population widely varied, in part because of differences in both definitions of AKI and inclusion criteria...and AKIN-3 as a >3-fold increase from baseline (or an increase of 0.5 mg/dl when the baseline was more than 4 mg/dl).10 By definition , all patients...patients requiring RRT who survived to discharge, only one required maintenance hemodialysis . The prevalence of AKIN-2 or AKIN-3, death, and RRT

  17. Normalization of creatine kinase values in a case of rhabdomyolysis during daptomycin treatment

    PubMed Central

    Ferrández, Olivia; Urbina, Olatz; Luque, Sònia; Espona, Mercè; Berenguer, Nuria; Grau, Santiago

    2013-01-01

    A 41-year-old woman presented in the Emergency Department with suspected compartment syndrome of lower left leg (creatine kinase [CK]: 12,502 IU/L, Cr: 4.31 mg/dL). Fasciotomy of the four limb compartments was conducted. By day 2, the patient presented oliguria during previous 24 h, so daily intermittent dialysis was carried out. On day 12, the patient presented an episode of bacteremia due to Staphylococcus hominis. Treatment with vancomycin was initiated and was changed after 4 days to daptomycin due to unsatisfactory clinical progression (6 mg/kg every 48 h, according to renal function and patient's weight) (CK: 2,972 IU/L). After 15 days of treatment, the dose of daptomycin was increased to 6 mg/kg every 24 h (CrCL: 46 mL/min, CK: 83 IU/L). The antibiotic was continued for another 4 days. Fourteen days later, the patient was discharged (CK: 26 IU/L). Daptomycin could be prescribed in some patients with elevated CK values. A cut-off value of baseline CK for use of daptomycin needs to be determined. PMID:23716901

  18. [Rhabdomyolysis and acute renal failure in human influenza A H1N1 mediated infection].

    PubMed

    Carrillo-Esper, Raúl; Ornelas-Arroyo, Sofía; Pérez-Bustos, Estela; Sánchez-Zúñiga, Jesús; Uribe-Esquivel, Misael

    2009-01-01

    Rabdomiolysis and acute renal failure secondary to influenza infection are rare. Up to now, few cases have been reported and most of them are primarily among children. Myositis associated to influenza infection is caused by the toxic effect of the virus in the muscular fiber, dysregulation of inflammatory cytokines and a cross reaction between the muscle fiber and the viral particles. We present the case of a 57 year old male with a diagnosis of H1N1 influenza who developed polyuria, oligoanuria, elevation of lactic dehydrogenase, myoglobin, creatinin phosphokinase and an electromyography with a myopathic pattern. The diagnosis of rabdomyolisis and acute renal failure were made, hemodyalisis was started and the patient improved satisfactorily. This is the first report of a patient with radmoyolisis and acute renal failure secondary to A H1N1 influenza treated during the Mexico epidemic.

  19. [Rhabdomyolysis and lumbosacral plexopathy in intravenous drug addict: report of a case].

    PubMed

    Diaz Guzman, J; Pastor Valverde, C; Gil Grande, R; Alonso Ortiz, A; Trueba Gutierrez, J L

    1996-02-01

    There are several neuromuscular complications in the intravenous heroin addict (IHA). Someone may be due to direct toxic effect of the substance, but other ones may be associated to abuser's typical diseases (i.e. HIV infection). We present a 27 year-old IHA patient, HIV positive, that develop acute rhabdomyolisis with severe neuromuscular involvement, and consistent clinical and electrodiagnostic features of lumbosacral plexus neuropathy, forteen hours after an heroin inyection. Thirty months later, the patient is severely disabled, but her initial painfull and paretic picture have improved. The association of rhabdomyolisis-lumbosacral plexopathy (RLPS) is ocasionally reported. It has been proposed that RLSP is etiologically related to mecanic, toxic and immunologic factors.

  20. 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.

  1. 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.

  2. Aeromonas sobria sepsis complicated by rhabdomyolysis in an HIV-positive patient: case report and evaluation of traits associated with bacterial virulence.

    PubMed

    Stano, Francesca; Brindicci, Gaetano; Monno, Rosa; Rizzo, Caterina; Ghezzani, Francesca; Carbonara, Sergio; Guaglianone, Emilio; Donelli, Gianfranco; Monno, Laura

    2009-05-01

    Human infection with Aeromonas species is uncommon and most often due to trauma with exposure to contaminated water or soil. A 43-year-old HIV- and hepatitis C virus (HCV)-infected male, after a two-week course of corticosteroid therapy for an autoimmune anemia, developed diarrhea, dermatologic manifestations and a multiple organ dysfunction syndrome, resulting in death. Although stool samples were repeatedly negative, two sets of blood cultures obtained during a single peak of fever yielded the post-mortem isolation of a Gram-negative, oxidase-positive, beta-hemolytic bacillus that was identified as Aeromonas sobria. Empiric antibiotic therapy was unsuccessful. Evaluation of the virulence-associated traits of the clinical isolate (adhesion, cytotoxicity activity, biofilm production) showed that the strain was a poor producer of recognized virulence factors, thereby indicating that the unfortunate coexistence of HIV infection, HCV-related liver cirrhosis and corticosteroids played a key role in the clinical course.

  3. 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.

  4. 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 Central

    Mancano, Michael A.

    2015-01-01

    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

  5. Acute myoedema: an unusual presenting manifestation of hypothyroid myopathy

    PubMed Central

    Bhansali, A; Chandran, V; Ramesh, J; Kashyap, A; Dash, R

    2000-01-01

    We describe a patient with primary hypothyroidism due to autoimmune thyroiditis, presenting with acute myoedema and spontaneous rhabdomyolysis. During his hospital stay, he developed altered sensorium due to hypo-osmolal hyponatraemia and later developed bilateral foot drop that responded to appropriate treatment.


Keywords: hypothyroidism; myoedema; rhabdomyolysis PMID:10644388

  6. Use of Performance Measures to Evaluate, Document Competence and Deterioration of Advanced Surgical Skills Exposure for Trauma (ASSET) Surgical Skills

    DTIC Science & Technology

    2014-03-01

    Bicarbonate Monitor for arrhythmia Already lengthy ischemic time: Temporary vascular shunt Recognize need for fasciotomy Monitor for...Monitor for arrhythmia Already lengthy ischemic time: Temporary vascular shunt Recognize need for fasciotomy Monitor for rhabdomyolysis

  7. Dystonia not dystopia: effects of the legal high, 'Clockwork Orange'.

    PubMed

    Mackey, Helen Elizabeth; Hawksley, Oliver

    2015-12-10

    A 27-year-old man presented to hospital after smoking a legal high named 'Clockwork Orange'. He suffered dystonia, acute kidney injury, rhabdomyolysis, lactic acidosis and a troponin rise. He was treated with procyclidine and intravenous fluids.

  8. Acute phosphate nephropathy.

    PubMed

    Monfared, Ali; Habibzadeh, Seyed Mahmoud; Mesbah, Seyed Alireza

    2014-05-01

    We present acute phosphate nephropathy in a 28-year-old man, which was developed after a car accident due to rhabdomyolysis. Treatment of acute kidney injury was done with administration of sodium bicarbonate.

  9. Phenotype standardization for statin-induced myotoxicity.

    PubMed

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

    2014-10-01

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

  10. Medical Surveillance Monthly Report (MSMR). Volume 20, Number 3

    DTIC Science & Technology

    2013-03-01

    subgroup members may refl ect, at least in part, an increased risk of exertional rhabdomyolysis among individuals with sickle cell trait.4-6 Supervisors...patients with sickle cell trait: is it time to change our approach? Hematology. 2007;12(4):349-352. 5. Ferster K, Eichner ER. Exertional sickling ...deaths in Army recruits with sickle cell trait. Mil Med. 2012 Jan;177(1):56-59. 6. Gardner JW, Kark JA. Fatal rhabdomyolysis presenting as mild heat

  11. [Postural trauma and rhabdomyolosis causing acute renal failure].

    PubMed

    Vecer, J; Kubátová, H; Soucek, M; Charvát, J; Kvapil, M; Matousovic, K; Martínek, V

    2000-02-01

    Rhabdomyolysis (damage of the muscles of various origin) leads to the efflux of the intracellular fluids in the circulation. The common complication of this status is the renal failure. The early diagnosis and the proper treatment makes the fall of renal function reversible. That is why the possibility of the rhabdomyolysis must be consider. The case report describes the development of renal failure in young, previously healthy men, followed by trauma mechanism after drug and alcohol abuse.

  12. 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.

  13. Acute forearm compressive myopathy syndrome secondary to upper limb entrapment: an unusual cause of renal failure.

    PubMed

    Tachtsi, Maria D; Kalogirou, Thomas E; Atmatzidis, Stefanos K; Papadimitriou, Dimitrios K; Atmatzidis, Konstantinos S

    2011-05-01

    Compressive myopathy syndrome (SCM) is a syndrome characterized by the lesion of skeletal muscle resulting in subsequent release of intracellular contents (myoglobin, creatine phosphokinase, potassium, etc.) into the circulatory system, which can cause potentially lethal complications. There are numerous causes that can lead to SCM resulting to acute rhabdomyolysis, and many patients present with multiple causes. The most common potentially lethal complication is acute renal failure. The occurrence of acute rhabdomyolysis should be considered as a possibility in any patient who can remain stationary for long periods, or is in a coma, or is intoxicated in any form. We report the rare case of a 26-year-old patient who developed SCM caused by ischemia reperfusion, with subsequent acute rhabdomyolysis and acute renal failure after prolonged compression of the right upper extremity.

  14. Presumed interaction of fusidic acid with simvastatin.

    PubMed

    Burtenshaw, A J; Sellors, G; Downing, R

    2008-06-01

    A 63-year-old man was admitted 6 weeks after an elective abdominal aortic aneurysm repair following which methicillin resistant Staphylococcus aureus (MRSA) had been cultured from the aneurysmal sac. He had been commenced on a course of fusidic acid at discharge in addition to his ongoing statin prescription and presented 4 weeks later with symptoms consistent with rhabdomyolysis. Severe rhabdomyolysis was confirmed and despite prolonged and complicated critical care management, his treatment was unsuccessful. Extensive investigations ruled out other known causes of this clinical presentation and failed to identify any other precipitating cause of rhabdomyolysis. We believe the most likely cause was hepatic inhibition of the CYP3A4 hepatic isoenzyme by fusidic acid resulting in an acute severe rise in plasma simvastatin level and extensive myocellular damage. Increasing MRSA colonisation and infection rates together with increased statin usage have the potential to increase the incidence of this presumed drug interaction.

  15. 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

  16. Partial muscle carnitine palmitoyltransferase-A deficiency

    SciTech Connect

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

    1987-01-02

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

  17. Elevated levels of serum creatine kinase induced by hyponatraemia.

    PubMed

    Goldenberg, I; Jonas, M; Thaler, M; Grossman, E

    1997-08-01

    Elevated serum creatine kinase levels are one of the major criteria for the diagnosis of myocardial injury. Noncardiac causes such as muscular and brain damage may also be associated with elevated serum creatine kinase levels. Hyponatremia may induce increased serum creatine kinase in association with rhabdomyolysis or with hypothyroidism. A patient is described where three episodes of hyponatraemia not associated with rhabdomyolysis or hypothyroidism induced transient elevations of serum creatine kinase levels. The association between hyponatraemia and elevated creatine kinase levels should be emphasized to prevent erroneous diagnosis of myocardial injury.

  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. Red mold dioscorea: a potentially safe traditional function food for the treatment of hyperlipidemia.

    PubMed

    Chen, Chien-Li; Pan, Tzu-Ming

    2012-09-15

    A study was undertaken to evaluate whether the interaction between Monascus-fermented products and lovastatin contributes to increased risk of rhabdomyolysis. Rhabdomyolysis is a potentially dangerous side effect of statin drugs. In this study with hyperlipidemic hamsters fed lovastatin only, lovastatin with 1-fold red mold dioscorea (RMD), and lovastatin, the functional components of red mold fermented products, HMG-CoA reductase inhibitors, did not exacerbate pre-existing diseases, and actually helped in improving existing disease conditions, respectively, as compared with the control. Administration of RMD, alone or in combination with lovastatin did not cause significant rhabdomyolysis as assessed by measuring the levels of creatinine phosphokinase. Further, we did not find any study that clearly implicates the involvement of RMD, which have long been considered a food product, in liver and kidney toxicity. RMD alone or in combination with lovastatin, does not increase the risk of rhabdomyolysis, even when administered at a high dosage (including HMG-CoA reductase inhibitors >75 mg/day/adult).

  20. Military Enlistment of Hispanic Youth: Obstacles and Opportunities

    DTIC Science & Technology

    2008-01-01

    pneumothorax after surgical correction or pleural sclerosis. q. Sarcoidosis (135). (See para 2–34.) 160 Military Enlistment of Hispanic Youth...Disease (099.3). h. Rheumatoid arthritis (714). i. Rhabdomyolysis (728.9). j. Sarcoidosis (135), unless there is substantiated evidence of a complete

  1. Pregabalin and Simvastatin

    PubMed Central

    Kaufman, Michele B.; Choy, Mary

    2012-01-01

    Purpose: We sought to determine whether a case of rhabdomyolysis was a probable adverse reaction associated with pregabalin (Lyrica) and simvastatin (Zocor). Pregabalin is not recognized as a cause of rhabdomyolysis, but statins are known to cause it. Patient Summary: A 70-year-old man with a history of fibromyalgia, type-2 diabetes, hypercholesterolemia, and chronic back pain presented to the emergency department with altered mental status, limb weakness, twitching, and slurred speech. He was taking multiple pain and neuropathic medications and had recently started taking lisinopril (e.g., Zestril) and simvastatin. His pregabalin dose was also increased from 50 mg to 100 mg three times daily. On admission, serum creatinine (SCr) and creatine phosphokinase (CPK) levels were 1.5 mg/dL (normal, 0.7–1.5 mg/dL) and 1,391 units/L (normal, 30–170 units/L), respectively. Metformin (Glucophage) was discontinued, and insulin was started. He was alert and oriented. The review of symptoms was normal except for leg weakness. He had no seizure activity. Simvastatin was discontinued, and the patient was aggressively hydrated. The following day, the SCr level was 1.6 mg/dL and the CPK level was 14,191 units/L. Pregabalin was then discontinued. The rhabdomyolysis resulted from simvastatin and perhaps also pregabalin. The Naranjo Causality Algorithm indicates a probable relationship between rhabdomyolysis and combined therapy. Three days later, the patient had significantly improved, and CPK began to decline. His discharge plan included all prior medications except simvastatin and pregabalin. Conclusion: It is not well known that pregabalin can cause rhabdomyolysis, and there is only one published report on pregabalin-induced hepatotoxicity. When different therapies are combined, the risk of rhabdomyolysis may be increased. The cause of rhabdomyolysis in our patient might be related to decreased renal elimination of both pregabalin and simvastatin (e.g., renal tubular

  2. 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

  3. Acute kidney injury after massive attack of Africanised bees

    PubMed Central

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

    2014-01-01

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

  4. 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.

  5. A patient fatality following the ingestion of a small amount of chlorfenapyr

    PubMed Central

    Kang, Changwoo; Kim, Dong Hoon; Kim, Seong Chun; Kim, Dong Seob

    2014-01-01

    Chlorfenapyr has been used worldwide for agricultural pest control since 1995. Despite its widespread use, acute human poisoning data are insufficient; only a small number of fatalities from chlorfenapyr poisoning have been reported. The signs and symptoms of chlorfenapyr toxicity include nausea, vomiting, fever, rhabdomyolysis, among others. In addition, central nervous system effects in association with delayed toxicity have also been observed. Here, we detail a fatality resulting from delayed chlorfenapyr toxicity following the ingestion of a small amount of pesticide. PMID:25114438

  6. A patient fatality following the ingestion of a small amount of chlorfenapyr.

    PubMed

    Kang, Changwoo; Kim, Dong Hoon; Kim, Seong Chun; Kim, Dong Seob

    2014-07-01

    Chlorfenapyr has been used worldwide for agricultural pest control since 1995. Despite its widespread use, acute human poisoning data are insufficient; only a small number of fatalities from chlorfenapyr poisoning have been reported. The signs and symptoms of chlorfenapyr toxicity include nausea, vomiting, fever, rhabdomyolysis, among others. In addition, central nervous system effects in association with delayed toxicity have also been observed. Here, we detail a fatality resulting from delayed chlorfenapyr toxicity following the ingestion of a small amount of pesticide.

  7. Medical Surveillance Monthly Report (MSMR). Volume 17, Number 03, March 2010

    DTIC Science & Technology

    2010-03-01

    less driving experience and are more likely to take risks while driving (such as to drive without seatbelts or while under the infl uence of alcohol).3...military activities in heat.1-3 Although numerous and eff ective countermeasures are available, physical exertion in hot environments still...military members, rhabdomyolysis is a signifi cant threat during physical exertion, particularly under heat stress. Each year, the MSMR summarizes

  8. 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.

  9. Medical Services: Standards of Medical Fitness

    DTIC Science & Technology

    2002-03-28

    pneumothorax after surgical correction or pleural sclerosis. q. Sarcoidosis (135). (See para 2–34.) 11AR 40–501 • 28 March 2002 r . S i l i c o n e b...h. Rheumatoid arthritis (714). i. Rhabdomyolysis (728.9). j. Sarcoidosis (135), unless there is substantiated evidence of a complete spontaneous...moderate reduction in pulmonary function. o. Pulmonary sarcoidosis . If not responding to therapy and complicated by demonstrable moderate reduction in

  10. Medical Surveillance Monthly Report. Volume 21, Number 3

    DTIC Science & Technology

    2014-03-01

    Makaryus JN, Catanzaro JN, Katona KC. Exertional rhabdomyolysis and renal failure in patients with sickle cell trait: is it time to change our...approach? Hematology. 2007;12(4):349–352. 5. Ferster K, Eichner ER. Exertional sickling deaths in Army recruits with sickle cell trait. Mil Med. 2012...among individuals with sickle cell trait (SCT).4-6 MSMR Vol. 21 No. 3 March 2014 Page 18 Update: Exertional Hyponatremia, Active Component

  11. Acute Onset Significant Muscle Weakness in a Patient Awaiting Liver Transplantation: Look for Statins.

    PubMed

    Choudhary, Narendra S; Saigal, Sanjiv; Saraf, Neeraj; Soin, Arvinder S

    2017-03-01

    Statins are commonly used drugs in patients with liver and cardiac disease. Statin-induced severe myopathy is a very uncommon presentation and rhabdomyolysis may occur in extreme cases which leads to renal failure. Patients with comorbidities like diabetes, hypothyroidism, and liver disease have higher chances of development of statin-induced myopathy. We describe a case of Child's C cirrhosis wherein the patient had acute onset significant muscle weakness and improved on statin discontinuation.

  12. Lymphangitis From Scolopendra heros Envenomation: The Texas Redheaded Centipede.

    PubMed

    Essler, Shannon E; Julakanti, Maneesha; Juergens, Andrew L

    2017-03-01

    Envenomation by Scolopendra heros, the Texas redheaded centipede, can present variably. Although transient pain and erythema are often treated conservatively, complications may include cellulitis, necrosis, myocardial infarction, and rhabdomyolysis. We present a case of an elderly man who came to the emergency department with lymphangitis and dermatitis secondary to a centipede sting that awoke him from sleep. It is important to recognize the potential of centipede envenomation to have severe local and systemic manifestations.

  13. 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.

  14. Effects of blood purification therapy on a patient with ifosfamide-induced neurotoxicity and acute kidney injury.

    PubMed

    Nishimura, Hiroaki; Enokida, Hideki; Nagano, Satoshi; Yokouchi, Masahiro; Hayami, Hiroshi; Komiya, Setsuro; Nakagawa, Masayuki

    2014-03-01

    Ifosfamide combined with other antineoplastic agents has been effective in the treatment of osteosarcoma, although adverse effects are reported in the increasing use of ifosfamide. The most serious complications among the ifosfamide intoxications are neurotoxicity and nephrotoxicity. We report on a patient who suffered from ifosfamide-induced neurotoxicity and nephrotoxicity and rhabdomyolysis after chemotherapy, and was successfully treated with blood purification therapy. The patient had osteosarcoma with multiple lung metastases, wherein the chemotherapy included ifosfamide (3 g/m(2)) and VP-16 (60 mg/m(2)) per day for 3 days. The first day after chemotherapy, the patient experienced impaired consciousness and renal function. Based on the clinical course and laboratory data, the diagnosis was ifosfamide-induced neurotoxicity and the acute kidney injury caused by ifosfamide-induced nephrotoxicity and rhabdomyolysis. As a detoxification treatment, blood purification procedures were performed daily for 3 days. Thirty-six hours after the first hemodialysis session, the symptoms of neurotoxicity disappeared. In the lead-up to the 10th day following intoxication, the serum creatinine recovered to the baseline level. Serum ifosfamide concentration decreased from 41.9 to 12.1 ng/ml by the second session of blood purification. Despite the absence of an established detoxification method when complications present simultaneously, blood purification therapy should be considered for treating severe concurrent neurotoxicity and nephrotoxicity and rhabdomyolysis.

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

    PubMed

    Redshaw, Charlotte; Stewart, Catherine

    2014-11-01

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

  16. [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.

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

    PubMed

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

    2013-12-01

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

  18. 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

  19. [Withdrawal of cerivastatin revealed a flaw of post-marketing surveillance system in the United States].

    PubMed

    Saito, Mitsuo; Hirata-Koizumi, Mutsuko; Miyake, Shinji; Hasegawa, Ryuichi

    2005-01-01

    Cerivastatin, a lipid-lowering agent, was voluntarily withdrawn from the market because of high risk of rhabdomyolysis when used as monotherapy and as comedication with fibrates, especially gemfibrozil. Thereafter, investigators found a five-fold increase in the area under the curve (AUC) when cerivastatin was used as comedication with gemfibrozil and theorized that the increase was associated with inhibition of the hepatic uptake and metabolism. By contrast, a number of pharmacoepidemiological investigations--one of which involved evaluation of the Food and Drug Administration (FDA) database for suspected adverse drug reactions and 11 cohort studies of statin and fibrate users in United States showed the risk of rhabdomyolysis to be greater in cerivastatin than in other statins used in either monotherapy or in comedication with fibrates, especially gemfibrozil. This incident regarding risk of rhabdomyolysis in cerivastatin monotherapy was taken to court in the United States and unpublished company (manufacturer of cerivastatin) documents were opened. The incident was then analyzed and discussed in the Journal of American Medical Association (JAMA) as a concern of the current US post-marketing surveillance system. The company's action and timing were judged and found to be inappropriate (although companies of this sort generally have insurmountable conflicts of interest), and the work of the US regulatory system and funding for post-marketing safety management were found to be insufficient. On the basis of the current situation, the authors and editors recommend further improvement of post-marketing regulations including the establishment of an independent drug safety board to oversee post-marketing surveillance. Among the opened, unpublished data, was the finding that cerivastatin obviously induced myopathy in a dose-dependent manner when administrated as monotherapy. As for other statins, only limited data was available for the relationship between the dosage and

  20. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors.

    PubMed

    Williams, David; Feely, John

    2002-01-01

    The HMG-CoA reductase inhibitors (statins) are effective in both the primary and secondary prevention of ischaemic heart disease. As a group, these drugs are well tolerated apart from two uncommon but potentially serious adverse effects: elevation of liver enzymes and skeletal muscle abnormalities, which range from benign myalgias to life-threatening rhabdomyolysis. Adverse effects with statins are frequently associated with drug interactions because of their long-term use in older patients who are likely to be exposed to polypharmacy. The recent withdrawal of cerivastatin as a result of deaths from rhabdomyolysis illustrates the clinical importance of such interactions. Drug interactions involving the statins may have either a pharmacodynamic or pharmacokinetic basis, or both. As these drugs are highly extracted by the liver, displacement interactions are of limited importance. The cytochrome P450 (CYP) enzyme system plays an important part in the metabolism of the statins, leading to clinically relevant interactions with other agents, particularly cyclosporin, erythromycin, itraconazole, ketoconazole and HIV protease inhibitors, that are also metabolised by this enzyme system. An additional complicating feature is that individual statins are metabolised to differing degrees, in some cases producing active metabolites. The CYP3A family metabolises lovastatin, simvastatin, atorvastatin and cerivastatin, whereas CYP2C9 metabolises fluvastatin. Cerivastatin is also metabolised by CYP2C8. Pravastatin is not significantly metabolised by the CYP system. In addition, the statins are substrates for P-glycoprotein, a drug transporter present in the small intestine that may influence their oral bioavailability. In clinical practice, the risk of a serious interaction causing myopathy is enhanced when statin metabolism is markedly inhibited. Thus, rhabdomyolysis has occurred following the coadministration of cyclosporin, a potent CYP3A4 and P-glycoprotein inhibitor, and

  1. Exercise-Associated Hyponatremia: 2017 Update

    PubMed Central

    Hew-Butler, Tamara; Loi, Valentina; Pani, Antonello; Rosner, Mitchell H.

    2017-01-01

    Exercise-associated hyponatremia (EAH) was initially described in the 1980s in endurance athletes, and work done since then has conclusively identified that overdrinking beyond thirst and non-osmotic arginine vasopressin release are the most common etiologic factors. In recent years, EAH has been described in a broader variety of athletic events and also has been linked to the development of rhabdomyolysis. The potential role of volume and sodium depletion in a subset of athletes has also been described. This review focuses on the most recent literature in the field of EAH and summarizes key new findings in the epidemiology, pathophysiology, treatment, and prevention of this condition. PMID:28316971

  2. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    PubMed

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

  3. Medical Surveillance Monthly Report (MSMR). Volume 4, Number 4, May/June 1998

    DTIC Science & Technology

    1998-06-01

    tion, rhabdomyolysis, carbon monoxide intoxica- tion, chemical agent exposure, Guillain - Barre syn- drome) were reported through the MSS. Com...intoxication 0 3 0.0 Chemical agent exposure 0 2 0.0 Coccidioidomycosis 0 3 0.0 Encephalitis 0 1 0.0 Guillain - Barre Syndrome 0 5 0.0 Hepatitis C, Acute 0 2 0.0...in previous MSMRs.1,2 In brief, for defined periods, records of hospitalizations of ac- tive duty soldiers were searched to identify those with

  4. PubMed Central

    Dallaire, M; Chamberland, M

    1994-01-01

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

  5. [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.

  6. Medical Surveillance Monthly Report (MSMR). Volume 3, Number 3, April 1997

    DTIC Science & Technology

    1997-04-01

    Leishmaniasis 27 22 81.5% Malaria 18 12 66.7% Heat exhaustion 16 5 31.3% Varicella 151 44 29.1% Rhabdomyolysis 98 26 26.5% Lyme disease 5 1 20.0...diseases during calendar years 1995 and 1996. Arthropod-borne: Between 1995 and 1996, reports of Lyme disease (1995: 4, 1996: 11) and malaria (1995: 22...1996: 27) increased among soldiers. Among other beneficiaries, Lyme disease reports decreased (1995: 14, 1996: 9), and ma- laria reports were

  7. Hypothyroid acute renal failure.

    PubMed

    Birewar, Sonali; Oppenheimer, Mark; Zawada, Edward T

    2004-03-01

    Muscular disorders and even hypothyroid myopathy with elevated muscle enzymes are commonly seen in hypothyroidism. In this paper, we report a case of acute renal failure in a 35-year old male patient with myalgia. His serum creatinine reached a level of 2.4 mg/dl. Later, his myalgia was found to be due to hypothyroidism with TSH of over 500 uiv/ml. With thyroid replacement therapy, myalgia and his serum creatinine stabilized and subsequently improved. Hypothyroidism, although rare, has been reported as a definite and authentic cause of rhabdomyolysis. As a result, hypothyroidism must be considered in patients presenting with acute renal failure and elevated muscle enzymes.

  8. 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

  9. Spotted black snake (Pseudechis guttatus) envenomation in a maned wolf (Chrysocyon brachyurus).

    PubMed

    Portas, Timothy J; Montali, Richard J

    2007-09-01

    Envenomation by a spotted black snake (Pseudechis guttatus), following multiple bites on the buccal mucosa of a captive maned wolf (Chrysocyon brachyurus), caused the animal's collapse, hemolysis, rhabdomyolysis, local tissue necrosis, hepatic and renal failure, and subsequent death. The wolf died despite intensive supportive care including antivenom administration, fluid support, and a blood transfusion. Gross necropsy findings included myocardial and intestinal hemorrhage, pulmonary congestion, hepatomegaly, and splenomegaly. Microscopic examination of formalin-fixed tissues demonstrated pulmonary and abdominal visceral hemorrhage, acute nephrosis with casts, multifocal hepatic necrosis, and splenic congestion.

  10. Joint Influence of Protein Supplements, Soft Drinks and Extreme Physical Activity on the Development of Acute Renal Failure and Hypokalaemia.

    PubMed

    Djordjevic, S; Kitic, D; Kostic, M; Apostolovic, B; Brankovic, S; Ciric, I M; Velickovic-Radovanovic, R

    2015-11-13

    We present a case of a 33-year old man who complained of weakness, fever and decreased urinating. A personal history revealed a consumption of creatine, protein supplements, soft drinks containing caffeine and stevia, and extreme physical activity which included lifting of heavy weights. The patient developed anuria, uraemia, fatigue, rhabdomyolysis and paradoxical hypokalaemia. After the patient had seven successive dialysis treatments, normal kidney function was restored. The report presents the first case of acute renal failure followed by hypokalaemia due to the combined action of the excessive consumption of supplements, soft drinks with stevia and caffeine, and extreme physical activity.

  11. Cocaine-induced mesenteric ischaemia.

    PubMed

    Osorio, J; Farreras, N; Ortiz De Zárate L; Bachs, E

    2000-01-01

    We report a 33-year-old man with distal ileum infarction after intravenous abuse of cocaine. He underwent resection of a gangrenous bowel segment and survived. We review the literature regarding intestinal ischaemia related to cocaine. To date, 19 cases have been published. Like most previously reported cases, our patient was young and had no previous history of arteriosclerosis. He suffered cocaine-induced rhabdomyolysis and acute renal failure. Mesenteric ischaemia should be considered in the differential diagnosis of acute or chronic abdominal pain in cocaine consumers.

  12. Wound wise: wounds in surgical patients who are obese.

    PubMed

    Baugh, Nancy; Zuelzer, Helen; Meador, Jill; Blankenship, Jolie

    2007-06-01

    The number of surgical patients who are obese in the United States is rising, a trend that's likely to continue. Such patients are at higher risk than nonobese patients are for surgical site infections and other complications such as dehiscence, pressure ulcers, deep tissue injury, and rhabdomyolysis. This article details the factors that can contribute to such complications, including a high number of comorbidities, and offers practical suggestions for preventing them. Nurses should understand that special equipment, precautions, and protocols may be needed at every stage of care, and that obese patients aren't anomalies but rather a part of a growing population with particular needs.

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

    PubMed

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

    2013-01-01

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

  14. Mitochondrial function is altered in horse atypical myopathy.

    PubMed

    Lemieux, Hélène; Boemer, François; van Galen, Gaby; Serteyn, Didier; Amory, Hélène; Baise, Etienne; Cassart, Dominique; van Loon, Gunther; Marcillaud-Pitel, Christel; Votion, Dominique-M

    2016-09-01

    Equine atypical myopathy in Europe is a fatal rhabdomyolysis syndrome that results from the ingestion of hypoglycin A contained in seeds and seedlings of Acer pseudoplatanus (sycamore maple). Acylcarnitine concentrations in serum and muscle OXPHOS capacity were determined in 15 atypical myopathy cases. All but one acylcarnitine were out of reference range and mitochondrial respiratory capacity was severely decreased up to 49% as compared to 10 healthy controls. The hallmark of atypical myopathy thus consists of a severe alteration in the energy metabolism including a severe impairment in muscle mitochondrial respiration that could contribute to its high death rate.

  15. Multiple mononeuropathy following cocaine abuse

    PubMed Central

    Beniczky, Sándor; Tfelt-Hansen, Peer; Fabricius, Martin; Andersen, Kjeld V

    2009-01-01

    A 31-year-old man with acute-onset of left-sided weakness following the sniffing of cocaine was admitted with rhabdomyolysis. Neurophysiological studies showed axonal degeneration in 4/10 sensory and 3/8 motor nerves, and conduction block outside the typical compression-sites in 3/8 motor nerves. The findings are consistent with a diagnosis of multiple mononeuropathy. Ischaemia due to vasoconstriction is currently believed to be the cause of muscle necrosis following cocaine abuse and we hypothesise that it also explains the neuropathy in this case. PMID:21686808

  16. Bath Salts: A Newly Recognized Cause of Acute Kidney Injury

    PubMed Central

    McNeely, Jonathan; Parikh, Samir; Valentine, Christopher; Haddad, Nabil; Shidham, Ganesh; Rovin, Brad; Hebert, Lee; Agarwal, Anil

    2012-01-01

    Bath salts are substance of abuse that are becoming more common and are difficult to recognize due to negative toxicology screening. Acute kidney injury due to bath salt use has not previously been described. We present the case of a previously healthy male who developed acute kidney injury and dialysis dependence after bath salt ingestion and insufflation. This was self-reported with negative toxicology screening. Clinical course was marked by severe hyperthermia, hyperkalemia, rhabdomyolysis, disseminated intravascular coagulation, oliguria, and sepsis. We discuss signs and symptoms, differential diagnoses, potential mechanisms of injury, management, and review of the literature related to bath salt toxicity. PMID:24555135

  17. Acute ischaemia of the leg following accidental intra-arterial injection of dissolved flunitrazepam tablets.

    PubMed

    Leifert, J A; Bossaller, L; Uhl, M

    2008-11-01

    Accidental intra-arterial injection of drugs is a sporadic complication in i.v. drug addicts. A 22-year-old drug-abuser injected flunitrazepam tablets dissolved in tap water into her left femoral artery and presented with clinical signs of acute ischaemia of the left leg. Severe rhabdomyolysis developed within 5 hours after the injection. Selective arterial catheter angiography showed an acute occlusion of the posterior tibial artery. Combination therapy with i.a. urokinase, i.a. prostaglandines and i.v. anticoagulation resulted in re-opening of the obstructed distal artery and complete cessation of symptoms.

  18. 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

  19. 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

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

    PubMed

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

    2014-12-14

    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.

  1. Classic heat stroke in a case of simple hypohydrosis with "bad prognostic indicators" but a remarkable recovery.

    PubMed

    Sinha, A K; Ghacha, R; Youmbissi, J T; Khursany, I A

    2001-09-01

    Heat stroke occurs in the desert area of Saudi Arabia quite frequently and manifest in different patterns including coagulopathy. Frequently encountered complications include renal or hepatic failure, rhabdomyolysis, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and seizure. Not all of these complications usually occur in the same patient, in case it occurs the mortality reported is significantly high. We describe a case of heat stroke that had nearly all the known complications of heat stroke but recovered from all, except minor neurological deficit in the form of dysarthria and exaggerated deep reflexes.

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

    PubMed

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

    2012-01-01

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

  3. Acute renal failure: A rare presentation of Sheehan's syndrome.

    PubMed

    Bhat, Manzoor A; Laway, Bashir A; Allaqaband, Faheem A; Kotwal, Suman K; Wani, Imtiyaz A; Banday, Khursheed A

    2012-03-01

    Sheehan's syndrome occurs as a result of ischemic pituitary necrosis secondary to severe postpartum bleeding. It is one of the most common causes of hypopituitarism, characterized by variable clinical presentation. Acute kidney injury occurs rarely in Sheehan's syndrome and most of the cases have been found to be precipitated by rhabdomyolysis. We here present a case of Sheehan's syndrome with acute kidney injury where theprecipitating cause was chronic hypocortisolemia. We believe this is the first reported case of Sheehan's syndrome in which acute kidney injury was precipitated by adrenal insufficiency.

  4. 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.

  5. 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.

  6. Challenging Return to Play Decisions

    PubMed Central

    Asplund, Chad A.; O’Connor, Francis G.

    2015-01-01

    Context: Sports medicine providers frequently return athletes to play after sports-related injuries and conditions. Many of these conditions have guidelines or medical evidence to guide the decision-making process. Occasionally, however, sports medicine providers are challenged with complex medical conditions for which there is little evidence-based guidance and physicians are instructed to individualize treatment; included in this group of conditions are exertional heat stroke (EHS), exertional rhabdomyolysis (ER), and exertional collapse associated with sickle cell trait (ECAST). Evidence Acquisition: The MEDLINE (2000-2015) database was searched using the following search terms: exertional heat stroke, exertional rhabdomyolysis, and exertional collapse associated with sickle cell trait. References from consensus statements, review articles, and book chapters were also utilized. Study Design: Clinical review. Level of Evidence: Level 4. Results: These entities are unique in that they may cause organ system damage capable of leading to short- or long-term detriments to physical activity and may not lend to complete recovery, potentially putting the athlete at risk with premature return to play. Conclusion: With a better understanding of the pathophysiology of EHS, ER, and ECAST and the factors associated with recovery, better decisions regarding return to play may be made. PMID:26896216

  7. Increased toxicity when fibrates and statins are administered in combination--a metabolomics approach with rats.

    PubMed

    Strauss, V; Mellert, W; Wiemer, J; Leibold, E; Kamp, H; Walk, T; Looser, R; Prokoudine, A; Fabian, E; Krennrich, G; Herold, M; van Ravenzwaay, B

    2012-06-01

    Combination therapies with fibrates and statins are used to treat cardiovascular diseases, because of their synergistic effect on lowering plasma lipids. However, fatal side-effects like rhabdomyolysis followed by acute renal necrosis sometimes occur. To elucidate biochemical changes resulting from the interaction of fibrates and statins, doses of 100 mg/kg fenofibrate, 50mg/kg clofibrate, 70 mg/kg atorvastatin and 200 mg/kg pravastatin as well as combinations thereof were administered to Crl:Wi(Han) rats for 4 weeks. Plasma metabolome profile was measured on study days 7, 14 and 28. Upon study termination, clinical pathology parameters were measured. In a separate experiment plasmakinetic data were measured in male rats after 1 week of drug administration in monotherapy as well as in combinations. Lowering of blood lipid levels as well as toxicological effects, like liver cell degradation (statins) and anemia (fibrates) and distinct blood metabolite level alterations were observed in monotherapy. When fibrates and statins were co-administered metabolite profile interactions were generally underadditive or at the utmost additive according to the linear mixed effect model. However, more metabolite levels were significantly altered during combination therapy. New effects on the antioxidant status and the cardiovascular system were found which may be related to a development of rhabdomyolysis. Accumulation of drugs during the combination therapy was not observed.

  8. Narrative review: statin-related myopathy.

    PubMed

    Joy, Tisha R; Hegele, Robert A

    2009-06-16

    Statin-related myopathy is a clinically important cause of statin intolerance and discontinuation. The spectrum of statin-related myopathy ranges from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. Observational studies suggest that myalgia can occur in up to 10% of persons prescribed statins, whereas rhabdomyolysis continues to be rare. The mechanisms of statin-related myopathy are unclear. Options for managing statin myopathy include statin switching, particularly to fluvastatin or low-dose rosuvastatin; nondaily dosing regimens; nonstatin alternatives, such as ezetimibe and bile acid-binding resins; and coenzyme Q10 supplementation. Few of these strategies have high-quality evidence supporting them. Because statin-related myopathy will probably become more common with greater numbers of persons starting high-dose statin therapy and the increasing stringency of low-density lipoprotein cholesterol level targets, research to better identify patients at risk for statin myopathy and to evaluate management strategies for statin-related myopathy is warranted.

  9. Ecstasy (MDMA) and its effects on kidneys and their treatment: a review

    PubMed Central

    Bora, Feyza; Yılmaz, Fatih; Bora, Taner

    2016-01-01

    Ecstasy (MDMA; 3,4-methylenedioxymethylamphetamine) is an illicit drug that has been increasingly abused by young people. Its effects include euphoria, enhanced sociability and heightened mental awareness. These come about via the increase of serotonin in both the central nervous system and the sympathetic nervous system. Despite the drug’s prevalent abuse, serious or adverse effects are rare. Due to personal pharmacokinetics, effects from the same dosage vary according to the individual. Fatal instances may include acute hyponatremia, hyperthermia (>42 °C), disseminated intravascular coagulation (DIC) resulting from hyperthermia affecting the kidneys, and non-traumatic rhabdomyolysis. However, it is seldom the case that hyponatremia and hyperthermia co-exist. Hyponatremia is thought to be caused by HMMA – a metabolite of MDMA. Hyponatremia is caused by the inappropriate secretion of arginine vasopressin (AVP) and the excessive intake of hypotonic liquid accompanied by increased hyperthermia. Symptomatic, even deadly hyponatremia is seen more frequently in females, with the effects of oestrogen on arginine vasopressin believed to be the cause. Onset in such cases is acute, and treatment should be given to symptomatic patients as quickly as possible, with 3% saline administered when necessary. Reasons for acute kidney injury may include rhabdomyolysis, malign hypertension, and necrotizing vasculitis. PMID:27917269

  10. 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

  11. 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

  12. Polysaccharide storage myopathy in the M. longissimus lumborum of showjumpers and dressage horses with back pain.

    PubMed

    Quiroz-Rothe, E; Novales, M; Aguilera-Tejero, E; Rivero, J L L

    2002-03-01

    This study was designed to investigate whether horses with clinical signs of back pain due to suspected soft tissue injuries were affected by polysaccharide storage myopathy (PSSM). Diagnosis of PSSM in muscle biopsies obtained from the M. longissimus lumborum of 5 showjumpers and 4 dressage horses with a history of back pain is reported. M. longissimus lumborum biopsies of these horses were characterised histopathologically and in 3/9 cases also by electron microscopy. Observations were compared with M. gluteus biopsies of the same horses, and with M. gluteus biopsies obtained from 6 Standardbreds with recurrent exertional rhabdomyolysis and from 6 healthy trotters. M. longissimus biopsies from horses with back pain showed pathognomonic signs of PSSM, i.e. high glycogen and/or abnormal complex amylase-resistant polysaccharide deposits. Similar features were found in M. gluteus biopsies of the same horses. Sections of horses with rhabdomyolysis had increased PAS stain when compared with healthy horses, but did not show amylase-resistant material. Qualitative observations were corroborated by quantitative histochemistry (optical densities) of sections stained with PAS and amylase PAS. This study demonstrated the presence of PSSM in the M. longissimus of showjumpers and dressage horses with back pain and indicates that epaxial muscle biopsy is an option in diagnosing back problems in horses when clinical examination and imaging techniques do not provide a precise diagnosis.

  13. [Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

    PubMed

    Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

    2011-01-01

    Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

  14. 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.

  15. Biological Membrane-Packed Mesenchymal Stem Cells Treat Acute Kidney Disease by Ameliorating Mitochondrial-Related Apoptosis

    PubMed Central

    Geng, Xiaodong; Hong, Quan; Wang, Weiwei; Zheng, Wei; Li, Ou; Cai, Guangyan; Chen, Xiangmei; Wu, Di

    2017-01-01

    The mortality of rhabdomyolysis-induced AKI remains high because no effective therapy exists. We investigated a new therapeutic method using MSCs. The aim of this study was to investigate the therapeutic potential and anti-apoptotic mechanisms of action of MSCs in the treatment of AKI induced by glycerol in vivo and in vitro. We used Duragen as a biological membrane to pack MSCs on the glycerol-injured renal tissue in vivo. The anti-apoptotic mechanism was investigated. In vitro, HK-2 cells were incubated with ferrous myoglobin and MSCs-conditioned medium, followed by cell proliferation and apoptosis assays. We founded that packing MSCs on the injured renal tissue preserved renal function, ameliorated renal tubular lesions, and reduced apoptosis in the mice with glycerol-induced AKI. The MSC-conditioned medium improved HK-2 cell viability and inhibited apoptosis. These effects were reversed by the PI3K inhibitor LY294002. Biological membrane packing of MSCs on the renal tissue has a therapeutic rescue function by inhibiting cell apoptosis in vivo. MSCs protect renal cells from apoptosis induced by myoglobin in vitro. We have thus demonstrated MSCs reduced rhabdomyolysis-associated renal injury and cell apoptosis by activating the PI3K/Akt pathway and inhibiting apoptosis. PMID:28117405

  16. 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

  17. 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.

  18. Appropriate risk criteria for OATP inhibition at the drug discovery stage based on the clinical relevancy between OATP inhibitors and drug-induced adverse effect.

    PubMed

    Nakakariya, Masanori; Goto, Akihiko; Amano, Nobuyuki

    2016-10-01

    DDI could be caused by the inhibition of OATP-mediated hepatic uptakes. The aim of this study is to set the risk criteria for the compounds that would cause DDI via OATP inhibition at the drug discovery stage. The IC50 values of OATP inhibitors for human OATP-mediated atorvastatin uptake were evaluated in the expression system. In order to set the risk criteria for OATP inhibition, the relationship was clarified between OATP inhibitory effect and severe adverse effects of OATP substrates, rhabdomyolysis, hyperbilirubinemia and jaundice. Rhabdomyolysis would be caused in the atorvastatin AUC more than 9-fold of that at a minimum therapeutic dose. The atorvastatin AUC was 6- to 9-fold increased with the OATP inhibitors of which IC50 values were ≤1 μmol/L. Hyperbilirubinemia and jaundice would be caused with the OATP inhibitors of which IC50 values were ≤6 μmol/L. This investigation showed that the compounds with IC50 of ≤1 μmol/L would have high risk for OATP-mediated DDI that would cause severe side effects. Before the detailed analysis based on the dosage, unbound fraction in blood and effective concentration to evaluate the clinical DDI potency, this criteria enable high throughput screening and optimize lead compounds at the drug discovery stage.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  1. 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

  2. Skeletal muscle metabolic response to exercise in horses with 'tying-up' due to polysaccharide storage myopathy.

    PubMed

    Valberg, S J; Macleay, J M; Billstrom, J A; Hower-Moritz, M A; Mickelson, J R

    1999-01-01

    Polysaccharide storage myopathy (PSSM) is a distinct cause of exertional rhabdomyolysis in Quarter Horses that results in glycogen and abnormal polysaccharide accumulation. The purpose of this study was to determine if excessive glycogen storage in PSSM is due to a glycolytic defect that impairs utilisation of this substrate during exercise. Muscle biopsies, blood lactates and serum CK were obtained 1) at rest from 5 PSSM Quarter Horses, 4 normal Quarter Horses (QH controls) and 6 Thoroughbreds with recurrent exertional rhabdomyolysis (TB RER) and 2) after a maximal treadmill exercise test in PSSM and QH controls. In addition, 3 PSSM horses performed a submaximal exercise test. At rest, muscle glycogen concentrations were 2.4x and 1.9x higher in PSSM vs. QH controls or TB RER, respectively. Muscle lactates at rest were similar between PSSM and QH controls but significantly higher in PSSM vs. TB RER. Muscle glucose-6-phosphate concentrations were also higher in PSSM horses than controls combined. During maximal exercise, mean muscle glycogen concentrations declined 2.7x more and mean lactate increased 2x more in PSSM vs. QH controls; however, differences were not statistically significant. Blood lactate concentrations after maximal exercise did not reflect generally higher muscle lactate in PSSM vs. QH controls. No change in blood lactate concentrations occurred in PSSM horses with submaximal exercise. Serum CK activity increased significantly 4 h after maximal and submaximal exercise and was significantly higher in PSSM vs. QH controls. These results show that during maximal exercise, PSSM horses utilised muscle glycogen and produce lactic acid via a functional glycolytic pathway and that during submaximal exercise oxidative metabolism was unimpaired. The excessive glycogen storage and formation of abnormal polysaccharide in PSSM horses therefore appear to reflect increased glycogen synthesis rather than decreased utilisation. The specific subset of horses with

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

    PubMed Central

    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

    2014-01-01

    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-1β) 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-1β inhibitors. Our data suggest that the pathogenic

  4. Pemphigus erythematosus relapse associated with atorvastatin intake

    PubMed Central

    Lo Schiavo, Ada; Puca, Rosa Valentina; Romano, Francesca; Cozzi, Roberto

    2014-01-01

    Statins, also known as 3-hydroxy-3-methylglutaril-CoA reductase inhibitors, are well-tolerated drugs used for prevention of atherosclerosis and cardiovascular events. Although they are generally considered safe, some serious adverse effects, such as myositis, myopathy, and rhabdomyolysis can rarely occur. Furthermore, recent data from long-term follow-up on patients who have been taking statins for a long period of time suggest that prolonged exposure to statins may trigger autoimmune reactions. The exact mechanism of statin-induced autoimmune reactions is unclear. Statins, as proapoptotic agents, release nuclear antigen into the circulation and may induce the production of pathogenic autoantibodies. Herein we report the case of a 70 year-old man who developed a relapse of pemphigus erythematosus, a syndrome with features of both lupus erythematosus and pemphigus, after atorvastatin intake. PMID:25258514

  5. Post-influenza aspergillosis, do not underestimate influenza B

    PubMed Central

    Nulens, Eric FL; Bourgeois, Marc JC; Reynders, Marijke BML

    2017-01-01

    Our objective is to highlight and focus on post-influenza aspergillosis, triggered by influenza B virus. This relatively new clinical entity is often associated with a fulminant course of respiratory decline and high mortality. A 51-year immunocompetent woman, without any medical history or risk factors for developing a complicated influenza infection, was admitted to the intensive care unit. During admission, she presented with an afebrile flu-like syndrome, myocarditis, rhabdomyolysis, multiple organ failure, and evolved to severe respiratory distress. The broncho-alveolar lavage contained influenza B RNA, and the culture revealed Aspergillus fumigatus. Despite maximal organ support, immunoglobulin, antiviral and antifungal therapy, the patient died. This case demonstrates that influenza B virus may be life threatening even to immunocompetent adults and may trigger an invasive Aspergillus superinfection. PMID:28260935

  6. Telithromycin: review of adverse effects.

    PubMed

    2014-11-01

    Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.

  7. Exertional heat stroke: the runner's nemesis.

    PubMed Central

    Hart, L. E.; Egier, B. P.; Shimizu, A. G.; Tandan, P. J.; Sutton, J. R.

    1980-01-01

    Heat stroke in distance runners is increasing in frequency. A case is reported of a 41-year-old man who collapsed during a 10-km "fun run" held when the temperature was 31.6 degrees C and the humidity 80%. Acute renal failure (serum creatinine level 1530 mumol/l [17.3 mg/dl]), rhabdomyolysis, disseminated intravascular coagulation and hepatic damage complicated the clinical picture. Repeated peritoneal dialysis and one cycle of hemodialysis because of a very high serum level of uric acid (1.23 mmol/l [20.7 mg/dl]) were required. Although the illness was prolonged, recovery was almost complete, and 4 months after the man's collapse the serum creatinine level had fallen to 133 mumol/l (1.5 mg/dl). PMID:7388706

  8. Haff disease complicated by multiple organ failure after crayfish consumption: a case study

    PubMed Central

    Feng, Gang; Luo, Qiancheng; Zhuang, Ping; Guo, Enwei; Yao, Yulan; Gao, Zhongyu

    2014-01-01

    Haff disease is a syndrome consisting of unexplained rhabdomyolysis. Patients suffering from Haff disease report having eaten fish within 24 hours before the onset of illness. Most patients survive and recover quickly. The present study is the first report of Haff disease complicated by multiple organ failure after crayfish consumption. A 66-year-old Chinese man ate cooked crayfish on the night of June 23, 2013. He arrived at our hospital 2 days later and was admitted to the intensive care unit. After admission, the patient was diagnosed with Haff disease complicated by multiple organ failure. Despite supportive and symptomatic treatments, the condition of the patient deteriorated, and he died due to his illness. Haff disease is a rare clinical syndrome that is sometimes misdiagnosed. Early diagnosis and proper treatment are essential to prevent progression to multiple organ failure. PMID:25607271

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

    PubMed Central

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

    2014-01-01

    The Malignant Hyperthermia Association of the United States (MHAUS) and the Department of Anesthesia at the University of Toronto sponsored a Scientific Conference on November 1–2, 2013 in Toronto, Canada. The multidisciplinary group of experts, including clinicians, geneticists and physiologists involved in research related to malignant hyperthermia (MH), shared new insights into the pathophysiology of type-1 ryanodine receptor gene (RYR1)-linked diseases, as well as the relationship between MH and “awake MH” conditions, such as exertional rhabdomyolysis (ER) and exertional heat illness (EHI). In addition, the molecular genetics of MH, and clinical issues related to the diagnosis and management of RYR1-linked disorders, were presented. The conference also honored Dr. David H. MacLennan for his contributions to our understanding of the genetics, pathogenesis and treatment of MH and other RYR1-related myopathies. This report represents a summary of the proceedings of this conference. PMID:25189431

  10. Statin-associated myopathy.

    PubMed

    Hamilton-Craig, I

    2001-11-05

    Myopathy occurs in 0.1%-0.2% of patients receiving statins in clinical trials. This adverse effect is shared by all statins, but is more common with cerivastatin, especially in combination with gemfibrozil. The risk of myopathy is increased by: the use of high doses of statins, concurrent use of fibrates, concurrent use of hepatic cytochrome P450 inhibitors, acute viral infections, major trauma, surgery, hypothyroidism and other conditions. Statin-associated myopathy should be suspected when a statin-treated patient complains of unexplained muscle pain, tenderness or weakness. Statin therapy should be stopped in cases of suspected myopathy, and serum creatine kinase levels should be checked and monitored. No specific therapies other than statin withdrawal and supportive measures for rhabdomyolysis are currently available.

  11. Neurological Complications of Bariatric Surgery.

    PubMed

    Goodman, Jerry Clay

    2015-12-01

    Obesity has attained pandemic proportions, and bariatric surgery is increasingly being employed resulting in turn to more neurological complications which must be recognized and managed. Neurological complications may result from mechanical or inflammatory mechanisms but primarily result from micro-nutritional deficiencies. Vitamin B12, thiamine, and copper constitute the most frequent deficiencies. Neurological complications may occur at reasonably predictable times after bariatric surgery and are associated with the type of surgery used. During the early post-operative period, compressive or stretch peripheral nerve injury, rhabdomyolysis, Wernicke's encephalopathy, and inflammatory polyradiculoneuropathy may occur. Late complications ensue after months to years and include combined system degeneration (vitamin B12 deficiency) and hypocupric myelopathy. Bariatric surgery patients require careful nutritional follow-up with routine monitoring of micronutrients at 6 weeks and 3, 6, and 12 months post-operatively and then annually after surgery and multivitamin supplementation for life. Sustained vigilance for common and rare neurological complications is essential.

  12. Propofol Infusion Syndrome in Adults: A Clinical Update

    PubMed Central

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

    2015-01-01

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

  13. 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.

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

    PubMed

    López Álvarez, A; Román Fernández, A; Vilanova Vázquez, V; Corujeira Rivera, M C; Areán González, I; Valiño Hortas, C

    2014-01-01

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

  15. Hypothermia and hypokalemia in a patient with diabetic ketoacidosis.

    PubMed

    Saito, Osamu; Saito, Takako; Sugase, Taro; Kusano, Eiji; Nagata, Daisuke

    2015-01-01

    We present the case of a 36-year-old man with type-1 diabetes who was hospitalized with diabetic ketoacidosis (DKA). On admission, he had hypothermia, hypokalemia and combined metabolic and respiratory alkalosis, in addition to hyperglycemia. Hypothermia, hypokalemia and metabolic alkalosis, with a concurrent respiratory alkalosis, are not commonly seen in DKA. After admission, intravenous infusion of 0.45% saline was administered, which resulted in the development of pure metabolic acidosis. After starting insulin infusion, hypokalemia and hypophosphatemia became evident and finally resulted in massive rhabdomyolysis. Hyperkalemia accompanying oliguric acute kidney injury (AKI) warranted initiation of hemodialysis (HD) on Day-five. On the 45th hospital day, his urine output started to increase and a total of 22 HD sessions were required. We believe that in this case severe dehydration, hypothermia and hypokalemia might have contributed to the initial symptoms of DKA as well as the prolongation of AKI.

  16. 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

  17. Evidence-based management of statin myopathy.

    PubMed

    Harper, Charles R; Jacobson, Terry A

    2010-09-01

    Statin-associated muscle symptoms are a relatively common condition that may affect 10% to 15% of statin users. Statin myopathy includes a wide spectrum of clinical conditions, ranging from mild myalgia to rhabdomyolysis. The etiology of myopathy is multifactorial. Recent studies suggest that statins may cause myopathy by depleting isoprenoids and interfering with intracellular calcium signaling. Certain patient and drug characteristics increase risk for statin myopathy, including higher statin doses, statin cytochrome metabolism, and polypharmacy. Genetic risk factors have been identified, including a single nucleotide polymorphism of SLCO1B1. Coenzyme Q10 and vitamin D have been used to prevent and treat statin myopathy; however, clinical trial evidence demonstrating their efficacy is limited. Statin-intolerant patients may be successfully treated with either low-dose statins, alternate-day dosing, or using twice-weekly dosing with longer half-life statins. An algorithm is presented to assist the clinician in managing myopathy in patients with dyslipidemia.

  18. Approach to clinical and genetic characterization of statin-induced myopathy.

    PubMed

    Feng, QiPing

    2014-01-01

    HMG CoA reductase inhibitors (statins) are among the most commonly prescribed medications in the industrialized world. They are generally regarded as safe. Mild myalgias can occur in up to 10 % of patients exposed to statins, but skeletal muscle damage (accompanied by an increase in circulating creatine kinase levels) occurs much less frequently. Clinical predictors of statin-induced rhabdomyolysis (severe muscle damage with end organ failure) include female gender, advanced age, and concomitant medications known to interact with critical pharmacokinetic and pharmacodynamic processes. The influence of genetic variations has been investigated by candidate gene association studies, genome-wide association studies, and whole-genome sequencing. This chapter summarizes current available approaches to clinical and genetic characterization of statin-related adverse effect.

  19. Statin-associated myopathy and its exacerbation with exercise.

    PubMed

    Meador, Benjamin M; Huey, Kimberly A

    2010-10-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are a common and effective treatment for hypercholesterolemia, with a low overall rate of side-effects. The most common complication is some degree of skeletal muscle myopathy, ranging from painless serum creatine kinase elevations to rhabdomyolysis. Unfortunately, the likelihood and/or severity of complications increases with the combination of statin treatment and physical activity. The specific pathways that mediate statin-associated myopathy are unclear, and research directly addressing the exacerbation with exercise is limited. Potential mechanisms include the induction of skeletal muscle fiber apoptosis, alterations in ubiquitin-proteasome pathway activity, mitochondrial dysfunction, and terpenoid depletion. In this review we provide an overview of research that specifically addresses the combination of statin-associated myopathy and physical activity and highlight some deficiencies in the available literature, as well as future directions for this important subset of statin-associated myopathy.

  20. Statin-associated autoimmune myopathy and anti-HMGCR autoantibodies.

    PubMed

    Mohassel, Payam; Mammen, Andrew L

    2013-10-01

    Statins are among the most commonly prescribed medications that significantly reduce cardiovascular risk in selected individuals. However, these drugs can also be associated with muscle symptoms ranging from mild myalgias to severe rhabdomyolysis. Although statin myotoxicity is usually self-limited, in some instances statin-exposed subjects can develop an autoimmune myopathy typically characterized by progressive weakness, muscle enzyme elevations, a necrotizing myopathy on muscle biopsy, and autoantibodies that recognize 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the pharmacologic target of statins. These antibodies are also found in some autoimmune myopathy patients without statin exposure. Importantly, anti-HMGCR antibodies are not found in the vast majority of statin-exposed subjects without autoimmune myopathy, including those with self-limited statin intolerance. Thus, testing for these antibodies may help differentiate those with self-limited statin myopathy who recover after statin discontinuation from those with a progressive statin-associated autoimmune myopathy who typically require immunosuppressive therapy.

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

    PubMed

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

    2014-09-01

    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.

  2. The management of acute hyperkalaemia in neonates and children.

    PubMed

    Masilamani, Kavitha; van der Voort, Judith

    2012-04-01

    This review article describes the pathophysiology and common aetiologies of hyperkalaemia including pseudohyperkalaemia, renal impairment, medication, rhabdomyolysis and aldosterone deficiency. Two clinical cases are used to describe symptoms (mainly muscle weakness and arrhythmias) and illustrate different management options. An approach to management including relevant investigations and interpretation of ECG changes is described. Emergency drug treatments are outlined and the effectiveness of individual therapeutic methods in reducing the potassium concentration described. Chronic management is mentioned but is outside the scope of this article. Hyperkalaemia is a rare but potentially life threatening emergency. It is a manifestation of a disease and therefore the incidence in children is not known. Quick and effective intervention may be necessary and clinicians must be adept at managing this condition. This overview provides two clinical scenarios and summarises aetiologies, investigations and management.

  3. Toxicological profiles of poisonous, edible, and medicinal mushrooms.

    PubMed

    Jo, Woo-Sik; Hossain, Md Akil; Park, Seung-Chun

    2014-09-01

    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.

  4. [Recent trends of mushroom poisoning in Japan].

    PubMed

    Yamaura, Yoshio

    2013-03-01

    The incidence of mushroom poisoning was studied statistically from 2001 to 2010 in Japan. The total incident of mushroom poisoning was 569 cases, which involved 1,920 patients and 10 deaths. The average incident was 56.9 cases per year, involving 192 patients and 1 death. On regional differences, the mushroom poisoning was more frequent in the northeastern part of Japan. The rate of total incidents for each type of poisoning, which were classified according to symptoms caused, 54.6% in the type of gastro-intestinal disorder, 11.6% in the type of neurological symptoms, and 2.4% in the type of intracellular disorder (violent vomiting, diarrhea and dehydration and hepato-nephrosis, or rhabdomyolysis, or erroneous perception, etc.), respectively. Two species of poisonous mushrooms with gastro-intestinal disorder, Lampteromyces japonicus and Rhodophyllus rhodopolius caused the majority (52%) of all poisonings in Japan.

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

    PubMed

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

    2002-08-01

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

  6. Legionnaire's Disease and Acute Renal Failure: A Case Report and Literature Review

    PubMed Central

    Boucree, Michael C.

    1988-01-01

    A case report is presented of a young man admitted to a general hospital with leukocytosis, elevated temperature, right lower lobe infiltrate, and confusion. A diagnosis of rhabdomyolysis, acute renal failure, and Legionnaire's disease was made. The patient subsequently had a respiratory arrest and died on the 29th hospital day. This triad is currently an enigma in the field of internal medicine. The diagnosis of each entity is elusive, and in many cases must be made by the astute clinician. Diagnostic features along with early intervention measures and their expected outcomes are discussed. Recognition of the interrelationship of these diseases, risk factors, and vague clinical presentations might allow further prospective intervention methods and diagnostic procedures to be undertaken to avoid the fatal consequences seen in this disease triad. PMID:3074172

  7. Heat illness in the emergency department: keeping your cool.

    PubMed

    Santelli, Jaron; Sullivan, Julie M; Czarnik, Ann; Bedolla, John

    2014-08-01

    Heat illness spans a broad spectrum of disease, with outcomes ranging from benign rash to fatal heat stroke. Heat illness is broadly divided into 2 types: classic and exertional. Both types occur as a result of exposure to elevated temperature with inadequate thermoregulation; however, classic illness occurs without preceding physical activity. Treatment consists of rapid cooling, fluid replacement, and physiologic support. Other milder forms of heat illness include heat fatigue, heat syncope, heat edema, and heat rash. Drugs, drug combinations, drug side effects, and infections can also cause or complicate heat illness and these manifestations may not respond to standard cooling maneuvers and treatments alone; each requires specific additional therapy or antidotes to reverse the cycle of heat and organ damage. This review examines the physiology, diagnosis, and treatment of exertional, classic, and drug-induced hypothermia. Field and prehospital diagnosis and treatment are also reviewed, with recommendations for rehydration and monitoring in rhabdomyolysis.

  8. Transient IgA nephropathy with acute kidney injury in a patient with dengue fever.

    PubMed

    Upadhaya, Bala Krishna; Sharma, Alok; Khaira, Ambar; Dinda, Amit K; Agarwal, Sanjay K; Tiwari, Suresh C

    2010-05-01

    Dengue virus infection can clinically manifest as dengue fever, dengue shock syndrome and dengue hemorrhagic fever. Acute kidney injury as a result of dengue virus infection can occur due to various reasons including hypotension, rhabdomyolysis, sepsis and rarely immune complex mediated glomerular injury. However, glomerulonephritis associated with IgA Nephropathy in dengue virus infection has not been reported previously. We report a case of 15-year-old boy who was admitted with dengue fever and dialysis dependant acute kidney injury. Urine examination showed microscopic glomerular hematuria and proteinuria. Kidney biopsy showed mesangial proliferation with mesangial IgA dominant immune complex deposits and acute tubular necrosis. A repeated kidney biopsy 6 weeks after clinical recovery showed reversal of glomerular changes as well as resolution of mesangial IgA deposits.

  9. Muscle disorders and rehabilitation in canine athletes.

    PubMed

    Steiss, Janet E

    2002-01-01

    Muscle disorders associated with physical exertion in human athletes include delayed-onset muscle soreness, muscle strain, muscle tears, rhabdomyolysis, and acute and chronic compartment syndromes. Given that the structure of muscle is similar among different species, it is reasonable to expect that dogs experience the same phenomena. This article focuses on several of the muscle disorders of bird dogs, namely, coccygeal muscle injury and infraspinatus muscle contracture, and on those of dogs involved in tracking-obedience-protection training, namely, fibrotic myopathy, with an additional discussion of muscle strain. For injury prevention, one important area that can be adapted to canine athletes is the incorporation of warm-up and cool-down into the training program.

  10. Patient positioning and prevention of injuries in patients undergoing laparoscopic and robot-assisted urologic procedures.

    PubMed

    Sukhu, Troy; Krupski, Tracey L

    2014-04-01

    Positioning injuries in the perioperative period are one of the inherent risks of surgery, but particularly in robot-assisted urologic surgery, and can result in often unrecognized morbidity. Injuries such as upper or lower extremity peripheral neuropathies occur via neural mechanisms and injuries such as compartment syndrome, rhabdomyolysis, ischemic optic neuropathy, and acute arterial occlusion occur via vascular mechanisms. The risk of injury may be exacerbated by operative and patient-related risk factors. Patient-related risk factors include ASA class and BMI, while surgery-related risk factors include physical orientation of the patient and operative length. These injuries can be prevented or reduced by joint effort of the surgeon, anesthesiologist, and operating room staff.

  11. Nephrotoxicity of recreational party drugs.

    PubMed

    Berney-Meyer, Linda; Putt, Tracey; Schollum, John; Walker, Robert

    2012-02-01

    N-benzylpiperazine (BZP) is the active ingredient in recreational 'party' pills with a stimulant, euphoric mechanism of action akin to that of 3,4-methylenedioxymethamphetamine (MDMA or ecstasy). Many people (ab)use BZP-based party pills usually without any significant toxic effects. However, nephrotoxicity secondary to hyperthermia and rhabdomyolysis has been reported. Another serious renal-related side-effect is hyponatraemia with acute cerebral oedema. There is also evidence that these agents may have a specific toxic effect producing acute kidney injury. Thus, acute kidney injury either direct or secondary to the effects of BZP or MDMA need to be considered when any individual presents with symptoms of a recreational party drug overdose.

  12. An Unusual Case of LCHAD Deficiency Presenting With a Clinical Picture of Hemophagocytic Lymphohistiocytosis: Secondary HLH or Coincidence?

    PubMed

    Erdol, Sahin; Ture, Mehmet; Baytan, Birol; Yakut, Tahsin; Saglam, Halil

    2016-11-01

    There are published reports stating that some of the congenital metabolic diseases, such as lysinuric protein intolerance, multiple sulphatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis, might lead to secondary hemophagocytic lymphohistiocytosis (HLH). However, to date, to our knowledge, the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has never been investigated among patients with HLH. Here, we report on a patient who was referred to our institution for a differential diagnosis of pancytopenia, liver failure, and rhabdomyolysis. The patient was diagnosed with HLH. Further investigation revealed an underlying diagnosis of the LCHAD deficiency. Our case was reported to contribute to the literature, as well as the HLH clinic, emphasizing the consideration of LCHAD deficiency, especially in 1 to 6 months' old infants with laboratory findings of hypoglycemia, metabolic acidosis, and elevated creatine kinase.

  13. 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.

  14. 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

  15. Malignant hyperthermia and the clinical significance of type-1 ryanodine receptor gene (RYR1) variants: proceedings of the 2013 MHAUS Scientific Conference.

    PubMed

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

    2014-11-01

    The Malignant Hyperthermia Association of the United States and the Department of Anesthesia at the University of Toronto sponsored a Scientific Conference on November 1-2, 2013 in Toronto, ON, Canada. The multidisciplinary group of experts, including clinicians, geneticists, and physiologists involved in research related to malignant hyperthermia (MH), shared new insights into the pathophysiology of diseases linked to the type-1 ryanodine receptor gene (RYR1) as well as the relationship between MH and "awake MH" conditions, such as exertional rhabdomyolysis and exertional heat illness. In addition, the molecular genetics of MH and clinical issues related to the diagnosis and management of disorders linked to RYR1 were presented. The conference also honoured Dr. David H. MacLennan for his contributions to our understanding of the genetics, pathogenesis, and treatment of MH and other RYR1-related myopathies. This report represents a summary of the proceedings of this conference.

  16. 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.

  17. The clinical manifestation of MCAD deficiency: challenges towards adulthood in the screened population.

    PubMed

    Schatz, Ulrich A; Ensenauer, Regina

    2010-10-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common fatty acid oxidation disorder. Typically, undiagnosed individuals are asymptomatic until an episode of increased energy demand and fasting occurs, resulting in metabolic derangement. Phenotypic heterogeneity has been increasingly realized, with reports of both neonates and adults manifesting with life-threatening symptoms including encephalopathy, rhabdomyolysis, and cardiac failure. If diagnosed presymptomatically, outcome is favorable basically by avoidance of fasting. Early detection by newborn screening (NBS) has significantly reduced the incidence of severe adverse events including deaths. In this manuscript we focus on the natural course of the disease in both children and adults. Although NBS for MCADD has been successfully established, continuing efforts need to be made to avoid acute crises and deterioration of outcome in screened patients entering adolescence and adulthood.

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

    PubMed

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

    2016-02-04

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

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

    PubMed Central

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

    2016-01-01

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

  20. 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

  1. Successful treatment of refractory cerebral oedema in ecstasy/cocaine-induced fulminant hepatic failure using a new high-efficacy liver detoxification device (FPSA-Prometheus).

    PubMed

    Kramer, Ludwig; Bauer, Edith; Schenk, Peter; Steininger, Rudolf; Vigl, Marion; Mallek, Reinhold

    2003-09-15

    Ecstasy-induced fulminant hepatic failure is associated with high mortality. If complicated by cerebral oedema, orthotopic liver transplantation is the only established treatment. We report a case of combined ecstasy/cocaine-induced fulminant hepatic failure presenting with severe rhabdomyolysis, myocardial infarction and multiorgan failure. Transplantation was declined by the transplant surgeons because of a history of intravenous drug abuse. As excessive hyperammonaemia (318 mumol/l) and refractory transtentorial herniation developed, treatment with a new liver detoxification device combining high-flux haemodialysis and adsorption (FPSA-Prometheus) was initiated. Within a few hours of treatment, ammonia levels normalised. Cerebral oedema was greatly reduced by day 4 and hepatic function gradually recovered. Following neurologic rehabilitation for ischaemic sequelae of herniation, the patient was discharged from hospital with only minimal deficits. In conclusion, efficient extracorporeal detoxification may be an option for reversal of hyperammonaemia and refractory cerebral oedema in ecstasy/cocaine-induced acute liver failure.

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

    PubMed Central

    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

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

    PubMed

    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.

  4. 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.

  5. A man with worsening weakness.

    PubMed

    Proietti, G; Puliti, M; Tulli, F; Silvestri, M

    1999-01-01

    The contemporary presence of organomegaly, skin manifestations, polyneuropathy, endocrinopathy and monoclonal component characterises the POEMS syndrome, often associated with osteosclerotic myeloma and Castelman's disease and more frequent in the Japanese. Clinical manifestations seem to be related to the production of many interleukins, mainly IL-1, IL-6 and TNF. Several endocrinopathies have been described, the most frequent being diabetes. Only one previous case of hypoparathyroidism associated with the syndrome has been described in medical reviews. Polyneuropathy is often sensitivo-motory and skin disease accounts for Raynaud phenomenon, skin pigmentation, hypertricosis and others. We describe the case of a 74-year-old man who underwent clinical examination for weakness mainly in the legs. Clinical and instrumental data showed rhabdomyolysis due to hypoparathyroidism. The contemporary presence of a monoclonal band of light chains on proteic electrophoresis, organomegaly and distal leg neuropathy allowed us to make a diagnosis of POEMS syndrome.

  6. Status spasticus and psoas muscle edema due to anti-GAD antibody associated stiff-man syndrome.

    PubMed

    Maramattom, Boby Varkey

    2015-08-01

    Severe muscle rigidity and spasms are uncommon causes of Intensive Care Unit (ICU) admissions. Stiff-man syndrome (SMS) is a rare disorder characterized by continuous muscle spasms, axial muscle rigidity, "tin soldier gait," and continuous motor unit activity on electromyography. There are three clinical variants of SMS; stiff-limb syndrome, classical SMS, and paraneoplastic encephalomyelitis with rigidity and myoclonus. Three types of antibodies have been associated with SMS; however, anti-glutamic acid decarboxylase (GAD) antibodies are the most frequent and are seen in the idiopathic type of SMS. The spasms of SMS can be very disabling and severe enough to cause muscle ruptures and skeletal fractures. We present a case of anti-GAD positive SMS with "status spasticus" causing bilateral psoas myoedema and rhabdomyolysis due to repeated axial muscle jerking in a 64-year-old man and discuss the differential diagnosis of a "jerking patient in the ICU."

  7. Management of Crush Syndrome Casualties after Disasters

    PubMed Central

    Sever, Mehmet Sukru; Vanholder, Raymond

    2011-01-01

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

  8. Acute liver failure following intravenous methamphetamine.

    PubMed

    Kamijo, Yoshito; Soma, Kazui; Nishida, Manami; Namera, Akira; Ohwada, Takashi

    2002-08-01

    A 41-y-o Pakistani man presented with psychosis, hyperthermia, rhabdomyolysis, and liver dysfunction approximately 6 h after i.v. injection of methamphetamine. Serum concentrations of methamphetamine and amphetamine on admission were 0.30 microg/mL and 0.04 microg/mL, respectively. Total serum bilirubin and alanine aminotransferase concentrations peaked on the 3rd hospital day at 8.6 mg/dL and 4155 IU/L, respectively, and gradually returned to normal with supportive care. The patient had no evidence of infectious hepatitis or intake of other drugs. Histologic examination of a liver biopsy specimen obtained on the 11th d showed confluent necrosis and ballooning degeneration in centrilobular zones. No inflammatory changes were seen in portal tracts. Liver damage can be a complication of illicit methamphetamine use, even in patients without viral infection or intake of other drugs.

  9. Statin induced myotoxicity.

    PubMed

    Sathasivam, Sivakumar

    2012-06-01

    Statins are an effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, myotoxicity induced by statins is a common adverse event and a major barrier to maximising cardiovascular risk reduction. The clinical spectrum of statin induced myotoxicity includes asymptomatic rise in creatine kinase concentration, myalgia, myositis and rhabdomyolysis. In certain cases, the cessation of statin therapy does not result in the resolution of muscular symptoms or the normalization of creatine kinase, raising the possibility of necrotizing autoimmune myopathy. There is increasing understanding and recognition of the pathophysiology and risk factors of statin induced myotoxicity. Careful history and physical examination in conjunction with selected investigations such as creatine kinase measurement, electromyography and muscle biopsy in appropriate clinical scenario help diagnose the condition. The management of statin induced myotoxicity involves statin cessation, the use of alternative lipid lowering agents or treatment regimes, and in the case of necrotizing autoimmune myopathy, immunosuppression.

  10. Managing statin myopathy.

    PubMed

    Venero, Carmelo V; Thompson, Paul D

    2009-03-01

    Approximately 10% of patients treated with statins experience some form of muscle-related side effects in clinical practice. These can range from asymptomatic creatine kinase (CK) elevation, to muscle pain, weakness, and its most severe form, rhabdomyolysis. Higher risk patients for statin myopathy are those older than 80, with a small body frame, on higher statin doses, on other medications, or with other systemic diseases including hepatic or renal diseases, diabetes mellitus, or hypothyroidism. The cause of statin myopathy is presumed to be the same for its variable presentation but has not been defined. In patients with myopathic symptoms, their symptoms and CK levels determine whether statin therapy can be continued or must be stopped.

  11. Antiglomerular basement membrane antibody-mediated glomerulonephritis after intranasal cocaine use.

    PubMed

    Peces, R; Navascués, R A; Baltar, J; Seco, M; Alvarez, J

    1999-01-01

    We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury.

  12. McArdle disease: a case report and review

    PubMed Central

    Leite, Alberto; Oliveira, Narciso; Rocha, Manuela

    2012-01-01

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

  13. 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.

  14. 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

  15. Distributive shock due to systemic capillary leak syndrome treated with high-dose immunosuppression.

    PubMed

    Sheehan, James Robert; Keating, Liza; Chan, Antoni; Walden, Andrew

    2013-04-09

    A female patient in her 60s presented with a history of malaise, chills, headache and vomiting. She was in shock on presentation with a high haematocrit and a low albumin with evidence of rhabdomyolysis. Severe limb and truncal oedema developed with worsening hypotension leading to intensive care unit admission for multiple organ support. Extensive radiological, microbiological and immunological work up was negative with the exception of a monoclonal gammopathy. A review of patient investigations led to a diagnosis of Clarkson's disease. Treatment with high-dose methylprednisolone and intravenous immunoglobulins led to a rapid decline in the creatine kinase (CK) level and vasopressor requirements. The patient was discharged home on long-term terbutaline and has made a good recovery.

  16. Assessment of ADRs associated with lipid-lowering agents recorded in the Department of Internal Medicine, University Hospital, Jena.

    PubMed

    Hippius, M; Farker, K; Helble, S; Hoffmann, A

    2002-03-01

    Drug-related illness is an important cause of admission to hospital. Little information is available regarding the frequency of ADRs caused by antilipidemic agents classified as HMG-CoA reductase inhibitors (statins). Treatment with statins has been associated with the occurrence of myopathy or liver toxicity in case reports. Recent lipid intervention studies have involved the implementation of lipid lowering therapy with HMG-CoA reductase inhibitors in cardiovascular risk management. Since January 1997 we have been involved in a study, the aim of which was to improve the spontaneous drug information reporting system in Germany. The study was supported by the German Federal Institute for Drugs and Medical Devices, the "Bundesinstitut für Arzneimittel und Medizinprodukte", Berlin BfArM. Between early 1997 and late 2000, as a result of this monitoring of ADRs, we analyzed all patient histories concerning therapy with statins. A total of 550 ADR patients were evaluated, (209 male, 341 female) with a mean age of 66.4 years. 27 (4.9%) of all patients had received statins (atorvastatin = 12, fluvastatin = 7, simvastatin as well as pravastatin = 3, lovastatin = 2). Only 2 of the 27 patients admitted to hospital for typical ADRs of statins such as skeletal muscle toxicity (e.g. myalgia, rhabdomyolysis) or disorders involving hepatic structure or function were receiving statins (atorvastatin). An increased risk of rhabdomyolysis has been reported in the case of several statins, following concomitant use with erythromycin, cyclosporine or itraconazole, all of which are potent inhibitors of CYP3A4 enzyme. But only 1 atorvastatin patient had received cyclosporine as a CYP3A4 inhibitor. After discontinuing medication, signs of intoxication disappeared. The antihyperlipidemic drugs available are generally safe and effective, and rate of ADRs is low if concomitant intake of other drugs and the differing pharmacokinetic profiles of the statins are considered.

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

    PubMed Central

    Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

    2011-01-01

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

  18. 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

  19. 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

  20. Productive infection of human skeletal muscle cells by pandemic and seasonal influenza A(H1N1) viruses.

    PubMed

    Desdouits, Marion; Munier, Sandie; Prevost, Marie-Christine; Jeannin, Patricia; Butler-Browne, Gillian; Ozden, Simona; Gessain, Antoine; Van Der Werf, Sylvie; Naffakh, Nadia; Ceccaldi, Pierre-Emmanuel

    2013-01-01

    Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1) in 2009. The pathogenesis of these influenza-associated myopathies (IAM) remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1) isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes) were highly susceptible to infection by both influenza A(H1N1) isolates, whereas undifferentiated cells (i. e. myoblasts) were partially resistant. The receptors for influenza viruses, α2-6 and α2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP) expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients.

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

    PubMed

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

    2014-11-07

    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.

  2. The Emergence and Epidemiology of Haff Disease in China

    PubMed Central

    Chan, Thomas Y. K.

    2016-01-01

    Haff disease is a rare syndrome of unexplained myalgia and rhabdomyolysis occurring within 24 h of consumption of certain types of cooked freshwater fish or crustacean. It is caused by a yet unidentified heat-stable toxin. In the present review of published case studies and official press releases, the main objective is to report the emergence and epidemiology of Haff disease in China. Haff disease first occurred in Beijing in 2000 and in Lianzhou and Liannan, Guangdong Province in 2009. Subsequent outbreaks mostly occurred in the Jiangsu Province—Nanjing, Yangzhou, Huai’an, and Yancheng. Isolated outbreaks occurred in other cities since 2010—Shijiazhuang, Yueyang, Shanghai, Wuhu, Baoding, Shenzhen, and Hong Kong (imported cases from Shenzhen). Outbreaks occurred predominately in the summer. Crayfish accounted for almost all the outbreaks. Two large outbreaks occurred in Lianzhou and Liannan in 2009 (n = 54) after eating pomfrets and in Nanjing in 2010 (n = 42) after eating crayfish. Other reports or outbreaks involved only 1–9 subjects (median 2 subjects). Variability in individual susceptibility and attack rates were noted, with many subjects remaining asymptomatic despite sharing the same seafood meal as the index cases. Adults were predominately involved. Symptoms occurred within 3–20 h of seafood ingestion, including myalgia, weakness, and, less frequently, nausea, vomiting, abdominal pain, and diarrhea. Myalgia and muscle weakness should normally subside within 2–3 days. Serum creatine phosphokinase became normal within 5–6 days. Abnormal renal function was uncommon. Serious complications (renal failure, multi-organ failure, and prolonged myopathy) and death were rare. In any subjects with unexplained myalgia and rhabdomyolysis, seafood consumption should be included in the history. All suspected cases of Haff disease, including milder presentations, should be reported to public health authorities. PMID:27916937

  3. The Association Between Use of a Clinical Decision Support Tool and Adherence to Monitoring for Medication-Laboratory Guidelines in the Ambulatory Setting

    PubMed Central

    Lau, B.; Overby, C. L.; Wirtz, H. S.; Devine, E. B.

    2013-01-01

    Summary Background Stage 2 Meaningful Use criteria require the use of clinical decision support systems (CDSS) on high priority health conditions to improve clinical quality measures. Although CDSS hold great promise, implementation has been fraught with challenges, evidence of their impact is mixed, and the optimal method of content delivery is unknown. Objective The authors investigated whether implementation of a simple clinical decision support (CDS) tool was associated with improved prescriber adherence to national medication-laboratory monitoring guidelines for safety (hepatic function, renal function, myalgias/rhabdomyolysis) and intermediate outcomes for antidiabetic (Hemoglobin A1c; HbA1c) and antihyperlipidemic (low density lipoprotein; LDL) medications prescribed within a diabetes registry. Methods This was a retrospective observational study conducted in three phases of CDS implementation (2008–2009): pre-, transition-, and post-Prescriptions evaluated were ordered from an electronic health record within a multispecialty medical group. Adherence was evaluated within and without applying guideline-imposed time constraints. Results Forty-thousand prescriptions were ordered over three timeframes. For hepatic and renal function, the proportion of prescriptions for which labs were monitored at any time increased from 52% to 65% (p<0.001); those that met time guidelines, from 14% to 21% (p<0.001). Only 6% of required labs were drawn to monitor for myalgias/rhabdomyolysis, regardless of timeframe. Over 90% of safety labs were within normal limits. The proportion of labs monitored at any time for LDL increased from 56% to 64% (p<0.001); those that met time guidelines from 11% to 17% (p<0.001). The proportion of labs monitored at any time for HbA1c remained the same (72%); those that met time guidelines decreased from 45% to 41% (p<0.001). Conclusion A simple CDS tool may be associated with improved adherence to guidelines. Efforts are needed to confirm

  4. McArdle Disease Misdiagnosed as Meningitis

    PubMed Central

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

    2016-01-01

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

  5. Renal Involvement in Idiopathic Inflammatory Myopathies.

    PubMed

    Cucchiari, David; Angelini, Claudio

    2017-02-01

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

  6. 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

  7. Benefit versus risk in statin treatment.

    PubMed

    Guyton, John R

    2006-04-17

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

  8. 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.

  9. Statin-induced apoptosis and skeletal myopathy.

    PubMed

    Dirks, Amie J; Jones, Kimberly M

    2006-12-01

    Over 100 million prescriptions were filled for statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) in 2004. Statins were originally developed to lower plasma cholesterol in patients with hypercholesterolemia and are the most effective drugs on the market in doing so. Because of the discovered pleiotropic effects of statins, the use has expanded to the treatment of many other conditions, including ventricular arrythmias, idiopathic dilated cardiomyopathy, cancer, osteoporosis, and diabetes. The elderly population is growing. Therefore, it is estimated that the number of statin users will also increase. Fortunately, the use of statins is relatively safe with few side effects. Myopathy is the most common side effect with symptoms ranging from fatigue, weakness, and pain to symptoms associated with rhabdomyolysis which is a life-threatening condition. The development of statin-induced rhabdomyolysis is rare occurring in approximately 0.1% of patients; however, the occurrence of less severe symptoms is underreported and may be 1-5% or more. Physical exercise appears to increase the likelihood for the development of myopathy in patients taking statins. It is thought that as many as 25% of statin users who exercise may experience muscle fatigue, weakness, aches, and cramping due to statin therapy and potentially dismissed by the patient and physician. The mechanisms causing statin-induced myopathy have not been elucidated; however, research efforts suggest that apoptosis of myofibers may contribute. The mitochondrion is considered a regulatory center of apoptosis, and therefore its role in the induction of apoptosis will be discussed as well as the mechanism of statin-induced apoptosis and myopathy.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Malignant hyperthermia

    PubMed Central

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

    2007-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene

  16. Physiological responses to the endurance test of a 3-day-event during hot and cool weather.

    PubMed

    Kohn, C W; Hinchcliff, K W

    1995-11-01

    Physiological data were collected during two 3-day-event competitions: one (H) held in hot and the other (CL) in cool conditions. During H, ambient temperature and relative humidity were 2.5 degrees C-35 degrees C and 74-36% respectively, while during CL, ambient temperature and relative humidity were 7.8 degrees C-8.3 degrees C and 46%-41%, respectively. Rectal temperature, heart and respiratory rates were recorded on arrival at the event, at the end of Phase C and 6 min later, at the end of Phase D and for 30 min at 10 min intervals after each horse finished Phase D (Recovery Period). Because of the heat, the rest-pause during the Endurance Test was extended from 10 to 15 min for horses competing in H, and horses at H were aggressively cooled by repetitive bathing with ice water during the rest-pause and the 30 min Recovery Period. Heart rate was significantly higher (P < 0.05) at the end of Phase C in horses participating at H, as compared to those participating at CL. Heart rates were significantly decreased in both groups after 6 min in the rest-pause and by 10 min after the finish of Phase D. Rectal temperature were significantly higher in horses competing at H than in those competing at CL at the end of Phase C and 6 min later, and at 10 and 20 min after the finish of Phase D. In both groups, rectal temperatures decreased significantly during the first 6 min in the rest-pause and at 10 and 20 min after the finish of Phase D. Fifty-five of 79 (69.6%) horses starting Phase A at H completed Phase D, as compared to 23 of 28 (82.1%) of starters at CL (P > 0.05). Of 10 horses eliminated during the rest-pause at H, 3 were lame, 1 had exertional rhabdomyolysis, 4 were exhausted and 2 were lame and exhausted. Two horses were eliminated during the rest-pause at CL:1 was lame and the other had exertional rhabdomyolysis. There was marked individual variation in horses' responses to heat at H. Heat may have limited the effectiveness of evaporative cooling in horses at H

  17. Mechanisms of exercise-induced delayed onset muscular soreness: a brief review.

    PubMed

    Armstrong, R B

    1984-12-01

    Delayed-onset muscular soreness (DOMS), the sensation of pain and stiffness in the muscles that occurs from 1 to 5 d following unaccustomed exercise, can adversely affect muscular performance, both from voluntary reduction of effort and from inherent loss of capacity of the muscles to produce force. This reduction in performance is temporary; permanent impairment does not occur. A number of clinical correlates are associated with DOMS, including elevations in plasma enzymes, myoglobinemia, and abnormal muscle histology and ultrastructure; exertional rhabdomyolysis appears to be the extreme form of DOMS. Presently, the best treatment for DOMS appears to be muscular activity, although the sensation again returns following the exercise. Training for the specific contractile activity that causes DOMS reduces the soreness response. The etiology and cellular mechanisms of DOMS are not known, but a number of hypotheses exist to explain the phenomenon. The following model may be proposed: 1) high tensions (particularly those associated with eccentric exercise) in the contractile/elastic system of the muscle result in structural damage; 2) cell membrane damage leads to disruption of Ca++ homeostasis in the injured fibers, resulting in necrosis that peaks about 2 d post-exercise; and 3) products of macrophage activity and intracellular contents accumulate in the interstitium, which in turn stimulate free nerve endings of group-IV sensory neurons in the muscles leading to the sensation of DOMS.

  18. Evaluation of vascular tone and cardiac contractility in response to silver nanoparticles, using Langendorff rat heart preparation.

    PubMed

    Alejandro, Ramirez-Lee Manuel; Pablo, Martinez-Cuevas Pedro; Hector, Rosas-Hernandez; Cuauhtémoc, Oros-Ovalle; Mariela, Bravo-Sanchez; Alejandro, Martinez-Castañon Gabriel; Carmen, Gonzalez

    2017-02-16

    Silver nanoparticles (AgNPs) have been widely used because of their antimicrobial properties. However, several reports suggest that AgNPs exposure promote cardiac effects that involve nitric oxide (NO) and oxidative stress (OS). Nevertheless, there are no studies related to AgNPs-induced effects in cardiac physiology. The aim of this study was to evaluate the AgNPs direct actions on coronary vascular tone and cardiac contractility using Langendorff rat heart preparation. Low concentrations of AgNPs (0.1 and 1 μg/mL) increased NO derived from inducible NO-synthase (iNOS), without modifying cardiac parameters. Meanwhile, high concentrations (10 and 100 μg/mL) promoted a sustained vasoconstriction and increased cardiac contractility related to OS, leading to rhabdomyolysis. Furthermore, AgNPs were internalized in the cardiac muscle, hindering classic actions induced by phenylephrine (Phe) and acetylcholine (ACh). These data suggest that AgNPs affect cardiac physiology in function of the concentration and in part of the NO generation, NOS expression and OS.

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

    PubMed

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

    2015-12-15

    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.

  20. 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.

  1. Evidence for a role of human organic anion transporters in the muscular side effects of HMG-CoA reductase inhibitors.

    PubMed

    Takeda, Michio; Noshiro, Rie; Onozato, Maristela Lika; Tojo, Akihiro; Hasannejad, Habib; Huang, Xiu-Lin; Narikawa, Shinichi; Endou, Hitoshi

    2004-01-12

    The purpose of this study was to elucidate the role of human organic anion transporters (human OATs) in the induction of drug-induced skeletal muscle abnormalities. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have been clinically used for lowering plasma cholesterol levels, and are known to induce various forms of skeletal muscle abnormalities including myopathy and rhabdomyolysis. Immunohistochemical analysis revealed that human OAT1 and human OAT3 are localized in the cytoplasmic membrane of the human skeletal muscles. The activities of human OATs were measured using mouse cell lines from renal proximal tubules stably expressing human OATs. Human OAT3, but not human OAT1, mediates the transport of pravastatin. Fluvastatin inhibited organic anion uptake mediated by human OAT1 in a mixture of competitive and noncompetitive manner, whereas simvastatin and fluvastatin noncompetitively inhibited the organic anion uptake mediated by human OAT3. In conclusion, the organic anion transporters OAT1 and OAT3 are localized in the cytoplasmic membrane of human skeletal muscles. Pravastatin, simvasatin, and fluvasatin inhibit human OATs activity. These results suggest that muscle organic anion transporters play a role in the muscular side effects of HMG-CoA reductase inhibitors.

  2. Differential sensitivity of C2-C12 striated muscle cells to lovastatin and pravastatin.

    PubMed

    Gadbut, A P; Caruso, A P; Galper, J B

    1995-10-01

    One of the major side-effects of the use of HMG CoA reductase inhibitors for the treatment of hypercholesterolemia is the development of myositis and, in some patients undergoing concomitant immunosuppressive treatment, the development of rhabdomyolysis. Experiments outlined in these studies demonstrate that inhibitors of HMG-CoA reductase activity which differ primary in the substitution of a methyl group for a hydroxyl group have differential effects on both cholesterol levels and cell viability in a striated muscle cell model, the mouse C2-C12 myoblast. Thus, concentrations as high as 200 microM of pravastatin had little effect on total cholesterol level while 25 microM of lovastatin decreased cellular cholesterol by over 90%. Simvastatin and lovastatin decreased viability of C2-C12 myoblasts by nearly 50% at concentrations as low as 1 and 5 microM, respectively, and decreased viability by almost 90% at 10 and 15 microM respectively. However, 300 microM of pravastatin decreased cell viability by less than 50%. The order of potency for the effects on cell viability wassimvastatin>lovastatin>pravastatin. The possible relationship between effects on cell viability and the development of myositis is discussed.

  3. Rab-small GTPases are involved in fluvastatin and pravastatin-induced vacuolation in rat skeletal myofibers.

    PubMed

    Sakamoto, Kazuho; Honda, Takashi; Yokoya, Sachihiko; Waguri, Satoshi; Kimura, Junko

    2007-12-01

    Three-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, known as statins, induce skeletal muscle injury including myalgia, myositis, and rhabdomyolysis. The mechanism of this myotoxicity remains unknown. This study examined the effect of statins on single skeletal myofibers enzymatically isolated from the rat flexor digitorum brevis muscles. Fluvastatin and pravastatin induced the formation of numerous vacuoles in the myofibers after 72 h of treatment. This effect progressed in a time- and concentration-dependent manner and, consequently, cell death occurred after 120 h. Electron micrographs revealed craters along the sarcolemma and swelling of the sarcoplasmic reticula and mitochondria, in addition to intracellular vacuoles. When caffeine was added after 72 h of fluvastatin treatment, contractile shortening of statin-treated myofibers was significantly attenuated and blebs formed on the surface of the myofibers. The coapplication of geranylgeranylpyrophosphate (GGPP) with fluvastatin prevented the morphological changes, while that of farnesylpyrophosphate (FPP) was ineffective. Furthermore, perillyl alcohol, an inhibitor of Rab geranylgeranyl transferase and geranylgeranyl transferase-I (GGTase-I), mimicked the effect of statins, while a specific GGTase-I inhibitor (GGTI-298) or a farnesyl transferase inhibitor (FTI-277) failed to do so. These results suggest that the inactivation of Rab GTPase, which involved in intracellular membrane transport, is a crucial factor in statin-induced-morphological abnormality in skeletal muscle fibers.

  4. Eisai hyperbilirubinemic rat (EHBR) as an animal model affording high drug-exposure in toxicity studies on organic anions.

    PubMed

    Naba, Hiroyasu; Kuwayama, Chitose; Kakinuma, Chihaya; Ohnishi, Shuhei; Ogihara, Takuo

    2004-10-01

    The Eisai hyperbilirubinemic rat (EHBR) should be a useful animal model for studies on the toxicity of organic anions which are substrates of multidrug resistance-associated protein 2 (Mrp2), since the systemic exposure to these compounds is expected to be increased in EHBR. In this study, we tested the value of EHBR for this purpose, using pravastatin (PV) and methotrexate (MTX) as model compounds. In the case of a single oral dose of PV (200 mg/kg), C(max) in plasma was 4.0-fold higher and AUC(0-infinity) was 3.6-fold larger than those of normal Sprague-Dawley rats (SDR), respectively. When multiple doses of PV were given to EHBR without co-administration of any other compound, drug-induced skeletal muscle toxicity (myopathy/rhabdomyolysis) and increased creatine phosphokinase (CPK) level were observed, whereas a control experiment using SDR did not show any toxic change. When a single dose of MTX (0.6 mg/kg) was given to EHBR orally, C(max) was 1.7-fold higher and AUC(0-infinity) was 1.6-fold larger than those of SDR, respectively. When multiple doses of MTX were given to EHBR, the changes in bone marrow, spleen and intestines were more severe than those in SDR. These findings support the view that EHBR would be a valuable animal model for toxicity studies on organic anion compounds which are substrates of Mrp2.

  5. Ca2+-releasing effect of cerivastatin on the sarcoplasmic reticulum of mouse and rat skeletal muscle fibers.

    PubMed

    Inoue, Ryotaku; Tanabe, Mitsuo; Kono, Keita; Maruyama, Kei; Ikemoto, Takaaki; Endo, Makoto

    2003-11-01

    We analyzed the effect of HMG-CoA reductase inhibitors on Ca(2+) release from the sarcoplasmic reticulum (SR) using chemically skinned skeletal muscle fibers from the mouse and the rat. Cerivastatin (>20 microM) released Ca(2+) from the SR, while pravastatin showed only a little effect. The rates of Ca(2+) release were increased by cerivastatin at all Ca(2+) concentrations tested. Cerivastatin-induced Ca(2+) release in the presence of Ca(2+) was affected by adenosine monophosphate, Mg(2+), and procaine in essentially the same way as for caffeine-induced Ca(2+) release. The Ca(2+)-uptake capacity of the SR was reduced after co-treatment with ryanodine and cerivastatin at pCa 6.0 to a much greater extent than with ryanodine alone. Thus, cerivastatin-induced Ca(2+) release in the presence of Ca(2+) must be a result of the activation of the Ca(2+)-induced Ca(2+) release (CICR) mechanism of the ryanodine receptor. However, even when CICR was maximally inhibited by Mg(2+) and procaine, or in the practical absence of Ca(2+) (pCa >8), cerivastatin still caused Ca(2+) release. These results indicate that cerivastatin causes Ca(2+) release also by activating some other mechanism(s) in addition to the activation of CICR. Either or both of these effects might be related to its adverse effect, rhabdomyolysis.

  6. Effects of HMG-CoA reductase inhibitors on growth and differentiation of cultured rat skeletal muscle cells.

    PubMed

    Veerkamp, J H; Smit, J W; Benders, A A; Oosterhof, A

    1996-04-12

    HMG-CoA reductase inhibitors have been associated with skeletal muscle myopathy, ranging from asymptomatic elevations of serum creatine kinase (CK) activity to rhabdomyolysis. In this study, we assessed the effects of addition of different concentrations of simvastatin and pravastatin on growth and differentiation of cultured primary rat skeletal muscle cells. Protein concentrations, CK activity and percentage CK-MM, which is a parameter for maturation, were determined. Effects were generally stronger if inhibitors were added to both growth and differentiation medium rather than only to differentiation medium. Addition of 25 microM pravastatin caused only a decrease of CK activity. Addition of 1-5 microM simvastatin resulted in a decrease of protein concentration, CK activity and percentage CK-MM, whereas 25 microM simvastatin resulted in cell death. Addition of mevalonic acid or cholesterol could not prevent the effects of 1 microM simvastatin. In addition, 1 microM simvastatin did not influence the cholesterol and phospholipid content of the cells. Superfusion of cultured cells with simvastatin concentrations of 10 microM and higher caused a transient increase of the cytoplasmic calcium concentration followed by an apparent second rise and cell puncture. The results indicate that HMG-CoA reductase inhibitors may affect skeletal muscle cell regeneration in vivo by a direct toxic effect on growth and differentiation.

  7. 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

  8. The lightning heart: a case report and brief review of the cardiovascular complications of lightning injury.

    PubMed

    McIntyre, William F; Simpson, Christopher S; Redfearn, Damian P; Abdollah, Hoshiar; Baranchuk, Adrian

    2010-09-05

    Lightning strike is a rare natural phenomenon, which carries a risk of dramatic medical complications to multiple organ systems and a high risk of fatality. The known complications include but are not limited to: myocardial infarction, arrhythmia, cardiac contusion, stroke, cutaneous burns, respiratory disorders, neurological disorders, acute kidney injury and death. We report a case of a healthy young man who suffered a lightning injury and discuss the cardiovascular complications of lightning injury, ranging from ECG changes to death. The patient in our case, a 27-year old previously healthy male, developed a syndrome of rhabdomyolysis and symptomatic cardiogenic pulmonary edema. Electrocardiographic findings included transient T-wave inversions, late transition shift and long QT. His clinical condition improved with supportive measures.Early recognition of lightning injury syndromes and anticipation of complications may help us improve outcomes for these patients. Evaluation of patients having experienced a lightning injury should include a minimum of a detailed history and physical examination, 12-lead ECG and drawing of baseline troponins. Prolonged electrocardiographical monitoring (for monitoring of ventricular arrhythmias) and assessment for signs and symptoms of hemodynamic compromise may be warranted.

  9. [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.

  10. Hypermetabolism in B–lymphocytes from malignant hyperthermia susceptible individuals

    PubMed Central

    Hoppe, Kerstin; Hack, Guido; Lehmann–Horn, Frank; Jurkat–Rott, Karin; Wearing, Scott; Zullo, Alberto; Carsana, Antonella; Klingler, Werner

    2016-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism which is characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca2+ release in myotubes via the ryanodine receptor type 1 (RyR1). As RyR1 is also expressed in B–lymphocytes, this study investigated whether cellular metabolism of native B–lymphocytes was also altered in MH susceptible (MHS) individuals. A potent activator of RyR1, 4–chloro–m–cresol (4-CmC) was used to challenge native B-lymphocytes in a real–time, metabolic assay based on a pH–sensitive silicon biosensor chip. At the cellular level, a dose–dependent, phasic acidification occurred with 4–CmC. The acidification rate, an indicator of metabolic activation, was significantly higher in B–lymphocytes from MHS patients and required 3 to 5 fold lower concentrations of 4–CmC to evoke similar acidification rates to MHN. Native B–lymphocytes from MHS individuals are more sensitive to 4–CmC than those from MHN, reflecting a greater Ca2+ turnover. The acidification response, however, was less pronounced than in muscle cells, presumably reflecting the lower expression of RyR1 in B–lymphocytes. PMID:27646467

  11. 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.

  12. 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

  13. [Acute poisoning with anticholinesterase carbamate pesticides: methomyl-lannate®].

    PubMed

    Chaouali, Nadia; Amira, Dorra; Zitouni, Eya; Gana, Ines; Nouioui, Anouer; Khelifi, Fathia; Belwaer, Ines; Masri, Wafa; Ghorbal, Hayet; Hedhili, Abderazzek

    2014-01-01

    The methomyl is increasingly involved in suicidal and autolytic attempts. Intoxication with carbamate (CM) compounds is still a frequent cause for admission in the Emergency department of the medical assistance center (MAC) in Tunis, Tunisia. The aim of this study was to describe the demographics, clinical features and hospital course of patients presenting with CM intoxication to the ED of MAC in Tunis, Tunisia. This was a retrospective study about 52 cases of acute poisoning by methomyl, compiled in the MAC from 1st January, 2009 to December 31, 2012. Intoxications were all oral, mostly intentional (33 cases: 65%) and in young patients (29 years old). Females outnumbered males by almost 2:1. The most frequent symptom was hypotension (41 cases: 80%), followed by miosis (39 cases: 75%), rhabdomyolysis (29 cases: 55%), vomiting (18 cases: 43%), bronchorrhea (14 cases: 27%), diarrhea (11 cases: 21%) and fasciculations (8 cases: 17%). Treatments included gastric lavage in 16 patients (32%), assisted ventilation in 8 cases (17%) and atropine in 44 patients (85%). Seven patients died during hospitalization. Pesticide poisoning is a significant public health problem and some preventive measures must be strictly enforced to limit this kind of intoxication.

  14. Human CD133+ Renal Progenitor Cells Induce Erythropoietin Production and Limit Fibrosis After Acute Tubular Injury

    PubMed Central

    Aggarwal, Shikhar; Grange, Cristina; Iampietro, Corinne; Camussi, Giovanni; Bussolati, Benedetta

    2016-01-01

    Persistent alterations of the renal tissue due to maladaptive repair characterize the outcome of acute kidney injury (AKI), despite a clinical recovery. Acute damage may also limit the renal production of erythropoietin, with impairment of the hemopoietic response to ischemia and possible lack of its reno-protective action. We aimed to evaluate the effect of a cell therapy using human CD133+ renal progenitor cells on maladaptive repair and fibrosis following AKI in a model of glycerol-induced rhabdomyolysis. In parallel, we evaluated the effect of CD133+ cells on erythropoietin production. Administration of CD133+ cells promoted the restoration of the renal tissue, limiting the presence of markers of injury and pro-inflammatory molecules. In addition, it promoted angiogenesis and protected against fibrosis up to day 60. No effect of dermal fibroblasts was observed. Treatment with CD133+ cells, but not with PBS or fibroblasts, limited anemia and increased erythropoietin levels both in renal tissue and in circulation. Finally, CD133+ cells contributed to the local production of erythropoietin, as observed by detection of circulating human erythropoietin. CD133+ cells appear therefore an effective source for cell repair, able to restore renal functions, including erythropoietin release, and to limit long term maldifferentiation and fibrosis. PMID:27853265

  15. 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.

  16. Oxidative Capacity and Fatigability in Run Trained Malignant Hyperthermia Susceptible Mice

    PubMed Central

    Rouviere, Clement; Corona, Benjamin T.; Ingalls, Christopher P.

    2011-01-01

    Introduction The purpose of this study was to test the hypothesis that Malignant Hyperthermia model mice (RyR1Y522S/wt) are more vulnerable to exercise-induced muscle injury and fatigability and adapt less to run training. Methods Following 6 weeks of voluntary wheel running, we measured anterior crural muscle fatigability, muscle injury, and cytochrome oxidase (COX) and citrate synthase (CS). Results Although RyR1Y522S/wt mice ran without experiencing MH episodes, they ran 42% less distance than wild type (WT) mice. Muscles from WT mice exhibited increased fatigue resistance and COX content after training. Muscles from RyR1Y522S/wt mice demonstrated no significant change in fatigability or COX and CS after training. However, muscles from RyR1Y522S/wt mice displayed less intrinsic fatigability and greater COX/CS content and muscle damage than WT mice. Discussion RyR1Y522S/wt mice can run without experiencing rhabdomyolysis, and their inability to adapt to training appears to stem from intrinsic enhancement of mitochondrial enzymes and fatigue resistance. PMID:22431093

  17. 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

  18. Physiologic amputation: a case study.

    PubMed

    Long, Jeri; Hall, Virginia

    2014-03-01

    Acute limb ischemia is a complication of severe peripheral arterial disease that can be a threatening limb as well as life. Multiple procedures exist today to help revascularize extremities; however, even with the latest technologies, surgical amputation of the limb may still be necessary. Cryoamputation, or physiologic amputation, is a method used to treat patients who are hemodynamically unstable for the operating room and who are in need of urgent amputation owing to arterial ischemia. This procedure is used in the rare instance where not only a persons' limb is threatened, but also their life. This is a case study regarding one patient who presented to the hospital with limb-threatening ischemia who became hemodynamically unstable owing to the rhabdomyolysis associated with the ischemia of his lower extremity. Cryoamputation was used to stabilize the patient and prevent further deterioration, so that he could safely undergo surgical amputation of the limb without an increase in mortality risk. Cryoamputation must be followed by formal surgical amputation when the patient is hemodynamically stabilized. It is not a limb salvaging, procedure but it is a life-saving procedure. This case study demonstrates the usefulness of the procedure and discusses the technique used for cryoamputation.

  19. Short- and long-term regulation of 3-hydroxy 3-methylglutaryl coenzyme A reductase by a 4-methylcoumarin.

    PubMed

    Trapani, Laura; Segatto, Marco; Simeoni, Veronica; Balducci, Valentina; Dhawan, Ashish; Parmar, Virinder S; Prasad, Ashok K; Saso, Luciano; Incerpi, Sandra; Pallottini, Valentina

    2011-07-01

    Dyslipidemia is one of the most significant risk factors for cardiovascular diseases. Cholesterol homeostasis is regulated by both the receptor-mediated endocytosis of Low Density Lipoproteins by LDL receptors and de novo cholesterol synthesis via the rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. Although statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase substrate competitors, have revolutionized the management of cardiovascular diseases by lowering serum LDL, their side effects range from myalgia to rhabdomyolysis. Treatment with antioxidant compounds could represent an efficient alternative in the modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Indeed it has already been demonstrated that the rise in reactive oxygen species levels causes the complete dephosphorylation and, in turn activation of the enzyme. Many coumarins and their derivatives have the special ability to scavenge reactive oxygen species or show a lipid lowering potential. Here we evaluated whether the coumarin, 4-methylesculetin could exert both the ability to scavenge ROS and to modulate 3-hydroxy-3-methylglutaryl coenzyme A reductase in HepG2 cell line where the enzyme activity dysregulation induced by reactive oxygen species has already been reported. The antioxidant property of 4-methylesculetin led to the reduction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activation state through the increase of the enzyme phosphorylation. In addition, this coumarin showed the ability to modulate 3-hydroxy-3-methylglutaryl coenzyme A reductase protein levels both by transcriptional and degradational events independent of its antioxidant activity.

  20. Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions.

    PubMed

    Trapani, Laura; Melli, Luca; Segatto, Marco; Trezza, Viviana; Campolongo, Patrizia; Jozwiak, Adam; Swiezewska, Ewa; Pucillo, Leopoldo Paolo; Moreno, Sandra; Fanelli, Francesca; Linari, Marco; Pallottini, Valentina

    2011-11-01

    The rate-limiting step of cholesterol biosynthetic pathway is catalyzed by 3-hydroxy-3-methylglutaryl coenzyme reductase (HGMR), whose inhibitors, the statins, widely used in clinical practice to treat hypercholesterolemia, often cause myopathy, and rarely rhabdomyolysis. All studies to date are limited to the definition of statin-induced myotoxicity omitting to investigate whether and how HMGR inhibition influences muscle functions. To this end, 3-mo-old male rats (Rattus norvegicus) were treated for 3 wk with a daily intraperitoneal injection of simvastatin (1.5 mg/kg/d), and biochemical, morphological, mechanical, and functional analysis were performed on extensor digitorum longus (EDL) muscle. Our results show that EDL muscles from simvastatin-treated rats exhibited reduced HMGR activity; a 15% shift from the fastest myosin heavy-chain (MHC) isoform IIb to the slower IIa/x; and reduced power output and unloaded shortening velocity, by 41 and 23%, respectively, without any change in isometric force and endurance. Moreover, simvastatin-treated rats showed a decrease of maximum speed reached and the latency to fall off the rotaroad (∼-30%). These results indicate that the molecular mechanism of the impaired muscle function following statin treatment could be related to the plasticity of fast MHC isoform expression.

  1. 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.

  2. SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink.

    PubMed

    Carr, D F; O'Meara, H; Jorgensen, A L; Campbell, J; Hobbs, M; McCann, G; van Staa, T; Pirmohamed, M

    2013-12-01

    This study aimed to determine whether patients with statin-induced myopathy could be identified using the United Kingdom Clinical Practice Research Datalink, whether DNA could be obtained, and whether previously reported associations of statin myopathy with the SLCO1B1 c.521T>C and COQ2 rs4693075 polymorphisms could be replicated. Seventy-seven statin-induced myopathy patients (serum creatine phosphokinase (CPK) > 4× upper limit of normal (ULN)) and 372 statin-tolerant controls were identified and recruited. Multiple logistic regression analysis showed the SLCO1B1 c.521T>C single-nucleotide polymorphism to be a significant risk factor (P = 0.009), with an odds ratio (OR) per variant allele of 2.06 (1.32-3.15) for all myopathy and 4.09 (2.06-8.16) for severe myopathy (CPK > 10× ULN, and/or rhabdomyolysis; n = 23). COQ2 rs4693075 was not associated with myopathy. Meta-analysis showed an association between c.521C>T and simvastatin-induced myopathy, although power for other statins was limited. Our data replicate the association of SLCO1B1 variants with statin-induced myopathy. Furthermore, we demonstrate how electronic medical records provide a time- and cost-efficient means of recruiting patients with severe adverse drug reactions for pharmacogenetic studies.

  3. Statin myopathy: significant problem with minimal awareness by clinicians and no emphasis by clinical investigators.

    PubMed

    Whayne, Thomas F

    2011-07-01

    High cardiovascular risk patients need reduction of low-density-lipoprotein cholesterol (LDL-C) to <70 mg/dL (1.8 mmol/L). Statins are optimal treatment but myopathy can be a limitation to their use. The incidence of statin-related myopathy is difficult to determine but up to 10.5% appears an appropriate estimate. Short-term trials report lower incidence than long-term trials. Statin-related myopathy may be influenced by genetics and tends to be dose-dependent. Ezetimibe can contribute to LDL-C reduction allowing a lower dose of statin to be used. Another approach is to administer rosuvastatin twice weekly. Statins have been shown to interfere with the cellular role of coenzyme Q10. Coenzyme Q10 supplementation may decrease or prevent statin myopathy, but this has not been proven. The occurrence of the most serious complication of myopathy-rhabdomyolysis-is very rare, but awareness of the problem, risks, and prevention are essential.

  4. [Current views on lipid metabolism: statin-induced myopathy].

    PubMed

    Teichmann, L L; Fleck, M

    2010-10-01

    Cardiovascular diseases are the most common causes of death in Germany and the prevalence is increased in patients with inflammatory rheumatic diseases. Statins are often employed for primary and secondary prophylaxis of cardiovascular events but can potentially induce myopathy as a side-effect. In addition to an asymptomatic elevation of muscle enzymes, myalgia and myositis as well as rhabdomyolysis, the most severe side-effect, have been observed, which are mostly manifested within 6 months after initiation of therapy. Statin-induced myopathy is rare but if risk factors are present, the individual risk can be much higher. Such factors are in particular interaction with other medications, statin dosage, the characteristics of the statin preparation used, comorbidities, age and sex of the patient. Regular testing of muscle enzymes after induction of statin therapy is not generally recommended for asymptomatic patients, but is indispensable when muscle symptoms appear. Statin therapy must be immediately terminated and a diagnostic evaluation must be carried out at the latest when creatine kinase values show a more than 10-fold increase.

  5. Troponin elevation after black widow spider envenomation.

    PubMed

    Bush, Sean P; Davy, J Veeran

    2015-09-01

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

  6. Cardiovascular, haematological and neurological effects of the venom of the Papua New Guinean small-eyed snake (Micropechis ikaheka) and their neutralisation with CSL polyvalent and black snake antivenoms.

    PubMed

    Tibballs, J; Kuruppu, S; Hodgson, W C; Carroll, T; Hawdon, G; Sourial, M; Baker, T; Winkel, K

    2003-11-01

    Cardiovascular and haematological effects of venom of the small-eyed Snake (Micropechis ikaheka) were examined in ventilated anaesthetised piglets. Neurotoxic effects were examined in chick biventer cervicis nerve-muscle preparations. Immunoreactivity of venom was tested against the monovalent antivenom components in a CSL Ltd Venom Detection Kit. Neutralisation was tested in vivo and in vitro with CSL Ltd polyvalent snake and Black Snake (Pseudechis australis) antivenoms. Venom in 0.1% bovine serum albumin in saline was infused into piglets in doses 1-2000 microg/kg. Pulmonary hypertension (P= 0.0007) and depression of cardiac output (P= 0.002) were observed up to 3 h after 150-160 microg/kg. The concentration of plasma free-haemoglobin increased more than 50-fold, indicating haemolysis. Neither coagulopathy nor thrombocytopenia occurred. Creatine phosphokinase and serum potassium levels did not increase suggesting absence of acute rhabdomyolysis. The venom caused post-synaptic neurotoxicty. Immunoreactivity of venom with Black Snake antivenom was observed at very high venom concentrations. Cardiovascular effects were absent and haemolysis was less after venom was pre-incubated at 37 degrees C for 30 min with polyvalent antivenom. Neutralisation by Black Snake antivenom was less effective. The neurotoxicity was neutralised by polyvalent or Black Snake antivenoms. Human envenomation may be treated with CSL Ltd polyvalent snake antivenom.

  7. Anuric renal failure in a dog after red-bellied black snake (Pseudechis porphyriacus) envenomation.

    PubMed

    Heller, J; Bosward, K L; Hodgson, D R; Pottie, R

    2006-05-01

    A case of Red-bellied Black snake envenomation resulting in intravascular haemolytic anaemia, rhabdomyolysis and anuric renal failure is described in the dog. A 12-year-old female desexed Golden Retriever was presented with a 15 hour history of profuse salivation, progressive lethargy, obtundence, inappetence and collapse. Significant findings on clinical examination were pallor, icterus, tachypnoea and dyspnoea with increased respiratory sounds and crackles in all lung fields. Generalised abdominal and muscular pain was apparent and dark red-brown urine was present around the perineal region. A diagnosis of Red-bellied Black snake (Pseudechis porphyriacus) envenomation was made and the dog was treated with intravenous fluid therapy, Tiger/Brown snake antivenom, packed red cell transfusions and Intermittent Positive Pressure Ventilation. Continued clinical deterioration occurred and a diagnosis of acute renal failure secondary to myohaemoglobinuric pigmenturia was made 12 hours after admission. Intensive treatment was attempted with diuresis and volume expansion. Oliguria and subsequent anuria ensued and the dog was euthanased due to a grave prognosis and lack of clinical response to treatment. Necropsy examination revealed muscular necrosis, accumulation of fluid in the thoracic and peritoneal cavities, and marked renal tubular necrosis with intraluminal occlusion secondary to pigmentary casts.

  8. Methamphetamine abuse.

    PubMed

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

    2007-10-15

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

  9. 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.

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

    PubMed

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

    1989-01-01

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

  11. Bowel Ischemia from Heat Stroke: A Rare Presentation of an Uncommon Complication

    PubMed Central

    Sharma, Anuj; Syed, Wajihuddin; Manocha, Divey

    2016-01-01

    A healthy 27-year-old female presented to the hospital after she collapsed an hour into her first marathon run on a hot humid day. On presentation, she was hyperthermic, encephalopathic, tachycardic, and hypotensive. On admission, she was found to have lactic acidosis, rhabdomyolysis, and acute kidney injury and was treated with cold normal saline and cooling blankets. She subsequently started having abdominal pain and bloody bowel movements. Computed tomography of the abdomen revealed ascending colon thickening. Furthermore, her lab findings showed transaminitis and elevated coagulation parameters. Due to the acute hypotensive state from the heat stroke, patient had developed bowel ischemia, ischemic hepatitis, and disseminated intravascular coagulation, all of which are uncommon complications of heat stroke. She was managed aggressively with intravenous fluid hydration with resolution of her symptoms over the course of 4 days. In addition to the uncommon complications, early presentation of this bowel ischemia despite adequate hydration in such a healthy individual is another unique aspect of the case. PMID:27840645

  12. 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.

  13. Delayed uric Acid accumulation in plasma provides additional anti-oxidant protection against iron-triggered oxidative stress after a wingate test.

    PubMed

    Souza-Junior, Tp; Lorenço-Lima, L; Ganini, D; Vardaris, Cv; Polotow, Tg; Barros, Mp

    2014-12-01

    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.

  14. Near-fatal Anorexia Nervosa in a Middle-aged Woman.

    PubMed

    Foppiani, Luca; Massobrio, Bruno; Cascio, Christian; Antonucci, Giancarlo

    2017-01-01

    Anorexia nervosa (AN) is a serious psychiatric disorder which typically occurs in young women; however, more and more cases in middle-aged women are being reported. The management of this complex disease requires a team approach, and full recovery occurs only in 50% of patients. Endocrine and metabolic complications are commonly observed, the latter of which may even be life-threatening, and require prompt and proper management. Infections, albeit reported, are not usually a major clinical problem in these patients. We herein report the case of a severely malnourished middle-aged woman with long-standing AN who was hospitalized with marked hypokalaemia (1.5 mEq/L) and rhabdomyolysis; during hospitalization she developed septic shock and acute respiratory distress syndrome, which required urgent admission to the intensive care unit. She underwent sedation and tracheal intubation for mechanical ventilation and was managed with combined therapies, which eventually led to a successful outcome. Life-threatening medical complications can occur not only in young women but in middle-aged women with AN as well and require a combined multidisciplinary approach.

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

    PubMed

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

    2014-03-01

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

  16. 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.

  17. Anaesthetic management of a child with Freeman-sheldon syndrome undergoing spinal surgery.

    PubMed

    Richa, F C; Yazbeck, P H

    2008-03-01

    Freeman-Sheldon syndrome, or distal arthrogryposis type 2A, is a rare congenital myopathy and dysplasia characterised by multiple contractures, abnormalities of the head and face, defective development of the hands and feet and skeletal malformations. The facial muscle contracture produces the typical 'whistling face' appearance. Anaesthetic issues include difficult intravenous access, difficult airway and postoperative pulmonary complications. Although an association with malignant hyperthermia has been suggested, this has not been confirmed. We report the management of a seven-year-old girl with Freeman-Sheldon syndrome undergoing anterior and posterior spinal surgery and describe a successful anaesthetic regimen based on a total intravenous anaesthesia technique with remifentanil and propofol without neuromuscular blocking agents. The child had an uneventful anaesthetic and postoperative course. We believe the presence of the myopathy warranted the use of a 'non-triggering' anaesthetic, as suxamethonium and volatile agents may be associated with significant complications such as muscle rigidity and rhabdomyolysis in myopathic patients, even in the absence of malignant hyperthermia.

  18. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-10-01

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

  1. Prostatic surgery associated acute kidney injury

    PubMed Central

    Costalonga, Elerson Carlos; Costa e Silva, Verônica Torres; Caires, Renato; Hung, James; Yu, Luis; Burdmann, Emmanuel A

    2014-01-01

    Acute kidney injury (AKI) is associated with extended hospital stays, high risks of in-hospital and long-term mortality, and increased risk of incident and progressive chronic kidney disease. Patients with urological diseases are a high-risk group for AKI owing to the coexistence of obstructive uropathy, older age, and preexistent chronic kidney disease. Nonetheless, precise data on the incidence and outcomes of postoperative AKI in urological procedures are lacking. Benign prostatic hyperplasia and prostate cancer are common diagnoses in older men and are frequently treated with surgical procedures. Whereas severe AKI after prostate surgery in general appears to be unusual, AKI associated with transurethral resection of the prostate (TURP) syndrome and with rhabdomyolysis (RM) after radical prostatectomy have been frequently described. The purpose of this review is to discuss the current knowledge regarding the epidemiology, risk factors, outcomes, prevention, and treatment of AKI associated with prostatic surgery. The mechanisms of TURP syndrome and RM following prostatic surgeries will be emphasized. PMID:25374813

  2. 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.

  3. The propofol infusion 'syndrome' in intensive care unit: from pathophysiology to prophylaxis and treatment.

    PubMed

    Papaioannou, V; Dragoumanis, C; Theodorou, V; Pneumatikos, I

    2008-01-01

    Propofol is a short-acting intravenous anesthetic agent widely used for sedation in anesthesia and intensive care. However, during the last 15 years there have been quite a lot of publications reporting unexplained deaths among pediatric and adult critically ill patients. These cases shared common symptoms and signs unrelated with initial admission diagnosis and were under long-term propofol infusion at high doses. A new syndrome called 'propofol infusion syndrome' was defined, including cardiovascular instability, metabolic acidosis, hyperkalaemia and rhabdomyolysis, with no evidence for other known causes of myocardial failure. One common denominator in these patients was the presence of hypoxia and tissue hypoperfusion. It seems that during states of increased metabolic demand, the reduced energy production related to an inhibitory propofol action at the level of mitochondrial oxidative phosphorylation and lipid metabolism may lead to the manifestation of the syndrome. Furthermore, cases of early toxicity due to failure in cellular energy production with development of lactic acidosis have been also described during anesthesia. For the above reasons, recommendations for the limitation of propofol use have been devised by various institutions, whereas physicians need to be cautious when using prolonged propofol sedation and alert for early signs of toxicity.

  4. 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.

  5. Thiocolchicoside: review of adverse effects.

    PubMed

    2016-02-01

    Thiocolchicoside has long been used as a muscle relaxant, despite a lack of proven efficacy beyond the placebo effect. Its chemical structure consists of colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its adverse effects are therefore likely to be similar to those of colchicine. Using the standard Prescrire methodology, we reviewed the available data on the adverse effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.

  6. Chemical and toxicological investigations of a previously unknown poisonous European mushroom Tricholoma terreum.

    PubMed

    Yin, Xia; Feng, Tao; Shang, Jian-Hua; Zhao, Yun-Li; Wang, Fang; Li, Zheng-Hui; Dong, Ze-Jun; Luo, Xiao-Dong; Liu, Ji-Kai

    2014-06-02

    The established tradition of consuming and marketing wild mushrooms has focused attention on mycotoxicity, which has become a global issue. In the present study, we describe the toxins found in a previously unknown poisonous European mushroom Tricholoma terreum. Fifteen new triterpenoids terreolides A-F (1-6) and saponaceolides H-P (8-16) were isolated from the fruiting bodies of the toxic mushroom T. terreum. Terreolides A-C (1-3) possessed a unique 5/6/7 trioxaspiroketal system, whereas terreolides D-F (4-6) possessed an unprecedented carbon skeleton. Two abundant compounds in the mushroom, saponaceolide B (7) and saponaceolide M (13), displayed acute toxicity, with LD50 values of 88.3 and 63.7 mg kg(-1) when administered orally in mice. Both compounds were found to increase serum creatine kinase levels in mice, indicating that T. terreum may be the cause of mushroom poisoning ultimately leading to rhabdomyolysis.

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

    PubMed

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

    2014-12-01

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

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

    PubMed

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

    2010-12-01

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

  10. Sixteen years of severe Tiger snake (Notechis) envenoming in Perth, Western Australia.

    PubMed

    Scop, J; Little, M; Jelinek, G A; Daly, F F S

    2009-07-01

    We aimed to describe the characteristics, clinical course, management and outcome of patients presenting to Perth teaching hospitals after envenoming by Tiger snakes. We undertook a chart review from six Perth teaching hospitals over a 16 year period from 1990 to 2005. Data were collected by a trained investigator using a preformatted data abstraction tool. We included patients bitten in the appropriate geographical area, with defibrination coagulopathy and positive Venom Detection Kit result for Tiger snake or response to specific antivenom. Of 381 charts reviewed, 23 patients were envenomed by a Tiger snake. The mean age was 36 years, 83% were male and all were bitten on a limb. First aid was applied poorly and all patients were symptomatic on presentation. Six patients developed rhabdomyolysis, one renal failure, four clinical bleeding, three neurotoxicity, one non-fatal respiratory arrest and one fatal cardiac arrest. All patients received antivenom, 13 received adrenaline premedication, with two mild allergic reactions developing in non-premedicated patients. The average dose of antivenom was four ampoules. Mean hospital stay was 2.6 days. This is the largest series of Tiger snake envenoming reported in Australia. Only one patient of 23 (4%) died, despite all patients being significantly envenomed. With rapid antivenom treatment and modem emergency and intensive care management, most patients envenomed by Tiger snakes survive.

  11. Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions

    PubMed Central

    Garone, Caterina; Bordoni, Andreina; Gutierrez Rios, Purificacion; Calvo, Sarah E.; Ripolone, Michela; Ranieri, Michela; Rizzuti, Mafalda; Villa, Luisa; Magri, Francesca; Corti, Stefania; Bresolin, Nereo; Mootha, Vamsi K.; Moggio, Maurizio; DiMauro, Salvatore; Comi, Giacomo P.; Sciacco, Monica

    2012-01-01

    The molecular diagnosis of mitochondrial disorders still remains elusive in a large proportion of patients, but advances in next generation sequencing are significantly improving our chances to detect mutations even in sporadic patients. Syndromes associated with mitochondrial DNA multiple deletions are caused by different molecular defects resulting in a wide spectrum of predominantly adult-onset clinical presentations, ranging from progressive external ophthalmoplegia to multi-systemic disorders of variable severity. The mutations underlying these conditions remain undisclosed in half of the affected subjects. We applied next-generation sequencing of known mitochondrial targets (MitoExome) to probands presenting with adult-onset mitochondrial myopathy and harbouring mitochondrial DNA multiple deletions in skeletal muscle. We identified autosomal recessive mutations in the DGUOK gene (encoding mitochondrial deoxyguanosine kinase), which has previously been associated with an infantile hepatocerebral form of mitochondrial DNA depletion. Mutations in DGUOK occurred in five independent subjects, representing 5.6% of our cohort of patients with mitochondrial DNA multiple deletions, and impaired both muscle DGUOK activity and protein stability. Clinical presentations were variable, including mitochondrial myopathy with or without progressive external ophthalmoplegia, recurrent rhabdomyolysis in a young female who had received a liver transplant at 9 months of age and adult-onset lower motor neuron syndrome with mild cognitive impairment. These findings reinforce the concept that mutations in genes involved in deoxyribonucleotide metabolism can cause diverse clinical phenotypes and suggest that DGUOK should be screened in patients harbouring mitochondrial DNA deletions in skeletal muscle. PMID:23043144

  12. LC-MS/MS analysis of palytoxin analogues in blue humphead parrotfish Scarus ovifrons causing human poisoning in Japan.

    PubMed

    Suzuki, Toshiyuki; Watanabe, Ryuichi; Matsushima, Ryoji; Ishihara, Kenji; Uchida, Hajime; Kikutsugi, Saori; Harada, Tomoko; Nagai, Hiroshi; Adachi, Masao; Yasumoto, Takeshi; Murata, Masakazu

    2013-01-01

    Since 1953, a total of 27 human poisoning cases caused by the consumption of blue humphead parrotfish, Scarus ovifrons, have been reported in Japan. Characteristic symptoms are severe muscle pain associated with rhabdomyolysis. Although it is believed that palytoxin, which is one of the most potent non-protein marine biotoxins, is the most likely causative toxin in blue humphead parrotfish poisoning, palytoxin has not been proven conclusively as the causative toxin because of lack of a reliable and sensitive analytical method for palytoxin. In 2011, human poisoning cases caused by the consumption of blue humphead parrotfish occurred in Miyazaki and Tokyo. In our present study, an LC-MS/MS method for palytoxin and its analogues in the blue humphead parrotfish samples causing the human poisoning cases in 2011 was developed and the samples were analysed by using the newly developed LC-MS/MS method. Palytoxin and its analogues were not detected in the samples from the food poisoning cases. The LC-MS/MS findings therefore do not support the recently accepted hypothesis that palytoxin is the causative agent in blue humphead parrotfish poisoning in Japan.

  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.

  14. Changing a limb muscle growth program into a resorption program

    PubMed Central

    Cai, Liquan; Das, Biswajit; Brown, Donald D.

    2007-01-01

    Summary Transgenic Xenopus laevis tadpoles that express a dominant negative form of the thyroid hormone receptor (TRDN) controlled by the cardiac actin muscle promoter (pCar) develop with very little limb muscle. Under the control of the tetracycline system the transgene can be induced at will by adding doxycycline to the rearing water. Pre existing limb muscle fibers begins to disintegrate within 2 days after up-regulation of the TRDN transgene. The muscle cells do not die even after weeks of transgene exposure when the myofibrils have degenerated completely and the tadpole is nearing death. A micro array analysis after 2 weeks of exposure to the transgene identified 25 muscle genes whose expression was altered in such a way that they might cause the muscle phenotype. These candidate genes are normally activated in growing limb muscle but they are repressed by the TRDN transgene. Several of these genes have been implicated in mammalian myopathies. However, the expression of only one of these genes, calsequestrin, is down regulated in 48 hrs and therefore might initiate the degeneration. Calsequestrin is one of several affected genes that encode proteins involved in calcium sequestration, transport and utilization in muscle suggesting that uncontrolled calcium influx into the growing limb muscle fibers causes rhabdomyolysis. Many of the same genes that are down regulated in the tail at the peak of metamorphic climax just before it is resorbed are suppressed in the transgenic limb muscle in effect turning the limb growth program into a tail resorption program. PMID:17234173

  15. Mimicry between mitochondrial disorder and multiple sclerosis.

    PubMed

    Finsterer, Josef; Höftberger, Romana; Stöllberger, Claudia; Rolinski, Boris

    2012-06-01

    Under certain conditions or at certain stages of the disease course, multiple sclerosis (MS) and mitochondrial disorder (MID) may be differential diagnoses and thus may be confused with each other. In a 30 years old female MS was diagnosed at age 16 year upon recurrent sensory disturbances of the right lower leg, an "inflammatory" cerebrospinal fluid, and a cerebral MRI with multiple non-enhancing white matter lesions. Steroids were repeatedly given but because of rapid deterioration treatment was switched to interferon and mitoxantrone, without improvement. Fourteen years after onset the patient additionally presented with a history of rhabdomyolysis, hypothyroidism, ophthalmoparesis, anarthria, tetraspasticity, tetraparesis, and joint contractures. After MID had been diagnosed in her mother she was re-evaluated and elevated resting lactate, axonal polyneuropathy, and empty sella were additionally found. Muscle biopsy revealed myophagy, fat deposition, and type-II predominance, and biochemical investigations showed a deficiency of complex I and IV of the respiratory chain. MID was diagnosed also in the index patient. It is concluded that even if CSF investigations or imaging studies suggest MS, differentials such as MIDs need to be excluded before prescribing medication possibly toxic to a MID. An "inflammatory CSF" may also occur in MIDs.

  16. 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

  17. 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.

  18. 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

  19. 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

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

    PubMed Central

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

    2015-01-01

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

  1. Metabolic neuropathies and myopathies.

    PubMed

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

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

  2. Animal models of acute renal failure.

    PubMed

    Singh, Amrit Pal; Junemann, Anselm; Muthuraman, Arunachalam; Jaggi, Amteshwar Singh; Singh, Nirmal; Grover, Kuldeep; Dhawan, Ravi

    2012-01-01

    The animal models are pivotal for understanding the characteristics of acute renal failure (ARF) and development of effective therapy for its optimal management. Since the etiology for induction of renal failure is multifold, therefore, a large number of animal models have been developed to mimic the clinical conditions of renal failure. Glycerol-induced renal failure closely mimics the rhabdomyolysis; ischemia-reperfusion-induced ARF simulate the hemodynamic changes-induced changes in renal functioning; drug-induced such as gentamicin, cisplatin, NSAID, ifosfamide-induced ARF mimics the renal failure due to clinical administration of respective drugs; uranium, potassium dichromate-induced ARF mimics the occupational hazard; S-(1,2-dichlorovinyl)-L-cysteine-induced ARF simulate contaminated water-induced renal dysfunction; sepsis-induced ARF mimics the infection-induced renal failure and radiocontrast-induced ARF mimics renal failure in patients during use of radiocontrast media at the time of cardiac catheterization. Since each animal model has been created with specific methodology, therefore, it is essential to describe the model in detail and consequently interpret the results in the context of a specific model.

  3. 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

  4. Near-fatal Anorexia Nervosa in a Middle-aged Woman

    PubMed Central

    Foppiani, Luca; Massobrio, Bruno; Cascio, Christian; Antonucci, Giancarlo

    2017-01-01

    Anorexia nervosa (AN) is a serious psychiatric disorder which typically occurs in young women; however, more and more cases in middle-aged women are being reported. The management of this complex disease requires a team approach, and full recovery occurs only in 50% of patients. Endocrine and metabolic complications are commonly observed, the latter of which may even be life-threatening, and require prompt and proper management. Infections, albeit reported, are not usually a major clinical problem in these patients. We herein report the case of a severely malnourished middle-aged woman with long-standing AN who was hospitalized with marked hypokalaemia (1.5 mEq/L) and rhabdomyolysis; during hospitalization she developed septic shock and acute respiratory distress syndrome, which required urgent admission to the intensive care unit. She underwent sedation and tracheal intubation for mechanical ventilation and was managed with combined therapies, which eventually led to a successful outcome. Life-threatening medical complications can occur not only in young women but in middle-aged women with AN as well and require a combined multidisciplinary approach. PMID:28154278

  5. Skeletal muscle involvement in falciparum malaria: biochemical and ultrastructural study.

    PubMed

    Davis, T M; Pongponratan, E; Supanaranond, W; Pukrittayakamee, S; Helliwell, T; Holloway, P; White, N J

    1999-10-01

    Biochemical evidence of skeletal muscle damage is common in malaria, but rhabdomyolysis appears to be rare. To investigate the relationship between serum creatine kinase and myoglobin levels, muscle histology, and renal function in Plasmodium falciparum infections, we studied 13 patients with uncomplicated malaria, 13 with severe noncerebral malaria, and 10 with cerebral malaria. A muscle biopsy specimen was obtained from each patient for light microscopy and electron microscopy. Mean serum creatine kinase concentrations +/- SD were raised but similar for the three groups (258 +/- 277, 149 +/- 158, and 203 +/- 197 U/L, respectively; P = .5). The mean serum myoglobin level +/- SD was highest in cerebral malaria (457 +/- 246 vs. 170 +/- 150 and 209 +/- 125 ng/mL in uncomplicated and severe malaria, respectively; P < .01) and correlated with the mean serum creatinine level (r = .39 for 36 patients; P = .02). The number of intravascular parasites, proportion of mature forms, and glycogen depletion were highest in biopsy specimens from patients with cerebral malaria. Myonecrosis was not observed. Muscle appears to be an important site for P. falciparum sequestration, which could contribute to metabolic and renal complications.

  6. 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

  7. 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.

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

    PubMed

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

    2014-08-05

    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.

  9. Does the traditional snakebite severity score correctly classify envenomated patients?

    PubMed Central

    Kang, Seungho; Moon, Jeongmi; Chun, Byeongjo

    2016-01-01

    Objective This study aims to help set domestic guidelines for administration of antivenom to envenomated patients after snakebites. Methods This retrospective observational case series comprised 128 patients with snake envenomation. The patients were divided into two groups according to the need for additional antivenom after the initial treatment based on the traditional snakebite severity grading scale. One group successfully recovered after the initial treatment and did not need any additional antivenom (n=85) and the other needed an additional administration of antivenom (n=43). Results The group requiring additional administration of antivenom showed a higher local effect score and a traditional snakebite severity grade at presentation, a shorter prothrombin and activated partial prothrombin time, a higher frequency of rhabdomyolysis and disseminated intravascular coagulopathy, and longer hospitalization than the group that did not need additional antivenom. The most common cause for additional administration was the progression of local symptoms. The independent factor that was associated with the need for additional antivenom was the local effect pain score (odds ratio, 2.477; 95% confidence interval, 1.309 to 4.689). The optimal cut-off value of the local effect pain score was 1.5 with 62.8% sensitivity and 71.8% specificity. Conclusion When treating patients who are envenomated by a snake, and when using the traditional snakebite severity scale, the local effect pain score should be taken into account. If the score is more than 2, additional antivenom should be considered and the patient should be frequently assessed. PMID:27752613

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

    PubMed Central

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

    1999-01-01

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

  11. Estimated prevalence of the Type 1 Polysaccharide Storage Myopathy mutation in selected North American and European breeds.

    PubMed

    McCue, M E; Anderson, S M; Valberg, S J; Piercy, R J; Barakzai, S Z; Binns, M M; Distl, O; Penedo, M C T; Wagner, M L; Mickelson, J R

    2010-12-01

    The GYS1 gene mutation that is causative of Type 1 Polysaccharide Storage Myopathy (PSSM) has been identified in more than 20 breeds of horses. However, the GYS1 mutation frequency or Type 1 PSSM prevalence within any given breed is unknown. The purpose of this study was to determine the frequency of the GYS1 mutation and prevalence of genetic susceptibility to Type 1 PSSM in selected breeds from Europe and North America. The GYS1 mutation was detected in 11 breeds, including, in order of increasing allele frequency, Shires, Morgans, Appaloosas, Quarter Horses, Paints, Exmoor Ponies, Saxon-Thuringian Coldbloods, South German Coldbloods, Belgians, Rhenish German Coldbloods and Percherons. The prevalence of genetic susceptibility to Type 1 PSSM in these breeds varied from 0.5% to 62.4%. The GYS1 mutation was not found in the sampled Thoroughbreds, Akhal-Tekes, Connemaras, Clydesdales, Norwegian Fjords, Welsh Ponies, Icelandics, Schleswig Coldbloods or Hanoverians, but failure to detect the mutation does not guarantee its absence. This knowledge will help breed associations determine whether they should screen for the GYS1 mutation and will alert veterinarians to a possible differential diagnosis for muscle pain, rhabdomyolysis or gait abnormalities.

  12. 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.

  13. Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens.

    PubMed

    Halberstadt, Adam L

    2017-01-18

    Serotonergic hallucinogens induce profound changes in perception and cognition. The characteristic effects of hallucinogens are mediated by 5-HT2A receptor activation. One class of hallucinogens are 2,5-dimethoxy-substituted phenethylamines, such as the so-called 2C-X compounds 2,5-dimethoxy-4-bromophenethylamine (2C-B) and 2,5-dimethoxy-4-iodophenethylamine (2C-I). Addition of an N-benzyl group to phenethylamine hallucinogens produces a marked increase in 5-HT2A-binding affinity and hallucinogenic potency. N-benzylphenethylamines ("NBOMes") such as N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (25I-NBOMe) show subnanomolar affinity for the 5-HT2A receptor and are reportedly highly potent in humans. Several NBOMEs have been available from online vendors since 2010, resulting in numerous cases of toxicity and multiple fatalities. This chapter reviews the structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of members of the NBOMe hallucinogen class. Based on a review of 51 cases of NBOMe toxicity reported in the literature, it appears that rhabdomyolysis is a relatively common complication of severe NBOMe toxicity, an effect that may be linked to NBOMe-induced seizures, hyperthermia, and vasoconstriction.

  14. Statin-induced Myopathy.

    PubMed

    Fitzgerald, Kara; Redmond, Elizabeth; Harbor, Cathryn

    2012-05-01

    Heart disease (HD) is the number one killer in the United States.(1) In 2006, the direct and indirect costs associated with cardiovascular disease in the United States were estimated at 400 billion dollars.(2) Statin therapy for cholesterol reduction is a mainstay intervention for cardiovascular disease (CVD) as reflected in atorvastatin's status as the number one prescribed medication in the United States.(3) Statin therapy, however, is also associated with side effects that signal mitochondrial distress. A commonly reported statin-induced symptom is myalgia, which is defined as muscle pain without an associated elevation of serum creatine kinase (CK). In clinical trials, the reports of myalgia vary from less than 1% to 25% of patients.(4) Myopathy is a general term defined as an abnormal condition or disease of muscle tissue. Myopathy includes myalgia, myositis (inflammation of muscle tissue associated with elevated CK) and the very serious condition rhabdomyolysis (extreme myositis). Histological findings in statin-induced myopathy demonstrate electron chain dysfunction making "mitochondrial myopathy" the more precise term.(5) Mitochondrial myopathy has been associated with statin-induced CoQ10 depletion.(5) Given the density of mitochondria in cardiomyocytes, and CoQ10's role in mitochondrial energy production, depletion has long been associated with increased risk for heart disease.(6-7) In the case below, mitochondrial-specific organic acids, serum CoQ10, vitamin D and clinical history all suggest statin-induced mitochondrial myopathy, despite normal serum CK.

  15. 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

  16. Curcumin: An effective adjunct in patients with statin-associated muscle symptoms?

    PubMed

    Sahebkar, Amirhossein; Saboni, Nikou; Pirro, Matteo; Banach, Maciej

    2017-02-01

    In spite of the unequivocal efficacy of statins in reducing primary and secondary cardiovascular events, the use of these drugs in a considerable number of patients is limited because of statin intolerance, mainly statin-associated muscle symptoms (SAMS). SAMS encompass a broad spectrum of clinical presentations, including mild muscular aching and other types of myalgias, myopathy with the significant elevation of creatine kinase, and the rare but life-threatening rhabdomyolysis. Among several pathophysiologic mechanisms of SAMS, mitochondrial dysfunction is thought to be one of the main one. Curcumin is the polyphenolic ingredient of Curcuma longa L., which has various pharmacological properties against a vast range of diseases. Curcumin has several mechanisms of actions relevant to the treatment of SAMS. These effects include the capacity to prevent and reduce delayed onset muscle soreness by blocking the nuclear factor inflammatory pathway, attenuation of muscular atrophy, enhancement of muscle fibre regeneration following injury, and analgesic and antioxidant effects. Curcumin can also increase the levels of cyclic adenosine monophosphate, which leads to an increase in the number of mitochondrial DNA duplicates in skeletal muscle cells. Finally, owing to its essential lipid-modifying properties, curcumin might serve as an adjunct to statin therapy in patients with SAMS, allowing for effective lowering of low-density lipoprotein cholesterol and possibly for statin dose reduction. Owing to the paucity of effective treatments, and the safety of curcumin in clinical practice, proof-of-concept trials are recommended to assess the potential benefit of this phytochemical in the treatment of SAMS.

  17. Skin manifestations in ultra-marathon runners: experience in the Marathon des Sables 2014.

    PubMed

    Descamps, V; Claessens, Y-E; Doumenc, B

    2016-11-18

    Ultra-marathons are becoming increasingly popular (1). In 2014 (4(th) to 14(th) April), the 29(th) Sultan Marathon des Sables (MDS) took place in Morocco. Overall, 1100 runners, men and women aged 16 to 80, met this challenge. Their goal was an endurance race of around 250 km in 5 self-sufficient stages in the desert over 6 days. Each runner carried their own rucksack of 7-10 kg with all of the necessary equipment and food (except water). Ultra-marathons are associated with well-known problems including dehydration, changes in body mass, loss of skeletal muscle mass, rhabdomyolysis with renal failure, and an increase in total body water. Lower limb and foot injuries are frequent in ultra-marathon runners, but specific skin manifestations may occur as a consequence of the extreme conditions of the MDS: high temperature with high rate of perspiration and salt loss, sun exposure, and contact with the sand. This article is protected by copyright. All rights reserved.

  18. Normal results of post-race thallium-201 myocardial perfusion imaging in marathon runners with elevated serum MB creatine kinase levels

    SciTech Connect

    Siegel, A.J.; Silverman, L.M.; Holman, B.L.

    1985-10-01

    Elevated cardiac enzyme values in asymptomatic marathon runners after competition can arise from skeletal muscle through exertional rhabdomyolysis, silent injury to the myocardium, or a combined tissue source. Peak post-race levels of the MB isoenzyme of creatine kinase are similar to values in patients with acute myocardial infarction. Previously reported normal results of infarct-avid myocardial scintigraphy with technetium 99m pyrophosphate in runners after competition suggest a non-cardiac source but cannot exclude silent injury to the myocardium. Therefore, thallium 201 myocardial perfusion imaging was performed in runners immediately after competition together with determination of sequential cardiac enzyme levels. Among 15 runners tested, the average peak in serum MB creatine kinase 24 hours after the race was 128 IU/liter with a cumulative MB creatine kinase release of 117 IU/liter; these values are comparable to those in patients with acute transmural myocardial infarction. Thallium 201 myocardial scintigraphic results were normal in five runners randomly selected from those who volunteered for determination of sequential blood levels. It is concluded that elevations of serum MB creatine kinase in marathon runners arise from a skeletal muscle source and that thallium 201 myocardial scintigraphy is useful to assess runners for myocardial injury when clinical questions arise.

  19. 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

  20. 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

  1. AICAR prevents heat-induced sudden death in RyR1 mutant mice independent of AMPK activation.

    PubMed

    Lanner, Johanna T; Georgiou, Dimitra K; Dagnino-Acosta, Adan; Ainbinder, Alina; Cheng, Qing; Joshi, Aditya D; Chen, Zanwen; Yarotskyy, Viktor; Oakes, Joshua M; Lee, Chang Seok; Monroe, Tanner O; Santillan, Arturo; Dong, Keke; Goodyear, Laurie; Ismailov, Iskander I; Rodney, George G; Dirksen, Robert T; Hamilton, Susan L

    2012-01-08

    Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation that is associated with malignant hyperthermia in humans, die when exposed to short periods of temperature elevation (≥37 °C). We show here that treatment with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) prevents this heat-induced sudden death in this mouse model. The protection by AICAR is independent of AMP-activated protein kinase (AMPK) activation and results from a newly identified action of the compound on mutant Ryr1 to reduce Ca(2+) leak from the sarcoplasmic reticulum to the sarcoplasm. AICAR thus prevents Ca(2+)-dependent increases in the amount of both reactive oxygen species (ROS) and reactive nitrogen species (RNS) that act to further increase resting Ca(2+) concentrations. If unchecked, the temperature-driven increases in resting Ca(2+) concentrations and the amounts of ROS and RNS create an amplifying cycle that ultimately triggers sustained muscle contractions, rhabdomyolysis and death. Although antioxidants are effective in reducing this cycle in vitro, only AICAR prevents heat-induced death in vivo. Our findings suggest that AICAR is probably effective in prophylactic treatment of humans with enhanced susceptibility to exercise- and/or heat-induced sudden death associated with RYR1 mutations.

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

    PubMed

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

    2009-06-01

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

  3. [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.

  4. Clinical and forensic signs related to cocaine abuse.

    PubMed

    Dinis-Oliveira, Ricardo Jorge; Carvalho, Félix; Duarte, José Alberto; Proença, Jorge Brandão; Santos, Agostinho; Magalhães, Teresa

    2012-03-01

    Good laboratory practice in toxicological analysis requires pre-analytical steps for collection of detailed information related to the suspected poisoning episodes, including biological and non-biological circumstantial evidences, which should be carefully scrutinized. This procedure provides great help to unveil the suspected cause of poisoning, to select the appropriate and correct samples to be analyzed and can facilitate the decision about the analytical techniques to perform. This implies a good knowledge of the signs related to acute and chronic intoxications by drugs of abuse. In this manuscript we highlight and discuss clinical and forensic imaging related to cocaine abuse, namely the midline destructive lesion, dental health, pseudoscleradermatous triad and crack hands, necrosis and gangrene of extremities and several other skin manifestations, reticular purpura, intracerebral and peripheral hemorrhages, angioneurotic edema, rhabdomyolysis, and crack lung. For this purpose, the state of the art on this topic is discussed, using clinical and forensic cases from our professional database in complement to images and mechanistic data from literature.

  5. Ascorbate removes key precursors to oxidative damage by cell-free haemoglobin in vitro and in vivo.

    PubMed

    Dunne, Jacqueline; Caron, Alexis; Menu, Patrick; Alayash, Abdu I; Buehler, Paul W; Wilson, Michael T; Silaghi-Dumitrescu, Radu; Faivre, Beatrice; Cooper, Chris E

    2006-11-01

    Haemoglobin initiates free radical chemistry. In particular, the interactions of peroxides with the ferric (met) species of haemoglobin generate two strong oxidants: ferryl iron and a protein-bound free radical. We have studied the endogenous defences to this reactive chemistry in a rabbit model following 20% exchange transfusion with cell-free haemoglobin stabilized in tetrameric form [via cross-linking with bis-(3,5-dibromosalicyl)fumarate]. The transfusate contained 95% oxyhaemoglobin, 5% methaemoglobin and 25 microM free iron. EPR spectroscopy revealed that the free iron in the transfusate was rendered redox inactive by rapid binding to transferrin. Methaemoglobin was reduced to oxyhaemoglobin by a slower process (t(1/2) = 1 h). No globin-bound free radicals were detected in the plasma. These redox defences could be fully attributed to a novel multifunctional role of plasma ascorbate in removing key precursors of oxidative damage. Ascorbate is able to effectively reduce plasma methaemoglobin, ferryl haemoglobin and globin radicals. The ascorbyl free radicals formed are efficiently re-reduced by the erythrocyte membrane-bound reductase (which itself uses intra-erythrocyte ascorbate as an electron donor). As well as relating to the toxicity of haemoglobin-based oxygen carriers, these findings have implications for situations where haem proteins exist outside the protective cell environment, e.g. haemolytic anaemias, subarachnoid haemorrhage, rhabdomyolysis.

  6. Disturbance of mitochondrial functions provoked by the major long-chain 3-hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies in skeletal muscle.

    PubMed

    Cecatto, Cristiane; Godoy, Kálita Dos Santos; da Silva, Janaína Camacho; Amaral, Alexandre Umpierrez; Wajner, Moacir

    2016-10-01

    The pathogenesis of the muscular symptoms and recurrent rhabdomyolysis that are commonly manifested in patients with mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiencies is still unknown. In this study we investigated the effects of the major long-chain monocarboxylic 3-hydroxylated fatty acids (LCHFA) accumulating in these disorders, namely 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, on important mitochondrial functions in rat skeletal muscle mitochondria. 3HTA and 3HPA markedly increased resting (state 4) and decreased ADP-stimulated (state 3) and CCCP-stimulated (uncoupled) respiration. 3HPA provoked similar effects in permeabilized skeletal muscle fibers, validating the results obtained in purified mitochondria. Furthermore, 3HTA and 3HPA markedly diminished mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded mitochondria. Mitochondrial permeability transition (mPT) induction probably underlie these effects since they were totally prevented by cyclosporin A and ADP. In contrast, the dicarboxylic analogue of 3HTA did not alter the tested parameters. Our data strongly indicate that 3HTA and 3HPA behave as metabolic inhibitors, uncouplers of oxidative phosphorylation and mPT inducers in skeletal muscle. It is proposed that these pathomechanisms disrupting mitochondrial homeostasis may be involved in the muscle alterations characteristic of MTP and LCHAD deficiencies.

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

    PubMed

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

    1994-05-01

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

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

    PubMed

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

    2015-03-01

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

  9. A clinician's guide to statin drug-drug interactions.

    PubMed

    Kellick, Kenneth A; Bottorff, Michael; Toth, Peter P; The National Lipid Association's Safety Task Force

    2014-01-01

    The statins are widely used worldwide to reduce risk for cardiovascular events in both the primary and secondary prevention settings. Although generally quite safe, the statins can be associated with a variety of serious side adverse effects, including myalgia, myopathy, and changes in plasma enzymes of hepatic origin. Although rare, the most serious of these is rhabdomyolysis. Several drugs can interfere with the metabolism and disposal of the statins, thereby increasing risk for adverse events. It is important that clinicians treating patients with statins be aware of the potential for drug-drug interactions between each statin and specific other drugs and take measures to prevent them. The prediction of potential drug-drug interactions derives from basic pharmacokinetic principles. Certain drug interactions are predicted by measuring the effect of interacting drugs on blood plasma concentrations of the statin. Individual patient variations resulting in part from polymorphisms in the metabolizing enzymes confound some of these predictions. Based on these known effects, a new classification for predicting statin drug interactions is proposed. This report discusses likely prescription and nonprescription interactions as well as potential alternatives for special populations.

  10. Ciprofloxacin strongly inhibits clozapine metabolism: two case reports.

    PubMed

    Brouwers, E E M; Söhne, M; Kuipers, S; van Gorp, E C M; Schellens, J H M; Koks, C H W; Beijnen, J H; Huitema, A D R

    2009-01-01

    We report on two cases of drug-drug interactions between ciprofloxacin and clozapine. The first case was a 46-year-old male patient receiving a daily dose of clozapine 900 mg. He was admitted to hospital with urosepsis and was treated with a 5-day course of ciprofloxacin and amoxicillin. Two days after completion of antibacterial therapy, the patient developed symptoms of rhabdomyolysis. Clozapine therapy was discontinued and measurement of the patient's clozapine plasma concentration 1 day after cessation of clozapine therapy and 3 days after cessation of ciprofloxacin treatment showed that it was in excess of recommended therapeutic levels. The second patient was a 58-year-old male patient treated with a daily dose of clozapine 300 mg. He was admitted to hospital because of delirium and suspected urinary tract infection or pneumonia. Treatment with ciprofloxacin was initiated. Measurement of clozapine plasma concentrations prior to and 3 days after commencement of ciprofloxacin showed that clozapine concentrations doubled over that time period. We suggest that inhibition of cytochrome P450 (CYP) enzymes 1A2 and 3A4 by ciprofloxacin resulted in delayed clozapine metabolism and elevated clozapine plasma concentrations. This might cause severe adverse effects. We advise using another antibacterial agent or reducing the clozapine dose and monitoring clozapine levels when this antipsychotic agent is used in combination with ciprofloxacin.

  11. 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.

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

    PubMed

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

    2016-02-01

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

  13. Who is the real killer? Chlorfenapyr or detergent micelle-chlorfenapyr complex?

    PubMed

    Periasamy, Srinivasan; Deng, Jou-Fang; Liu, Ming-Yie

    2016-10-03

    1. Chlorfenapyr [4-bromo-2-(4-chlorophenyl)-1-(ethoxymethl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile] is a commonly employed pesticide throughout the world. The mechanism of chlorfenapyr action is to uncouple oxidative phosphorylation in the mitochondria. The characteristic features of chlorfenapyr intoxication are high fever, rhabdomyolysis and neurologic symptoms that gradually get worse until death. 2. In recent years, suicide attempt cases using commercial chlorfenapyr pesticide were reported. Even small doses of commercial chlorfenapyr pesticide intoxication caused human fatality. However, world health organization (WHO) has classified chlorfenapyr as class 2-moderately hazardous chemical. Animal studies using technical grade (94.5%; AC 7504-59A) chlorfenapyr in 0.5% carboxy methyl cellulose as the vehicle, single dose through oral route in male rats were well tolerated. 3. We planned a therapeutic strategy for suicidal chlorfenapyr intoxication, therefore we evaluated the three different toxic doses of chlorfenapyr (10% chlorfenapyr and 90% detergent) through oral route in male rats for human extrapolation. The major difference between the technical grade chlorfenapyr and commercial grade chlorfenapyr was the vehicle. In the technical grade chlorfenapyr study, 0.5% carboxy methyl cellulose was used as a vehicle, whereas in the present study 90% detergent acted as a vehicle. The LD50 of commercial grade chlorfenapyr-40.63 mg/kg bw, which was approximately tenfold decrease than technical grade chlorfenapyr, LD50 - 441 mg/kg bw. 4. The combination of chlorfenapyr and detergent, a deadly cocktail to form micelle complex that can greatly influence bioavailability by attaching to biological membranes in vivo. To conclude, the enhanced bioavailability of chlorfenapyr by the detergent causes the fatality in suicidal attempts using chlorfenapyr.

  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.

  15. Safety of rosuvastatin.

    PubMed

    Shepherd, James; Hunninghake, Donald B; Stein, Evan A; Kastelein, John J P; Harris, Susan; Pears, John; Hutchinson, Howard G

    2004-10-01

    The safety and tolerability of rosuvastatin were assessed (as of August 2003) using data from 12,400 patients who received 5 to 40 mg of rosuvastatin in a multinational phase II/III program, which represented 12,212 patient-years of continuous exposure to rosuvastatin. An integrated database was used to examine adverse events and laboratory data. In placebo-controlled trials, adverse events, irrespective of causality assessment, occurred in 57.4% of patients who received 5 to 40 mg of rosuvastatin (n = 744) and 56.8% of patients who received placebo (n = 382). In fixed-dose trials with comparator statins, 5 to 40 mg of rosuvastatin showed an adverse event profile similar to those for 10 to 80 mg of atorvastatin, 10 to 80 mg of simvastatin, and 10 to 40 mg of pravastatin. Clinically significant elevations in alanine aminotransferase (>3 times the upper limit of normal) and creatine kinase (>10 times the upper limit of normal) were uncommon (10 times the upper limit of normal with muscle symptoms) that was possibly related to treatment occurred in rhabdomyolysis occurred in patients who received 5 to 40 mg of rosuvastatin. Rosuvastatin was well tolerated by a broad range of patients who had dyslipidemia, and its safety profile was similar to those of the comparator statins investigated in this extensive clinical program.

  16. Adverse effects of statins - myths and reality.

    PubMed

    Šimić, Iveta; Reiner, Željko

    2015-01-01

    Statins reduce cardiovascular mortality and morbidity as well as cardiovascular events in patients with a very high risk of cardiovascular disease (CVD) and also in subjects with high or moderate risk by reducing the levels of low-density lipoprotein cholesterol (LDL-C). Although they are considered to be drugs with a very good safety profile, because of their wide use there are many concerns that their adverse effects might compromise their proven beneficial effects. Therefore this article reviews all the data and provides an evidence- based insight what are the proven adverse effects of statins and what are the "myths" about them. The most important side effects include myopathy and rhabdomyolysis. Another side effect is increased activity of liver tests which occurs occasionally and is reversible. However, recent studies even suggest that statin therapy can improve hepatic steatosis. It is beyond any doubt that statins do slightly increase the incidence of type 2 diabetes mellitus in people with two or more components of metabolic syndrome but the cardiovascular benefits of such a treatment by far exceed this risk. Statin therapy has also been associated with some adverse renal effects, eg. acute renal failure, but recent data suggest even a possible protective effect of these drugs on renal dysfunction. Concerns that statins might increase cancer have not been proven. On the contrary, several studies have indicated a possible benefit of these drugs in patients with different types of cancer. Early concerns about cognitive dysfunction and memory loss associated with statins use could not be proven and most recent data even suggest a possible beneficial effect of statins in the prevention of dementia. Systematic reviews and clinical guidelines suggest that the cardiovascular benefits of statins by far out-weight non-cardiovascular harms in patients with cardiovascular risk.

  17. Statins as a potential risk factor for autoimmune diseases: a case report and review.

    PubMed

    John, Santhosh G; Thorn, Jennifer; Sobonya, Richard

    2014-01-01

    Association of statins with autoimmune disorders is rarely reported. We report a case of an apparently healthy 76-year-old woman who was on long-term statin therapy presenting with severe rhabdomyolysis, autoimmune hepatitis, and positive lupus antibodies. Patient presented with complaints of worsening fatigue, leg cramps, and progressive weakening of lower extremities over 3 weeks. The patient was on simvastatin daily for several years. Clinical examination on admission included muscle tenderness, lower extremity edema, and ascites. Her laboratory values on admission showed elevated creatine kinase and transaminases. Immunologic workup revealed positive ANA, anti-dsDNA and anti-SSA antibodies. F-actin antibody was also positive at high titer. Magnetic resonance imaging of the lower extremities showed findings consistent with myositis. Patient underwent biopsy of the thigh muscles, which showed inflammatory myositis. Liver biopsy was characteristic of autoimmune hepatitis. Patient responded well to immunosuppressive therapy with azathioprine and prednisone. Although statins are generally considered safe, recent data from long-term follow-up on patients who are on statins for long duration suggest that prolonged exposure to statins may trigger autoimmune reactions. The exact mechanism of statin-induced autoimmune reaction is unclear. Statins, as proapoptotic agents, release nuclear antigen into the circulation and may induce the production of pathogenic autoantibodies. The role of statins in inducing an endoplasmic reticular stress response with associated upregulation of major histocompatibility complex-1 expression and antigen presentation by muscle fibers has also been reported. Systemic immunosuppressive therapy has proven to be effective in many reported cases.

  18. 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

    2015-03-02

    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.

  19. Statin Therapy: Review of Safety and Potential Side Effects

    PubMed Central

    Ramkumar, Satish; Raghunath, Ajay; Raghunath, Sudhakshini

    2016-01-01

    Background Hydroxymethyl glutaryl coenzyme A reductase inhibitors, commonly called statins, are some of the most commonly prescribed medications worldwide. Evidence suggests that statin therapy has significant mortality and morbidity benefit for both primary and secondary prevention from cardiovascular disease. Nonetheless, concern has been expressed regarding the adverse effects of long term statin use. The purpose of this article was to review the current medical literature regarding the safety of statins. Methods Major trials and review articles on the safety of statins were identified in a search of the MEDLINE database from 1980 to 2016, which was limited to English articles. Results Myalgia is the most common side effect of statin use, with documented rates from 1-10%. Rhabdomyolysis is the most serious adverse effect from statin use, though it occurs quite rarely (less than 0.1%). The most common risk factors for statin-related myopathy include hypothyroidism, polypharmacy and alcohol abuse. Derangement in liver function tests is common, affecting up to 1% of patients; however, the clinical significance of this is unknown. Some statin drugs are potentially diabetogenic and the risk appears to increase in those patients on higher doses. Pitavastatin has not been associated with increased risk of diabetes. Statins have not been proven to increase the risk of malignancy, dementia, mood disorders or acute interstitial nephritis. However, statins do have multiple drug interactions, primarily those which interact with the cytochrome p450 enzyme group. Conclusions Overall, statin drugs appear to be safe for use in the vast majority of patients. However, patients with multiple medical co-morbidities are at increased risk of adverse effects from long-term statin use. PMID:27899849

  20. 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

  1. 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

  2. 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.

  3. 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

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

    PubMed

    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.

  5. 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.

  6. Clinical-Grade Isolated Human Kidney Perivascular Stromal Cells as an Organotypic Cell Source for Kidney Regenerative Medicine.

    PubMed

    Leuning, Daniëlle G; Reinders, Marlies E J; Li, Joan; Peired, Anna J; Lievers, Ellen; de Boer, Hetty C; Fibbe, Willem E; Romagnani, Paola; van Kooten, Cees; Little, Melissa H; Engelse, Marten A; Rabelink, Ton J

    2017-02-01

    Mesenchymal stromal cells (MSCs) are immunomodulatory and tissue homeostatic cells that have shown beneficial effects in kidney diseases and transplantation. Perivascular stromal cells (PSCs) identified within several different organs share characteristics of bone marrow-derived MSCs (BM-MSCs). These PSCs may also possess tissue-specific properties and play a role in local tissue homeostasis. We hypothesized that human kidney-derived PSCs (hkPSCs) would elicit improved kidney repair in comparison with BM-MSCs. Here we introduce a novel, clinical-grade isolation method of hkPSCs from cadaveric kidneys by enriching for the perivascular marker, NG2. hkPSCs show strong transcriptional similarities to BM-MSCs but also show organotypic expression signatures, including the HoxD10 and HoxD11 nephrogenic transcription factors. Comparable to BM-MSCs, hkPSCs showed immunosuppressive potential and, when cocultured with endothelial cells, vascular plexus formation was supported, which was specifically in the hkPSCs accompanied by an increased NG2 expression. hkPSCs did not undergo myofibroblast transformation after exposure to transforming growth factor-β, further corroborating their potential regulatory role in tissue homeostasis. This was further supported by the observation that hkPSCs induced accelerated repair in a tubular epithelial wound scratch assay, which was mediated through hepatocyte growth factor release. In vivo, in a neonatal kidney injection model, hkPSCs reintegrated and survived in the interstitial compartment, whereas BM-MSCs did not show this potential. Moreover, hkPSCs gave protection against the development of acute kidney injury in vivo in a model of rhabdomyolysis-mediated nephrotoxicity. Overall, this suggests a superior therapeutic potential for the use of hkPSCs and their secretome in the treatment of kidney diseases. Stem Cells Translational Medicine 2017;6:405-418.

  7. 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.

  8. 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

  9. Managing the underestimated risk of statin-associated myopathy.

    PubMed

    Rallidis, Loukianos S; Fountoulaki, Katerina; Anastasiou-Nana, Maria

    2012-09-06

    In clinical practice 5-10% of patients receiving statins develop myopathy, a side effect that had been systematically underestimated in the randomized controlled trials with statins. The most common manifestation of myopathy is muscle pain (usually symmetrical, involving proximal muscles) without creatinine kinase (CK) elevation or less frequently with mild CK elevation. Clinically significant rhabdomyolysis (muscle symptoms with CK elevation >10 times the upper limit of normal and with creatinine elevation) is extremely rare. Myopathy complicates the use of all statins (class effect) and is dose-dependent. The pathophysiologic mechanism of statin-associated myopathy is unknown and probably multifactorial. The risk of statin-associated myopathy can be minimized by identifying vulnerable patients (i.e. patients with impaired renal or liver function, advanced age, hypothyroidism, etc.) and/or by eliminating-avoiding statin interactions with specific drugs (cytochrome P-450 3A4 inhibitors, gemfibrozil, etc.). In symptomatic patients, the severity of symptoms, the magnitude of CK elevation and the risk/benefit ratio of statin continuation should be considered before statin treatment is discontinued. Potential strategies are the use of the same statin at a lower dose and if symptoms recur the initiation of fluvastatin XL 80 mg daily or rosuvastatin intermittently in low dose (5-10mg), combined usually with ezetimibe 10mg daily. Failure of these approaches necessitates the use of non-statin lipid lowering drugs (ezetimibe, colesevelam). In order to provide evidence based recommendations for the appropriate management of statin-intolerant patients we need randomized clinical trials directly comparing the myopathic potential of different lipid-lowering medications at comparable doses.

  10. Procainamide Inhibits DNA Methylation and Alleviates Multiple Organ Dysfunction in Rats with Endotoxic Shock

    PubMed Central

    Shih, Chih-Chin; Liao, Mei-Hui; Hsiao, Tsan-Seng; Hii, Hiong-Ping; Shen, Ching-Hui; Chen, Shiu-Jen; Ka, Shuk-Man; Chang, Yung-Lung; Wu, Chin-Chen

    2016-01-01

    Excessive inflammatory and oxidative stress lead to circulatory failure, multiple organ dysfunction, and high mortality in patients with sepsis. Microbial infection-induced DNA hypermethylation is associated with the augmentation of inflammation and oxidative stress. In our previous study, the antiarrhythmic drug procainamide inhibits the expression of DNA methyltransferase 1 (DNMT1) and diminishes IL-6 levels in rats with rhabdomyolysis. Thus, we further evaluated the effects of procainamide on the development of circulatory failure and multiple organ dysfunction in rats with endotoxic shock. Male Wistar rats were intravenously infused with saline or lipopolysaccharide (LPS) followed by procainamide administration. The changes of hemodynamics, blood glucose, biochemical variables, and plasma nitric oxide (NO) levels were analyzed during the experimental period. At the end of experiments, animal organs were also obtained for examining superoxide production, neutrophil infiltration, and DNA methylation status. Our results showed that LPS induced circulatory failure, multiple organ dysfunction, and high mortality rate in endotoxemic rats. Overt neutrophil infiltration and superoxide production, accompanied by the elevations of DNMT1 and 5-methylcytosine levels in the lung of endotoxemic rats were also observed. Treatment of endotoxemic animals with procainamide not only inhibited the increased levels of DNMT1 and 5-methylcytosine but also ameliorated neutrophil infiltration and superoxide production in the lung. In addition, the anti-inflammatory gene, IL27RA, was down-regulated in the LPS group and up-regulated in the LPS + Procainamide group. Procainamide also diminished IL27RA methylation in the lung of endotoxemic rat. Moreover, both DNMT inhibitors procainamide and hydralazine improved hypotension, hypoglycemia, and multiple organ dysfunction of LPS-treated rats. Thus, we suggest that the beneficial effects of procainamide could be attributed to the suppression

  11. Safety profile of lamotrigine in overdose

    PubMed Central

    Alabi, Akintunde; Todd, Adam; Husband, Andrew; Reilly, Joe

    2016-01-01

    Background: Lamotrigine is an anticonvulsant as well as a mood stabilizer. Apart from its established use in the treatment of epilepsy, there has been an expansion of its use in the treatment of mental disorders. Patients with epilepsy as well as those with mental disorders are at increased risk of deliberate drug overdoses. An evidence base for the safety profile of lamotrigine in overdose is an essential tool for prescribers. The objective of this study was to carry out a narrative synthesis of the existing evidence for the safety profile of lamotrigine in overdose. Methods: A systematic search was conducted of EMBASE (1974 to December 2015), MEDLINE (1946 to December 2015), PsycINFO (1806 to December 2015) and CINAHL (1981 to December 2015) databases. Studies were included in which there was a deliberate or accidental single drug overdose of lamotrigine, with its toxic effects described. Studies that did not involve an overdose were excluded. A narrative synthesis of the described toxic effects was carried out. Results: Out of 562 articles identified, 26 studies were included, mainly in the form of case reports and series. The most commonly described toxic effects of lamotrigine were on the central nervous system, specifically seizures, movement disorders and reduced consciousness. Other toxic effects included QTc interval and QRS complex prolongations, hypersensitivity reactions, serotonin syndrome as well as rhabdomyolysis possibly due to seizures and/or agitation. Deaths were recorded in two studies, with cardiovascular and neurological toxic effects described. Conclusions: Even though lamotrigine has been reported to be well tolerated, there is a risk of toxic effects which can be life threatening in overdose. This needs to be borne in mind when prescribing to patients at an increased risk of deliberate drug overdose. PMID:28008350

  12. 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

  13. Species-dependent variations in the in vitro myotoxicity of death adder (Acanthophis) venoms.

    PubMed

    Wickramaratna, Janith C; Fry, Bryan G; Hodgson, Wayne C

    2003-08-01

    Based on early studies on Acanthophis antarcticus (common death adder) venom, it has long been thought that death adder snake venoms are devoid of myotoxicity. However, a recent clinical study reported rhabdomyolysis in patients following death adder envenomations, in Papua New Guinea, by a species thought to be different to A. antarcticus. Subsequently, a myotoxic phospholipase A2 component was isolated from A. rugosus (Irian Jayan death adder) venom. The present study examined the venoms of A. praelongus (northern), A. pyrrhus (desert), A. hawkei (Barkly Tableland), A. wellsi (black head), A. rugosus, A. sp. Seram and the regional variants of A. antarcticus for in vitro myotoxicity. Venoms (10-50 microg/ml) were examined for myotoxicity using the chick directly (0.1 Hz, 2 ms, supramaximal V) stimulated biventer cervicis nerve-muscle preparation. A significant contracture of skeletal muscle and/or inhibition of direct twitches were considered signs of myotoxicity. This was confirmed by histological examination. All venoms displayed high phospholipase A2 activity. The venoms (10-50 microg/ml) of A. sp. Seram, A. praelongus, A. rugosus,and A. wellsi caused a significant inhibition of direct twitches and an increase in baseline tension compared to the vehicle (n=4-6; two-way ANOVA, p<0.05). Furthermore, these venoms caused dose-dependent morphological changes in skeletal muscle. In contrast, the venoms (10-50 microg/ml; n=3-6) of A. hawkei, A. pyrrhus, and regional variants of A. antarcticus were devoid of myotoxicity. Prior incubation (10 min) of CSL death adder antivenom (5 U/ml) prevented the myotoxicity caused by A. sp. Seram, A. praelongus, A. rugosus, and A. wellsi venoms (50 microg/ml; n=4-7). In conclusion, clinicians may need to be mindful of possible myotoxicity following envenomations by A. praelongus, A. rugosus, A. sp. Seram, and A. wellsi species.

  14. Comparison of rosuvastatin versus atorvastatin in Hispanic-Americans with hypercholesterolemia (from the STARSHIP trial).

    PubMed

    Lloret, Ramon; Ycas, Joseph; Stein, Michael; Haffner, Steven

    2006-09-15

    In a multicenter, open-label trial, 696 Hispanic patients with low-density lipoprotein (LDL) cholesterol levels > or =130 and < or =300 mg/dl and triglyceride levels <400 mg/dl at medium or high risk of coronary heart disease were randomized to receive 10 or 20 mg of rosuvastatin or 10 or 20 mg of atorvastatin for 6 weeks. At week 6, LDL cholesterol was decreased more by 10 mg of rosuvastatin than by 10 mg of atorvastatin (45% vs 36%, p <0.0001) and more by 20 mg of rosuvastatin than by 20 mg of atorvastatin (50% vs 42%, p <0.0001). Significantly greater decreases were also observed with rosuvastatin for total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein-B, and lipid ratios compared with milligram-equivalent doses of atorvastatin. Overall, National Cholesterol Education Program Adult Treatment Program III LDL cholesterol goals were achieved by 78% and 88% of patients who received 10 and 20 mg of rosuvastatin and by 60% and 73% of patients who received 10 and 20 mg of atorvastatin, respectively. Among high-risk patients, the LDL cholesterol goal of <100 mg/dl was achieved by 74% and 91% of patients who received 10 and 20 mg of rosuvastatin and by 52% and 62% who received 10 and 20 mg of atorvastatin, respectively. All treatments were well tolerated, and adverse events were similar in frequency across treatment groups. No cases of myopathy or rhabdomyolysis were observed. In conclusion, treatment with rosuvastatin and atorvastatin produced beneficial lipid changes in this group of Hispanic patients that appear comparable in magnitude to those observed in primarily non-Hispanic white study populations. These benefits were accompanied by a favorable safety profile that suggests no concerns particular to this population.

  15. Prometheus system: a technological support in liver failure.

    PubMed

    Santoro, A; Faenza, S; Mancini, E; Ferramosca, E; Grammatico, F; Zucchelli, A; Facchini, M G; Pinna, A D

    2006-05-01

    The Prometheus system is a plasma filtration treatment coupling adsorption and hemodialysis (FPSA) aimed to blood purification in liver failure. After separation through an albumin-permeable membrane, plasma enters a secondary circuit where protein-bound toxic substances are removed by two adsorbers; p01, a neutral resin, and p02, an anion exchanger. Plasma is then returned to the venous line, where a high-flux hemodialyzer removes water-soluble substances. We used the Prometheus system in 12 patients with acute or acute-on-chronic liver insufficiency: eight cirrhosis, one posttransplant dysfunction, and three secondary liver insult (two cardiogenic shock and one rhabdomyolysis). All patients were severely hyperbilirubinemic, hypercholemic, and hyperammonemic. Twenty-eight sessions each lasting 340 +/- 40 minutes were performed (2.5/patient). The mean total bilirubin decreased from 33.6 +/- 20 to 22.2 +/- 13.6 mg/dL (P < .001); the reduction ratios for cholic acid and ammonia were 48.6% and 51.6%, respectively. The pre- to postsession urea reduction was 57.6% +/- 9.5% and creatinine 42.7% +/- 10%. A significant reduction was observed in the circulating levels of soluble interleukin (IL) 2 receptor (pre: 2687.2 +/- 1434.7; post: 1977.1 +/- 602 Ul/ml; P < .001) and in IL 6 (pre: 56.1 +/- 11.1; post: 35.9 +/- 10.3 pg/mL, P = .05). During treatments the hemodynamics were stable. Two patients received liver transplantations. The secondary liver insult was completely overcome in all three patients. The overall survival at 30 days was 41.6% (5/12 patients). Prometheus, based on FPSA, produced high clearance for protein-bound and water soluble markers, which resulted in high treatment efficacy.

  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. [Survey of food poisoning incidents in Japan due to ingestion of marine boxfish and their toxicity].

    PubMed

    Taniyama, Shigeto; Sagara, Takefumi; Nishio, Sachio; Kuroki, Ryoichi; Asakawa, Manabu; Noguchi, Tamao; Yamasaki, Shuhei; Takatani, Tomohiro; Arakawa, Osamu

    2009-10-01

    From 1990 to 2008, 9 food poisoning incidents due to ingestion of marine boxfish occurred in Nagasaki, Miyazaki, Mie and Kagoshima Prefectures, Japan, and a total of 13 persons were poisoned. Their main symptom was severe muscle pain arising from rhabdomyolysis, which was usually accompanied by the discharge of black urine and abnormal elevation of serum creatine phosphokinase. Twelve out of the 13 victims recovered in a few days to two months, while one died after approximately 2 weeks. Since the symptoms were very similar to those caused by parrotfish "aobudai" Scarus ovifrons poisoning, the causative substance was considered to be parrotfish toxin, i.e., a palytoxin-like substance. Epidemic surveys after the incidents in Miyazaki and Nagasaki identified the leftovers as "hakofugu" Ostracion immaculatus. During screening tests to clarify the toxicity of boxfish from Western Japan, 47 of 129 specimens (36.4%) of O. immaculatus, and 7 of 18 specimens (38.9%) of "umisuzume" Lactoria diaphana were found to show acute and/or delayed lethal activity to mice (0.5-2.0 mouse unit/g). Among the tissues tested, the frequency of toxicity was highest in the viscera excluding liver (28.6% in O. cubicus, 33.3% in L. diaphana), followed by muscle (10.9%, 5.6%) and liver (6.2%, 5.6%). From the above results, we conclude that O. cubicus and L. diaphana inhabiting the coast of Japan sometimes contain toxic substance(s), which can sporadically cause food poisonings very similar to parrotfish poisoning.

  18. 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

  19. Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea

    PubMed Central

    Vernet, Marie-Astrid; Reynard, Stéphanie; Fizet, Alexandra; Schaeffer, Justine; Pannetier, Delphine; Rives, Max; Georges, Nadia; Garcia-Bonnet, Nathalie; Sylla, Aboubacar I.; Grovogui, Péma; Kerherve, Jean-Yves; Savio, Christophe; Savio-Coste, Sylvie; de Séverac, Marie-Laure; Linares, Sandrine; Harouna, Souley; Abdoul, Bing M’Lebing; Petitjean, Frederic; Samake, Nenefing; Kinda, Moumouni; Koundouno, Fara Roger; Mateo, Mathieu; Lecine, Patrick; Page, Audrey; Tchamdja, Tang Maleki; Schoenhals, Matthieu; Barbe, Solenne; Simon, Bernard; Tran-Minh, Tuan; L’Hériteau, François

    2017-01-01

    BACKGROUND. The pathogenesis of Ebola virus (EBOV) disease (EVD) is poorly characterized. The establishment of well-equipped diagnostic laboratories close to Ebola treatment centers (ETCs) has made it possible to obtain relevant virological and biological data during the course of EVD and to assess their association with the clinical course and different outcomes of the disease. METHODS. We were responsible for diagnosing EBOV infection in patients admitted to two ETCs in forested areas of Guinea. The pattern of clinical signs was recorded, and an etiological diagnosis was established by RT-PCR for EBOV infection or a rapid test for malaria and typhoid fever. Biochemical analyses were also performed. RESULTS. We handled samples from 168 patients between November 29, 2014, and January 31, 2015; 97 patients were found to be infected with EBOV, with Plasmodium falciparum coinfection in 18%. Overall mortality for EVD cases was 58%, rising to 86% if P. falciparum was also present. Viral load was higher in fatal cases of EVD than in survivors, and fatal cases were associated with higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT), C-reactive protein (CRP), and IL-6 levels. Furthermore, regardless of outcome, EVD was characterized by higher creatine kinase (CPK), amylase, and creatinine levels than in febrile patients without EVD, with higher blood urea nitrogen (BUN) levels in fatal cases of EVD only. CONCLUSION. These findings suggest that a high viral load at admission is a marker of poor EVD prognosis. In addition, high AST, ALT, CRP, and IL-6 levels are associated with a fatal outcome of EVD. Damage to the liver and other tissues, with massive rhabdomyolysis and, probably, acute pancreatitis, is associated with EVD and correlated with disease severity. Finally, biochemical analyses provide substantial added value at ETCs, making it possible to improve supportive rehydration and symptomatic care for patients. FUNDING. The French Ministry of

  20. 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

  1. Biodistribution of diphenhydramine in reproductive organs in an overdose case.

    PubMed

    Oritani, Shigeki; Michiue, Tomomi; Chen, Jian-Hua; Tani, Naoto; Ishikawa, Takaki

    2016-11-12

    Motion sickness medications such as Travelmin(®) prescribed in Japan include diphenhydramine (DPH), dyphylline, diphenidol, and/or caffeine. Herein, we report a patient who died due to rhabdomyolysis after ingesting a DPH containing motion sickness medication. A Japanese male in his 30 s reported missing after going out for a drive early in the morning was found dead in his car in the evening of the same day. An autopsy showed moderate edema, congestion, and several petechiae in both lungs. The brain was congested and edematous with no atherosclerosis of cerebral arteries. The prostate and both testes were slightly edematous. Gastric contents included approximately 15 mL of dark-brown fluid without tablets or food residue. Toxicological examination showed that blood DPH levels in all tissues were between 4.90 and 7.27 μg/mL, which represented toxic to lethal levels. DPH (μg/mL) levels were approximately 3-9 times higher in the prostate (73.42) and testes (left, 28.23; right, 30.09) than those in all regions of the brain (range 7.75-12.33). Blood dyphylline, diphenidol and caffeine levels in reproductive organs reached high, but not toxic levels. In conclusion, DPH, dyphylline, diphenidol, and caffeine levels were higher in reproductive organs such as the prostate and testes than in the central nervous system and heart. As we determined in this case, motion sickness medications might accumulate in reproductive organs. Thus, further examination of tissue biodistribution of DPH, dyphylline, diphenidol, and caffeine is necessary to assess their potential long-term effects in these sites.

  2. 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

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

    PubMed Central

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

    2009-01-01

    Calsequestrin-1 (CASQ1) is a moderate-affinity, high-capacity Ca2+-binding protein in the sarcoplasmic reticulum (SR) terminal cisternae of skeletal muscle. CASQ1 functions as both a Ca2+-binding protein and a luminal regulator of ryanodine receptor (RYR1)-mediated Ca2+ release. Mice lacking skeletal CASQ1 are viable but exhibit reduced levels of releasable Ca2+ and altered contractile properties. Here we report that CASQ1-null mice exhibit increased spontaneous mortality and susceptibility to heat- and anesthetic-induced sudden death. Exposure of CASQ1-null mice to either 2% halothane or heat stress triggers lethal episodes characterized by whole-body contractures, elevated core temperature, and severe rhabdomyolysis, which are prevented by prior dantrolene administration. The characteristics of these events are remarkably similar to analogous episodes observed in humans with malignant hyperthermia (MH) and animal models of MH and environmental heat stroke (EHS). In vitro studies indicate that CASQ1-null muscle exhibits increased contractile sensitivity to temperature and caffeine, temperature-dependent increases in resting Ca2+, and an increase in the magnitude of depolarization-induced Ca2+ release. These results demonstrate that CASQ1 deficiency alters proper control of RYR1 function and suggest CASQ1 as a potential candidate gene for linkage analysis in families with MH/EHS where mutations in the RYR1 gene are excluded.—Dainese, M., Quarta, M., Lyfenko, A. D., Paolini, C., Canato, M., Reggiani, C., Dirksen, R. T., Protasi, F. Anesthetic- and heat-induced sudden death in calsequestrin-1-knockout mice. PMID:19237502

  4. 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

  5. The effect of varying dietary starch and fat content on serum creatine kinase activity and substrate availability in equine polysaccharide storage myopathy.

    PubMed

    Ribeiro, W P; Valberg, S J; Pagan, J D; Gustavsson, B Essen

    2004-01-01

    The effect of dietary starch and fat content on serum creatine kinase (CK) activity and substrate availability was evaluated in 4 mares of Quarter Horse-related breeds with polysaccharide storage myopathy (PSSM). Four isocaloric diets ranging in digestible energy (DE) from 21.2% (diet A), 14.8% (B), 8.4% (C), to 3.9% (D) for starch, and 7.2% DE (diet A), 9.9% (B), to 12.7% DE (diet C and D) for fat were fed for 6-week periods (4 weeks with exercise) using a 4 X 4 Latin square design. Postprandial glucose and insulin responses were measured, and 4 hours postexercise, serum CK activity, glucose, insulin, free fatty acids (FFA), and beta-hydroxybutyrate (beta-HBA) were analyzed. Glycogen, glucose-6-phosphate, citrate synthase, 3-hydroxy-acyl-CoA dehydrogenase, lactate dehydrogenase as well as abnormal polysaccharide and lipid content were measured in middle gluteal muscle samples. Postprandial insulin and glucose response was higher for diet A versus D. Log CK activity was higher with diets A, B, and C versus D. Daily insulin was higher and FFA lower on diet A versus B, C, and D, whereas glucose varied only slightly with diet. Muscle oxidative capacity and lipid stores were low in PSSM horses and muscle glycogen and abnormal polysaccharide content high on both diets A and D. Individual variation occurred in the response of PSSM horses to diets differing in starch and fat content. However, for those horses with clinical manifestations of PSSM, a diet with <5% DE starch and >12% DE fat can reduce exertional rhabdomyolysis, potentially by increasing availability of FFA for muscle metabolism.

  6. 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, Daniel M.; Tuomi, Pamela A.; 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.

  7. 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

  8. A study on the effect of cimetidine and L-carnitine on myoglobinuric acute kidney injury in male rats.

    PubMed

    Estaphan, Suzanne; Eissa, Hassan; Elattar, Samah; Rashed, Laila; Farouk, Mira

    2015-07-01

    Myoglobinuric acute renal failure is the most important life threatening complication of rhabdomyolysis. Iron, free radicals, nitric oxide and cytochrome p450 are involved in the pathogenesis of mARF. The aim of this study is to compare the effect of cimetidine, l-carnitine and both agents together on mARF in rats. Forty rats were divided into 5 groups; group I: control rats, group II: myoglobinuric ARF rats, group III: mARF rats received l-carnitine (200mg/kg, i.p.), group IV: mARF rats received cimetidine (150mg/kg i.p.) and group V: mARF rats received both agents together. 48h after glycerol injection, systolic blood pressure was measured. Urine and blood samples were collected to evaluate urine volume, GFR, BUN, creatinine, K, Na, serum creatine kinase, NO and glutathione levels. Kidney specimens were taken to investigate renal cytochrome p450 and for histological examinations. Cimetidine treatment significantly decreased creatinine, BUN, K, Na, SBP and creatine kinase and increased GFR and urine volume compared to group II. l-carnitine exerted similar changes except for the effect on K and GFR. NO was significantly decreased, while renal glutathione and cytochrome p450 were significantly increased in groups treated with l-carnitine or cimetidine as compared to group II. Combined treatment further improved renal functions, creatine kinase, oxidative stress parameters and SBP as compared to each therapy alone. The histological changes confirmed the biochemical findings. Cimetidine and l-carnitine have protective effects - almost equally - against mARF. Using both agents together, minimises the renal injury.

  9. Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features

    PubMed Central

    Lehmann, Diana; Motlagh, Leila; Robaa, Dina; Zierz, Stephan

    2017-01-01

    CPT (carnitine palmitoyltransferase) II muscle deficiency is the most common form of muscle fatty acid metabolism disorders. In contrast to carnitine deficiency, it is clinically characterized by attacks of myalgia and rhabdomyolysis without persistent muscle weakness and lipid accumulation in muscle fibers. The biochemical consequences of the disease-causing mutations are still discussed controversially. CPT activity in muscles of patients with CPT II deficiency ranged from not detectable to reduced to normal. Based on the observation that in patients, total CPT is completely inhibited by malony-CoA, a deficiency of malonyl-CoA-insensitive CPT II has been suggested. In contrast, it has also been shown that in muscle CPT II deficiency, CPT II protein is present in normal concentrations with normal enzymatic activity. However, CPT II in patients is abnormally sensitive to inhibition by malonyl-CoA, Triton X-100 and fatty acid metabolites. A recent study on human recombinant CPT II enzymes (His6-N-hCPT2 and His6-N-hCPT2/S113L) revealed that the wild-type and the S113L variants showed the same enzymatic activity. However, the mutated enzyme showed an abnormal thermal destabilization at 40 and 45 °C and an abnormal sensitivity to inhibition by malony-CoA. The thermolability of the mutant enzyme might explain why symptoms in muscle CPT II deficiency mainly occur during prolonged exercise, infections and exposure to cold. In addition, the abnormally regulated enzyme might be mostly inhibited when the fatty acid metabolism is stressed. PMID:28054946

  10. Parenteral iron compounds sensitize mice to injury-initiated TNF-alpha mRNA production and TNF-alpha release.

    PubMed

    Zager, Richard A; Johnson, A C M; Hanson, S Y; Lund, Steve

    2005-02-01

    Intravenous Fe is widely used to treat anemia in renal disease patients. However, concerns of potential Fe toxicity exist. To more fully define its spectrum, this study tested Fe's impact on systemic inflammation following either endotoxemia or the induction of direct tissue damage (glycerol-mediated rhabdomyolysis). The inflammatory response was gauged by tissue TNF-alpha message expression and plasma TNF-alpha levels. CD-1 mice received either intravenous Fe sucrose, -gluconate, or -dextran (FeS, FeG, or FeD, respectively; 2 mg), followed by either endotoxin (LPS) or glycerol injection 0-48 h later. Plasma TNF-alpha was assessed by ELISA 2-3 h after the LPS or glycerol challenge. TNF-alpha mRNA expression (RT-PCR) was measured in the kidney, heart, liver, lung, and spleen with Fe +/- LPS treatment. Finally, the relative impacts of intramuscular vs. intravenous Fe and of glutathione (GSH) on Fe/LPS- induced TNF-alpha generation were assessed. Each Fe preparation significantly enhanced LPS- or muscle injury-mediated TNF-alpha generation. This effect was observed for at least 48 h post-Fe injection, a time at which plasma iron levels were increased by levels insufficient to fully saturate transferrin. Fe did not independently increase plasma TNF-alpha or tissue mRNA. However, it potentiated postinjury-induced TNF-alpha mRNA increments and did so in an organ-specific fashion (kidney, heart, and lung; but not in liver or spleen). Intramuscular administration, but not GSH treatment, negated Fe's ability to synergize LPS-mediated TNF-alpha release. We conclude 1) intravenous Fe can enhance TNF-alpha generation during LPS- or glycerol-induced tissue damage; 2) increased TNF-alpha gene transcription in the kidney, heart, and lung may contribute to this result; and 3) intramuscular administration, but not GSH, might potentially mitigate some of Fe's systemic toxic effects.

  11. 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.

  12. [Clinical features of malignant hyperthermia crisis].

    PubMed

    Cornet, C; Moeller, R; Laxenaire, M C

    1989-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder. It is classically described as a hypermetabolic state triggered by halogenated anaesthetics and/or depolarizing muscle relaxants. In fact, since Denborough and Lovel's case, it has been shown that MH has a great number of clinical forms. The overwhelming picture of muscular hypercatabolism with fulminating hyperthermia and generalized rigidity is becoming rare. A better knowledge of the first symptoms explains in part the better prognosis: masseter spasm after suxamethonium, an increase in expired CO2 concentration, unexplained tachycardia, ventricular arrhythmias. The use of dantrolene reduced the mortality of MH. The different types of clinical manifestations are due to genetic differences, the concentration of the anaesthetic agent, and the length of time of exposure to the drug. The severity of the episode is linked to environmental factors such as stress, physical exercise, ambient temperature, concomitant use of other drugs. Masseter spasm after suxamethonium is specific for MH, but not pathognomonic. It occurs in 1% of cases in children when using halothane with suxamethonium. However, in those patients who displayed such a spasm, more than 50% had a positive contracture test. Masseter spasm is often associated with severe rhabdomyolysis in patients with muscle dystrophy, especially Duchenne's dystrophy. In the latter case, major cardiac problems may occur at the time of anaesthetic induction. Even if there are no other signs of MH, all patients who have had a masseter spasm must be considered as open to doubt, and should be further explored. MH is often difficult to diagnose in medium severity types.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Warning against co-administration of 3,4-methylenedioxymethamphetamine (MDMA) with methamphetamine from the perspective of pharmacokinetic and pharmacodynamic evaluations in rat brain.

    PubMed

    Yuki, Fuchigami; Rie, Ikeda; Miki, Kuzushima; Mitsuhiro, Wada; Naotaka, Kuroda; Kenichiro, Nakashima

    2013-04-11

    3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine often cause serious adverse effects (e.g., rhabdomyolysis, and cardiac disease) following hyperthermia triggered by release of brain monoamines such as dopamine and serotonin. Therefore, evaluation of brain monoamine concentrations is useful to predict these drugs' risks in human. This study aimed to evaluate risks of co-administration of MDMA and methamphetamine, both of which are abused frequently in Japan, based on drug distribution and monoamine level in the rat brain. Rats were allocated to three groups: (1) sole MDMA administration (12 or 25 mg/kg, intraperitoneally), (2) sole methamphetamine administration (10 mg/kg, intraperitoneally) and (3) co-administration of MDMA (12 mg/kg, intraperitoneally) and methamphetamine (10 mg/kg, intraperitoneally). We monitored pharmacokinetic and pharmacodynamic variables for drugs and monoamines in the rat brain. Area under the curve for concentration vs. time until 600 min from drug administration (AUC₀₋₆₀₀) increased from 348.0 to 689.8 μgmin/L for MDMA and from 29.9 to 243.4 μMmin for dopamine in response to co-administration of methamphetamine and MDMA compared to sole MDMA (12 mg/kg) administration. After sole methamphetamine or that with MDMA administration, AUC₀₋₆₀₀ of methamphetamine were 401.8 and 671.1 μgmin/L, and AUC₀₋₆₀₀ of dopamine were 159.9 and 243.4 μMmin. In conclusion, the brain had greater exposure to MDMA, methamphetamine and dopamine after co-administration of MDMA and methamphetamine than when these two drugs were given alone. This suggests co-administration of MDMA with methamphetamine confers greater risk than sole administration, and that adverse events of MDMA ingestion may increase when methamphetamine is co-administered.

  14. Familial very long chain acyl-CoA dehydrogenase deficiency as a cause of neonatal sudden infant death: improved survival by prompt diagnosis.

    PubMed

    Scalais, Emmanuel; Bottu, Jean; Wanders, Ronald J A; Ferdinandusse, Sacha; Waterham, Hans R; De Meirleir, Linda

    2015-01-01

    In neonates, very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is often characterized by cardiomyopathy, hepatic encephalopathy, or severe hypoketotic hypoglycemia, or a combination thereof. The purpose of this study was to further elucidate a familial VLCAD deficiency in three patients, two of whom died in the neonatal period. We report on a family with VLCAD deficiency. Acyl-carnitine profiles were obtained from dried blood spot and/or from oxidation of (13) C-palmitate by cultured skin fibroblasts. In the index patient, VLCAD deficiency was ascertained by enzyme activity measurement in fibroblasts and by molecular analysis of ACADVL. At 30 hr of life, the proband was diagnosed with hypoglycemia (1.77 mmol/L), rhabdomyolysis (CK: 12966 IU/L) and hyperlactacidemia (10.6 mmol/L). Acylcarnitine profile performed at 31 hr of life was consistent with VLCAD deficiency and confirmed by cultured skin fibroblast enzyme activity measurement. Molecular analysis of ACADVL revealed a homozygous splice-site mutation (1077 + 2T>C). The acyl-carnitine profile obtained from the sibling's original newborn screening cards demonstrated a similar, but less pronounced abnormal profile. In the proband, the initial metabolic crisis was controlled with 10% dextrose solution and oral riboflavin followed by specific diet (Basic-F and medium chain triglyceride (MCT). This clinical report demonstrates a familial history of repeated neonatal deaths explained by VLCAD deficiency, and the clinical evolution of the latest affected, surviving sibling. It shows that very early metabolic screening is an effective approach to avoid sudden unexpected death.

  15. Clinical and Pathological Findings of a Fatal Systemic Capillary Leak Syndrome (Clarkson Disease)

    PubMed Central

    Zancanaro, Andrea; Serafini, Francesco; Fantin, Giuseppe; Murer, Bruno; Cicardi, Marco; Bonanni, Luca; Dalla Vestra, Michele; Scanferlato, Mauro; Mazzanti, Giovanni; Presotto, Fabio

    2015-01-01

    Abstract Systemic capillary leak syndrome (SCLS) is a rare disorder with episodes of hypotension, hypoalbuminemia, and hemoconcentration. During attacks endothelial hyperpermeability results in leakage of plasma proteins into the interstitial space. Attacks vary in severity and may be lethal. A 49-year-old previously healthy man was admitted to hospital for hypovolemic shock, anasarca with pleuropericardial effusion, muscle fatigue, and oliguria occurring after a flu-like syndrome. Laboratory data showed an increase in hematocrit (65%), leucocytes (24.590 μ/L), creatinine (2.5 mg/dL), creatine phosphokinase (10.000 U/L), and a decrease in serum albumin (17 g/L) without proteinuria. Immunoglobulins of class G/λ monoclonal gammopathy were detected (1.3 g/L). The initial suspicions addressed to a protein-loosing syndrome or to an effort-related rhabdomyolysis. Initial therapy was based on steroids, albumin, and high molecular weight plasma expanders (hydroxyethyl starch). Because of high hematocrit, phlebotomy was also performed. The patient had complete clinical remission and a diagnosis of SCLS was finally made. He received prophylactic therapy with verapamil and theophylline that was self-stopped for intolerance (hypotension and tachycardia). He had a new crisis 2 days after a physical effort, and was admitted in intensive care unit. The patient died for severe hypovolemic shock with multiorgan failure and sudden cardiac arrest 15 hours after hospital admission. Postmortem investigation revealed massive interstitial edema of main organs with myocardial hyperacute ischemia. Studies on SCLS are limited for the rarity of the disease and its unpredictable course. Both prophylactic and acute crisis treatments are empirical and optimal management of severe attacks is still lacking. PMID:25738482

  16. 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.

  17. Fatal water intoxication and cardiac arrest in runners during marathons: prevention and treatment based on validated clinical paradigms.

    PubMed

    Siegel, Arthur J

    2015-10-01

    Cerebral edema due to exercise-associated hyponatremia and cardiac arrest due to atherosclerotic heart disease cause rare marathon-related fatalities in young female and middle-aged male runners, respectively. Studies in asymptomatic middle-aged male physician-runners during races identified inflammation due to skeletal muscle injury after glycogen depletion as the shared underlying cause. Nonosmotic secretion of arginine vasopressin as a neuroendocrine stress response to rhabdomyolysis mediates hyponatremia as a variant of the syndrome of inappropriate antidiuretic hormone secretion. Fatal hyponatremic encephalopathy in young female runners was curtailed using emergent infusion of intravenous hypertonic (3%) saline to reverse cerebral edema on the basis of this paradigm. This treatment was arrived at through a consensus process within the medical community. An increasing frequency of cardiac arrest and sudden death has been identified in middle-aged male runners in 2 studies since the year 2000. Same-aged asymptomatic male physician-runners showed post-race elevations in interleukin-6 and C-reactive protein, biomarkers that predict acute cardiac events in healthy persons. Hypercoagulability with in vivo platelet activation and release of cardiac troponin and N-terminal pro-brain natriuretic peptide were also observed post-race in these same subjects. High short-term risk for atherothrombosis during races as shown by stratification of biomarkers in asymptomatic men may render nonobstructive coronary atherosclerotic plaques vulnerable to rupture. Pre-race aspirin use in this high-risk subgroup is prudent according to conclusive evidence for preventing first acute myocardial infarctions in same-aged healthy male physicians. On the basis of validated clinical paradigms, taking a low-dose aspirin before a marathon and drinking to thirst during the race may avert preventable deaths in susceptible runners.

  18. Multiphoton imaging for assessing renal disposition in acute kidney injury

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Liang, Xiaowen; Wang, Haolu; Roberts, Darren M.; Roberts, Michael S.

    2016-11-01

    Estimation of renal function and drug renal disposition in acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but is challenging due to fluctuations in kidney function. Multiphoton microscopy has been shown to be a useful tool in studying drug disposition in liver and can reflect dynamic changes of liver function. We extend this imaging technique to investigate glomerular filtration rate (GFR) and tubular transporter functional change in various animal models of AKI, which mimic a broad range of causes of AKI such as hypoxia (renal ischemia- reperfusion), therapeutic drugs (e.g. cisplatin), rhabdomyolysis (e.g. glycerol-induced) and sepsis (e.g. LPSinduced). The MPM images revealed acute injury of tubular cells as indicated by reduced autofluorescence and cellular vacuolation in AKI groups compared to control group. In control animal, systemically injected FITC-labelled inulin was rapidly cleared from glomerulus, while the clearance of FITC-inulin was significantly delayed in most of animals in AKI group, which may reflect the reduced GFR in AKI. Following intravenous injection, rhodamine 123, a fluorescent substrate of p-glycoprotein (one of tubular transporter), was excreted into urine in proximal tubule via p-glycoprotein; in response to AKI, rhodamine 123 was retained in tubular cells as revealed by slower decay of fluorescence intensity, indicating P-gp transporter dysfunction in AKI. Thus, real-time changes in GFR and transporter function can be imaged in rodent kidney with AKI using multiphoton excitation of exogenously injected fluorescent markers.

  19. Pre-exercise medium-chain triglyceride application prevents acylcarnitine accumulation in skeletal muscle from very-long-chain acyl-CoA-dehydrogenase-deficient mice.

    PubMed

    Primassin, Sonja; Tucci, Sara; Herebian, Diran; Seibt, Annette; Hoffmann, Lars; ter Veld, Frank; Spiekerkoetter, Ute

    2010-06-01

    Dietary modification with medium-chain triglyceride (MCT) supplementation is one crucial way of treating children with long-chain fatty acid oxidation disorders. Recently, supplementation prior to exercise has been reported to prevent muscular pain and rhabdomyolysis. Systematic studies to determine when MCT supplementation is most beneficial have not yet been undertaken. We studied the effects of an MCT-based diet compared with MCT administration only prior to exercise in very-long-chain acyl-CoA dehydrogenase (VLCAD) knockout (KO) mice. VLCAD KO mice were fed an MCT-based diet in same amounts as normal mouse diet containing long-chain triglycerides (LCT) and were exercised on a treadmill. Mice fed a normal LCT diet received MCT only prior to exercise. Acylcarnitine concentration, free carnitine concentration, and acyl-coenzyme A (CoA) oxidation capacity in skeletal muscle as well as hepatic lipid accumulation were determined. Long-chain acylcarnitines significantly increased in VLCAD-deficient skeletal muscle with an MCT diet compared with an LCT diet with MCT bolus prior to exercise, whereas an MCT bolus treatment significantly decreased long-chain acylcarnitines after exercise compared with an LCT diet. C8-carnitine was significantly increased in skeletal muscle after MCT bolus treatment and exercise compared with LCT and long-term MCT treatment. Increased hepatic lipid accumulation was observed in long-term MCT-treated KO mice. MCT seems most beneficial when given in a single dose directly prior to exercise to prevent acylcarnitine accumulation. In contrast, continuous MCT treatment produces a higher skeletal muscle content of long-chain acylcarnitines after exercise and increases hepatic lipid storage in VLCAD KO mice.

  20. 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.

  1. Clinical and pathological findings of a fatal systemic capillary leak syndrome (Clarkson disease): a case report.

    PubMed

    Zancanaro, Andrea; Serafini, Francesco; Fantin, Giuseppe; Murer, Bruno; Cicardi, Marco; Bonanni, Luca; Dalla Vestra, Michele; Scanferlato, Mauro; Mazzanti, Giovanni; Presotto, Fabio

    2015-03-01

    Systemic capillary leak syndrome (SCLS) is a rare disorder with episodes of hypotension, hypoalbuminemia, and hemoconcentration. During attacks endothelial hyperpermeability results in leakage of plasma proteins into the interstitial space. Attacks vary in severity and may be lethal.A 49-year-old previously healthy man was admitted to hospital for hypovolemic shock, anasarca with pleuropericardial effusion, muscle fatigue, and oliguria occurring after a flu-like syndrome. Laboratory data showed an increase in hematocrit (65%), leucocytes (24.590 μ/L), creatinine (2.5 mg/dL), creatine phosphokinase (10.000 U/L), and a decrease in serum albumin (17 g/L) without proteinuria. Immunoglobulins of class G/λ monoclonal gammopathy were detected (1.3 g/L). The initial suspicions addressed to a protein-loosing syndrome or to an effort-related rhabdomyolysis. Initial therapy was based on steroids, albumin, and high molecular weight plasma expanders (hydroxyethyl starch). Because of high hematocrit, phlebotomy was also performed. The patient had complete clinical remission and a diagnosis of SCLS was finally made. He received prophylactic therapy with verapamil and theophylline that was self-stopped for intolerance (hypotension and tachycardia). He had a new crisis 2 days after a physical effort, and was admitted in intensive care unit. The patient died for severe hypovolemic shock with multiorgan failure and sudden cardiac arrest 15 hours after hospital admission. Postmortem investigation revealed massive interstitial edema of main organs with myocardial hyperacute ischemia.Studies on SCLS are limited for the rarity of the disease and its unpredictable course. Both prophylactic and acute crisis treatments are empirical and optimal management of severe attacks is still lacking.

  2. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes.

    PubMed

    Kwak, Hyo-Bum; Thalacker-Mercer, Anna; Anderson, Ethan J; Lin, Chien-Te; Kane, Daniel A; Lee, Nam-Sihk; Cortright, Ronald N; Bamman, Marcas M; Neufer, P Darrell

    2012-01-01

    Statins, the widely prescribed cholesterol-lowering drugs for the treatment of cardiovascular disease, cause adverse skeletal muscle side effects ranging from fatigue to fatal rhabdomyolysis. The purpose of this study was to determine the effects of simvastatin on mitochondrial respiration, oxidative stress, and cell death in differentiated primary human skeletal muscle cells (i.e., myotubes). Simvastatin induced a dose-dependent decrease in viability of proliferating and differentiating primary human muscle precursor cells, and a similar dose-dependent effect was noted in differentiated myoblasts and myotubes. Additionally, there were decreases in myotube number and size following 48 h of simvastatin treatment (5 μM). In permeabilized myotubes, maximal ADP-stimulated oxygen consumption, supported by palmitoylcarnitine+malate (PCM, complex I and II substrates) and glutamate+malate (GM, complex I substrates), was 32-37% lower (P<0.05) in simvastatin-treated (5 μM) vs control myotubes, providing evidence of impaired respiration at complex I. Mitochondrial superoxide and hydrogen peroxide generation were significantly greater in the simvastatin-treated human skeletal myotube cultures compared to control. In addition, simvastatin markedly increased protein levels of Bax (proapoptotic, +53%) and Bcl-2 (antiapoptotic, +100%, P<0.05), mitochondrial PTP opening (+44%, P<0.05), and TUNEL-positive nuclei in human skeletal myotubes, demonstrating up-regulation of mitochondrial-mediated myonuclear apoptotic mechanisms. These data demonstrate that simvastatin induces myotube atrophy and cell loss associated with impaired ADP-stimulated maximal mitochondrial respiratory capacity, mitochondrial oxidative stress, and apoptosis in primary human skeletal myotubes, suggesting that mitochondrial dysfunction may underlie human statin-induced myopathy.

  3. Drug-drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors.

    PubMed

    Chauvin, Benoit; Drouot, Sylvain; Barrail-Tran, Aurélie; Taburet, Anne-Marie

    2013-10-01

    The HMG-CoA reductase inhibitors are a class of drugs also known as statins. These drugs are effective and widely prescribed for the treatment of hypercholesterolemia and prevention of cardiovascular morbidity and mortality. Seven statins are currently available: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. Although these drugs are generally well tolerated, skeletal muscle abnormalities from myalgia to severe lethal rhabdomyolysis can occur. Factors that increase statin concentrations such as drug-drug interactions can increase the risk of these adverse events. Drug-drug interactions are dependent on statins' pharmacokinetic profile: simvastatin, lovastatin and atorvastatin are metabolized through cytochrome P450 (CYP) 3A, while the metabolism of the other statins is independent of this CYP. All statins are substrate of organic anion transporter polypeptide 1B1, an uptake transporter expressed in hepatocyte membrane that may also explain some drug-drug interactions. Many HIV-infected patients have dyslipidemia and comorbidities that may require statin treatment. HIV-protease inhibitors (HIV PIs) are part of recommended antiretroviral treatment in combination with two reverse transcriptase inhibitors. All HIV PIs except nelfinavir are coadministered with a low dose of ritonavir, a potent CYP3A inhibitor to improve their pharmacokinetic properties. Cobicistat is a new potent CYP3A inhibitor that is combined with elvitegravir and will be combined with HIV-PIs in the future. The HCV-PIs boceprevir and telaprevir are both, to different extents, inhibitors of CYP3A. This review summarizes the pharmacokinetic properties of statins and PIs with emphasis on their metabolic pathways explaining clinically important drug-drug interactions. Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the

  4. 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

  5. Risk factors and drug interactions predisposing to statin-induced myopathy: implications for risk assessment, prevention and treatment.

    PubMed

    Chatzizisis, Yiannis S; Koskinas, Konstantinos C; Misirli, Gesthimani; Vaklavas, Christos; Hatzitolios, Apostolos; Giannoglou, George D

    2010-03-01

    HMG-CoA reductase inhibitors ('statins') represent the most effective and widely prescribed drugs currently available for the reduction of low-density lipoprotein cholesterol, a critical therapeutic target for primary and secondary prevention of cardiovascular atherosclerotic disease. In the face of the established lipid lowering and the emerging pleiotropic properties of statins, the patient population suitable for long-term statin treatment is expected to further expand. An overall positive safety and tolerability profile of statins has been established, although adverse events have been reported. Skeletal muscle-related events are the most common adverse events of statin treatment. Statin-induced myopathy can (rarely) manifest with severe and potentially fatal cases of rhabdomyolysis, thus rendering the identification of the underlying predisposing factors critical. The purpose of this review is to summarize the factors that increase the risk of statin-related myopathy. Data from published clinical trials, meta-analyses, postmarketing studies, spontaneous report systems and case reports for rare effects were reviewed. Briefly, the epidemiology, clinical spectrum and molecular mechanisms of statin-associated myopathy are discussed. We further analyse in detail the risk factors that precipitate or increase the likelihood of statin-related myopathy. Individual demographic features, genetic factors and co-morbidities that may account for the significant interindividual variability in the myopathic risk are presented. Physicochemical properties of statins have been implicated in the differential risk of currently marketed statins. Pharmacokinetic interactions with concomitant medications that interfere with statin metabolism and alter their systemic bioavailability are reviewed. Of particular clinical interest in cases of resistant dyslipidaemia is the interaction of statins with other classes of lipid-lowering agents; current data on the relative safety of available

  6. 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-resistant Staphylococcus aureus strains 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 and kinact= 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 IC50 value 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 IC50 values 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.

  7. EU-ADR healthcare database network vs. spontaneous reporting system database: preliminary comparison of signal detection.

    PubMed

    Trifirò, Gianluca; Patadia, Vaishali; Schuemie, Martijn J; Coloma, Preciosa M; Gini, Rosa; Herings, Ron; Hippisley-Cox, Julia; Mazzaglia, Giampiero; Giaquinto, Carlo; Scotti, Lorenza; Pedersen, Lars; Avillach, Paul; Sturkenboom, Miriam C J M; van der Lei, Johan; Eu-Adr Group

    2011-01-01

    The EU-ADR project aims to exploit different European electronic healthcare records (EHR) databases for drug safety signal detection. In this paper we report the preliminary results concerning the comparison of signal detection between EU-ADR network and two spontaneous reporting databases, the Food and Drug Administration and World Health Organization databases. EU-ADR data sources consist of eight databases in four countries (Denmark, Italy, Netherlands, and United Kingdom) that are virtually linked through distributed data network. A custom-built software (Jerboa©) elaborates harmonized input data that are produced locally and generates aggregated data which are then stored in a central repository. Those data are subsequently analyzed through different statistics (i.e. Longitudinal Gamma Poisson Shrinker). As potential signals, all the drugs that are associated to six events of interest (bullous eruptions - BE, acute renal failure - ARF, acute myocardial infarction - AMI, anaphylactic shock - AS, rhabdomyolysis - RHABD, and upper gastrointestinal bleeding - UGIB) have been detected via different data mining techniques in the two systems. Subsequently a comparison concerning the number of drugs that could be investigated and the potential signals detected for each event in the spontaneous reporting systems (SRSs) and EU-ADR network was made. SRSs could explore, as potential signals, a larger number of drugs for the six events, in comparison to EU-ADR (range: 630-3,393 vs. 87-856), particularly for those events commonly thought to be potentially drug-induced (i.e. BE: 3,393 vs. 228). The highest proportion of signals detected in SRSs was found for BE, ARF and AS, while for ARF, and UGIB in EU-ADR. In conclusion, it seems that EU-ADR longitudinal database network may complement traditional spontaneous reporting system for signal detection, especially for those adverse events that are frequent in general population and are not commonly thought to be drug

  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.

  9. Blood glucose clearance after feeding and exercise in polysaccharide storage myopathy.

    PubMed

    De La Corte, F D; Valberg, S J; Mickelson, J R; Hower-Moritz, M

    1999-07-01

    feeding without altering insulin:glucose ratios. At rest, PSSM horses have lower insulin:glucose ratios after feeding than normal horses, however, exercise in PSSM horses significantly increases insulin:glucose ratios. This may explain the beneficial effect of daily exercise for preventing rhabdomyolysis in horses with PSSM.

  10. A molecular contribution to the assessment of the Tricholoma equestre species complex.

    PubMed

    Moukha, Serge; Férandon, Cyril; Beroard, Erika; Guinberteau, Jacques; Castandet, Benoît; Callac, Philippe; Creppy, Edmond; Barroso, Gérard

    2013-02-01

    In recent years, interest in the Tricholoma equestre species complex has increased because of several cases of severe and sometimes fatal rhabdomyolysis reported in France and Poland. These occurred after repeated consumption of large portions of T. equestre sporophores during consecutive meals, despite the fact that this species is renowned as a tasty edible wild mushroom. The T. equestre species complex includes three ectomycorrhizal species Tricholoma flavovirens (Pers.) S. Lundell, Tricholoma auratum (Paulet) Gillet, and T. equestre (L.) P. Kummer. All these species produce sporophores with intense yellow gills but are difficult to distinguish by morphological analyses at both the macroscopic and microscopic levels. In T. equestre, two additional varieties are recognized: T. equestre var. populinum (Christensen & Noordeloos) associated with Populus sp. and/or Betula sp. trees and sometimes recognized as Tricholoma frondosae (Kalamees & Shchukin) and T. equestre var. pallidifolia characterized by pale to white gills, frequently recognized as Tricholoma joachimii (Bon & Riva). To explore the taxonomic (species delimitation), ecological, and geographical extent and limits of the T. equestre species complex, we have carried out a molecular comparison of worldwide strains belonging to this complex by using sequences of two molecular markers: the internal transcript spacer (ITS)1/5.8S/ITS2 region of the nuclear ribosomal unit and the 5' part of the mitochondrial cox1 gene. Phylogenetic analyses support the placement of European T. equestre, T. flavovirens, and T. auratum strains as representatives of a single species. This species appears associated with various conifers trees, depending on the geographic origin (Pinus pinaster for T. auratum, Pinus sylvestris or Abies alba for T. equestre and T. flavovirens). However, in the context of a single T. equestre species, the geographical location could lead to the characterization of sub-species or varieties, as suggested

  11. Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise in patients with or without renal hypouricemia.

    PubMed

    Ishikawa, Isao

    2002-08-01

    Acute renal failure induced by rhabdomyolysis after strenuous exercise is well known. We describe here a new type of acute renal failure with severe loin pain which develops after anaerobic exercise (ALPE), for example, 200-meter track racing. The patients complained of severe loin pain several hours after exercise and presented at the emergency room. Since our first description 118 cases have been reported. The serum creatinine concentration was 4.7 +/- 2.9 mg/dl (mean +/- SD) at the initial examination and 6.0 +/- 3.0 mg/dl at maximum. Forty-nine of 96 cases whose serum uric acid levels were described revealed renal hypouricemia (51.0%). A specific risk factor is suggested by the fact that acute renal failure recurred after exercise in 20 of 118 cases. The creatine phosphokinase and serum myoglobin concentrations were normal or only slightly elevated, suggesting damaged type 2 muscle fibers. Renal computed tomography scans, performed several hours to 1-2 days after contrast medium administration, revealed multiple wedge-shaped areas of contrast enhancement. Forty-six of 50 cases examined by delayed computed tomography scan revealed bilateral wedge-shaped contrast enhancement. Although less efficient, radioisotopic scans, such as a methylene diphosphonate bone scan, have also been employed to detect patchy accumulation of isotopes in the kidneys (12 of 19 cases). The pathogenesis of ALPE may be patchy vasoconstriction of the renal vessels, because of its wedge-shaped distribution and its reversibility. Such vascular spasm would account for the renal pain. The prognosis was good, although 20 of 109 cases required dialysis treatment. In conclusion, there are two types of exercise-induced acute renal failure: one is the well-known myoglobin-induced acute renal failure, and the other is ALPE that may be nonmyoglobin induced or induced by myolysis of type 2 muscle fibers due to anaerobic exercise. One hundred and eighteen cases of ALPE were collected from the

  12. Quantification of Na+,K+ pumps and their transport rate in skeletal muscle: functional significance.

    PubMed

    Clausen, Torben

    2013-10-01

    During excitation, muscle cells gain Na(+) and lose K(+), leading to a rise in extracellular K(+) ([K(+)]o), depolarization, and loss of excitability. Recent studies support the idea that these events are important causes of muscle fatigue and that full use of the Na(+),K(+)-ATPase (also known as the Na(+),K(+) pump) is often essential for adequate clearance of extracellular K(+). As a result of their electrogenic action, Na(+),K(+) pumps also help reverse depolarization arising during excitation, hyperkalemia, and anoxia, or from cell damage resulting from exercise, rhabdomyolysis, or muscle diseases. The ability to evaluate Na(+),K(+)-pump function and the capacity of the Na(+),K(+) pumps to fill these needs require quantification of the total content of Na(+),K(+) pumps in skeletal muscle. Inhibition of Na(+),K(+)-pump activity, or a decrease in their content, reduces muscle contractility. Conversely, stimulation of the Na(+),K(+)-pump transport rate or increasing the content of Na(+),K(+) pumps enhances muscle excitability and contractility. Measurements of [(3)H]ouabain binding to skeletal muscle in vivo or in vitro have enabled the reproducible quantification of the total content of Na(+),K(+) pumps in molar units in various animal species, and in both healthy people and individuals with various diseases. In contrast, measurements of 3-O-methylfluorescein phosphatase activity associated with the Na(+),K(+)-ATPase may show inconsistent results. Measurements of Na(+) and K(+) fluxes in intact isolated muscles show that, after Na(+) loading or intense excitation, all the Na(+),K(+) pumps are functional, allowing calculation of the maximum Na(+),K(+)-pumping capacity, expressed in molar units/g muscle/min. The activity and content of Na(+),K(+) pumps are regulated by exercise, inactivity, K(+) deficiency, fasting, age, and several hormones and pharmaceuticals. Studies on the α-subunit isoforms of the Na(+),K(+)-ATPase have detected a relative increase in their

  13. A Systematic Review of Iranian Experiences in Seismo-Nephrology

    PubMed Central

    Hashemi, Behrooz; Safari, Saeed; Hosseini, Mostafa; Yousefifard, Mahmoud; Erfani, Elham; Baratloo, Alireza; Rahmati, Farhad; Motamedi, Maryam; Forouzanfar, Mohammad Mehdi; Najafi, Iraj

    2016-01-01

    Context Crush syndrome and its potentially life-threatening complications, such as acute kidney injury (AKI), are one of the most important medical problems of disaster victims. However, today, many unanswered questions abound about the potential risk factors of crush syndrome, predictive factors of AKI, proper amount of prophylactic hydration therapy, type of fluid, time of continuing fluid, intravenous versus oral hydration, etc. Therefore, this study was designed to review the findings on Iranian nephrologist experiences in diagnosis and management of traumatic rhabdomyolysis following the last two strong earthquakes of Bam (2003) and Manjil-Rudbar (1990). Evidence Acquisition The study was conducted according to the MOOSE reporting guideline. A literature review was conducted on the nephrologic aspects of earthquakes in Iran. Relevant articles were identified through a comprehensive search of online databases until 2014. The search was limited to articles studying the Iranian population published in English and Persian languages. The validated combination of MeSH terms and key words was used. In addition, a manual search was run among the references of all articles that met the entrance criteria and previous reviews. Only cohort, case-control, and cross-sectional studies were enrolled. Two reviewers independently reviewed the eligible studies, and another reviewer contributed in case of a disagreement. Basic information from each study was evaluated from the aspects of purpose and design, year of publication, methodology, main population, and source of data. The quality of the included studies was assessed using methods guide for effectiveness and comparative effectiveness reviews. Two reviewers independently rated each paper as “good”, “fair”, or “poor”. Results A total of 1256 non-duplicate articles were identified, but only 35 potentially relevant papers were screened. Finally, 21 articles were found eligible and studied in details. In addition

  14. 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

  15. 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

  16. Isolation and pharmacological characterization of a phospholipase A2 myotoxin from the venom of the Irian Jayan death adder (Acanthophis rugosus)

    PubMed Central

    Wickramaratna, Janith C; Fry, Bryan G; Aguilar, Marie-Isabel; Kini, R Manjunatha; Hodgson, Wayne C

    2003-01-01

    It has long been thought that death adder venoms are devoid of myotoxic activity based on studies done on Acanthophis antarcticus (Common death adder) venom. However, a recent clinical study reported rhabdomyolysis in patients following death adder envenomations, in Papua New Guinea, by a species thought to be different to A. antarcticus. Consequently, the present study examined A. rugosus (Irian Jayan death adder) venom for myotoxicity, and isolated the first myotoxin (acanmyotoxin-1) from a death adder venom. A. rugosus (10–50 μg ml−1) and acanmyotoxin-1 (MW 13811; 0.1–1 μM) were screened for myotoxicity using the chick directly (0.1 Hz, 2 ms, supramaximal V) stimulated biventer cervicis nerve-muscle (CBCNM) preparation. A significant contracture of skeletal muscle and/or inhibition of direct twitches were considered signs of myotoxicity. This was confirmed by histological examination. High phospholipase A2 (PLA2) activity was detected in both A. rugosus venom (140.2±10.4 μmol min−1 mg−1; n=6) and acanmyotoxin-1 (153.4±11 μmol min−1 mg−1; n=6). Both A. rugosus venom (10–50 μg ml−1) and acanmyotoxin-1 (0.1–1 μM) caused dose-dependent inhibition of direct twitches and increase in baseline tension (n=4–6). In addition, dose-dependent morphological changes in skeletal muscle were observed. Prior incubation (10 min) of CSL death adder antivenom (5 units ml−1; n=4) or inactivation of PLA2 activity with 4-bromophenacyl bromide (1.8 mM; n=4) prevented the myotoxicity caused by acanmyotoxin-1 (1 μM). Acanmyotoxin-1 (0.1 μM; n=4) displayed no significant neurotoxicity when it was examined using the indirectly (0.1 Hz, 0.2 ms, supramaximal V) stimulated CBCNM preparation. In conclusion, clinicians may need to be mindful of possible myotoxicity following death adder envenomation in Irian Jaya. PMID:12540524

  17. Interpretation of the evidence for the efficacy and safety of statin therapy.

    PubMed

    Collins, Rory; Reith, Christina; Emberson, Jonathan; Armitage, Jane; Baigent, Colin; Blackwell, Lisa; Blumenthal, Roger; Danesh, John; Smith, George Davey; DeMets, David; Evans, Stephen; Law, Malcolm; MacMahon, Stephen; Martin, Seth; Neal, Bruce; Poulter, Neil; Preiss, David; Ridker, Paul; Roberts, Ian; Rodgers, Anthony; Sandercock, Peter; Schulz, Kenneth; Sever, Peter; Simes, John; Smeeth, Liam; Wald, Nicholas; Yusuf, Salim; Peto, Richard

    2016-11-19

    kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50-100 new cases of diabetes, and 5-10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about 50-100 patients (ie, 0·5-1·0% absolute harm) per 10 000 treated for 5 years. However, placebo-controlled randomised trials have shown definitively that almost all of the symptomatic adverse events that are attributed to statin therapy in routine practice are not actually caused by it (ie, they represent misattribution). The large-scale evidence available from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery. Consequently, any further findings that emerge about the effects of statin therapy would not be expected to alter materially the balance of benefits and harms. It is, therefore, of concern that exaggerated claims about side-effect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events. For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.

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

    PubMed

    Quinlivan, Rosaline; Martinuzzi, Andrea; Schoser, Benedikt

    2014-11-12

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

  19. Hyponatremia and antidiuresis syndrome.

    PubMed

    Vantyghem, Marie-Christine; Balavoine, Anne-Sophie; Wémeau, Jean-Louis; Douillard, Claire

    2011-12-01

    Antidiuretic hormone (ADH), or arginine vasopressin (AVP), is primarily regulated through plasma osmolarity, as well as non-osmotic stimuli including blood volume and stress. Links between water-electrolyte and carbohydrate metabolism have also been recently demonstrated. AVP acts via the intermediary of three types of receptors: V1a, or V1, which exerts vasoconstrictive effects; pituitary gland V1b, or V3, which participates in the secretion of ACTH; and renal V2, which reduces the excretion of pure water by combining with water channels (aquaporin 2). Antidiuresis syndrome is a form of euvolaemic, hypoosmolar hyponatraemia, which is characterised by a negative free water clearance with inappropriate urine osmolality and intracellular hyper-hydration in the absence of renal, adrenal and thyroid insufficiency. Ninety percent of cases of antidiuresis syndrome occur in association with hypersecretion of vasopressin, while vasopressin is undetectable in 10% of cases. Thus the term "antidiuresis syndrome" is more appropriate than the classic name "syndrome of inappropriate ADH secretion" (SIADH). The clinical symptoms, morbidity and mortality of hyponatraemia are related to its severity, as well as to the rapidity of its onset and duration. Even in cases of moderate hyponatraemia that are considered asymptomatic, there is a very high risk of falls due to gait and attention disorders, as well as rhabdomyolysis, which increases the fracture risk. The aetiological diagnosis of hyponatraemia is based on the analysis of calculated or measured plasma osmolality (POsm), as well as blood volume (skin tenting of dehydration, oedema). Hyperglycaemia and hypertriglyceridaemia lead to hyper- and normoosmolar hyponatraemia, respectively. Salt loss of gastrointestinal, renal, cutaneous and sometimes cerebral origin is hypovolaemic, hypoosmolar hyponatraemia (skin tenting), whereas oedema is present with hypervolaemic, hypoosmolar hyponatraemia of heart failure, nephrotic syndrome

  20. Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case-Control Studies.

    PubMed

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

    2015-09-01

    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 statin-related myopathy