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1

Drug induced rhabdomyolysis  

PubMed Central

Rhabdomyolysis is a clinical condition of potential life threatening destruction of skeletal muscle caused by diverse mechanisms including drugs and toxins. Given the fact that structurally not related compounds cause an identical phenotype pinpoints to common targets or pathways, responsible for executing rhabdomyolysis. A drop in myoplasmic ATP paralleled with sustained elevations in cytosolic Ca2+ concentration represents a common signature of rhabdomyolysis. Interestingly, cardiac tissue is hardly affected or only secondary, as a consequence of imbalance in electrolytes or acid–base equilibrium. This dogma is now impaired by compounds, which show up with combined toxicity in heart and skeletal muscle. In this review, cases of rhabdomyolysis with novel recently approved drugs will be explored for new target mechanisms in the light of previously described pathomechanisms. PMID:22560920

Hohenegger, Martin

2012-01-01

2

Rhabdomyolysis following shoulder arthroscopy.  

PubMed

Fluid extravasation is not uncommon after shoulder arthroscopy. We report a case of massive fluid extravasation that resulted in rhabdomyolysis and renal shutdown following routine shoulder arthroscopic surgery. Compartment pressures in the deltoid, supraspinatus, and infraspinatus were normal. Magnetic resonance imaging of the shoulder revealed extensive subcutaneous edema and high-signal changes in the entire deltoid muscle. The patient made an uneventful recovery with adequate supportive treatment and renal dialysis. Repeat imaging studies 3 months later revealed complete restoration to normal of the deltoid muscle. In addition to extensive fluid extravasation in this patient, the use of nonsteroidal anti-inflammatory medication, the development of a transient allergic reaction to a prescribed antibiotic, and the inclusion of epinephrine in the infusion fluid may have collectively contributed to rhabdomyolysis. We recommend that the use of infusion pumps should be limited to the shortest time possible, and that gravity inflow should be used as much as possible. Inflow should preferably occur through the arthroscope itself, rather than through a separate portal cannula, which may dislodge, inadvertently causing infusion of high-pressure fluid into the surrounding tissue. PMID:17157744

Lim, Jit-Kheng; Ang, Kian-Chuan; Wang, Shih-Chang; Kumar, V Prem

2006-12-01

3

[Rhabdomyolysis: role of the nephrologist].  

PubMed

Rhabdomyolysis is characterized by skeletal muscle necrosis resulting in release of large amounts of toxic muscle cell components, including electrolytes, myoglobin, and other sarcoplasmic proteins into circulation. Creatinine phosphokinase (CPK) and myoglobin serum levels constitute the diagnostic hallmark. Nowadays, drugs have become one of the most frequent cause of rhabdomyolysis and acute kidney injury (AKI) is a potential life-threatening complication. The mechanisms involved in the development of AKI in rhabdomyolysis are intrarenal vasoconstriction, direct and ischemic tubule injury and tubular obstruction. According to some clinical series, the mortality rate in patients who develop AKI due to rhabdomyolysis is highly variable. The cornerstone in managing this condition is the early, aggressive repletion of fluids. The composition of replacement fluid remains controversial. Saline and sodium bicarbonate, especially in patients with metabolic acidosis, seem to be a reasonable approach. When AKI produces refractory hyperkalemia, acidosis or volume overload, renal replacement therapy is indicated. PMID:25504160

Forcellini, Silvia; Fabbian, Fabio; Battaglia, Yuri; Storari, Alda

2014-01-01

4

Rhabdomyolysis  

MedlinePLUS

... temperature Ischemia or death of muscle tissue Low phosphate levels Seizures or muscle tremors Severe exertion, such as marathon running or calisthenics Lengthy surgical procedures Severe dehydration

5

Fatal rhabdomyolysis in systemic lupus erythematosus.  

PubMed

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

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

2011-09-01

6

Renal Replacement Therapy in Acute Kidney Failure due to Rhabdomyolysis  

PubMed Central

Rhabdomyolysis is a syndrome caused by skeletal muscle cells destruction which can occur for many reasons, including prolonged immobilization. The main complication of the syndrome is the development of acute renal failure. Rhabdomyolysis and myoglobinuria are responsible for approximately 5% of all causes of acute renal failure in the USA. The cause of rhabdomyolysis is often multifactorial, and approximately 8–20% of such patients develop myoglobinuric acute renal failure. PMID:24826338

Maggi, G.; Quinteros Hinojosa, F.; Villagran, M. J.; Guasch Arévalo, E.; Gilsanz Rodríguez, F.

2012-01-01

7

Rhabdomyolysis: a review, with emphasis on the pediatric population  

Microsoft Academic Search

Rhabdomyolysis is a common clinical syndrome and accounts for 7% of all cases of acute kidney injury (AKI) in the USA. It\\u000a can result from a wide variety of disorders, such as trauma, exercise, medications and infection, but in the pediatric population,\\u000a infection and inherited disorders are the most common causes of rhabdomyolysis. Approximately half of patients with rhabdomyolysis\\u000a present

Essam F. Elsayed; Robert F. Reilly

2010-01-01

8

Acute kidney injury and rhabdomyolysis due to multiple wasp stings  

PubMed Central

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

Radhakrishnan, Hemachandar

2014-01-01

9

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

ERIC Educational Resources Information Center

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…

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

2012-01-01

10

Hypothyroidism Induced Severe Rhabdomyolysis in a Hemodialysis Patient  

PubMed Central

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

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

2014-01-01

11

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

PubMed Central

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

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

2005-01-01

12

Rhabdomyolysis in a young vegetarian athlete.  

PubMed

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

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

2009-11-01

13

Gluteal compartment syndrome due to rhabdomyolysis after heroin abuse.  

PubMed

We report a 30-year-old man who developed painful swelling of his right leg and complete sciatic nerve palsy after an i.v. injection of heroin. Excessive elevation of serum creatine phosphokinase indicated the presence of rhabdomyolysis. Fasciotomy of the gluteus maximus led to rapid and complete recovery from sciatic nerve palsy. Nontraumatic rhabdomyolysis may cause a gluteal compartment syndrome that requires immediate fasciotomy. PMID:9008535

Klockgether, T; Weller, M; Haarmeier, T; Kaskas, B; Maier, G; Dichgans, J

1997-01-01

14

Clinical spectrum of rhabdomyolysis presented to pediatric emergency department  

PubMed Central

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

2013-01-01

15

Rhabdomyolysis caused by co-medication with simvastatin and clarithromycin  

Microsoft Academic Search

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

Judith Wagner; Christine Suessmair; Hans-Walter Pfister

2009-01-01

16

Bilateral femoral neuropathy complicating rhabdomyolysis and acute renal failure.  

PubMed

Simultaneous bilateral femoral neuropathies are uncommon and are usually seen as a consequence of pelvic surgery or related to pregnancy. This report describes the case of a young man with rhabdomyolysis after a drug-induced coma, which led to intramuscular dystrophic calcification and compression of the femoral nerves. Acute dystrophic calcification has been documented in the setting of rhabdomyolysis with renal failure. This is the first reported case of a compressive neuropathy occurring as a result of such dystrophic calcification. PMID:19078767

Nicolle, Michael; Doherty, Timothy; Algahtani, Hussein

2005-06-01

17

Polydipsia, hyponatremia and rhabdomyolysis in schizophrenia: A case report  

PubMed Central

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

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

2014-01-01

18

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

PubMed

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

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

2014-12-22

19

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

PubMed

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

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

2014-12-01

20

Genetic polymorphisms associated with exertional rhabdomyolysis.  

PubMed

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

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

2013-08-01

21

Acute myocardial injury and rhabdomyolysis caused by multiple bee stings.  

PubMed

Massive envenomation by honey bees is capable of causing multiorgan dysfunction as a result of direct toxic effect of massive envenomation and secondary to systemic anaphylactic reactions. Acute myocardial ischemia due to bee envenomation is a rare event. We report the case of a 65 year old lady who presented with acute myocardial ischemia, severe rhabdomyolysis and angioedema following massive bee envenomation. PMID:21887913

Mathew, Anu; Chrispal, Anugrah; David, Thambu

2011-08-01

22

Rhabdomyolysis induced acute renal failure secondary to statins  

PubMed Central

Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation. We report a patient with chronic kidney disease who had deterioration of renal function due to combination of risk factors like hypothyroidism and interaction of amlodipine and clopidogrel with statins. PMID:23814421

Ram, R.; Swarnalatha, G.; Ramesh, V.; Rao, K. Nageswar; Dakshinamurty, K. V.

2013-01-01

23

Rhabdomyolysis induced acute renal failure secondary to statins.  

PubMed

Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation. We report a patient with chronic kidney disease who had deterioration of renal function due to combination of risk factors like hypothyroidism and interaction of amlodipine and clopidogrel with statins. PMID:23814421

Ram, R; Swarnalatha, G; Ramesh, V; Rao, K Nageswar; Dakshinamurty, K V

2013-05-01

24

Rhabdomyolysis in an HIV-infected patient following coronary angiography: case report and literature review.  

PubMed

Rhabdomyolysis is a rare, but possible, complication of combination antiretroviral therapy (cART). We report a unique case of an HIV-positive patient on cART who came to our attention for suspected ischaemic heart disease. Coronary angiography was carried out and complicated in the following days by rhabdomyolysis. We discuss the possible links between rhabdomyolysis, iodinated contrast media and HAART. PMID:24256695

Sbrana, Francesco; Coceani, Michele; Iapoce, Riccardo; Petersen, Christina; Rovai, Daniele

2014-05-01

25

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

PubMed

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

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

2002-01-01

26

Exercise Induced Rhabdomyolysis with Compartment Syndrome and Renal Failure  

PubMed Central

Exertional rhabdomyolysis is sequela that is occasionally seen after strenuous exercise. The progression to compartment syndrome or renal failure is a rare complication that requires prompt recognition and treatment to prevent morbidity (Giannoglou et al. 2007). We present a case of a 22-year-old college football player who presented to the emergency department (ED) after a typical leg workout as part of his weight conditioning. He was found to have rhabdomyolysis with evidence of renal insufficiency. His condition progressed to bilateral compartment syndrome and renal failure requiring dialysis. After bilateral fasciotomies were performed he had resolution of his compartment syndrome. He continued to be dialysis dependent and had no return of his renal function at discharge 12 days after admission. PMID:25105034

Bhalla, Mary Colleen; Dick-Perez, Ryan

2014-01-01

27

A case of rhabdomyolysis complicated with acute renal failure after resumption of fenofibrate therapy: A first report  

PubMed Central

Adverse effects due to use of fibrates often relate to the skeletal muscle, kidneys, or liver. Rhabdomyolysis is a most serious potential adverse effect. We present a case of resumed fenofibrate induced rhabdomyolysis complicated with acute renal failure. PMID:23833382

Kiskac, Muharrem; Zorlu, Mehmet; Cakirca, Mustafa; Karatoprak, Cumali; Peru, Celalettin; Erkoc, Reha; Yavuz, Erdinc

2013-01-01

28

[A case of nemaline myopathy combined with recurrent rhabdomyolysis].  

PubMed

A four-year-old boy with cerebral palsy showed marked myoglobinemia and developed acute renal failure. Peritoneal dialysis and exchange transfusion resulted in saving the patient. He had a second episode of rhabdomyolysis after one month. Renal failure did not develop due to forced solute-alkaline diuresis therapy. Muscle biopsy revealed nemaline bodies by the Gomori trichome stain. Serum and muscle carnitine showed a marked decrease. PMID:8074897

Ishikawa, A; Tanaka, S; Ogawa, Y; Fukushima, N; Takase, A; Wagatsuma, Y; Goto, Y; Sugie, H; Kajii, N

1994-07-01

29

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

PubMed

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

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

2015-01-01

30

Rhabdomyolysis. The role of diagnostic and prognostic factors  

PubMed Central

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

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

2013-01-01

31

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

PubMed Central

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.

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

2014-01-01

32

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

PubMed

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

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

2014-01-01

33

Severe rhabdomyolysis associated with a primary cytomegalovirus infection in an immunocompetent patient  

PubMed Central

Virus-induced rhabdomyolysis rarely induces respiratory failure. We discuss here a case of severe rhabdomyolysis with acute respiratory failure secondary to a cytomegalovirus (CMV) primary infection. We report a case of severe acute rhabdomyolysis, leading to respiratory failure and mechanical ventilation, associated with CMV primary infection in a young and otherwise healthy woman. We excluded other aetiologies such as metabolic myopathies, electrolyte disorders or Guillain-Barré syndrome with exhaustive researches. After 1?year, the patient recovered completely, apart from a slight muscle deconditioning. In this report, we compare our patient with five other similar cases found in the literature; our patient had the most severe presentation. The mechanism of acute viral-induced rhabdomyolysis remains elusive. PMID:23413290

Gindre, Héloïse; Féasson, Léonard; Auboyer, Christian; Cathébras, Pascal

2013-01-01

34

Dermatomyositis presenting with rhabdomyolysis and acute renal failure; an uncommon manifestation  

PubMed Central

Rhabdomyolysis and myoglobinuria are a rare complication of dermatomyositis. Such patient can land up in acute renal failure. Recognition of this fact has important therapeutic implications as patients require immunotherapy in addition to the symptomatic treatment for renal failure. We report a case of dermatomyositis with evidence of rhabdomyolysis and myoglobinuria presenting with acute renal failure. The patient responded dramatically to corticosteroid therapy. PMID:20151010

Joshi, Deepika; Kumar, Niraj; Rai, Anand

2009-01-01

35

[Compartment syndrome caused by rhabdomyolysis in the context of pychogenic polydipsia.  

PubMed

Psychogenic polydipsia leading to severe hyponatremia is well documented in the literature. This electrolyte disorder can result in encephalopathy, cerebral edema and epileptic seizures. Another rare effect is rhabdomyolysis with all its well known complications (e.g. renal failure, hyperkalemia and cardiac arrhythmia) and even resulting in compartment syndrome due to severe muscle edema.We present the case of a patient with severe hyponatremia caused by psychogenic polydipsia leading to rhabdomyolysis and compartment syndrome. PMID:25277729

Sauer, F; Lenz, A; Popp, D; Strecker, W

2014-10-01

36

Exertional rhabdomyolysis following excessive exercise of university freshman cheer-training.  

PubMed

Exertional rhabdomyolysis is a life threatening condition resulting from lysis of muscle cells after vigorous exercise. It can cause many complications such as renal failure. It occurs most commonly in military personnel but also in civilians who have excessive excercise after work. Two cases of freshmen who had exertional rhabdomyolysis were reported to illustrate the potential risk of cheer-training. Appropriate measures should be arranged to prevent this condition. Diagnosis and treatment should be given promptly to prevent serious complications. PMID:12948279

Mahakkanukrauh, Ajanee; Sangchan, Apichat; Mootsikapun, Piroon

2003-08-01

37

Acute renal failure due to rhabdomyolysis following dengue viral infection: a case report  

PubMed Central

Introduction With more than one-third of the world’s population living in areas at risk for transmission, dengue fever is a leading cause of illness and death in the tropics and subtropics. Despite the high incidence of dengue fever, rhabdomyolysis leading to acute renal failure is an extremely rare complication of dengue fever. Only a few such cases have been reported in the literature. Case presentation We describe the case of a 42-year-old, previously healthy Sri Lankan Sinhalese man who developed acute renal failure due to rhabdomyolysis following dengue virus infection. He was transferred to our institution with a five-day history of fever, headache, myalgia, impaired level of consciousness, and reduced urinary output. He was hemodynamically stable and did not have evidence of plasma leakage. His serology for dengue immunoglobulin M and immunoglobulin G was positive, and biochemical investigations disclosed evidence of rhabdomyolysis and acute renal failure. He was treated with induced alkaline diuresis and hemodialysis, and he experienced an uncomplicated recovery. Conclusion The occurrence of acute renal failure significantly increases the mortality of patients with dengue fever. Therefore, early diagnosis and early management are crucial in rhabdomyolysis complicating dengue fever to prevent established acute renal failure. It should be kept in mind that the threshold for suspecting rhabdomyolysis is very low in dengue fever. Creatinine phosphokinase levels should routinely be measured in all patients with severe dengue fever for early detection of rhabdomyolysis to prevent acute renal failure. PMID:23889764

2013-01-01

38

Acute Exertional Rhabdomyolysis and Triceps Compartment Syndrome During a High School Football Camp  

PubMed Central

Background: Acute exertional rhabdomyolysis has been infrequently reported among adolescents. In August 2010, several high school football players from one team developed rhabdomyolysis and triceps compartment syndrome following an upper arm exercise held in a non-air-conditioned wrestling room. Purpose: To confirm the diagnoses, characterize the spectrum of illnesses, and determine the factors contributing to rhabdomyolysis and triceps compartment syndromes. Study Design: Descriptive epidemiology study. Methods: The authors reviewed hospital medical records and interviewed players, coaches, school administrators, and hospital staff, using a standardized questionnaire that assessed symptoms, exposures, and activities. Results: Among 43 players, 22 (51%) experienced rhabdomyolysis (peak creatine kinase range, 2434-42 000 U/L): 22 patients had upper arm myalgia; 12 were hospitalized; 3 experienced triceps compartment syndrome; none experienced renal failure. Illnesses started 1 to 3 days after the triceps exercise. Forty players (93%) completed questionnaires. Among 19 players receiving at least 1 vote from a teammate as 1 of the 3 hardest working players, 13 (68%) experienced rhabdomyolysis versus 7 (33%) of 21 not considered hardest working (relative risk, 2.1; 95% confidence interval, 1.04-4.0). Of 40 players, 10 (25%) reported creatine supplement use, which was not associated with rhabdomyolysis. No player acknowledged use of alcohol, illicit drugs, or performance-enhancing drugs; results of performance-enhancing drug tests on the 4 players tested were negative. Environmental investigation did not identify additional factors contributing to illness. Conclusions: The upper arm exercise, possibly exacerbated by heat, led to rhabdomyolysis and compartment syndrome. Greater awareness of specific exercise hazards and prevention strategies can minimize risk for clinically significant muscle injury. PMID:23016070

Oh, John Y.; Laidler, Matthew; Fiala, Steven C.; Hedberg, Katrina

2012-01-01

39

Rhabdomyolysis and acute renal failure in severely burned patients.  

PubMed

Rhabdomyolysis (RML) is a precarious complication in severely burned patients and the principal treatment goal is prevention of acute renal failure (ARF). This 10-year retrospective study analyses the causes for RML in severely burned patients and evaluates treatment algorithms. Eight of 714 patients (1%) were diagnosed with RML. Percentage TBSA burn was 25 ± 13%. The mean abbreviated burn severity index score (ABSI) was 9 ± 2. ARF was found in 75% (6/8) of the patients. Serum myoglobin (MB) was reduced by 41 ± 16% after 24-h treatment by solitary volume repletion (VR) and by 44 ± 20% through VR+continuous veno-venous hemodiafiltration (CVVHDF). Mortality was 50% (4/8). Peak mean CPK-levels were more than two and MB-levels more than four times higher in non-survivors than in survivors. Burns associated with RML result in poor survival. VR and CVVHDF are effective measures in treating RML. CVVHDF is effective in removing MB when using high flux filter membranes. Early CVVHDF (within 24h of diagnosis) with high-cut off membranes could reduce the risk of ARF and mortality. PMID:20965664

Stollwerck, Peter L; Namdar, Thomas; Stang, Felix H; Lange, Thomas; Mailänder, Peter; Siemers, Frank

2011-03-01

40

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

PubMed Central

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

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

2014-01-01

41

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

PubMed

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

Petrov, Mikhail; Yatsynovich, Yan; Lionte, Catalina

2015-01-01

42

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

PubMed Central

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

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

2014-01-01

43

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

PubMed

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

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

2012-01-01

44

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

PubMed

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

Parr, M J; Willatts, S M

1991-07-01

45

[Rhabdomyolysis and arterial hypertension caused by apparent excess of mineralocorticoids: a case report].  

PubMed

We report the case of a 61-year-old man who was referred to our Institution because of severe hypokalemia, rhabdomyolysis and high blood pressure. Severe hypokalemia may lead to rhabdomyolysis. The plasma aldosterone concentrations were low and the plasma renin activity was suppressed. A diagnosis of apparent mineralocorticoid excess, attributable to licorice and grapefruit juice ingestion, was made. Glycyrrhizic acid and glycyrrhetinic acid, its hydrolytic product, in licorice extracts, and polyphenols, in grapefruit juice, can inhibit 11 beta-hydroxysteroid dehydrogenase type 2, the enzyme that converts cortisol to cortisone. Moreover, having suspended licorice and grapefruit juice ingestion, the plasma K+ levels and blood pressure values progressively and simultaneously returned to normal. We would like to stress the diagnostic weight of a careful history taking. PMID:12150047

Sardi, Alberto; Geda, Claudio; Nerici, Luigi; Bertello, Pierdomenico

2002-01-01

46

Rhabdomyolysis and acute renal failure in a sickle cell trait athlete: a case study.  

PubMed

This case study reports the clinical details and pathologic mechanisms of a nonfatal case of rhabdomyolysis secondary to heat exhaustion and sickle cell trait (SCT) resulting in acute renal failure. A 19-year-old African American male college football player collapsed after running 5 intervals of 300 m during a preseason conditioning test. After 17 days of treatment, the athlete was released from the hospital to a short-term noncritical care facility for further treatment and dialysis. Scientific literature reports that at least 15 college football players with SCT have died as a result of a sickling crisis after intense physical exertion. This case study presents the clinical importance of prompt medical treatment and sustained low-efficiency dialysis in treating rhabdomyolysis and its sequelae after collapse in an SCT athlete. PMID:22894971

Shelmadine, Brian D; Baltensperger, Austin; Wilson, Ronald L; Bowden, Rodney G

2013-05-01

47

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

PubMed

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

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

2010-02-01

48

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

PubMed

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

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

2013-03-01

49

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

PubMed Central

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

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

50

Mechanisms of nephroprotective effect of mitochondria-targeted antioxidants under rhabdomyolysis and ischemia\\/reperfusion  

Microsoft Academic Search

Oxidative stress-related renal pathologies apparently include rhabdomyolysis and ischemia\\/reperfusion phenomenon. These two pathologies were chosen for study in order to develop a proper strategy for protection of the kidney. Mitochondria were found to be a key player in these pathologies, being both the source and the target for excessive production of reactive oxygen species (ROS). A mitochondria-targeted compound which is

E. Y. Plotnikov; A. A. Chupyrkina; S. S. Jankauskas; I. B. Pevzner; D. N. Silachev; V. P. Skulachev; D. B. Zorov

2011-01-01

51

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

PubMed

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

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

2014-01-15

52

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

PubMed Central

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

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

2013-01-01

53

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

PubMed

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

Kästner, Andreas; Braun, Markus; Meyer, Tim

2014-10-28

54

[A case of rhabdomyolysis with water intoxication confirmed by muscle biopsy].  

PubMed

A 32-year-old woman with chronic schizophrenia who took 8-10 liters of water for three years due to thirsty, admitted to our hospital because of convulsion and muscle weakness. Neurological finding on admission showed a mild disturbance of consciousness, moderate proximal muscle weakness, and muscle pain. Laboratory examination revealed marked serum hyponatremia(102 mEq/l) and high value of creatin kinase (1,259 IU/l). The level of creatin kinase reached a peak(39,700 IU/l) at the 5th hospital day. An analysis of the muscle biopsy specimen showed necrotic muscle fibers and opaque fibers, that was compatible with rhabdomyolysis. T 2 weighted magnetic resonance imaging of the brain showed a transient high signals in bilateral putamen but not in pons. She was diagnosed to have rhabdomyolysis due to water intoxication. The present case is the first rhabdomyolysis in Japan that was confirmed by muscle biopsy at an acute stage of water intoxication related with schizophrenia. PMID:10689692

Nagata, T; Aoki, M; Kato, H; Mochizuki, H; Tateyama, M; Itoyama, Y

2000-01-01

55

Rhabdomyolysis after midazolam administration in a cirrhotic patient treated with atorvastatin  

PubMed Central

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

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

2014-01-01

56

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

PubMed

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

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

2014-08-01

57

A case of rhabdomyolysis induced acute renal failure secondary to statin-fibrate-derivative combination and occult hypothyroidism.  

PubMed

Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation. We hereby report a patient proved to be a case of unrecognized hypothyroidism presenting with rhabdomyolytic acute renal failure precipitated by the combined use of statin and fenofibrate. A 63-year-old woman was referred to our department because of fatigue, diffuse muscle pain and oliguria. On the basis of pathogenesis, clinical and laboratory examination the diagnoses of acute renal failure secondary to the statin-fibrate-derivative combination induced rhabdomyolysis and auto-immune thyroiditis induced hypothyroidism were made. Although saline, furosemide and sodium bicarbonate infusions enabled diuresis and have led to a rapid recovery of renal function and normalization of blood pressure in five days (creatinine level decreased from 4.5 mg/dl to 1.2 mg/dl), only thyroid replacement therapy (0,1 mg thyroxine) that begun after the exclusion of adrenal insufficiency resulted in complete resolution of rhabdomyolysis. This prompted the diagnosis of background, clinically silent rhabdomyolysis aggrevated by the statin-fibrate-derivative combination. To our knowledge this case illustrates the first example of rhabdomyolytic acute renal failure induced by a statin-fibrate-derivative combination with underlying hypothyroidism which was responsible for the basal clinically unobservable rhabdomyolysis. PMID:16312269

Kursat, S; Alici, T; Colak, H B

2005-11-01

58

Blood cell exchange in the treatment of exercise-induced rhabdomyolysis in a patient with sickle cell trait.  

PubMed

We report the use of red blood cell exchange (RBCex) to treat rhabdomyolysis complicated by acute kidney injury in a 16-year-old African-American female with sickle cell trait (SCT). Treatment with aggressive fluid and electrolyte management failed to stem the rise in her creatine kinase, and RBCex was instituted 27 hours after symptom onset. She had a transient improvement in her creatine kinase following this treatment although it failed to resolve a developing lower extremity compartment syndrome, requiring bilateral lower extremity fasciotomies. The mechanism of exercise-induced rhabdomyolysis in individuals with SCT is theorized to result from localized hypoxia and acidosis within exercising muscle significant enough to cause a localized sickling crisis with resultant rhabdomyolysis. Despite the unique pathophysiology of rhabdomyolysis in individuals with SCT, there is a paucity of adjunctive treatment options beyond fluid and electrolyte therapy. To the best of our knowledge, RBCex for treatment of rhabdomyolysis in a patient with SCT has been described only once before by Huang et al. We report here a second case in the use of RBCex in the treatment of rhadbomyolysis in a patient with SCT. PMID:25562874

Papacostas, Michael F; McLean, Matthew

2015-01-01

59

Fenofibrate-induced rhabdomyolysis in a patient with chronic kidney disease: an unusual presenting feature of hypothyroidism.  

PubMed

Clinical and most often moderate skeletal muscle involvement is a frequent problem in adults with hypothyroidism, and includes a number of different manifestations. Severe involvement with rhabdomyolysis, however, is very rare, and only a few cases have been reported to date, most of them with an additional factor of muscle injury. We described a patient with stage 3 chronic kidney disease who presented with rhabdomyolysis while taking fenofibrate, and was found to have hypothyroidism. We also highlighted the importance of excluding the diagnosis of thyroid dysfunction before treatment with lipid-lowering agents. PMID:19578603

Sousa, Alessandra Alves de; Kronit, Hans Stauber; Neves, Francisco de Assis Rocha; Amato, Angélica Amorim

2009-04-01

60

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

PubMed

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

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

2013-11-01

61

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

PubMed

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

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

2008-01-01

62

Severe Hypercalcemia Complicating Recovery of Acute Kidney Injury due to Rhabdomyolysis  

PubMed Central

Patient: Male, 23 Final Diagnosis: Rabdomyolysis Symptoms: Cardiac arrest • cardiac arrhythmia • hypercalcemia Medication: — Clinical Procedure: — Specialty: — Objective: Unusual clinical course Background: Rhabdomyolysis is frequently complicated by multiple electrolyte abnormalities, including hyperkalemia, hyperphosphatemia, and hypo/hypercalcemia. Hypercalcemia can be severe and life-threatening. Case Report: A 23-year-old white male suffered severe trauma to his lower extremities after a motor vehicle accident, leading to severe muscle damage, cardiac arrhythmia, cardiac arrest, and oliguric acute kidney injury (AKI), requiring hemodialysis treatment. As expected, he was hypocalcemic during the oliguric phase but during the diuretic phase he developed severe symptomatic hypercalcemia requiring hemodialysis treatment in spite of volume replacement and administration of pamidronate. Hypercalcemia reached a peak of 17.1 mg/dL, corrected for serum albumin and urine output was as high as 11.9 liters daily. Hypercalcemia lasted for 3 weeks and then it returned back to normal levels. Plasma levels of 25-OH and 1–25(OH)2 vitamin D were low, intact parathyroid hormone level was appropriately suppressed, and 24-hour urine calcium was 1194 mg (normal up to 350 mg/daily). Mobilization of calcium from calcium phosphate deposits in the injured muscles seems to be the main reason for hypercalcemia and hypercalciuria in rhabdomyolysis-induced AKI. Conclusions: Hypercalcemia is not uncommon during the recovery phase of ATN. Unattended, it can cause severe morbidity and even mortality. Fluid administration, pamidronate, and calcium-free dialysis are some methods used to correct severe hypercalcemia. Over time, hypercalcemia improves in almost all cases. PMID:25218143

Hechanova, Lisa Aimee; Sadjadi, Seyed-Ali

2014-01-01

63

TNF-?-mediated cardio-renal injury after rhabdomyolysis in rats.  

PubMed

Tumor necrosis factor-? (TNF-?) serum level increases after rhabdomyolysis and is involved in the subsequent cardio-renal injury. In this study, we investigated TNF-?-dependent cell signaling pathways implicated in the cellular injury in these organs. Rhabdomyolysis was induced by intramuscular glycerol injection in rats. The renal function, cardiac and renal pathology and activation of the caspases were evaluated during the first 24 hours after glycerol injection. TNF-? blockade with infliximab reduced the tubular necrosis and cardio-renal apoptosis. cFLIP, an inhibitor of caspase-8, was overexpressed in the kidney, but not in the heart. The inhibitory effect of cFLIP blunted caspase-8 activation in the kidney. In this condition, cellular response to TNF-? stimulus was driven to RIP1-mediated necroptosis. The treatment with RIP1 inhibitor (necrostatin-1) isolated or in combination with infliximab showed similar reduction in the tubular necrosis, underscoring the importance TNF-?-mediated tubular necroptosis in this model. TNF-? played a positive regulatory role in the transcription of the pro-apoptotic Bax and PUMA proteins. Infliximab treatment reduced the caspase-9-mediated apoptosis in both organs. Treatment with a caspase-8 inhibitor showed that caspase-8 participated in the process of apoptosis only in the heart, upstream to caspase-9 activation. TNF-?-mediated necroptosis is the predominant form of tubular injury observed in the glycerol model. TNF-? up regulates Bax and PUMA pro-apoptotic proteins resulting in activation of the intrinsic pathway of apoptosis in the kidney and in the heart. PMID:25391899

Homsi, Eduardo; Andreazzi, Diego Duarte; Lopes de Faria, José B; Janino, Patricia

2014-11-12

64

Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report  

PubMed Central

Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS). However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA). In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects. PMID:24396655

Sa, Young Kyoung; Yang, Hyeon; Jung, Hee Kyoung; Son, Jang Won; Lee, Seong Su; Kim, Seong Rae; Cha, Bong Yeon; Son, Ho Young; Pae, Chi-Un

2013-01-01

65

Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of M2 macrophages  

PubMed Central

Introduction The mortality of rhabdomyolysis-induced acute kidney injury (AKI) is still high, as there is no effective therapy. It has been shown that bone marrow-derived mesenchymal stem cells (MSCs) can induce M2 macrophages, which mediate MSC protection in other experimental inflammation-related organ injury. This study was designed to investigate the protective effects of macrophage activation in MSC therapy of rhabdomyolysis-induced AKI. Methods MSCs were injected into glycerol-induced rhabdomyolysis mice. Renal injury was evaluated using the serum creatinine, urea nitrogen, renal pathology and acute tubular necrosis score. The distribution of MSCs was detected using two-photon fluorescence confocal imaging. Immunofluorescence of anti-F4/80 and anti-CD206 was performed to determine macrophages and M2 macrophages in the tissues of the kidney, and M2 macrophage infiltration was also evaluated using western blotting analyses. After depletion of macrophages using clodronate liposomes at the phase of kidney repair, renal injury was re-evaluated. RAW 264.7 macrophages were incubated with lipopolysaccharide and co-cultured with MSCs and subsequently visualised using immunofluorescence staining and flow cytometry analysis. Finally, disparate phenotype macrophages, including normal macrophages (M0), lipopolysaccharide-stimulated macrophages (M1), and MSC-co-cultured macrophages (M2), were infused into mice with AKI, which were pre-treated with liposomal clodronate. Results In vivo infusion of MSCs protected AKI mice from renal function impairment and severe tubular injury, which was accompanied by a time-dependent increase in CD206-positive M2 macrophage infiltration. In addition, depleting macrophages with clodronate delayed restoration of AKI. In vitro, macrophages co-cultured with MSCs acquired an anti-inflammatory M2 phenotype, which was characterised by an increased expression of CD206 and the secretory cytokine interleukin (IL)-10. The concentrations of IL-10, IL-6 and tumor necrosis factor ? were evaluated using enzyme-linked immunosorbent assay. Furthermore, macrophage-depleted mice with intramuscular injection of glycerol were subjected to a single injection of different types of RAW 264.7 macrophages. Mice infused with M0 and M1 macrophages suffered a more severe histological and functional injury, while mice transfused with MSC-educated M2 macrophages showed reduced kidney injury. Conclusions Our findings suggested that MSCs can ameliorate rhabdomyolysis-induced AKI via the activation of macrophages to a trophic M2 phenotype, which supports the transition from tubule injury to tubule repair. PMID:24961539

2014-01-01

66

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

PubMed

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

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

2010-12-01

67

Moderate endurance exercise is not a risk for rhabdomyolysis or renal failure in sickle cell trait carriers.  

PubMed

This study tested the hypothesis that trained sickle cell trait (SCT) carriers are not subjected to greater risk of rhabdomyolysis or renal failure in response to moderate submaximal exercise than subjects with normal hemoglobin (CONT). Blood markers in 11 trained SCT carriers and 12 control counterparts were measured before and after 40 min of exercise at 55% of peak power output (Ppeak) conducted in thermoneutral environment. Body weights decreased with exercise in the same proportion in the two groups (from 65.1 ± 7.0 kg to 64.1 ± 7.0 kg and from 70.2 ± 6.6 to 68.6 ± 6.6 kg at the end of exercise in SCT and CONT, respectively). Heart rate and rectal temperature increased in the two groups in response to exercise, but the groups remained closely matched. Serum urea, CRP, CK and LDH were similar in the two groups and remained unchanged in response to exercise. Creatinine, Na(+), K(+), Cl(-) and myoglobin concentrations increased above baseline in response to exercise, with changes of the same magnitude in the two groups. In summary, the results of the present study suggest that moderate submaximal exercise is not unsafe from a biochemical point of view for sportsmen carrying SCT. PMID:22240384

Messonnier, Laurent; Samb, Abdoulaye; Tripette, Julien; Gogh, Bertin Doubi; Loko, Gylna; Sall, Niama Diop; Féasson, Léonard; Hue, Olivier; Lamothe, Sandrine; Bogui, Pascal; Connes, Philippe

2012-01-01

68

Ubiquinol rescues simvastatin-suppression of mitochondrial content, function and metabolism: implications for statin-induced rhabdomyolysis.  

PubMed

Statin medications diminish cholesterol biosynthesis and are commonly prescribed to reduce cardiovascular disease. Statins also reduce production of ubiquinol, a vital component of mitochondrial energy production; ubiquinol reduction may contribute to rhabdomyolysis. Human rhabdomyosarcoma cells were treated with either ethanol and dimethyl sulfoxide (DMSO) control, or simvastatin at 5 µM or 10 µM, or simvastatin at 5 µM with ubiquinol at 0.5 µM or 1.0 µM for 24 h or 48 h. PGC-1? RNA levels were determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mitochondrial content was determined using flow cytometry and immunocytochemistry. Metabolism was determined by quantification of extracellular acidification rate and oxygen consumption rate. Treatment of human rhabdomyosarcoma cells with simvastatin significantly reduced oxidative, total metabolism, and cellular ATP content in a time- and dose-dependent manner which was rescued by concurrent treatment with ubiquinol. Treatment with simvastatin significantly reduced mitochondrial content as well as cell viability which were both rescued by simultaneous treatment with ubiquinol. This work demonstrates that the addition of ubiquinol to current statin treatment regimens may protect muscle cells from myopathies. PMID:23624330

Vaughan, Roger A; Garcia-Smith, Randi; Bisoffi, Marco; Conn, Carole A; Trujillo, Kristina A

2013-07-01

69

Anti-PD1 following Ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis  

PubMed Central

Treatment with fully human monoclonal antibodies against programmed death 1 (anti-PD1) have demonstrated great promise for the treatment of a number of advanced malignancies. While inflammatory adverse events have been well-described with anti-Cytotoxic T-Lymphocyte Antigen (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near complete response, but developed severe hypothyroidism, rhabdomyolysis and acute kidney injury. To our knowledge, this is the first case reportedof a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated CK levels and thyroid disorders in patients who receive anti-PD1 therapy is important. PMID:24778161

Min, Le; Hodi, F. Stephen

2014-01-01

70

Anti-PD1 following ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis.  

PubMed

Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important. PMID:24778161

Min, Le; Hodi, F Stephen

2014-01-01

71

Hyponatraemia, rhabdomyolysis, alterations in blood pressure and persistent mydriasis in patients envenomed by Malayan kraits (Bungarus candidus) in southern Viet Nam.  

PubMed

Between 1998 and 2007, 42 patients admitted to Choray hospital, Ho Chi Minh City, and to two hospitals in adjacent regions in southern Viet Nam brought the Malayan kraits (Bungarus candidus) that had been responsible for biting them. Half of the patients had been bitten while they were asleep. Fang marks and numbness were the only local features of the bites. Common signs of neurotoxic envenoming included bilateral ptosis, persistently dilated pupils, limb weakness, breathlessness, hypersalivation, dysphonia and dysphagia. Thirty patients (71.4%) required endotracheal intubation of whom all but one were mechanically ventilated. Fourteen patients (33.3%) developed hypertension, 13 (31.0%) shock, 31 (73.8%) hyponatraemia (plasma sodium concentration < 130 mEq/l) and 30 (71.4%) showed evidence of mild rhabdomyolysis (peak plasma creatine kinase concentration 1375 +/- 140 micro/l). None developed acute kidney injury. All the patients were treated with a new monospecific B. candidus antivenom. There were no fatalities. Hyponatraemia has been reported previously in victims of Chinese kraits (Bungarus multicinctus) in northern Viet Nam and rhabdomyolysis in patients envenomed by B. niger in Bangladesh. These features of envenoming pose new problems for the management of krait bite cases in South east Asia and should stimulate a search for the causative venom toxins. PMID:20637219

Trinh, Kiem Xuan; Khac, Quyen Le; Trinh, Long Xuan; Warrell, David A

2010-11-01

72

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

PubMed Central

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

2013-01-01

73

Rhabdomyolysis following accidental intra-arterial injection of local anesthetic.  

PubMed

Drug-induced myopathy, also named Nicolau syndrome, is a well-known phenomenon following intramuscular injection of certain agents, most commonly reported with penicillin or diclofenac. The mechanism responsible for the pathology is proposed to be incidental administration of the drug into the small arterioles. In this report, we present a Nicolau syndrome-like case that developed following accidental injection of a local anesthetic agent into the femoral artery during coronary angiography. PMID:18388104

Selimoglu, Ozer; Basaran, Murat; Ugurlucan, Murat; Ogus, Temucin Noyan

2009-01-01

74

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

PubMed Central

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

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

2013-01-01

75

Myoglobin causes oxidative stress, increase of NO production and dysfunction of kidney's mitochondria  

Microsoft Academic Search

Rhabdomyolysis or crush syndrome is a pathology caused by muscle injury resulting in acute renal failure. The latest data give strong evidence that this syndrome caused by accumulation of muscle breakdown products in the blood stream is associated with oxidative stress with primary role of mitochondria. In order to evaluate the significance of oxidative stress under rhabdomyolysis we explored the

Egor Y. Plotnikov; Anastasia A. Chupyrkina; Irina B. Pevzner; Nickolaj K. Isaev; Dmitry B. Zorov

2009-01-01

76

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

PubMed Central

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

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

2013-01-01

77

Superwarfarin (brodifacoum) poisoning.  

PubMed

A case of self-ingestion of brodifacoum that resulted in spontaneous intra-abdominal haemorrhage, circulatory shock, rhabdomyolysis and acute renal failure is reported. Current knowledge and management of superwarfarin poisoning are discussed. PMID:9452861

Corke, P J

1997-12-01

78

Phenotype standardization for statin-induced myotoxicity.  

PubMed

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

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

2014-10-01

79

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

PubMed Central

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

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

2012-01-01

80

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

PubMed Central

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

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

2005-01-01

81

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

PubMed

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

1998-12-25

82

Hypothyroidism Complicating Nephropathy in a Diabetes Patient  

PubMed Central

We describe a patient with type 2 diabetes mellitus and autoimmune hypothyroidism who presented with elevated serum creatinine possibly due to subclinical rhabdomyolysis induced by hypolipidemic drug therapy in the background of diabetic nephropathy. Both hypothyroidism and rhabdomyolysis were asymptomatic in this case as evidenced by lack of classical clinical features of hypothyroidism despite elevated serum TSH and absent pigment cast in renal biopsy. The combination of diabetes mellitus and hypothyroidism is common in the general population and should not be forgotten in patients with diabetes and kidney disease. PMID:23304572

Veerappan, Ilangovan; Abraham, Anila; Hariharan, Somasundaram

2012-01-01

83

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

PubMed Central

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

Mcinnes, Andrew D.; DeGroote, Richard J.

2014-01-01

84

The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome  

Microsoft Academic Search

Propofol infusion syndrome (PRIS) is a rare and often fatal syndrome described in critically ill children undergoing long-term propofol infusion at high doses. Recently several cases have been reported in adults, too. The main features of the syndrome consist of cardiac failure, rhabdomyolysis, severe metabolic acidosis and renal failure. To date 21 paediatric cases and 14 adult cases have been

Beatrice Vasile; Frank Rasulo; Andrea Candiani; Nicola Latronico

2003-01-01

85

Clinical Characteristics and Time Course Associated with Malignant Hyperthermia Presenting in the Postoperative Period  

Microsoft Academic Search

Introduction: The Malignant Hyperthermia (MH) hotline of the Malignant Hyperthermia Association of the United States (MHAUS) receives a large volume of calls from physicians reporting symptoms from patients suspected of suffering from MH during the postoperative period. The most commonly reported signs include fever, acidosis, hypercarbia, tachycardia, and rhabdomyolysis. On further investigation it is found that very few, if any,

Christopher D Flood; Ronald S. Litman; Joseph R. Tobin; Richard Kaplan

86

Myoglobinemia and endurance exercise: A study of twenty-five participants in a triathlon competition  

Microsoft Academic Search

Twenty-five athletes competing in a triathlon, an endur ance competition, were studied to determine the rela tionship of sustained muscle exertion with myoglobin emia and clinical rhabdomyolysis. Of 24 athletes who completed the event, each individual demonstrated a dramatic rise and fall in serum myoglobin over a 24 hour period, with an average peak level of 842 ng\\/ml. While all

Ben D. Thomas; Carol P. Motley

1984-01-01

87

Treatment of hyperlipidemia with combined niacin–statin regimens  

Microsoft Academic Search

Combined use of niacin with a statin is an attractive option, since these types of medication have the best records in clinical trials for reduction in cardiovascular events and improvement in progression\\/regression of coronary lesions. In early use, the niacin–statin combination generated a few case reports documenting severe myopathy and rhabdomyolysis. Subsequent prospective trials in >400 patients, however, have not

John R Guyton; David M Capuzzi

1998-01-01

88

Acute renal failure in association with cosmetic suction lipectomy.  

PubMed Central

A case of severe non-oliguric acute renal failure following cosmetic suction lipectomy in a 33 year old woman is described. The renal failure, although requiring emergency treatment, resolved spontaneously with only negligible residual impairment of renal function. An aetiology involving rhabdomyolysis and myoglobinuria is proposed and other mechanisms are discussed. Images Figure 1 PMID:4095055

Rose, G. E.

1985-01-01

89

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

ERIC Educational Resources Information Center

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…

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

2009-01-01

90

Injuries in the event horse: Training versus competition  

Microsoft Academic Search

Two related studies on injuries sustained by event horses during competition and during training are reported. During the cross-country phase of competition, the most common injuries were lacerations and abrasions to the carpus and stifle. Superficial digital flexor tendonitis and exertional rhabdomyolysis were significantly more common during Cours Complete Internationale (CCI) competitions compared to one-day event (ODE) competitions. The difference

Ellen R. Singer; Jane Barnes; Fiona Saxby; Jane K. Murray

2008-01-01

91

Acute liver damage and ecstasy ingestion  

Microsoft Academic Search

Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted

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

1996-01-01

92

Drugs of abuse (Amfetamines, BZP, cannabis, cocaine, GHB)  

Microsoft Academic Search

The features of amfetamine poisoning are related predominantly to stimulation of central and peripheral adrenergic receptors, and in severe cases, excitability, agitation, paranoid delusions, hallucinations with violent behaviour, hypertonia and hyperreflexia develop. Convulsions, rhabdomyolysis, hyperthermia, intracerebral haemorrhage and cardiac arrhythmias are less common. In addition, hyperthermia and hyponatraemia are features of severe MDMA toxicity.Benzylpiperazine (BZP) has stimulant and amfetamine-like properties.

Allister Vale

93

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

PubMed

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

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

2014-12-01

94

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

PubMed

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

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

2015-03-01

95

[Muscle crush injury and crush syndrome].  

PubMed

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

Reingardien?, Dagmara; Jodži?nien?, Liucija; Lažauskas, Robertas

2010-01-01

96

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

PubMed

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

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

2015-02-01

97

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

Microsoft Academic Search

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

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

1993-01-01

98

Haff disease: from the Baltic Sea to the U.S. shore.  

PubMed Central

Haff disease, identified in Europe in 1924, is unexplained rhabdomyolysis in a person who ate fish in the 24 hours before onset of illness. We describe a series of six U.S. patients from 1997 and report new epidemiologic and etiologic aspects. Although Haff disease is traditionally an epidemic foodborne illness, these six cases occurred in two clusters and as one sporadic case. PMID:10756156

Buchholz, U.; Mouzin, E.; Dickey, R.; Moolenaar, R.; Sass, N.; Mascola, L.

2000-01-01

99

Creatine phosphokinase elevation exacerbated by levetiracetam therapy  

PubMed Central

A 19-year-old muscular male with a history of epilepsy presented following two convulsive events. Levetiracetam (LEV) was given as an additional therapy, resulting in a marked boost in creatine phosphokinase (CPK) that could not easily be explained by renal dysfunction or rhabdomyolysis alone. Levetiracetam discontinuation caused CPK levels to quickly normalize and should be considered in patients with persisting CPK elevations postconvulsive seizure.

Isaacson, Julia E.; Choe, Dongwhoon J.; Doherty, Michael J.

2014-01-01

100

Carbon monoxide poisoning and nonoliguric acute renal failure.  

PubMed Central

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

Bessoudo, R.; Gray, J.

1978-01-01

101

Acute tubulointerstitial nephritis after wasp stings  

Microsoft Academic Search

A 61-year-old Caucasian man presented with acute renal failure after multiple wasp stings. The patient required dialysis support temporarily. Work-up failed to show rhabdomyolysis or hemolysis and a kidney biopsy revealed acute allergic interstitial nephritis. The patient's renal function recovered completely after a short course of steroid therapy. Acute renal failure after wasp stings is typically caused by acute tubular

Rubin Zhang; Suzanne Meleg-Smith; Vecihi Batuman

2001-01-01

102

Delayed Onset Malignant Hyperthermia after Sevoflurane  

PubMed Central

Malignant hyperthermia is a hypermetabolic response to inhalation agents (such as halothane, sevoflurane, and desflurane), succinylcholine, vigorous exercise, and heat. Reactions develop more frequently in males than females (2?:?1). The classical signs of malignant hyperthermia are hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity and rhabdomyolysis. In this case report, we present a case of delayed onset malignant hyperthermia-like reaction after the second exposure to sevoflurane. PMID:23819066

Turhan, K. Sanem Cakar; Bayta?, Volkan; Batislam, Ye?im; Özatamer, Oya

2013-01-01

103

The syndrome of irreversible acidosis after prolonged propofol infusion  

Microsoft Academic Search

Introduction: Propofol infusion syndrome is described in the pediatric literature as metabolic acidosis, rhabdomyolysis, and bradycardia\\u000a that results in death. The pathogenesis of this syndrome is thought to be activation of the systemic inflammatory response,\\u000a which culminates in acidosis and muscle necrosis.\\u000a \\u000a \\u000a Materials and Methods: Retrospective chart review of three patients in the Neurological Critical Care Units at Hahnemann and

Monisha A. Kumar; Victor C. Urrutia; Carole E. Thomas; Karine J. Abou-Khaled; Robert J. Schwartzman

2005-01-01

104

Safety of statins  

PubMed Central

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

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

2013-01-01

105

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

PubMed

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

Redshaw, Charlotte; Stewart, Catherine

2014-11-01

106

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

PubMed

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

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

2015-01-01

107

An Atropa belladonna L. poisoning with acute subdural hematoma.  

PubMed

Atropa belladonna L. is a plant long known to cause poisoning. But no cases of acute subdural hematoma resulting from such poisoning have been reported so far. Care must also be taken in terms of acute pancreatitis and rhabdomyolysis in cases of such poisoning. The plant may sometimes be mistaken for the Caucasian blueberry, V. arctostaphylos L. At least one anti-cholinesterase toxidrome finding was determined in all the nine cases of belladonna poisoning in this series. No elevated creatine kinase was reported in one case with acute subdural hematoma and hyperamylasemia. PMID:21540312

Cikla, Ulas; Turkmen, Suha; Karaca, Yunus; Ayaz, Faik Ahmet; Ayaz, Ahmet Faik; Turedi, Suleyman; Gunduz, Abdulkadir

2011-12-01

108

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

PubMed

Envenomation by a spotted black snake (Pseudechis guttatus), following multiple bites on the buccal mucosa of a captive maned wolf (Chrysocyon brachyurus), caused the animal's collapse, hemolysis, rhabdomyolysis, local tissue necrosis, hepatic and renal failure, and subsequent death. The wolf died despite intensive supportive care including antivenom administration, fluid support, and a blood transfusion. Gross necropsy findings included myocardial and intestinal hemorrhage, pulmonary congestion, hepatomegaly, and splenomegaly. Microscopic examination of formalin-fixed tissues demonstrated pulmonary and abdominal visceral hemorrhage, acute nephrosis with casts, multifocal hepatic necrosis, and splenic congestion. PMID:17939361

Portas, Timothy J; Montali, Richard J

2007-09-01

109

Elevations of creatine kinase in patients treated with imatinib mesylate (Gleevec).  

PubMed

Imatinib mesylate is used with increasing frequency and duration for the treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumor (GIST), and other neoplastic conditions. Although muscular complaints are common, elevations of creatine kinase (CK) are listed as <1% in the product label. We describe here a case of rhabdomyolysis likely related to imatinib as well as the results of a prospective evaluation of CK levels in a cohort of patients on imatinib for CML or GIST. We found a high prevalence of CK abnormalities in this group and believe that CKs should be monitored during therapy with imatinib. PMID:19963273

Gordon, Jessica K; Magid, Steven K; Maki, Robert G; Fleisher, Martin; Berman, Ellin

2010-06-01

110

Neuroleptic malignant syndrome in a patient with Parkinson's disease: a case study.  

PubMed

Neuroleptic malignant syndrome (NMS) is a potentially lethal condition that has been described in patients with idiopathic Parkinson's disease (PD) after long-term dopaminergic medications are suddenly stopped or moderately decreased. If patients with PD develop severe rigidity, stupor, and hyperthermia, L-Dopa withdrawal should be suspected and the dopaminergic drug restarted as soon as possible to prevent rhabdomyolysis and renal failure. Nurses who are knowledgeable about NMS can provide prompt identification of the PD patient's condition and prevent a potentially lethal cascade of symptoms. PMID:16001822

Ward, Constance

2005-06-01

111

Statin induced myopathy presenting as mechanical musculoskeletal pain observed in two chiropractic patients  

PubMed Central

Lipid lowering drugs, such as statins, are commonly used to treat approximately 10 million Canadians affected by hypercholesterolemia. The most commonly experienced side-effect of statin medication is muscle pain. Statin induced myopathy consists of a spectrum of myopathic disorders ranging from mild myalgia to fatal rhabdomyolysis. The following is a presentation of 2 cases of statin induced myopathy in patients presenting in a chiropractic setting. In addition, discussion will surround the mechanism, predisposing risk factors and frequency of statin induced myopathy while highlighting the role that chiropractors and other manual therapists may play in its recognition and management. PMID:20195425

Rodine, Robert J; Tibbles, Anthony C; Kim, Peter SY; Alikhan, Neetan

2010-01-01

112

The greater black krait (Bungarus niger), a newly recognized cause of neuro-myotoxic snake bite envenoming in Bangladesh.  

PubMed

Prospective studies of snake bite patients in Chittagong, Bangladesh, included five cases of bites by greater black kraits (Bungarus niger), proven by examination of the snakes that had been responsible. This species was previously known only from India, Nepal, Bhutan and Burma. The index case presented with descending flaccid paralysis typical of neurotoxic envenoming by all Bungarus species, but later developed generalized rhabdomyolysis (peak serum creatine kinase concentration 29,960 units/l) with myoglobinuria and acute renal failure from which he succumbed. Among the other four patients, one died of respiratory paralysis in a peripheral hospital and three recovered after developing paralysis, requiring mechanical ventilation in one patient. One patient suffered severe generalized myalgia and odynophagia associated with a modest increase in serum creatine kinase concentration. These are the first cases of Bungarus niger envenoming to be reported from any country. Generalized rhabdomyolysis has not been previously recognized as a feature of envenoming by any terrestrial Asian elapid snake, but a review of the literature suggests that venoms of some populations of Bungarus candidus and Bungarus multicinctus in Thailand and Vietnam may also have this effect in human victims. To investigate this unexpected property of Bungarus niger venom, venom from the snake responsible for one of the human cases of neuro-myotoxic envenoming was injected into one hind limb of rats and saline into the other under buprenorphine analgesia. All animals developed paralysis of the venom-injected limb within two hours. Twenty-four hours later, the soleus muscles were compared histopathologically and cytochemically. Results indicated a predominantly pre-synaptic action (?-bungarotoxins) of Bungarus niger venom at neuromuscular junctions, causing loss of synaptophysin and the degeneration of the terminal components of the motor innervation of rat skeletal muscle. There was oedema and necrosis of extrafusal muscle fibres in envenomed rat soleus muscles confirming the myotoxic effect of Bungarus niger venom, attributable to phospholipases A?. This study has demonstrated that Bungarus niger is widely distributed in Bangladesh and confirms the risk of fatal neuro-myotoxic envenoming, especially as no specific antivenom is currently manufactured. The unexpected finding of rhabdomyolysis should prompt further investigation of the venom components responsible. The practical implications of having to treat patients with rhabdomyolysis and consequent acute renal failure, in addition to the more familiar respiratory failure associated with krait bite envenoming, should not be underestimated in a country that is poorly equipped to deal with such emergencies. PMID:20855420

Faiz, Abul; Ghose, Aniruddha; Ahsan, Farid; Rahman, Ridwanur; Amin, Robed; Hassan, Mahtab Uddin; Chowdhury, A Wahed; Kuch, Ulrich; Rocha, Thalita; Harris, John B; Theakston, R David G; Warrell, David A

2010-11-01

113

The management of hyperkalaemia in the emergency department  

PubMed Central

Life threatening hyperkalaemia (> 7.0 mmol/l ) is commonly associated with acute renal failure. Moderate hyperkalaemia ( 6.1–6.9 mmol/l ) is also common and well tolerated in patients with chronic renal failure. Renal failure is the most common cause of hyperkalaemia although other causes to consider include drugs (potassium sparing diuretics, angiotensin converting enzyme inhibitors), hyperglycaemia, rhabdomyolysis and adrenal insufficiency. Hyperkalaemia affects the cardiac conducting tissue and can cause serious arrhythmias including ventricular fibrillation and asystolic arrest. Therefore it is important to treat hyperkalaemia promptly in the emergency department. This paper evaluates the therapeutic options available for treatment of hyperkalaemia. PMID:10819381

Ahee, P.; Crowe, A.

2000-01-01

114

 

PubMed Central

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

Dallaire, M; Chamberland, M

1994-01-01

115

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

PubMed

Accidental intra-arterial injection of drugs is a sporadic complication in i.v. drug addicts. A 22-year-old drug-abuser injected flunitrazepam tablets dissolved in tap water into her left femoral artery and presented with clinical signs of acute ischaemia of the left leg. Severe rhabdomyolysis developed within 5 hours after the injection. Selective arterial catheter angiography showed an acute occlusion of the posterior tibial artery. Combination therapy with i.a. urokinase, i.a. prostaglandines and i.v. anticoagulation resulted in re-opening of the obstructed distal artery and complete cessation of symptoms. PMID:19003750

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

2008-11-01

116

Sloughing Esophagitis: A Not So Common Entity  

PubMed Central

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

Akhondi, Hossein

2014-01-01

117

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

PubMed Central

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

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

118

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

PubMed Central

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

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

119

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

PubMed Central

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

Aghabiklooei, Abbas; Edalatparvar, Maryam; Mostafazadeh, Babak

2014-01-01

120

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

PubMed Central

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

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

121

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

PubMed

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 an 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

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

2012-08-01

122

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

PubMed

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

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

2013-07-01

123

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

PubMed Central

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

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

124

An unusual electrical burn caused by alkaline batteries.  

PubMed

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

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

2015-02-01

125

Exertional heat stroke: clinical significance and practice indications for special operations medics and providers.  

PubMed

Exertional heat stroke is an acute injury associated with high morbidity and mortality, and is commonly encountered within military and Special Operations environments. With appropriate planning, rapid diagnosis, and aggressive treatment significant mortality reduction can be obtained. Planning for both training and real world operations can decrease the patient?s morbidity and mortality and increase the chances of successful handling of a patient with exertional heat stroke. The mainstay of treatment is rapid reduction of the core body temperature. This is paramount both at the field level of care as well as in a clinical setting. Diligent surveillance for commonly encountered complications includes anticipating electrolyte abnormalities, rhabdomyolysis, acute renal failure, and hepatic injuries. Treatment with dantrolene may be indicated in patients with continued hyperthermia despite aggressive traditional treatment. PMID:22707019

Johnston, J; Donham, B

2012-01-01

126

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

PubMed

Positioning injuries in the perioperative period are one of the inherent risks of surgery, but particularly in robot-assisted urologic surgery, and can result in often unrecognized morbidity. Injuries such as upper or lower extremity peripheral neuropathies occur via neural mechanisms and injuries such as compartment syndrome, rhabdomyolysis, ischemic optic neuropathy, and acute arterial occlusion occur via vascular mechanisms. The risk of injury may be exacerbated by operative and patient-related risk factors. Patient-related risk factors include ASA class and BMI, while surgery-related risk factors include physical orientation of the patient and operative length. These injuries can be prevented or reduced by joint effort of the surgeon, anesthesiologist, and operating room staff. PMID:24574090

Sukhu, Troy; Krupski, Tracey L

2014-04-01

127

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

PubMed

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

Fujii, K; Iranami, H; Hatano, Y

2011-01-01

128

Extreme Procalcitonin Elevation without Proven Bacterial Infection Related to Amphetamine Abuse  

PubMed Central

Systemic inflammatory response with rhabdomyolysis and consequent multiorgan failure is a known sequela of psychotropic drug abuse. However, in cases with uncertain past medical history the initial diagnosis can be challenging. Here we report the case of a 21-year-old male who was admitted to the intensive care unit with severe neurological impairment caused by amphetamine intoxication. First laboratory investigations revealed extremely high serum procalcitonin (PCT) levels reaching a maximum concentration of 1640?ng/mL on the second day of observation. Although PCT has high sensitivity and specificity in differentiating bacterial sepsis from nonbacterial inflammation, our case report shows for the first time that it can be extremely elevated following serious amphetamine intoxication without bacterial infection. PMID:24826347

Lovas, András; Ágoston, Zsuzsanna; Késmárky, Klára; Hankovszky, Péter; Molnár, Zsolt

2014-01-01

129

Statin induced myotoxicity.  

PubMed

Statins are an effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, myotoxicity induced by statins is a common adverse event and a major barrier to maximising cardiovascular risk reduction. The clinical spectrum of statin induced myotoxicity includes asymptomatic rise in creatine kinase concentration, myalgia, myositis and rhabdomyolysis. In certain cases, the cessation of statin therapy does not result in the resolution of muscular symptoms or the normalization of creatine kinase, raising the possibility of necrotizing autoimmune myopathy. There is increasing understanding and recognition of the pathophysiology and risk factors of statin induced myotoxicity. Careful history and physical examination in conjunction with selected investigations such as creatine kinase measurement, electromyography and muscle biopsy in appropriate clinical scenario help diagnose the condition. The management of statin induced myotoxicity involves statin cessation, the use of alternative lipid lowering agents or treatment regimes, and in the case of necrotizing autoimmune myopathy, immunosuppression. PMID:22560377

Sathasivam, Sivakumar

2012-06-01

130

Statin-associated autoimmune myopathy and anti-HMGCR autoantibodies.  

PubMed

Statins are among the most commonly prescribed medications that significantly reduce cardiovascular risk in selected individuals. However, these drugs can also be associated with muscle symptoms ranging from mild myalgias to severe rhabdomyolysis. Although statin myotoxicity is usually self-limited, in some instances statin-exposed subjects can develop an autoimmune myopathy typically characterized by progressive weakness, muscle enzyme elevations, a necrotizing myopathy on muscle biopsy, and autoantibodies that recognize 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the pharmacologic target of statins. These antibodies are also found in some autoimmune myopathy patients without statin exposure. Importantly, anti-HMGCR antibodies are not found in the vast majority of statin-exposed subjects without autoimmune myopathy, including those with self-limited statin intolerance. Thus, testing for these antibodies may help differentiate those with self-limited statin myopathy who recover after statin discontinuation from those with a progressive statin-associated autoimmune myopathy who typically require immunosuppressive therapy. PMID:23519993

Mohassel, Payam; Mammen, Andrew L

2013-10-01

131

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

PubMed

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

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

2014-01-01

132

Update on toxic myopathies.  

PubMed

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

Mastaglia, F L; Needham, M

2012-02-01

133

Opsoclonus-Myoclonus Syndrome Associated with Mumps Virus Infection  

PubMed Central

Background Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder that is characterized by involuntary eye movements and myoclonus. OMS exhibits various etiologies, including paraneoplastic, parainfectious, toxic-metabolic, and idiopathic causes. The exact immunopathogenesis and pathophysiology of OMS are uncertain. Case Report We report the case of a 19-year-old male who developed opsoclonus and myoclonus several days after a flu-like illness. Serological tests revealed acute mumps infection. The findings of cerebrospinal fluid examinations and brain magnetic resonance imaging were normal. During the early phase of the illness, he suffered from opsoclonus and myoclonus that was so severe as to cause acute renal failure due to rhabdomyolysis. After therapies including intravenous immunoglobulin, the patient gradually improved and had fully recovered 2 months later. Conclusions This is the first report of OMS associated with mumps infection in Korea. Mumps infection should be considered in patients with OMS. PMID:25045383

Kang, Bong-Hui

2014-01-01

134

Evaluation of hypophosphatemia: lessons from patients with genetic disorders  

PubMed Central

Phosphate is a key element for several physiological pathways, such as skeletal development, bone mineralization, membrane composition, nucleotide structure, maintenance of plasma pH, and cellular signaling. The kidneys have a key role in phosphate homeostasis with three hormones playing important roles in renal phosphate handling (i.e., parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1-25 dihydroxy-vitamin D). Independently of the genetic diseases affecting the FGF23 pathway (such as hypophosphatemic rickets), hypophosphatemia is a frequent condition in daily practice, and untreated severe hypophosphatemia can induce hemolysis, rhabdomyolysis, respiratory failure, cardiac dysfunction and neurological impairment, thus requiring a rapid correction to avoid severe complications. The aims of this case report are to summarize the etiologies and the biological evaluation of hypophosphatemia in adults, and to provide an overview of our current understanding of phosphate metabolism. PMID:22075221

Bacchetta, Justine; Salusky, Isidro B

2014-01-01

135

Toxicological Profiles of Poisonous, Edible, and Medicinal Mushrooms  

PubMed Central

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

Jo, Woo-Sik; Hossain, Md. Akil

2014-01-01

136

Management of Crush Syndrome Casualties after Disasters  

PubMed Central

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

Sever, Mehmet Sukru; Vanholder, Raymond

2011-01-01

137

McArdle disease: a case report and review  

PubMed Central

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

Leite, Alberto; Oliveira, Narciso; Rocha, Manuela

2012-01-01

138

Anesthetic considerations in myofibrillar myopathy.  

PubMed

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

Latham, Gregory J; Lopez, Grace

2015-03-01

139

Non-traditional dosing of statins in statin-intolerant patients-is it worth a try?  

PubMed

In this manuscript, three manifestations of statin intolerance will be covered. The first, myopathy, is mostly subjective with variable complaints of myalgias often worsened by exercise, muscle cramping or weakness, and at times associated with a biomarker, elevations in creatine kinase (CK). A rare but serious manifestation can be rhabdomyolysis. The second, liver toxicity, is associated with reversible biochemical increases in transaminases and rarely other liver function tests. Finally, statin-related central nervous system (CNS) toxicity typically defined as cognitive impairment is quite rare and appears to be idiosyncratic. Statin dose alternatives will then be discussed and highlighted in the setting of the new cholesterol-lowering guidelines. Non-statin lipid-altering therapies as well as other alternative therapies will also be reviewed. PMID:25432858

Cornier, Marc-Andre; Eckel, Robert H

2015-02-01

140

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

PubMed

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

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

2014-11-01

141

[Ecstasy--cool dope with long-lasting effects?].  

PubMed

The amphetamine derivative MDMA (3,4-methylenedioxymethamphetamine) was first synthesised in 1914 as an appetite suppressant, but was never used as such. MDMA is commonly known as "ecstasy" and has become a popular recreational drug of abuse at dance-clubs and rave parties, where it is combined with all-night dancing, crowded conditions, poor hydration and loud sound. This combination is probably the main reason why we have seen an upsurge in toxicity problems at rave parties, since all these factors are thought to promote or increase the toxicity of MDMA. The desired effects of MDMA are euphoria, increased energy and enhanced communication with others. Adverse effects are hyperthermia, rhabdomyolysis, acute renal failure, hepatotoxicity, depression and psychosis. PMID:9889612

Liberg, J P; Hovda, K E; Nordby, G; Jacobsen, D

1998-11-20

142

A comprehensive review of MDMA and GHB: two common club drugs.  

PubMed

"Club drugs" have become alarmingly popular. The use of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and gamma-hydroxybutyrate (GHB), in particular, has increased dramatically from 1997-1999. The pharmacokinetics of MDMA and GHB appear to be nonlinear, making it difficult to estimate a dose-response relationship. The drug MDMA is an amphetamine analog with sympathomimetic properties, whereas GHB is a gamma-aminobutyric acid analog with sedative properties. Symptoms of an MDMA toxic reaction include tachycardia, sweating, and hyperthermia. Occasional severe sequelae include disseminated intravascular coagulation, rhabdomyolysis, and acute renal failure. Treatment includes lowering the body temperature and maintaining adequate hydration. Symptoms of GHB intoxication include coma, respiratory depression, unusual movements, confusion, amnesia, and vomiting. Treatment includes cardiac and respiratory support. Because of the popularity of these agents and their potentially dangerous effects, health care professionals must be familiar with these substances and the treatment options for patients who present with symptoms of a toxic reaction. PMID:11765302

Teter, C J; Guthrie, S K

2001-12-01

143

Heat illness in the emergency department: keeping your cool.  

PubMed

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

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

2014-08-01

144

Heat-related illness in sports and exercise.  

PubMed

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

Nichols, Andrew W

2014-12-01

145

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

PubMed Central

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

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

2014-01-01

146

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

PubMed Central

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

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

2014-01-01

147

Excited delirium: Consideration of selected medical and psychiatric issues  

PubMed Central

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

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

2009-01-01

148

Acute Kidney Injury in HIV- Infected Patients  

PubMed Central

Acute kidney injury is common in HIV-infected patients, and has been associated with increased morbidity and mortality. Prior to the introduction of effective antiretroviral therapy, acute kidney injury in HIV-positive patients was most commonly the result of volume depletion, septicemia, or nephrotoxic medications. Acute kidney injury remains a significant problem in the antiretroviral era, and is still commonly attributed to infection or nephrotoxic medications. Less common causes such as direct infectious insults, immune restoration inflammatory syndrome, rhabdomyolysis, and obstruction should be considered when the underlying process is not obvious. In addition to advanced HIV disease, several other patient characteristics have emerged as potential risk factors for acute kidney injury in the antiretroviral era, including older age, diabetes, pre-existing chronic kidney disease, and hepatitis co-infection or liver disease. PMID:19013326

Kalim, Sahir; Szczech, Lynda A.; Wyatt, Christina M.

2008-01-01

149

Chinese Herbal Medicine on Dyslipidemia: Progress and Perspective  

PubMed Central

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

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

2014-01-01

150

Paraphenylene diamine ingestion: an uncommon cause of acute renal failure.  

PubMed

Paraphenylene diamine (PPD) is a major component of hair dyes. The aim is to study the renal manifestations and outcome of PPD consumption. During a four-year period from 2002 to February 2006, 10 persons were admitted to our Institute after consuming a hair dye in a suicidal bid. The percentage of ARF due to PPD at our Institute was 0.95%. Seven patients out of 10 (70%) who consumed PPD developed ARF. All 10 patients, including the patients who had normal renal function had features of rhabdomyolysis. Two patients required ventilator support for respiratory distress and two more required tracheostomy due to upper airway tract edema. One patient has expired after two sessions of dialysis. Renal biopsy in two patients (one, postmortem) showed acute tubular necrosis along with presence of casts in tubules due to myoglobin. PMID:17699992

Ram, R; Swarnalatha, G; Prasad, N; Dakshinamurty, K V

2007-01-01

151

Diagnosis of mitochondrial myopathies.  

PubMed

Mitochondria are ubiquitous organelles and play crucial roles in vital functions, most importantly, the oxidative phosphorylation and energy metabolism. Therefore, mitochondrial dysfunction can affect multiple tissues, with muscle and nerve preferentially affected. Mitochondrial myopathy is a common clinical phenotype, which is characterized by early fatigue and/or fixed muscle weakness; rhabdomyolysis can seldom occur. Muscle biopsy often identifies signs of diseased mitochondria by morphological studies, while biochemical analysis may identify respiratory chain deficiencies. The clinical, morphological and biochemical data guide molecular analysis. Being the mitochondrial function under the control of both mitochondrial DNA and nuclear DNA, the search for mitochondrial DNA mutations and mitochondrial DNA quantitation, may not be sufficient for the molecular diagnosis of mitochondrial myopathies. Approximately 1500 nuclear genes can affect mitochondrial structure and function and the targeting of such genes may be necessary to reach the diagnosis. The identification of causative molecular defects in nuclear or mitochondrial genome leads to the definite diagnosis of mitochondrial myopathy. PMID:23911206

Milone, Margherita; Wong, Lee-Jun

2013-01-01

152

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

PubMed Central

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

Boucree, Michael C.

1988-01-01

153

Mass envenomations by honey bees and wasps.  

PubMed Central

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

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

1999-01-01

154

Pemphigus erythematosus relapse associated with atorvastatin intake  

PubMed Central

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

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

2014-01-01

155

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

PubMed Central

Background Crohn’s disease is a relapsing, systemic inflammatory disease affecting the gastrointestinal tract with associated extraintestinal manifestations and immune disorders. Among the few cases reported, the association of Crohn’s disease with polymyositis varies in its complexity and severity. We report here the first known case of inflammatory polymyositis leading to rhabdomyolysis in a male patient diagnosed with Crohn’s ileocolitis. Case presentation A 42-year-old previously healthy man presented with acute polymyositis leading to rhabdomyolysis. The acute nature of the illness raised the suspicion of an infective, toxic, or metabolic insult, which was excluded during further investigations. Prolonged low-grade fever and raised inflammatory markers led to the suspicion of inflammatory polymyositis, which was confirmed by electromyography and muscle histology. In the absence of an infective cause, the concurrent association of prolonged diarrhea containing blood and mucous after recovery from an acute phase of myositis proved a diagnostic challenge. Ileocolonoscopy findings of extensive aphthous ulceration with skip lesions extending to the terminal ileum, and histology showing polymorph infiltration of the lamina propria, transmural involvement, and micro abscess formation was suggestive of Crohn’s disease. Sensory motor axonal peripheral neuropathy, which is another rare association of inflammatory bowel disease, was also present. Conclusion An unrecognized genetic predisposition or altered gut permeability causing disruption of the gut immune barrier triggering an immune response against skeletal muscles may have contributed to this unique association. Both polymyositis and Crohn’s ileocolitis responded well to corticosteroids and azathioprine, which is supportive of their immune pathogenesis. Myositis can be considered to be a rare extraintestinal manifestation of Crohn’s disease and can be used in the differential diagnosis of corticosteroid or hypokalemia-induced myopathy in Crohn’s disease. PMID:24552185

2014-01-01

156

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

PubMed Central

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

2013-01-01

157

Nephrotoxic effects of common and emerging drugs of abuse.  

PubMed

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

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

2014-11-01

158

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

PubMed

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

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

2012-03-01

159

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

PubMed Central

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

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

2014-01-01

160

No evident association between efavirenz use and suicidality was identified from a disproportionality analysis using the FAERS database  

PubMed Central

Objective To assess the potential association of selected antiretrovirals (ARVs), including efavirenz, with suicidality. Design Retrospective analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS), by performing a Multi-Item Gamma Poisson Shrinker (MGPS) disproportionality analysis. Methods MGPS disproportionality analysis, a technique to identify associations between drugs and adverse events, was performed using cumulative data from the FAERS database collected up to August 2012. This method yields an Empirical Bayesian Geometric Mean score and corresponding 90% confidence interval (EB05, EB95). EB05 scores ?2 were pre-defined as a signal for a potential drug-event association. The FAERS database includes spontaneous adverse-event reports from consumers and healthcare professionals. All FAERS reports of suicidality (including suicidal ideation, suicide attempt and completed suicide or a composite of these) in patients taking efavirenz (as single agent or in fixed-dose combination), atazanavir, darunavir, etravirine, nevirapine and raltegravir were identified. A number of parallel analyses were performed to assess the validity of the methodology: fluoxetine and sertraline, antidepressants with a known association with suicidality, and raltegravir, an ARV with rhabdomyolysis and myopathy listed as “uncommon” events in the US-prescribing information. Results A total of 29,856 adverse event reports were identified among patients receiving efavirenz, atazanavir, darunavir, etravirine, nevirapine and raltegravir, of which 457 were reports of suicidality events. EB05 scores observed for the composite suicidality term for efavirenz (EB05=0.796), and other ARVs (EB05=0.279–0.368), were below the pre-defined threshold. Fluoxetine and sertraline gave EB05 scores for suicidality >2. Raltegravir gave EB05 scores >2 for myopathy and rhabdomyolysis. Conclusions The pre-determined threshold for signals for suicidality, including suicidal ideation, suicide attempt, completed suicide and a composite suicidality endpoint, was not exceeded for efavirenz and other ARVs in this analysis. Efavirenz has been associated with suicidality in clinical trials. Further studies that adjust for confounding factors are needed to better understand any potential association with ARVs and suicidality. PMID:25192857

Napoli, Andrew A; Wood, Jennifer J; Coumbis, John J; Soitkar, Amit M; Seekins, Daniel W; Tilson, Hugh H

2014-01-01

161

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

PubMed

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

Bush, S P; Siedenburg, E

1999-01-01

162

Clinical and forensic signs related to cocaine abuse.  

PubMed

Good laboratory practice in toxicological analysis requires pre-analytical steps for collection of detailed information related to the suspected poisoning episodes, including biological and non-biological circumstantial evidences, which should be carefully scrutinized. This procedure provides great help to unveil the suspected cause of poisoning, to select the appropriate and correct samples to be analyzed and can facilitate the decision about the analytical techniques to perform. This implies a good knowledge of the signs related to acute and chronic intoxications by drugs of abuse. In this manuscript we highlight and discuss clinical and forensic imaging related to cocaine abuse, namely the midline destructive lesion, dental health, pseudoscleradermatous triad and crack hands, necrosis and gangrene of extremities and several other skin manifestations, reticular purpura, intracerebral and peripheral hemorrhages, angioneurotic edema, rhabdomyolysis, and crack lung. For this purpose, the state of the art on this topic is discussed, using clinical and forensic cases from our professional database in complement to images and mechanistic data from literature. PMID:22280333

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

2012-03-01

163

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

PubMed

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

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

2014-10-01

164

Acute liver damage and ecstasy ingestion.  

PubMed Central

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

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

1996-01-01

165

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

PubMed

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

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

2011-06-01

166

Metformin induced severe hypophosphatemia in a patient on hemodialysis.  

PubMed

A 67-year-old diabetic and hypertensive woman presented to us with very low serum phosphate levels (PO?? =1.1 mg/dL) about 40 days after initiation of hemodialysis (HD). The phosphate binders were discontinued, because they were thought to be the cause of hypophosphatemia. However, the serum phosphate levels continued to remain low during subsequent follow-up visits over one month (PO???? = 0.7 and 0.6 mg/dL respectively). The patient had been started on metformin hydrochloride (850 mg thrice a day) about 18 days after the beginning of HD. The drug was stopped immediately (approximately 50 days after it was started) and the serum phosphate levels increased progressively, reaching 4.3 mg/dL. During the period with hypophosphatemia, the patient suffered from very intense fatigue and weakness (she was unable to walk), anorexia, diarrhea and tenesmus. There were no features suggestive of rhabdomyolysis, hemolysis, low blood pressure or hypoglycemia; she had low white blood cell and platelet counts. The patient was in good clinical condition 2-3 days after the discontinuation of metformin and she recovered totally 15 days later. This case is presented due to its rarity as well as the observation that despite the patient having severe hypophosphatemia, she showed only side effects of metformin. Hypophosphatemia caused only intense fatigue and no other symptoms. PMID:20814133

Tsitsios, Tilemachos; Sotirakopoulos, Nikolaos; Armentzioiou, Karmen; Kalogiannidou, Irini; Kolaggis, Alexandros; Mavromatidis, Konstantinos

2010-09-01

167

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

PubMed Central

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

2013-01-01

168

Novel influenza A (H1N1) virus-induced hemophagocytosis: first case reported in Saudi Arabia.  

PubMed

H1N1 is a novel subtype of the influenza A virus. Since its reemergence in 2008, it has been reported to cause a variety of illnesses ranging from mild flu-like symptoms to severe multiorgan failure. We report a case of a young immunocompetent man who presented with progressive shortness of breath and rapidly developed multiorgan dysfunction, including pancytopenia from H1N1 infection during the 2010-2011 influenza season. His H1N1 pneumonia caused severe acute respiratory distress syndrome, respiratory failure requiring mechanical ventilation, rhabdomyolysis, myocarditis, hepatitis, encephalitis, and renal failure. During the diagnostic workup, a bone marrow biopsy was performed, showing hemophagocytosis secondary to the H1N1 infection. Unfortunately the patient died despite aggressive measures. Published reports contain only a few records of H1N1-induced hemophagocytosis. This is the first case report from Saudi Arabia with H1N1-induced secondary hemophagocytosis. It also highlights the fact that the virus is still very virulent and will pose a major annual health risk along with the seasonal influenza for at least the next few years. PMID:22156644

Ur Rehman, Jalil; Wali, Ghassan; Sayes, Najla M; Maulawi, Abdulghani; Aslam, Mohammad; Khalid, Imran

2012-01-01

169

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

PubMed

In São Paulo State, Brazil, five males, aged between 8 and 64 years, were attacked by 'Africanized' honey bees (Apis mellifera scutellata). The estimated number of stings received by each patient ranged from > 200 to > 1000. All five were transferred to intensive care units in São Paulo City. Clinical features included intravascular haemolysis, respiratory distress with ARDS, hepatic dysfunction, rhabdomyolysis (with myoglobinaemia and myoglobinuria), hypertension and myocardial damage (perhaps explained by release of endogenous catecholamines by venom phospholipase A2 and mellitin), shock, coma, acute renal failure and bleeding. Laboratory findings included gross neutrophil leucocytosis, elevated serum enzymes [AST, ALT, LDH, CPK (predominantly CPK-MM)] and creatinine. Clotting times were slightly prolonged. Despite treatment with antihistamines, corticosteroids, bronchodilators, vasodilators, bicarbonate, mannitol and mechanical ventilation, three of the patients died between 22 and 71 h after the attacks, with histopathological features of ARDS, hepatocellular necrosis, acute tubular necrosis, focal subendocardial necrosis and disseminated intravascular coagulation. Whole bee venom and phospholipase A2 (PLA2) antigen concentrations were measured in serum and urine for the first time, using enzyme immunoassay. High venom and PLA2 concentrations were detected in serum and urine for more than 50 h after the stings in two fatal cases, in one of which the total circulating unbound whole venom was estimated at 27 mg, one hour after the attack. An antivenom should be developed to treat the increasing numbers of victims of mass attacks by Africanized 'killer' bees in USA, Middle and South America. PMID:7938407

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

1994-05-01

170

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

PubMed

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

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

2014-03-01

171

Rapidly reversible multiorgan failure after ingestion of “Molly” (pure 3,4-methylenedioxymethamphetamine): a case report  

PubMed Central

Introduction “Molly” is a street name for pure 3,4-methylenedioxymethamphetamine, an amphetamine derivative which acts by enhancing the release of neurotransmitters such as serotonin, dopamine and norepinephrine. This produces euphoria, increased sensory awareness and central stimulation that make it a popular club drug. Nevertheless, it is also associated with serious side effects. We report an unusual case of rapid multiorgan failure after ingestion of “Molly”. Unlike previously described patterns of 3,4-methylenedioxymethamphetamine-related organ failure, our case does not appear to be related to hyperthermia, rhabdomyolysis or hyponatremia. Case presentation A 24-year-old Hispanic man presented to our hospital with an episode of seizure and subsequently developed acute kidney injury, respiratory failure requiring mechanical ventilation and congestive heart failure after ingestion of “Molly”. He rapidly recovered with supportive care and was discharged home. Conclusions The spectrum of complications associated with 3,4-methylenedioxymethamphetamine is wide and patient presentation may vary. Moreover, there appears to be multiple mechanisms involved in organ failure. Drug toxicity should be suspected while evaluating a patient with multisystem organ failure of unclear etiology. Treatment is generally supportive sometimes requiring mechanical ventilation and hemodialysis. Nevertheless, complete reversal of organ failure can be expected. PMID:24942782

2014-01-01

172

[Necrotizing autoimmune myopathies].  

PubMed

Necrotizing autoimmune myopathies are included in the spectrum of inflammatory myopathies, together with polymyosis, dermatopolymyosis and inclusion body myositis, despite the characteristic feature of marked muscular necrosis without inflammatory infiltrates. The clinical presentation is highly variable, often similar to the other inflammatory myopathies. The most common finding is nevertheless the severe form with rhabdomyolysis. The creatine kinase level is elevated (around 10,000IU/l) and electromyography shows myopathic changes with increased spontaneous activities reflecting the importance of the muscular necrosis. Muscle biopsy is required for diagnosis, revealing active necrosis of the muscle fibers without inflammatory invasion by CDA+ or CD8+ T-cells. Deposition of a microvascular membrane attack complex (C5b9) is often noted, whereas the upregulation of MHC class 1 is rarely detected. Signs of endomysial microangiopathy are frequently reported. Necrotizing autoimmune myopathies can be associated with antisignal recognition particle (SRP) antibodies or more rarely with the usual inflammatory myopathy antibodies. Paraneoplasic forms are described but remain exceptional. Lastly, necrotizing autoimmune myopathies, sometimes associated with statin therapy, have been recently described. They are linked with an antibody directed against 3-hydroxy-3-methyglutaryl-coenzyme A. Treatment is based on corticosteroid therapy, immunosuppressive drugs or intravenous immunoglobulins. Response is variable, depending on the clinical form. PMID:23999024

Petiot, P; Choumert, A; Hamelin, L; Devic, P; Streichenberger, N

2013-01-01

173

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

PubMed Central

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.

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

2014-01-01

174

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

PubMed Central

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

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

2014-01-01

175

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

PubMed

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

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

2014-12-01

176

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

PubMed

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

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

2014-08-01

177

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

PubMed

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

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

2014-03-01

178

Statin Pharmacogenomics: Opportunities to Improve Patient Outcomes and Healthcare Costs with Genetic Testing  

PubMed Central

HMG-CoA reductase inhibitors, commonly known as statins, are some of the most widely prescribed medications worldwide and have been shown to be effective at lowering cholesterol in numerous long-term prospective trials, yet there are significant limitations to their use. First, patients receiving statin therapy have relatively low levels of medication adherence compared with other drug classes. Next, numerous statin formulations are available, each with its own unique safety and efficacy profile, and it may be unclear to prescribers which treatment is optimal for their patients. Finally, statins have class-wide side effects of myopathy and rhabdomyolysis that have resulted in a product recall and dosage limitations. Recent evidence suggests that two genomic markers, KIF6 and SLCO1B1, may inform the therapy choice of patients initiating statins. Given the prevalence of statin usage, their potential health advantages and their overall cost to the healthcare system, there could be significant clinical benefit from creating personalized treatment regimens. Ultimately, if this approach is effective it may encourage higher adoption of generic statins when appropriate, promote adherence, lower rates of myopathy, and overall achieve higher value cardiovascular care. This paper will review the evidence for personalized prescribing of statins via KIF6 and SLCO1B1 and consider some of the implications for testing these markers as part of routine clinical care.

Canestaro, William J.; Brooks, David G.; Chaplin, Donald; Choudhry, Niteesh K.; Lawler, Elizabeth; Martell, Lori; Brennan, Troyen; Wassman, E. Robert

2012-01-01

179

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

PubMed

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

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

2014-07-01

180

Club drugs: MDMA, gamma-hydroxybutyrate (GHB), Rohypnol, and ketamine.  

PubMed

Club drugs are substances commonly used at nightclubs, music festivals, raves, and dance parties to enhance social intimacy and sensory stimulation. The most widely used club drugs are 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy; gamma-hydroxybutyrate (GHB); flunitrazepam (Rohypnol); and ketamine (Ketalar). These drugs are popular because of their low cost and convenient distribution as small pills, powders, or liquids. Club drugs usually are taken orally and may be taken in combination with each other, with alcohol, or with other drugs. Club drugs often are adulterated or misrepresented. Any club drug overdose should therefore be suspected as polydrug use with the actual substance and dose unknown. Persons who have adverse reactions to these club drugs are likely to consult a family physician. Toxicologic screening generally is not available for club drugs. The primary management is supportive care, with symptomatic control of excess central nervous system stimulation or depression. There are no specific antidotes except for flunitrazepam, a benzodiazepine that responds to flumazenil. Special care must be taken for immediate control of hyperthermia, hypertension, rhabdomyolysis, and serotonin syndrome. Severe drug reactions can occur even with a small dose and may require critical care. Club drug over-dose usually resolves with full recovery within seven hours. Education of the patient and family is essential. PMID:15202696

Gahlinger, Paul M

2004-06-01

181

[Abuse of Ecstasy (3,4-methylenedioxymethamphetamine). Pharmacological, neuropsychiatric and behavioral aspects].  

PubMed

Ecstasy (3,4-methylenedioxymethamphetamine) is a popular recreational drug, a "designer drug", which has been developed from the basic structure in amphetamine. Ecstasy has now reached the illegal drug market in Denmark via the US, Great Britain and Sweden. The drug is related to a certain youth culture from which it is estimated that many drug abusers have been recruited. The desired effects of ecstasy, namely enhanced openness, awareness and empathy, have previously been used in various therapeutic connections. In later years the drug has led to abuse which, in connection with certain cultural behaviour patterns (for example in discotheques), can cause dangerous psychiatric as well as somatic effects. The undesirable psychiatric effects range from fear through depression to actual psychoses, and the somatic effects vary from symptoms of increased sympathetic activity to malignant hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, renal failure, and lethal hepatotoxicity. The last mentioned symptoms occur in connection with prolonged physical activities such as exhausting dancing sessions. The article discusses the available treatments for conditions of abuse and stresses the need for prophylactic efforts in the form of information and awareness of the problem. PMID:7701630

Nielsen, J C; Nicholson, K; Pitzner-Jørgensen, B L; Undén, M

1995-02-01

182

Metabolic neuropathies and myopathies.  

PubMed

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

D'Amico, Adele; Bertini, Enrico

2013-01-01

183

Clinical toxicology: a tropical Australian perspective.  

PubMed

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

Currie, B J

2000-02-01

184

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

PubMed

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

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

2013-01-01

185

Rare complications of pediatric diabetic ketoacidosis  

PubMed Central

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.

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

2015-01-01

186

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

PubMed Central

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

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

2010-01-01

187

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

PubMed

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

Zhao, Xuesheng; Song, Qing; Gao, Yan

2014-11-01

188

Illnesses and deaths among persons attending an electronic dance-music festival - new york city, 2013.  

PubMed

Outdoor electronic dance-music festivals (EDMFs) are typically summer events where attendees can dance for hours in hot temperatures. EDMFs have received increased media attention because of their growing popularity and reports of illness among attendees associated with recreational drug use. MDMA (3,4-methylenedioxymethamphetamine) is one of the drugs often used at EDMFs. MDMA causes euphoria and mental stimulation but also can cause serious adverse effects, including hyperthermia, seizures, hyponatremia, rhabdomyolysis, and multiorgan failure. In this report, MDMA and other synthetic drugs commonly used at dance festivals are referred to as "synthetic club drugs." On September 1, 2013, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) received reports of two deaths of attendees at an EDMF (festival A) held August 31-September 1 in NYC. DOHMH conducted an investigation to identify and characterize adverse events resulting in emergency department (ED) visits among festival A attendees and to determine what drugs were associated with these adverse events. The investigation identified 22 cases of adverse events; nine cases were severe, including two deaths. Twenty-one (95%) of the 22 patients had used drugs or alcohol. Of 17 patients with toxicology testing, MDMA and other compounds were identified, most frequently methylone, in 11 patients. Public health messages and strategies regarding adverse health events might reduce illnesses and deaths at EDMFs. PMID:25522087

Ridpath, Alison; Driver, Cynthia R; Nolan, Michelle L; Karpati, Adam; Kass, Daniel; Paone, Denise; Jakubowski, Andrea; Hoffman, Robert S; Nelson, Lewis S; Kunins, Hillary V

2014-12-19

189

McArdle disease: a unique study model in sports medicine.  

PubMed

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

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

2014-11-01

190

Emergent hip arthroscopy: life-saving intervention for septic hip and secondary multiorgan failure.  

PubMed

This article describes the case of a 27-year-old female athletic trainer who presented to the emergency department in acute renal failure with rhabdomyolysis and disseminated intravascular coagulation following a brief onset of right hip pain and staphylococcal facial infection. Despite the absence of fever, peripheral leukocytosis, or organisms on gram stain from emergent joint aspiration, magnetic resonance imaging revealed a large hip effusion; a presumptive diagnosis of septic hip was made. Emergent hip arthroscopy was performed in the middle of the night within 3 hours of presentation. Minimally invasive, high-volume irrigation and debridement was rapidly performed using dual-portal arthroscopy. Although this approach required prolonged critical respiratory and hemodynamic support, the patient recovered from a life-threatening situation not often seen by arthroscopic or sports medicine surgeons. The unusual diagnosis of staphylococcal hip sepsis with multifocal dissemination was established, as was an atypical but important indication for emergent hip arthroscopy. Although generally implemented to improve quality of life, this case represents the use of hip arthroscopy to increase its quantity as well. Hip arthroscopy may have an emergent indication with life-saving potential. PMID:22784906

Matsuda, Dean K; Calipusan, Charito P

2012-07-01

191

Neuroleptic malignant syndrome from central nervous system insult: 4 cases and a novel treatment strategy. Clinical article.  

PubMed

Neuroleptic malignant syndrome (NMS) is a potentially life-threatening entity characterized by hyperthermia, autonomic deregulation, decreased mental status, increased muscle tone, and, frequently, by renal failure due to rhabdomyolysis. Classically, it follows administration of antipsychotic medication. The authors report on 4 patients (2 children and 2 adults) in whom NMS was diagnosed after a CNS insult. No patient was receiving antipsychotic medication. The patients' hospital and clinic charts, radiographic data, and follow-up telephone conversations were reviewed retrospectively. All 4 patients met diagnostic criteria for NMS. Three patients presented with shunt failure, and 1 patient had undergone a functional hemispherectomy 2 days earlier. One patient with shunt failure received the diagnosis retrospectively. An endoscopic third ventriculostomy alleviated his shunt failure and he remains free of NMS. The other 2 patients underwent treatment for shunt failure, but NMS remained. These 2 patients and the one who had undergone hemispherectomy underwent a trial of intrathecal baclofen, and the NMS resolved. Subsequently, an intrathecal baclofen infusion device was placed in all 3 patients, and the NMS resolved. The 2 patients in shunt failure had a lumbar intrathecal baclofen infusion device. The patient who had undergone hemispherectomy had an intracranial baclofen catheter. Neuroleptic malignant syndrome is a rare, life-threatening disorder that can occur without the administration of neuroleptic medications. Alleviation of any CNS insult is the first order of treatment. Some patients with persistent symptoms of NMS may benefit from intrathecal delivery of baclofen. PMID:19772404

Wait, Scott D; Ponce, Francisco A; Killory, Brendan D; Wallace, Donna; Rekate, Harold L

2009-09-01

192

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

PubMed

McArdle disease is caused by an inherited deficiency of the enzyme myophosphorylase, resulting in exercise intolerance from childhood and acute crises of early fatigue and contractures. In severe cases, these manifestations can be accompanied by rhabdomyolysis, myoglobinuria, and fatal renal failure. Diagnosis of McArdle disease is based on clinical diagnostic tests, together with an absence of myophosphorylase activity in skeletal muscle biopsies and genetic analysis of the myophosphorylase-encoding gene, PYGM. The recently reported association between myophosphorylase and Rac1 GTPase in a T lymphocyte cell line prompted us to study myophosphorylase expression in white blood cells (WBCs) from 20 healthy donors and 30 McArdle patients by flow cytometry using a fluorescent-labeled PYGM antibody. We found that T lymphocytes expressed myophosphorylase in healthy donors, but expression was significantly lower in McArdle patients (p<0.001). PYGM mRNA levels were also lower in white blood cells from McArdle patients. Nevertheless, in 13% of patients (who were either heterozygotes or homozygotes for the most common PYGM pathogenic mutation among Caucasians (p.R50X)), the percentage of myophosphorylase-positive white blood cells was not different compared with the control group. Our findings suggest that analysis of myophosphorylase expression in white blood cells might be a useful, less-invasive, complementary test for diagnosing McArdle disease. PMID:25240406

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

2014-12-01

193

Narrative review: the systemic capillary leak syndrome.  

PubMed

The systemic capillary leak syndrome (SCLS) is a rare disease of reversible plasma extravasation and vascular collapse accompanied by hemoconcentration and hypoalbuminemia. Its cause is unknown, although it is believed to be a manifestation of transient endothelial dysfunction due to endothelial contraction, apoptosis, injury, or a combination of these. Fewer than 150 cases of SCLS have been reported, but the condition is probably underrecognized because of its nonspecific symptoms and signs and high mortality rate. Patients experience shock and massive edema, often after a nonspecific prodrome of weakness, fatigue, and myalgias, and are at risk for ischemia-induced organ failure, rhabdomyolysis and muscle compartment syndromes, and venous thromboembolism. Shock and edema reverse almost as quickly as they begin, at which time patients are at risk for death from flash pulmonary edema during rapid fluid remobilization. Diagnosis is made clinically and by exclusion of other diseases that cause similar symptoms and signs, most notably sepsis, anaphylaxis, and angioedema. Acute episodes are treated with vasopressor therapy and judicious fluid replacement, possibly with colloid solutions for their osmotic effects, to prevent the sequelae of underperfusion. Between episodes, patients may be treated with theophylline and terbutaline, which clinical experience suggests may reduce the severity and frequency of acute episodes. Prognosis is uncertain, but patients who survive an initial severe SCLS episode are estimated to have a 10-year survival rate greater than 70%. Much remains to be learned about SCLS, and clinicians should consider the diagnosis in patients with unexplained edema, increased hematocrit, and hypotension. PMID:20643990

Druey, Kirk M; Greipp, Philip R

2010-07-20

194

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

PubMed

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

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

2014-01-01

195

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

PubMed

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

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

2012-09-01

196

Rare complications of pediatric diabetic ketoacidosis.  

PubMed

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

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

2015-02-15

197

Bacterial, Fungal, Parasitic, and Viral Myositis  

PubMed Central

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

Crum-Cianflone, Nancy F.

2008-01-01

198

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

PubMed Central

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

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

2014-01-01

199

Prostatic surgery associated acute kidney injury  

PubMed Central

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

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

2014-01-01

200

Muscular damage during telbivudine treatment in a chronic hepatitis B patient  

PubMed Central

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

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

2011-01-01

201

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

PubMed

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

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

2011-04-01

202

[Crush syndrome in severe trauma].  

PubMed

Crush injury or traumatic rhabdomyolysis is caused by crushing of large muscule mass, usually of the femoral and gluteal compartment. Crush syndrome is general manifestation of crush injury with renal failure (ARF). ARF is caused by deposition of myoglobin in distal tubules. The concentration of serum creatin phosphokinase is an indicator of the extent of injured muscule. The serum concentration of myoglobin is an indicator of the extent of injured muscule and the main cause of development of crush syndrome. In a prospective study the concentration of myoglobin and CPK was measured in 81 patients with injuries of lower extremities and pelvis as a part of severe trauma. The increase of CPK concentration above 1000 U/L was measured in all patients. The increase of CPK concentration above 2000 U/L was measured in 78 (96.3%) patients. The increase of myoglobin concentration of >700 mcg/L was measured in 19 (23.5%) patients. In the group of 19 patients with CPK concentration of >2000 U/L and myoglobin concentration of >700 mcg/L crush syndrome developed in 6 (7.4%) patients with oliguria (urin output <50 ml/h) and the increase of serum potassium, phosphate and creatinine concentrations. The decrease of CPK and myoglobin concentrations was achieved in 5 patients during 10-12 days and 1 patient with associated craniocrebral injury died. PMID:18283895

Poznanovi?, Marija Rakari?; Sulen, Nina

2007-01-01

203

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

PubMed

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

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

2014-08-01

204

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

PubMed Central

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

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

2013-01-01

205

Inborn errors of cytoplasmic triglyceride metabolism.  

PubMed

Triglyceride (TG) synthesis, storage, and degradation together constitute cytoplasmic TG metabolism (CTGM). CTGM is mostly studied in adipocytes, where starting from glycerol-3-phosphate and fatty acyl (FA)-coenzyme A (CoA), TGs are synthesized then stored in cytoplasmic lipid droplets. TG hydrolysis proceeds sequentially, producing FAs and glycerol. Several reactions of CTGM can be catalyzed by more than one enzyme, creating great potential for complex tissue-specific physiology. In adipose tissue, CTGM provides FA as a systemic energy source during fasting and is related to obesity. Inborn errors and mouse models have demonstrated the importance of CTGM for non-adipose tissues, including skeletal muscle, myocardium and liver, because steatosis and dysfunction can occur. We discuss known inborn errors of CTGM, including deficiencies of: AGPAT2 (a form of generalized lipodystrophy), LPIN1 (childhood rhabdomyolysis), LPIN2 (an inflammatory condition, Majeed syndrome, described elsewhere in this issue), DGAT1 (protein loosing enteropathy), perilipin 1 (partial lipodystrophy), CGI-58 (gene ABHD5, neutral lipid storage disease (NLSD) with ichthyosis and "Jordan's anomaly" of vacuolated polymorphonuclear leukocytes), adipose triglyceride lipase (ATGL, gene PNPLA2, NLSD with myopathy, cardiomyopathy and Jordan's anomaly), hormone-sensitive lipase (HSL, gene LIPE, hypertriglyceridemia, and insulin resistance). Two inborn errors of glycerol metabolism are known: glycerol kinase (GK, causing pseudohypertriglyceridemia) and glycerol-3-phosphate dehydrogenase (GPD1, childhood hepatic steatosis). Mouse models often resemble human phenotypes but may diverge markedly. Inborn errors have been described for less than one-third of CTGM enzymes, and new phenotypes may yet be identified. PMID:25300978

Wu, Jiang Wei; Yang, Hao; Wang, Shu Pei; Soni, Krishnakant G; Brunel-Guitton, Catherine; Mitchell, Grant A

2015-01-01

206

Integration of Biosensors and Drug Delivery Technologies for Early Detection and Chronic Management of Illness  

PubMed Central

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

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

207

Quantitative Structure Activity Relationship for Inhibition of Human Organic Cation/Carnitine Transporter (OCTN2)  

PubMed Central

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

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

2010-01-01

208

Integration of biosensors and drug delivery technologies for early detection and chronic management of illness.  

PubMed

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

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

209

Harmonization process for the identification of medical events in eight European healthcare databases: the experience from the EU-ADR project  

PubMed Central

Objective Data from electronic healthcare records (EHR) can be used to monitor drug safety, but in order to compare and pool data from different EHR databases, the extraction of potential adverse events must be harmonized. In this paper, we describe the procedure used for harmonizing the extraction from eight European EHR databases of five events of interest deemed to be important in pharmacovigilance: acute myocardial infarction (AMI); acute renal failure (ARF); anaphylactic shock (AS); bullous eruption (BE); and rhabdomyolysis (RHABD). Design The participating databases comprise general practitioners’ medical records and claims for hospitalization and other healthcare services. Clinical information is collected using four different disease terminologies and free text in two different languages. The Unified Medical Language System was used to identify concepts and corresponding codes in each terminology. A common database model was used to share and pool data and verify the semantic basis of the event extraction queries. Feedback from the database holders was obtained at various stages to refine the extraction queries. Measurements Standardized and age specific incidence rates (IRs) were calculated to facilitate benchmarking and harmonization of event data extraction across the databases. This was an iterative process. Results The study population comprised overall 19?647?445 individuals with a follow-up of 59?929?690 person-years (PYs). Age adjusted IRs for the five events of interest across the databases were as follows: (1) AMI: 60–148/100?000 PYs; (2) ARF: 3–49/100?000 PYs; (3) AS: 2–12/100?000 PYs; (4) BE: 2–17/100?000 PYs; and (5) RHABD: 0.1–8/100?000 PYs. Conclusions The iterative harmonization process enabled a more homogeneous identification of events across differently structured databases using different coding based algorithms. This workflow can facilitate transparent and reproducible event extractions and understanding of differences between databases. PMID:22955495

Avillach, Paul; Coloma, Preciosa M; Gini, Rosa; Schuemie, Martijn; Mougin, Fleur; Dufour, Jean-Charles; Mazzaglia, Giampiero; Giaquinto, Carlo; Fornari, Carla; Herings, Ron; Molokhia, Mariam; Pedersen, Lars; Fourrier-Réglat, Annie; Fieschi, Marius; Sturkenboom, Miriam; van der Lei, Johan; Pariente, Antoine; Trifirò, Gianluca

2013-01-01

210

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

PubMed Central

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

2011-01-01

211

The determinants of transverse tubular volume in resting skeletal muscle  

PubMed Central

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

Sim, Jingwei; Fraser, James A

2014-01-01

212

The determinants of transverse tubular volume in resting skeletal muscle.  

PubMed

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

Sim, Jingwei; Fraser, James A

2014-12-15

213

Muscle- and skeletal-related side-effects of statins: tip of the iceberg?  

PubMed

The clinical spectrum of muscle- and skeletal-related side-effects of statins includes varied myalgias and weakness, an asymptomatic increase in the concentration of creatine kinase and other biochemical parameters, myositis and rhabdomyolysis. Currently, there is no consensus on the definition of 'statin myopathy'. Evidence suggests that deleterious effects may also be associated with the volume or dosage of structured exercise and/or the intensity of physical activity. Moreover, non-muscle adverse effects on the joints and tendons are often overlooked and underemphasized. The incidence of myopathy associated with statin treatment typically ranges between 1.5% and 10%. Few data are available regarding the prevalence of muscle- related symptoms associated with different statins and the distribution of affected muscles. Furthermore, discrepancies between clinical trials and daily practice may emanate, in part, because of inconsistent definitions or exclusion criteria. The pathophysiology of statin-related myopathy is incompletely understood. A dose-dependent and proapoptotic effect, direct effects on mitochondria, drug interactions and genetic factors, or combinations thereof, may be involved. Recently, a rare immune-mediated myopathy triggered by statin use has been described. With the increasing number of patients treated with statins and with more patients being prescribed high doses of potent statins to achieve low-density lipoprotein targets, muscle-related side-effects will become more prevalent. Currently, the only effective treatment is the discontinuation of statin use. Further research is needed to develop alternative LDL-lowering drugs when statins are not well tolerated and to establish additional effective strategies to manage lipids and lipoproteins. PMID:25230981

Auer, Johann; Sinzinger, Helmut; Franklin, Barry; Berent, Robert

2014-09-17

214

Emerging drugs of abuse: current perspectives on substituted cathinones  

PubMed Central

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

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

2014-01-01

215

Metabolic myopathies: update 2009.  

PubMed

Metabolic myopathies are inborn errors of metabolism that result in impaired energy production due to defects in glycogen, lipid, mitochondrial, and possibly adenine nucleotide metabolism. Fatty acid oxidation defects (FAOD), glycogen storage disease, and mitochondrial myopathies represent the 3 main groups of disorders, and some consider myoadenylate deaminase (AMPD1 deficiency) to be a metabolic myopathy. Clinically, a variety of neuromuscular presentations are seen at different ages of life. Newborns and infants commonly present with hypotonia and multisystem involvement (liver and brain), whereas onset later in life usually presents with exercise intolerance with or without progressive muscle weakness and myoglobinuria. In general, the glycogen storage diseases result in high-intensity exercise intolerance, whereas the FAODs and the mitochondrial myopathies manifest predominately during endurance-type activity or under fasted or other metabolically stressful conditions. The clinical examination is often normal, and testing requires various combinations of exercise stress testing, serum creatine kinase activity and lactate concentration determination, urine organic acids, muscle biopsy, neuroimaging, and specific genetic testing for the diagnosis of a specific metabolic myopathy. Prenatal screening is available in many countries for several of the FAODs through liquid chromatography-tandem mass spectrometry. Early identification of these conditions with lifestyle measures, nutritional intervention, and cofactor treatment is important to prevent or delay the onset of muscle weakness and to avoid potential life-threatening complications such as rhabdomyolysis with resultant renal failure or hepatic failure. This article will review the key clinical features, diagnostic tests, and treatment recommendations for the more common metabolic myopathies, with an emphasis on mitochondrial myopathies. PMID:19258857

van Adel, Brian A; Tarnopolsky, Mark A

2009-03-01

216

Hyperlipoproteinemia in chronic renal failure: pathophysiological and therapeutic aspects.  

PubMed

Dyslipidemia of chronic renal failure is of multifactorial origin. Decreased activity of lipoprotein lipase and hepatic triglyceride lipase, peripheral insulin resistance, hyperparathyroidism and L-carnitine deficiency are the contributing factors. This results in a disturbed catabolism of chylomicron, accumulation of very-low-density (VLDL) and intermediate-density (IDL) lipoproteins as well as incompletely cleared remnant particles, whereas low-density lipoprotein (LDL) levels are diminished. There is current debate as to whether cardiovascular disease is accelerated and whether hyperlipidemia should specifically be treated. In addition, there have been few means of influencing these metabolic alterations. Drug incompatibility and consequently side effects render treatment difficult. The drugs that have been most tested for lipid lowering in chronic renal failure are the fibric acids. By their mode of action, they are the logical choice. Dose reduction overcomes major side effects such as myopathy and rhabdomyolysis. The second generation of fibric acid derivatives (gemfibrozil and beclobrate) show several advantages over formerly used derivatives. Treatment with lovastatin and simvastatin appears to be safe and is recommended in a minority of patients with predominantly elevations of LDL. HMG-CoA reductase inhibitors also lower remnant particles effectively in hemodialysis (HD) patients. L-Carnitine and low-molecular-weight heparin have been shown to influence VLDL rich in triglycerides in a subset of patients on HD. In posttransplant hyperlipidemia, diet remains the first course of action in all patients. When this approach fails, the new lipid-lowering agents, especially fibric acids, appear to be safe in short-term studies in azathioprine- and ciclosporin-treated patients. Lovastatin has been shown to be safe in stable renal transplant patients. Its toxicity seems to depend mainly on high ciclosporin whole blood through or plasma levels. PMID:1868498

Wanner, C; Frommherz, K; Hörl, W H

1991-01-01

217

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

USGS Publications Warehouse

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.

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

2003-01-01

218

The influence of acute renal injury on arginine and methylarginines metabolism.  

PubMed

Arginine (ARG) and its methylated analogs (methylarginines) are the crucial regulators of nitric oxide (NO) bioavailability. ARG is the substrate for NO synthesis, whereas monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA) are potent inhibitors. Symmetric dimethylarginine (SDMA) does not interfere with NO synthesis, but competes with ARG for the intracellular transport. The kidneys play the major role in ARG and methylarginines metabolism. They synthesize ARG de novo and eliminate methylarginines by excretion into urine and also by enzyme dimethylarginine dimethylaminohydrolase (DDAH) degrading only ADMA and MMA. Acute renal injury (ARI) is known to be accompanied by reduced NO production in the body. This study aimed to investigate the influence of ARI on ARG and methylarginines metabolism, and to establish the relationship between disturbances in the latter and reduced NO bioavailability in ARI. The rhabdomyolysis-related ARI model in rats was used. ARI reduced renal synthesis of ARG and its level in circulation as well as renal DDAH activity. However, ADMA did not accumulate because of its increased urinary excretion. Whole-body production of SDMA was increased significantly, whereas whole-body metabolism of MMA did not change. ARG and methylarginines content in renal tissue was decreased. Moreover, the balance between the substrate and inhibitors for NO synthesis was changed in favor of the inhibitors in renal tissue as well as in blood, and daily urinary excretion of NO metabolites was significantly decreased. Thus, ARI provokes severe disturbances in ARG and methylarginines metabolism that results in reduced NO bioavailability in the kidney and the whole body. PMID:23991715

Sukhovershin, Roman A; Gilinsky, Mikhail A

2013-01-01

219

Psychoactive "bath salts" intoxication with methylenedioxypyrovalerone.  

PubMed

Abuse of the psychoactive "designer drug" methylenedioxypyrovalerone (MDPV) has become a serious international public health concern because of the severity of its physical and behavioral toxicities. MDPV is the primary ingredient in so-called "bath salts," labeled as such to avoid criminal prosecution and has only been classified recently as a controlled substance in the United States and some other countries. However, it remains a danger because of illegal sources, including the Internet. MDPV is a synthetic, cathinone-derivative, central nervous system stimulant and is taken to produce a cocaine- or methamphetamine-like high. Administered via oral ingestion, nasal insufflation, smoking, intravenous or intramuscular methods, or the rectum, the intoxication lasts 6 to 8 hours and has high addictive potential. Overdoses are characterized by profound toxicities, causing increased attention by emergency department and law enforcement personnel. Physical manifestations range from tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, and seizures to those as severe as stroke, cerebral edema, cardiorespiratory collapse, myocardial infarction, and death. Behavioral effects include panic attacks, anxiety, agitation, severe paranoia, hallucinations, psychosis, suicidal ideation, self-mutilation, and behavior that is aggressive, violent, and self-destructive. Treatment is principally supportive and focuses on counteracting the sympathetic overstimulation, including sedation with intravenous benzodiazepines, seizure-prevention measures, intravenous fluids, close (eg, intensive care unit) monitoring, and restraints to prevent harm to self or others. Clinical presentation is often complicated by coingestion of other psychoactive substances that may alter the treatment approach. Clinicians need to be especially vigilant in that MDPV is not detected by routine drug screens and overdoses can be life-threatening. PMID:22682791

Ross, Edward A; Reisfield, Gary M; Watson, Mary C; Chronister, Chris W; Goldberger, Bruce A

2012-09-01

220

Familial very long chain acyl-CoA dehydrogenase deficiency as a cause of neonatal sudden infant death: Improved survival by prompt diagnosis.  

PubMed

In neonates, very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is often characterized by cardiomyopathy, hepatic encephalopathy, or severe hypoketotic hypoglycemia, or a combination thereof. The purpose of this study was to further elucidate a familial VLCAD deficiency in three patients, two of whom died in the neonatal period. We report on a family with VLCAD deficiency. Acyl-carnitine profiles were obtained from dried blood spot and/or from oxidation of (13) C-palmitate by cultured skin fibroblasts. In the index patient, VLCAD deficiency was ascertained by enzyme activity measurement in fibroblasts and by molecular analysis of ACADVL. At 30?hr of life, the proband was diagnosed with hypoglycemia (1.77?mmol/L), rhabdomyolysis (CK: 12966 IU/L) and hyperlactacidemia (10.6?mmol/L). Acylcarnitine profile performed at 31?hr of life was consistent with VLCAD deficiency and confirmed by cultured skin fibroblast enzyme activity measurement. Molecular analysis of ACADVL revealed a homozygous splice-site mutation (1077?+?2T>C). The acyl-carnitine profile obtained from the sibling's original newborn screening cards demonstrated a similar, but less pronounced abnormal profile. In the proband, the initial metabolic crisis was controlled with 10% dextrose solution and oral riboflavin followed by specific diet (Basic-F and medium chain triglyceride (MCT). This clinical report demonstrates a familial history of repeated neonatal deaths explained by VLCAD deficiency, and the clinical evolution of the latest affected, surviving sibling. It shows that very early metabolic screening is an effective approach to avoid sudden unexpected death. © 2014 Wiley Periodicals, Inc. PMID:25338548

Scalais, Emmanuel; Bottu, Jean; Wanders, Ronald J A; Ferdinandusse, Sacha; Waterham, Hans R; De Meirleir, Linda

2015-01-01

221

Major diet-drug interactions affecting the kinetic characteristics and hypolipidaemic properties of statins.  

PubMed

Concomitant administration of statins with food may alter statin pharmacokinetics or pharmacodynamics, increasing the risk of adverse reactions such as myopathy or rhabdomyolysis or reducing their pharmacological action. This paper reviews major interactions between statins and dietary compounds. Consumption of pectin or oat bran together with Lovastatin reduces absorption of the drug, while alcohol intake does not appear to affect the efficacy and safety of Fluvastatin treatment. Grapefruit juice components inhibit cytochrome P-4503A4, reducing the presystemic metabolism of drugs such as Simvastatin, Lovastatin and Atorvastatin. Follow-up studies on the therapeutic effect of statins in patients consuming a Mediterranean-style diet are necessary to assure the correct prescription because the oil-statin and minor oil compound-statin possible interactions have been only briefly studied. Preliminary study suggests that olive oil can increase the hypolipaemiant effect of Simvastatin with respect sunflower oil. The consumption of polyunsaturated rich oils, throughout the cytochrome P- 450 activation could decrease the half-life of some statins and therefore their hypolipaemic effects. The statins and n-3 fatty acids combined therapy gives rise to pharmacodinamic interaction that improves the lipid profile and leads greater cardioprotection. Although statins are more effective in high endogenous cholesterol production subjects and plant sterols are more effective in high cholesterol absorption efficacy subjects, plant esterols-statins combined therapy generates very positive complementary effects. This review ends suggesting possible diet-stain interactions that require further investigations (e.g. types of olive oils, fruit juices other than grapefruit, fibre or consumption of alcoholic beverages rich in polyphenols or ethanol). PMID:20449528

Vaquero, M P; Sánchez Muniz, F J; Jiménez Redondo, S; Prats Oliván, P; Higueras, F J; Bastida, S

2010-01-01

222

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

PubMed Central

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

2013-01-01

223

EU-ADR healthcare database network vs. spontaneous reporting system database: preliminary comparison of signal detection.  

PubMed

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

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

224

Interactions between grapefruit juice and cardiovascular drugs.  

PubMed

Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by commercial grapefruit juice given as a single normal amount (e.g. 200-300 mL) or by whole fresh fruit segments. As a result, presystemic metabolism is reduced and oral drug bioavailability increased. Enhanced oral drug bioavailability can occur 24 hours after juice consumption. Inhibition of P-glycoprotein (P-gp) is a possible mechanism that increases oral drug bioavailability by reducing intestinal and/or hepatic efflux transport. Recently, inhibition of organic anion transporting polypeptides by grapefruit juice was observed in vitro; intestinal uptake transport appeared decreased as oral drug bioavailability was reduced. Numerous medications used in the prevention or treatment of coronary artery disease and its complications have been observed or are predicted to interact with grapefruit juice. Such interactions may increase the risk of rhabdomyolysis when dyslipidemia is treated with the HMG-CoA reductase inhibitors atorvastatin, lovastatin, or simvastatin. Potential alternative agents are pravastatin, fluvastatin, or rosuvastatin. Such interactions might also cause excessive vasodilatation when hypertension is managed with the dihydropyridines felodipine, nicardipine, nifedipine, nisoldipine, or nitrendipine. An alternative agent could be amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1 receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit juice interacting with the antidiabetic agent repaglinide may cause hypoglycemia, and interaction with the appetite suppressant sibutramine may cause elevated BP and HR. In angina pectoris, administration of grapefruit juice could result in atrioventricular conduction disorders with verapamil or attenuated antiplatelet activity with clopidrogel. Grapefruit juice may enhance drug toxicity for antiarrhythmic agents such as amiodarone, quinidine, disopyramide, or propafenone, and for the congestive heart failure drug, carvediol. Some drugs for the treatment of peripheral or central vascular disease also have the potential to interact with grapefruit juice. Interaction with sildenafil, tadalafil, or vardenafil for erectile dysfunction, may cause serious systemic vasodilatation especially when combined with a nitrate. Interaction between ergotamine for migraine and grapefruit juice may cause gangrene or stroke. In stroke, interaction with nimodipine may cause systemic hypotension. If a drug has low inherent oral bioavailability from presystemic metabolism by CYP3A4 or efflux transport by P-gp and the potential to produce serious overdose toxicity, avoidance of grapefruit juice entirely during pharmacotherapy appears mandatory. Although altered drug response is variable among individuals, the outcome is difficult to predict and avoiding the combination will guarantee toxicity is prevented. The elderly are at particular risk, as they are often prescribed medications and frequently consume grapefruit juice. PMID:15449971

Bailey, David G; Dresser, George K

2004-01-01

225

A CACNA1C Variant Associated with Reduced Voltage-Dependent Inactivation, Increased CaV1.2 Channel Window Current, and Arrhythmogenesis  

PubMed Central

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

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

226

Treatment of dyslipidemia in chronic kidney disease: Effectiveness and safety of statins  

PubMed Central

Several cardiovascular (CV) risk factors may explain the high rate of CV death among patients with chronic kidney disease (CKD). Among them both traditional and uremia-related risk factors are implicated and, moreover, the presence of kidney disease represents “per se” a multiplier of CV risk. Plasma lipid and lipoprotein profiles are changed in quantitative, but above all in qualitative, structural, and functional ways, and lipoprotein metabolism is influenced by the progressive loss of renal function. Statin therapy significantly reduces cholesterol synthesis and both CV morbidity and mortality either directly, by reducing the lipid profile, or via pleiotropic effects; it is supposed to be able to reduce both the progression of CKD and also proteinuria. These observations derive from a post-hoc analysis of large trials conducted in the general population, but not in CKD patients. However, the recently published SHARP trial, including over 9200 patients, either on dialysis or pre-dialysis, showed that simvastatin plus ezetimibe, compared with placebo, was associated with a significant low-density lipoprotein cholesterol reduction and a 17% reduction in major atherosclerotic events. However, no benefit was observed in overall survival nor in preserving renal function in patients treated. These recent data reinforce the conviction among nephrologists to consider their patients at high CV risk and that lipid lowering drugs such as statins may represent an important tool in reducing atheromatous coronary disease which, however, represents only a third of CV deaths in patients with CKD. Therefore, statins have no protective effect among the remaining two-thirds of patients who suffer from sudden cardiac death due to arrhythmia or heart failure, prevalent among CKD patients. The safety of statins is demonstrated in CKD by several trials and recently confirmed by the largest SHARP trial, in terms of no increase in cancer incidence, muscle pain, creatine kinase levels, severe rhabdomyolysis, hepatitis, gallstones and pancreatitis; thus confirming the handiness of statins in CKD patients. Here we will review the latest data available concerning the effectiveness and safety of statin therapy in CKD patients. PMID:24175258

Scarpioni, Roberto; Ricardi, Marco; Albertazzi, Vittorio; Melfa, Luigi

2012-01-01

227

Marked hydronephrosis and hydroureter after distigmine therapy in an adult male patient with paraplegia due to spinal cord injury: a case report  

PubMed Central

Introduction Distigmine, a long-acting anti-cholinesterase, is associated with side effects such as Parkinsonism, cholinergic crisis, and rhabdomyolysis. We report a spinal cord injury patient, who developed marked hydronephrosis and hydroureter after distigmine therapy, which led to a series of complications over subsequent years. Case presentation A 38-year-old male developed T-9 paraplegia in 1989. Intravenous urography, performed in 1989, showed normal kidneys, ureters and bladder. He was prescribed distigmine bromide orally and was allowed to pass urine spontaneously. In 1992, intravenous urography showed bilateral marked hydronephrosis and hydroureter. Distigmine was discontinued. He continued to pass urine spontaneously. In 2006, intravenous urography showed moderate dilatation of both pelvicalyceal systems and ureters down to the level of urinary bladder. This patient was performing self-catheterisation only once a day. He was advised to do catheterisations at least three times a day. In December 2008, this patient developed haematuriawhich lasted for nearly four months.. He received trimethoprim, then cephalexin, followed by Macrodantin, amoxicillin and ciprofloxacin. In February 2009, intravenous urography showed calculus at the lower pole of left kidney. Both kidneys were moderately hydronephrotic. Ureters were dilated down to the bladder. Dilute contrast was seen in the bladder due to residual urine. This patient was advised to perform six catheterisations a day, and take propiverine hydrochloride 15 mg, three times a day. Microbiology of urine showed Klebsiella oxytoca, Pseudomonas aeruginosa, and Enterococcus faecalis. Cystoscopy revealed papillary lesions in bladder neck and trigone. Transurethral resection was performed. Histology showed marked chronic cystitis including follicular cystitis and papillary/polypoid cystitis. There was no evidence of malignancy. Conclusion Distigmine therapy resulted in marked bilateral hydronephrosis and hydroureter. Persistence of hydronephrosis after omitting distigmine, and presence of residual urine in bladder over many years probably predisposed to formation of polypoid cystitis and follicular cystitis, and contributed to prolonged haematuria, which occurred after an episode of urine infection. This case illustrates the dangers of prescribing distigmine to promote spontaneous voiding in spinal cord injury patients. Instead of using distigmine, spinal cord injury patients should be advised to consider intermittent catheterisation together with oxybutynin or propiverine to achieve complete, low-pressure emptying of urinary bladder. PMID:19918519

Mansour, Paul; Soni, Bakul M; Hughes, Peter L; Singh, Gurpreet; Oo, Tun

2009-01-01

228

HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment  

PubMed Central

Aims Niacin has potentially favourable effects on lipids, but its effect on cardiovascular outcomes is uncertain. HPS2-THRIVE is a large randomized trial assessing the effects of extended release (ER) niacin in patients at high risk of vascular events. Methods and results Prior to randomization, 42 424 patients with occlusive arterial disease were given simvastatin 40 mg plus, if required, ezetimibe 10 mg daily to standardize their low-density lipoprotein (LDL)-lowering therapy. The ability to remain compliant with ER niacin 2 g plus laropiprant 40 mg daily (ERN/LRPT) for ?1 month was then assessed in 38 369 patients and about one-third were excluded (mainly due to niacin side effects). A total of 25 673 patients were randomized between ERN/LRPT daily vs. placebo and were followed for a median of 3.9 years. By the end of the study, 25% of participants allocated ERN/LRPT vs. 17% allocated placebo had stopped their study treatment. The most common medical reasons for stopping ERN/LRPT were related to skin, gastrointestinal, diabetes, and musculoskeletal side effects. When added to statin-based LDL-lowering therapy, allocation to ERN/LRPT increased the risk of definite myopathy [75 (0.16%/year) vs. 17 (0.04%/year): risk ratio 4.4; 95% CI 2.6–7.5; P < 0.0001]; 7 vs. 5 were rhabdomyolysis. Any myopathy (definite or incipient) was more common among participants in China [138 (0.66%/year) vs. 27 (0.13%/year)] than among those in Europe [17 (0.07%/year) vs. 11 (0.04%/year)]. Consecutive alanine transaminase >3× upper limit of normal, in the absence of muscle damage, was seen in 48 (0.10%/year) ERN/LRPT vs. 30 (0.06%/year) placebo allocated participants. Conclusion The risk of myopathy was increased by adding ERN/LRPT to simvastatin 40 mg daily (with or without ezetimibe), particularly in Chinese patients whose myopathy rates on simvastatin were higher. Despite the side effects of ERN/LRPT, among individuals who were able to tolerate it for ?1 month, three-quarters continued to take it for ?4 years. PMID:23444397

Haynes, Richard; Jiang, Lixin; Hopewell, Jemma C; Li, Jing; Chen, Fang; Parish, Sarah; Landray, Martin J.; Collins, Rory; Armitage, Jane; Collins, R.; Armitage, J.; Baigent, C.; Chen, Z.; Landray, M.; Chen, Y.; Jiang, L.; Pedersen, T.; Landray, M.; Bowman, L.; Chen, F.; Hill, M.; Haynes, R.; Knott, C.; Rahimi, K.; Tobert, J.; Sleight, P.; Simpson, D.; Parish, S.; Baxter, A.; Lay, M.; Bray, C.; Wincott, E.; Leijenhorst, G.; Skattebol, A.; Moen, G.; Mitchel, Y.; Kuznetsova, O.; MacMahon, S.; Kjekshus, J.; Hill, C.; Lam, T.H.; Sandercock, P.; Peto, R.; Hopewell, J.C.

2013-01-01

229

Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies.  

PubMed

Ecteinascidin 743 (ET-743) is a cytotoxic tetrahydroisoquinoline alkaloid that covalently binds to DNA in the minor groove. The in vitro chemosensitivity of cancer cells to ET-743 is markedly enhanced by prolonging the duration of exposure to the drug. A Phase I study of ET-743 given as a 72-h continuous i.v. infusion every 21 days was performed. Characteristics of the 21 adult patients with refractory solid tumors enrolled in the study were as follows: (a) 12 men; (b) 9 women; (c) median age, 59 years; (d) Eastern Cooperative Oncology Group performance status < or = 1, 20 patients; and (e) two prior regimens of chemotherapy, 7 patients. Dose limiting toxicity (DLT) was defined by typical criteria, except that grade 3 transaminitis did not constitute a DLT. There were no DLTs in the six patients evaluated at the first two dose levels of 600 and 900 microg/m2. Reversible grade 4 transaminitis occurred in two of nine patients after treatment with the first cycle of therapy at the third dose level of 1200 microg/m2. Another patient experienced grade 4 rhabdomyolysis, renal failure requiring hemodialysis, grade 4 neutropenia, and grade 3 thrombocytopenia during the second cycle of therapy with this dose. The maximum tolerated dose was 1200 microg/m2, and an additional six patients were enrolled at an intermediate dose level of 1050 microg/m2. This well-tolerated dose was established as the recommended Phase II dose. The disposition of ET-743 was distinctly biexponential, and a departure from linear pharmacokinetic behavior was evident at the 1200-microg/m2 dose level. Pharmacokinetic parameters determined at 1050 microg/m2 were (mean +/- SD): maximum plasma concentration, 318 +/- 147 pg/ml; initial disposition phase half-life, 9.0 +/- 10.3 min; terminal phase half-life, 69.0 +/- 56.7 h; and total plasma clearance, 28.4 +/- 22.5 liters/h/m2. Prolonged systemic exposure to concentrations of the agent that are cytotoxic in vitro were achieved. Toxicity of the drug is clearly schedule-dependent, because increasing the duration of infusion from 3 or 24 h to 72 h results in decreased myelosuppression and comparable hepatotoxicity. Although there were no objective responses to therapy, clear evidence of antitumor activity was observed in a patient with epithelioid mesothelioma, as confirmed by positron emission tomography studies. A Phase II trial to assess the efficacy of ET-743 against this highly refractory neoplasm has been initiated on the basis of this observation. The therapeutically optimal administration schedule remains to be established, inasmuch as there have been indications of activity against a variety of tumors during Phase I studies when the drug was infused over times ranging from 1 to 72 h. Characterizing the pharmacokinetics of ET-743 during the course of Phase II trials and Phase I combination studies is recommended to assure that this promising new anticancer drug can be used with an acceptable margin of safety. PMID:11234874

Ryan, D P; Supko, J G; Eder, J P; Seiden, M V; Demetri, G; Lynch, T J; Fischman, A J; Davis, J; Jimeno, J; Clark, J W

2001-02-01

230

Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V).  

PubMed

Background McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria rhabdomyolysis and acute renal failure. This is an update of a review first published in 2004.Objectives To review systematically the evidence from randomised controlled trials (RCTs) of pharmacological or nutritional treatments for improving exercise performance and quality of life in McArdle disease.Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE on 11 August 2014.Selection criteria We included RCTs (including cross-over studies) and quasi-RCTs. We included unblinded open trials and individual patient studies in the discussion. Interventions included any pharmacological agent or nutritional supplement. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO2) max, walking speed, muscle force or power and fatigability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase and a reduction in the frequency of myoglobinuria), subjective measures (including quality of life scores and indices of disability) and serious adverse events.Data collection and analysis Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. Two review authors independently assessed the risk of bias of relevant studies, with comments from a third author. Two authors extracted data onto a specially designed form.Main results We identified 31 studies, and 13 fulfilled the criteria for inclusion. We described trials that were not eligible for the review in the Discussion. The included studies involved a total of 85 participants, but the number in each individual trial was small; the largest treatment trial included 19 participants and the smallest study included only one participant. There was no benefit with: D-ribose,glucagon, verapamil, vitamin B6, branched chain amino acids, dantrolene sodium, and high-dose creatine. Minimal subjective benefit was found with low dose creatine and ramipril only for patients with a polymorphism known as the D/Dangiotens in converting enzyme(ACE) phenotype. A carbohydrate-rich diet resulted in better exercise performance compared with a protein-rich diet. Two studies of oral sucrose given at different times and in different amounts before exercise showed an improvement in exercise performance. Four studies reported adverse effects. Oral ribose caused diarrhoea and symptoms suggestive of hypoglycaemia including light-headedness and hunger. In one study, branched chain amino acids caused a deterioration of functional outcomes. Dantrolene was reported to cause a number of adverse effects including tiredness, somnolence, dizziness and muscle weakness. Low dose creatine (60 mg/kg/day) did not cause side-effects but high-dose creatine (150 mg/kg/day) worsened the symptoms of myalgia.Authors' conclusions Although there was low quality evidence of improvement in some parameters with creatine, oral sucrose, ramipril and a carbohydrate rich diet, none was sufficiently strong to indicate significant clinical benefit. PMID:25391139

Quinlivan, Rosaline; Martinuzzi, Andrea; Schoser, Benedikt

2014-01-01