Rhabdomyolysis

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Rhabdomyolysis

  • exertional rhabdomyolysi


  • Selected Abstracts


    Rhabdomyolysis and brain ischemic stroke in a heroin-dependent male under methadone maintenance therapy

    ACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2009
    W.-Y. Hsu
    Objective:, There are several complications associated with heroin abuse, some of which are life-threatening. Methadone may aggravate this problem. Method:, A clinical case description. Results:, A 33-year-old man presented with rhabdomyolysis and cerebral ischemic stroke after intravenous heroin. He had used heroin since age 20, and had used 150 mg methadone daily for 6 months. He was found unconsciousness at home and was sent to our hospital. In the ER, his opiate level was 4497 ng/ml. In the ICU, we found rhabdomyolysis, acute renal failure and acute respiratory failure. After transfer to an internal ward, we noted aphasia and weakness of his left limbs. After MRI, we found cerebral ischemic infarction. Conclusion:, Those using methadone and heroin simultaneously may increase risk of rhabdomyolysis and ischemic stroke. Patients under methadone maintenance therapy should be warned regarding these serious adverse events. Hypotheses of heroin-related rhabdomyolysis and stroke in heroin abusers are discussed. [source]


    Decreased activities of mitochondrial respiratory chain complexes in non-mitochondrial respiratory chain diseases

    DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2006
    Joannie Hui MBBS
    The aim of this study was to illustrate the difficulties in establishing a diagnosis of mitochondrial respiratory chain (MRC) disorders based on clinical grounds in combination with intermediate activities of the MRC enzyme complexes. We reviewed retrospectively all medical and laboratory records of patients initially considered likely to have MRC disorders on clinical grounds, and subsequently diagnosed with other disorders (n=20; 11 males, 9 females). Data were retrieved from hospital records, referral letters, and results of enzymatic analysis at a reference laboratory. Clinical symptoms included developmental delay, epilepsy, hypotonia, movement disorder, spastic quadriplegia, tetany, microcephaly, visual problems, carpopedal spasms, dysmorphism, hearing loss, muscle weakness and rhabdomyolysis, and fulminant hepatitis. Blood and cerebrospinal fluid lactate levels were elevated in 13/20 and 9/20 respectively. One or more MRC complex activities (expressed as ratios relative to citrate synthase and/or complex II activity) were less than 50% of control mean activity in 11/20 patients (including patients with deficiencies of pyruvate dehydrogenase complex, pantothenate kinase, holocarboxylase synthetase, long-chain hydroxy acyl-CoA dehydrogenase, molybdenum co-factor, and neonatal haemochromatosis). One patient had a pattern suggestive of mitochondrial proliferation. We conclude that intermediate results of MRC enzymes should be interpreted with caution and clinicians should be actively looking for other underlying diagnoses. [source]


    Severe rhabdomyolysis due to polysaccharide storage myopathy in an Arabian mare

    EQUINE VETERINARY EDUCATION, Issue 3 2007
    C. T. Estill
    First page of article [source]


    Does dantrolene sodium prevent recurrent exertional rhabdomyolysis in horses?

    EQUINE VETERINARY EDUCATION, Issue 2 2007
    M. A. Holmes
    No abstract is available for this article. [source]


    Equine muscle disorders 1: Chronic intermittent rhabdomyolysis

    EQUINE VETERINARY EDUCATION, Issue 3 2000
    J. Beech
    [source]


    An epidemiological study of myopathies in Warmblood horses

    EQUINE VETERINARY JOURNAL, Issue 2 2008
    L. M. HUNT
    Summary Reasons for performing study: There are few detailed reports describing muscular disorders in Warmblood horses. Objectives: To determine the types of muscular disorders that occur in Warmblood horses, along with presenting clinical signs, associated risk factors and response to diet and exercise recommendations, and to compare these characteristics between horses diagnosed with polysaccharide storage myopathy (PSSM), those diagnosed with a neuromuscular disorder other than PSSM (non-PSSM) and control horses. Methods: Subject details, muscle biopsy diagnosis and clinical history were compiled for Warmblood horses identified from records of biopsy submissions to the University of Minnesota Neuromuscular Diagnostic Laboratory. A standardised questionnaire was answered by owners at least 6 months after receiving the muscle biopsy report for an affected and a control horse. Results: Polysaccharide storage myopathy (72/132 horses) was the most common myopathy identified followed by recurrent exertional rhabdomyolysis (RER) (7/132), neurogenic or myogenic atrophy (7/132), and nonspecific myopathic changes (14/132). Thirty-two biopsies were normal. Gait abnormality, ,tying-up', Shivers, muscle fasciculations and atrophy were common presenting clinical signs. Forty-five owners completed questionnaires. There were no differences in sex, age, breed, history or management between control, PSSM and non-PSSM horses. Owners that provided the recommended low starch fat supplemented diet and regular daily exercise reported improvement in clinical signs in 68% (19/28) of horses with a biopsy submission and 71% of horses diagnosed with PSSM (15/21). Conclusions: Muscle biopsy evaluation was a valuable tool to identify a variety of myopathies in Warmblood breeds including PSSM and RER. These myopathies often presented as gait abnormalities or overt exertional rhabdomyolysis and both a low starch fat supplemented diet and regular exercise appeared to be important in their successful management. Potential relevance: Warmbloods are affected by a variety of muscle disorders, which, following muscle biopsy diagnosis can be improved through changes in diet and exercise regimes. [source]


    The efficacy of dantrolene sodium in controlling exertional rhabdomyolysis in the Thoroughbred racehorse

    EQUINE VETERINARY JOURNAL, Issue 7 2003
    J. G. T. Edwards
    Summary Reasons for performing study: Dantrolene sodium (Dantrium) has been used extensively for the treatment of myopathies in man and anecdotal evidence suggests it is of clinical benefit in the control of exercise-induced rhabdomyolysis (ER) in racehorses, although data to support this are currently lacking. Objectives: To investigate the efficacy of oral dantrolene sodium in controlling ER in a randomised, double-blind, placebo-controlled crossover trial involving 77 Thoroughbred racehorses in Newmarket, UK. Methods: Horses were treated on 2 occasions 1 week apart, with treatment days coinciding with a return to exercise following 2 days box rest on each occasion. For the first treatment, each horse was randomly selected to receive either 800 mg dantrolene sodium or a colour- matched placebo administered orally 1 h before exercise. This was followed by crossover to the other treatment on the second occasion, with each horse thereby acting as its own control. Degree of ER was assessed using rising serum creatine kinase (CK) levels, by subtracting pre-exercise blood CK levels from those measured in 6 h post exercise blood samples. For each horse, the difference in change between pre- and post exercise CK values between placebo and dantrolene treatments was calculated, with positive values indicating a greater rise with placebo than with dantrolene sodium treatment. Results: The overall mean difference for all horses was +104.8 iu/l and the null hypothesis, that there was no true difference in non-normally distributed post exercise rises in CK values between placebo and dantrolene treatments, was rejected (P = 0.0013) using the nonparametric Wilcoxon signed rank test. Additionally, no horses given dantrolene sodium showed clinical signs of ER, whereas 3 horses given the placebo developed ER following exercise. The incidence of ER in the study was 4% (3/77). Conclusions: The results confirmed that oral administration of dantrolene sodium, 1 h before exercise, had a statistically significant effect on reducing the difference between pre - and post exercise plasma CK levels compared with a placebo in the same animals, and preventing clinical ER in susceptible individuals. Potential relevance: This study suggested that dantrolene sodium is of use in controlling ER in the Thoroughbred racehorse. Further investigation into pre- and post exercise myoplasmic calcium levels and the repeat of the study late in the season when horses receive a much higher energy ration and more strenuous exercise would appear to be warranted. [source]


    Phosphoglycerate kinase deficiency in two brothers with McArdle-like clinical symptoms

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2000
    J. Aasly
    Phosphoglycerate kinase (PGK) catalyses the transfer of the acylphosphate group of 1,3-diphosphoglycerate to ADP with formation of 3-phosphoglycerate and ATP in the terminal stage of the glycolytic pathway. Two young brothers are presented who both experienced muscle pain, cramps and stiffness shortly after beginning heavy exercise. After these episodes they noticed that the urine was dark brown, indicating rhabdomyolysis and myoglobinuria. The neurological examinations were without remarks. There was no lactate increase in the ischaemic forearm exercise test. Both had very low PGK levels in muscle, erythrocytes, leukocytes and fibroblasts. This is the first family with more than one affected case of PGK deficiency and exercise-induced stiffness, myalgia and rhabdomyolysis. The clinical manifestations may resemble myophosphorylase deficiency (McArdle's disease: glycogenosis Type V) and muscle phosphofructokinase deficiency (Tarui's disease: glycogenosis Type VII). PGK deficiency is inherited as an X-linked trait and may show other features such as mental retardation and/or haemolytic anaemia. [source]


    The influence of statin characteristics on their safety and tolerability

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2004
    G. De Angelis
    Summary The efficacy of the statins for both primary and secondary prevention has now been clearly established in patients across the spectrum of cardiovascular risk. In addition to their primary effect in reducing plasma cholesterol, the statins possess various ,pleiotropic' effects that may contribute to their clinical effectiveness in reducing cardiovascular events, e.g. improvement of endothelial function, reduction of low-density lipoprotein-cholesterol oxidation and stabilisation of atheromatous plaques. Although statins share similar chemical characteristics, they differ significantly in terms of their molecular synthesis, solubility and pharmacokinetic behaviour and metabolism. Side-effects secondary to long-term statin therapy are rare, but rhabdomyolysis may occur when statins are administered together with other drugs that have a direct toxic effect on muscle or which inhibit statin metabolism. Among the various statins, it would appear that fluvastatin has the lowest propensity to interact with other drugs and the least potential to induce myotoxicity. [source]


    Minocycline hypersensitivity syndrome manifesting with rhabdomyolysis

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2002
    Zakia Rahman md
    No abstract is available for this article. [source]


    A case of fatal caffeine poisoning

    ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010
    T. RUDOLPH
    Caffeine is a natural alkaloid methylxanthine that is found in various plants such as coffee or tea. Symptoms of a severe overdose may present with hypokalemia, hyponatremia, ventricular arrhythmias, hypertension followed by hypotension, respiratory failure, seizures, rhabdomyolysis, ventricular fibrillation and finally circulatory collapse. A 21-year-old woman called for the ambulance herself soon after the ingestion of about 10,000 mg of caffeine. At the arrival of the ambulance, the patient went into cardiac arrest almost immediately. After a total resuscitation period of 34 min including seven counter-shocks and 2 mg epinephrine, the patient was stable enough to be transferred to the hospital. The patient soon went into VF again and received two more counter-shocks and 1 mg epinephrine and finally an intravenous bolus dose of 300 mg amiodarone. The initial arterial blood gas showed pH at 6.47, lactate at 33 mmol/l and potassium level at 2.3 mmol/l. Unfortunately, no blood samples for caffeine analysis were taken. Three days after hospital admission, the patient developed myoclonus, which did not respond to medical treatment. Excessive intake of caffeine may produce arrhythmias and pronounced hypokalemia and ensuing ventricular fibrillation. In case of counter-shock-resistant VF, it can be necessary to give an early loading dose of amiodarone. Furthermore, it may be beneficial to replace the potassium as early as possible. Epinephrine and buffer solutions used during resuscitation may further decrease blood potassium levels and should be administrated cautiously. Epinephrine can be replaced by other vasopressor drugs, such as vasopressin without effects on ,-receptors. [source]


    Who should receive a statin these days?

    JOURNAL OF INTERNAL MEDICINE, Issue 4 2006
    Lessons from recent clinical trials
    Abstract. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1,2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease. [source]


    Acute encephalopathy and rhabdomyolysis following rotavirus gastroenteritis

    JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1-2 2007
    Koichi Minami
    Abstract: Rotavirus is a common cause of severe gastroenteritis in children, and other unusual extraintestinal manifestations have also been attributed to the virus. We report a case of acute encephalopathy and rhabdomyolysis following rotavirus gastroenteritis in a 6-month-old infant. [source]


    Synergistic action of statins and nitrogen-containing bisphosphonates in the development of rhabdomyolysis in L6 rat skeletal myoblasts

    JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2009
    Sumio Matzno PhD
    Abstract Objectives Nitrogen-containing bisphosphonates, which are widely used to treat osteoporosis, act as inhibitors of farnesyl pyrophosphate synthase, one of the key enzymes of the mevalonate pathway, and thus may have the potential to enhance the effect of statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase). In this study, we evaluated the synergistic effect of two nitrogen-containing bisphosphonates, alendronate and risedronate, in statin-induced apoptosis in rat skeletal L6 myoblasts. Methods L6 rat myoblasts were differentiated with drugs. DNA fragmentation was measured and small GTPase was detected by immunoblotting. Key findings Alendronate and risedronate caused dose-dependent apoptosis of L6 myoblasts. Risedronate induced detachment of rho GTPase from the cell membrane, followed by activation of the caspase-8-related cascade. Risedronate-induced apoptosis was synergistically enhanced with atorvastatin and significantly reduced by addition of geranylgeraniol. By contrast, alendronate did not reduce membrane GTPases and the apoptosis was caspase independent. Conclusions These results suggest that risedronate-induced apoptosis is related to geranylgeranyl pyrophosphate depletion followed by rho detachment, whereas alendronate affects are independent of rho. Our results suggest a risk of synergistic action between nitrogen-containing bisphosphonates and statins in the development of rhabdomyolysis when treating osteoporosis in women with hyperlipidaemia. [source]


    Hypocalcemia in a critically ill patient

    JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2005
    Tamara B. Wills DVM
    Abstract Objective: To present a case of clinical hypocalcemia in a critically ill septic dog. Case summary: A 12-year old, female spayed English sheepdog presented in septic shock 5 days following hemilaminectomy surgery. Streptococcus canis was cultured from the incision site. Seven days after surgery, muscle tremors were noted and a subsequent low serum ionized calcium level was measured and treated. Intensive monitoring, fluid therapy, and antibiotic treatment were continued because of the sepsis and hypocalcemia, but the dog was euthanized 2 weeks after surgery. New or unique information provided: Low serum ionized calcium levels are a common finding in critically ill human patients, especially in cases of sepsis, pancreatitis, and rhabdomyolysis. In veterinary patients, sepsis or streptococcal infections are not commonly thought of as a contributing factor for hypocalcemia. Potential mechanisms of low serum ionized calcium levels in critically ill patients include intracellular accumulation of calcium ions, altered sensitivity and function of the parathyroid gland, alterations in Vitamin D levels or activity, renal loss of calcium, and severe hypomagnesemia. Pro-inflammatory cytokines and calcitonin have also been proposed to contribute to low ionized calcium in the critically ill. Many veterinarians rely on total calcium levels instead of serum ionized calcium levels to assess critical patients and may be missing the development of hypocalcemia. Serum ionized calcium levels are recommended over total calcium levels to evaluate critically ill veterinary patients. [source]


    A case of suspected non-neurosurgical adult fatal propofol infusion syndrome

    ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2006
    J. Eriksen
    A previously healthy woman (20 years old) was admitted to our hospital with several fractures after a car accident. She was sedated with propofol, etc. in doses ranging from 1.4 to 5.1 mg/kg/h for 88 h. She developed multiple organ failure with rhabdomyolysis and died. This case fulfils (except acidosis) the criteria of propofol,infusion syndrome (PRIS) in a young adult. [source]


    Paramethoxyamphetamine (PMA) poisoning; a ,party drug' with lethal effects

    ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2003
    S. Refstad
    Among young people in Norway the recreational use of amphetamine derivatives seems to be increasing. Methylenedioxymethamphetamine (MDMA), known as ecstasy, is the dominant substance, having both stimulant and psychedelic properties. Depending on the illegal source of these so-called ,party drugs' the content and purity can vary. This case report describes the first lethal case of paramethoxyamphetamine (PMA) and paramethoxymethamphetamine (PMMA) intoxication reported in Norway. A 16-year-old male was admitted to a local hospital in a coma with seizures and hyperthermia after he had been found undressed and barefooted in a local forest (temperature 2°C). He was intubated and given supportive care. Blood chemistry revealed hypoglycaemia, hypocalcaemia and hyperkalaemia. Shortly after transfer to the central hospital he developed bradycardia with continuous seizures and asystole. Adverse effects of MDMA are well described and include serotonergic and sympathomimetic symptoms with hyperthermia, coagulopathy, rhabdomyolysis and acute kidney and liver failure. Case reports of PMA deaths collectively suggest PMA to be more toxic than MDMA. A delayed effect after intake of PMA compared with MDMA can lead to increased intake. Hypoglycaemia and hyperkalaemia may be specific to PMA poisoning. Increased thermo genesis will result in a search for cooling, which explains the attempt to undress and a desire to submerge in water. In a cool climate this behaviour itself can be lethal. Measures to treat seizures, hypoglycaemia, electrolyte anomalies and hyperthermia are the therapeutic goals. No specific treatment is available. [source]


    Atypical presentation of VLCAD deficiency associated with a novel ACADVL splicing mutation

    MUSCLE AND NERVE, Issue 3 2009
    Oleg Shchelochkov MD
    Abstract Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive inborn error of metabolism characterized by impaired mitochondrial ,-oxidation of fatty acids with a chain length between 14 and 18 carbons. While expansion of newborn screening has improved our ability to detect VLCAD deficiency in early childhood, the late-onset form of the disease still presents a significant diagnostic challenge. We report a 20-year-old female with VLCAD deficiency who first presented in infancy with hypoketotic hypoglycemia. In childhood the patient developed complex partial seizures that were aggravated by Lamotrigine treatment. The clinical course in early adulthood was complicated by recurrent, often unprovoked, episodes of rhabdomyolysis and myoglobinuria. In addition, she suffered from chronic myalgia, muscle weakness, and diffuse abdominal tenderness. A muscle biopsy revealed accumulation of fat droplets. Her acylcarnitine profile showed significantly elevated C14, C14:1, C16, and C18-carnitines. Sequence analysis of ACADVL revealed a heterozygous recurrent mutation c.848T>C (p.V283A) and a heterozygous novel splice mutation c.879-8T>A that results in the inclusion of six nucleotides from intron 9 into the transcript sequence. The molecular characterization of this novel mutation and its correlation with the clinical phenotype are discussed. Muscle Nerve 39: 374,382, 2009 [source]


    Neuromuscular manifestations of critical illness,

    MUSCLE AND NERVE, Issue 2 2005
    Charles F. Bolton MD
    Abstract Critical illness, more precisely defined as the systemic inflammatory response syndrome (SIRS), occurs in 20%,50% of patients who have been on mechanical ventilation for more than 1 week in an intensive care unit. Critical illness polyneuropathy (CIP) and myopathy (CIM), singly or in combination, occur commonly in these patients and present as limb weakness and difficulty in weaning from the ventilator. Critical illness myopathy can be subdivided into thick-filament (myosin) loss, cachectic myopathy, acute rhabdomyolysis, and acute necrotizing myopathy of intensive care. SIRS is the predominant underlying factor in CIP and is likely a factor in CIM even though the effects of neuromuscular blocking agents and steroids predominate in CIM. Identification and characterization of the polyneuropathy and myopathy depend upon neurological examination, electrophysiological studies, measurement of serum creatine kinase, and, if features suggest a myopathy, muscle biopsy. The information is valuable in deciding treatment and prognosis. Muscle Nerve, 2005 [source]


    Vitamin E as a protective antioxidant in progressive renal failure

    NEPHROLOGY, Issue 1-2 2000
    Michael J Fryer
    SUMMARY: Progression to renal failure is significantly worsened by oxidative stress in chronic inflammatory kidney disease (IgA nephropathy, antiglomerular basement membrane nephritis, focal segmental glomerulosclerosis), rhabdomyolysis (myoglobinic acute renal failure), diabetic nephropathy and in poisoning by nephrotoxic compounds such as transition metals, paraquat and drugs such as cyclosporine A and cisplatin. The membrane antioxidant vitamin E (,-tocopherol) is examined as a potential therapeutic intervention that may help to slow the rate of decline of kidney function in such conditions. An impaired plasma antioxidant defence system is characteristic of chronic renal failure and the uremic state. Vitamin E therapy is also considered as a means of correcting plasma antioxidant status and attenuating the cardiovascular disease that accompanies kidney failure. [source]


    Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): A report from the therapeutic advances in childhood leukemia (TACL) consortium,

    PEDIATRIC BLOOD & CANCER, Issue 2 2010
    Yoav Messinger MD
    Abstract Background Outcomes remain poor for children after relapse of acute lymphoblastic leukemia (ALL), especially after early marrow relapse. Bortezomib is a proteasome inhibitor with in vitro synergy with corticosteroids and clinical activity in human lymphoid malignancies. Procedure This is a Phase I study of escalating doses bortezomib administered days 1, 4, 8, and 11, added to 4-drug induction chemotherapy with vincristine, dexamethasone, pegylated L -asparaginase, and doxorubicin (VXLD) in children with relapsed ALL. Results Ten patients were enrolled, five in first marrow relapse, and five in second relapse. Four patients were enrolled at dose level 1 (bortezomib 1,mg/m2). One patient was not evaluable for toxicity because of omitted dexamethasone doses. No dose-limiting toxicity (DLT) was observed. Six patients were enrolled at dose level 2 (bortezomib 1.3,mg/m2). One patient had dose-limiting hypophosphatemia and rhabdomyolysis after 1 dose of bortezomib, and died from a diffuse zygomyces infection on day 17. Five additional patients were enrolled with no subsequent DLTs. As planned, no further dose escalation was pursued. The regimen had predictable toxicity related to the chemotherapy drugs. Two patients had mild peripheral neuropathy (grades 1 and 2). Six of nine evaluable patients (67%) achieved a complete response (CR), and one had a bone marrow CR with persistent central nervous system leukemia. Conclusions The combination of bortezomib (1.3,mg/m2) with VXLD is active with acceptable toxicity in pretreated pediatric patients with relapsed ALL. We are expanding the 1.3,mg/m2 cohort for a phase II estimate of response. Study registered at ClinicalTrials.gov (http://clinicaltrials.gov/ct2/show/NCT00440726). Pediatr Blood Cancer 2010;55:254,259. © 2010 Wiley-Liss, Inc. [source]


    Ureterosygmoidostomy-associated hypokalemia-induced quadriparesis and rhabdomyolysis

    PEDIATRICS INTERNATIONAL, Issue 3 2005
    M Said Berilgen
    No abstract is available for this article. [source]


    Muscle toxicity with statins,

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2010
    Karin Hedenmalm MD
    Abstract Purpose Statins rarely cause serious muscle toxicity and rhabdomyolysis. The aim of our investigation was to identify and quantify potential risk factors for statin-induced rhabdomyolysis. Methods All cases of suspected adverse reactions to statins reported to the Swedish Adverse Drug Reactions Advisory Committee until 15 September 2006 containing the codes myalgia, myopathy, increased serum creatine kinase (CK), myoglobinuria or rhabdomyolysis were included in the study. Cases were classified into different CK categories, where cases with CK levels >10 times the upper limit of normal (ULN) laboratory range were compared with cases with normal CK levels (in some analyses cases with CK not measured were also included as controls). Fisher's test and multiple logistic regression were used to test the degree of association. Results A total of 338 cases with muscle toxicity were identified. CK had not been measured in 148 cases. Of the remaining 190 cases, 59 were classified as rhabdomyolysis, 62 had CK increases below the level of rhabdomyolysis, 69 had normal CK and 2 contained insufficient information to classify the degree of CK increase. A high statin dose and concomitant interacting drug treatment were over-represented among cases with rhabdomyolysis compared with cases with normal CK. Renal disease and unusual strenuous muscular activity were also associated with an increased risk of rhabdomyolysis when the control group included cases with CK not measured. Conclusion Results from our study support previous studies indicating that the risk of rhabdomyolysis with statin treatment increases with increase in systemic exposure to the statin. Renal disease and unusual strenuous muscular activity may also contribute to an increased risk of rhabdomyolysis. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    The safety of rosuvastatin in comparison with other statins in over 100,000 statin users in UK primary care,,

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2008
    Luis Alberto García-Rodríguez MD
    Abstract Purpose To compare mortality and the incidence of hospitalization for myopathy, rhabdomyolysis, acute renal failure and acute liver injury in patients receiving rosuvastatin and those taking other statins. Methods Patients prescribed a statin that they had not used before were selected from the UK General Practice Research Database (GPRD) and followed up from 1 April 2003 to 31 December 2005. Results We studied 10,289 patients on rosuvastatin and 117,102 taking other statins. No cases of myopathy, rhabdomyolysis or acute liver injury occurred among rosuvastatin users. In those taking statins other than rosuvastatin, the incidence of myopathy was 0.4 (95% confidence interval (CI): 0.1,0.9), of rhabdomyolysis was 0.4 (95%CI: 0.1,0.9) and of acute liver injury was 0.4 (95%CI: 0.2,1.0), per 10,000 person-years. Fourteen cases of acute renal failure were identified (two among rosuvastatin users and 12 among other statin users). Among current users, the relative risk (RR) of acute renal failure in rosuvastatin users compared with other statin users was 1.16 (95%CI: 0.15,9.03). We identified 3232 deaths during the study period (173 in the rosuvastatin-treated group and 3059 in the other statin group). The RR of death associated with current use of rosuvastatin compared with other statins was 0.55 (95%CI: 0.44,0.68). Conclusions We found no evidence that patients prescribed rosuvastatin were at greater risk of these outcomes than patients prescribed other statins. There was no evidence of increased mortality among patients taking rosuvastatin, even after allowing for age, sex and prior statin use. Copyright © 2008 John Wiley & Sons, Ltd. [source]


    The safety of rosuvastatin in comparison with other statins in over 25,000 statin users in the Saskatchewan Health Databases,,

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2008
    Luis Alberto García-Rodríguez MD
    Abstract Purpose To compare mortality and the incidence of hospitalization for myopathy, rhabdomyolysis, acute renal failure and acute liver injury in patients receiving rosuvastatin and those taking other statins. Methods Patients prescribed a statin that they had not used before were selected from the Saskatchewan Health Databases (SHD) and followed up from 1 July 2003 until 31 March 2005. Results We studied 10,384 patients on rosuvastatin and 14,854 taking other statins. Two cases of myopathy were identified (one on rosuvastatin, one on another statin). The relative risk (RR) of myopathy in patients currently taking rosuvastatin compared with other statins was 1.31 (95% confidence interval [CI]: 0.13,13.41). Two cases of rhabdomyolysis were detected among current rosuvastatin users (incidence: 2.9 [95% CI: 0.8,10.7] per 10,000 person-years). No cases of acute liver injury occurred among rosuvastatin patients. Seventeen cases of acute renal failure were identified (five among rosuvastatin users, 12 taking other statins). The RR of acute renal failure in current rosuvastatin users compared with other statins was 0.49 (95% CI: 0.16,1.50). We identified 285 deaths during the study period (87 among rosuvastatin users, 198 taking other statins). The RR of death in current rosuvastatin users compared with other statins was 0.42 (95% CI: 0.32,0.57). Conclusions We found no evidence that patients prescribed rosuvastatin were at greater risk of the study outcomes than patients prescribed other statins. There was no evidence of increased mortality among patients taking rosuvastatin, even after allowing for age, sex and prior statin use. Copyright © 2008 John Wiley & Sons, Ltd. [source]


    Systematic review and meta-analysis of clinically relevant adverse events from HMG CoA reductase inhibitor trials worldwide from 1982 to present,

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2007
    David L. McClure PhD
    Abstract Purpose Our objective was to determine the association of clinically relevant adverse events from a systematic review and meta-analysis of statin randomized controlled trials (RCT). Methods We performed the meta-analysis in the manner of a Cochrane Collaboration systematic review. Outcomes were discontinuances of therapy or muscle-related symptoms due to adverse events. We searched for articles from 1982 through June 2006 in MEDLINE and other databases. The main inclusion criteria were double blind, placebo controlled RCTs with a monotherapy intervention of any marketed statin and active surveillance of adverse events. We excluded studies of drug interactions, organ transplants, or exercise, or those not meeting all of the study quality criteria. The primary analysis was a statin formulation stratified fixed-effect model using Peto odds-ratios (POR). Secondary analyses explored the stability of the primary results. Results Over 86,000 study participants from 119 studies were included. Available statins were associated with a lower POR of discontinuance (overall: 0.88 [0.84, 0.93], largest effect with pravastatin: 0.79 [0.74, 0.84]), an elevated POR of rhabdomyolysis (1.59 [0.54, 4.70]) and myositis (2.56 [1.12, 5.85]), and null odds of myalgia (1.09 [0.97, 1.23]). Cerivastatin by comparison demonstrated larger PORs for discontinuances and muscle-related adverse events. Secondary analyses demonstrated the stability of the results. Conclusions Overall, discontinuation of statin therapy due to adverse events was no worse than placebo. The risks of muscle-related adverse events were in general agreement with the known risks of statins. Copyright © 2006 John Wiley & Sons, Ltd. [source]


    The comparative safety of rosuvastatin: a retrospective matched cohort study in over 48,000 initiators of statin therapy,

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2006
    Andrew T. McAfee MD
    Abstract Purpose The purpose of this study was to compare incidence rates of hospitalization associated with rhabdomyolysis, myopathy, renal, or hepatic dysfunction, and of in-hospital death, between initiators of rosuvastatin and other statins. Methods This was a matched cohort study of statin initiators from the administrative database of a large health insurer in the US, during the first 6 months of rosuvastatin availability with up to 18 months of follow-up. All outcome events were verified by medical record review. Incidence rates, risk ratios, and associated 95% confidence intervals were estimated. Results From an initial pool of 12,217, 11,249 eligible rosuvastatin initiators were matched to 37,282 initiators of other statins. The incidence rate (IR) per 1000 person-years for rhabdomyolysis was 0.10 [0.00, 0.55] for rosuvastatin initiators (n,=,1) and 0.06 [0.01, 0.22] for other statin initiators (n,=,2), for a hazard ratio (HR) of 1.98 [0.18, 21.90]. The IR for myopathy was 0.20 [0.02, 0.71] for rosuvastatin initiators (n,=,2) and 0.00 [0.00, 0.09] for other statin initiators (n,=,0). The IR for renal dysfunction was 1.18 [0.61, 2.06] for rosuvastatin initiators (n,=,12) and 1.26 [0.91, 1.71] for other statin initiators (n,=,42), for a HR of 0.90 [0.47, 1.73]. The IR for hepatic dysfunction was 0.20 (0.02, 0.71) for rosuvastatin initiators (n,=,2) and 0.24 (0.10, 0.47) for other statin initiators (n,=,8), for a HR of 0.87 (0.18, 4.14). Conclusions This study found no difference between rosuvastatin and the other statins in the incidence of hospitalizations associated with renal or hepatic events, or death. The absolute incidence rates of rhabdomyolysis and myopathy were reassuringly low among all statin initiators but remain too small for firm conclusions to be drawn on any difference between the statins. Copyright © 2006 John Wiley & Sons, Ltd. [source]


    Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy,,

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2004
    Jennie T. Chang PharmD
    Abstract Context Elevated total cholesterol (total-C) and low-density lipoprotein cholesterol (LDL-C) levels are established risk factors for cardiovascular disease (CVD). HMG-CoA reductase inhibitors (statins) are effective cholesterol-lowering drugs that are commonly prescribed to treat this condition. These drugs are often combined with another class of drugs, fibric acid derivatives, to lower both cholesterol and triglyceride levels. Rhabdomyolysis is a known, rare serious side effect of statin monotherapy and of statin-fibrate combination therapy. Objective To examine Food and Drug Administration's (FDA's) postmarketing database for cases of rhabdomyolysis in relation to monotherapy and combination use and calculate reporting rates for this event. Design Domestic cases of statin- and statin/gemfibrozil-associated rhabdomyolysis were culled from FDA's database and reviewed. Rhabdomyolysis was defined by CPK,,,10,000 IU/L, myopathic signs and symptoms and clinical diagnosis of rhabdomyolysis. Reporting rates, consisting of number of reported cases/number of prescriptions for each drug, were then calculated to determine whether the reporting of rhabdomyolysis cases was commensurate with extent of use of each statin in the population. Setting Cases were obtained from the FDA adverse event reporting system (AERS) database. Patients NA. Main Outcome Measures Number of rhabdomyolysis cases were evaluated, along with outcomes, such as renal failure, dialysis and death. Results Of 866 total reported cases, 482 (56%) were associated with monotherapy and 384 (44%) related to combination therapy. More than 80% of reported cases for each drug resulted in hospitalization for renal failure and dialysis. 80 patients expired from events related directly to rhabdomyolysis. Reporting rates for all statins, except for cerivastatin, were similar and much lower than 1 per 100,000 prescriptions. The cerivastatin-reporting rate was much higher at 4.24/100,000 prescriptions. Conclusions Rhabdomyolysis is a rare, serious side effect of statin monotherapy and of statin-fibrate combination therapy. Clinicians need to remain cognizant of this potential adverse event and discuss signs and symptoms of muscle toxicity with patients in order improve the benefits-to-risks of treating dyslipidemia with statins. Copyright © 2004 John Wiley & Sons, Ltd. [source]


    Disorders of carnitine transport and the carnitine cycle,

    AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2006
    Nicola Longo
    Abstract Carnitine plays an essential role in the transfer of long-chain fatty acids across the inner mitochondrial membrane. This transfer requires enzymes and transporters that accumulate carnitine within the cell (OCTN2 carnitine transporter), conjugate it with long chain fatty acids (carnitine palmitoyl transferase 1, CPT1), transfer the acylcarnitine across the inner plasma membrane (carnitine-acylcarnitine translocase, CACT), and conjugate the fatty acid back to Coenzyme A for subsequent beta oxidation (carnitine palmitoyl transferase 2, CPT2). Deficiency of the OCTN2 carnitine transporter causes primary carnitine deficiency, characterized by increased losses of carnitine in the urine and decreased carnitine accumulation in tissues. Patients can present with hypoketotic hypoglycemia and hepatic encephalopathy, or with skeletal and cardiac myopathy. This disease responds to carnitine supplementation. Defects in the liver isoform of CPT1 present with recurrent attacks of fasting hypoketotic hypoglycemia. The heart and the muscle, which express a genetically distinct form of CPT1, are usually unaffected. These patients can have elevated levels of plasma carnitine. CACT deficiency presents in most cases in the neonatal period with hypoglycemia, hyperammonemia, and cardiomyopathy with arrhythmia leading to cardiac arrest. Plasma carnitine levels are extremely low. Deficiency of CPT2 present more frequently in adults with rhabdomyolysis triggered by prolonged exercise. More severe variants of CPT2 deficiency present in the neonatal period similarly to CACT deficiency associated or not with multiple congenital anomalies. Treatment for deficiency of CPT1, CPT2, and CACT consists in a low-fat diet supplemented with medium chain triglycerides that can be metabolized by mitochondria independently from carnitine, carnitine supplements, and avoidance of fasting and sustained exercise. © 2006 Wiley-Liss, Inc. [source]


    Deceased Donor Kidney Transplantation from Donors with Acute Renal Failure due to Rhabdomyolysis

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009
    K. L. Mekeel
    With the current shortage of solid organs for transplant, the transplant community continues to look for ways to increase the number of organ donors, including extending the criteria for donation. In rhabdomyolysis, the byproducts of skeletal muscle breakdown leak into the circulation resulting in acute renal failure in up to 30% of patients. In nonbrain dead patients, this condition is reversible and most patients recover full renal function. Seven potential donors had rhabdomyolysis with acute renal failure as evidenced by the presence of urine hemoglobin, plasma creatinine kinase levels of greater than five times the normal and elevated creatinine. One donor required dialysis. At our institution, 10 kidneys were transplanted from the seven donors. Two grafts had immediate function, five grafts experienced slow graft function and three grafts had delayed graft function requiring hemodialysis. At a mean of 8.7 months posttransplant (2.4,25.2 months), all patients have good graft function, are off dialysis and have a mean creatinine of 1.3 (0.7,1.8). In conclusion, our experience suggests that rhabdomyolysis with acute renal failure should not be a contraindication for donation, although recipients may experience slow or delayed graft function. [source]