Sample records for rhabdomyolysis

  1. 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. PMID:25802939

  2. MR imaging of rhabdomyolysis

    SciTech Connect

    Zagoria, R.J.; Karstaedt, N.; Koubek, T.D.

    1986-03-01

    The use of magnetic resonance (MR) imaging in two cases of rhabdomyolysis, one resulting from prolonged muscle compression and one from electrical burns, is described. The involved muscles were clearly demonstrated with MR. Recognition and assessment of the extent of rhabdomyolysis are important since life-threatening sequelae including severe metabolic disorders are possible. In one case, spin-echo and inversion-recovery MR imaging provided greater detail of muscle abnormalities than did 99mTc-pyrophosphate radionuclide scanning. Both cases illustrate the usefulness of MR in evaluation of skeletal muscle disorders.

  3. 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.

  4. Rhabdomyolysis in a recreational swimmer.

    PubMed

    Stella, J J; Shariff, A H

    2012-02-01

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

  5. 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. PMID:21458945

  6. Nelarabine Associated Myotoxicity and Rhabdomyolysis

    PubMed Central

    Haider, Mahnur; Rizvi, Syed Ahsan

    2015-01-01

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

  7. [Myocardial rhabdomyolysis following paraphenylene diamine poisoning].

    PubMed

    Ababou, A; Ababou, K; Mosadik, A; Lazreq, C; Sbihi, A

    2000-02-01

    Acute intoxication with paraphenylene diamine, a mineral compound used as hair dye, associated asphyxia due to cervical oedema and rhabdomyolysis. We report the case of a patient with lethal cardiogenic shock secondary to myocardial rhabdomyolysis confirmed by a postmortem biopsy. PMID:10730172

  8. Early fluid resuscitation in patients with rhabdomyolysis

    Microsoft Academic Search

    Zaid A. Abassi; Ori S. Better

    2011-01-01

    Extensive rhabdomyolysis is often lethal unless treated immediately. Early mortality arises from hypovolemic shock, hyperkalemia, acidosis and myoglobinuric acute kidney injury (AKI). Many individuals with rhabdomyolysis could be saved, and myoglobinuric AKI prevented, by early vigorous fluid resuscitation with ?12 l daily intravenous infusion of alkaline solution started at the scene of injury. This regimen stabilizes the circulation and mobilizes

  9. [Severe hypokalemic rhabdomyolysis. Report of six cases].

    PubMed

    Luzardo, Leonella; Silvariño, Ricardo; Boggia, José; Noboa, Oscar; Gadola, Liliana

    2014-05-01

    Rhabdomyolysis results from acute necrosis of skeletal muscle fibers and consequent leakage of muscle constituents into the circulation. It ranges from an asymptomatic state to a severe condition associated with extreme elevations in creatine kinase and acute renal failure. Reported etiologies of rhabdomyolysis include alcohol abuse, drugs, muscle trauma and muscle overexertion. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, toxins and endocrine disorders. Hypokalemia is a rare cause of rhabdomyolysis. We report six patients aged 31 to 57 years (three women) with a severe hypokalemic rhabdomyolysis, secondary to chronic diarrhea in two patients, treatment with loop diuretics in one and Gitelman syndrome in three. Rhabdomyolysis may be underdiagnosed in the context of hypokalemia, because the neuromuscular symptoms can be attributed solely to the electrolyte disorder. PMID:25427024

  10. Exertional rhabdomyolysis in an adolescent athlete.

    PubMed

    Moghtader, J; Brady, W J; Bonadio, W

    1997-12-01

    Exertional rhabdomyolysis has been previously reported in adult patients following such strenuous activities as military basic training, weight lifting, and marathon running. Exertional rhabdomyolysis in previously healthy pediatric athletes, however, is rarely encountered. The presentation of rhabdomyolysis is characterized by the classical triad of myalgias, muscle weakness, and darkened urine. This classic presentation, however, is not noted the majority of patients, especially early in the disease course when the patient may complain only of myalgias or weakness. Thus, the emergency physician must have a high index of suspicion for this entity based on the appropriate clinical setting. We report a classic case of exercise-induced rhabdomyolysis complicated by acute renal failure in a previously healthy adolescent athlete, whose initial presentation was nonspecific, prompting the diagnosis of overexertion. PMID:9434995

  11. 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

  12. Rhabdomyolysis: advances in diagnosis and treatment.

    PubMed

    Parekh, Ram; Care, David A; Tainter, Christopher R

    2012-03-01

    Rhabdomyolysis is a potentially life-threatening condition caused by a breakdown of skeletal muscle and the release of the intracellular contents into the circulatory system. There are many possible causes, including crush injury, excessive muscular activity, medications, infections, and varied metabolic, connective tissue, rheumatologic, and endocrine disorders. It is vital that emergency clinicians consider the diagnosis when patients present with circumstances known to be high-risk for rhabdomyolysis, including intoxication, prolonged immobilization, and/or altered mentation. Optimal crystalloid selection is still debated, but immediate, aggressive intravenous volume expansion is indicated to prevent myoglobinuric renal failure. Serum potassium levels must be obtained and electrocardiograms must be evaluated to identify life- and limb-threatening complications of hyperkalemia. This review examines the current evidence on symptoms and diagnostic methods as well as standard first-line treatments of rhabdomyolysis. In addition, evidence from animal models on urine alkalinization with sodium bicarbonate infusion is discussed. PMID:22497086

  13. [Rhabdomyolysis secondary to simvastatin and phenofibrate].

    PubMed

    Forcadell-Peris, M J; de Diego-Cabanes, C

    2014-01-01

    Statins, which are used as first-line drugs in the prevention of cardiovascular disease, are usually safe, but in some cases there may be muscular toxicity. Statin-associated myopathy, can present as myalgia, myositis or rhabdomyolysis. Only 0.44 per 10,000 treated and per year, develop rhabdomyolysis. There are many risk factors associated with the patient and with the pharmacological treatment. A risk of muscle injury of 1-5% has been reported with some statins combined with fibrates. The fibrate with the highest risk of myopathy in combination with statins is gemfibrozil, while phenofibrate seems to be the safest. The case is presented of a 60 year-old woman with clinical symptoms and laboratory findings that suggested rhabdomyolysis secondary to a combination of simvastatin and phenofibrate. This case reminds physicians of the need to closely monitor these patients, in addition to alert them to the onset of muscle pain or weakness. PMID:24768027

  14. Rhabdomyolysis induced by excessive coffee drinking.

    PubMed

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

    2014-08-01

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

  15. 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…

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

    Microsoft Academic Search

    Ana L Huerta-Alardín; Joseph Varon; Paul E Marik

    2005-01-01

    Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and

  17. Exertional rhabdomyolysis in a patient with calcium adenosine triphosphatase deficiency

    Microsoft Academic Search

    P J Poels; R A Wevers; J P Braakhekke; A A Benders; J H Veerkamp; E M Joosten

    1993-01-01

    A patient with exertional rhabdomyolysis and continuously elevated serum creatine kinase (CK) was investigated. The known causes of recurrent attacks of rhabdomyolysis were ruled out by appropriate histochemical and biochemical investigations. During ischaemic exercise tests an abnormal K(+)-efflux from exercising muscles was observed. The patient was found to have a deficiency of muscular Ca(2+)-ATPase. Dantrolene sodium therapy gave relief of

  18. Hypothyroidism Induced Severe Rhabdomyolysis in a Hemodialysis Patient

    PubMed Central

    Tatar, Erhan; Isikyakar, Tolgay; Yeniay, Kezban Pinar; Uzuner, Hasan Huseyin; Sevinc Ok, Ebru

    2014-01-01

    Hypothyroidism occurs relatively common and is a significant cause of morbidity and mortality during the course of chronic kidney disease. Rhabdomyolysis is a potentially life-threatening condition characterised by necrosis of muscular tissue and rarely associates with hypothyroidism. Here we describe a case of rhabdomyolysis due to severe hypothyroidism in a 56-year-old female hemodialysis patient. PMID:24803938

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

    PubMed

    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

  20. Rhabdomyolysis after laparoscopic radical nephrectomy -A case report-

    PubMed Central

    Kim, Tae Kwane; Lee, Myeong Ha

    2010-01-01

    Rhabdomyolysis is a rare but potentially lethal clinical syndrome that results from acute muscle fiber necrosis with leakage of muscle constituents into blood. This devastating disease could be due to muscle compression caused by urologic positioning for a lengthy nephrectomy. In this regard, laparoscopic renal surgery may be a risk for the development of rhabdomyolysis. This phenomenon of massive muscle necrosis can produce secondary acute renal failure. The risk factors have to be managed carefully during anesthetic management. Here, we report a case of a patient with rhabdomyolysis that developed in the flexed lateral decubitus position during laparoscopic nephrectomy. PMID:21286457

  1. Rhabdomyolysis: A rare presentation of aldosterone-producing adenoma

    PubMed Central

    Cooray, M. Samanthi A.; Bulugahapitiya, Uditha S.; Peiris, D. Natasha

    2013-01-01

    Rhabdomyolysis results from acute damage of the skeletal muscle brought on by various conditions of which hypokalemia is a recognized, but less common condition. Although primary aldosteronism may cause severe hypokalemia leading to rhabdomyolysis, the patients may have potassium levels within the normal range on routine biochemistry. In addition, hypokalemia may be triggered by initiation of diuretic therapy for control of hypertension. Here, we describe a patient with an aldosterone secreting adrenal adenoma, who presented with acute rhabdomyolysis secondary to severe hypokalemia triggered by initiation of diuretic therapy. PMID:24251171

  2. Superimposed cocaine-induced rhabdomyolysis in a patient with aortic dissection rhabdomyolysis.

    PubMed

    Goldberg, Andrew

    2015-03-15

    A 52-year-old man presented with acute, sharp chest pain radiating to the back and abdomen after using cocaine 18 hours previously. Computed tomographic angiography revealed a type B aortic dissection that extended to the iliac arteries. The patient underwent balloon fenestration, placement of multiple aortic stents, and bilateral leg fasciotomy. He eventually went into hyperkalemic arrest but was successfully resuscitated, after which his serum lactate and creatine kinase levels peaked at 7.4 mmol/L and 990,400 U/L, respectively. The combination of aortic dissection and creatine kinase toxicity was extensive enough to cause permanent renal failure and paraplegia below T6. The severity of the patient's symptoms was attributed to concomitant cocaine-induced rhabdomyolysis and aortic dissection rhabdomyolysis. PMID:25774753

  3. Rhabdomyolysis caused by co-medication with simvastatin and clarithromycin

    Microsoft Academic Search

    Judith Wagner; Christine Suessmair; Hans-Walter Pfister

    2009-01-01

    Springer-Verlag 2009 Sirs, Rhabdomyolysis is a rare side-effect of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase-inhibitors. Co-medication with inhibitors of the cytochrome P450 3A4 (CYP34A) pathway may increase this risk. We describe the case of a female patient who developed severe rhabdomyolysis due to concomitant use of simvastatin (20 mg) and clarithromycin. Previous reports on this interaction involved patients on high doses

  4. Polydipsia, hyponatremia and rhabdomyolysis in schizophrenia: A case report

    PubMed Central

    Chen, Li-Chi; Bai, Ya-Mei; Chang, Meng-Han

    2014-01-01

    The prevalence of polydipsia among patients with schizophrenia is 6%-20%. Around 10%-20% of patients with polydipsia may develop hyponatremia and even complicated with rhabdomyolysis. Here we presented a 40-year-old man with schizophrenia, who had received paliperidone 15 mg/d for more than one year, and polydipsia was noted. In Jan, 2014, he developed hyponatremia (Na 113 mEq/L) with consciousness disturbance. After 3% NaCl (500 cc/d) intravenous supplement for three days, the hyponatremia was corrected, but rhabdomyolysis developed with a substantial elevation in the level of creatine kinase (CK) to 30505 U/L. After hydration, the CK level gradually decreased to 212 U/L. Both the hyponatremia itself and quick supplementation of NaCl can cause rhabdomyolysis. If rhabdomyolysis is not recognized, insufficient hydration or water restriction for polydipsia may further exacerbate the rhabdomyolysis with a lethal risk. In this case, we highlight the possible complication of rhabdomyolysis with polydipsia-induced hyponatremia. In addition to monitoring the serum sodium level, the monitoring of CK is also important; and switching of antipsychotic may improve the polydipsia. PMID:25540730

  5. Prevalence of Rhabdomyolysis in Sympathomimetic Toxicity: a Comparison of Stimulants.

    PubMed

    O'Connor, Ayrn D; Padilla-Jones, Angie; Gerkin, Richard D; Levine, Michael

    2014-12-01

    Synthetic cathinones have emerged as popular drugs of abuse and produce sympathomimetic toxicity. It is unknown if rhabdomyolysis occurs more frequently following the use of synthetic cathinones compared to other stimulants. This retrospective study sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Patients greater than 14 years of age with sympathomimetic toxicity and detection of a stimulant agent in urine via gas chromatography-mass spectroscopy (GC-MS) were included. Patients were excluded if clinical sympathomimetic toxicity was not present, a serum creatine kinase (CK) was not measured, or urine GC-MS was not performed. Rhabdomyolysis and severe rhabdomyolysis were defined as CK?>?1000 and 10,000 IU/L, respectively. Prevalence of rhabdomyolysis and severe rhabdomyolysis were reported. Logistic regression was performed to determine the relative effect in single-agent exposures of a synthetic cathinone compared to other sympathomimetics on rhabdomyolysis. A secondary outcome, a composite endpoint defined as need for mechanical ventilation, renal replacement therapy, development of compartment syndrome, or death, was also analyzed. One hundred two subjects met inclusion criteria; median age (IQR) was 32 (25-42)?years with a range of 14-65 years; 74 % were male. Rhabdomyolysis occurred in 42 % (43/102) of subjects. Patients whose sympathomimetic toxicity could be ascribed to a single agent were considered for further statistical analysis and placed into four groups: methamphetamine (n?=?55), synthetic cathinone (n?=?19), cocaine (n?=?9), and other sympathomimetic (n?=?6). In 89 subjects with single stimulant exposure, the prevalence of rhabdomyolysis was as follows: synthetic cathinone, 12/19 (63 %); methamphetamine, 22/55 (40 %); cocaine, 3/9 (33 %); and other single agent, 0/6 (0 %). The occurrence of severe rhabdomyolysis (CK?>?10,000 IU/L) for each of the four groups was synthetic cathinone with 5/19 (26 %), methamphetamine with 2/55 (3.6 %), cocaine with 1/9 (11 %), and other with 0/6 (0 %). Median maximal CK (range) by groups was as follows: synthetic cathinone, 2638 (62-350,000+)?IU/L; methamphetamine, 665 (61-50,233)?IU/L; cocaine, 276 (87-25,614)?IU/L; and other, 142 (51-816)?IU/L. A statistically significant difference (p?=?0.004) was found when comparing maximal CK among the four groups. Exposure to a synthetic cathinone compared with other sympathomimetics was associated with increased risk of developing rhabdomyolysis and severe rhabdomyolysis with odds ratios of 3.09 and 7.98, respectively. In this cohort of patients with sympathomimetic toxicity, 42 % developed rhabdomyolysis. Synthetic cathinones were associated with an increased risk of rhabdomyolysis and severe rhabdomyolysis compared with other stimulants. PMID:25468315

  6. Bullous Lesions, Sweat Gland Necrosis and Rhabdomyolysis in Alcoholic Coma

    PubMed Central

    Asokan, Neelakandhan; Binesh, Vayappurath Gangadharan; Andrews, Andrews Mekkattukunnel; Jayalakshmi, Pattomthadathil Sankaran

    2014-01-01

    A 42-year-old male developed hemorrhagic bullae and erosions while in alcohol induced coma. The lesions were limited to areas of the body in prolonged contact with the ground in the comatose state. He developed rhabdomyolysis, progressing to acute renal failure (ARF). Histopathological examination of the skin showed spongiosis, intraepidermal vesicles, and necrosis of eccrine sweat glands with denudation of secretory epithelial lining cells. With supportive treatment and hemodialysis, the patient recovered in 3 weeks time. This is the first reported case of bullous lesions and sweat gland necrosis occurring in alcohol-induced coma complicated by rhabdomyolysis and ARF. PMID:25484420

  7. Paraphenylene diamine hair dye poisoning: an uncommon cause of rhabdomyolysis.

    PubMed

    Elevli, Murat; Civilibal, Mahmut; Ersoy, Ozlem; Demirkol, Demet; Gedik, Ahmet Hakan

    2014-07-01

    Paraphenylene daimine (PPD) is a kind of aromatic amine that is widely used in several industrial products. Women also use PPD added to henna (Lawasonia alba) as a hair dye. Though rare in Western countries, PPD poisoning is quite common in East Africa, India and Middle Eastern countries because it is a traditional product at these countries. Different pathologies were described as caused by PPD ingestion including angioedema of head and neck, rhabdomyolysis, and acute renal failure. The authors report a case of systemic poisoning with PPD that lead to angioedema resulting in tracheostomy and rhabdomyolysis. PMID:23723080

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

    PubMed Central

    Fadila, Mario F.; Wool, Kenneth J.

    2015-01-01

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

  9. Marked Hypokalemic Rhabdomyolysis with Myoglobinuria due to Diuretic Treatment

    Microsoft Academic Search

    Shuzo Shintani; Tatsuo Shiigai; Hiroshi Tsukagoshi

    1991-01-01

    A 74-year-old male was admitted to hospital with acute rhabdomyolysis and myoglobinuria due to hypokalemia. The hypokalemia resulted from diuretic treatment. He had no family history of myopathy, and no diarrhea and vomiting. The neurological examination revealed painful quadriplegia. The blood pressure was 160\\/74 mm Hg. Laboratory examination showed hypokalemic and hypochloremic metabolic alkalosis (serum K 1.5 mEq\\/1, serum CI

  10. Fulminant hepatic failure accompanied by fatal rhabdomyolysis following exertional heatstroke

    Microsoft Academic Search

    Hideaki Miura; Hiroshi Yoshimoto; Shigehiro Kitamura; Haruki Yamada

    2010-01-01

    We present a previously healthy 38-year-old Japanese man who developed exertional heatstroke (EHS) following a long-distance\\u000a run and presented with fulminant hepatic failure (FHF) accompanied by a life-threatening flare-up of rhabdomyolysis. Intensive\\u000a life-supporting medical procedures, including plasma exchange, hemodiafiltration, steroid pulse therapy, and anticoagulant\\u000a treatment enabled the patient to survive FHF. Initially, his general condition was thought to be improving;

  11. Severe generalised rhabdomyolysis with fatal outcome associated with isotretinoin.

    PubMed

    Hartung, Benno; Merk, Hans F; Huckenbeck, Wolfgang; Daldrup, Thomas; Neuen-Jacob, Eva; Ritz-Timme, Stefanie

    2012-11-01

    Isotretinoin is considered to be a safe and effective therapy in otherwise therapy-resistant acne. Elevated serum creatine phosphokinase values with or without muscle-related symptoms in isotretinoin-treated patients have been reported and interpreted as benign phenomena, lethal cases have not been described yet. We present the case of a 20-year-old male who died from severe generalised rhabdomyolysis associated with isotretinoin treatment. PMID:22895802

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

    PubMed Central

    Mendes, Polyana; Robles, Priscila Games

    2014-01-01

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

  13. Rhabdomyolysis due to Lamivudine administration in acute viral hepatitis B infection: a case report from Malaysia

    PubMed Central

    Baharin, Janudin; Sahari, Narisa Sulaiman; Lim, Sazlyna Mohd Sazlly

    2014-01-01

    Rhabdomyolysis is a serious but rare side effect of Lamivudine treatment. Therefore, appropriate biochemical monitoring should be undertaken when it is used in the treatment of hepatitis B. This paper presents a case of Lamivudine-associated rhabdomyolysis in a 31-year-old man with congenital heart disease and hepatitis B. Three days after starting Lamivudine, the patient developed myalgia. Significant muscle tenderness and swelling of the upper and lower limbs was discovered during a physical examination. Creatine kinase was markedly raised. Lamivudine-induced rhabdomyolysis was suspected and the drug was discontinued. Symptoms and creatine kinase activity improved within four days of Lamivudine cessation and hydration. Early identification of Lamivudine-induced rhabdomyolysis is key in preventing this potentially fatal drug reaction; withdrawal of Lamivudine may contribute to complete remission of rhabdomyolysis.

  14. Risk Factors for Acute Kidney Injury in Severe Rhabdomyolysis

    PubMed Central

    Rodríguez, Eva; Soler, María J.; Rap, Oana; Barrios, Clara; Orfila, María A.; Pascual, Julio

    2013-01-01

    Background Acute kidney injury (AKI) is a life-threatening complication of severe rhabdomyolysis. This study was conducted to assess risk factors for AKI and to develop a risk score for early prediction. Methods Retrospective observational cohort study with a 9-year follow-up, carried out in an acute-care teaching-affiliated hospital. A total of 126 patients with severe rhabdomyolysis defined as serum creatine kinase (CK) > 5,000 IU/L fulfilled the inclusion criteria. Univariate and logistic regression analyses were performed to determine risk factors for AKI. Based on the values obtained for each variable, a risk score and prognostic probabilities were estimated to establish the risk for developing AKI. Results The incidence of AKI was 58%. Death during hospitalization was significantly higher among patients with AKI, compared to patients without AKI (19.2% vs 3.6%, p?=?0.008). The following variables were independently associated with AKI: peak CK (odds ratio [OR] 4.9, 95%CI 1.4-16.8), hypoalbuminemia (< 33 mg/dL, [OR 5.1, 95%CI 1.4-17-7]), metabolic acidosis (OR 5.3, 95%CI 1.4-20.3), and decreased prothrombin time (OR 4.4, 95% CI 1.3-14.5). A risk score for AKI was calculated for each patient, with an OR of 1.72 (95%CI 1.45-2.04). The discrimination value of the predictive model was established by means of a ROC curve, with the area under the curve of 0.871 (p<0.001). Conclusions The identification of independent factors associated with AKI and a risk score for early prediction of this complication in patients with severe rhabdomyolysis may be useful in clinical practice, particularly to implement early preventive measures. PMID:24367578

  15. Encephalopathy and rhabdomyolysis induced by iotrolan during epiduroscopy

    Microsoft Academic Search

    Ju Mizuno; Tobias Gauss; Masahiro Suzuki; Masakazu Hayashida; Hideko Arita; Kazuo Hanaoka

    2007-01-01

    Purpose  We describe a complication of epiduroscopy with encephalopathy and rhabdomyolysis associated with the contrast medium iotrolan.\\u000a \\u000a \\u000a \\u000a Clinical features  A 76-yr-old man with failed back surgery syndrome underwent epiduroscopy. Sufficient lysis could not be achieved in the epidural\\u000a space above the level of L4 due to dense adhesions and scar tissue. After epidural injections of iotrolan and mepivacaine, he developed motor weakness

  16. Protracted hypocalcemia following post-thyroidectomy lumbar rhabdomyolysis secondary to evolving hypoparathyroidism.

    PubMed

    Cheema, Usman Y; Vogler, Carrie N; Thompson, Joshua; Sattovia, Stacy L; Vallurupalli, Srikanth

    2015-03-01

    Rhabdomyolysis is characterized by skeletal muscle breakdown. It is a potential cause of serious electrolyte and metabolic disturbances, acute kidney insufficiency, and death. Recently, rhabdomyolysis has been increasingly recognized following certain surgical procedures. We discuss the case of a morbidly obese 51-year-old woman who developed postoperative rhabdomyolysis of the lumbar muscles following a prolonged thyroidectomy for a large goiter. We discuss how her morbid obesity, the supine surgical position, the duration of surgery (including prolonged exposure to anesthetic agents), and postoperative immobility contributed to the development of rhabdomyolysis. Immediately after surgery, the patient developed hypocalcemia, which was likely due to rhabdomyolysis since her serum parathyroid hormone level was normal. Later, however, persistent hypocalcemia despite resolution of the rhabdomyolysis raised a suspicion of iatrogenic hypoparathyroidism, which was confirmed by a suppressed parathyroid hormone level several days after surgery. In post-thyroidectomy patients with risk factors for rhabdomyolysis, maintaining a high degree of clinical suspicion and measuring serum creatine kinase and parathyroid hormone levels can allow for an accurate interpretation of hypocalcemia. PMID:25738717

  17. 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

  18. Massive pericardial effusion and rhabdomyolysis secondary to untreated severe hypothyroidism: the first report.

    PubMed

    Zare-Khormizi, M R; Rahmanian, M; Pourrajab, F; Akbarnia, S

    2014-10-01

    Hypothyroidism is an endocrine disease with various clinical manifestations. It is a rare cause for rhabdomyolysis and massive pericardial effusion. We describe a case of severe hypothyroidism secondary to autoimmune hashimoto thyroiditis with massive pericardial effusion and rhabdomyolysis. Improvement of mentioned complications after hypothyroidism treatment and rule out of other possible causes are supportive clues that hypothyroidism is the main cause of patient's rare presentation. With the best of our knowledge, it is the first report of rhabdomyolysis and massive pericardial effusion coincidence in a patient of adult population with primary uncontrolled hypothyroidism for years. PMID:25056490

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

    PubMed

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

    2015-04-01

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

  20. [Rhabdomyolysis as an unspecyfic symptom of mushroom poisoning--a case report].

    PubMed

    Chwaluk, Pawe?

    2013-01-01

    Since 2001 a number of cases of mushroom poisoning with concomitant rhabdomyolysis have been described. Among the edible mushrooms growing in Europe, these reports concerned only Tricholoma equestre. The results of animal studies suggest that rhabdomyolysis could be a consequence of consumption of other edible fungi, and its occurrence depends on the amount of ingested mushrooms and individual sensitivity. To the best of our knowledge, this is the first report of rhabdomyolysis associated with the consumption of edible mushrooms from Leccinum and Boletus species. A 57-years old man was admitted to the hospital due to severe pain and weakness of thigh muscles with a high serum creatine kinase activity -3811 U/L. Within two days before hospitalization he consumed repeatedly large quantities of stewed Leccinum and Boletus mushrooms. Clinical signs of toxicity and biochemical changes subsided after several days of hospitalization. Rhabdomyolysis after ingestion of a large amount of mushrooms can be an unspecific symptom, unrelated to fungi species. PMID:24466721

  1. A case of rhabdomyolysis in which levetiracetam was suspected as the cause

    PubMed Central

    Akiyama, Hisanao; Haga, Yoshiteru; Sasaki, Naoshi; Yanagisawa, Toshiyuki; Hasegawa, Yasuhiro

    2014-01-01

    Several studies have reported rhabdomyolysis induced by various drugs but not by the antiepileptic drug levetiracetam. We present a case of suspected levetiracetam-induced rhabdomyolysis. A 29-year-old woman was hospitalized for generalized tonic–clonic seizure and given levetiracetam for the first time. One day after starting levetiracetam, she developed myalgia, particularly backache, and weakness in both lower limbs. Based on her clinical symptoms and blood test results indicating hyperCKemia, our diagnosis was levetiracetam-induced rhabdomyolysis. Withdrawal of levetiracetam immediately improved the clinical symptoms and hyperCKemia. This first report of suspected levetiracetam-induced rhabdomyolysis provides important information for treating patients early in levetiracetam administration. PMID:25667895

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

    PubMed

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

    2010-04-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. [Dialysis for severe rhabdomyolysis 7 days after multiple trauma].

    PubMed

    Malin, A; Freyhoff, J; Nobis, W; Bone, H G

    2012-03-01

    A case report of severe rhabdomyolysis in a 33-year-old motorcyclist after multiple trauma is described. The injuries included severe thoracic and abdominal trauma as well as injuries to the extremities and spinal column. During the first 3 days of treatment a forced volume therapy was performed because of increased levels of creatine kinase during which the patients condition stabilized both hemodynamically and respiratorily. On day 10 the patient developed a rise in temperature to 42°C with no evidence of a re-infection and the creatine kinase levels rose to 109,830 U/l. A continuous hemofiltration was started because of acute renal failure. The creatine kinase levels declined significantly and renal function also returned to normal with adequate diuresis up to day 20. After intensive questioning of the relatives a history of long-term use of anabolic steroids, clenbuterol as well as the intake of testosterone enanthate was conceded. Cocaine and amphetamines were also taken regularly by the patient. PMID:22430552

  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. PMID:22768426

  6. 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

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

    PubMed

    Petrov, Mikhail; Yatsynovich, Yan; Lionte, Catalina

    2015-01-01

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

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

    PubMed Central

    Issa, Mayada

    2014-01-01

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

  9. Fatal Rhabdomyolysis following Spine Surgery in a Morbidly Obese Patient: A Case Report

    PubMed Central

    Jung, Se Ho; Kim, Dong Min; Ju, Chang Il

    2014-01-01

    We generally believe that obese patients are faced on higher risk of developing perioperative complications. Rhabdomyolysis is a rare but potentially life-threatening condition caused by the release of injured skeletal muscle components into the circulation. It usually results from mechanical damage to the muscle, intoxication, or a postictal state after a seizure. In the present study, we have reported a rare case of rhabdomyolysis developing in a morbidly obese patient after upper thoracic spinal fusion surgery. We have found acute renal failure that evolved during the course of treatment resulted in a fatal outcome even though the patient received intensive supportive care. Our experience suggests that this rare complication should be considered in morbidly obese patients and those efforts should be made to avoid rhabdomyolysis. PMID:25620985

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

    PubMed

    Shah, S V; Reddy, K

    2010-01-01

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

  11. Seizures, Ventricular Tachycardia, and Rhabdomyolysis as a Result of Ingestion of Venlafaxine and Lamotrigine

    Microsoft Academic Search

    Claudia Peano; Jerrold B Leikin; Paul K Hanashiro

    1997-01-01

    Few cases of overdoses have been described involving venlafaxine, lamotrigine, or a combination of the two agents. We describe a combined venlafaxine and lamotrigine ingestion in a patient presenting with a seizure, ventricular tachycardia, and rhabdomyolysis. We conclude that patients with overdoses that involve venlafaxine can exhibit severe cardiac effects in addition to seizures, especially if venlafaxine is combined with

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

    PubMed

    Parr, M J; Willatts, S M

    1991-07-01

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

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

    PubMed

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

    2013-07-01

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

  14. Myopericarditis and exertional rhabdomyolysis following an influenza A (H3N2) infection

    PubMed Central

    2013-01-01

    Background Acute myopericarditis and exertional rhabdomyolysis, two uncommon but well-described diseases with potentially life-threatening effects, are generally considered as independent clinical entities. However, they may in fact be pathophysiologically related under certain circumstances. This is the first ever report of influenza myopericarditis provoked by exertional rhabdomyolysis to the best of our knowledge. Case presentation A 25-year-old immunocompetent Chinese man presented with bilateral leg pain, dizziness, and shortness of breath on admission soon after completing vigorous training comprising running drills. Exertional rhabdomyolysis was diagnosed with 44 fold high serum creatine phosphokinase. Then he developed chest pain, pericardial effusion, changes of electrocardiography and positive troponin I suggestive of myopericarditis. Influenza A (H3N2) virus infection was confirmed by polymerase chain reaction analysis of nasopharyngeal wash samples. Other possible infective and autoimmune causes were excluded. Patient recovered completely with anti-inflammatory therapy and the supportive care. Conclusion This case suggests that clinicians who treat patients with exertional rhabdomyolysis should be aware of the potential vulnerability to acute myopericarditis, especially in the presence of recent influenza A infection. PMID:23786640

  15. Epidemiology of Exertional Rhabdomyolysis Susceptibility in Standardbred Horses Reveals Associated Risk Factors and Underlying Enhanced Performance

    PubMed Central

    Isgren, Cajsa M.; Upjohn, Melissa M.; Fernandez-Fuente, Marta; Massey, Claire; Pollott, Geoff; Verheyen, Kristien L. P.; Piercy, Richard J.

    2010-01-01

    Background Exertional rhabdomyolysis syndrome is recognised in many athletic horse breeds and in recent years specific forms of the syndrome have been identified. However, although Standardbred horses are used worldwide for racing, there is a paucity of information about the epidemiological and performance-related aspects of the syndrome in this breed. The objectives of this study therefore were to determine the incidence, risk factors and performance effects of exertional rhabdomyolysis syndrome in Standardbred trotters and to compare the epidemiology and genetics of the syndrome with that in other breeds. Methodology/Principal Findings A questionnaire-based case-control study (with analysis of online race records) was conducted following identification of horses that were determined susceptible to exertional rhabdomyolysis (based on serum biochemistry) from a total of 683 horses in 22 yards. Thirty six exertional rhabdomyolysis-susceptible horses were subsequently genotyped for the skeletal muscle glycogen synthase (GYS1) mutation responsible for type 1 polysaccharide storage myopathy. A total of 44 susceptible horses was reported, resulting in an annual incidence of 6.4 (95% CI 4.6–8.2%) per 100 horses. Female horses were at significantly greater risk than males (odds ratio 7.1; 95% CI 2.1–23.4; p?=?0.001) and nervous horses were at a greater risk than horses with calm or average temperaments (odds ratio 7.9; 95% CI 2.3–27.0; p?=?0.001). Rhabdomyolysis-susceptible cases performed better from standstill starts (p?=?0.04) than controls and had a higher percentage of wins (p?=?0.006). All exertional rhabdomyolysis-susceptible horses tested were negative for the R309H GYS1 mutation. Conclusions/Significance Exertional rhabdomyolysis syndrome in Standardbred horses has a similar incidence and risk factors to the syndrome in Thoroughbred horses. If the disorder has a genetic basis in Standardbreds, improved performance in susceptible animals may be responsible for maintenance of the disorder in the population. PMID:20644724

  16. Pravastatin-induced rhabdomyolysis and purpura fulminans in a patient with chronic renal failure

    PubMed Central

    Kato, Kazuya; Onodera, Kazuhiko; Iwasaki, Yoshiaki; Matsuda, Minoru; Kawakami, Takako; Higuchi, Mineko; Kato, Kimitaka; Kato, Yurina; Taniguchi, Masahiko; Furukawa, Hiroyuki

    2015-01-01

    Introduction Rhabdomyolysis associated with the use of pravastatin has been demonstrated to be a rare but potentially life-threatening adverse effect of statins. Here, we report a rare case of rhabdomyolysis and purpura fulminans in a patient who had used pravastatin and developed chronic renal failure (CRF) necessitating the initiation of dialysis. Presentation of case We present the case of an 86-year-old man with chronic kidney disease (CKD) treated with dialysis who was admitted with back pain. He was prescribed and took pravastatin for almost 3 years to treat hyperlipidemia. He received hemodialysis therapy 7 times prior to presentation. Laboratory values included a serum creatine concentration of 6.6 mg/dl and a creatinine phosphokinase (CPK) concentration of 2350 IU/L. An abdominal computed tomography scan showed swollen muscles with reduced muscle density and air density in the multifidus muscle. Two days after admission, he had large, tender ecchymotic lesions and purpuric progressive skin necrosis over the back, abdomen, and upper and lower extremities. The patient died 6 days after the initial admission due to disseminated intravascular coagulation (DIC). Based on these findings and the clinical history, a diagnosis of pravastatin-induced rhabdomyolysis and purpura fulminans was made. Discussion The long-term use of statin therapy and the initiation of dialysis therapy due to ESRD, followed by a rapid onset of rhabdomyolysis within 6 days, is indicative of an elevated statin concentration. Conclusion We report an extremely rare case of pravastatin-induced rhabdomyolysis and purpura fulminans with DIC in a patient with CRF. PMID:25644555

  17. Severe recurrent rhabdomyolysis-induced acute kidney injury in a HIV-infected patient on antiretroviral therapy.

    PubMed

    Spiegel, Louis R; Schrier, Peter B; Shah, Hitesh H

    2013-09-01

    Antiretroviral medications, specifically tenofovir, have been linked to acute tubular necrosis in humans with a suggested mechanism of direct tubular injury. Rhabdomyolysis has rarely been described in patients on highly active antiretroviral therapy (HAART). To the best of our knowledge, severe recurrent rhabdomyolysis-induced acute kidney injury (AKI) in a HIV-infected patient on two different triple antiretroviral regimens has not been reported. We present a HIV-positive patient who first developed heme pigment-induced oliguric AKI due to non-traumatic rhabdomyolysis, 5 days after initiation of triple antiretroviral therapy. Renal function normalized 2 months after discontinuation of antiretroviral therapy. Two weeks after reinitiating a different HAART regimen, our patient developed a recurrent episode of severe rhabdomyolysis-induced AKI. Both rhabdomyolysis and AKI resolved after discontinuation of the second antiretroviral regimen. First tenofovir and subsequently abacavir seem to be the likely culprits in our case. We also briefly discuss tenofovir nephrotoxicity followed by a literature review on rhabdomyolysis in HIV-infected patients. PMID:23883141

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

    PubMed

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

    2010-09-01

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

  19. 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

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

    PubMed

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

    2004-01-01

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

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

    PubMed

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

    2014-01-01

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

  2. Rhabdomyolysis in an elderly multitreated patient: multiple drug interactions after statin withdrawal.

    PubMed

    Ginanneschi, Federica; Volpi, Nila; Giannini, Fabio; Rocchi, Raffaele; Donati, Donatella; Aglianò, Margherita; Lorenzoni, Paola; Rossi, Alessandro

    2014-01-15

    Rhabdomyolysis precipitated by multitherapy is most frequently described during statin treatment, due to impairment of statin clearance by drugs sharing cytochrome P450 biotransformation pathway. Modulation of membrane transporters for drug efflux, operated by substrates, can also affect drugs' tissue levels. We report rhabdomyolysis in an elderly patient, in multitreatment with different potentially myotoxic medications, taking place seven months after atorvastatin discontinuation. Affected by ischaemic heart disease, arterial hypertension and dementia-related behaviour disturbances, the patient was receiving angiotensin 2-receptor inhibitors, beta-blockers, vasodilators, diuretics, salycilates, allopurinol, proton pump inhibitors, antipsychotics and antidepressants. He had taken atorvastatin for 14 years, with constantly normal creatine-kinase plasma levels. Two months after addition of the antianginal drug ranolazine, creatine-kinase mildly increased and atorvastatin was withdrawn. Nonetheless, creatine-kinase progressively rose, with severe weakness and rhabdomyolysis developing seven months later. Muscle biopsy showed a necrotizing myopathy with no inflammation or autoimmune changes. After ranolazine withdrawal, creatine-kinase and myoglobin returned to normal levels and strength was restored. Several psychotropic and cardiovascular medications prescribed to the patient share either cytochrome P450 biotransformation and permeability-glycoprotein efflux transport. In the event of cardiovascular/neuropsychiatric polypharmacy in geriatric patients, the risk of muscle severe adverse effects from pharmacokinetic drug-drug interaction should be considered beyond the direct myotoxicity of statins. PMID:24252882

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

    PubMed Central

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

    2013-01-01

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

  4. Dopamine-deficiency-enhanced hyperthermia and rhabdomyolysis during a heat wave in a metachromatic leucodystrophy heterozygote with metabolic myopathy.

    PubMed

    Finsterer, Josef; Reining-Festa, Alice; Stollbergr, Claudia; Voigtlander, Till

    2011-12-01

    Whether a dopamine-deficiency syndrome in a Parkinson-syndrome (PS) may occur more easily during a heat wave than during more temperate climate conditions is unknown. We report a case that may suggest this. A 56 yo male with heterozygosity for metachromatic leucodystrophy and a history of metabolic myopathy, PS and diabetes experienced worsening of the PS during a heat wave. His condition further deteriorated upon reduction of ropinirol, resulting in hyperthermia, respiratory insufficiency, rhabdomyolysis, and severe thrombocytopenia. One month later he was alert but tetraplegic and required ventilatory support. Hyper-CK-emia returned to similar levels as before rhabdomyolysis. Reduction of dopamine agonists during a heat wave may induce a dopamine deficiency syndrome with hyperthermia, rhabdomyolysis and thrombocytopenia. PMID:22368973

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

    PubMed Central

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

    2015-01-01

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

  6. Ticagrelor-induced renal failure leading to statin-induced rhabdomyolysis.

    PubMed

    van Vuren, A J; de Jong, B; Bootsma, H P R; Van der Veen, M J; Feith, G W

    2015-03-01

    Renal function deterioration is a rather frequent side effect of ticagrelor; this is especially so in patients over the age of 75, with pre-existent mild renal failure and÷or taking an angiotensin receptor inhibitor. We describe a patient in whom deterioration of renal function due to ticagrelor led to a rise in serum concentration of rosuvastatin which resulted in rhabdomyolysis. The presented case emphasises the importance to check renal function routinely before and one month after starting ticagrelor and to screen carefully for possible interactions with other drugs. PMID:25852115

  7. Rhabdomyolysis Occurring under Statins after Intense Physical Activity in a Marathon Runner.

    PubMed

    Toussirot, Éric; Michel, Fabrice; Meneveau, Nicolas

    2015-01-01

    Statins are widely used in the treatment of hypercholesterolemia and their side effects on muscles are well established. Conversely, data are sparse regarding the safety of this class of drugs in subjects who engage in sports, particularly those who have intense sports activity. We report the case of a marathon runner who presented with acute rhabdomyolysis during competition while being under rosuvastatin treatment. This case raises the question of the need for temporary discontinuation of statin therapy when intense physical activity is planned. PMID:25815236

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

    PubMed Central

    2013-01-01

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

  9. Rhabdomyolysis Occurring under Statins after Intense Physical Activity in a Marathon Runner

    PubMed Central

    Toussirot, Éric; Michel, Fabrice; Meneveau, Nicolas

    2015-01-01

    Statins are widely used in the treatment of hypercholesterolemia and their side effects on muscles are well established. Conversely, data are sparse regarding the safety of this class of drugs in subjects who engage in sports, particularly those who have intense sports activity. We report the case of a marathon runner who presented with acute rhabdomyolysis during competition while being under rosuvastatin treatment. This case raises the question of the need for temporary discontinuation of statin therapy when intense physical activity is planned. PMID:25815236

  10. [Severe rhabdomyolysis and intracranial hemorrhage associated with synthetic cannabinoid: a case report].

    PubMed

    Tanei, Takafumi; Morita, Yoshiki; Yashima, Akihito; Wakita, Hiroyuki; Takebayashi, Shigenori; Nakahara, Norimoto; Wakabayashi, Toshihiko

    2014-09-01

    A 28-year-old male presented with language and behavior disorders a few days prior to examination. Magnetic resonance images and cerebral angiography revealed an arteriovenous malformation (AVM) in the right frontal lobe. The size of the nidus was 2.0 cm, and it was fed by the middle cerebral arteries and drained by the superior sagittal and transverse sinuses. The AVM was completely surgically resected without any complications. Ten months after the surgery, the patient presented with behavior disorders again and general convulsion. Computed tomography showed a small intracranial hemorrhage at the right frontal lobe, where the AVM was located. Blood examination revealed severe rhabdomyolysis (CK:536,620U/L)and acute kidney injury (Cr:5.20mg/dL). After admission, it became clear that the patient had used synthetic cannabinoid (SC). SC refers to a variety of herbal/chemical mixtures, which mimic the effects of marijuana. Little data is available on the psychopathological and physical effects of SC. This is the first report of severe rhabdomyolysis and intracranial hemorrhage associated with SC use in Japan. PMID:25179201

  11. 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

  12. [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. PMID:20456775

  13. Takotsubo Cardiomyopathy with Involvement of Delayed-onset Rhabdomyolysis and Acute Kidney Injury after Rosuvastatin Treatment.

    PubMed

    Kamada, Tomohito; Hayashi, Mutsuharu; Yokoi, Hiroatsu; Fujiwara, Wakaya; Yoshikawa, Daiji; Mukaide, Daisuke; Sugishita, Yoshinori; Yoshinaga, Masataka; Ito, Takehiro; Ozaki, Yukio; Izawa, Hideo

    2015-01-01

    Takotsubo cardiomyopathy is a disorder characterized by left ventricular apical ballooning with preceding emotional and/or physical stressors. This condition is also an important differential diagnosis of acute coronary syndrome. We herein describe a case of Takotsubo cardiomyopathy, a significant clinical phenomenon, triggered by delayed-onset rhabdomyolysis following the administration of long-term statin treatment, without any preceding stressors or changes in the patient's medical condition, in association with complaints of non-specific muscle-related symptoms. Although an electrocardiogram showed remarkable ST-segment elevation, a careful reading of the electrocardiogram findings revealed the features of Takotsubo cardiomyopathy. Withdrawing the statin therapy improved the patient's cardiac function. PMID:25742890

  14. Cerivastatin in vitro metabolism by CYP2C8 variants found in patients experiencing rhabdomyolysis

    PubMed Central

    Kaspera, Rüdiger; Naraharisetti, Suresh B.; Tamraz, Bani; Sahele, Tariku; Cheesman, Matthew J.; Kwok, Pui-Yan; Marciante, Kristin; Heckbert, Susan R.; Psaty, Bruce M.; Totah, Rheem A.

    2010-01-01

    Cerivastatin, an HMG-CoA reductase inhibitor withdrawn from the market due to serious adverse effects, is metabolized primarily by CYP2C8. The occurrence of associated myotoxicity and rhabdomyolysis were attributed to altered cerivastatin pharmacokinetics due to gemfibrozil-inhibition or genetic variations in CYP2C8 and drug transporters involved in cerivastatin clearance. However, the effect of CYP2C8 genetic variation on cerivastatin metabolism has not been fully elucidated. In this study, patients (n=126) with confirmed cases of rhabdomyolysis following cerivastatin administration had their CYP2C8 gene resequenced and the metabolism of cerivastatin by the discovered CYP2C8 variants was investigated. In this unique patient population, twelve novel SNPs were discovered of which six were exclusively found in patients not using gemfibrozil. Three rare exonic variants resulted in amino acid substitutions and a frame shift deletion (V472fsL494 generating a defective mostly heme-free CYP2C8 protein). A particular promotor located deletion (-635_-634delTA) was tightly linked to CYP2C8*3. Seven exonic variants were heterologously expressed in E.coli to assess their influence on cerivastatin metabolism. Recombinant CYP2C8.3 and CYP2C8.4 displayed an increase in cerivastatin metabolic clearance up to six fold compared to the wild type enzyme. Similarly, an independent sample of microsomes from human livers carrying the CYP2C8*3 and CYP2C8*4 alleles exhibited a 2 to 14-fold increase in normalized cerivastatin intrinsic clearance, compared to microsomes from livers carrying only the wild type allele. This gain or loss of catalytic function could certainly alter cerivastatin pharmacokinetics and may influence, at least in part, susceptibility to the development of myotoxicity. PMID:20739906

  15. Rhabdomyolysis as a Presenting Manifestation of Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency

    PubMed Central

    Oliveira, Sara Freitas; Pinho, Liliana; Rocha, Hugo; Nogueira, Célia; Vilarinho, Laura; Dinis, Maria José; Silva, Conceição

    2013-01-01

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

  16. 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

  17. 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 ?g 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. PMID:24211759

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

    PubMed Central

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

    2013-01-01

    Abstract Acute kidney injury (AKI) is a manifestation of rhabdomyolysis (RM). Extracellular myoglobin accumulating in the kidney after RM promotes oxidative damage, which is implicated in AKI. Aim: To test whether selenium (Se) supplementation diminishes AKI and improves renal function. Results: Dietary selenite increased Se in the renal cortex, as demonstrated by X-ray fluorescence microscopy. Experimental RM-stimulated AKI as judged by increased urinary protein/creatinine, clusterin, and kidney injury molecule-1 (KIM-1), decreased creatinine clearance (CCr), increased plasma urea, and damage to renal tubules. Concentrations of cholesterylester (hydro)peroxides and F2-isoprostanes increased in plasma and renal tissues after RM, while aortic and renal cyclic guanidine monophosphate (cGMP; marker of nitric oxide (NO) bioavailability) decreased. Renal superoxide dismutase-1, phospho-P65, TNF? gene, MCP-1 protein, and the 3-chloro-tyrosine/tyrosine ratio (Cl-Tyr/Tyr; marker of neutrophil activation) all increased after RM. Dietary Se significantly decreased renal lipid oxidation, phospho-P65, TNF? gene expression, MCP-1 and Cl-Tyr/Tyr, improved NO bioavailability in aorta but not in the renal microvasculature, and inhibited proteinuria. However, CCr, plasma urea and creatinine, urinary clusterin, and histopathological assessment of AKI remained unchanged. Except for the Se++ group, renal angiotensin-receptor-1/2 gene/protein expression increased after RM with parallel increases in MEK1/2 inhibitor-sensitive MAPkinase (ERK) activity. Innovation: We employed synchrotron radiation to identify Se distribution in kidneys, in addition to assessing reno-protection after RM. Conclusion: Se treatment has some potential as a therapeutic for AKI as it inhibits oxidative damage and inflammation and decreases proteinuria, albeit histopathological changes to the kidney and some plasma and urinary markers of AKI remain unaffected after RM. Antioxid Redox Signal. 18, 756–769. PMID:22937747

  19. Clearance of myoglobin by high cutoff continuous veno-venous hemodialysis in a patient with rhabdomyolysis: a case report.

    PubMed

    Wu, Buyun; Gong, Dehua; Ji, Daxi; Xu, Bin; Liu, Zhihong

    2015-01-01

    Continuous veno-venous hemodialysis using high cutoff filters (HCO-CVVHD) is a promising technique, which may be effective to decrease the extremely high level of circulating myoglobin in patients with rhabdomyolysis (RM). Here, we report a patient with RM caused by heat stroke who was successfully treated by HCO-CVVHD. A male patient received HCO-CVVHD with 4?L/h dialysate for 5 days and then pre-dilution continuous veno-venous hemofiltration (CVVH) at a dose of 4?L/h until recovery of renal function. The clearance of myoglobin and albumin at 5 minutes, and at 4, 12, and 24 hours were calculated. The serum myoglobin level decreased from a peak of 25,400?ng/mL on admission to 133?ng/mL at discharge. During HCO-CVVHD, the mean clearances of serum myoglobin at four timepoints were 61.3 (range, 61.0-61.6), 52.3 (38.9-65.8), 47.3 (46.8-47.9), and 43.7 (39.5-48.0) mL/min, respectively, and the mean clearances of albumin were 12.4 (range, 11.8-13.1), 3.1 (2.5-3.8), 1.2 (1.0-1.4), and 0.8 (0.6-1.0) mL/min, respectively. During CVVH, the clearance rates of myoglobin at 5 minutes and 24 hours were 17.0 and 3.8?mL/min, respectively, with a negligible clearance of albumin. HCO-CVVHD can effectively decrease serum myoglobin in patients with RM because of much higher clearance of myoglobin than CVVH. However, attention should be paid to albumin loss during HCO-CVVHD. PMID:24766332

  20. An autopsy case of licorice-induced hypokalemic rhabdomyolysis associated with acute renal failure: special reference to profound calcium deposition in skeletal and cardiac muscle.

    PubMed

    Saito, T; Tsuboi, Y; Fujisawa, G; Sakuma, N; Honda, K; Okada, K; Saito, K; Ishikawa, S; Saito, T

    1994-11-01

    A 78-year-old man was hospitalized because of muscular weakness and acute renal failure. He had been taking glycyrrhizin (280 mg/day) for the last 7 years. Hypertension was noted in his history. Serum potassium was 1.9 mEq/l with metabolic alkalosis. There was hyporeninemic hypoaldosteronism. Serum enzymes, including GOT, LDH and CPK were markedly elevated. In addition, serum myoglobin was as high as 46 micrograms/ml with massive myoglobinuria. Oliguria occurred and blood urea nitrogen and serum creatinine rapidly elevated from 20.9 to 87 mg/dl and from 1.3 to 6.7 mg/dl, respectively. Profound calcium deposition was found in the damaged skeletal muscles, including the quadriceps femoris, axillar, neck, and cardiac muscles. These results indicate that licorice-induced pseudoaldosteronism produces hypokalemic rhabdomyolysis, resulting in acute renal failure and profound deposition of calcium into the damaged skeletal and cardiac muscles. PMID:7853765

  1. Exercise-induced rhabdomyolysis and stress-induced malignant hyperthermia events, association with malignant hyperthermia susceptibility, and RYR1 gene sequence variations.

    PubMed

    Carsana, Antonella

    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

  2. Transcriptome analysis of muscle in horses suffering from recurrent exertional rhabdomyolysis revealed energetic pathway alterations and disruption in the cytosolic calcium regulation.

    PubMed

    Barrey, E; Jayr, L; Mucher, E; Gospodnetic, S; Joly, F; Benech, P; Alibert, O; Gidrol, X; Mata, X; Vaiman, A; Guérin, G

    2012-06-01

    Recurrent exertional rhabdomyolysis (RER) is frequently observed in race horses like trotters. Some predisposing genetic factors have been described in epidemiological studies. However, the exact aetiology is still unknown. A calcium homeostasis disruption was suspected in previous experimental studies, and we suggested that a transcriptome analysis of RER muscles would be a possible way to investigate the pathway disorder. The purpose of this study was to compare the gene expression profile of RER vs. control muscles in the French Trotter to determine any metabolic or structural disruption. Total RNA was extracted from the gluteal medius and longissimus lumborum muscles after biopsies in 15 French Trotter horses, including 10 controls and 5 RER horses affected by 'tying-up' with high plasmatic muscular enzyme activities. Gene expression analysis was performed on the muscle biopsies using a 25K oligonucleotide microarray, which consisted of 24,009 mouse and 384 horse probes. Transcriptome analysis revealed 191 genes significantly modulated in RER vs. control muscles (P < 0.05). Many genes involved in fatty acid oxidation (CD36/FAT, SLC25A17), the Krebs cycle (SLC25A11, SLC25A12, MDH2) and the mitochondrial respiratory chain were severely down-regulated (tRNA, MT-ND5, MT-ND6, MT-COX1). According to the down-regulation of RYR1, SLC8A1 and UCP2 and up-regulation of APP and HSPA5, the muscle fibre calcium homeostasis seemed to be greatly affected by an increased cytosolic calcium and a depletion of the sarcoplasmic reticulum calcium. Gene expression analysis suggested an alteration of ATP synthesis, with severe mitochondrial dysfunction that could explain the disruption of cytosolic calcium homeostasis and inhibition of muscular relaxation. PMID:22486498

  3. A new syndrome sheds light on old medical & rehabilitative dilemmas: paraparesis due to rhabdomyolysis and bilaterally symmetric compartment syndrome in four patients. Cases study.

    PubMed

    Goldin, Diana; Shemesh, Frida; Eljashev-Shimshon, Rachel; Ohry, Avi

    2010-01-01

    Via our description of a seemingly heterogeneous group of four patients who presented to our rehabilitation facility with a rather unusual clinical presentation of compartment syndrome with development of a flaccid paraparesis and rhabdomyolysis immediately after awakening from a prolonged sleep episode in an unusual posture - which might, in fact, be a 'new syndrome' - we have also come to address an important issue linking our group of patients - specifically, the complexities which present to a rehabilitative facility in the cases of unusual and unclear diagnoses. Eventually, all four of our patients remained severely disabled. All had suffered sensorimotor axonal demyelinative polyneuropathies and two patients had subclinical hypothyroidism. Prior to the prolonged sleep episode, they had all consumed alcohol and drugs. Using these four rather demanding diagnostic rehabilitative cases we address the ever-important issue of timely mutual communication and patience. For when a rehabilitative facility is confronted with patients whose diagnoses are not clear, the scope of the long-term comprehensive rehabilitation management faces some major obstacles with respect to how the rehabilitative team can succeed in designing a 'tailor-made' rehabilitation program for these patients, which often-times proves to be a rather tricky task requiring innovative and creative efforts on the parts of all those involved in the care of the patient. Quite a challenging task, indeed, yet one genuinely necessary to attempt to achieve so that the patient, family and, of course, the 'payer agency/provider' can all prepare themselves, realistically so as to obtain the best overall rehabilitative outcome for these patients. We conclude that what is most necessary for these unique patients is patience. PMID:21273651

  4. Myoglobin clearance by super high-flux hemofiltration in a case of severe rhabdomyolysis: a case report

    PubMed Central

    Naka, Toshio; Jones, Daryl; Baldwin, Ian; Fealy, Nigel; Bates, Samantha; Goehl, Hermann; Morgera, Stanislao; Neumayer, Hans H; Bellomo, Rinaldo

    2005-01-01

    Objective To test the ability of a novel super high-flux (SHF) membrane with a larger pore size to clear myoglobin from serum. Setting The intensive care unit of a university teaching hospital. Subject A patient with serotonin syndrome complicated by severe rhabodomyolysis and oliguric acute renal failure Method Initially continuous veno-venous hemofiltration was performed at 2 l/hour ultrafiltration (UF) with a standard polysulphone 1.4 m2 membrane (cutoff point, 20 kDa), followed by continuous veno-venous hemofiltration with a SHF membrane (cutoff point, 100 kDa) at 2 l/hour UF, then at 3 l/hour UF and then at 4 l/hour UF, in an attempt to clear myoglobin. Results The myoglobin concentration in the ultrafiltrate at 2 l/hour exchange was at least five times greater with the SHF membrane than with the conventional membrane (>100,000 ?g/l versus 23,003 ?g/l). The sieving coefficients with the SHF membrane at 3 l/hour UF and 4 l/hour UF were 72.2% and 68.8%, respectively. The amount of myoglobin removed with the conventional membrane was 1.1 g/day compared with 4.4–5.1 g/day for the SHF membrane. The SHF membrane achieved a clearance of up to 56.4 l/day, and achieved a reduction in serum myoglobin concentration from >100,000 ?g/l to 16,542 ?g/l in 48 hours. Conclusions SHF hemofiltration achieved a much greater clearance of myoglobin than conventional hemofiltration, and it may provide a potential modality for the treatment of myoglobinuric acute renal failure. PMID:15774055

  5. Paralysis, rhabdomyolysis and haemolysis caused by bites of Russell's viper (Vipera russelli pulchella) in Sri Lanka: failure of Indian (Haffkine) antivenom.

    PubMed

    Phillips, R E; Theakston, R D; Warrell, D A; Galigedara, Y; Abeysekera, D T; Dissanayaka, P; Hutton, R A; Aloysius, D J

    1988-09-01

    In Sri Lanka, Russell's viper, Vipera russelli pulchella, kills more people than any other species of snake. At Anuradhapura in the dry central zone of the island we studied 23 patients with systemic envenoming after proven bites. Seventy-three per cent had swelling at the bite site. Neurotoxicity was the commonest sign of systemic envenoming: 82 per cent had external ophthalmoplegia and 77 per cent had ptosis. Incoagulable blood was found in 59 per cent but only 36 per cent had spontaneous bleeding. Other signs included generalized muscle tenderness (32 per cent), black urine (27 per cent) and persistent oliguria (9 per cent). Laboratory studies showed evidence of a severe clotting disorder: fibrinogen was often depleted as were factors V and X. Fibrin degradation products, including cross-linked moieties, were grossly elevated, clear evidence for enhanced fibrinolysis. Intravascular haemolysis, unrelated to G6PD deficiency, was often present. Myoglobin was detected in the plasma of all 19 patients tested (range 100- greater than 8000 ng/ml) and in the urine in 14 of 18 patients (110- greater than 16,000 ng/ml). Venom antigen (16.5-702 ng/ml) was detected by specific ELISA in the serum of all patients. Its concentration fell with the administration of 50-200 ml of Haffkine polyspecific antivenom raised against Indian venoms. Complete permanent clearance of venom antigen from the circulation was seen in only one of 21 patients who were followed until discharge. Blood coagulability was restored between one and 25 h (mean 8.8) after the first dose of antivenom in the 12 surviving patients whose clotting defect could be followed; no dramatic reversal of neuromyotoxic signs was seen. Haffkine antivenom thus has limited efficacy against systemic poisoning by Russell's viper in Sri Lanka. PMID:3256900

  6. Phenotype Standardization for Statin-Induced Myotoxicity

    PubMed Central

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

    2014-01-01

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

  7. 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.

  8. 1 A Small-Molecule Screening Strategy To Identify Suppressors of 2 Statin Myopathy

    E-print Network

    Mootha, Vamsi K.

    -threatening rhabdomyolysis,2 which 34 can occur in 0.1À0.5% of patients.3 Vigorous exercise is a risk 35 factor) levels and 29 decreasing the risk of cardiac events and mortality. They are 30 taken by tens of millions of people worldwide.1 A common 31 side effect of statin use is muscle toxicity, ranging from patient- 32

  9. Management of a mixed overdose of calcium channel blockers, ?-blockers and statins.

    PubMed

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

    2014-01-01

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

  10. Acidosis, lactate, electrolytes, muscle enzymes, and other factors in the blood of Sus scrofa following repeated TASER ® exposures

    Microsoft Academic Search

    James R. Jauchem; Clifford J. Sherry; David A. Fines; Michael C. Cook

    2006-01-01

    Repeated exposure to electro-muscular incapacitating devices could result in repetitive, sustained muscle contraction, with little or no muscle recovery period. Therefore, rhabdomyolysis and other physiological responses, including acidosis, hyperkalaemia, and altered levels of muscle enzymes in the blood, would be likely to occur. Experiments were performed to investigate effects of repeated exposures of TASER® International's Advanced TASER® X26 on muscle

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

    PubMed Central

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

    2014-01-01

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

  12. Haemorrhagic shock encephalopathy syndrome presenting with myoglobinuria.

    PubMed

    Teig, N; Nuesslein, T G

    1996-02-01

    An infant with haemorrhagic shock encephalopathy syndrome (HSES) who in addition presented with hyperpyrexia and myoglobinuria is reported. As rhabdomyolysis is a feature of heat stroke and malignant hyperthermia, the association of HSES with myoglobinuria supports the hypothesis that HSES may be a form of hypermetabolic state triggered by hyperthermia. PMID:8660084

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

    PubMed

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

    2014-07-01

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

  14. Acute kidney injury and dermonecrosis after Loxosceles reclusa envenomation

    PubMed Central

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

    2014-01-01

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

  15. 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…

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

    PubMed

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

    2014-01-01

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

  17. Cerebellar syndrome following neuroleptic induced heat stroke.

    PubMed Central

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

    1983-01-01

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

  18. 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 reabsorption). It is important to be aware of this potentially serious and possibly life-threatening reaction especially when medication doses are increased or combined with other agents with similar safety issues. PMID:23115467

  19. Lifesaving liver transplantation for multi-organ failure caused by Bacillus cereus food poisoning.

    PubMed

    Tschiedel, Eva; Rath, Peter-Michael; Steinmann, Jörg; Becker, Heinz; Dietrich, Rudolf; Paul, Andreas; Felderhoff-Müser, Ursula; Dohna-Schwake, Christian

    2015-02-01

    Bacillus cereus is a spore-forming, gram-positive bacterium that causes food poisoning presenting with either emesis or diarrhea. Diarrhea is caused by proteinaceous enterotoxin complexes, mainly hemolysin BL, non-hemolytic enterotoxin (NHE), and cytotoxin K. In contrast, emesis is caused by the ingestion of the depsipeptide toxin cereulide, which is produced in B. cereus contaminated food, particularly in pasta or rice. In general, the illness is mild and self-limiting. However, due to cereulide intoxication, nine severe cases with rhabdomyolysis and/or liver failure, five of them lethal, are reported in literature. Here we report the first case of life-threatening liver failure and severe rhabdomyolysis in this context that could not be survived without emergency hepatectomy and consecutive liver transplantation. PMID:25323120

  20. Expanding the phenotype of GMPPB mutations.

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2015-03-01

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

  2. Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several-fold in patients with atorvastatin-induced myopathy

    Microsoft Academic Search

    Monica Hermann; Martin P. Bogsrud; Espen Molden; Anders Åsberg; Beata U. Mohebi; Leiv Ose; Kjetil Retterstøl

    2006-01-01

    Background: The most serious side effect from statin treatment is myopathy, which may proceed to rhabdomyolysis. This is the first study to investigate whether the pharmacokinetics of either atorvastatin or its metabolites, or both, is altered in patients with atorvastatin-related myopathy compared with healthy controls.Methods: A 24-hour pharmacokinetic investigation was performed in 14 patients with atorvastatin-related myopathy. Relevant polymorphisms in

  3. Acidosis, lactate, electrolytes, muscle enzymes, and other factors in the blood of Sus scrofa following repeated TASER1 exposures

    Microsoft Academic Search

    James R. Jauchem; Clifford J. Sherry; David A. Fines; Michael C. Cook

    2006-01-01

    Repeated exposure to electro-muscular incapacitating devices could result in repetitive, sustained muscle contraction, with little or no muscle recovery period. Therefore, rhabdomyolysis and other physiological responses, including acidosis, hyperkalaemia, and altered levels of muscle enzymes in the blood, would be likely to occur. Experiments were performed to investigate effects of repeated exposures of TASER1 International's Advanced TASER1 X26 on muscle

  4. Perioperative thrombotic occlusion of left external iliac artery during anterior lumbar interbody fusion

    Microsoft Academic Search

    Jen-Hsuan Huang; Cheng-Hung Lee; Tzung-chieh Tsai; Shih-Yen Peng

    2008-01-01

    We report a case of thrombotic occlusion of left external iliac artery during the procedure of anterior lumbar interbody fusion.\\u000a The diagnosis was confirmed by computed tomography angiography. The patient also developed severe rhabdomyolysis postoperatively.\\u000a In spite of receiving emergent thromboendarterectomy, the patient expired on postoperative day 3. This report attempts to\\u000a remind spinal surgeons and anesthesiologists of this rare but

  5. Evidence-Based Management of Statin Myopathy

    Microsoft Academic Search

    Charles R. Harper; Terry A. Jacobson

    2010-01-01

    Statin-associated muscle symptoms are a relatively common condition that may affect 10% to 15% of statin users. Statin myopathy\\u000a includes a wide spectrum of clinical conditions, ranging from mild myalgia to rhabdomyolysis. The etiology of myopathy is\\u000a multifactorial. Recent studies suggest that statins may cause myopathy by depleting isoprenoids and interfering with intracellular\\u000a calcium signaling. Certain patient and drug characteristics

  6. Abrupt withdrawal from intrathecal baclofen: Recognition and management of a potentially life-threatening syndrome

    Microsoft Academic Search

    Robert J. Coffey; Terence S. Edgar; Gerard E. Francisco; Virginia Graziani; Jay M. Meythaler; Patrick M. Ridgely; Saud A. Sadiq; Michael S. Turner

    2002-01-01

    Coffey RJ, Edgar TS, Francisco GE, Graziani V, Meythaler JM, Ridgely PM, Sadiq SA, Turner MS. Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome. 2002;83:735-41. Objective: To suggest guidelines for the prevention, recognition, and management of a life-threatening syndrome (high fever, altered mental status, profound muscular rigidity that sometimes progressed to fatal rhabdomyolysis) in patients

  7. Le syndrome de loge antérieure de l?avant-bras provoqué par l?exercice : une cause rare d?épisodes récidivant de rhabdomyolyse aiguë d?effort

    Microsoft Academic Search

    A Drouet; O Jaquin; L Guilloton; P Dumas; P Volckmann; C Ribot

    2001-01-01

    Introduction. – An effort-related compartmental syndrome is well known in the leg, but may be present infrequently, acutely or chronically in the anterior compartment of the forearm.Exegesis. – We report a case of a 32-year-old man who presented four times after climbing exercices a bilateral compartment of the forearm, unusual because of the observation of rhabdomyolysis, but without irreversible damage.

  8. Bilateral compartment syndrome of the anterior thigh following functional fitness exercises: a case report.

    PubMed

    McDonald, Lucas S; Mitchell, Ronald J; Deaton, Travis G

    2012-08-01

    We present a case of delayed, acute bilateral exertional compartment syndrome of the anterior thigh induced by callisthenic exercise. Symptoms consisted of pain out of proportion to examination findings, inability to ambulate, and severe pain with knee flexion. Treatment consisted of bilateral thigh fasciotomies and supportive therapy for concomitant rhabdomyolysis. Full strength, range of motion, and return to all military duties were achieved by 4 months postinjury. PMID:22934383

  9. Plasma Concentration Profiles of Simvastatin 3Hydroxy3-Methylglutaryl-Coenzyme A Reductase Inhibitory Activity in Kidney Transplant Recipients with and without Ciclosporin

    Microsoft Academic Search

    Margret Arnadottir; Lars-Olof Eriksson; Hans Thysell; John D. Karkas

    1993-01-01

    A few cases of severe rhabdomyolysis have been reported in heart transplant recipients treated simultaneously with ciclosporin (CS) and the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin. When measured, plasma lovastatin HMG-CoA reductase inhibitor concentrations in these patients were higher than expected. This prompted us to study the plasma concentration profiles of simvastatin HMG-CoA reductase inhibitory activity after a single dose

  10. Hoffman’s Syndrome: Muscle Stiffness, Pseudohypertrophy and Hypothyroidism

    Microsoft Academic Search

    Maria Mastropasqua; Gaetano Spagna; Valentina Baldini; Ilaria Tedesco; Anna Paggi

    2003-01-01

    Primary hypothyroidism is a chronic and insidious disease caused by failure of thyroid hormone production. We observed a 38-year-old woman admitted to our hospital due to progressive proximal weakness, muscle pain and fatigue during mild exercise. Laboratory tests showed features of rhabdomyolysis and hypothyroidism. After examination of the thyroid, we reached a diagnosis of Hashimoto’s thyroiditis and hypothyroid myopathy. Hypothyroidism

  11. Two patients subdued with a TASER® device: cases and review of complications.

    PubMed

    Sanford, Janyce M; Jacobs, Gregory J; Roe, Edward J; Terndrup, Thomas E

    2011-01-01

    In the United States, an increasing number of law enforcement agencies have employed the use of TASER® (TASER International Inc., Scottsdale, AZ) devices to temporarily immobilize violent subjects. There are reports in the lay press of adverse outcomes occurring in patients on whom TASER® devices have been deployed. Rhabdomyolysis has been associated with patients sustaining a TASER® shock, with a 1% incidence rate in subjects subdued with earlier versions of the device and then brought to the Emergency Department (ED). We present the cases of 2 patients who were seen in our ED after exhibiting violent behavior and receiving TASER® shocks. Both were hospitalized and received treatment for mild rhabdomyolysis. Both patients had multiple other characteristics that have been found to have an association with the development of rhabdomyolysis, in addition to the shocks they received. A review and discussion of the available medical literature on the subject follows, describing several complications that have been documented in patients after receiving TASER® shocks. Although a direct link between the TASER® and the reported adverse effects has not been established, patients who undergo restraint via this device frequently have pre-existing conditions or have exhibited behavior that places them at risk for the development of those effects. Such awareness of these possible complications is vital because the evaluation and management of patients developing adverse effects after these events will commonly occur in the ED. PMID:18439781

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

    PubMed

    Redshaw, Charlotte; Stewart, Catherine

    2014-11-01

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

  13. 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

  14. Severe colchicine intoxication in a renal transplant recipient on cyclosporine.

    PubMed

    Garrouste, C; Philipponnet, C; Kaysi, S; Enache, I; Tiple, A; Heng, A E

    2012-11-01

    Using colchicine to treat an acute gout crisis in an organ transplant recipient (TR) on cyclosporine (CsA) may result in life-threatening intoxication. We report the case of a 59-year-old kidney transplant recipient on CsA who was treated with colchicine for acute gout crisis. Seven days later, he developed rhabdomyolysis with progressive quadriparesis, hematologic toxicity and acute renal failure. CsA inhibits P-glycoprotein resulting in decreased hepatic metabolism and renal excretion of colchicine. Colchicine and CsA withdrawal as well as appropriate supportive treatments were effective to manage all of these complications. PMID:23146540

  15. Black Coloured Urine following Organophosphorus Poisoning: Report of Two Cases

    PubMed Central

    Mookkappan, Sudhagar; Shanmugham, Vijay; Kulirankal, Kiran

    2014-01-01

    Organophosphorus poisoning is common in rural Asia. Clinical features result from overactivity of acetylcholine receptors. Blackish discoloration of urine is not a feature of organophosphorus poisoning. Only one case of black colored urine following quinalphos poisoning has been reported in literature. We report two cases of organophosphorus poisoning from two different compounds, following which patients passed black colored urine, in the absence of haemolysis or rhabdomyolysis. These cases indicate that blackish discoloration of urine in organophosphorus poisoning might not be as uncommon as it was believed to be. Besides, urinary excretion of metabolites might be an underlying mechanism, rather than hemolysis. PMID:24826348

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

    PubMed

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

    1999-09-30

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

  17. Multiple mononeuropathy following cocaine abuse.

    PubMed

    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

  18. Coenzyme Q 10 and Statin Myalgia: What is the Evidence?

    Microsoft Academic Search

    Emilie Mas; Trevor A. Mori

    2010-01-01

    Statins lower cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme\\u000a in the biosynthesis of cholesterol. However, severe adverse events, including myalgias and rhabdomyolysis, have been reported\\u000a with statin treatment. Different mechanisms have been proposed to explain statin-induced myopathy, including reduction of\\u000a mevalonate pathway products, induction of apoptosis, mitochondrial dysfunction, and genetic predisposition. A decrease in\\u000a coenzyme Q10

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

    Pereira, Bernadette; Heath, Dugal

    2015-01-01

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

  1. [Diseases of the shipwrecked: apropos of 3 cases].

    PubMed

    Dalger, J M; Belat, C; Le Marec, C; Genco, G; Le Guern, G

    1994-01-01

    Three men (31, 34, 36 yr old) were rescued after they had drifted for 50 hours on their wrecked catamaran. While their apparent clinical condition was not worrying, besides multiple bruises, marked dehydration, epigastralgias, mild hypothermia in one patient and 50, severe biological disorders were present in all four: haemoconcentration, functional renal insufficiency, metabolic acidosis, severe rhabdomyolysis, hepatic cytolysis. After intravenous rehydration for 24 hr hydroelectrolytic and acid-base anomalies were corrected. Pathophysiology of shipwreck casualties is recalled. Initial management in ICU is necessary. Psychological and emotional aspects should not be underrated. PMID:8087631

  2. Sloughing Esophagitis: A Not So Common Entity

    PubMed Central

    Akhondi, Hossein

    2014-01-01

    BACKGROUND: Sloughing esophagitis, also known as esophagitis dissecans superficialis, is a very rare and underdiagnosed entity with unknown incidence rate. It can be associated with bullous dermatoses and medications such as central nervous system depressants and those causing esophageal injury. CASE REPORT: A 55-years-old woman was recovering from renal failure due to rhabdomyolysis when she developed dysphagia and odynophagia. Esophagogastroduodenoscopy with biopsy was performed for suspected bullous pemphigus and confirmed sloughing esophagitis. She improved with intravenous steroids. CONCLUSIONS: Sloughing Esophagitis should enter our differential diagnosis more frequently. It is mostly a benign, self-limiting process but when associated with bullous dermatoses will require steroid treatment. PMID:25598761

  3. Search for rare liver diseases: the case of glycosylation defects mimicking Wilson Disease ->.

    PubMed

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

    2014-09-01

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

  4. 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.

  5. Prognostic Factors in Acute Methadone Toxicity: A 5-Year Study

    PubMed Central

    Aghabiklooei, Abbas; Edalatparvar, Maryam; Mostafazadeh, Babak

    2014-01-01

    Background. Delayed or recurrent profound respiratory depression, ventricular dysrhythmias, acute lung injury, and death are the major complications of MTD overdose. We aimed to clarify the prognostic factors in MTD toxicity. Materials and Methods. Retrospectively, medical files of all patients poisoned by MTD and older than 12 years of age who had presented to Loghman Hakim Poison Center between 2007 and 2012 were evaluated. The data was compared between survivors and nonsurvivors. Results. Twenty-eight out of 322 patients died (mortality rate = 8.7%). MTD-related death was higher in patients with acute on chronic toxicity who were on daily dose of MTD and had ingested higher doses (in comparison to those with acute toxicity due to first-time exposure; 13% versus 6%). Renal failure was the most common medical complication related to deaths due to MTD toxicity. Conclusions. Based on previous researches, the most common cause of MTD overdose-related deaths is respiratory impairment; however, in our study, acute renal failure with or without rhabdomyolysis was the main delayed cause of deaths in MTD-poisoned patients. Antidotal therapy, early recognition, and treatment of hemodynamic compromise and rhabdomyolysis can be life-saving in these patients. PMID:25197273

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

    PubMed Central

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

    2012-01-01

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

  7. Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury

    PubMed Central

    Zarjou, Abolfazl; Bolisetty, Subhashini; Joseph, Reny; Traylor, Amie; Apostolov, Eugene O.; Arosio, Paolo; Balla, Jozsef; Verlander, Jill; Darshan, Deepak; Kuhn, Lukas C.; Agarwal, Anupam

    2013-01-01

    Ferritin plays a central role in iron metabolism and is made of 24 subunits of 2 types: heavy chain and light chain. The ferritin heavy chain (FtH) has ferroxidase activity that is required for iron incorporation and limiting toxicity. The purpose of this study was to investigate the role of FtH in acute kidney injury (AKI) and renal iron handling by using proximal tubule–specific FtH-knockout mice (FtHPT–/– mice). FtHPT–/– mice had significant mortality, worse structural and functional renal injury, and increased levels of apoptosis in rhabdomyolysis and cisplatin-induced AKI, despite significantly higher expression of heme oxygenase-1, an antioxidant and cytoprotective enzyme. While expression of divalent metal transporter-1 was unaffected, expression of ferroportin (FPN) was significantly lower under both basal and rhabdomyolysis-induced AKI in FtHPT–/– mice. Apical localization of FPN was disrupted after AKI to a diffuse cytosolic and basolateral pattern. FtH, regardless of iron content and ferroxidase activity, induced FPN. Interestingly, urinary levels of the iron acceptor proteins neutrophil gelatinase–associated lipocalin, hemopexin, and transferrin were increased in FtHPT–/– mice after AKI. These results underscore the protective role of FtH and reveal the critical role of proximal tubule FtH in iron trafficking in AKI. PMID:24018561

  8. [Exploratory studies on genetic biomarkers related to serious drug adverse reactions].

    PubMed

    Kaniwa, Nahoko; Hasegawa, Ryuichi

    2009-01-01

    Serious adverse events (SAEs) induced by drugs occur rarely, but the symptoms are very critical and generally not related to their pharmacological activities. Although SAEs should be avoided wherever possible, their occurrence is unpredictable at this time. In this article, we describe the clinical condition, figures on reported occurrence in Japan and studies on genetic markers related to serious cutaneous adverse reactions (SCARs), drug induced liver injury (DILI and rhabdomyolysis among SAEs. Then we introduce our last 3 years' approach of exploratory study on genetic markers for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), two of SCARs, useful for Japanese patients, including construction of a new case collection system, study methodology and progress. As the result at this moment, no Japanese SJS/TEN patients including 12 carbamazepine-related and 23 aromatic anti-epileptic agent-related ones carried HLA-B 1502 that was reported to have a strong association with carbamazepine-induced SJS/TEN in Han Chinese patients. On the other hand, 5 in 15 allopurinol-related SJS/TEN patients were found to have HLA-B 5801 that was detected as a genetic marker for allopurinol-induced SCARs in Han Chinese and Caucasians. Hereafter, we have a plan to begin the new exploratory studies on genetic markers for DILI and rhabdomyolysis, in addition to SJS/TEN patients. PMID:20306701

  9. 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 2.5?M L-carnitine solution in presence of 500 ?M 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

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

    PubMed

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

    2013-07-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2014-01-01

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

  13. 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.

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

    PubMed Central

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

    2014-01-01

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

  15. 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 (PPAR?, PPAR?), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1?), 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(TNF1? + IL-1?) designed to mimic febrile illness, resulted in increased malonyl-carnitine levels, reduced CPT1 activity and enhanced LD accumulation, a phenomenon reversed by dexamethasone and TNF? or IL-1? inhibitors. Our data suggest that the pathogenic mechanism of rhabdomyolysis in lipin-1-deficient patients combines the predisposing constitutive impairment of lipid metabolism and its exacerbation by pro-inflammatory cytokines. PMID:23928362

  16. Pathogenesis, diagnosis and management of hyperkalemia.

    PubMed

    Lehnhardt, Anja; Kemper, Markus J

    2011-03-01

    Hyperkalemia is a potentially life-threatening condition in which serum potassium exceeds 5.5 mmol/l. It can be caused by reduced renal excretion, excessive intake or leakage of potassium from the intracellular space. In addition to acute and chronic renal failure, hypoaldosteronism, and massive tissue breakdown as in rhabdomyolysis, are typical conditions leading to hyperkalemia. Symptoms are non-specific and predominantly related to muscular or cardiac dysfunction. Treatment has to be initiated immediately using different therapeutic strategies to increase potassium shift into the intracellular space or to increase elimination, together with reduction of intake. Knowledge of the physiological mechanisms of potassium handling is essential in understanding the causes of hyperkalemia as well as its treatment. This article reviews the pathomechanisms leading to hyperkalemic states, its symptoms, and different treatment options. PMID:21181208

  17. Scleromyxedema (lichen myxedematosus) associated with dermatomyositis.

    PubMed

    Launay, D; Hatron, P Y; Delaporte, E; Hachulla, E; Devulder, B; Piette, F

    2001-02-01

    A 41-year-old white man is described with papules of the lower and upper back, the neck and the upper chest, a marked deposition of mucin in the upper reticular dermis, and an IgG lambda monoclonal gammopathy strongly evocative of scleromyxedema (lichen myxedematosus). Additionally, he developed intense myalgia, muscle weakness and rhabdomyolysis, which were associated with heliotrope erythema, photosensitivity and an erythematous rash of the dorsum of the hands with Gottron's papules. Muscle biopsy revealed an inflammatory myositis, and dermatomyositis was diagnosed. The association of dermatomyositis and secondary mucinosis, or muscle involvement in primary papular mucinosis are not rare. However, the association between scleromyxedema and dermatomyositis has only exceptionally been reported. PMID:11251573

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

    SciTech Connect

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

    1983-04-01

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

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

    PubMed

    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

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

    PubMed Central

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

    2013-01-01

    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. PMID:23576661

  1. Exacerbation of acetazolamide-responsive sodium channel myotonia by uterotonic agents.

    PubMed

    Fujii, K; Iranami, H; Hatano, Y

    2011-01-01

    The symptoms of myotonia can worsen during pregnancy and tocolysis with ritodrine has been associated with rhabdomyolysis. We describe a patient with myotonia who developed hypertonus immediately following the administration of uterotonic agents. A 24-year-old, G2P1 at 31 weeks of gestation with a history of acetazolamide-responsive myotonia presented with premature rupture of membranes. During cesarean delivery she experienced significant hypertonus of the upper limbs, shoulders, fingers, and mouth immediately after intravenous administration of oxytocin 5 IU and methylergometrine maleate 0.2mg. The mechanism underlying increased muscle tone in response to these drugs remains unclear. Anesthesiologists should be especially attentive to the administration of uterotonic drugs during the management of pregnant myotonia patients. PMID:21074404

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

    PubMed

    Michael White, C

    2014-03-01

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

  3. [Complex regional pain syndrome in a patient with acute drug poisoning: a case report].

    PubMed

    Hiraiwa, Toshihisa; Okada, Hiroyuki; Sawada, Naotaka; Nakayama, Kimiya; Senda, Noriyasu; Kawanishi, Minoru

    2014-12-01

    We report a case with transition to complex regional pain syndrome (CRPS) caused by nerve injury associated with crush syndrome. The diagnosis was delayed because of coma due to acute drug poisoning. A 44-year-old man had attempted suicide by taking massive amounts of psychotropic drugs 2 days earlier and was transported to our hospital by ambulance. His arms had been compressed due to the prolonged (2 days) consciousness disturbance, and he experienced non-traumatic crush syndrome and rhabdomyolysis. Acute renal failure was prevented with massive infusion and hemofiltration. However, he experienced muscle and nerve injury at the compressed area, which presumably led to CRPS. In cases of suspected crush syndrome associated with acute drug poisoning, it is also important to recognize the possibility of developing CRPS. PMID:25771666

  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. 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

  6. Myopathy associated with atorvastatin-ezetimibe combination therapy.

    PubMed

    Weffald, Linda A; Flach, Lynn A

    2007-02-01

    The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) play a prominent role in the treatment of dyslipidemia. Overall, statins are well tolerated, with a low occurrence of adverse effects. More serious reactions to statins have been reported, although they are rare (e.g., rhabdomyolysis 0.3-13.5 cases/million statin prescriptions). Combination therapy to treat dyslipidemia has become common in many patients; however, it can also increase the risk of serious adverse effects. We report the case of a patient who experienced muscle pain and elevated creatine kinase levels 16 days after the addition of ezetimibe to his atorvastatin therapy for hypercholesterolemia. Twelve days after stopping the ezetimibe, his muscle pain resolved and his serum creatine kinase level returned to baseline. This case report raises questions regarding the safety of high-dose atorvastatin and ezetimibe combination therapy and suggests that caution and careful monitoring may be warranted. PMID:17253923

  7. MDEA related death in Crete: a case report and literature review.

    PubMed

    Tsatsakis, A M; Michalodimitrakis, M N; Patsalis, A N

    1997-08-01

    "Designer drugs" are derivatives of approved drugs abused for recreational effect and created by underground laboratories to circumvent legal restriction. By far the most controversial drug has been MDMA (3,4-methylenedioxymethamphetamine) and the newer derivative MDEA (3,4-methylenedioxymethamphetamine) often called "Eve". MDEA-related deaths have not been reported in the US, but there have been a death of MDMA and MDEA severe poisonings. Convulsions, collapse, hyperpyrexia, disseminated intravascular coagulation rhabdomyolysis, and acute liver and renal damage result from the ingestion of the drug. Complications may occur and severity and death possibly result. The case of a 31-y-old male, the first victim of MDEA in Greece, is reported. Blood MDEA was 3.1 micrograms/mL; MDEA concentrations in liver, lung and kidney were 4.8, 5.2, and 4.8 micrograms/g respectively. PMID:9251177

  8. Protocols cure diseases, not patients: flaccid paresis in post-NSTEMI statin treatment.

    PubMed

    Rosada, Javier; Rebelos, Eleni; Petruccelli, Stefania; Taddei, Marco

    2015-01-01

    An 82-year-old white woman presented at our Internal Medicine ward with flaccid tetraparesis. Two months earlier, she had suffered a non-ST elevation myocardial infarction treated with percutaneous coronary intervention (PCI) and stenting, and she had been prescribed the classical post-PCI therapy (?-blockers, statins and antiplatelet agents). At admission, she was haemodynamically stable and the physical examination revealed reduced reflexes in the four limbs. Urgent laboratory findings revealed mild hypokalaemia. Considering the high statin doses she was taking, we also performed an urgent creatine phosphokinase test, which indicated rhabdomyolysis. Statin therapy was immediately stopped and aggressive fluid treatment begun, supplemented with potassium for increased urinary potassium losses. The patient progressively regained muscle strength. PMID:25903205

  9. 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. PMID:25422847

  10. Possible fatal acetaminophen intoxication with atypical clinical presentation.

    PubMed

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

    2013-09-01

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

  11. Severe theophylline poisoning: charcoal haemoperfusion or haemodialysis?

    PubMed Central

    Higgins, R. M.; Hearing, S.; Goldsmith, D. J.; Keevil, B.; Venning, M. C.; Ackrill, P.

    1995-01-01

    Theophylline poisoning with a blood level of 183 mg/l in a 38-year-old man was treated with activated charcoal by mouth, but despite this the blood level of theophylline rose and there was circulatory collapse with rhabdomyolysis, acute renal failure and hyperthermia. Treatment with charcoal haemoperfusion and simultaneous haemodialysis was given, followed by continuous arteriovenous haemodialysis (CAVHD). Mean extraction rates of theophylline were 26% during CAVHD, and 86% during combined dialysis and charcoal haemoperfusion. During combined treatment, the mean extraction rate of haemodialysis was 62%, compared with 48% for charcoal haemoperfusion. In summary, activated charcoal given by mouth may be unable to prevent a rise in blood levels and the development of complications after substantial theophylline overdose. If theophylline is to be removed from the blood, a combination of charcoal haemoperfusion and haemodialysis will give the best clearance, but haemodialysis alone may be effective. PMID:7784283

  12. Severe theophylline poisoning: charcoal haemoperfusion or haemodialysis?

    PubMed

    Higgins, R M; Hearing, S; Goldsmith, D J; Keevil, B; Venning, M C; Ackrill, P

    1995-04-01

    Theophylline poisoning with a blood level of 183 mg/l in a 38-year-old man was treated with activated charcoal by mouth, but despite this the blood level of theophylline rose and there was circulatory collapse with rhabdomyolysis, acute renal failure and hyperthermia. Treatment with charcoal haemoperfusion and simultaneous haemodialysis was given, followed by continuous arteriovenous haemodialysis (CAVHD). Mean extraction rates of theophylline were 26% during CAVHD, and 86% during combined dialysis and charcoal haemoperfusion. During combined treatment, the mean extraction rate of haemodialysis was 62%, compared with 48% for charcoal haemoperfusion. In summary, activated charcoal given by mouth may be unable to prevent a rise in blood levels and the development of complications after substantial theophylline overdose. If theophylline is to be removed from the blood, a combination of charcoal haemoperfusion and haemodialysis will give the best clearance, but haemodialysis alone may be effective. PMID:7784283

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

    PubMed Central

    Jo, Woo-Sik; Hossain, Md. Akil

    2014-01-01

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

  14. Increased plasma creatine kinase activities triggered by edible wild mushrooms.

    PubMed

    Nieminen, Petteri; Mustonen, Anne-Mari; Kirsi, Markku

    2005-01-01

    The consumption of wild mushrooms is mostly based on tradition and not scientific evidence. Recently the widely consumed Tricholoma flavovirens caused delayed rhabdomyolysis in humans. In this study, 42 mice and 4 humans consumed T. flavovirens mixed with regular food items. In mice, the plasma creatine kinase activity increased at 9 g kg(-1)day(-1). However, the same was observed with the well-known and commercially important Boletus edulis. The observed effect is probably not species-specific but represents an unspecific response and requires individual sensitivity and a great amount of ingested mushroom to manifest itself. A screening program of wild mushrooms is recommended to clarify how widespread this effect is. PMID:15582205

  15. Exercise Collapse Associated with Sickle Cell Trait (ECAST): Case Report and Literature Review.

    PubMed

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

    2015-01-01

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

  16. [Child poisoning after ingestion of a wild apiaceae: a case report].

    PubMed

    Durand, M-F; Pommier, P; Chazalette, A; de Haro, L

    2008-02-01

    Apiaceae family (formerly Umbelliferae) contains several highly toxic species, including Poison Hemlock (Conium maculatum), Water Hemlock (Cicuta virosa) and Hemlock Water Dropwort (Oenanthe crocata) which are the three main poisonous Apiaceae species growing in France. Thinking he was identifying wild carrots, an 11-year-old boy without previous history ingested the root from a wild Apiaceae. One hour later, he was confused, had drowsiness, headache as well as abdominal pain, vomiting and diarrhoea. Upon hospital admission, myosis, ophtalmoplegia and a moderate rhabdomyolysis were noted. The patient recovered after 24 h of symptomatic treatments. In this case, the description of the ingested plant allowed to identify the Apiaceae family but not the species involved. The geographical location (Southern France in a humid area), the clinical features and the aspect of the ingested root, with an orange secretion led to implicate Oenanthe crocata as the origin of this unusual poisoning. PMID:18206356

  17. Dantrolene for the treatment of MDMA toxicity.

    PubMed

    Grunau, Brian E; Wiens, Matthew O; Greidanus, Marc

    2010-09-01

    MDMA (3,4-methylenedioxymethamphetamine), popularly known as “Ecstasy,” was first introduced and patented by Merck & Co., Inc., in 1914 as an appetite suppressant. Currently, its primary role is as an illegal stimulant used to produce a euphoric effect during parties. This case report de scribes a 31-year-old man who, after taking 3 tablets of Ecstasy, presented to an emergency department with a decreased level of consciousness and became progressively hyperthermic and rigid. During the course of his acute illness, his temperature reached 42.2°C rectally. He was given mechanical ventilation. He was aggressively cooled and dantrolene was initiated. Soon after the administration of dantrolene his temperature decreased and his rigidity began to resolve. The only complication was rhabdomyolysis with a creatine kinase level increasing to over 150 ?kat/L. This did not progress to acute renal failure. The patient made a full recovery and was discharged to psychiatry for assessment. PMID:20925170

  18. 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. PMID:24035539

  19. [Multiorgan failure associated with hyperthermia in an infant with Prader-Willi syndrome. case report].

    PubMed

    Donoso, Alejandro; Arriagada, Daniela; Campbell, Stephanie; Cruces, Pablo

    2013-10-01

    Heat stroke is a medical emergency characterized primarily by an elevated core temperature associated with a systemic inflammatory response, which causes multiple organ dysfunction in which encephalopathy predominates. If it is not early treated has high mortality. The Prader-Willi syndrome is a multisystem genetic disorder secondary to an abnormality in long arm chromosome 15 (15q11-q13), characterized by neonatal central hypotonia, developmental delay, hypogonadism, hyperphagia and obesity. These patients are susceptible to developing thermoregulatory problems. We report the case of a 5-month-old infant, in whom a diagnosis of Prader-Willi syndrome was established in the course of a febrile episode without known focus, who developed multiorganic failure and rhabdomyolysis secondary to hyperthermia. PMID:24092035

  20. [Ischaemic stroke secondary to viper envenomation in Morocco in the absence of adequate antivenom].

    PubMed

    Chani, M; Abouzahir, A; Haimeur, C; Kamili, N Drissi; Mion, G

    2012-01-01

    An ischaemic stroke is a rare complication of viper envenomation that is due to multifactorial pathophysiological mechanisms. The authors describe the case of a 55-year-old patient bitten by the viper Cerastes cerastes. The patient was admitted to the intensive care unit with multiple organ failure, disseminated intravascular coagulopathy, rhabdomyolysis, anuria and elevated troponin level. The persistent disturbance of consciousness has motivated a brain scan which has revealed a bifocal ischemic stroke. The complex venom of the species C. cerastes may induce hypotension, tissue necrosis, acute renal failure, bleeding disorders or DIC. With the cessation of a non-indicated heparintherapy and haemodialysis, the patient recovered in a few weeks despite the initial infusion of an unsuitable antivenom due to the late identification of the reptile. The preventive treatment of the complications of this envenomation is based on the infusion of the polyvalent antivenom Favirept(®). PMID:22154446

  1. Update on toxic myopathies.

    PubMed

    Mastaglia, F L; Needham, M

    2012-02-01

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

  2. Carnitine palmitoyl transferase deficiency--unrecognized cause of recurrent acute kidney injury.

    PubMed

    Ale?kovi?-Halilovi?, Mirna; Meši?, Enisa; Sinanovi?, Osman; Zuki?, Sanela; Mustedanagi?, Jasminka

    2013-01-01

    Metabolic myopathies represent a small percentage of rhabdomyolysis causes that could lead to acute kidney injury (AKI). This could be prevented if this condition is suspected and timely treated. Carnitine palmityl transferase (CPT) deficiency is the most frequent metabolic myopathy and should be considered whenever recurrent myoglobinuria is suspected, and distinguished from the second frequent one, McArdle disease. We present a case of a patient with two medically misinterpreted episodes of AKI in whom the subsequent diagnosis of CPT deficiency was established based on high index of clinical suspicion and correlation of clinical manifestations to specific metabolic defects. Application of simple measures and lifestyle changes improved our patient's life quality and prevented potential new life-threatening complications. PMID:23560446

  3. [Nicolau syndrome after intramuscular injection].

    PubMed

    Bellot, B; Bonnet, C; Retornaz, K; Panuel, M; Garnier, J-M; Dubus, J-C; Jurquet, A-L

    2014-04-01

    Nicolau syndrome is a rare, potentially severe complication that may occur after any drug injection, particularly after intramuscular injection. It is characterized by the acute onset of cutaneous and soft-tissue aseptic necrosis. Here, we report the case of a 14-year-old boy diagnosed with Nicolau syndrome on the right lower limb, after a benzathine-penicillin intramuscular injection for suspected rheumatic fever. The short-term progression was marked by uncomplicated rhabdomyolysis and the constitution of homolateral testicular torsion. The cutaneous-muscular disorders evolved favorably under symptomatic treatment. We discuss this insufficiently known complication of intramuscular injection, which may motivate reduced use of this route of drug administration in children and strict adherence to the procedure. Furthermore, it is important to note that Nicolau syndrome may evolve to homolateral testicular torsion, as, to the best of our knowledge, is reported for the first time in this case. PMID:24630542

  4. 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

  5. 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. PMID:25346597

  6. Heat-related illness in sports and exercise.

    PubMed

    Nichols, Andrew W

    2014-12-01

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

  7. 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

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

    SciTech Connect

    Frydman, M.; Straussberg, R.; Shomrat, R.; Legum, C. [Tel Aviv Univ. (Israel)] [and others

    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.

  9. Anesthetic considerations in myofibrillar myopathy.

    PubMed

    Latham, Gregory J; Lopez, Grace

    2015-03-01

    Myofibrillar myopathy (MFM) is a relatively newly recognized genetic disease that leads to progressive muscle deterioration. MFM has a varied phenotypic presentation and impacts cardiac, skeletal, and smooth muscles. Affected individuals are at increased risk of respiratory failure, significant cardiac conduction abnormalities, cardiomyopathy, and sudden cardiac death. In addition, significant skeletal muscle involvement is common, which may lead to contractures, respiratory insufficiency, and airway compromise as the disease progresses. This study is the first report of anesthetic management of a patient with MFM. We report multiple anesthetic encounters of a child with genetically confirmed BAG3-myopathy, a subtype of MFM with severe childhood disease onset. A review of the anesthetic implications of the disease is provided, with specific exploration of possible susceptibility to malignant hyperthermia, rhabdomyolysis, and sensitivity to other anesthetic agents. PMID:25216331

  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. PMID:22448507

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

    PubMed

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

    2014-11-01

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

  13. A method for controlling complex confounding effects in the detection of adverse drug reactions using electronic health records

    PubMed Central

    Li, Ying; Salmasian, Hojjat; Vilar, Santiago; Chase, Herbert; Friedman, Carol; Wei, Ying

    2014-01-01

    Objective Electronic health records (EHRs) contain information to detect adverse drug reactions (ADRs), as they contain comprehensive clinical information. A major challenge of using comprehensive information involves confounding. We propose a novel data-driven method to identify ADR signals accurately by adjusting for confounders. Materials and methods We focused on two serious ADRs, rhabdomyolysis and pancreatitis, and used information in 264?155 unique patient records. We identified an ADR using established criteria, selected potential confounders, and then used penalized logistic regressions to estimate confounder-adjusted ADR associations. A reference standard was created to evaluate and compare the precision of the proposed method and four others. Results Precision was 83.3% for rhabdomyolysis and 60.8% for pancreatitis when using the proposed method, and we identified several drug safety signals that are interesting for further clinical review. Discussion The proposed method effectively estimated ADR associations after adjusting for confounders. A main cause of error was probably due to the nature of the dataset in that a substantial number of patients had a single visit only and, therefore, it was not possible to determine correctly the appropriate sequence of events for them. It is likely that performance will be improved with use of EHR data that contain more longitudinal records. Conclusions This data-driven method is effective in controlling for confounding, resulting in either a higher or similar precision when compared with four comparators, has the unique ability to provide insight into confounders for each specific medication–ADR pair, and can be easily adapted to other EHR systems. PMID:23907285

  14. 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

  15. Productive Infection of Human Skeletal Muscle Cells by Pandemic and Seasonal Influenza A(H1N1) Viruses

    PubMed Central

    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, ?2-6 and ?2-3 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. PMID:24223983

  16. 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 sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%. PMID:17456235

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

    PubMed Central

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

    2014-01-01

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

  18. Progressive histone alterations and proinflammatory gene activation: consequences of heme protein/iron-mediated proximal tubule injury

    PubMed Central

    Johnson, Ali C. M.

    2010-01-01

    Rhabdomyolysis (Fe)-induced acute renal failure (ARF) causes renal inflammation, and, with repetitive insults, progressive renal failure can result. To gain insights into these phenomena, we assessed the impact of a single episode of glycerol-induced rhabdomyolysis on proinflammatory/profibrotic [TNF-?, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-?1 (TGF-?1)] gene expression and the time course of these changes. CD-1 mice were studied 1–7 days after glycerol injection. Normal mice served as controls. RNA polymerase II (Pol II) binding to the TNF-?, MCP-1, and TGF-?1 genes, “gene-activating” histone modifications [histone 3 lysine 4 (H3K4) trimethylation (H3K4m3) and histone 2 variant H2A.Z], and cognate mRNA levels were assessed. Results were contrasted to changes in anti-inflammatory heme oxygenase-1 (HO-1). Glycerol produced severe ARF (blood urea nitrogen ?150–180 mg/dl) followed by marked improvement by day 7 (blood urea nitrogen ?40 mg/dl). Early increases in TNF-?, MCP-1, and TGF-?1 mRNAs, Pol II gene binding, and H3K4m3/H2A.Z levels were observed. These progressed with time, despite resolution of azotemia. Comparable early HO-1 changes were observed. However, HO-1 mRNA normalized by day 7, and progressive Pol II binding/histone alterations did not occur. Fe-mediated injury to cultured proximal tubule (HK-2) cells recapitulated these in vivo results. Hence, this in vitro model was used for mechanistic assessments. On the basis of these studies, it was determined that 1) the H3K4m3/H2A.Z increases are early events (i.e., they precede mRNA increases), 2) subsequent mRNA elevations reflect transcription, not mRNA stabilization (actinomycin D assessments), and 3) increased transcription, per se, helps sustain elevated H2A.Z levels. We conclude that 1) Fe/glycerol-induced tubular injury causes sustained proinflammatory gene activation, 2) decreasing HO-1 expression, as reflected by mRNA levels, may facilitate this proinflammatory state, and 3) gene-activating histone modifications are early injury events and progressively increase at selected proinflammatory genes. Thus they may help sustain a proinflammatory state, despite resolving ARF. PMID:20032114

  19. 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, and multiple drugs as well as the patients with delayed admission to the hospital, and it is necessary to seek appropriate treatment to prevent this significant side effect. PMID:24783168

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. McArdle disease: what do neurologists need to know?

    PubMed

    Lucia, Alejandro; Nogales-Gadea, Gisela; Pérez, Margarita; Martín, Miguel A; Andreu, Antoni L; Arenas, Joaquín

    2008-10-01

    McArdle disease (also known as glycogen storage disease type V) is a pure myopathy caused by an inherited deficit of myophosphorylase, the skeletal muscle isoform of the enzyme glycogen phosphorylase. The disease exhibits clinical heterogeneity, but patients typically experience exercise intolerance, that is, reversible, acute crises (early fatigue and contractures, sometimes with rhabdomyolysis and myoglobinuria) triggered by static muscle contractions (e.g. lifting weights) or dynamic exercise (e.g. climbing stairs or running). In this Review, we discuss the main features of McArdle disease, with the aim of providing neurologists with up-to-date, useful information to assist their patients. The topics covered include diagnostic tools-for example, molecular genetic diagnosis, the classic ischemic forearm test and the so-called 'second wind' phenomenon-and current therapeutic options-for example, a carbohydrate-rich diet and carbohydrate ingestion shortly before strenuous exercise, in combination with medically supervised aerobic training of low to moderate intensity. PMID:18833216

  4. 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.

  5. Evaluation and treatment of heat-related illnesses.

    PubMed

    Wexler, Randell K

    2002-06-01

    The body's ability to regulate core temperature depends on both host (internal) and environmental (external) factors. Although athletes are commonly thought to be most at risk for heat illnesses, children and the elderly are particularly vulnerable. Heat cramps, which are caused by fluid and electrolyte imbalances, are treated with massage, and fluid and electrolyte replacement. Heat exhaustion occurs both as water- and sodium-depleted types, with associated symptoms such as malaise, vomiting, and confusion. Treatment involves taking the affected person to a cool environment and replacing fluids and electrolytes if needed. In more serious cases, intravenous hydration may be necessary, although monitoring of serum sodium levels is important to prevent cerebral edema. If not treated promptly, heat exhaustion may evolve into heatstroke, a deadly form of heat illness. Heatstroke occurs in classic and exertional forms and is present when the core body temperature exceeds 40 degrees C (104 degrees F). The patient may experience cardiac arrhythmias, rhabdomyolysis, serum chemistry abnormalities, disseminated intravascular coagulation, and death. Heatstroke is a medical emergency that should be treated immediately with temperature-lowering techniques such as immersion in an ice bath or evaporative cooling. Fluid resuscitation is important but should be closely monitored, and renal function may need to be protected with mannitol and diuretics. It is important to be vigilant for heat illnesses because they occur insidiously but progress rapidly. PMID:12074531

  6. Risks and management of prolonged suspension in an Alpine harness.

    PubMed

    Mortimer, Roger B

    2011-03-01

    Suspension trauma is a state of shock induced by passive hanging. Those who survive passive suspension are at risk for rhabdomyolysis. In a wilderness setting, one can see this in cases of persons suspended on rope by their harness. In a conscious person, leg movements work the venous pump to return blood to the central circulation. In the person passively hanging, blood pools in the legs leading to hypoperfusion of vital organs. In the experimental setting, passive hanging has led to unconsciousness in a matter of minutes. Based on a previous series of deaths on rope that included 7 after rescue, many authors have recommended nonstandard treatment for shock including keeping rescued patients upright or squatting for 30 minutes prior to laying them down. This recommendation assumes that sudden death is a risk from acute volume overload or exposure to waste products in the returning blood. This suggestion is not supported by the original series that demonstrated sudden deaths after rescue nor by modern understandings of physiology. Search and rescue teams and party members assisting a colleague suspended unconscious on rope should follow standard resuscitation measures to restore circulation to vital organs immediately. PMID:21377125

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

    PubMed Central

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

    2011-01-01

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

  8. McArdle disease: a unique study model in sports medicine.

    PubMed

    Santalla, Alfredo; Nogales-Gadea, Gisela; Ørtenblad, Niels; Brull, Astrid; de Luna, Noemi; Pinós, Tomàs; Lucia, Alejandro

    2014-11-01

    McArdle disease is arguably the paradigm of exercise intolerance in humans. This disorder is caused by inherited deficiency of myophosphorylase, the enzyme isoform that initiates glycogen breakdown in skeletal muscles. Because patients are unable to obtain energy from their muscle glycogen stores, this disease provides an interesting model of study for exercise physiologists, allowing insight to be gained into the understanding of glycogen-dependent muscle functions. Of special interest in the field of muscle physiology and sports medicine are also some specific (if not unique) characteristics of this disorder, such as the so-called 'second wind' phenomenon, the frequent exercise-induced rhabdomyolysis and myoglobinuria episodes suffered by patients (with muscle damage also occurring under basal conditions), or the early appearance of fatigue and contractures, among others. In this article we review the main pathophysiological features of this disorder leading to exercise intolerance as well as the currently available therapeutic possibilities. Patients have been traditionally advised by clinicians to refrain from exercise, yet sports medicine and careful exercise prescription are their best allies at present because no effective enzyme replacement therapy is expected to be available in the near future. As of today, although unable to restore myophosphorylase deficiency, the 'simple' use of exercise as therapy seems probably more promising and practical for patients than more 'complex' medical approaches. PMID:25028051

  9. AICAR Prevents Heat Induced Sudden Death in RyR1 Mutant Mice Independent of AMPK Activation

    PubMed Central

    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.

    2011-01-01

    Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (RyR1) die when exposed to short periods of temperature elevation (? 37 °C). We demonstrate that treatment with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) prevents heat-induced sudden death in Y524S mice. The AICAR protection is independent of AMPK activation and results from a newly identified action on the mutant RyR1 to reduce Ca2+ leak, preventing Ca2+ dependent increases in both reactive oxygen and reactive nitrogen species that act to further increase resting Ca2+ concentrations. If unchecked, the temperature driven increases in resting Ca2+ and ROS/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 the heat induced death in vivo. Our findings suggest that AICAR is likely to be effective in prophylactic treatment of humans with enhanced susceptibility to exercise/heat-induced sudden death associated with RyR1 mutations. PMID:22231556

  10. 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

    2012-02-01

    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. PMID:22231556

  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. 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. PMID:24793440

  13. Heat-related injury in lambs.

    PubMed

    Sula, Mee Ja M; Winslow, Christine M; Boileau, Melanie J; Barker, L D; Panciera, Roger J

    2012-07-01

    The broad spectrum of heat-related injury (HRI) and its associated lesions is well described in the human literature, with rare reports of similar findings in farm animals. In the current case series, lesions from 4 of 8 lambs that presented with clinical signs of heat stress are reported. Gross lesions at necropsy consisted of acute renal swelling and pallor in 2 of 4 lambs, muscle pallor in 2 of 4 lambs, and chronic bronchointerstitial pneumonia in each of the 4 lambs. Histological lesions considered heat-related included acute renal tubular necrosis, pigment casts, tubular epithelial regeneration, multifocal myocyte degeneration, necrosis, and dropout with histiocytic influx and regeneration. Chronic, bronchointerstitial pneumonia, present in each lamb, was considered a condition predisposing to HRI. Compatibility between observed lesions and those reported in human beings with injury secondary to elevated body temperatures established a diagnosis of HRI in these animals. Diagnostic pathologists should consider HRI in lambs with histological evidence of renal tubular necrosis and/or rhabdomyolysis and even in cases where the clinical picture is strongly suggestive but lesions are not demonstrable. PMID:22585957

  14. Strategies to Prevent Positioning-Related Complications Associated with the Lateral Suboccipital Approach

    PubMed Central

    Furuno, Yuichi; Sasajima, Hiroyasu; Goto, Yukihiro; Taniyama, Ichita; Aita, Kazuyasu; Owada, Kei; Tatsuzawa, Kazunori; Mineura, Katsuyoshi

    2013-01-01

    The lateral positioning used for the lateral suboccipital surgical approach is associated with various pathophysiologic complications. Strategies to avoid complications including an excessive load on the cervical vertebra and countermeasures against pressure ulcer development are needed. We retrospectively investigated positioning-related complications in 71 patients with cerebellopontine angle lesions undergoing surgery in our department between January 2003 and December 2010 using the lateral suboccipital approach. One patient postoperatively developed rhabdomyolysis, and another presented with transient peroneal nerve palsy on the unaffected side. Stage I and II pressure ulcers were noted in 22 and 12 patients, respectively, although neither stage III nor more severe pressure ulcers occurred. No patients experienced cervical vertebra and spinal cord impairments, brachial plexus palsy, or ulnar nerve palsy associated with rotation and flexion of the neck. Strategies to prevent positioning-related complications, associated with lateral positioning for the lateral suboccipital surgical approach, include the following: atraumatic fixation of the neck focusing on jugular venous perfusion and airway pressure, trunk rotation, and sufficient relief of weightbearing and protection of nerves including the peripheral nerves of all four extremities. PMID:24498587

  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

    2014-06-30

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

  16. Proteasome inhibition and oxidative reactions disrupt cellular homeostasis during heme stress

    PubMed Central

    Vallelian, F; Deuel, J W; Opitz, L; Schaer, C A; Puglia, M; Lönn, M; Engelsberger, W; Schauer, S; Karnaukhova, E; Spahn, D R; Stocker, R; Buehler, P W; Schaer, D J

    2015-01-01

    Dual control of cellular heme levels by extracellular scavenger proteins and degradation by heme oxygenases is essential in diseases associated with increased heme release. During severe hemolysis or rhabdomyolysis, uncontrolled heme exposure can cause acute kidney injury and endothelial cell damage. The toxicity of heme was primarily attributed to its pro-oxidant effects; however additional mechanisms of heme toxicity have not been studied systematically. In addition to redox reactivity, heme may adversely alter cellular functions by binding to essential proteins and impairing their function. We studied inducible heme oxygenase (Hmox1)-deficient mouse embryo fibroblast cell lines as a model to systematically explore adaptive and disruptive responses that were triggered by intracellular heme levels exceeding the homeostatic range. We extensively characterized the proteome phenotype of the cellular heme stress responses by quantitative mass spectrometry of stable isotope-labeled cells that covered more than 2000 individual proteins. The most significant signals specific to heme toxicity were consistent with oxidative stress and impaired protein degradation by the proteasome. This ultimately led to an activation of the response to unfolded proteins. These observations were explained mechanistically by demonstrating binding of heme to the proteasome that was linked to impaired proteasome function. Oxidative heme reactions and proteasome inhibition could be differentiated as synergistic activities of the porphyrin. Based on the present data a novel model of cellular heme toxicity is proposed, whereby proteasome inhibition by heme sustains a cycle of oxidative stress, protein modification, accumulation of damaged proteins and cell death. PMID:25301065

  17. Retrospective study on antihyperlipidemic efficacy and safety of simvastatin, ezetimibe and their combination in Korean adults.

    PubMed

    Lee, Young-Hee; Kim, Mi-Jeong; Choi, Chang-Ik; Bae, Jung-Woo; Jang, Choon-Gon; Lee, Seok-Yong

    2011-08-01

    Antihyperlipidemic agents such as 3-hydroxymethyglutaryl-coenzyme A reductase inhibitors and cholesterol transporter inhibitors are used in coronary heart disease. However, controversy remains over the pharmacologic effects and safety of these drugs, especially when used in combination therapies. This retrospective study evaluated the therapeutic effect and safety of simvastatin 20 mg and ezetimibe 10 mg combination therapy compared to simvastatin 20 mg or ezetimibe 10 mg monotherapy in Korean patients according to gender, age, baseline low-density lipoprotein cholesterol, and cardiovascular risk factors. We observed significant differences among patient subgroups. Simvastatin and ezetimibe monotherapies and combination therapy reduced low-density lipoprotein cholesterol levels by 27.6%, 10.1%, and 36.8% (p < 0.001) and total cholesterol levels by 17.5%, 9.2%, and 25.3% (p < 0.001), respectively. Both monotherapy and combination therapy groups had similar incidences of all types of adverse events. However, one case of rhabdomyolysis was observed in the combination therapy group. These results suggest that, compared to monotherapy, combination therapy has an additive effect that is not influenced by risk factors. Despite the low incidence of adverse events, caution is required when using these drugs, especially in the context of musculoskeletal side effects. PMID:21910055

  18. 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 ?-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, ?-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney. PMID:23622366

  19. Unusual reactions to hymenoptera stings: what should we keep in mind?

    PubMed

    Mingomataj, Ervin Ç; Bakiri, Alketa H; Ibranji, Alkerta; Sturm, Gunter J

    2014-08-01

    This review includes a variety of extremely rare and unusual hymenoptera sting (HS) circumstances with regard to sting localization, geographic region, massivity of multiple stings, and particularly related to clinical symptoms. Such reactions occur in a temporal relationship to HS (s), differ from typical allergic symptomatology, and sometimes need follow-up during many months. With respect to pathogenesis, the major mechanisms involved are toxic, autoimmune, and other delayed immunological ones. While delayed inflammatory symptoms of the nervous system are considered as delayed hypersensitization or autoimmune entities, generalized rhabdomyolysis and consecutive acute kidney injury is considered a toxic reaction, mostly induced by massive envenomation to wasps or "Africanized" bees. Hemorrhagic episodes of targeted organ (s) could be additional potential risk for acute kidney injury, while the bee venom-induced hemorrhage is proposed to be a nonimmune-mediated anaphylactic symptom. The hemodynamic involvement of vital organs and systems with hypoxia and hypovolemia together with simultaneous immunoglobulin E (IgE) sensitization are considered potential indications for venom immunotherapy. In contrast, patients who have experienced various complications with unknown or nonallergic mechanisms should be informed about the importance of epinephrine's use and additional measures on future sting avoidance. In conclusion, although unusual reactions are extremely rare, it is important to keep them in mind. PMID:24962710

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

    PubMed

    Jauchem, James R

    2011-05-01

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

  1. Suspected myotoxicity of edible wild mushrooms.

    PubMed

    Nieminen, Petteri; Kirsi, Markku; Mustonen, Anne-Mari

    2006-02-01

    Recently, the widely consumed yellow tricholoma Tricholoma flavovirens caused delayed rhabdomyolysis and fatalities in humans in France and Poland and triggered elevated plasma creatine kinase activities in mice. Furthermore, the highly appreciated king boletus (Boletus edulis) caused similar responses in experimental mice. Because of this, it was hypothesized that other fungi could also contain chemical compounds that would cause similar myotoxic effects. To test the suspected myotoxicity of other wild mushrooms consumed by tradition, 86 mice were exposed for 5 days to 3, 6, or 9 g/kg body mass/day of edible mushrooms representing diverse genera (Russula spp, Cantharellus cibarius, Albatrellus ovinus, and Leccinium versipelle) mixed with regular laboratory rodent diet. The plasma creatine kinase activity increased with all studied mushroom species at 9 g/kg body mass/day, whereas the histologic appearance of muscle and liver samples was unaffected. The results support the hypothesis that the previously observed toxic effects are not specific to T. flavovirens, but probably represent an unspecific response requiring individual sensitivity and a significant amount of ingested mushroom to manifest itself. PMID:16446499

  2. Fatal heat stroke associated with topiramate therapy.

    PubMed

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

    2013-12-01

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

  3. [Excess mineralocorticoid syndrome secondary to nasal sprays containing 9 alpha-fluoroprednisolone].

    PubMed

    Foresti, V; Parisio, E; Ricci, G

    1987-09-15

    Two patients with signs of hypermineralcorticism and suppressed plasma aldosterone levels are reported. For both patients the use of a nasal spray containing 9 alpha-fluoroprednisolone had been ascertained, the withdrawal of which was followed by the normalization of the clinical picture as well as by the normal reactivity of the renin-aldosterone system. The endocrine studies excluded the presence of enzymatic defects or the hypersecretion of minor mineralocorticoids. The tests with angiotensin II and ACTH did not result in an increase in aldosterone, which instead increased in a significant way after metoclopramide, even with still suppressed basal values. Since the PRA was normal at the time of the metoclopramide test, a persisting inhibition of the factors directly controlling aldosterone secretion by 9 alpha-fluoroprednisolone could be possibly envisaged. An interesting findings was the onset of severe hypokalemia, conditioning rhabdomyolysis with myoglobinuria in patient 1, after a treatment of few weeks only. Since the factitious use of mineral corticoids is not taken into account, the need of an accurate collection of case history in the differential diagnosis of hyporeninemic hypoaldosteronism with hypokalemia is stressed. PMID:2444906

  4. Proteasome inhibition and oxidative reactions disrupt cellular homeostasis during heme stress.

    PubMed

    Vallelian, F; Deuel, J W; Opitz, L; Schaer, C A; Puglia, M; Lönn, M; Engelsberger, W; Schauer, S; Karnaukhova, E; Spahn, D R; Stocker, R; Buehler, P W; Schaer, D J

    2015-04-01

    Dual control of cellular heme levels by extracellular scavenger proteins and degradation by heme oxygenases is essential in diseases associated with increased heme release. During severe hemolysis or rhabdomyolysis, uncontrolled heme exposure can cause acute kidney injury and endothelial cell damage. The toxicity of heme was primarily attributed to its pro-oxidant effects; however additional mechanisms of heme toxicity have not been studied systematically. In addition to redox reactivity, heme may adversely alter cellular functions by binding to essential proteins and impairing their function. We studied inducible heme oxygenase (Hmox1)-deficient mouse embryo fibroblast cell lines as a model to systematically explore adaptive and disruptive responses that were triggered by intracellular heme levels exceeding the homeostatic range. We extensively characterized the proteome phenotype of the cellular heme stress responses by quantitative mass spectrometry of stable isotope-labeled cells that covered more than 2000 individual proteins. The most significant signals specific to heme toxicity were consistent with oxidative stress and impaired protein degradation by the proteasome. This ultimately led to an activation of the response to unfolded proteins. These observations were explained mechanistically by demonstrating binding of heme to the proteasome that was linked to impaired proteasome function. Oxidative heme reactions and proteasome inhibition could be differentiated as synergistic activities of the porphyrin. Based on the present data a novel model of cellular heme toxicity is proposed, whereby proteasome inhibition by heme sustains a cycle of oxidative stress, protein modification, accumulation of damaged proteins and cell death. PMID:25301065

  5. Neurotoxicity associated with suspected southern Pacific rattlesnake (Crotalus viridis helleri) envenomation.

    PubMed

    Bush, S P; Siedenburg, E

    1999-01-01

    An 18-year-old man was bitten on the hand by a snake he believed to be a Southern Pacific rattlesnake (Crotalus viridis helleri). Within minutes he developed generalized weakness, difficulty breathing, diplopia, dysphagia, and dysphonia. Neurological examination revealed ptosis and decreased motor strength. These symptoms partially improved after administration of Antivenin (Crotalidae) Polyvalent, but the patient continued to have difficulty walking for several days due to weakness. In addition to neurological symptoms, the patient also experienced pain immediately after the bite occurred and rapid swelling of the entire extremity, which extended beyond the shoulder. He complained of a metallic taste in his mouth and developed intense muscle fasciculations of the face, tongue, and upper extremities, which lasted for 2 days and did not improve with antivenin treatment. He exhibited laboratory evidence of coagulopathy and rhabdomyolysis. Although neurotoxins are known to occur in the venom of certain populations of rattlesnakes, only a few clinical reports describing severe neurological symptoms appear in the literature. To our knowledge, this is the first reported case of neurotoxicity associated with a suspected Southern Pacific rattlesnake envenomation. PMID:10628285

  6. Fatal poisoning by butachlor and chlornitrofen ingested from a bottle marked as nitrofen.

    PubMed

    Lin, T J; Li, H P; Wong, S S; Hung, D Z; Yang, D Y

    2001-08-01

    Nitrofen has been banned in Taiwan since January 1, 1983 due to its tetrogenicity. A 78-y-o female consumed about 500 ml of herbicide, labeled as nitrofen, in a suicide attempt. Consciousness disturbance occurred immediately. After 9 h, bloody-tarry stool was noted. Hematemesis occurred 19 h later. Hepatotoxicity and nephrotoxicity also developed. Twitching of head and both upper extremities lasting 20-30 sec and up to 5 min developed on day 3. Sometimes an upward gaze with the face turned to the right or a convulsion of the right upper extremity was observed. EEG showed alpha coma, generalized slow spike-and-wave complexes, and isolated generalized sharp waves mainly in the left occipital area. On day 7, endotracheal intubation was performed due to apnea; she expired on day 9. The pesticide was found to contain butachlor and chlornitrofen. The Agricultural Committee prohibited the marketing of chlornitrofen due to its generation of tumors in animals. The combination of butachlor and chlornitrofen can result in consciousness disturbance, leucocytosis, gastrointestinal hemorrhage, rhabdomyolysis, hypocalcemia, hypoalbuminemia, elevated amylase, nephrotoxicity, hepatotoxicity, seizures and death. The cytotoxicity of butachlor may be related to the patient's death. Active components of pesticides should be checked if the clinical course of a poisoned patient is unusual to allow appropriate interventions. PMID:11474734

  7. Effort Thrombosis (Paget-Schroetter Syndrome) in a 16-Year-Old Male

    PubMed Central

    Spencer, Taylor R.; Lagace, Richard E.; Waterman, George

    2014-01-01

    Patient: Male, 16 Final Diagnosis: Effort thrombosis (Paget-Schroetter Sydnrome) Symptoms: Swollen arms Medication: — Clinical Procedure: — Specialty: Metabolic Disorders and Diabetics Objective: Rare disease Background: Thrombotic events in otherwise healthy pediatric patients are rare. In patients presenting with limb swelling, thrombosis must be considered in the differential diagnosis. In pediatric patients with thrombosis, there has been wide variability in the rates of associated thrombophilia. Many pediatric patients may instead have other contributors such as venous catheters or physical activity. Case Report: We present a case of bilateral upper extremity deep venous thrombi in a previously healthy 16-year-old male. The patient presented with swelling and pain in both arms after several days of weight-bearing exercise. Following emergency department evaluation with ultrasound and laboratory testing, the patient was diagnosed with effort thrombosis – also known as Paget-Schroetter syndrome – and rhabdomyolysis. Conclusions: This case of Paget-Schroetter syndrome is distinguished by elevation in creatine kinase and transaminases. While these findings can be due to physical exertion and effort, effort thrombosis is not classically associated with laboratory abnormalities except an elevated D-dimer. The significance of these laboratory test result abnormalities remains unclear. Given the rarity of effort thrombosis, further epidemiological study is warranted to determine if these laboratory findings are seen in other cases, and, if so, what implications they may have for management and prognosis. PMID:25098327

  8. Hypokalemic paralysis in a professional bodybuilder.

    PubMed

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

    2012-09-01

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

  9. Methamphetamine abuse.

    PubMed

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

    2007-10-15

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

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

    PubMed

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

    2014-03-01

    Statins, or 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, such as lovastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, rosuvastatin and pitavastatin, are cholesterol-lowering drugs used in clinical practice to prevent coronary heart disease. These drugs are generally well tolerated and have been rarely associated with severe adverse effects (e.g. rhabdomyolysis). Over the years, case series and data from national registries of spontaneous adverse drug reaction reports have demonstrated the occurrence of neuropsychiatric reactions associated with statin treatment. They include behavioural alterations (severe irritability, homicidal impulses, threats to others, road rage, depression and violence, paranoia, alienation, antisocial behaviour); cognitive and memory impairments; sleep disturbance (frequent awakenings, shorter sleep duration, early morning awakenings, nightmares, sleepwalking, night terrors); and sexual dysfunction (impotence and decreased libido). Studies designed to investigate specific neuropsychiatric endpoints have yielded conflicting results. Several mechanisms, mainly related to inhibition of cholesterol biosynthesis, have been proposed to explain the detrimental effects of statins on the central nervous system. Approaches to prevent and manage such adverse effects may include drug discontinuation and introduction of dietary restrictions; maintenance of statin treatment for some weeks with close patient monitoring; switching to a different statin; dose reduction; use of ?-3 fatty acids or coenzyme Q10 supplements; and treatment with psychotropic drugs. The available information suggests that neuropsychiatric effects associated with statins are rare events that likely occur in sensitive patients. Additional data are required, and further clinical studies are needed. PMID:24435290

  11. Medical complications of drug abuse.

    PubMed

    Becker, C E

    1979-01-01

    Because we do not fully understand the cause of drug abuse, we do not currently have specific therapy for the abuse phenomenon. It is likely that those patients who abuse drugs are not a homogeneous treatment group. The patients seen most frequently because of medical complications probably represent only a small percentage of the total number of drug abusers. The medical complications of drug abuse affect almost all organ systems, and may result acutely from overdose or may not become apparent until after prolonged or recurrent use. Special emphasis has been placed on recognizing the key points of the physical examination in the overdose setting and in the drug-abusing patient that will give clues as to the nature and degree of the drug abuse. It is not clear whether drug abuse causes behavioral problems or vice versa. Physicians need to develop the medical expertise necessary to care for patients with drug abuse problems. Special attention is called to new drug abuse problems: complications associated with phencyclidine, amyl nitrate, and layman's remedies; acute and pulmonary complications; rhabdomyolysis; the brown heroin syndrome; and methylphenidate abuse. Although each of these complications has individual importance, a high incidence of alcohol use and smoking further compromises the general health of drug-abusing patients. Treating all of the medical complications of drugs must be viewed as only the beginning of a therapeutic attempt to restore these patients to a more physically and emotionally healthy life. PMID:371359

  12. 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

  13. 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

  14. Complications and outcomes of brown recluse spider bites in children.

    PubMed

    Hubbard, Jonathan J; James, Laura P

    2011-03-01

    Brown recluse spider bites may cause severe local and systemic morbidity, but data regarding morbidity in children are limited. This study reviewed inpatient medical records (n = 26; 10 years) with a discharge diagnosis of "spider bite" from a tertiary pediatric hospital. The majority (85%) of children had an inflammatory response accompanying necrosis, usually with signs of secondary cellulitis (77%). Hemolytic anemia (50%), rhabdomyolysis (27%), and acute renal failure (12%) were the most prevalent systemic effects. Hemolytic anemia was bimodal in distribution relative to the time-of-onset of the bite (early, 2.2 ± 0.4; late, 6.9 ± 1.5 days postbite, respectively; P = .004). Although no fatalities occurred in the population, 65% of children had major morbidity, including wound complications requiring surgical care and acute orbital compartment syndrome. The findings emphasize the importance of anticipatory patient/family education for outpatients and careful monitoring for systemic morbidity in inpatients. Timely and appropriate supportive care should yield favorable outcomes in most cases. PMID:21307081

  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. Pemoline ingestion in children: a report of five cases and review of the literature.

    PubMed

    Nakamura, Hidefumi; Blumer, Jeffrey L; Reed, Michael D

    2002-03-01

    The authors describe five pediatric cases of excessive pemoline ingestion. Based on their experience compared with previously reported cases in the literature, they describe the clinical presentation and rational treatment recommendations for acute pemoline ingestion. Overall, patients experienced a relatively benign clinical course following pemoline ingestion. Symptoms of pemoline ingestion appear to be primarily an accentuation of the drug's pharmacological effects on the central nervous and cardiovascular systems with sinus tachycardia, hypertension, hyperactivity, choreoathetoid movements, and hallucinations being most commonly observed. These findings are consistent with previously reported cases. Possible rhabdomyolysis manifested by evaluation of serum CPK was also observed in 3 of 4 patients in whom this laboratory parameter was measured and appears to be a common finding in acute pemoline poisoning. After acute ingestion, symptoms occurred within 6 hours, lasting up to 48 hours in all patients. Gastric lavage and/or activated charcoal would be effective decontamination measures, whereas ipecac-induced emesis should be avoided after massive ingestion due to the possibility of seizures. Aggressive use of a benzodiazepine appears a reasonable first choice to treat associated involuntary movements, tremor, hyperactivity, irritability, and agitation. Phenothiazines or butyrophenones may also be used especially for serious life-threatening symptoms, including hypertensive crisis and severe hyperthermia, although these serious complications of stimulant overdose have not been reported after pemoline ingestion. If a patient should experience pemoline-induced hypertensive crisis, individual dose titration of labetalol or sodium nitroprusside would appear reasonable pharmacologic approaches for rapid stabilization of blood pressure. PMID:11865963

  17. Rare complications of pediatric diabetic ketoacidosis

    PubMed Central

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

    2015-01-01

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

  18. Clinical toxicology: a tropical Australian perspective.

    PubMed

    Currie, B J

    2000-02-01

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

  19. Ten years of snake bites at Fremantle Hospital.

    PubMed

    Jelinek, G A; Breheny, F X

    Seventy-six patients (30% children) were admitted to Fremantle Hospital over 10 years with suspected snake bite. Twenty-nine patients were definitely bitten, with 26 bites being witnessed. Of the 13 patients definitely envenomated, 11 had a coagulopathy although seven were asymptomatic; four other patients may have been envenomated. The dugite (Pseudonaja affinis) was probably responsible for most envenomations. Eleven of the 13 envenomated patients received antivenom (six brown snake, four polyvalent and one tiger snake antivenom). The patient envenomated by the tiger snake (Notechis ater occidentalis), a 13-year-old girl, was initially incorrectly treated with brown snake antivenom at a country hospital, and did not receive appropriate antivenom until 50 hours after the bite. She developed profound paralysis, rhabdomyolysis and renal failure, and required prolonged ventilation during her 53-day hospital admission, but survived without disability. Snake bite wounds should not be washed, so that venom can be identified from the wound. Attempts to kill snakes are dangerous, often leading to bites on the fingers. First aid measures of a pressure bandage and immobilisation, used in 13 of the 29 cases (45%), should be more widely publicised. PMID:2246987

  20. 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. PMID:25435669

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

    PubMed

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

    2014-03-01

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

  2. Multiple MDMA (Ecstasy) overdoses at a rave event: a case series.

    PubMed

    Armenian, Patil; Mamantov, Tanya M; Tsutaoka, Ben T; Gerona, Roy R L; Silman, Eric F; Wu, Alan H B; Olson, Kent R

    2013-01-01

    Twelve patients with 3,4-methylenedioxymethamphetamine (MDMA) toxicity from a single rave event presented to multiple San Francisco Bay area hospitals with various life-threatening complications including seizures and hyperthermia. Eight required emergent endotracheal intubation and six had hypotension. Hyperkalemia, acute kidney injury, and rhabdomyolysis were present in most of the patients. In all, 2 patients died, 4 survived with permanent neurologic, musculoskeletal, and/or renal sequelae, and 6 survived without any apparent lasting deficits. Hyperthermia was present in 10 patients and was severe (40.9-43° C) in 7. Using multiple cooling methods, the average time to achieve cooling was 2.7 hours. Serum drug analysis was performed on 3 patients, demonstrating toxic MDMA concentrations without the presence of other xenobiotics. Two capsules confiscated by police at the event contained 82% and 98% MDMA, respectively, without other pharmacologically active compounds. Capsule #2 contained 270 mg MDMA, which is more than twice the amount of MDMA usually contained in 1 dose. The MDMA-induced hyperthermia significantly contributed to the morbidity and mortality in this case series. Factors contributing to the severity of the hyperthermia include ingestion of large doses of MDMA, a warm ambient environment, and physical exertion. PMID:22640978

  3. Congenital Cataracts – Facial Dysmorphism – Neuropathy

    PubMed Central

    Kalaydjieva, Luba

    2006-01-01

    Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance. To date, CCFDN has been found to occur exclusively in patients of Roma (Gypsy) ethnicity; over 100 patients have been diagnosed. Developmental abnormalities include congenital cataracts and microcorneae, primary hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, mild facial dysmorphism and hypogonadism. Para-infectious rhabdomyolysis is a serious complication reported in an increasing number of patients. During general anaesthesia, patients with CCFDN require careful monitoring as they have an elevated risk of complications. CCFDN is a genetically homogeneous condition in which all patients are homozygous for the same ancestral mutation in the CTDP1 gene. Diagnosis is clinical and is supported by electrophysiological and brain imaging studies. The major differential diagnosis is Marinesco-Sjögren syndrome. The definitive diagnosis is molecular, based on homozygosity for the CTDP1 mutation. CTDP1 maps to 18qter and encodes a protein phosphatase whose only known substrate is the phosphorylated serine residues of the carboxy-terminal domain of the largest subunit of RNA polymerase II, indicating that CCFDN affects basic cellular processes of gene expression and developmental regulation. Families benefit from genetic counselling and predictive testing. Management includes surgical treatment of the cataracts, and rehabilitation and corrective orthopaedic surgery for the peripheral neuropathy. Thus, the most disabling manifestations, though not curable, are manageable, and allow an acceptable quality of life and everyday living. Current data indicate that patients survive well into adulthood. PMID:16939648

  4. Envenoming by the common krait (Bungarus caeruleus) and Sri Lankan cobra (Naja naja naja): efficacy and complications of therapy with Haffkine antivenom.

    PubMed

    Theakston, R D; Phillips, R E; Warrell, D A; Galagedera, Y; Abeysekera, D T; Dissanayaka, P; de Silva, A; Aloysius, D J

    1990-01-01

    In Anuradhapura, Sri Lanka, 5 patients proved to have been bitten by common kraits (Bungarus caeruelus) and 2 by Sri Lankan cobras (Naja naja naja) were investigated. In all the cases of krait bite the patients were bitten while they were asleep: local signs were negligible but 4 developed symptoms of systemic envenoming including paralysis, muscle pain and tenderness and abdominal pain. Mild myoglobinaemia was found in one case. Of the 2 patients bitten by cobras, one developed severe local swelling which progressed to necrosis and the other local swelling and respiratory paralysis. Response to polyspecific antivenom (Haffkine, India) was neither rapid nor convincing. Venom antigenaemia became undetectable within 2 h of the start of antivenom treatment, but recurred 25 and 65 h later in 2 cases. Among a group of 27 patients treated with this antivenom (including 21 bitten by Russell's vipers), the incidence of early anaphylactic and pyrogenic reactions was high at 52% and 65% respectively. Anticholinesterase did not improve paralysis in 2 patients bitten by kraits. The respiratory failure in 2 patients was successfully treated by mechanical ventilation for 8 and 30 h. These observations confirm the importance of neurotoxic symptoms following bites by these species but also suggest a contributory role of generalized rhabdomyolysis in krait victims and emphasize the problem of severe local tissue necrosis in cobra victims. There is a need for safer and more potent antivenoms for use in Sri Lanka. PMID:2389328

  5. The Lightning Heart: A Case Report and Brief Review of the Cardiovascular Complications of Lightning Injury

    PubMed Central

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

    2010-01-01

    Lightning strike is a rare natural phenomenon, which carries a risk of dramatic medical complications to multiple organ systems and a high risk of fatality. The known complications include but are not limited to: myocardial infarction, arrhythmia, cardiac contusion, stroke, cutaneous burns, respiratory disorders, neurological disorders, acute kidney injury and death. We report a case of a healthy young man who suffered a lightning injury and discuss the cardiovascular complications of lightning injury, ranging from ECG changes to death. The patient in our case, a 27-year old previously healthy male, developed a syndrome of rhabdomyolysis and symptomatic cardiogenic pulmonary edema. Electrocardiographic findings included transient T-wave inversions, late transition shift and long QT. His clinical condition improved with supportive measures. Early recognition of lightning injury syndromes and anticipation of complications may help us improve outcomes for these patients. Evaluation of patients having experienced a lightning injury should include a minimum of a detailed history and physical examination, 12-lead ECG and drawing of baseline troponins. Prolonged electrocardiographical monitoring (for monitoring of ventricular arrhythmias) and assessment for signs and symptoms of hemodynamic compromise may be warranted. PMID:20930961

  6. 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. PMID:21070288

  7. [Synthetic cannabinoids: spread, addiction biology & current perspective of personal health hazard].

    PubMed

    Bonnet, U; Mahler, H

    2015-04-01

    Among the new psychoactive substances (NPS), most frequently synthetic cannabinoids (SCBs) have been found in Europe. These are sold as active compounds in e.?g. so-called "herbal blends". When inhaled or ingested, besides intoxication symptoms, as they occur with heavy cannabis use (e.?g., tachycardia, myocardial infarction, confusion, hallucinations, panic attacks, and paranoia), harmful effects (severe agitation, coma, catatonic stupor, hypertension, cardiac arrhythmia, dyspnoea, seizures, myoclonus, rhabdomyolysis, hyperthermia, diaphoresis, acute kidney injury, vomiting, headache, and hypokalemia) arise, which are mostly unusual about cannabis use. In addition, the first cases of addiction and death related to SCBs have been reported. Taking into account the newest literature and using an algorithm with two main criteria (addiction potential, toxicity), the authors made a first attempt to rank the personal health hazard of SCBs in comparison to that of other psychoactive drugs. Accordingly, the relative health hazard of SCBs is found to be somewhat higher than that of cannabis and lower than that of synthetic cathinones ("bath salts"). However, the toxicity of SCBs, is significantly greater than the toxicity of cannabis, thus being similar to that of synthetic cathinones and benzodiazepines. The addiction potential appears to be lower than that of synthetic cathinones, benzodiazepines, or cannabis. Due to the fluctuation of substances and the availability in internet resources, legislation is facing a serious "hare-hedgehog" problem to control the manufacture, trade and possession of SCBs. PMID:25893495

  8. 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

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

    PubMed

    Grenha, Joana; Garrido, Ana; Brito, Hernani; Oliveira, Maria José; Santos, Fátima

    2013-01-01

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

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

    PubMed Central

    Garrido, Ana; Brito, Hernani; Oliveira, Maria José; Santos, Fátima

    2013-01-01

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

  11. Propofol Infusion Syndrome: A Retrospective Analysis at a Level 1 Trauma Center

    PubMed Central

    Diaz, James H.; Prabhakar, Amit; Urman, Richard D.; Kaye, Alan David

    2014-01-01

    Objectives. The propofol infusion syndrome (PRIS), a rare, often fatal, condition of unknown etiology, is defined by development of lipemic serum, metabolic acidosis, rhabdomyolysis, hepatomegaly, cardiac arrhythmias, and acute renal failure. Methods. To identify risk factors for and biomarkers of PRIS, a retrospective chart review of all possible PRIS cases during a 1-year period was conducted at a level 1 trauma hospital in ICU patients over 18 years of age receiving continuous propofol infusions for ?3 days. Additional study inclusion criteria included vasopressor support and monitoring of serum triglycerides and creatinine. Results. Seventy-two patients, 61 males (84.7%) and 11 females (15.3%), satisfied study inclusion criteria; and of these, 3 males met the study definition for PRIS, with 1 case fatality. PRIS incidence was 4.1% with a case-fatality rate of 33%. The mean duration of propofol infusion was 6.96 days. A positive linear correlation was observed between increasing triglyceride levels and infusion duration, but no correlation was observed between increasing creatinine levels and infusion duration. Conclusions. Risk factors for PRIS were confirmed as high dose infusions over prolonged periods. Increasing triglyceride levels may serve as reliable biomarkers of impending PRIS, if confirmed in future investigations with larger sample sizes. PMID:25580289

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

    PubMed

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

    2014-08-01

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

  13. Management and treatment of gamma butyrolactone withdrawal syndrome: a case report and review.

    PubMed

    Ghio, Lucio; Cervetti, Alice; Respino, Matteo; Belvederi Murri, Martino; Amore, Mario

    2014-07-01

    Gamma butyrolactone (GBL) is an increasingly popular drug of abuse that is readily available in most countries, and it is often purchased over the Internet. In addition to the acute hazards of intoxication and overdose, users who are dependent on GBL can also experience severe withdrawal reactions, including hallucinations, agitation, confusion, delusions, delirium, rhabdomyolysis, and seizures. Most of the existing literature suggests the use of a high-dose benzodiazepine as a first-line treatment for GBL withdrawal. However, several cases of resistance to benzodiazepines have been observed, which likely reflect some pharmacological differences between benzodiazepines and GBL. Specifically, the effects of benzodiazepines are primarily mediated by gamma-aminobutyric acid (GABA)-A receptors, while GBL and its analogues act mainly at GABA-B receptors, with possible additional effects via the ionotropic GABA-A receptors. In this regard, recent studies have found that GBL and its analogues possess a high affinity for a specific form of extrasynaptic GABA-A receptors that are strongly activated by barbiturates, such as phenobarbital, but that are insensitive to benzodiazepines. Taken together, these findings suggest that barbiturates could be evaluated as first-choice agents for the treatment of GBL/gamma hydroxybutyrate (GHB) withdrawal instead of benzodiazepines. In support of this view, we describe a clinical case of difficult to manage GBL withdrawal symptoms in a 42-year-old male. We also review the literature on treatment options for GBL/GHB withdrawal, including benzodiazepine-resistant withdrawal. PMID:25036586

  14. 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

  15. Electronic health records for biological sample collection: feasibility study of statin-induced myopathy using the Clinical Practice Research Datalink

    PubMed Central

    O'Meara, Helen; Carr, Daniel F; Evely, Jane; Hobbs, Mark; McCann, Gerard; van Staa, Tjeerd; Pirmohamed, Munir

    2014-01-01

    AIMS Electronic healthcare records (EHRs) are increasingly used to store clinical information. A secondary benefit of EHRs is their use, in an anonymized form, for observational research. The Clinical Practice Research Datalink (CPRD) contains EHRs from primary care in the UK and, despite 1083 peer-reviewed research publications, has never been used to obtain pharmacogenetic samples. Using a statin-induced myopathy paradigm, we evaluated using the CPRD to obtain patient samples for a pharmacogenetic study targeting 250 cases and 500 controls from UK general practitioner (GP) practices. METHODS The CPRD identified potential patients fitting specific case-definition criteria (active rhabdomyolysis or creatine phosphokinase > four times the upper limit of normal), and corresponding GP practices were asked to invite patient participation. Consenting patients were requested to provide either saliva or blood samples and to complete an ethnicity questionnaire. Control subjects were recruited from the same GP practice (saliva) or a small number of practices (blood). Samples were forwarded for DNA extraction. RESULTS Thirty-six months of recruitment yielded DNA samples from 149 statin-induced myopathy cases and 587 tolerant controls. Data show that contacting patients through their GP is a reliable method for obtaining samples without compromising anonymity. Saliva collection directly from patients was considerably less effective than blood sampling. After 10 months of recruitment, saliva sampling was suspended in favour of blood sampling. CONCLUSIONS We demonstrate the potential of EHRs for identifying accurately phenotyped cases and controls for pharmacogenetic studies. Recruitment was successful only because of the willingness of GP practices to participate and the existence of strong doctor–patient relationships. The present study provides a model that can be implemented in future genetic analyses using EHRs. PMID:24308359

  16. Sitagliptin/Simvastatin: a first combination tablet to treat type 2 diabetes and hypercholesterolemia – a review of its characteristics

    PubMed Central

    Ramadan, Wijdan H; Kabbara, Wissam K

    2015-01-01

    Background The purpose of this study was to review the current literature and information on the combination product Juvisync™ (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011. Methods PubMed (2001–2014) was searched for primary and review articles on sitagliptin, simvastatin, or the combination product. Drug manufacturing data and product labeling were also used. Studies of simvastatin, sitagliptin, or the combination were screened and analyzed to include relevant and recent papers. Selected English language trials were limited to those with human subjects and included both safety and efficacy outcomes. Results When compared with glipizide as add-on therapy to metformin, sitagliptin was noninferior but had lower rates of hypoglycemia and weight gain. In addition, when compared with insulin glargine, sitagliptin was less effective in decreasing glycosylated hemoglobin, but was associated with significantly lower rates of hypoglycemia. Further, trials have shown a beneficial effect of using statins in patients with diabetes mellitus with regard to decreasing cardiovascular risk, regardless of baseline lipid levels or the presence of a cardiac disease. Both medications have also demonstrated an acceptable side effect profile. However, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of myopathy and rhabdomyolysis. Conclusion Juvisync should be used in patients requiring both sitagliptin and simvastatin. Both agents have shown good efficacy and acceptable safety profiles. Sitagliptin is a good option for diabetic patients to improve glycemic control with a lower risk of hypoglycemia and weight gain. PMID:25709467

  17. Adverse effects of statins - myths and reality.

    PubMed

    Šimi?, 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. PMID:25312733

  18. Clinical Features of Severe Wasp Sting Patients with Dominantly Toxic Reaction: Analysis of 1091 Cases

    PubMed Central

    Ding, Fengfei; Xie, Minjie; Lv, Jiagao; Yao, Jihua; Pan, Dengji; Sun, Qian; Liu, Chenchen; Chen, Tie; Li, Shusheng; Wang, Wei

    2013-01-01

    Background Massive wasp stings have been greatly underestimated and have not been systematically studied. The aim of this study was to identify the clinical features and treatment strategies of severe wasp stings. Methods and Findings A multicenter retrospective study was undertaken in 35 hospitals and medical centers including 12 tertiary care hospitals and 23 secondary care hospitals in the Hubei Province, China. The detailed clinical data of 1091 hospitalized wasp sting patients were investigated. Over three-fourths (76.9%) of the cases had 10 or more stings and the in-hospital mortality of patients was 5.1%. Forty-eight patients died of organ injury following toxic reactions to the stings, whereas six died from anaphylactic shock. The in-hospital mortality in patients with >10 stings was higher than that of ?10 stings (5.2% vs. 1.0%, p?=?0.02). Acute kidney injury (AKI) was seen in 21.0% patients and most patients required blood purification therapy. Rhabdomyolysis was seen in 24.1% patients, hemolysis in 19.2% patients, liver injury in 30.1% patients, and coagulopathy in 22.5% patients. Regression analysis revealed that high creatinine level, shock, oliguria, and anemia were risk factors for death. Blood purification therapy was beneficial for patients with ?20 stings and delayed hospital admission of patients (?4 hours after sting). Conclusions In China, most patients with multiple wasp stings presented with toxic reactions and multiple organ dysfunction caused by the venom rather than an anaphylactic reaction. AKI is the prominent clinical manifestation of wasp stings with toxic reaction. High creatinine levels, shock, oliguria, and anemia were risk factors for death. PMID:24391743

  19. Differential Mortality of Male Spectacled Eiders (Somateria fischeri) and King Eiders (Somateria spectabilis) Subsequent to Anesthesia with Propofol, Bupivacaine, and Ketoprofen

    USGS Publications Warehouse

    Mulcahy, D.M.; Tuomi, P.; Larsen, R.S.

    2003-01-01

    Twenty free-ranging spectacled eiders (Somateria fischeri; 10 male, 10 female), 11 free-ranging king eiders (Somateria spectabilis; 6 male, 5 female), and 20 female common eiders (Somateria mollissima) were anesthetized with propofol, bupivacaine, and ketoprofen for the surgical implantation of satellite transmitters. Propofol was given to induce and maintain anesthesia (mean total dose, 26.2-45.6 mg/kg IV), bupivacaine (2-10 mg/kg SC) was infused into the incision site for local analgesia, and ketoprofen (2-5 mg/kg IM) was given at the time of surgery for postoperative analgesia. Four of 10 male spectacled eiders and 5 of 6 male king eiders died within 1-4 days after surgery. None of the female spectacled or common eiders and only 1 of the 5 female king eiders died during the same postoperative period. Histopathologic findings in 2 dead male king eiders were severe renal tubular necrosis, acute rhabdomyolysis, and mild visceral gout. Necropsy findings in 3 other dead male king eiders were consistent with visceral gout. We suspect that the perioperative use of ketoprofen caused lethal renal damage in the male eiders. Male eiders may be more susceptible to renal damage than females because of behavioral differences during their short stay on land in mating season. The combination of propofol, bupivacaine, and ketoprofen should not be used to anesthetize free-ranging male eiders, and nonsteroidal anti-inflammatory drugs should not be used perioperatively in any bird that may be predisposed to renal insufficiency.

  20. Protein conjugated with aldehydes derived from lipid peroxidation as an independent parameter of the carbonyl stress in the kidney damage

    PubMed Central

    2011-01-01

    Background One of the well-defined and characterized protein modifications usually produced by oxidation is carbonylation, an irreversible non-enzymatic modification of proteins. However, carbonyl groups can be introduced into proteins by non-oxidative mechanisms. Reactive carbonyl compounds have been observed to have increased in patients with renal failure. In the present work we have described a procedure designed as aldehyde capture to calculate the protein carbonyl stress derived solely from lipid peroxidation. Methods Acrolein-albumin adduct was prepared as standard at alkaline pH. Rat liver microsomal membranes and serum samples from patients with diabetic nephropathy were subjected to the aldehyde capture procedure and aldol-protein formation. Before alkalinization and incubation, samples were precipitated and redisolved in 6M guanidine. The absorbances of the samples were read with a spectrophotometer at 266 nm against a blank of guanidine. Results Evidence showed abundance of unsaturated aldehydes derived from lipid peroxidation in rat liver microsomal membranes and in the serum of diabetic patients with advanced chronic kidney disease. Carbonyl protein and aldol-proteins resulted higher in the diabetic nephropathy patients (p < 0.004 and p < 0.0001 respectively). Conclusion The aldehyde-protein adduct represents a non oxidative component of carbonyl stress, independent of the direct amino acid oxidation and could constitute a practical and novelty strategy to measure the carbonyl stress derived solely from lipid peroxidation and particularly in diabetic nephropathy patients. In addition, we are in a position to propose an alternative explanation of why alkalinization of urine attenuates rhabdomyolysis-induced renal dysfunction. PMID:22059738

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

    PubMed

    Jacobson, Terry A

    2006-04-17

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

  2. Sympathomimetic syndrome, choreoathetosis, and acute kidney injury following "bath salts" injection.

    PubMed

    Sutamtewagul, Grerk; Sood, Vineeta; Nugent, Kenneth

    2014-01-01

    "Bath salts" is a well known street drug which can cause several cardiovascular and neuropsychiatric symptoms. However, only one case of acute kidney injury has been reported in the literature. We present a case with sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury following the use of bath salts. A 37-year-old man with past medical history of hypertension and depression was brought to the emergency center with body shaking. Three days before admission he injected 3 doses of bath salts intravenously and felt eye pain with blurry vision followed by a metallic taste, strange smells, profuse sweating, and body shaking. At presentation he had a sympathomimetic syndrome including high blood pressure, tachycardia, tachypnea, and hyperhydrosis with choreoathetotic movements. Laboratory testing revealed leukocytosis and acute kidney injury with a BUN of 95 mg/ dL and a creatinine of 15.2 mg/dL. Creatine kinase was 4,457 IU/dL. Urine drug screen is negative for amphetamine, cannabinoids, and cocaine; blood alcohol level was zero. During his ICU stay he became disoriented and agitated. Supportive treatment with 7.2 liters of intravenous fluid over 3 days, haloperidol, and lorazepam gradually improved his symptoms and his renal failure. Bath salts contain 3,4-methylenedioxypyrovalerone, a psychoactive norepinephrine and dopamine reuptake inhibitor. Choreoathetosis in this patient could be explained through dopaminergic effect of bath salts or uremic encephalopathy. The mechanism for acute kidney injury from bath salts may involve direct drug effects though norepinephrine and dopamine-induced vasoconstriction (renal ischemia), rhabdomyolysis, hyperthermia, and/or volume contraction. PMID:24356039

  3. One Hundred Seventy-Nine Consecutive Bariatric Operations after Introduction of Protocol Inspired by the Principles of Enhanced Recovery after Surgery (ERAS®) in Bariatric Surgery

    PubMed Central

    Mat?ok, Maciej; P?dziwiatr, Micha?; Major, Piotr; K??k, Stanis?aw; Budzy?ski, Piotr; Ma?czak, Piotr

    2015-01-01

    Background Obese patients are a very large high-risk group for complications after surgical procedures. In this group, optimized perioperative care and a faster recovery to full activity can contribute to a decreased rate of postoperative complications. The introduction of ERAS®-based protocol is now even more important in bariatric surgery centers. The results of our study support the idea of implementation of ERAS®-based protocol in this special group of patients. Material/Methods This analysis included 170 patients (62 male/108 female, mean BMI 46.7 kg/m2) who had undergone laparoscopic bariatric surgery, and whose perioperative care was conducted according to a protocol inspired by ERAS® principles. Examined factors included oral nutrition tolerance, time until mobilization after surgery, requirements for opioids, duration of hospitalization, and readmission rate. Results During the first 24 postoperative hours, oral administration of liquid nutrition was tolerated by 162 (95.3%) patients and 163 (95.8%) were fully mobile. In 44 (25.8%) patients it was necessary to administer opioids to relieve pain. Intravenous liquid supply was discontinued within 24 hours in 145 (85.3%) patients. The complication rate was 10.5% (mainly rhabdomyolysis and impaired passage of gastric contents). The average time of hospitalization was 2.9 days and the readmission rate was 1.7%. Conclusions The introduction of an ERAS® principles-inspired protocol in our center proved technically possible and safe for our patients, and allowed for reduced hospitalization times without increased rate of complications or readmissions. PMID:25779669

  4. 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

  5. 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

  6. Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate.

    PubMed

    Smith, Kelly M; Larive, Lisa L; Romanelli, Frank

    2002-06-01

    The abuse of methylenedioxymethamphetamine (MDMA), flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate (GHB) is discussed. Club drugs are chemical substances used recreationally in social settings. Use is increasingly frequent among young people, especially during all-night dance parties. All four agents have been classified as controlled substances. MDMA ("ecstasy") is available as a tablet, a capsule, and a powder; formulations may contain many adulterants. MDMA increases the release of neurotransmitters. The desired effects are euphoria, a feeling of intimacy, altered visual perception, enhanced libido, and increased energy. The most common adverse effects are agitation, anxiety, tachycardia, and hypertension. More serious adverse effects include arrhythmias, hyperthermia, and rhabdomyolysis. Flunitrazepam is a potent benzodiazepine. At higher doses, the drug can cause lack of muscle control and loss of consciousness. Other adverse effects are hypotension, dizziness, confusion, and occasional aggression. Ketamine is a dissociative anesthetic used primarily in veterinary practice. It may be injected, swallowed, snorted, or smoked. Like phencyclidine, ketamine interacts with the N-methyl-D-aspartate channel. Analgesic effects occur at lower doses and amnestic effects at higher doses. Cardiovascular and respiratory toxicity may occur, as well as confusion, hostility, and delirium. GHB, a naturally occurring fatty acid derivative of gamma-aminobutyric acid, was introduced as a dietary supplement. Increasing doses progressively produce amnesia, drowsiness, dizziness, euphoria, seizures, coma, and death. Flunitrazepam, ketamine, and GHB have been used to facilitate sexual assault. Supportive care is indicated for most cases of club drug intoxication. The increasing abuse of MDMA, flunitrazepam, ketamine hydrochloride, and GHB, particularly by young people in social settings such as clubs, should put health care professionals on guard to recognize and manage serious reactions. PMID:12063892

  7. Hemolysis as a rare but potentially life-threatening complication of hemodialysis: a case report

    PubMed Central

    2014-01-01

    Background The burden of end-stage renal disease (ESRD) in the United States has increased dramatically over the past 30 years with almost 613,000 patients receiving renal replacement therapy in 2011. That same year, more than 112,000 new patients initiated dialysis with 92% of them receiving hemodialysis (HD). These patients experience significant morbidity and mortality with very frequent emergency room visits. Acute hemolysis associated with HD is a rare complication; however, if it’s not recognized early and managed adequately, it can be associated with life-threatening complications such as hyperkalemia and even myocardial infarction. Case presentation 66-year-old African-American female with a history of ESRD secondary to hypertension developed a blood infiltration on the arterial side of her arteriovenous fistula followed by sudden onset of diffuse abdominal pain with nausea and vomiting during her regular HD treatment. She was referred to the emergency department where she was found to have shortness of breath with improved gastrointestinal symptoms. Her initial work-up revealed a severe anemia with a hematocrit of 10%. Further work-up revealed massive hemolysis, likely mechanical in nature and believed to be induced by malpositioning of her HD needle in the fistula. Her hospital course was complicated by rhabdomyolysis and acute myocardial infarction thought to be secondary to supply–demand ischemia in the setting of her profound anemia. Within a week, she eventually had a full recovery. Conclusion It is extremely important for physicians and particularly emergency department physicians to be aware of this potentially life-threatening complication of HD and have a high index of suspicion in the setting of acute anemia with hemolysis in this population. PMID:25065406

  8. One Hundred Seventy-Nine Consecutive Bariatric Operations after Introduction of Protocol Inspired by the Principles of Enhanced Recovery after Surgery (ERAS®) in Bariatric Surgery.

    PubMed

    Mat?ok, Maciej; P?dziwiatr, Micha?; Major, Piotr; K??k, Stanis?aw; Budzy?ski, Piotr; Ma?czak, Piotr

    2015-01-01

    BACKGROUND Obese patients are a very large high-risk group for complications after surgical procedures. In this group, optimized perioperative care and a faster recovery to full activity can contribute to a decreased rate of postoperative complications. The introduction of ERAS®-based protocol is now even more important in bariatric surgery centers. The results of our study support the idea of implementation of ERAS®-based protocol in this special group of patients. MATERIAL AND METHODS This analysis included 170 patients (62 male/108 female, mean BMI 46.7 kg/m2) who had undergone laparoscopic bariatric surgery, and whose perioperative care was conducted according to a protocol inspired by ERAS® principles. Examined factors included oral nutrition tolerance, time until mobilization after surgery, requirements for opioids, duration of hospitalization, and readmission rate. RESULTS During the first 24 postoperative hours, oral administration of liquid nutrition was tolerated by 162 (95.3%) patients and 163 (95.8%) were fully mobile. In 44 (25.8%) patients it was necessary to administer opioids to relieve pain. Intravenous liquid supply was discontinued within 24 hours in 145 (85.3%) patients. The complication rate was 10.5% (mainly rhabdomyolysis and impaired passage of gastric contents). The average time of hospitalization was 2.9 days and the readmission rate was 1.7%. CONCLUSIONS The introduction of an ERAS® principles-inspired protocol in our center proved technically possible and safe for our patients, and allowed for reduced hospitalization times without increased rate of complications or readmissions. PMID:25779669

  9. Deaths from exposure to paramethoxymethamphetamine in Alberta and British Columbia, Canada: a case series

    PubMed Central

    Yarema, Mark C.; Jones, Graham R.; Martz, Walter; Purssell, Roy A.; MacDonald, Judy C.; Wishart, Ian; Durigon, Monica; Tzemis, Despina; Buxton, Jane A.

    2015-01-01

    Background Paramethoxymethamphetamine (PMMA) is a ring-substituted amphetamine similar in structure to 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”), but substantially more toxic. We describe the clinical features of fatal exposures in the provinces of Alberta and British Columbia, Canada. Methods We conducted a retrospective case series on deaths in Alberta and BC between June 2011 and April 2012 for which forensic toxicologic analysis was positive for PMMA and the drug was implicated as the primary toxic agent. Data collected included patient demographics, exposure history, clinical features, investigations, therapy provided and postmortem toxicologic findings. Results A total of 27 PMMA-associated deaths (20 in Alberta, 7 in BC) were reported in the 11-month period. The median age was 24 (range 14–52) years, and 22 (81%) were male. Ten patients were pronounced dead at the scene, and 17 died in hospital. The median time from exposure to death was 17 (range 5–264) hours. The median first-recorded vital signs (and ranges) were: heart rate 160 (86–201) beats/min, blood pressure 89/43 (69/30–162/83) mm Hg, respiratory rate 40 (26–48) breaths/min, oxygen saturation 81% (68%–100%) and temperature 39.4°C (34–43.8°C). Sixteen of the 17 people who died in hospital presented with clinical features consistent with serotonin syndrome. End-organ dysfunction included hepatic (30%) and acute kidney injury (85%), rhabdomyolysis (54%), coagulopathy (61%) and cardiac ischemia (15%). Other drugs identified on toxicologic analysis were MDMA (n = 27), cocaine or its metabolite benzoylecgonine (n = 14) and methamphetamine (n = 12). Interpretation Exposure to PMMA was characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. In addition to PMMA, multiple synthetic amphetamines were present on toxicologic analysis. When evaluating patients suspected of exposure to sympathomimetic drugs of abuse, clinicians must anticipate multiple clinical effects from the increased release of dopamine, serotonin, norepinephrine and other neurotransmitters.

  10. 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

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

    PubMed Central

    Paillet-Loilier, Magalie; Cesbron, Alexandre; Le Boisselier, Reynald; Bourgine, Joanna; Debruyne, Danièle

    2014-01-01

    Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines. PMID:24966713

  12. Lessons from calsequestrin-1 ablation in vivo: much more than a Ca(2+) buffer after all.

    PubMed

    Protasi, Feliciano; Paolini, Cecilia; Canato, Marta; Reggiani, Carlo; Quarta, Marco

    2011-12-01

    Calsequestrin type-1 (CASQ1), the main sarcoplasmic reticulum (SR) Ca(2+) binding protein, plays a dual role in skeletal fibers: a) it provides a large pool of rapidly-releasable Ca(2+) during excitation-contraction (EC) coupling; and b) it modulates the activity of ryanodine receptors (RYRs), the SR Ca(2+) release channels. We have generated a mouse lacking CASQ1 in order to further characterize the role of CASQ1 in skeletal muscle. Contrary to initial expectations, CASQ1 ablation is compatible with normal motor activity, in spite of moderate muscle atrophy. However, CASQ1 deficiency results in profound remodeling of the EC coupling apparatus: shrinkage of junctional SR lumen; proliferation of SR/transverse-tubule contacts; and increased density of RYRs. While force development during a twitch is preserved, it is nevertheless characterized by a prolonged time course, likely reflecting impaired Ca(2+) re-uptake by the SR. Finally, lack of CASQ1 also results in increased rate of SR Ca(2+) depletion and inability of muscle to sustain tension during a prolonged tetani. All modifications are more pronounced (or only found) in fast-twitch extensor digitorum longus muscle compared to slow-twitch soleus muscle, likely because the latter expresses higher amounts of calsequestrin type-2 (CASQ2). Surprisingly, male CASQ1-null mice also exhibit a marked increased rate of spontaneous mortality suggestive of a stress-induced phenotype. Consistent with this idea, CASQ1-null mice exhibit an increased susceptibility to undergo a hypermetabolic syndrome characterized by whole body contractures, rhabdomyolysis, hyperthermia and sudden death in response to halothane- and heat-exposure, a phenotype remarkably similar to human malignant hyperthermia and environmental heat-stroke. The latter findings validate the CASQ1 gene as a candidate for linkage analysis in human muscle disorders. PMID:22130610

  13. Dengue-associated kidney disease

    PubMed Central

    J Lizarraga, Karlo; Nayer, Ali

    2014-01-01

    Context: A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue is considered a major global health threat by the World Health Organization. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: An RNA virus from the genus Flavivirus, dengue virus is transmitted by Aedes aegypti,the yellow fever mosquito. Dengue is asymptomatic in as many as one half of infected individuals. Dengue fever is an acute febrile illness accompanied by constitutional symptoms. Dengue hemorrhagic fever and dengue shock syndrome are the severe forms of dengue infection.Dengue infection has been associated with a variety of renal disorders. Acute renal failure is a potential complication of severe dengue infection and is typically associated with hypotension, rhabdomyolysis, or hemolysis. Acute renal failure complicates severe dengue infection in 2-5% of the cases and carries a high mortality rate. Proteinuria has been detected in as high as 74% of patients with severe dengue infection. Hematuria has been reported in up to 12.5% of patients. Various types of glomerulonephritis have been reported during or shortly after dengue infection in humans and mouse models of dengue infection. Mesangial proliferation and immune complex deposition are the dominant histologic features of dengue-associated glomerulonephritis. On a rare occasion, dengue infection is associated with systemic autoimmune disorders involving the kidneys. Conclusions: In the vast majority of cases, dengue infection and associated renal disorders are self-limited. PMID:24772398

  14. Perioperative Intravenous Acetaminophen Attenuates Lipid Peroxidation in Adults Undergoing Cardiopulmonary Bypass: A Randomized Clinical Trial

    PubMed Central

    Billings IV, Frederic T.; Petracek, Michael R.; Roberts II, L. Jackson; Pretorius, Mias

    2015-01-01

    Background Cardiopulmonary bypass (CPB) lyses erythrocytes and induces lipid peroxidation, indicated by increasing plasma concentrations of free hemoglobin, F2-isoprostanes, and isofurans. Acetaminophen attenuates hemeprotein-mediated lipid peroxidation, reduces plasma and urine concentrations of F2-isoprostanes, and preserves kidney function in an animal model of rhabdomyolysis. Acetaminophen also attenuates plasma concentrations of isofurans in children undergoing CPB. The effect of acetaminophen on lipid peroxidation in adults has not been studied. This was a pilot study designed to test the hypothesis that acetaminophen attenuates lipid peroxidation in adults undergoing CPB and to generate data for a clinical trial aimed to reduce acute kidney injury following cardiac surgery. Methods and Results In a prospective double-blind placebo-controlled clinical trial, sixty adult patients were randomized to receive intravenous acetaminophen or placebo starting prior to initiation of CPB and for every 6 hours for 4 doses. Acetaminophen concentrations measured 30 min into CPB and post-CPB were 11.9±0.6 ?g/mL (78.9±3.9 ?M) and 8.7±0.3 ?g/mL (57.6±2.0 ?M), respectively. Plasma free hemoglobin increased more than 15-fold during CPB, and haptoglobin decreased 73%, indicating hemolysis. Plasma and urinary markers of lipid peroxidation also increased during CPB but returned to baseline by the first postoperative day. Acetaminophen reduced plasma isofuran concentrations over the duration of the study (P = 0.05), and the intraoperative plasma isofuran concentrations that corresponded to peak hemolysis were attenuated in those subjects randomized to acetaminophen (P = 0.03). Perioperative acetaminophen did not affect plasma concentrations of F2-isoprostanes or urinary markers of lipid peroxidation. Conclusions Intravenous acetaminophen attenuates the increase in intraoperative plasma isofuran concentrations that occurs during CPB, while urinary markers were unaffected. Trial Registration ClinicalTrials.gov NCT01366976 PMID:25705899

  15. Inhibition of prenyltransferase activity by statins in both liver and muscle cell lines is not causative of cytotoxicity.

    PubMed

    Gee, Rowena H; Spinks, Jenny N; Malia, Jason M; Johnston, Jonathan D; Plant, Nick J; Plant, Kathryn E

    2015-03-01

    As inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, statins are an important first-line treatment for hypercholesterolemia. However, a recognized side-effect of statin therapy is myopathy, which in severe cases can present as potentially fatal rhabdomyolysis. This represents an important impediment to successful statin therapy, and despite decades of research the molecular mechanisms underlying this side-effect remain unclear. Current evidence supports a role for reduced levels of mevalonate pathway intermediates, with the most accepted hypothesis being a reduction in isoprenoids formation, leading to faulty post-translational modifications of membrane-associated proteins. We have undertaken a comprehensive analysis of the impact of nine statins on two human cell lines; Huh7 hepatoma and RD rhabdomyosarcoma. In both cell lines, concentration-dependent inhibition of prenylation was observed for cerivastatin and simvastatin, which could be rescued with the pathway intermediate mevalonate; in general, muscle cells were more sensitive to this effect, as measured by the levels of unprenylated Rap1A, a marker for prenylation by geranylgeranyl transferase I. Concentration-dependent toxicity was observed in both cell lines, with muscle cells again being more sensitive. Importantly, there was no correlation between inhibition of prenylation and cell toxicity, suggesting they are not causally linked. The lack of a causal relationship was confirmed by the absence of cytotoxicity in all cell lines following exposure to specific inhibitors of geranylgeranyl transferases I and II, and farnesyl transferase. As such, we provide strong evidence against the commonly accepted hypothesis linking inhibition of prenylation and statin-mediated toxicity, with the two processes likely to be simultaneous but independent. PMID:25578243

  16. 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; Vestra, Michele Dalla; 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??/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/? 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

  17. 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 by the gathering of the four Asian (Japanese) T. auratum strains in a strongly supported distinct phylogenetic clade. Moreover, our analysis strongly argues for considering T. joachimii and the synonymised T. equestre var. pallidifolia as two representatives of a different species not belonging to the T. equestre group. This species would be phylogenetically related to the Tricholoma columbetta species with which they share white gills. Similarly, the phylogenetic analysis of the molecular data and the lack of gene flow between the strains associated with broad-leaved trees and those of the T. equestre complex, rather argues for two distinct species depending on the ecological niche: T. frondosae under broad-leaved trees and T. equestre under conifers. PMID:23452952

  18. Acidosis, lactate, electrolytes, muscle enzymes, and other factors in the blood of Sus scrofa following repeated TASER exposures.

    PubMed

    Jauchem, James R; Sherry, Clifford J; Fines, David A; Cook, Michael C

    2006-08-10

    Repeated exposure to electro-muscular incapacitating devices could result in repetitive, sustained muscle contraction, with little or no muscle recovery period. Therefore, rhabdomyolysis and other physiological responses, including acidosis, hyperkalaemia, and altered levels of muscle enzymes in the blood, would be likely to occur. Experiments were performed to investigate effects of repeated exposures of TASER International's Advanced TASER X26 on muscle contraction and resultant changes in blood factors in an anaesthetized swine model. A total of 10 animals were used. Six swine were exposed for 5 s, followed by a 5-s period of no exposure, repeatedly for 3 min. (In five of the animals, after a 1-h delay, a second 3-min exposure period was added.) The remaining four animals were used for an additional pilot study. All four limbs of each animal exhibited contraction even though the electrodes were positioned in areas at some distances from the limbs. The degree of muscle contraction generated during the second exposure period was significantly lower than that in the first exposure series. This finding was consistent with previous studies showing that prolonged activity in skeletal muscle will eventually result in a decline of force production. There were some similarities in blood sample changes in the current experiments with previous studies of muscular exercise. Thus problems concerning biological effects of repeated TASER exposures may be related, not directly to the "electric output" per se, but rather to the resulting contraction of muscles (and related interruption of respiration) and subsequent sequelae. Transient increases in hematocrit, potassium, and sodium were consistent with previous reports in the literature dealing with studies of muscle stimulation or exercise. It is doubtful that these short-term elevations would have any serious health consequences in a healthy individual. Blood pH was significantly decreased for 1h following exposure, but subsequently returned toward a normal level. Leg muscle contractions and decreases in respiration each appeared to contribute to the acidosis. Lactate was highly elevated, with a slow return (time course greater than 1 h) to baseline. Other investigators have reported profound metabolic acidosis during restraint-associated cardiac arrest. Since restraint often occurs immediately after TASER exposure, this issue should be considered in further development of deployment concepts. On the basis of the results of the current studies, the repeated use of electro-muscular incapacitating devices in a short period of time is, at least, feasible, with the caveat that some medical monitoring of subjects may be required (to observe factors such as lactate and acidosis). PMID:16289999

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

    PubMed

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

    2013-09-01

    Consensus in the most recent literature indicates that psychoactive "bath salts" is a relatively new drug-combination that was added to Schedule I classification in October 2011. Common ingredients include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not yet been well studied. We propose an intensive systematic investigation to determine the potential for cathinones to produce neurotoxic effects in various brain regions. In spite of a lack of evidence, for neurotoxicity there are number of horrific cases now on record that suggest intensification of research is needed. For example, a suicide by hanging had high 3,4-MDPV concentration while a driver under the influence had the highest reported methylone (MEPH) concentration. More interestingly, there have been consistent case reports indicating delayed responses, including: severe agitation with possible psychosis, suicidal ideation, rhabdomyolysis, hypertension, tachycardia, and death. In animal studies, amphetamine (AMPH), methamphetamine (METH) and cocaine release dopamine (DA), similarly to the action of cathinone and particular cathinone analogues. Two components of bath salts, MEPH and MDPV produce opposite effects at human dopamine transporter (hDAT) comparable to METH and cocaine, respectively. Moreover, it has already been found by others that MEPH is almost as potent as METH; and MDPV is much more potent than cocaine with longer lasting effects. It has been conjectured correctly that bath salts containing MDPV and MEPH (or a similar drug) might be expected both, to initially release DA and subsequently prevent its reuptake via hDAT. The null hypothesis, that cathinones do not cause neurotoxicity to dopamine nerve endings of the striatum, seems parsimonious and requires intensive investigation. Our hypothesis is that when consumed by humans, cathinones may induce neurotoxic pathways involving the neuro-glial-microglia and/or specific inflammation, that may help explain the clinically observed delayed response. We intend to explore this hypothesis utilizing a novel proteomic and biomarker technique developed by scientists at the McKnight Brain Institute, University of Florida as well as magnetic-resonance imaging across pre-frontal orbital cortex-cingulate gyrus and mesolimbic pathways of the brain of rodents. PMID:23845561

  20. 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-induced. The methodology for signal detection in EU-ADR is still under development and testing phase. PMID:21685607

  1. A CACNA1C variant associated with reduced voltage-dependent inactivation, increased CaV1.2 channel window current, and arrhythmogenesis.

    PubMed

    Hennessey, Jessica A; Boczek, Nicole J; Jiang, Yong-Hui; Miller, Joelle D; Patrick, William; Pfeiffer, Ryan; Sutphin, Brittan S; Tester, David J; Barajas-Martinez, Hector; Ackerman, Michael J; Antzelevitch, Charles; Kanter, Ronald; Pitt, Geoffrey S

    2014-01-01

    Mutations in CACNA1C that increase current through the CaV1.2 L-type Ca2+ channel underlie rare forms of long QT syndrome (LQTS), and Timothy syndrome (TS). We identified a variant in CACNA1C in a male child of Filipino descent with arrhythmias and extracardiac features by candidate gene sequencing and performed functional expression studies to electrophysiologically characterize the effects of the variant on CaV1.2 channels. As a baby, the subject developed seizures and displayed developmental delays at 30 months of age. At age 5 years, he displayed a QTc of 520 ms and experienced recurrent VT. Physical exam at 17 years of age was notable for microcephaly, short stature, lower extremity weakness and atrophy with hyperreflexia, spastic diplegia, multiple dental caries and episodes of rhabdomyolysis. Candidate gene sequencing identified a G>C transversion at position 5731 of CACNA1C (rs374528680) predicting a glycine>arginine substitution at residue 1911 (p.G1911R) of CaV1.2. The allele frequency of this variant is 0.01 in Malays, but absent in 984 Caucasian alleles and in the 1000 genomes project. In electrophysiological analyses, the variant decreased voltage-dependent inactivation, thus causing a gain of function of CaV1.2. We also observed a negative shift of V1/2 of activation and positive shift of V1/2 of channel inactivation, resulting in an increase of the window current. Together, these suggest a gain-of-function effect on CaV1.2 and suggest increased susceptibility for arrhythmias in certain clinical settings. The p.G1911R variant was also identified in a case of sudden unexplained infant death (SUID), for which an increasing number of clinical observations have demonstrated can be associated with arrhythmogenic mutations in cardiac ion channels. In summary, the combined effects of the CACNA1C variant to diminish voltage-dependent inactivation of CaV1.2 and increase window current expand our appreciation of mechanisms by which a gain of function of CaV1.2 can contribute to QT prolongation. PMID:25184293

  2. Quantification of Na+,K+ pumps and their transport rate in skeletal muscle: Functional significance

    PubMed Central

    2013-01-01

    During excitation, muscle cells gain Na+ and lose K+, leading to a rise in extracellular K+ ([K+]o), depolarization, and loss of excitability. Recent studies support the idea that these events are important causes of muscle fatigue and that full use of the Na+,K+-ATPase (also known as the Na+,K+ pump) is often essential for adequate clearance of extracellular K+. As a result of their electrogenic action, Na+,K+ pumps also help reverse depolarization arising during excitation, hyperkalemia, and anoxia, or from cell damage resulting from exercise, rhabdomyolysis, or muscle diseases. The ability to evaluate Na+,K+-pump function and the capacity of the Na+,K+ pumps to fill these needs require quantification of the total content of Na+,K+ pumps in skeletal muscle. Inhibition of Na+,K+-pump activity, or a decrease in their content, reduces muscle contractility. Conversely, stimulation of the Na+,K+-pump transport rate or increasing the content of Na+,K+ pumps enhances muscle excitability and contractility. Measurements of [3H]ouabain binding to skeletal muscle in vivo or in vitro have enabled the reproducible quantification of the total content of Na+,K+ pumps in molar units in various animal species, and in both healthy people and individuals with various diseases. In contrast, measurements of 3-O-methylfluorescein phosphatase activity associated with the Na+,K+-ATPase may show inconsistent results. Measurements of Na+ and K+ fluxes in intact isolated muscles show that, after Na+ loading or intense excitation, all the Na+,K+ pumps are functional, allowing calculation of the maximum Na+,K+-pumping capacity, expressed in molar units/g muscle/min. The activity and content of Na+,K+ pumps are regulated by exercise, inactivity, K+ deficiency, fasting, age, and several hormones and pharmaceuticals. Studies on the ?-subunit isoforms of the Na+,K+-ATPase have detected a relative increase in their number in response to exercise and the glucocorticoid dexamethasone but have not involved their quantification in molar units. Determination of ATPase activity in homogenates and plasma membranes obtained from muscle has shown ouabain-suppressible stimulatory effects of Na+ and K+. PMID:24081980

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

    PubMed Central

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

    2015-01-01

    Introduction Many cases of carbon monoxide poisoning in Taiwan are due to burning charcoal. Nevertheless, few reports have analyzed the mortality rate of these patients who survive to reach a hospital and die despite intensive treatment. Therefore, this study examined the clinical features, physiological markers, and outcomes after carbon monoxide poisoning and the associations between these findings. Methods We analyzed the records of 261 patients who were referred for management of carbon monoxide intoxication between 2000 and 2010. Patients were grouped according to status at discharge as alive (survivor, n = 242) or dead (non-survivor, n = 19). Demographic, clinical, laboratory, and mortality data were obtained for analysis. Results Approximately half of the cases (49.4%) attempted suicide by burning charcoal. Most of the patients were middle-aged adults (33±19 years), and were referred to our hospital in a relatively short period of time (6±10 hours). Carbon monoxide produced many serious complications after exposure: fever (26.1%), hypothermia (9.6%), respiratory failure (34.1%), shock (8.4%), myocardial infarction (8.0%), gastrointestinal upset (34.9%), hepatitis (18.4%), renal failure (25.3%), coma (18.0%) and rhabdomyolysis (21.8%). Furthermore, the non-survivors suffered greater incidences of hypothermia (P<0.001), respiratory failure (P<0.001), shock (P<0.001), hepatitis ((P=0.016), renal failure (P=0.003), coma (P<0.001) than survivors. All patients were treated with high concentration of oxygen therapy using non-rebreather mask. However, hyperbaric oxygen therapy was only used in 18.8% of the patients. In a multivariate-Cox-regression model, it was revealed that shock status was a significant predictor for mortality after carbon monoxide poisoning (OR 8.696, 95% CI 2.053-37.370, P=0.003). Finally, Kaplan-Meier analysis confirmed that patients with shock suffered greater cumulative mortality than without shock (Log-rank test, Chi-square 147.404, P<0.001). Conclusion The mortality rate for medically treated carbon monoxide-poisoned patients at our center was 7.3%. Furthermore, the analysis indicates that shock was most strongly associated with higher risk of mortality. PMID:25745854

  4. 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 and cirrhosis. Some endocrinopathies (glucocorticoid deficiency and hypothyroidism) are associated with euvolaemic, hypoosmolar hyponatraemia, which must be distinguished from SIADH. Independent of adrenal insufficiency, isolated hypoaldosteronism can also be accompanied by hypersecretion of vasopressin secondary to hypovolaemia, which responds to mineralocorticoid administration. The causes of SIADH are classic: neoplastic (notably small-cell lung cancer), iatrogenic (particularly psychoactive drugs, chemotherapy), lung and cerebral. Some causes have been recently described: familial hyponatraemia via X-linked recessive disease caused by an activating mutation of the vasopressin 2 receptor; and corticotropin insufficiency related to drug interference between some inhaled glucocorticoids and cytochrome p450 inhibitors, such as the antiretroviral drugs and itraconazole, etc. SIADH in marathon runners exposes them to a risk of hypotonic encephalopathy with fatal cerebral oedema. SIADH treatment is based on water restriction and demeclocycline. V2 receptor antagonists are still not marketed in France. These aquaretics seem effective clinically and biologically, without demonstrated improvement to date of mortality in eu- and hypervolaemic hyponatraemia. Obviously treatment of a corticotropic deficit, even subtle, should not be overlooked, as well as the introduction of fludrocortisone in isolated hypoaldosteronism and discontinuation of iatrogenic drugs. PMID:22119069

  5. Are all statins the same? Focus on the efficacy and tolerability of pitavastatin.

    PubMed

    da Silva, Pedro Marques

    2011-01-01

    Pitavastatin is the newest member of the HMG-CoA reductase inhibitor family and is approved as adjunctive therapy to diet to reduce elevated levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (Apo) B, and triglycerides and to increase levels of high-density lipoprotein (HDL) cholesterol in adult patients with primary hyperlipidemia or mixed dyslipidemia. Pitavastatin undergoes minimal metabolism by cytochrome P450 (CYP) enzymes and, therefore, has a low propensity for drug-drug interactions with drugs metabolized by CYP enzymes or the CYP3A4 substrate grapefruit juice. In clinical trials, pitavastatin potently and consistently reduced serum levels of total, LDL, and non-HDL cholesterol, and triglycerides in patients with primary hypercholesterolemia where diet and other non-pharmacological measures were inadequate. Mean reductions from baseline in serum total and LDL cholesterol and triglyceride levels were 21-32%, 30-45%, and 10-30%, respectively. Moreover, a consistent trend towards increased HDL cholesterol levels of 3-10% was seen. Long-term extension studies show that the beneficial effects of pitavastatin are maintained for up to 2 years. Pitavastatin produces reductions from baseline in serum total and LDL cholesterol levels to a similar extent to those seen with the potent agent atorvastatin and to a greater extent than those seen with simvastatin or pravastatin. In the majority of other studies comparing pitavastatin and atorvastatin, no significant differences in the favorable effects on lipid parameters were seen, although pitavastatin was consistently associated with trends towards increased HDL cholesterol levels. Pitavastatin also produces beneficial effects on lipids in patients with type 2 diabetes mellitus and metabolic syndrome without deleterious effects on markers of glucose metabolism, such as fasting blood glucose levels or proportion of glycosylated hemoglobin. Pitavastatin appears to exert a number of beneficial effects on patients at risk of cardiovascular events independent of lipid lowering. In the JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) study, pitavastatin was non-inferior to atorvastatin at reducing plaque volume in patients with ACS undergoing percutaneous coronary intervention. Further beneficial effects, including favorable effects on the size and composition of atherosclerotic plaques, improvements in cardiovascular function, and improvements in markers of inflammation, oxidative stress, and renal function, have been demonstrated in a number of small studies. Pitavastatin is generally well tolerated in hyperlipidemic patients with or without type 2 diabetes, with the most common treatment-related adverse events being musculoskeletal or gastrointestinal in nature. Increases in plasma creatine kinase levels were seen in <5% of pitavastatin recipients and the incidence of myopathy or rhabdomyolysis was extremely low. In summary, pitavastatin, the latest addition to the statin family, produces potent and consistent beneficial effects on lipids, is well tolerated, and has a favorable pharmacokinetic profile. The combination of a potent decrease in total and LDL cholesterol levels and increase in HDL cholesterol levels suggest that pitavastatin may produce substantial cardiovascular protection. PMID:21446776

  6. [Arterial hypertension and dyslipidemia in patients with chronic kidney disease (CKD). Anti-platelet aggregation. Goal oriented treatment].

    PubMed

    Cases Amenós, A; Goicoechea Diezhandiño, M; de Alvaro Moreno, F

    2008-01-01

    TREATMENT OF ARTERIAL HYPERTENSION - Blood pressure (BP) should be regularly measured in all patients with CKD (Strength of Recommendation C). - BP control and proteinuria reduction delay progression of CKD (Strength of Recommendation A) and reduce cardiovascular risk (Strength of Recommendation C). Thus, control of both factors should be the treatment objective. - The BP target in patients with CKD should be < 130/80 mmHg, and 125/75 mmHg if proteinuria is > 1 g/24 hours (Strength of Recommendation A). - Lifestyle changes should be made: low-sodium diet (less than 100 mEq/day of sodium or 2.4 g/day of salt); weight reduction if patient is overweight (body mass index 20-25 kg/m2); regular aerobic physical exercise and moderate alcohol intake for BP control and prevention of cardiovascular risk (Strength of Recommendation A). - The choice of the antihypertensive drug in patients with CKD depends on the etiology of CKD, cardiovascular risk, or presence of clinical or subclinical cardiovascular disease (Strength of Recommendation A). - Two or more antihypertensive drugs are usually required to control blood pressure in patients with CKD (Strength of Recommendation B), and will frequently include a diuretic, which in stages 4-5 should be a loop diuretic (Strength of Recommendation B). - Renin-angiotensin-aldosterone system (RAAS) inhibitors are first choice drugs in patients with diabetic nephropathy, patients with non-diabetic nephropathy with a protein/creatinine ratio higher than 200 mg/g, and patients with heart failure (Strength of Recommendation A). The combination of ACEIs and ARBs is indicated for reducing proteinuria that remains high despite treatment with a RAAS inhibitor, provided potassium levels do not exceed 5.5 mEq/L (Strength of Recommendation B). - When RAAS blockers are started or their dose is changed in patients with advanced CKD, kidney function and serum potassium levels should be monitored at least after 1-2 weeks. DIAGNOSIS AND TREATMENT OF DYSLIPIDEMIA - A complete evaluation of the lipid profile including total cholesterol, LDL-C, HDL-C, and triglycerides should be performed in any patient with CKD at baseline and at least annually (Strength of Recommendation B). - In patients with stage 4-5 CKD and LDL-C >or= 100 mg/dL, treatment to decrease levels to < 100 mg/dL should be considered because of their high CV risk. This reduction is recommended in secondary prevention and in primary prevention in diabetic patients. Lipid-lowering treatment is recommended in all other patients, although no evidence showing its benefits is available yet (Strength of Recommendation C). - In patients with stage 4-5 CKD and triglyceride levels >or= 500 mg/dL which are not corrected by treating the underlying cases, treatment with triglyceride-lowering drugs may be considered to reduce the risk of pancreatitis. However, treatment with fibrates should be used with caution, and these drugs should not be associated to statins due to the risk of rhabdomyolysis (Strength of Recommendation C). There is little experience on the efficacy and safety of omega-3 fatty acids for the treatment of hypertriglyceridemia in patients with grade 4-5 CRF, but they may be considered a possibly safer alternative to fibrates (Strength of Recommendation C). SMOKING - Smoking is a cardiovascular risk factor and a risk factor for progression of kidney disease in patients with CRF (Strength of Recommendation B). - Use of active measures to achieve smoking cessation is recommended in patients with CRF (Strength of Recommendation C). HOMOCYSTEINE - Hyperhomocysteinemia has been postulated as a cardiovascular risk factor in the general population and in kidney patients, but the available evidence is not consistent. - There is no evidence that vitamin therapy decreases cardiovascular risk in patients with CRF, and recommendation of routine vitamin measurement and start of vitamin therapy to reduce cardiovascular risk in these patients is therefore questionable (Strength of Recommendation B). LEFT VENTRICULAR HYPERTROPHY - Left ventricul