Sample records for rhabdomyolysis

  1. Rhabdomyolysis after Laparoscopic Bariatric Surgery

    Microsoft Academic Search

    Philippe Mognol; Stéphane Vignes; Denis Chosidow; Jean-Pierre Marmuse

    2004-01-01

    Background: Postoperative rhabdomyolysis is an uncommon event. The aim of this study was to determine the incidence of rhabdomyolysis\\u000a following laparoscopic obesity surgery. Methods: Rhabdomyolysis was studied prospectively. Over a 6-month period, 66 consecutive\\u000a patients underwent bariatric surgery (gastric banding (n=50) and gastric bypass (n=16)). All patients underwent laparoscopic\\u000a procedures. A range of blood tests, including serum creatine phosphokinase (CPK)

  2. Rhabdomyolysis in a recreational swimmer.

    PubMed

    Stella, J J; Shariff, A H

    2012-02-01

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

  3. An unusual case of rhabdomyolysis

    PubMed Central

    Gentili, Giorgio; Verdura, Claudio; Calabrò, Giuseppe; Miele, Maria Luisa

    2011-01-01

    We report an unusual case of rhabdomyolysis due to coturnism (food poisoning caused by eating quails). The patient’s clinical course is described, and possible pathogenetic mechanisms of this syndrome are briefly discussed. PMID:25984149

  4. Hypokalemia and rhabdomyolysis

    PubMed Central

    Horwitz, Henrik; Woeien, Vidar A.; Petersen, Linda Wiuff; Jimenez-Solem, Espen

    2015-01-01

    The adverse drug event manager of the Capital Region of Denmark received a report of a 65-year-old male with type II diabetes and long-lasting treatment with indapamide. In addition, he had a history of a high consumption of licorice. For 2 weeks, the patient suffered from myalgia, which the general practitioner suspected to be polymyalgia rheumatica and referred him to the hospital. Initial blood samples revealed a reduced potassium concentration of 1.5 mmol/L (reference value: 6.6-4.6 mmol/L) and an elevated creatine kinase of 18,400 IU/L (reference value: 40-280 IU/L). We believe that the patient developed rhabdomyolysis due to severe hypokalemia, possibly induced by a pharmacodynamic interaction between licorice and indapamide. PMID:25969658

  5. Nelarabine associated myotoxicity and rhabdomyolysis.

    PubMed

    Haider, Mahnur; Rizvi, Syed Ahsan; Kasi, Pashtoon Murtaza

    2015-01-01

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

  6. Nelarabine Associated Myotoxicity and Rhabdomyolysis

    PubMed Central

    Haider, Mahnur; Rizvi, Syed Ahsan

    2015-01-01

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

  7. [Myocardial rhabdomyolysis following paraphenylene diamine poisoning].

    PubMed

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

    2000-02-01

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

  8. Rhabdomyolysis in 114 patients with acute poisonings

    PubMed Central

    Mousavi, Seyed Reza; Vahabzadeh, Maryam; Mahdizadeh, Adeleh; Vafaee, Mansooreh; Sadeghi, Mahmood; Afshari, Reza; Balali-Mood, Mahdi

    2015-01-01

    Background: Rhabdomyolysis is a clinical and biochemical syndrome, which is observed in some patients with acute chemical and/or pharmaceutical poisonings. We aimed to investigate rhabdomyolysis in patients with acute poisonings due to different chemicals, natural toxins or drug overdose. Materials and Methods: Following approval of the University medical research committee and obtaining informed consents from the patients or their relatives, all patients with acute poisonings who were treated between March 2009 and February 2010 in the Toxicologic Ward of Imam Reza Hospital and had serum creatine phosphokinase (CPK) above 975 IU/L (as a definition for rhabdomyolysis) were studied. Results: Of 3555 hospitalized poisoned patients, 114 patients had rhabdomyolysis with CPK of 5996 ± 892 IU/L (mean ± standard error). The most common intoxication to induce the rhabdomyolysis was opioid overdose (28%). Acute renal failure (ARF) was diagnosed in 11 (8.7%) patients. There was a linear correlation between CPK and creatinine (P < 0.001), which in turn had a significant correlation with death (P < 0.05). Conclusion: Patients with acute poisoning were at risk of rhabdomyolysis. Acute opioid poisoning was the most common cause of toxic rhabdomyolysis in the intoxicated patients, and ARF was the main complication.

  9. Hyponatraemia associated rhabdomyolysis following water intoxication

    PubMed Central

    Katsarou, Alexia; Singh, Suveer

    2010-01-01

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

  10. Rhabdomyolysis and Acute Renal Failure after Gardening

    PubMed Central

    Vucicevic, Zeljko

    2015-01-01

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

  11. Pressure-induced Rhabdomyolysis after Bariatric Surgery

    Microsoft Academic Search

    Gonzalo Torres-Villalobos; Eric Kimura; Juan Luis Mosqueda; Eduardo García-García; Miguel F. Herrera

    2003-01-01

    Rhabdomyolisis most commonly occurs after muscle injury, alcohol ingestion, drug intake and exhaustive exercise. Prolonged\\u000a muscle compression at the time of surgery may produce this complication. Obesity has been reported as a risk factor for pressure-induced\\u000a rhabdomyolysis, but no reports associated with bariatric surgery could be found in the literature. We report 3 superobese\\u000a patients who developed rhabdomyolysis after bariatric

  12. 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

  13. Rhabdomyolysis induced by excessive coffee drinking.

    PubMed

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

    2014-08-01

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

  14. Rhabdomyolysis in Community Acquired Bacterial Sepsis – A Retrospective Cohort Study

    Microsoft Academic Search

    Anita A. Kumar; Emmanuel Bhaskar; Ghanshyam Palamaner Subash Shantha; Porchelvan Swaminathan; Georgi Abraham

    2009-01-01

    Background and ObjectivesRhabdomyolysis is often associated with sepsis and gram positive bacterial pathogens are reported to be the most frequent cause of sepsis induced rhabdomyolysis. We report the pattern of infecting bacterial pathogens and associated causal factors in a South-Indian cohort.Design, Setting, Participants & MeasurementsRetrospective cohort study of adult patients with community acquired bacterial sepsis complicated by rhabdomyolysis from March

  15. Rhabdomyolysis: a review, with emphasis on the pediatric population

    Microsoft Academic Search

    Essam F. Elsayed; Robert F. Reilly

    2010-01-01

    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

  16. Rhabdomyolysis, compartment syndrome and thermal injury

    PubMed Central

    Coban, Yusuf Kenan

    2014-01-01

    Rhabdomyolysis (RML) after electrical burns and crush injuries is a well-known clinical entity, but its occurrence following thermal injury has not gained so much attention. Capillary leak syndrome and following polycompartmental syndrome are devastating end results of major thermal injuries. In the current review, polycompartment syndrome within the clinical picture of systemic oedema and its relationship to RML is discussed along with its management and prevention. PMID:24834396

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

    PubMed

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

    2009-05-01

    Rhabdomyolysis and peripheral neuropathy are two distinct disease entities which are rarely encountered in combination. We present a woman with rhabdomyolysis and peripheral neuropathy 3 weeks postpartum. Her symptoms were caused by bilateral femoral artery thrombosis due to postpartum cardiomyopathy (PPCM). This demonstrates that PPCM may present with predominantly non-cardial symptoms and underscores the importance of rapidly recognizing this disorder. PMID:18581059

  18. Rhabdomyolysis caused by hot air sauna burn.

    PubMed

    Koski, Antti; Koljonen, Virve; Vuola, Jyrki

    2005-09-01

    Sauna-related burns are rare, even in Finland where sauna bathing is a popular leisure pastime. Burns induced by hot air are even more rare and constitute a very small subgroup of all sauna burns. Hot air burns are characterised by a combination of full thickness skin damage with deep tissue destruction. We report here on six consecutive patients suffering from hot air sauna burns with rhabdomyolysis. All six patients were middle-aged, the majority of them men. Acute excessive consumption of alcohol exacerbated by a hot environment resulted in dehydration and loss of consciousness. Immobility and prolonged exposure to hot, dry air resulted in third degree regional burns with 5-32% TBSA. Rhabdomyolysis was evident on admission. The laboratory values of plasma creatine kinase (P-CK), plasma myoglobin (PM), blood pH, and serum potassium (S-K) during the first five days were evaluated. Aggressive fluid management and correction of acidosis and myoglobinuria were started on admission. Surgical management consisted of early, aggressive excision at fascial level, in some patients involving sacrifice of the upper layers of muscle. Even so, mortality in this small series was 50%. The best indicator of poor prognosis was a highly elevated CK value on the second post-injury day. PMID:16046074

  19. Rhabdomyolysis a result of azithromycin and statins: an unrecognized interaction

    PubMed Central

    Strandell, Johanna; Bate, Andrew; Hägg, Staffan; Edwards, I Ralph

    2009-01-01

    AIMS In a systematic screening of the World Health Organization Adverse Drug Reaction database, VigiBase, in July 2008, a measure of association used to detect interactions (Omega) highlighted azithromycin with the individual statins atorvastatin, lovastatin and simvastatin and rhabdomyolysis. The aim was to examine all reports including rhabdomyolysis-azithromycin and statins in VigiBase to assess if the data were suggestive of an interaction. METHODS The individual case reports in VigiBase and the original files were reviewed. In order to investigate the reporting over time for rhabdomyolysis with azithromycin and statins to VigiBase, Omega values were generated retrospectively. RESULTS The reporting over time showed that rhabdomyolysis under concomitant use of azithromycin and statins was reported more often than expected from 2000 and onwards in Vigibase. After exclusion of possible duplicates and follow-up reports, 53 cases from five countries remained. Rhabdomyolysis occurred shortly after initiation of azithromycin in 23% of cases. In 11 patients an interaction had been suggested by the reporter. With the exception of one patient, the statin doses reported were within the recommended daily doses. CONCLUSIONS Case reports in VigiBase are suggestive that interactions between azithromycin and statins resulting in rhabdomyolysis may occur. This analysis showed the potential of the newly developed disproportionality measure, Omega, which can help to identify drug interactions in VigiBase in the future. The results also showed that reviewing spontaneous reports can add information to drug interactions not established previously. PMID:19740401

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-12-22

    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

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

    PubMed Central

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

    2014-01-01

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

  3. Genetic polymorphisms associated with exertional rhabdomyolysis.

    PubMed

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

    2013-08-01

    Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER. DNA samples derived from a laboratory-based study of persons who had never experienced an episode of ER (controls) and clinical ER cases referred for testing over the past several years were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes. These included angiotensin I converting enzyme (ACE), ?-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

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

    PubMed Central

    Fadila, Mario F.; Wool, Kenneth J.

    2015-01-01

    Context: Rhabdomyolysis is a serious clinical syndrome that results from damage to skeletal muscles. Common causes include drugs, crush injuries, seizures, heat, exertion, and infection. Viral infections, particularly Influenza A, have been recognized as a cause of rhabdomyolysis. Case Report: Our report describes a 58-year-old male who presented with viral pneumonia secondary to Influenza A virus infection. His hospital course was complicated by acute renal failure secondary to rhabdomyolysis, which was attributed to an overwhelming viremia. We discuss the differential diagnosis of rhabdomyolysis and review the literature for cases of Influenza A-related rhabdomyolysis. We also discuss the proposed mechanisms for the condition. Conclusion: The scope of clinical manifestations of Influenza A infection extends beyond pulmonary syndromes. Rhabdomyolysis is being increasingly recognized as a complication of Influenza A infection with considerable morbidity and mortality. PMID:25839005

  5. Rhabdomyolysis and acute kidney injury in dengue fever.

    PubMed

    Mishra, Arvind; Singh, Varun Kumar; Nanda, Satyan

    2015-01-01

    Rhabdomyolysis is a rare but potentially lethal complication of severe dengue fever. We present a case of 21-year-old man with fever, bodyache and black coloured and decreasing amount of urine. He was positive for NS1 (non-structural protein-1) antigen and IgM antibody for dengue. Platelet count was below 20×10(9)/L and kidney function test was deranged. Urine was positive for myoglobin. The patient was managed emergently on conservative lines and improved in 10?days. Rhabdomyolysis should always be kept in mind in a patient with severe dengue, as its early detection and prompt management can prevent further progression to acute renal failure. PMID:26174727

  6. Exercise Induced Rhabdomyolysis with Compartment Syndrome and Renal Failure

    PubMed Central

    Bhalla, Mary Colleen; Dick-Perez, Ryan

    2014-01-01

    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

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

    PubMed Central

    Mendes, Polyana; Robles, Priscila Games

    2014-01-01

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

  8. Rare Acute Kidney Injury Secondary to Hypothyroidism-Induced Rhabdomyolysis

    PubMed Central

    Cai, Ying

    2013-01-01

    Purpose Acute kidney injury (AKI) caused by hypothyroidism-induced rhabdomyolysis is a rare and potentially life-threatening syndrome. The aim of this study was to investigate the clinical characteristics of such patients. Materials and Methods We retrospectively analyzed five patients treated at the Second Affiliated Hospital of Chongqing Medical University with AKI secondary to hypothyroidism-induced rhabdomyolysis from January 2006 to December 2010. Results Of the five cases reviewed (4 males, age range of 37 to 62 years), adult primary hypothyroidism was caused by amiodarone (1 case), chronic autoimmune thyroiditis (1 case), and by uncertain etiologies (3 cases). All patients presented with facial and lower extremity edema. Three patients presented with weakness, while two presented with blunted facies and oliguria. Only one patient reported experiencing myalgia and proximal muscle weakness, in addition to fatigue and chills. Creatine kinase, lactate dehydrogenase, and renal function normalized after thyroid hormone replacement, except in two patients who improved through blood purification. Conclusion Hypothyroidism should be considered in patients presenting with renal impairment associated with rhabdomyolysis. Moreover, further investigation into the etiology of the hypothyroidism is warranted. PMID:23225815

  9. Incidence, Etiology, and Outcomes of Rhabdomyolysis in a Single Tertiary Referral Center

    PubMed Central

    Park, Jae-Seok; Seo, Min-Sook; Gil, Hyo-Wook; Yang, Jong-Oh; Lee, Eun-Young

    2013-01-01

    We have encountered numerous cases of rhabdomyolysis associated with acute pesticide intoxication; however, the cause, incidence, and treatment outcomes of rhabdomyolysis have not been studied. The current study involved 2,125 patients hospitalized with acute chemical poisoning. Based on clinical and laboratory parameters and treatment outcomes, we found that overall incidence of rhabdomyolysis in our hospital was 0.06% (93 of 143,830 patients admitted), but the incidence associated with acute pesticide intoxication was 1.8% (33 of 1,793 cases). The incidence of rhabdomyolysis after pesticide intoxication was significantly higher in men than in women (P = 0.010). The amount of pesticide ingested was significantly higher in rhabdomyolysis patients than that in those who did not develop rhabdomyolysis (mean ± SD, 114.1 ± 79.5 mL vs 74.1 ± 94.2 mL, P = 0.010). Our results show that pesticide intoxication is a frequent cause of rhabdomyolysis and is more common among men than women. The volume of pesticide ingested, and not the degree of human toxicity, is the main factor influencing the incidence of rhabdomyolysis. PMID:23960447

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

    PubMed Central

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

    2014-01-01

    Rhabdomyolysis is a serious but rare side effect of Lamivudine treatment. Therefore, appropriate biochemical monitoring should be undertaken when it is used in the treatment of hepatitis B. This paper presents a case of Lamivudine-associated rhabdomyolysis in a 31-year-old man with congenital heart disease and hepatitis B. Three days after starting Lamivudine, the patient developed myalgia. Significant muscle tenderness and swelling of the upper and lower limbs was discovered during a physical examination. Creatine kinase was markedly raised. Lamivudine-induced rhabdomyolysis was suspected and the drug was discontinued. Symptoms and creatine kinase activity improved within four days of Lamivudine cessation and hydration. Early identification of Lamivudine-induced rhabdomyolysis is key in preventing this potentially fatal drug reaction; withdrawal of Lamivudine may contribute to complete remission of rhabdomyolysis. PMID:25763159

  11. Risk Factors for Acute Kidney Injury in Severe Rhabdomyolysis

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. TNF-?-mediated cardiorenal injury after rhabdomyolysis in rats.

    PubMed

    Homsi, Eduardo; Andreazzi, Diego Duarte; Faria, Jose Butori Lopes de; Janino, Patrícia

    2015-06-01

    The TNF-? serum level increases after rhabdomyolysis and is involved in the subsequent cardiorenal injury. In the present study, we investigated the TNF-?-dependent cell signaling pathways implicated in cellular injury in these organs. Rhabdomyolysis was induced by intramuscular glycerol injection in rats. Renal function, cardiac and renal pathology, and activation of caspases were evaluated during the first 24 h after glycerol injection. TNF-? blockade with infliximab reduced tubular necrosis and cardiorenal apoptosis. Cellular Fas-associated protein with death domain-like IL-1?-converting enzyme inhibitory protein (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, the cellular response to the TNF-? stimulus was driven to receptor-interacting protein-1 (RIP1)-mediated necroptosis. Treatment with RIP1 inhibitor (necrostatin-1) isolated or in combination with infliximab showed a similar reduction in tubular necrosis, underscoring the importance of TNF-?-mediated tubular necroptosis in this model. TNF-? played a positive regulatory role in the transcription of proapoptotic Bax and p53-upregulated modulator of apoptosis (PUMA) proteins. Infliximab treatment reduced 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 of caspase-9 activation. TNF-?-mediated necroptosis is the predominant form of tubular injury observed in the glycerol model. TNF-? up regulates Bax and PUMA proapoptotic proteins, resulting in activation of the intrinsic pathway of apoptosis in the kidney and heart. PMID:25391899

  15. Mechanism-Based Therapeutic Approaches to Rhabdomyolysis-Induced Renal Failure

    PubMed Central

    Boutaud, Olivier; Roberts, L. Jackson

    2010-01-01

    Rhabdomyolysis-induced renal failure represents up to 15% of all cases of acute renal failure. Many studies over the past four decades have demonstrated that accumulation of myoglobin in the kidney is central in the mechanism leading to kidney injury. However, some discussion exists regarding the mechanism mediating this oxidant injury. Although free iron-catalyzed fenton reaction has been proposed to explain the tissue injury, more recent evidence strongly suggests that the main cause of oxidant injury is myoglobin redox cycling and generation of oxidized lipids. These molecules can propagate tissue injury and cause renal vasoconstriction, two of the three main conditions associated with acute renal failure. This review presents the evidence supporting the two mechanisms of oxidative injury, describes the central role of myoglobin redox cycling in the pathology of renal failure associated with rhabdomyolysis, and discuss the value of therapeutic interventions aiming at inhibiting myoglobin redox cycling for the treatment of rhabdomyolysis-induced renal failure. PMID:21034813

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

    PubMed

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

    2012-06-01

    An 82-year-old man visited our hospital when he developed a fever of over 38 degrees C after having consumed 5 types of health foods. He had previously been treated for chronic obstructive pulmonary disease, hypertension and hyperuricemia. Blood examination on admission revealed renal dysfunction, marked elevation of C-reactive protein, and an elevated level of serum creatine kinase. According to the laboratory data and his clinical history, rhabdomyolysis complicated by acute renal failure was suspected, but his condition improved and his fever was reduced with fluid infusion. As a drug lymphocyte stimulation test was positive for only saw palmetto in the 5 health foods, we diagnosed the case as rhabdomyolysis induced by saw palmetto. We believe that this is the first case of a health food being the cause of rhabdomyolysis. PMID:22768426

  17. Myocarditis and Rhabdomyolysis in a Healthy Young Man Caused by Salmonella Gastroenteritis

    PubMed Central

    Ajaz, Yasmeen; Roy Narayanan, Sunil

    2015-01-01

    Salmonella gastroenteritis is a common, self-limiting, foodborne disease and a rare cause of life-threatening complications especially in immunocompetent individuals. Moreover, bacterial infections of the GI tract have been rarely reported as a cause of serious complications like acute myocarditis and rhabdomyolysis. While viral infections are commonly associated with myocarditis, bacterial infections are infrequently seen with these conditions. Similarly, bacterial infections may lead to only 5% of adult rhabdomyolysis events whereas viral-induced myositis appears to be the commonest. A 28-year-old young male with no past medical problems presented with acute salmonella gastroenteritis that was complicated by myocardial injury (most likely myocarditis), rhabdomyolysis, acute renal failure, and shock. He made an uneventful complete recovery of all complications by early recognition of these rare complications and prompt institution of appropriate therapy. PMID:26124970

  18. [Rhabdomyolysis following cerivastatin monotherapy--implications for therapy with HMG-CoA reductase inhibitors].

    PubMed

    Sparing, R; Sellhaus, B; Noth, J; Block, F

    2003-02-01

    Cerivastatine was administered as a reversible HMG-CoA reductase inhibitor (statine) to treat hypercholesterolemia until its withdrawal from the market following 52 reports of death due to drug-related rhabdomyolysis and acute renal failure. In most cases, cerivastatine was applied in combination with drugs which influenced the liver metabolism of cerivastatine via cytochromeoxidase P 450 isoenzymes. We report a well-documented case of acute rhabdomyolysis following cerivastatine monotherapy. The diagnosis was confirmed additionally by muscle biopsy.Finally,we give an overview of the current knowledge concerning therapy with HMG-CoA reductase inhibitors,1 year after the withdrawal of cerivastatine from the market. PMID:12596018

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

    PubMed

    Shah, S V; Reddy, K

    2010-01-01

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

  20. Technetium-99m pyrophosphate imaging in acute renal failure associated with nontraumatic rhabdomyolysis

    SciTech Connect

    Patel, R.; Mishkin, F.S.

    1986-10-01

    Technetium-99m pyrophosphate (Tc-PYP) imaging was performed in five patients with acute renal failure associated with nontraumatic rhabdomyolysis. Four patients had phencyclidine intoxication and one had viral pneumonia. During the acute phase, marked uptake of pyrophosphate was seen in all patients in several muscle groups, but always in the thigh adductors. The results show that phencyclidine intoxication can result in diffuse muscle uptake of Tc-PYP without overt evidence of muscle injury. Tc-PYP imaging may provide a clue to the cause of acute renal failure in patients with suspected rhabdomyolysis in whom elevations of serum creatine phosphokinase concentrations are equivocal.

  1. An autopsy case of rhabdomyolysis related to vegetamin and genetic analysis of the rhabdomyolysis-associated genes.

    PubMed

    Matsusue, Aya; Hara, Kenji; Kageura, Mitsuyoshi; Kashiwagi, Masayuki; Lu, Wang; Ishigami, Akiko; Gotohda, Takako; Tokunaga, Itsuo; Nisimura, Akiyoshi; Sugimura, Tomoko; Kubo, Shin-Ichi

    2010-01-01

    We report an autopsy case of a man who died 2 days after taking an overdose of vegetamin. The autopsy findings were as follows: the epidermis on the axillary fossa and the inguinal skin had become macerated. Skeletal muscle was discolored. Concentrations of urea nitrogen, creatinine and urine myoglobin were 1.95 g/day, 0.66 g/day and 1100 ng/mL, respectively. Immunohistochemically, myoglobin was strongly stained at the Bowman's capsule, and tubular lumen and epithelium. 8-OH-dG was strongly stained in renal tubular epithelium in which cell nuclei were strongly stained. ORP-150 was observed in intraglomerular cells and renal tubular epithelium. The concentrations of phenobarbital, promethazine and chlorpromazine ranged from therapeutic to toxic levels, from toxic to lethal levels and toxic level, respectively. His cause of death was considered to be vegetamin-induced rhabdomyolysis. In genetic analysis of this subject, there were two heterozygous silent mutations in the three hot-spot regions in the RYR1 gene. In the CPT II gene, the subject was found to be heterozygous for an amino acid substitution in exon 4, (1203)G>A causing a (368)Val>Ile amino acid substitution. There was no mutation in the VLCAD gene or CYP2C19 gene. The subject was heterozygous for CYP2D6*1 and CYP2D6*2. PMID:20083051

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

    PubMed

    Parr, M J; Willatts, S M

    1991-07-01

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

  3. Hyperthermia, rhabdomyolysis, and disseminated intravascular coagulation associated with baclofen pump catheter failure

    Microsoft Academic Search

    Ronald K. Reeves; Kathryn A. Stolp-Smith; Mark W. Christopherson

    1998-01-01

    A 29-year-old man with C6 tetraplegia (ASIA A) using an implanted baclofen pump and intrathecal catheter infusion system for spasticity control developed severe spasticity, hyperthermia, hypotension, rhabdomyolysis, and disseminated intravascular coagulation after catheter disconnection. Tracheal intubation and mechanical ventilation were necessary. Extensive workup for a concurrent infection was negative except for urine cultures. The patient remained febrile for 10 days

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

    PubMed Central

    Paparoupa, Maria; Pietrzak, Sebastian; Gillissen, Adrian

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. A Case of Paraspinal Muscle Rhabdomyolysis in a 22-Year-Old Male After Ingesting a Supplement Containing Higenamine.

    PubMed

    Jeter, Jonathan; DeZee, Kent J; Kennedy, Laura

    2015-07-01

    Rhabdomyolysis is a painful and potentially life-threatening injury in which muscle breaks down in response to an insult. In this case report, we describe the clinical course of a 22-year-old man who developed paraspinal muscle rhabdomyolysis and possible compartment syndrome in association with strenuous activity and the ingestion of an exercise supplement containing the stimulant higenamine. Although he did not experience any renal damage, he did experience a high level of pain acutely and for the next 4 months. A history of exercise supplement intake should increase the index of suspicion for rhabdomyolysis when a patient presents with moderate to severe muscle pain, even if the muscle group is not in a classic location for rhabdomyolysis. PMID:26126260

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2004-01-01

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

  10. Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient.

    PubMed

    Prasad, G V Ramesh; Wong, Timothy; Meliton, Galo; Bhaloo, Salma

    2002-10-27

    Rhabdomyolysis is a known complication of hepatic 3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor (statin) therapy for posttransplant hyperlipidemia, and thus monitoring for this effect is indicated. We report a case of an herbal preparation-induced rhabdomyolysis in a stable renal-transplant recipient, attributed to the presence of red yeast rice (Monascus purpureus) within the mixture. The condition resolved when consumption of the product ceased. Rice fermented with red yeast contains several types of mevinic acids, including monacolin K, which is identical to lovastatin. We postulate that the interaction of cyclosporine and these compounds through the cytochrome P450 system resulted in the adverse effect seen in this patient. Transplant recipients must be cautioned against using herbal preparations to lower their lipid levels to prevent such complications from occurring. PMID:12438974

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

    PubMed

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

    2005-01-01

    A 25-year-old housewife who presented with Mycoplasma pneumonia who developed acute respiratory distress syndrome (ARDS) and required assisted ventilation. During her hospital stay, she developed acute renal failure because of rhabdomyolysis and was put on haemodialysis. She also had difficulty in weaning from ventilator because of acute motor-sensory axonal neuropathy (AMSAN) variant of the Guillain-Barre syndrome. The patient was treated with antibiotics and corticosteroids. The patient recovered from both the complications gradually. PMID:16255404

  12. Simvastatin-associated rhabdomyolysis after coadministration of macrolide antibiotics in two patients.

    PubMed

    Molden, Espen; Andersson, Kirsti Svendsen

    2007-04-01

    Two men, aged 83 and 78 years, who received stable therapy with simvastatin 80 mg/day were hospitalized 1-2 weeks after completion of short-term treatment with erythromycin and clarithromycin, respectively. Both patients were admitted with myalgia, muscle weakness, functional disability (inability to raise arms and legs), and serum creatine kinase levels more than 60 times the upper limit of normal (ULN). Substantial elevations in aspartate aminotransferase (> 30 times the ULN) and alanine aminotransferase (> 7 times the ULN) levels were also observed. Rhabdomyolysis was diagnosed in both patients. Both recovered, but the combined events resulted in almost 40 days of hospitalization, the cost of which is considerable. According to the Naranjo adverse drug reaction probability scale, the likelihood that the rhabdomyolysis was secondary to a simvastatin-macrolide interaction was probable. Four cases of rhabdomyolysis after therapy with combined simvastatin and clarithromycin have been reported previously, but this is apparently the first report of rhabdomyolysis after coadministration of erythromycin. The interacting mechanism likely was inhibited cytochrome P450 (CYP) 3A4 metabolism and possibly P-glycoprotein transport of simvastatin as well. Previous reports of simvastatin-clarithromycin-related events involved additional drugs that inhibited CYP3A4 and P-glycoprotein. However, this was not the situation with our two patients. To prevent future events, it is crucial that clinicians recognize the interaction risk associated with concurrent use of simvastatin and clarithromycin or erythromycin. The risk could be managed by temporary interruption of simvastatin treatment or administration of a noninteracting antimicrobial agent. PMID:17381388

  13. A Substrate Pharmacophore for the Human Organic Cation/Carnitine Transporter Identifies Compounds Associated with Rhabdomyolysis

    PubMed Central

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

    2012-01-01

    The human Organic Cation/Carnitine Transporter (hOCTN2), is a high affinity cation/carnitine transporter expressed widely in human tissues and is physiologically important for the homeostasis of L-carnitine. The objective of this study was to elucidate the substrate requirements of this transporter via computational modelling based on published in vitro data. Nine published substrates of hOCTN2 were used to create a common features pharmacophore that was validated by mapping other known OCTN2 substrates. The pharmacophore was used to search a drug database and retrieved molecules that were then used as search queries in PubMed for instances of a side effect (rhabdomyolysis) associated with interference with L-carnitine transport. The substrate pharmacophore was comprised of two hydrogen bond acceptors, a positive ionizable feature and ten excluded volumes. The substrate pharmacophore also mapped 6 out of 7 known substrate molecules used as a test set. After searching a database of ~800 known drugs, thirty drugs were predicted to map to the substrate pharmacophore with L-carnitine shape restriction. At least 16 of these molecules had case reports documenting an association with rhabdomyolysis and represent a set for prioritizing for future testing as OCTN2 substrates or inhibitors. This computational OCTN2 substrate pharmacophore derived from published data partially overlaps a previous OCTN2 inhibitor pharmacophore and is also able to select compounds that demonstrate rhabdomyolysis, further confirming the possible linkage between this side effect and hOCTN2. PMID:22339151

  14. Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury

    PubMed Central

    Komada, Takanori; Usui, Fumitake; Kawashima, Akira; Kimura, Hiroaki; Karasawa, Tadayoshi; Inoue, Yoshiyuki; Kobayashi, Motoi; Mizushina, Yoshiko; Kasahara, Tadashi; Taniguchi, Shun’ichiro; Muto, Shigeaki; Nagata, Daisuke; Takahashi, Masafumi

    2015-01-01

    Rhabdomyolysis is one of the main causes of community-acquired acute kidney injury (AKI). Although inflammation is involved in the pathogenesis of rhabdomyolysis-induced AKI (RIAKI), little is known about the mechanism that triggers inflammation during RIAKI. Recent evidence has indicated that sterile inflammation triggered by tissue injury can be mediated through multiprotein complexes called the inflammasomes. Therefore, we investigated the role of NLRP3 inflammasomes in the pathogenesis of RIAKI using a glycerol-induced murine rhabdomyolysis model. Inflammasome-related molecules were upregulated in the kidney of RIAKI. Renal tubular injury and dysfunction preceded leukocyte infiltration into the kidney during the early phase of RIAKI, and they were markedly attenuated in mice deficient in NLRP3, ASC, caspase-1, and interleukin (IL)-1? compared with those in wild-type mice. No difference in leukocyte infiltration was observed between wild-type and NLRP3-deficient mice. Furthermore, NLRP3 deficiency strikingly suppressed the expression of renal injury markers and inflammatory cytokines and apoptosis of renal tubular cells. These results demonstrated that NLRP3 inflammasomes contribute to inflammation, apoptosis, and tissue injury during the early phase of RIAKI and provide new insights into the mechanism underlying the pathogenesis of RIAKI. PMID:26045078

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

    PubMed Central

    Vanikar, Aruna V.; Trivedi, Hargovind L.

    2015-01-01

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

  16. Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury.

    PubMed

    Komada, Takanori; Usui, Fumitake; Kawashima, Akira; Kimura, Hiroaki; Karasawa, Tadayoshi; Inoue, Yoshiyuki; Kobayashi, Motoi; Mizushina, Yoshiko; Kasahara, Tadashi; Taniguchi, Shun'ichiro; Muto, Shigeaki; Nagata, Daisuke; Takahashi, Masafumi

    2015-01-01

    Rhabdomyolysis is one of the main causes of community-acquired acute kidney injury (AKI). Although inflammation is involved in the pathogenesis of rhabdomyolysis-induced AKI (RIAKI), little is known about the mechanism that triggers inflammation during RIAKI. Recent evidence has indicated that sterile inflammation triggered by tissue injury can be mediated through multiprotein complexes called the inflammasomes. Therefore, we investigated the role of NLRP3 inflammasomes in the pathogenesis of RIAKI using a glycerol-induced murine rhabdomyolysis model. Inflammasome-related molecules were upregulated in the kidney of RIAKI. Renal tubular injury and dysfunction preceded leukocyte infiltration into the kidney during the early phase of RIAKI, and they were markedly attenuated in mice deficient in NLRP3, ASC, caspase-1, and interleukin (IL)-1? compared with those in wild-type mice. No difference in leukocyte infiltration was observed between wild-type and NLRP3-deficient mice. Furthermore, NLRP3 deficiency strikingly suppressed the expression of renal injury markers and inflammatory cytokines and apoptosis of renal tubular cells. These results demonstrated that NLRP3 inflammasomes contribute to inflammation, apoptosis, and tissue injury during the early phase of RIAKI and provide new insights into the mechanism underlying the pathogenesis of RIAKI. PMID:26045078

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

    PubMed

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

    1999-07-01

    The purpose of this study was to determine if chronic exertional rhabdomyolysis (ER) in Quarter Horses and Thoroughbreds represents one or several distinct myopathies. Eighteen Quarter Horses and 18 Thoroughbreds with ER were selected from cases presented to the Veterinary Hospital on the basis of a history of ER, assessment of muscle histopathology, and serum CK activity before and 4 h post exercise. In addition, 2 of 3 of the following parameters were evaluated: muscle glycogen concentrations, thyroid hormones (T3, T4), fractional excretion (FE) of sodium, potassium and chloride. The CK response to training, the metabolic response to a near maximal standardised exercise test (SET), blood glucose concentrations after an i.v. glucose challenge and a skeletal muscle in vitro caffeine contracture test were performed on 5 of the Quarter Horses, selected because of polysaccharide storage myopathy (PSSM), and 5 of the Thoroughbreds. Serum T3 and T4 were all within normal limits. Low FE of sodium and potassium were seen in < 20% of Quarter Horses and Thoroughbreds. Four hours post exercise, CK was increased in 77% of Quarter Horses and 72% of Thoroughbreds with ER. Muscle glycogen concentrations in Quarter Horses with ER were significantly higher than in normal Quarter Horses and Thoroughbreds with ER. No Thoroughbreds, but 15/18 Quarter Horses with ER had abnormal polysaccharide accumulation in muscle biopsies consistent with a diagnosis of PSSM. PSSM Quarter Horses had higher CK activity during training than Thoroughbreds and higher glycogen utilisation with the SET. PSSM Quarter Horses also had significantly enhanced glucose clearance compared to normal Quarter Horses and Thoroughbreds with ER. Thoroughbreds with ER had significantly lower thresholds for caffeine-induced contracture than normal horses and PSSM Quarter Horses. It was concluded that there are multiple causes for exertional rhabdomyolysis. In Quarter Horses, rhabdomyolysis is commonly due to a glycogen storage disorder, PSSM, and is readily expressed in untrained horses. In Thoroughbreds, ER is commonly due to an underlying abnormality of muscle contraction. Rhabdomyolysis in Thoroughbreds, however, is only expressed intermittently when key stressors are present. PMID:10659313

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

    Toussirot, Éric; Michel, Fabrice; Meneveau, Nicolas

    2015-01-01

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

  20. Severe rhabdomyolysis, acute renal failure and posterior encephalopathy after 'magic mushroom' abuse.

    PubMed

    Bickel, Markus; Ditting, Tilmann; Watz, Henrik; Roesler, Alexander; Weidauer, Stefan; Jacobi, Volkmar; Gueller, Saskia; Betz, Christoph; Fichtlscherer, Stephan; Stein, Juergen

    2005-12-01

    We report the case of a 25-year-old, hepatitis C-infected man, who presented with severe rhabdomyolysis and acute renal failure, and later developed posterior encephalopathy with cortical blindness after the ingestion of magic mushrooms. Conventional respiratory and cardiovascular support including mechanical ventilation, continuous veno-venous hemodialysis and corticosteroids led to improvement and the patient recovered completely over the following months. Magic mushrooms are becoming increasingly fashionable among drug users, as they are believed to be more harmless than other hallucinogenic designer drugs. So far, little is known about their possible severe side effects. PMID:16276262

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2013-11-01

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

  3. Bilateral acute necrosis of the globi pallidi and rhabdomyolysis due to combined methadone and benzodiazepine toxicity.

    PubMed

    Corliss, Robert F; Mandal, Rakesh; Soriano, Benjamin J

    2013-03-01

    Methadone continues to be a widely used maintenance therapy for opiate dependence. However, methadone-related deaths have been reported frequently for over 4 decades now. Anoxic brain injury with pulmonary edema secondary to respiratory depression is the recognized mechanism of methadone death, although pathological intracranial findings are rarely described in methadone deaths. A selective area of brain injury has never been reported with methadone use. We present a case of a 23-year-old man who had acute necrosis of the bilateral globi pallidi in the brain and systemic rhabdomyolysis after ingesting methadone and nasally insufflating alprazolam. We also present a review of the literature on deaths following opioid use and associated brain injury. PMID:23361067

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

    PubMed Central

    Diaz, James H.

    2015-01-01

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

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

    PubMed

    Finsterer, Josef; Stöllberger, Claudia

    2014-06-01

    Recurrent vomiting due to bulimia associated with abuse of furosemide and laxatives causing severe hypokalemia may result in recurrent aborted sudden cardiac death (SCD) and seizures. We report a 25-year-old female with a history of bulimia associated with abuse of furosemide and laxatives since the age of 15 years, migraine since puberty, renal abscesses at age 20 y, and rhabdomyolysis of unknown cause at age 24 y. She experienced aborted SCD due to severe hypokalemia with symptomatic seizures at 21 and 25 years of age. Bulimia patients additionally taking laxatives or furosemide are at particular risk of SCD and rhabdomyolysis and require periodic determination of electrolytes, potassium substitution, and adequate psychiatric therapy and surveillance. PMID:25327327

  6. Rhabdomyolysis of Gluteal Muscles Leading to Renal Failure: A Potentially Fatal Complication of Surgery in the Morbidly Obese

    Microsoft Academic Search

    David Bostanjian; Gary J. Anthone; Nahid Hamoui; Peter F. Crookes

    2003-01-01

    Background: Rhabdomyolysis is a well-known cause of renal failure and is most commonly caused by ischemia\\/reperfusion or crush\\u000a injury. We describe a new cause of this syndrome in a series of 6 patients who underwent necrosis of the gluteal muscles after\\u000a bariatric surgery, 3 of whom eventually died of renal failure. Methods: Potential etiologic factors were studied by comparing\\u000a these

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

    PubMed

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

    2011-06-01

    Minimally invasive spine surgery is increasingly used to treat various spinal pathologies with the goal of minimizing destruction of the surrounding tissues. Rhabdomyolysis (RM) is a rare but known complication of spine surgery, and acute renal failure (ARF) is in turn a potential complication of severe RM. The authors report the first known case series of RM and ARF following minimally invasive lateral spine surgery. The authors retrospectively reviewed data in all consecutive patients who underwent a minimally invasive lateral transpsoas approach for interbody fusion with the subsequent development of RM and ARF at 2 institutions between 2006 and 2009. Demographic variables, patient home medications, preoperative laboratory values, and anesthetic used during the procedure were reviewed. All patient data were recorded including the operative procedure, patient positioning, postoperative hospital course, operative time, blood loss, creatine phosphokinase (CPK), creatinine, duration of hospital stay, and complications. Five of 315 consecutive patients were identified with RM and ARF after undergoing minimally invasive lateral transpsoas spine surgery. There were 4 men and 1 woman with a mean age of 66 years (range 60-71 years). The mean body mass index was 31 kg/m2 and ranged from 25 to 40 kg/m2. Nineteen interbody levels had been fused, with a range of 3-6 levels per patient. The mean operative time was 420 minutes and ranged from 315 to 600 minutes. The CPK ranged from 5000 to 56,000 U/L, with a mean of 25,861 U/L. Two of the 5 patients required temporary hemodialysis, while 3 required only aggressive fluid resuscitation. The mean duration of the hospital stay was 12 days, with a range of 3-25 days. Rhabdomyolysis is a rare but known potential complication of spine surgery. The authors describe the first case series associated with the minimally invasive lateral approach. Surgeons must be aware of the possibility of postoperative RM and ARF, particularly in morbidly obese patients and in procedures associated with prolonged operative times. PMID:21417696

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

    PubMed

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

    2015-07-15

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

  9. Successful management of a dog that had severe rhabdomyolysis with myocardial and respiratory failure.

    PubMed

    Wells, Raegan J; Sedacca, Cassidy D; Aman, Anna M; Hackett, Timothy B; Twedt, David C; Shelton, G Diane

    2009-04-15

    CASE DESCRIPTION - A 6-year-old castrated male Llewelyn Setter was evaluated because of an acute onset of myalgia and respiratory distress. CLINICAL FINDINGS - Physical examination revealed a stiff stilted gait, swollen muscles that appeared to cause signs of pain, panting, and ptyalism. The dog had a decrease in palpebral reflexes bilaterally and a decrease in myotatic reflexes in all 4 limbs. The panniculus reflex was considered normal, and all other cranial nerve reflexes were intact. Serum biochemical analysis revealed markedly high cardiac troponin-I concentration and creatine kinase and aspartate aminotransferase activities. Urinalysis revealed myoglobinuria. Results for thoracic and abdominal radiography, blood pressure measurement, and an ECG were within anticipated limits. Echocardiographic findings were consistent with secondary systolic myocardial failure. Arterial blood gas analysis confirmed hypoxemia and hypoventilation. The dog had negative results when tested for infectious diseases. Examination of skeletal muscle biopsy specimens identified necrotizing myopathy. TREATMENT AND OUTCOME - Treatment included ventilatory support; IV administration of an electrolyte solution supplemented with potassium chloride; administration of dantrolene; vasopressor administration; parenteral administration of nutrients; use of multimodal analgesics; administration of clindamycin, furosemide, mannitol, and enrofloxacin; and dietary supplementation with L-carnitine and coenzyme Q(10). Other medical interventions were not required, and the dog made a rapid and complete recovery. CLINICAL RELEVANCE - Necrotizing myopathy resulting in rhabdomyolysis and myoglobinuria can lead to life-threatening physical and biochemical abnormalities. Making a correct diagnosis is essential, and patients require intensive supportive care. The prognosis can be excellent for recovery, provided there is no secondary organ dysfunction. PMID:19366338

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

    PubMed

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

    2010-12-01

    A total of 30 horses were divided into two groups, one served as a control whereas other was rhabdomyolysis diseased horses. After blood collection, the resulted sera were used for estimation of the activities of creatin kinase (CK), aspartate transaminase (AST), lactate dehydrogenase (LDH), lactic acid, triacylglycerol (TAG), glucose, total protein, albumin, globulin, urea, creatinine, Triiodothyronine (T(3)), calcium, sodium, potassium, phosphorus, chloride, vitamin E, interleukin-6 (IL-6) and tumor necrosis-? (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

  11. Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees

    Microsoft Academic Search

    M. Davis; R. Brown; A. Dickson; H. Horton; D. James; N. Laing; R. Marston; M. Norgate; D. Perlman; N. Pollock; K. Stowell

    2002-01-01

    Malignant hyperthermia (MH) is rarely associated with specific myopathies or musculoskeletal abnormalities. Three clinical investigations of MH associated with either non-specific myopa- thies or congenital disorders in three separate families are presented. Two of these cases also show evidence of exercise-induced rhabdomyolysis. In each case MH susceptibility was con- firmed by in vitro contracture testing of quadriceps muscle. DNA sequence

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

    PubMed

    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

    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

  13. Neurotoxicity, anticoagulant activity and evidence of rhabdomyolysis in patients bitten by death adders (Acanthophis sp.) in southern Papua New Guinea.

    PubMed

    Lalloo, D G; Trevett, A J; Black, J; Mapao, J; Saweri, A; Naraqi, S; Owens, D; Kamiguti, A S; Hutton, R A; Theakston, R D; Warrell, D A

    1996-01-01

    Thirty-two patients with enzyme-immunoassay-proven death adder (Acanthophis sp.) bites were studied in Port Moresby, Papua New Guinea. Eighteen were envenomed; local signs were rare and none had incoagulable blood, but all except one had signs of neurotoxicity. Five (27.7%) envenomed patients required intubation and ventilation. One patient developed renal failure, previously undescribed following death adder bites. Laboratory investigations showed mild prolongation of prothrombin and partial thromboplastin times in some patients. In vitro studies showed that the venom contains anticoagulant activity, but does not cause fibrinogenolysis. In contrast to taipan envenoming, neurotoxicity did not progress after antivenom administration, and there was reversal of neurotoxicity, evident within 6 h, in three severely envenomed patients treated less than 12 h after the bite. One patient treated with antivenom and anticholinesterases had the most dramatic response to treatment; the optimum management of bites by this species may include prompt treatment with both antivenom and anticholinesterases in addition to effective first aid. PMID:8730340

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

    PubMed

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

    1988-09-01

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

  15. Rhabdomyolyse aiguë révélatrice d’une polymyosite chez l’enfant

    Microsoft Academic Search

    B Tabarki; F Thabet; H Selmi; M Yacoub; M Mokni; S Korbi; A. S Essoussi

    2001-01-01

    Traumatic and non-traumatic rhabdomyolysis have been mostly reported in adults. Polymyositis rarely leads to rhabdomyolysis.Case report. – We report the case of a 13-year-old girl with rhabdomyolysis. Full recovery was observed after symptomatic treatment. Nine months later she developed polymyositis.Conclusion. – Long-term follow-up is necessary for rhabdomyolysis, even in those cases with an isolated occurrence caused by viral infection.

  16. Urinalysis

    MedlinePLUS

    ... distal Renal tubular acidosis, proximal Renal vein thrombosis Retrograde ejaculation Rhabdomyolysis Right-sided heart failure Secondary systemic amyloidosis Stress incontinence Systemic lupus erythematosus Systemic sclerosis (scleroderma) Thrombotic ...

  17. BRAINA JOURNAL OF NEUROLOGY Next-generation sequencing reveals DGUOK

    E-print Network

    Mootha, Vamsi K.

    ophthalmoplegia to multi-systemic dis- orders of variable severity. The mutations underlying these conditions mitochondrial myopathy with or without progressive external ophthalmoplegia, recurrent rhabdomyolysis in a young

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

    PubMed Central

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

    2013-01-01

    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

  19. Neuromyelitis optica following CMV primo-infection.

    PubMed

    Tran, C; Du Pasquier, R A; Cavassini, M; Guex-Crosier, Y; Meuli, R; Ciuffreda, D; Waeber, G

    2007-05-01

    We report the case of an acute optic neuromyelitis with rhabdomyolysis in a 34-year-old immunocompetent transsexual patient following a recent cytomegalovirus (CMV) infection. The combination of optic neuropathy and myelopathy is recognized as Devic's syndrome. Clinical presentation was unusual as the recent CMV infection induced rhabdomyolysis and was the suspected trigger of neuromyelitis. PMID:17444889

  20. Genetics Home Reference: Brody myopathy

    MedlinePLUS

    ... SERCA1). The SERCA1 enzyme is found in skeletal muscle cells, specifically in the membrane of a structure called ... breakdown ; calcium ; cell ; contraction ; enzyme ; gene ; inherited ; ions ; muscle cells ; mutation ; myoglobin ; myoglobinuria ; prevalence ; protein ; recessive ; rhabdomyolysis ; sarcoplasmic ...

  1. Phenotype Standardization for Statin-Induced Myotoxicity

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Floyd, James S.; Kaspera, Rüdiger; Marciante, Kristin D.; Weiss, Noel S.; Heckbert, Susan R.; Lumley, Thomas; Wiggins, Kerri L.; Tamraz, Bani; Kwok, Pui-Yan; Totah, Rheem A.; Psaty, Bruce M.

    2013-01-01

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

  3. Hypothyroidism Complicating Nephropathy in a Diabetes Patient

    PubMed Central

    Veerappan, Ilangovan; Abraham, Anila; Hariharan, Somasundaram

    2012-01-01

    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

  4. Intoxications par les champignons : principaux syndromes et traitement

    Microsoft Academic Search

    F Flesch; P Saviuc

    2004-01-01

    Mushroom poisoning syndromes are described with a presentation of the species, their toxins, the symptoms and the treatment. Some new mushroom poisoning syndromes have appeared in this last decade and are here described : acute renal failure with short onset with Amanita proxima, erythermalgia with Clitocybe amoenolens, rhabdomyolysis with Tricholoma equestre and central nervous system failure with Hapalopilus rutilans. The diagnosis

  5. Nutritional Management of Metabolic Disorders

    Microsoft Academic Search

    JOE D. PAGAN

    2009-01-01

    I N T R O D U C T I O N Several metabolic disorders are common in modern breeds of horses. Many of these disorders such as equine Cushing's disease (ECD), equine metabolic syndrome (EMS), osteochondritis dissecans (OCD), recur- rent equine rhabdomyolysis (RER), and polysaccharide storage myopathy (PSSM) can be managed nutritionally by careful regulation of caloric intake with

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

    PubMed Central

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

    2014-01-01

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

  7. Drug utilization in paediatrics: Non-medical factors affecting decision making by prescribers

    Microsoft Academic Search

    M. Stanulovi?; V. Jakovljevi?; N. Ron?evi?

    1984-01-01

    The study was done to show that in certain areas of paediatric pharmacotherapy unexpected discrepancies may arise between accepted therapeutic principles and the actual behaviour of a prescribing doctor. The first example was of a great reduction in penicillin use in a university teaching hospital after certain therapeutic accidents: in one year, there were 2 fatal cases of rhabdomyolysis due

  8. Reversal of Experimental Myoglobinuric Acute Renal Failure in Rats by Quercetin, a Bioflavonoid

    Microsoft Academic Search

    Vikas Chander; Devinder Singh; Kanwaljit Chopra

    2005-01-01

    The occurrence of acute renal failure (ARF) following rhabdomyolysis has been put at between 10 and 40% of cases, and accounts for between 3 and 15% of all cases of ARF. Reactive oxygen intermediates have been demonstrated to play an etiological role in myoglobinuric renal failure. This study was performed to explore the protective effect of quercetin, a bioflavonoid, in

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

    Microsoft Academic Search

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

    2006-01-01

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

  10. Status dystonicus resembling the intrathecal baclofen withdrawal syndrome: a case report and review of the literature

    Microsoft Academic Search

    William Muirhead; Ibrahim Jalloh; Michael Vloeberghs

    2010-01-01

    INTRODUCTION: Status dystonicus is a rare but life-threatening disorder characterized by increasingly frequent and severe episodes of generalized dystonia that may occur in patients with primary or secondary dystonia. Painful and repetitive spasms interfere with respiration and may cause metabolic disturbances such as hyperpyrexia, dehydration, respiratory insufficiency, and acute renal failure secondary to rhabdomyolysis. Intrathecally administered baclofen, delivered by an

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

    ERIC Educational Resources Information Center

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

    2009-01-01

    Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The…

  12. Insuffisance rénale aiguë révélant une hypothyroïdie auto-immune

    Microsoft Academic Search

    Dina Ibrahim Montasser; Mohamed Hassani; Yassir Zajjari; Abdelali Bahadi; Ahmed Alayoud; Amine Hamzi; Kawtar Hassani; Omar Moujoud; Mohamed Asseraji; Moncif Kadiri; Taoufik Aatif; Driss El Kabbaj; Mohamed Benyahia; Mustapha Allam; Ismail Akhmouch; Zouhir Oualim

    2010-01-01

    Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a

  13. ORIGINAL ARTICLE Transgenic mouse model reveals an unsuspected role of the

    E-print Network

    Lasalde Dominicc, Jose A. - Department of Biology, Universidad de Puerto Rico

    . Myalgia is defined as muscle weakness or pain without an elevation in serum creatine kinase (CK) levels to muscular symptoms with serum creatine kinase elevation, and the life-threatening rhabdomyolysis, which is characterized by a marked creatine kinase elevation and can cause severe muscle pain, renal failure

  14. Expanding the phenotype of GMPPB mutations.

    PubMed

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

    2015-04-01

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

  15. Acute sodium valproate intoxication: occurrence of renal failure and treatment with haemoperfusion-haemodialysis.

    PubMed

    Roodhooft, A M; Van Dam, K; Haentjens, D; Verpooten, G A; Van Acker, K J

    1990-02-01

    In a child who probably received an overdose of sodium valproate, progressive coma, intermittent tonic-clonic seizures and anuria developed. Laboratory investigations revealed coagulopathy, and anaemia and mildly disturbed liver function. Progressive renal insufficiency, probably due to rhabdomyolysis and myoglobulinuria, occurred later. Treatment consisted of supportive measures, combined haemoperfusion and haemodialysis and IV thiopentone. Clinical and biochemical normalisation was observed after 11 days. PMID:2107081

  16. A case of severe heatstroke and review of pathophysiology, clinical presentation, and treatment.

    PubMed

    Horseman, Michael A; Rather-Conally, Jacquelyn; Saavedra, Crystal; Surani, Salim

    2013-01-01

    Heatstroke is life-threatening condition characterized by hyperthermia and central nervous system disturbances. It can also be classified as a form of systemic inflammatory response syndrome with multiple organ dysfunction and in many ways resembles sepsis. Like sepsis, most patients with heatstroke demonstrate a hyperdynamic hemodynamic response. In contrast to sepsis, rhabdomyolysis may complicate management and initial fluid resuscitation is not well defined. We present an illustrative case report and review of literature. PMID:22232203

  17. Primary Adenosine Monophosphate (AMP) Deaminase Deficiency in a Hypotonic Infant

    Microsoft Academic Search

    Manuel Castro-Gago; Carmen Gómez-Lado; Laura Pérez-Gay; Jesús Eirís-Puñal; Elena Pintos Martínez; Inés García-Consuegra; Miguel Angel Martín

    2011-01-01

    The spectrum of the adenosine monophosphate (AMP) deaminase deficiency ranges from asymptomatic carriers to patients who manifest exercise-induced muscle pain, occasionally rhabdomyolysis, and idiopathic hyperCKemia. However, previous to the introduction of molecular techniques, rare cases with congenital weakness and hypotonia have also been reported. We report a 6-month-old girl with the association of congenital muscle weakness and hypotonia, muscle deficiency

  18. Safety of statins

    PubMed Central

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

    2013-01-01

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

  19. Dystrophinopathy mimicking metabolic myopathies.

    PubMed

    Liewluck, Teerin; Tian, Xia; Wong, Lee-Jun; Pestronk, Alan

    2015-08-01

    Recurrent rhabdomyolysis warrants comprehensive evaluations to search for underlying muscle diseases, including metabolic myopathies, LPIN1-myopathy, RYR1-myopathy, and less commonly muscular dystrophies. The absence of weakness and the normal or minimally elevated creatine kinase levels between attacks are typical of metabolic myopathies, LPIN1-myopathy, and RYR1-myopathy, while the presence of weakness and the highly elevated creatine kinase levels between attacks point toward muscular dystrophies. Here we report a 32-year-old man with a one-year history of recurrent rhabdomyolysis, who had normal strength, slightly elevated baseline creatine kinase level, and normal muscle histopathology. All workups for metabolic myopathies, LPIN1-myopathy and RYR1-myopathy were unrevealing. Next generation sequencing of muscular dystrophy-related genes revealed a hemizygous deletion of exons 17-34 of the dystrophin-encoding gene. Immunohistochemical study revealed absent staining for the rod domain of dystrophin. Dystrophinopathy should be considered in patients with recurrent rhabdomyolysis despite the absence of fixed weakness or highly elevated resting creatine kinase level. PMID:25998609

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

    PubMed

    Redshaw, Charlotte; Stewart, Catherine

    2014-11-01

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

  1. The investigation and management of metabolic myopathies.

    PubMed

    Olpin, Simon Edward; Murphy, Elaine; Kirk, Richard James; Taylor, Robert William; Quinlivan, Rosaline

    2015-06-01

    Metabolic myopathies (MM) are rare inherited primary muscle disorders that are mainly due to abnormalities of muscle energy metabolism resulting in skeletal muscle dysfunction. These diseases include disorders of fatty acid oxidation, glyco(geno)lytic muscle disorders and mitochondrial respiratory chain (MRC) disease. Clinically these disorders present with a range of symptoms including infantile hypotonia, myalgia/exercise tolerance, chronic or acute muscle weakness, cramps/spasms/stiffness or episodic acute rhabdomyolysis. The precipitant may be fasting, infection, general anaesthesia, heat/cold or most commonly, exercise. However, the differential diagnosis includes a wide range of both acquired and inherited conditions and these include exposure to drugs/toxins, inflammatory myopathies, dystrophies and channelopathies. Streamlining of existing diagnostic protocols has now become a realistic prospect given the availability of second-generation sequencing. A diagnostic pathway using a 'rhabdomyolysis' gene panel at an early stage of the diagnostic process is proposed. Following detailed clinical evaluation and first-line investigations, some patients will be identified as candidates for McArdle disease/glycogen storage disease type V or MRC disease and these will be referred directly to the specialised services. However, for the majority of patients, second-line investigation is best undertaken through next-generation sequencing using a 'rhabdomyolysis' gene panel. Following molecular analysis and careful evaluation of the findings, some patients will receive a clear diagnosis. Further functional or specific targeted testing may be required in other patients to evaluate the significance of uncertain/equivocal findings. For patients with no clear diagnosis, further investigations will be required through a specialist centre. PMID:25878327

  2. Idiopathic Systemic Capillary Leak Syndrome (Clarkson's Disease): The Mayo Clinic Experience

    PubMed Central

    Kapoor, Prashant; Greipp, Patricia T.; Schaefer, Eric W.; Mandrekar, Sumithra J.; Kamal, Arif H.; Gonzalez-Paz, Natalia C.; Kumar, Shaji; Greipp, Philip R.

    2010-01-01

    OBJECTIVE: To determine clinical features, natural history, and outcome of a well-defined cohort of 25 consecutive patients with idiopathic systemic capillary leak syndrome (SCLS) evaluated at a tertiary care center. PATIENTS AND METHODS: Records of patients diagnosed as having SCLS from November 1, 1981, through April 30, 2008, were reviewed. Descriptive statistics were used to analyze patient demographics, clinical features, complications, and therapeutic interventions. RESULTS: Of the 34 patients whose records were reviewed, 25 fulfilled all diagnostic criteria for SCLS. The median age at diagnosis of SCLS was 44 years. Median follow-up of surviving patients was 4.9 years, and median time to diagnosis from symptom onset was 1.1 years (interquartile range, 0.5-4.1 years). Flulike illness or myalgia was reported by 14 patients (56%) at onset of an acute attack of SCLS, and rhabdomyolysis developed in 9 patients (36%). Patients with a greater decrease in albumin level had a higher likelihood of developing rhabdomyolysis (p=.03). Monoclonal gammopathy, predominantly of the IgG-? type, was found in 19 patients (76%). The progression rate to multiple myeloma was 0.7% per person-year of follow-up. The overall response rate to the different therapies was 76%, and 24% of patients sustained durable (>2 years) complete remission. The estimated 5-year overall survival rate was 76% (95% confidence interval, 59%-97%). CONCLUSION: Systemic capillary leak syndrome, a rare disease that occurs in those of middle age, is usually diagnosed after a considerable delay from onset of symptoms. The degree of albumin decrement during an attack correlates with development of rhabdomyolysis. A reduction in the frequency and/or the severity of attacks was seen in nearly three-fourths of patients who were offered empirical therapies. The rate of progression to multiple myeloma appears to be comparable to that of monoclonal gammopathy of undetermined significance. PMID:20634497

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

    PubMed

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

    2013-01-01

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

  4. Deliberate overdose of uranium: toxicity and treatment.

    PubMed

    Pavlakis, N; Pollock, C A; McLean, G; Bartrop, R

    1996-01-01

    A case is described of deliberate ingestion of 15 g of uranium acetate which resulted in acute renal failure requiring dialytic therapy for 2 weeks, refractory anaemia, rhabdomyolysis, myocarditis, liver dysfunction with a disproportionate coagulopathy and paralytic ileus. Despite significant elevations in plasma uranium levels, treatment with both calcium EDTA and calcium DTPA were ineffective in promoting uranium excretion. Six months later the initial significant renal impairment exists with a persistent incomplete Fanconi syndrome. Future options for management of this unusual cause of acute renal failure are discussed. PMID:8684547

  5. Sloughing Esophagitis: A Not So Common Entity

    PubMed Central

    Akhondi, Hossein

    2014-01-01

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

  6. A Statin a Day to Keep the Doctor Away? Comparing Aspirin and Statins for Primary Prevention of Cardiovascular Disease.

    PubMed

    Dietrich, Eric; Davis, Kyle

    2014-06-23

    For the primary prevention of cardiovascular (CV) disease, aspirin reduces the risk for major vascular events by approximately 15% to 20% with an absolute reduction of approximately 0.1%. Major bleeding occurs at an excess of approximately 2 cases per 1000 patient-years with aspirin therapy. For primary prevention, statin therapy has been shown to reduce the risk of CV events by approximately 30% to 40% with an absolute reduction of 1% to 2%. Rhabdomyolysis is rare, with an incidence of 3.4 cases per 100 000 patient-years. Compared with aspirin, statins have a more favorable risk-to-benefit profile for primary prevention. PMID:24958491

  7. An Atropa belladonna L. poisoning with acute subdural hematoma.

    PubMed

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

    2011-12-01

    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

  8. Serotonin syndrome due to an overdose of moclobemide and clomipramine. A potentially life-threatening association.

    PubMed

    François, B; Marquet, P; Desachy, A; Roustan, J; Lachatre, G; Gastinne, H

    1997-01-01

    The serotonin syndrome is frequently characterized by minor neurologic manifestations that regress rapidly (such as confusion, tremor, ...). Many medications including tricyclic antidepressants, serotonin reuptake inhibitors, tryptophan and the association of monoamine oxidase inhibitors together with a serotoninergic agent have been implicated in this syndrome. In certain cases, and for poorly understood reasons, clinical manifestations can include circulatory collapse, malignant hyperthermia, convulsions and rhabdomyolysis. These forms are often fatal. Treatment, other than the withdrawal of the offending drug, is symptomatic. Dialysis may be of value in withdrawing the drug from the circulatory system. We report a patient with the serotonin syndrome of favorable outcome due to an overdose of moclobemide and clomipramine. PMID:9037653

  9. Oral Nanoparticulate Atorvastatin Calcium is More Efficient and Safe in Comparison to Lipicure ® in Treating Hyperlipidemia

    Microsoft Academic Search

    A. K. Meena; D. Venkat Ratnam; G. Chandraiah; D. D. Ankola; P. Rama Rao; M. N. V. Ravi Kumar

    2008-01-01

    Atorvastatin calcium (AC) is a second-generation 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor approved for clinical\\u000a use as a lipid lowering agent. AC, the world’s best selling drug is associated with poor oral bioavailability and serious\\u000a adverse effects like rhabdomyolysis on chronic administration. A biodegradable nanoparticulate approach was introduced here\\u000a with a view to improving the efficacy and safety of AC. Poly lactide-co-glycolic acid

  10. Serotonin syndrome.

    PubMed

    Bodner, R A; Lynch, T; Lewis, L; Kahn, D

    1995-02-01

    We describe a patient treated with trazodone, isocarboxazid, and methylphenidate hydrochloride who developed confusion, agitation, poor concentration, rigidity, myoclonus, involuntary movements, orthostatic hypotension, and hyperreflexia. CK was normal, and the syndrome resolved spontaneously over 12 hours. The serotonin syndrome occurs following the use of serotomimetic agents (serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, tryptophan, 3,4-methylenedioxy-methamphetamine, dextromethorphan, meperidine, S-adenosylmethionine) alone or in combination with monoamine oxidase inhibitors. It is characterized by various combinations of myoclonus, rigidity, hyperreflexia, shivering, confusion, agitation, restlessness, coma, autonomic instability, low-grade fever, nausea, diarrhea, diaphoresis, flushing, and rarely, rhabdomyolysis and death. PMID:7854515

  11. Burnt sugarcane harvesting is associated with acute renal dysfunction.

    PubMed

    Paula Santos, Ubiratan; Zanetta, Dirce Maria T; Terra-Filho, Mário; Burdmann, Emmanuel A

    2015-04-01

    Sugarcane harvesting has been associated with an epidemic of chronic kidney disease in Central America mainly affecting previously healthy young workers. Repeated episodes of acute kidney dysfunction are hypothesized to be one of the possible mechanisms for this phenomenon. Therefore, this exploratory study aimed to assess the acute effects of burnt sugarcane harvesting on renal function among 28 healthy non-African Brazilian workers. Urine and blood samples were collected at the beginning and at the end of the harvesting season and before and at the end of a harvesting workday. All individuals decreased their estimated glomerular filtration rate by ?20% at the end of the daily shift, and 18.5% presented with serum creatinine increases consistent with acute kidney injury. Those changes were associated with increased serum creatine phosphokinase (a known marker for exertional rhabdomyolysis) and oxidative stress-associated malondialdehyde levels, increased peripheral blood white cell counts, decreased urinary and serum sodium, decreased calculated fractional sodium excretion, and increased urine density. Thus, burnt sugarcane harvesting caused acute renal dysfunction in previously healthy workers. This was associated with a combination of dehydration, systemic inflammation, oxidative stress, and rhabdomyolysis. PMID:25229334

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

    PubMed Central

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

    2014-01-01

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

  13. Novel Inhibitors of Human Organic Cation/Carnitine Transporter (hOCTN2) via Computational Modeling and In Vitro Testing

    PubMed Central

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

    2010-01-01

    Purpose The objective was to elucidate the inhibition requirements of the human Organic Cation/Carnitine Transporter (hOCTN2). Methods Twenty-seven drugs were screened initially for their potential to inhibit uptake of L-carnitine into a stably transfected hOCTN2-MDCK cell monolayer. A HipHop common features pharmacophore was developed and used to search a drug database. Fifty-three drugs, including some not predicted to be inhibitors, were selected and screened in vitro. Results A common features pharmacophore was derived from initial screening data and consisted of three hydrophobic features and a positive ionizable feature. Among the 33 tested drugs that were predicted to map to the pharmacophore, 27 inhibited hOCTN2 in vitro (40% or less L-carnitine uptake from 2.5?M L-carnitine solution in presence of 500 ?M drug, compared to L-carnitine uptake without drug present). Hence, the pharmacophore accurately prioritized compounds for testing. Ki measurements showed low micromolar inhibitors belonged to diverse therapeutic classes of drugs, including many not previously known to inhibit hOCTN2. Compounds were more likely to cause rhabdomyolysis if the Cmax/Ki ratio was higher than 0.0025. Conclusion A combined pharmacophore and in vitro approach found new, structurally diverse inhibitors for hOCTN2 that may possibly cause clinical significant toxicity such as rhabdomyolysis. PMID:19437106

  14. Cocaine and kidney injury: a kaleidoscope of pathology

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Aghabiklooei, Abbas; Edalatparvar, Maryam; Mostafazadeh, Babak

    2014-01-01

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

  19. How electroshock weapons kill!

    NASA Astrophysics Data System (ADS)

    Lundquist, Marjorie

    2010-03-01

    Growing numbers of law enforcement officers now carry an electroshock weapon (ESW). Over 500 U.S. deaths have followed ESW use in the past 26 years; over 450 of these deaths followed use of an electromuscular disruptor in the past 9 years. Most training courses teach that ESWs are safe; that they can kill only by the direct effect of electric current on the heart; and that a death following use of an ESW always has some other cause. All these teachings are false! The last was disproved by Lundquist.^1 Williams^2 ruled out direct electrical effects as a cause of almost all the 213 deaths he studied, leaving disruption of normal physiological processes as the only alternative explanation. Careful study of all such deaths identifies 4 different ways that death has or could have been brought about by the ESW: kidney failure following rhabdomyolysis [rare]; cardiac arrest from hyperkalemia following rhabdomyolysis [undocumented]; lactic acid-induced ventricular fibrillation [conclusive proof impossible]; and [most common] anoxia from so much lactic acid in the circulating blood that it acts as an oxygen scavenger, continuously depleting the blood of oxygen until most of the lactate has been metabolized. ^1M. Lundquist, BAPS 54(1) K1.270(2009). ^2Howard E. Williams, Taser Electronic Control Devices and Sudden In-Custody Death, 2008.

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

    PubMed Central

    Michot, Caroline; Mamoune, Asmaa; Vamecq, Joseph; Viou, Mai Thao; Hsieh, Lu-Sheng; Testet, Eric; Lainé, Jeanne; Hubert, Laurence; Dessein, Anne-Frédérique; Fontaine, Monique; Ottolenghi, Chris; Fouillen, Laetitia; Nadra, Karim; Blanc, Etienne; Bastin, Jean; Candon, Sophie; Pende, Mario; Munnich, Arnold; Smahi, Asma; Djouadi, Fatima; Carman, George M.; Romero, Norma; de Keyzer, Yves; de Lonlay, Pascale

    2014-01-01

    Lipin-1 deficiency is associated with massive rhabdomyolysis episodes in humans, precipitated by febrile illnesses. Despite well-known roles of lipin-1 in lipid biosynthesis and transcriptional regulation, the pathogenic mechanisms leading to rhabdomyolysis remain unknown. Here we show that primary myoblasts from lipin-1-deficient patients exhibit a dramatic decrease in LPIN1 expression and phosphatidic acid phosphatase 1 activity, and a significant accumulation of lipid droplets (LD). The expression levels of LPIN1-target genes [peroxisome proliferator-activated receptors delta and alpha (PPAR?, PPAR?), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1?), acyl-coenzyme A dehydrogenase, very long (ACADVL), carnitine palmitoyltransferase IB and 2 (CPT1B and CPT2)] were not affected while lipin-2 protein level, a closely related member of the family, was increased. Microarray analysis of patients’ myotubes identified 19 down-regulated and 51 up-regulated genes, indicating pleiotropic effects of lipin-1 deficiency. Special attention was paid to the up-regulated ACACB (acetyl-CoA carboxylase beta), a key enzyme in the fatty acid synthesis/oxidation balance. We demonstrated that overexpression of ACACB was associated with free fatty acid accumulation in patients’ myoblasts whereas malonyl-carnitine (as a measure of malonyl-CoA) and CPT1 activity were in the normal range in basal conditions accordingly to the normal daily activity reported by the patients. Remarkably ACACB invalidation in patients’ myoblasts decreased LD number and size while LPIN1 invalidation in controls induced LD accumulation. Further, pro-inflammatory treatments tumor necrosis factor alpha + Interleukin-1beta(TNF1? + IL-1?) designed to mimic febrile illness, resulted in increased malonyl-carnitine levels, reduced CPT1 activity and enhanced LD accumulation, a phenomenon reversed by dexamethasone and TNF? or IL-1? inhibitors. Our data suggest that the pathogenic mechanism of rhabdomyolysis in lipin-1-deficient patients combines the predisposing constitutive impairment of lipid metabolism and its exacerbation by pro-inflammatory cytokines. PMID:23928362

  1. Exercise-induced cardiac arrest in a sickle cell trait-positive Air Force recruit: a case report.

    PubMed

    Fajardo, Kevin A; Tchandja, Juste

    2015-03-01

    In October 2011, a sickle cell trait (SCT)-positive Air Force recruit collapsed and died immediately following his physical fitness test. The cause of death was reported to be a cardiac dysrhythmia secondary to an acute sickling crisis. Although it is well known that SCT-positive individuals have a significant risk of exercise-related death (ERD), this case is notable in that none of the commonly cited risk factors were present, including exertional heat injury, dehydration, training at altitude, and rhabdomyolysis. Our findings challenge the commonly held assertion exertional heat illness is the fundamental underlying etiology in these cases, and that the current Department of Defense's policy on SCT screening is ineffective at mitigating the risk of ERD in SCT-positive recruits. Furthermore, we argue that without a clearer understanding of the precise risk factors for ERD in this population, screening programs may actually shift excessive health risks onto those without SCT. PMID:25735033

  2. Propofol Infusion Syndrome in Adults: A Clinical Update

    PubMed Central

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

    2015-01-01

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

  3. [Preoperative assessment, preparation and prospect of prognosis in schizophrenic patients].

    PubMed

    Kudoh, Akira

    2010-09-01

    Schizophrenic patients are at increased risk for perioperative complications such as hypotension and hypothermia during anesthesia, postoperative ileus, confusion and pneumonia. In addition, schizophrenic patients are predisposed to developing pulmonary thromboembolism, torsade de pointes, water intoxication and rhabdomyolysis. The increased complications are associated with physical disorders, antipsychotic agents, hazardous health behaviors, and interactions between antipsychotic agents and anesthetic drugs. Increased cortisol, norepinephrine and cytokine concentrations are considered as possible cause of postoperative confusion and ileus. Anesthesia with ketamine, propofol and fentanyl decreased the frequency of the postoperative confusion in schizophrenic patients. Epidural anesthesia with local anesthesia in schizophrenic patients undergoing abdominal surgery minimized postoperative ileus. Antipsychotic drugs administrated to schizophrenic patients should be continued before anesthesia for decreasing postoperative confusion. Thus, anesthesiologists must not only be aware of the perioperative problems of these patients but must also learn how to manage their perioperative course. PMID:20857665

  4. Mass envenomations by honey bees and wasps.

    PubMed Central

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

    1999-01-01

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

  5. Diagnosis of mitochondrial myopathies.

    PubMed

    Milone, Margherita; Wong, Lee-Jun

    2013-01-01

    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

  6. Hypoparathyroidism in a 3-year-old Korean boy with Sotos syndrome and a novel mutation in NSD1.

    PubMed

    Wejaphikul, Karn; Cho, Sung Yoon; Huh, Rimm; Kwun, Younghee; Lee, Jieun; Ki, Chang-Seok; Jin, Dong-Kyu

    2015-01-01

    Sotos syndrome is a common genetic overgrowth syndrome caused by a mutation of the NSD1 gene, which is located at chromosome 5q35 and normally encodes a histone methyltransferase protein. The general characteristics of this syndrome include a characteristic facial appearance, developmental delay, and overgrowth, resulting in macrocephaly and tall stature. We describe rhabdomyolysis and hypocalcemia due to hypoparathyroidism in a 3-year-old Korean boy with Sotos syndrome. He was diagnosed with Sotos syndrome based on the typical phenotype and has a heterozygous nonsense mutation (c.4710C>A [p.Cys1570*]) of the NSD1 gene, which causes a premature stop codon and a truncating protein mutation. Hypoparathyroidism has never been described in Sotos syndrome. This report may therefore expand the phenotypic spectrum of this syndrome. PMID:25887879

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

    SciTech Connect

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

    1995-09-11

    A 7-month-old boy with gross motor delay and failure to thrive presented with rhabdomyolysis following an acute asthmatic episode. During hospitalization an electrocardiographic conversion to a Wolff-Parkinson-White type 1 (WPW) pattern took place. Duchenne muscular dystrophy (DMD) was suspected based on elevated creatine kinase (CK) serum levels, muscle biopsy, and family history. The diagnosis was confirmed by molecular analysis, which documented a deletion corresponding to cDNA probe 1-2a in the dystrophin gene, in the propositus and in an affected male cousin of his mother. {open_quotes}Idiopathic{close_quotes} hyperCKemia was found in the propositus, his father, and 5 of his relatives. We suggest that the unusually early and severe manifestations of DMD in this patient may be related to the coincidental inheritance of the maternal DMD gene and of a paternal gene, causing hyperCKemia. 13 refs., 3 figs., 1 tab.

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

    SciTech Connect

    Bruninx, Guy; Wery, Didier; Dubois, Eric; El Nakadi, Badih; Dueren, Eric van; Verhelst, Guy; Delcour, Christian [Unite Vasculaire Integree, CHU de Charleroi, 92 Blvd. P. Janson, B-6000 Charleroi (Belgium)

    1999-11-15

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

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

    PubMed

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

    2014-01-01

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

  10. Negative health implications of sickle cell trait in high income countries: from the football field to the laboratory.

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Jo, Woo-Sik; Hossain, Md. Akil

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

    A female patient in her 60s presented with a history of malaise, chills, headache and vomiting. She was in shock on presentation with a high haematocrit and a low albumin with evidence of rhabdomyolysis. Severe limb and truncal oedema developed with worsening hypotension leading to intensive care unit admission for multiple organ support. Extensive radiological, microbiological and immunological work up was negative with the exception of a monoclonal gammopathy. A review of patient investigations led to a diagnosis of Clarkson's disease. Treatment with high-dose methylprednisolone and intravenous immunoglobulins led to a rapid decline in the creatine kinase (CK) level and vasopressor requirements. The patient was discharged home on long-term terbutaline and has made a good recovery. PMID:23576661

  14. Unusual Case of Acute Renal Failure Following Multiple Wasp Stings

    PubMed Central

    Rachaiah, Niranjan M; Jayappagowda, Lokesh A; Siddabyrappa, Harsha B; Bharath, Venkatesh K

    2012-01-01

    The wasp stings usually cause local reactions and rarely anaphylaxis. However the multiple wasp stings may cause multisystem involvement. We report a case of acute renal failure (ARF) following multiple wasp stings. A middle aged healthy gentleman presented with pain and swelling of the upper part of the body following multiple wasp stings. After 2 days, he developed progressive decrease in urine output with high colored urine. Physical examination revealed the edematous and tender affected part. On investigating, it was found to have sequential elevations in renal function tests. The markers of muscle injury were grossly elevated and liver enzymes were deranged. These findings suggest multisystem involvement predominantly ARF secondary to rhabdomyolysis. With the initiation of the intense hemodialysis, all the above parameters became normal. Timely intervention of multiple wasp stings causing ARF with multiorgan involvement by hemodialysis not only prevents mortality but also other complications. PMID:22408758

  15. Electronic gun (Taser) injuries.

    PubMed

    Ordog, G J; Wasserberger, J; Schlater, T; Balasubramanium, S

    1987-01-01

    The Taser is an electrical weapon used for immobilization. Two hundred eighteen patients who were shot by police with a Taser for violent or criminal behavior were compared to 22 similar patients shot by police with .38 Specials. The long-term morbidity rate was significantly different for "tasered" victims (0%) and for those with bullet wounds (50%) (P less than .05). The mortality rate was also significantly different between "tasered" victims (1.4%), and gunshot wound victims (50%) (P less than .05). Possible complications associated with Taser wounds included contusions, abrasions, and lacerations (38%); mild rhabdomyolysis (1%); and testicular torsion (0.5%). Although 48% of "tasered" patients required hospitalization, all but one was for a preexisting injury or toxic or psychiatric problem. We conclude that Tasers are relatively safe when compared to shooting with more conventional weapons. PMID:3800082

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

    PubMed Central

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

    2014-01-01

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

  17. Pemphigus erythematosus relapse associated with atorvastatin intake.

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2008-02-01

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

  20. [Nicolau syndrome after intramuscular injection].

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2014-12-01

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

  3. Successful treatment of an episode of malignant hyperthermia using a large dose of dantrolene.

    PubMed

    Blank, J W; Boggs, S D

    1993-01-01

    This clinical case report describes the use of extremely high doses of dantrolene in the management of an episode of malignant hyperthermia (MH). A 6-year-old, 25 kg girl underwent anesthetic induction with halothane for an elective inguinal herniorrhaphy. Tachydysrhythmias, laryngospasm, opisthotonos, rhabdomyolysis, and profound metabolic acidosis ensued as features of an MH crisis. Initial dantrolene administration did not alleviate the symptoms. Increasing doses of dantrolene eventually totaling 42 mg/kg, along with symptomatic supportive care, were administered successfully to treat the event. It is postulated that the severe muscle rigidity may have precluded the circulation of dantrolene to its site of action. The role of the Malignant Hyperthermia Association of the United States (MHAUS) Hotline as a 24-hour consultative service is noted. PMID:8442973

  4. [Treatment of heat stroke].

    PubMed

    Yagi, Keiichi; Kim, Soong-Ho

    2012-06-01

    Immediate cooling and support of organ-system function are the two main therapeutic objectives in patients with heat stroke. When cooling is rapidly initiated and both the body temperature and cognitive function return to the normal range within an hour of onset of symptoms, most patients recover fully. Immersion in an ice-water bath is the most effective cooling method, and evaporative cooling is a rapid and effective alternative. To prevent the development of rhabdomyolysis-induced acute renal failure, aggressive IV rehydration should be continued for first 24 to 72 hours with the goal of maintaining a minimum urine output of 2 mL/kg/h. Treatment of heat cramps also consists of fluid and salt replacement (PO or IV) and rest in a cool environment. In severe cases, IV magnesium sulphate may be effective to relieve muscle cramping. PMID:22690601

  5. Fatal propofol infusion syndrome in association with ketogenic diet.

    PubMed

    Baumeister, F A M; Oberhoffer, R; Liebhaber, G M; Kunkel, J; Eberhardt, J; Holthausen, H; Peters, J

    2004-08-01

    Propofol is used for the treatment of refractory status epilepticus. When given as a long-term infusion propofol may cause a rare but frequently fatal complication, the propofol infusion syndrome. The hallmarks are metabolic acidosis, lipemia, rhabdomyolysis and myocardial failure. Propofol infusion syndrome is caused by impaired fatty acid oxidation. Beside anticonvulsants the ketogenic diet, a high-fat, low-carbohydrate, adequate-protein diet, is an effective treatment for difficult-to-control seizures. We report a 10-year-old boy with catastrophic epilepsy, who developed fatal propofol infusion syndrome when a ketogenic diet was initiated. Substances like propofol which impair fatty acid oxidation may pose an increased risk if combined with ketogenic diet. PMID:15328567

  6. Muscle symptoms and creatine phosphokinase elevations in patients receiving raltegravir in clinical practice: Results from the SCOLTA project long-term surveillance.

    PubMed

    Madeddu, Giordano; De Socio, Giuseppe V L; Ricci, Elena; Quirino, Tiziana; Orofino, Giancarlo; Carenzi, Laura; Franzetti, Marco; Parruti, Giustino; Martinelli, Canio; Vichi, Francesca; Penco, Giovanni; Dentone, Chiara; Celesia, Benedetto Maurizio; Maggi, Paolo; Libertone, Raffaella; Bagella, Paola; Di Biagio, Antonio; Bonfanti, Paolo

    2015-03-01

    Muscle alterations ranging from asymptomatic creatine phosphokinase (CPK) increases to rhabdomyolysis and central nervous system (CNS) symptoms have been reported in patients receiving raltegravir. Muscle symptoms and CPK increases were investigated in a cohort of HIV-infected patients receiving raltegravir-based antiretroviral therapy, and possible associated predictors were evaluated. The SCOLTA Project is a prospective, observational, multicentre study created to assess the incidence of adverse events in patients receiving new antiretroviral drugs in clinical practice. In total, 496 HIV-infected patients were enrolled [333 (67.1%) male]. CDC stage was C in 196 patients (39.5%). Mean age at enrolment was 45.9 ± 9.3 years. Median follow-up was 21 months. Twenty-six patients (5.2%) reported muscle symptoms (16 muscle pain and 17 weakness; 7 had both). Of 342 patients with normal baseline CPK values, 72 (21.1%) had a CPK increase. Seven patients (1.4%) discontinued raltegravir because of muscular events (three for muscle pain/weakness and four CPK increases). No cases of rhabdomyolysis were observed. Patients with muscle symptoms were more frequently receiving in their regimen than those not receiving atazanavir (P=0.04) and were more likely to also report CNS symptoms (P<0.0001). Significant predictors of muscle symptoms were CNS symptoms and use of atazanavir. Female sex was associated with a reduced risk of CPK increase. In conclusion, muscle symptoms and CPK elevations occurred frequently and caused most discontinuations due to adverse events. Their monitoring in patients receiving raltegravir should be considered, especially when co-administered with atazanavir or when CNS symptoms are also present. PMID:25476452

  7. Enteral feeding improves outcome and protects against glycerol-induced acute renal failure in the rat.

    PubMed

    Roberts, P R; Black, K W; Zaloga, G P

    1997-10-01

    Acute renal failure is a common cause of morbidity and mortality in critically ill patients and frequently results from vasoconstrictive ischemic injury to the kidney. Protein and amino acids can vasodilate renal blood vessels. Thus, we tested the hypothesis that enteral feeding could prevent renal ischemic injury using an experimental model in which renal vasoconstriction is believed to cause ischemic renal injury. This study was performed using male Sprague-Dawley rats, and renal injury was induced by glycerol injection into the hind limbs. The resulting muscle necrosis (rhabdomyolysis) causes acute renal injury. In the first part of the study, 35 animals were randomized to a peptide-based enteral diet or water via a duodenal feeding tube and subsequently injected with glycerol. Seventy-eight percent (14 of 18) of the animals receiving the enteral diet survived 3 d compared with 35% (six of 17) of the water-fed animals (p < 0.05). Blood urea nitrogen (47+/-8 versus 137+/-27 mg/dl) and creatinine (0.8+/-0.1 versus 2.0+/-0.3 mg/dl) were significantly lower in the enteral survivors than in the water survivors. In the second part of the study, renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (insulin clearance) were measured in similarly treated animals (n = 14) 1 d after injury. Renal plasma flow (4.83+/-0.65 versus 2.37+/-0.62 ml/min) and glomerular filtration rate (2.05+/-0.27 versus 0.89+/-0.22 ml/min) were significantly higher in the enteral group than in the water group. These data indicate that enteral feeding can prolong survival and decrease renal injury after glycerol-induced rhabdomyolysis. The mechanism for the protection is partly related to maintenance of renal blood flow. PMID:9351632

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

    PubMed Central

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

    2014-01-01

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

  9. Currently available hypolipidaemic drugs and future therapeutic developments.

    PubMed

    Farmer, J A; Gotto, A M

    1995-10-01

    Dyslipidaemia may be treated with a number of safe and effective pharmacological agents that target specific lipid disorders through a variety of mechanisms. The bile-acid sequestrants--cholestyramine and colestipol--primarily decrease LDL cholesterol by binding bile acids, thereby decreasing intrahepatic cholesterol, and by increasing the activity of LDL receptors. Nicotinic acid lowers LDL cholesterol and triglyceride by decreasing VLDL synthesis and by decreasing free fatty acid mobilization from peripheral adipocytes. The HMG-CoA reductase inhibitors--fluvastatin, lovastatin, pravastatin and simvastatin--lower LDL cholesterol by partially inhibiting HMG-CoA reductase (the rate-limiting enzyme of cholesterol biosynthesis) and by increasing the activity of LDL receptors. The fibric-acid derivatives--bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil--primarily decrease triglyceride by increasing lipoprotein lipase activity and by decreasing the release of free fatty acids from peripheral adipose tissue. Probucol decreases LDL cholesterol by increasing non-receptor-mediated LDL clearance; as an anti-oxidant, probucol also decreases LDL oxidation; oxidized LDL which is thought to lead to atherogenesis. Although these agents have been proven safe in clinical trials, like any drug, they carry the risk for adverse effects. The bile-acid sequestrants may cause constipation, reflux oesophagitis, and dyspepsia, and may bind coadministered medications such as digitalis glycosides, beta blockers, warfarin, and exogenous thyroid hormone. Nicotinic acid use is commonly associated with flushing and pruritus and may also cause non-specific gastrointestinal complaints, hepatotoxicity (hepatic necrosis, hepatitis, or elevated liver enzymes), gout, myolysis, decreased glucose tolerance and increased fasting glucose levels, and ophthalmological complications including decreased visual acuity, toxic amblyopia, and cystic maculopathy. The HMG-CoA reductase inhibitors may produce liver enzyme elevations, creatine kinase elevations and rhabdomyolysis. The combination of a reductase inhibitor and a fibrate increases the risk for rhabdomyolysis. Possible adverse effects of the fibric-acid derivatives include abdominal discomfort, nausea, flatulence, increased lithogenicity of bile, liver enzyme elevations and creatine kinase elevations. Probucol may increase the QTc interval and may cause non-specific gastrointestinal complaints. PMID:8593127

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

    PubMed

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

    1990-01-01

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

  11. Neurotoxicity and haemostatic disturbances in patients envenomed by the Papuan black snake (Pseudechis papuanus).

    PubMed

    Lalloo, D; Trevett, A; Black, J; Mapao, J; Naraqi, S; Owens, D; Hutton, R; Theakston, R D; Warrell, D A

    1994-08-01

    Among 335 patients presenting with snakebites in Central Province, Papua New Guinea, nine were proved by enzyme immunoassay to have been bitten by Papuan black snakes (Pseudechis papuanus). Seven showed clinical evidence of envenoming. Early symptoms included vomiting and tender local lymph nodes. Five patients had neurotoxic signs and one required mechanical ventilation. Spontaneous systemic bleeding occurred in two patients. Coagulation studies in four patients showed thrombocytopenia, prolongation of prothrombin time, mild defibrination and depletion of other clotting factors with elevated fibrin(ogen) degradation products and other evidence of fibrinolysis. One patient developed mild renal dysfunction. There was no evidence of intravascular haemolysis or rhabdomyolysis. These clinical observations, which do not distinguish victims of P. papuanus from those of taipans (Oxyuranus scutellatus canni), suggest that the venom contains neurotoxic, haemorrhagic and mild procoagulant activities. Only two other cases of proven envenoming by this species have been reported. There appears to have been a decline in the abundance of this species, and hence its medical importance, over the last 25 years. PMID:7985197

  12. Four cases of tendinopathy in patients on statin therapy.

    PubMed

    Chazerain, P; Hayem, G; Hamza, S; Best, C; Ziza, J M

    2001-10-01

    During the last decade, statins have been widely prescribed as lipid-lowering drugs. Their overall safety profile is good. The main musculoskeletal side effects have consisted of muscle pain and weakness, peripheral neuropathy, and a few cases of drug-induced lupus. We report the first four cases of tendinopathy in patients receiving statin therapy. There were three men and one woman. The diagnoses were extensortenosynovitis at the hands (case 1), tenosynovitis of the tibialis anterior tendon (case 2), and Achilles tendinopathy (cases 3 and 4). Two patients were on simvastatin and two on atorvastatin. The tendinopathy developed 1 to 2 months after treatment initiation. The outcome was consistently favorable within 1 to 2 months after discontinuation of the drug. Similar cases have been reported to French pharmacovigilance centers. This report of four cases of tendinopathy draws attention to a possible and heretofore unrecognized side effect of a drug class that is becoming increasingly popular. Statins are effective in lowering high cholesterol levels in patients with type IIa or IIb hypercholesterolemia. They have been widely used for the last decade, particularly in the secondary and primary prevention of major coronary events. Statins act by inhibiting the enzyme hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Although most patients tolerate statins extremely well, a few experience side effects requiring treatment discontinuation. Reported musculoskeletal side effects include myalgia and a few cases of rhabdomyolysis and polymyositis. Induced lupus and peripheral neuropathy are exceedingly rare. PMID:11707010

  13. Hypokalemic paralysis in a professional bodybuilder.

    PubMed

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

    2012-09-01

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

  14. Prostatic surgery associated acute kidney injury.

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2014-08-01

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

  16. [Fibrate and statine myopathy].

    PubMed

    Finsterer, J

    2003-02-01

    Fibrates and statines are useful in preventing arteriosclerosis and thromboembolic events. However, they should be administered with caution. The risk of fibrate/statine myopathy, the most common side effect of fibrate/statine therapy, increases with dosage, combination of a fibrate with a statine,hypothyroidism, renal insufficiency, and intake of cytochrome P450 inhibitors. In case of clinical signs of a fibrate/statine myopathy such as proximal myalgias, stiffness,weakness, and dark urine, appropriate investigations should be initiated. If they establish the diagnosis of fibrate/statine myopathy, lipid lowering drugs should be immediately withdrawn. If rhabdomyolysis is present, prompt and adequate therapy is required. Though muscle abnormalities are rare side effects, fibrate/statine therapy should be regularly monitored with regard to clinical and laboratory alterations. The new "superstatines" rosuvastatine and pitavastatine reduce serum cholesterol more effectively than the established statines, but it is not known if they also have fewer muscular side effects than established statines. PMID:12596012

  17. Rare complications of pediatric diabetic ketoacidosis.

    PubMed

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

    2015-02-15

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

  18. Clinical toxicology: a tropical Australian perspective.

    PubMed

    Currie, B J

    2000-02-01

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

  19. Metabolic neuropathies and myopathies.

    PubMed

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

    Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are ?-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, ?-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney. PMID:23622366

  20. Asystolic Cardiac Arrest of Unknown Duration in Profound Hypothermia and Polysubstance Overdose: A Case Report of Complete Recovery

    PubMed Central

    Lubana, Sandeep Singh; Genin, Dennis Iilya; Singh, Navdeep; De La Cruz, Angel

    2015-01-01

    Patient: Male, 20 Final Diagnosis: Asystolic cardiac arrest in profound hypothermia and poly-substance overdose Symptoms: Cardiac arrest • cardiac arrhythmia Medication: — Clinical Procedure: Endotracheal intubation • hemodialysis Specialty: Critical Care Medicine Objective: Unusual clinical course Background: Opioid addiction and overdose is a serious problem worldwide. Fatal overdoses from opioids are responsible for numerous deaths and are increasing, especially if taken in combination with other psychoactive substances. Combined with environmental exposure, opioid overdose can cause profound hypothermia. Opioid abuse and other drugs of abuse impair thermoregulation, leading to severe hypothermia. Both drug overdose and severe hypothermia can cause cardiac arrest. Case Report: We report a case of 20-year-old man with history of polysubstance abuse presenting with severe hypothermia and asystole of unknown duration with return of spontaneous circulation (ROSC) achieved after 28 minutes of cardiopulmonary resuscitation (CPR). Urine toxicology was positive for cocaine, heroin, and benzodiazepine, along with positive blood alcohol level. The patient was rewarmed using non-invasive techniques. Hospital course was complicated by acute renal failure (ARF), severe rhabdomyolysis, severe hyperkalemia, ST-elevation myocardial infarction (STEMI), shock liver, coagulopathy, and aspiration pneumonia. Conclusions: Survival with full cardiovascular and neurologic recovery after a cardiac arrest caused by drug overdose in the setting of severe hypothermia is still possible, even if the cardiac arrest is of unknown or prolonged duration. Patients with severe hypothermia experiencing cardiac arrest/hemodynamic instability can be rewarmed using non-invasive methods and may not necessarily need invasive rewarming techniques. PMID:26054008

  1. SLCO1B1 Genetic Variant Associated With Statin-Induced Myopathy: A Proof-of-Concept Study Using the Clinical Practice Research Datalink

    PubMed Central

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

    2013-01-01

    This study aimed to determine whether patients with statin-induced myopathy could be identified using the United Kingdom Clinical Practice Research Datalink, whether DNA could be obtained, and whether previously reported associations of statin myopathy with the SLCO1B1 c.521T>C and COQ2 rs4693075 polymorphisms could be replicated. Seventy-seven statin-induced myopathy patients (serum creatine phosphokinase (CPK) > 4× upper limit of normal (ULN)) and 372 statin-tolerant controls were identified and recruited. Multiple logistic regression analysis showed the SLCO1B1 c.521T>C single-nucleotide polymorphism to be a significant risk factor (P = 0.009), with an odds ratio (OR) per variant allele of 2.06 (1.32–3.15) for all myopathy and 4.09 (2.06–8.16) for severe myopathy (CPK > 10× ULN, and/or rhabdomyolysis; n = 23). COQ2 rs4693075 was not associated with myopathy. Meta-analysis showed an association between c.521C>T and simvastatin-induced myopathy, although power for other statins was limited. Our data replicate the association of SLCO1B1 variants with statin-induced myopathy. Furthermore, we demonstrate how electronic medical records provide a time- and cost-efficient means of recruiting patients with severe adverse drug reactions for pharmacogenetic studies. PMID:23942138

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

    PubMed

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

    2014-12-01

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

  3. Mortality due to a retained circle hook in a longfin mako shark Isurus paucus (Guitart-Manday).

    PubMed

    Adams, D H; Borucinska, J D; Maillett, K; Whitburn, K; Sander, T E

    2015-07-01

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

  4. Postsynaptic neuromuscular dysfunction in organophosphate induced intermediate syndrome.

    PubMed

    De Wilde, V; Vogelaers, D; Colardyn, F; Vanderstraeten, G; Van den Neucker, K; De Bleecker, J; De Reuck, J; Van den Heede, M

    1991-02-26

    A 65-year-old Caucasian female developed an intermediate syndrome seven days after an acute cholinergic crisis, caused by the ingestion of fenthion. Cholinesterase activity in the blood, plasma and red cells was monitored daily by the method according to Nenner and serial serum fenthion levels were measured by capillary gas chromatography. Electromyographic studies showed fade on tetanic stimulation by means of surface electrodes at 20 Hz of the left M. abductor digiti quinti at day 7, which could no longer be observed at day 19. Fade on low-frequency stimulation and post-tetanic facilitation were both absent. A biopsy of the N. suralis was normal. A biopsy of the M. tibialis anterior revealed a limited rhabdomyolysis with a very weak staining for cholinesterase. It is hypothesized that the pathophysiologic process underlying the syndrome is the result of a time-confined phenomenon, which includes both changes in the postsynaptic structures by a desensitization process and a gradually restoring ratio of acetylcholine to acetylcholinesterase. This hypothesis is suggested by the similarity in the EMG-findings of this patient and those in myasthenia gravis, which is known to be characterized by a postsynaptic transmission defect. PMID:1645823

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

    PubMed

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

    2015-01-01

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

  6. Intentional self-poisoning with the chlorophenoxy herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA)

    PubMed Central

    Roberts, Darren M; Seneviratne, Ruwan; Mohammed, Fahim; Patel, Renu; Senarathna, Lalith; Hittarage, Ariyasena; Buckley, Nick A; Dawson, Andrew H; Eddleston, Michael

    2006-01-01

    Study Objective: Data on poisoning with MCPA (4-chloro-2-methylphenoxyacetic acid) is limited to six case reports. Our objective is to describe outcomes from intentional self-poisoning with MCPA in a prospective case series of 181 patients presenting to hospitals in Sri Lanka. Methods: Patient information was collected by on-site study doctors as part of an ongoing prospective cohort study of poisoned patients. History, clinical details and blood samples were obtained prospectively. Results: Overall clinical toxicity was minimal in 85% of patients, including mild gastrointestinal symptoms in 44% of patients. More severe clinical signs of chlorophenoxy poisoning reported previously such as rhabdomyolysis, renal dysfunction and coma also occurred, but were uncommon. Eight patients died (4.4%). Most deaths occurred suddenly from cardiorespiratory arrest within 48 hours of poisoning; the pathophysiological mechanism of death was not apparent. The correlation between admission plasma MCPA concentration and clinical markers of severity of toxicity (physical signs, symptoms and elevated creatine kinase) was poor. Conclusions: Intentional self-poisoning with MCPA generally causes mild toxicity, but cardiorespiratory arrest and death may occur. All patients should receive routine resuscitation and supportive care. It seems reasonable to correct acidosis and maintain an adequate urine output, but there is insufficient evidence to support other specific interventions. Our data do not support a clinical role for measurement of plasma MCPA in the acute management of poisoning and insufficient data were available to fully examine the utility of measured electrolytes and creatine kinase. PMID:16126140

  7. Non-cardiovascular effects associated with statins.

    PubMed

    Desai, Chintan S; Martin, Seth S; Blumenthal, Roger S

    2014-01-01

    Statins form the pharmacologic cornerstone of the primary and secondary prevention of atherosclerotic cardiovascular disease. In addition to beneficial cardiovascular effects, statins seem to have multiple non-cardiovascular effects. Although early concerns about statin induced hepatotoxicity and cancer have subsided owing to reassuring evidence, two of the most common concerns that clinicians have are myopathy and diabetes. Randomized controlled trials suggest that statins are associated with a modest increase in the risk of myositis but not the risk of myalgia. Severe myopathy (rhabdomyolysis) is rare and often linked to a statin regimen that is no longer recommended (simvastatin 80 mg). Randomized controlled trials and meta-analyses suggest an increase in the risk of diabetes with statins, particularly with higher intensity regimens in people with two or more components of the metabolic syndrome. Other non-cardiovascular effects covered in this review are contrast induced nephropathy, cognition, cataracts, erectile dysfunction, and venous thromboembolism. Currently, systematic reviews and clinical practice guidelines indicate that the cardiovascular benefits of statins generally outweigh non-cardiovascular harms in patients above a certain threshold of cardiovascular risk. Literature is also accumulating on the potential non-cardiovascular benefits of statins, which could lead to novel applications of this class of drug in the future. PMID:25035309

  8. High-dose itraconazole in the treatment of severe mycoses.

    PubMed Central

    Sharkey, P K; Rinaldi, M G; Dunn, J F; Hardin, T C; Fetchick, R J; Graybill, J R

    1991-01-01

    Eight patients with systemic mycoses and with prior treatment failures were treated with itraconazole (600 mg/day) for a mean duration of 5.5 months. All six patients without AIDS experienced improvement or stabilization of their fungal infections while receiving high-dose itraconazole, although two patients later experienced treatment failures, one by relapse and one by progression, on lower doses. Treatment failures also occurred in the two patients with AIDS and cryptococcal meningitis. The failures were associated with low serum itraconazole concentrations (less than 2.5 micrograms/ml) in both patients. All other patients had mean trough levels in serum above 5 micrograms/ml. One patient who was improving on 600 mg/day developed a progressive infection after reduction of the dose to 400 mg/day. Side effects included reversible adrenal insufficiency in one patient; severe hypokalemia, mild diastolic hypertension, and rhabdomyolysis in one patient; mild hypokalemia and hypertension in four other patients; and breast tenderness in one patient. The mean decrease in serum potassium during treatment was statistically significant (P = 0.05). Selected patients with severe systemic mycoses may benefit from prolonged high-dose itraconazole treatment. However, 600 mg/day may be approaching the upper limits of acceptable dosing for long-term treatment. PMID:1648887

  9. Biomarkers of multiorgan injury in a preclinical model of exertional heat stroke.

    PubMed

    King, Michelle A; Leon, Lisa R; Mustico, Danielle L; Haines, Joel M; Clanton, Thomas L

    2015-05-15

    It is likely that the pathophysiology of exertional heat stroke (EHS) differs from passive heat stroke (PHS), but this has been difficult to verify experimentally. C57Bl/6 mice were instrumented with temperature transponders and underwent 3 wk of training using voluntary and forced running wheels. An EHS group was exposed to environmental temperatures (Tenv) of 37.5, 38.5, or 39.5°C at either 30, 50, or 90% relative humidities (RH) while exercising on a forced running wheel. Results were compared with sham-matched exercise controls (EXC) and naïve controls (NC). In EHS, mice exercised in heat until they reached limiting neurological symptoms (loss of consciousness). The symptom-limited maximum core temperatures achieved were between 42.1 and 42.5°C at 50% RH. All mice that were followed for 4 days survived. Additional groups were killed at 0.5, 3, 24, and 96 h, post-EHS or -EXC. Histopathology revealed extensive damage in all regions of the small intestine, liver, and kidney. Plasma creatine kinase, blood urea nitrogen, alanine transaminase, and intestinal fatty acid binding protein-2 were significantly elevated compared with matched EXC and NC, suggesting multiple organ injury to striated muscle, kidney, liver, and intestine, respectively. EHS mice were hypoglycemic immediately following EHS but exhibited sustained hyperglycemia through 4 days. The results demonstrate unique features of survivable EHS in the mouse that included loss of consciousness, extensive organ injury, and rhabdomyolysis. PMID:25814640

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

    PubMed

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

    2015-03-01

    The use of statins for cardiovascular disease prevention is clearly supported by clinical evidence. However, in January 2014 the U.S. Food and Drug Administration released an advice on statin risk reporting that "statin benefit is indisputable, but they need to be taken with care and knowledge of their side effects". Among them the by far most common complication is myopathy, ranging from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. This class side effect appears to be dose dependent, with more lipophilic statin (i.e., simvastatin) carrying a higher overall risk. Hence, to minimize statin-associated myopathy, clinicians should take into consideration a series of factors that potentially increase this risk (i.e., drug-drug interactions, female gender, advanced age, diabetes mellitus, hypothyroidism and vitamin D deficiency). Whenever it is appropriate to stop statin treatment, the recommendations are to stay off statin until resolution of symptoms or normalization of creatine kinase values. Afterwards, clinicians have several options to treat dyslipidemia, including the use of a lower dose of the same statin, intermittent non-daily dosing of statin, initiation of a different statin, alone or in combination with nonstatin lipid-lowering agents, and substitution with red yeast rice. PMID:25640999

  11. [Intoxications specific to the Aquitaine region].

    PubMed

    Bédry, R; Gromb, S

    2009-07-01

    Some intoxications are more specifically linked to the Aquitaine region than to other regions of France, due to environmental circumstances (fauna, flora, climate) or traditional activities (gastronomy). Three types of intoxications are particular in this area. Pine processionary caterpillar envenomations (Thaumetopoea pityocampa), a Southern Europe pinewood parasite, are frequently encountered in the Landes' forest. They are responsible of ocular and/or skin lesions with urticaria or contact dermatitis, seldom associated with immediate IgE hypersensitivity. According to the south Atlantic coastal region geology and the marine streams, venomous marine animals are mainly located in Charente-Maritime for jellyfish, in Gironde and in Landes for weeverfish and in Atlantic Pyrenees for sea anemone. Usually not dangerous, first-aid workers treat most cases of these envenomations. Some endemic mushrooms (Tricholoma auratum) which grow on the dunes of the Atlantic coastal region, are usually considered as very good comestibles, but were recently responsible for serious intoxications: T.auratum was responsible of several cases of rhabdomyolysis, without neurological involvement, nor renal or hepatic lesion. Three deaths were notified. Animal studies confirmed the responsibility of the mushrooms. PMID:19375827

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

    PubMed Central

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

    2014-01-01

    Reactive oxygen species are produced during anaerobic exercise mostly by Fe ions released into plasma and endothelial/muscle xanthine oxidase activation that generates uric acid (UA) as the endpoint metabolite. Paradoxically, UA is considered a major antioxidant by virtue of being able to chelate pro-oxidative iron ions. This work aimed to evaluate the relationship between UA and plasma markers of oxidative stress following the exhaustive Wingate test. Plasma samples of 17 male undergraduate students were collected before, 5 and 60 min after maximal anaerobic effort for the measurement of total iron, haem iron, UA, ferric-reducing antioxidant activity in plasma (FRAP), and malondialdehyde (MDA, biomarker of lipoperoxidation). Iron and FRAP showed similar kinetics in plasma, demonstrating an adequate pro-/antioxidant balance immediately after exercise and during the recovery period (5–60 min). Slight variations of haem iron concentrations did not support a relevant contribution of rhabdomyolysis or haemolysis for iron overload following exercise. UA concentration did not vary immediately after exercise but rather increased 29% during the recovery period. Unaltered MDA levels were concomitantly measured. We propose that delayed UA accumulation in plasma is an auxiliary antioxidant response to post-exercise (iron-mediated) oxidative stress, and the high correlation between total UA and FRAP in plasma (R-Square = 0.636; p = 0.00582) supports this hypothesis. PMID:25435669

  13. Increased inflammation and decreased insulin sensitivity indicate metabolic disturbances in zoo-managed compared to free-ranging black rhinoceros (Diceros bicornis).

    PubMed

    Schook, Mandi W; Wildt, David E; Raghanti, Mary Ann; Wolfe, Barbara A; Dennis, Patricia M

    2015-01-01

    Black rhinoceros (rhinos) living in zoos express a host of unusual disease syndromes that are associated with increased morbidity and mortality, including hemolytic anemia, rhabdomyolysis, hepatopathy and ulcerative skin disease, hypophosphatemia and iron overload. We hypothesized that iron overload is a consequence and indicator of disturbances related to inflammation and insulin/glucose metabolism. The objectives of this study were to: (1) generate the first baseline information on biomarkers of inflammation (tumor necrosis factor alpha [TNF?], serum amyloid A [SAA]), insulin sensitivity (insulin, glucose and proxy calculations of insulin sensitivity), phosphate and iron stores (ferritin) using banked serum from free-ranging black rhinos; and (2) then compare serum biomarkers between zoo-managed (n=86 individuals) and free-ranging (n=120) animals. Enzyme immunoassays were validated for serum and then biomarker levels analyzed using mixed models while controlling for sex, age and year of sample collection. Concentrations of TNF?, SAA, insulin and insulin-to glucose ratio were higher (P<0.05) in black rhinos managed in ex situ conditions compared to free-living counterparts. Findings indicate that the captive environment is contributing to increased inflammation and decreased insulin sensitivity in this endangered species. PMID:25980685

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-06-01

    The established tradition of consuming and marketing wild mushrooms has focused attention on mycotoxicity, which has become a global issue. In the present study, we describe the toxins found in a previously unknown poisonous European mushroom Tricholoma terreum. Fifteen new triterpenoids terreolides?A-F (1-6) and saponaceolides?H-P (8-16) were isolated from the fruiting bodies of the toxic mushroom T. terreum. Terreolides?A-C (1-3) possessed a unique 5/6/7 trioxaspiroketal system, whereas terreolides D-F (4-6) possessed an unprecedented carbon skeleton. Two abundant compounds in the mushroom, saponaceolide?B (7) and saponaceolide?M (13), displayed acute toxicity, with LD50 values of 88.3 and 63.7?mg?kg(-1) when administered orally in mice. Both compounds were found to increase serum creatine kinase levels in mice, indicating that T. terreum may be the cause of mushroom poisoning ultimately leading to rhabdomyolysis. PMID:24753190

  16. Muscle strength, motor performance, cardiac and muscle biomarkers in detection of muscle side effects during and after acute lymphoblastic leukemia treatment in children.

    PubMed

    Akyay, Arzu; Olcay, Lale; Sezer, Nebahat; Atay Sönmez, Çi?dem

    2014-11-01

    Muscle side effects have not been frequently assessed in childhood acute lymphoblastic leukemia (ALL) patients. Our objective was to determine the early and late muscle side effects during childhood ALL treatment. To this end, we examined the early muscle side effects in 15 newly diagnosed "therapy patients" (group I), and the late side effects in 18 ALL survivors "off therapy patients" (group II). Muscle side effects were assessed by measuring hand grip strength (HGS), the "timed up and go" (TUG) test, creatine phosphokinase, myoglobin, plasma electrolytes, cardiac troponin I before and after induction chemotherapy in group I. The same parameters and cranial radiotherapy dose were examined in group II at a single timepoint. Cumulative doses of chemotherapy were calculated, and echocardiograms were obtained for each group. As a result, we found that the HGS and TUG measures of group I at the end of induction were poorer than measures of the first admission, control subjects, and group II. Low HGS measures had been normalized over time, but the TUG measures remained poor. Overt rhabdomyolysis and pyomyositis were not detected in any of the patients. These results suggested that muscle side effect monitoring might be helpful in the follow-up of children with ALL. PMID:25330012

  17. Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis.

    PubMed

    Perin, Laura; Sedrakyan, Sargis; Giuliani, Stefano; Da Sacco, Stefano; Carraro, Gianni; Shiri, Liron; Lemley, Kevin V; Rosol, Michael; Wu, Sam; Atala, Anthony; Warburton, David; De Filippo, Roger E

    2010-01-01

    Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kit(pos) stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN. PMID:20195358

  18. Protective Effect of Human Amniotic Fluid Stem Cells in an Immunodeficient Mouse Model of Acute Tubular Necrosis

    PubMed Central

    Perin, Laura; Sedrakyan, Sargis; Giuliani, Stefano; Da Sacco, Stefano; Carraro, Gianni; Shiri, Liron; Lemley, Kevin V.; Rosol, Michael; Wu, Sam; Atala, Anthony; Warburton, David; De Filippo, Roger E.

    2010-01-01

    Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kitpos stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN. PMID:20195358

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

    PubMed Central

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

    2014-01-01

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

  20. Phase I study of oral S-1 and concurrent radiotherapy in patients with head and neck cancer

    PubMed Central

    Nakata, Kensei; Sakata, Koh-ichi; Someya, Masanori; Miura, Katsutoshi; Hayashi, Junichi; Hori, Masakazu; Takagi, Masaru; Himi, Tetsuo; Kondo, Atsushi; Hareyama, Masato

    2013-01-01

    This study investigated the maximum tolerated dose (MTD) of S-1 with concurrent radiotherapy in patients with head and neck cancer, based on the frequency of dose-limiting toxicities (DLT). S-1 was administered orally at escalating doses from 40 mg/m2 b.i.d. on the days of delivering radiotherapy, which was given at a total dose of 64–70 Gy in 32–35 fractions over 6–7 weeks. A total of 12 patients (3 patients at 40 mg/m2, 6 patients at 60 mg/m2, and 3 patients at 80 mg/m2) were enrolled in this trial. At the dose of 80 mg/m2, two of the three patients developed DLT (Grade 3 anorexia and rhabdomyolysis) due to S-1, so the MTD was determined to be 80 mg/m2. Among the 12 enrolled patients, 9 (75%) showed a complete response and 3 (25%) showed a partial response. The overall response rate was 100%. The recommended dose of S-1 with concurrent radiotherapy is 60 mg/m2. PMID:23292146

  1. Congenital Cataracts – Facial Dysmorphism – Neuropathy

    PubMed Central

    Kalaydjieva, Luba

    2006-01-01

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

  2. Rare complications of pediatric diabetic ketoacidosis

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-03-01

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

  4. Asystolic Cardiac Arrest of Unknown Duration in Profound Hypothermia and Polysubstance Overdose: A Case Report of Complete Recovery.

    PubMed

    Singh Lubana, Sandeep; Genin, Dennis Iilya; Singh, Navdeep; De La Cruz, Angel

    2015-01-01

    BACKGROUND Opioid addiction and overdose is a serious problem worldwide. Fatal overdoses from opioids are responsible for numerous deaths and are increasing, especially if taken in combination with other psychoactive substances. Combined with environmental exposure, opioid overdose can cause profound hypothermia. Opioid abuse and other drugs of abuse impair thermoregulation, leading to severe hypothermia. Both drug overdose and severe hypothermia can cause cardiac arrest. CASE REPORT We report a case of 20-year-old man with history of polysubstance abuse presenting with severe hypothermia and asystole of unknown duration with return of spontaneous circulation (ROSC) achieved after 28 minutes of cardiopulmonary resuscitation (CPR). Urine toxicology was positive for cocaine, heroin, and benzodiazepine, along with positive blood alcohol level. The patient was rewarmed using non-invasive techniques. Hospital course was complicated by acute renal failure (ARF), severe rhabdomyolysis, severe hyperkalemia, ST-elevation myocardial infarction (STEMI), shock liver, coagulopathy, and aspiration pneumonia. CONCLUSIONS Survival with full cardiovascular and neurologic recovery after a cardiac arrest caused by drug overdose in the setting of severe hypothermia is still possible, even if the cardiac arrest is of unknown or prolonged duration. Patients with severe hypothermia experiencing cardiac arrest/hemodynamic instability can be rewarmed using non-invasive methods and may not necessarily need invasive rewarming techniques. PMID:26054008

  5. Acute cerebellar dysfunction with neuromuscular manifestations after scorpionism presumably caused by Tityus obscurus in Santarém, Pará / Brazil.

    PubMed

    Torrez, Pasesa P Q; Quiroga, Mariana M M; Abati, Paulo A M; Mascheretti, Melissa; Costa, Walter Silva; Campos, Luciana P; França, Francisco O S

    2015-03-01

    Scorpionism is a public health problem in many tropical countries, especially in North Africa, South India, Latin America and the Middle East. In Brazil, patients with severe scorpion envenoming have mainly cardiovascular events, including acute heart failure, acute respiratory distress syndrome and shock, death is rare. We described 58 accidents presumably caused by Tityus obscurus in Brazilian Amazonia. Patients reported a sensation of "electric shocks" which could last hours. The vast majority of patients presented a clinical picture compatible with acute cerebellar dysfunction, beginning minutes and lasting up to 2 days after the accident. They presented cerebellar ataxia, dysdiadochokinesia, dysmetry, dysarthria, dyslalia, nausea and vomiting. Besides, some patients presented myoclonus and fasciculation which can also be attributed to cerebellar dysfunction or maybe the result of direct action on skeletal muscle. Two patients had evidence of intense rhabdomyolysis and acute kidney injury. The clinical picture in this scorpion envenoming is mainly characterized by an acute dysfunction of cerebellar activities and abnormal neuromuscular manifestations and in some cases muscle injury which are not described in any other region of the world. This work presents clinical, epidemiologic, laboratory and treatment aspects of this unmatched scorpion envenoming in the state of Pará, northern Brazil. PMID:25549940

  6. Methamphetamine abuse.

    PubMed

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

    2007-10-15

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

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

    PubMed

    Bonnet, U; Mahler, H

    2015-04-01

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

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

    SciTech Connect

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

    1985-10-01

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

  9. Loxosceles gaucho Venom-Induced Acute Kidney Injury – In Vivo and In Vitro Studies

    PubMed Central

    Lucato, Rui V.; Abdulkader, Regina C. R. M.; Barbaro, Katia C.; Mendes, Glória E.; Castro, Isac; Baptista, Maria A. S. F.; Cury, Patrícia M.; Malheiros, Denise M. C.; Schor, Nestor; Yu, Luis; Burdmann, Emmanuel A.

    2011-01-01

    Background Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. Methodology/Principal Findings In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. Conclusions/Significance Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite. PMID:21655312

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

    PubMed Central

    2014-01-01

    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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

    The statins are widely used worldwide to reduce risk for cardiovascular events in both the primary and secondary prevention settings. Although generally quite safe, the statins can be associated with a variety of serious side adverse effects, including myalgia, myopathy, and changes in plasma enzymes of hepatic origin. Although rare, the most serious of these is rhabdomyolysis. Several drugs can interfere with the metabolism and disposal of the statins, thereby increasing risk for adverse events. It is important that clinicians treating patients with statins be aware of the potential for drug-drug interactions between each statin and specific other drugs and take measures to prevent them. The prediction of potential drug-drug interactions derives from basic pharmacokinetic principles. Certain drug interactions are predicted by measuring the effect of interacting drugs on blood plasma concentrations of the statin. Individual patient variations resulting in part from polymorphisms in the metabolizing enzymes confound some of these predictions. Based on these known effects, a new classification for predicting statin drug interactions is proposed. This report discusses likely prescription and nonprescription interactions as well as potential alternatives for special populations. PMID:24793440

  13. Snake bites by the jararacuçu (Bothrops jararacussu): clinicopathological studies of 29 proven cases in São Paulo State, Brazil.

    PubMed

    Milani Júnior, R; Jorge, M T; de Campos, F P; Martins, F P; Bousso, A; Cardoso, J L; Ribeiro, L A; Fan, H W; França, F O; Sano-Martins, I S; Cardoso, D; Ide Fernandez, C; Fernandes, J C; Aldred, V L; Sandoval, M P; Puorto, G; Theakston, R D; Warrell, D A

    1997-05-01

    The jararacuçu, one of the most dreaded snakes of Brazil, southern Bolivia, Paraguay and northeastern Argentina, is a heavily-built pit viper which may grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal venom may be milked from its venom glands on a single occasion. It has accounted for 0.8% to 10% of series of snake bites in São Paulo State, Brazil. We examined 29 cases of proven jararacuçu bites recruited over a 20-year period in two São Paulo hospitals. Severe signs of local and systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding, renal failure) were seen only in patients bitten by snakes longer than 50 cm; bites by shorter specimens were more likely to cause incoagulable blood. Fourteen patients developed coagulopathy, six local necrosis (requiring amputation in one) and five local abscesses. Two became shocked and four developed renal failure. Three patients, aged 3, 11 and 65 years, died 18.75, 27.75 and 83 h after being bitten, with respiratory and circulatory failure despite large doses of specific antivenom and intensive-care-unit management. In two patients, autopsies revealed acute renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the site of the bite and disseminated intravascular coagulation. In one survivor with chronic renal failure, renal biopsy showed bilateral cortical necrosis; the patient remains dependent on haemodialysis. Effects of polyspecific Bothrops antivenom were not impressive, and it has been suggested that anti-Bothrops and anti-Crotalus antivenoms should be given in combination. PMID:9205667

  14. A case of fatal caffeine poisoning.

    PubMed

    Rudolph, T; Knudsen, K

    2010-04-01

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

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

    PubMed

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

    2012-09-01

    In clinical practice 5-10% of patients receiving statins develop myopathy, a side effect that had been systematically underestimated in the randomized controlled trials with statins. The most common manifestation of myopathy is muscle pain (usually symmetrical, involving proximal muscles) without creatinine kinase (CK) elevation or less frequently with mild CK elevation. Clinically significant rhabdomyolysis (muscle symptoms with CK elevation >10 times the upper limit of normal and with creatinine elevation) is extremely rare. Myopathy complicates the use of all statins (class effect) and is dose-dependent. The pathophysiologic mechanism of statin-associated myopathy is unknown and probably multifactorial. The risk of statin-associated myopathy can be minimized by identifying vulnerable patients (i.e. patients with impaired renal or liver function, advanced age, hypothyroidism, etc.) and/or by eliminating-avoiding statin interactions with specific drugs (cytochrome P-450 3A4 inhibitors, gemfibrozil, etc.). In symptomatic patients, the severity of symptoms, the magnitude of CK elevation and the risk/benefit ratio of statin continuation should be considered before statin treatment is discontinued. Potential strategies are the use of the same statin at a lower dose and if symptoms recur the initiation of fluvastatin XL 80 mg daily or rosuvastatin intermittently in low dose (5-10mg), combined usually with ezetimibe 10mg daily. Failure of these approaches necessitates the use of non-statin lipid lowering drugs (ezetimibe, colesevelam). In order to provide evidence based recommendations for the appropriate management of statin-intolerant patients we need randomized clinical trials directly comparing the myopathic potential of different lipid-lowering medications at comparable doses. PMID:21813193

  16. Human rabies--Wisconsin, 2010.

    PubMed

    2011-09-01

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

  17. Acute methoxetamine and amphetamine poisoning with fatal outcome: a case report.

    PubMed

    Wiergowski, Marek; Anand, Jacek Sein; Krzy?anowski, Maciej; Jankowski, Zbigniew

    2014-08-01

    Methoxetamine (MXE) is a psychoactive substance distributed mostly via the Internet and is not liable to legal regulation in Poland. MXE has a toxicity profile similar to that of ketamine but longer-lasting effects. The paper describes a case of acute poisoning that resulted from recreational use of MXE and amphetamine and ended in death. In mid-July 2012, a 31-year old man was admitted to the clinical toxicology unit in Gda?sk because of poisoning with an unknown psychoactive substance. The patient was transported to the emergency department (ED) at 5:15 a.m. in a very poor general condition, in a deep coma, with acute respiratory failure, hyperthermia (> 39°C) and generalized seizures. Laboratory tests showed marked leukocytosis, signs of massive rhabdomyolysis, hepatic failure and beginning of acute renal failure. Despite intensive therapy, the patient died 4 weeks after the poisoning in the course of multi-organ dysfunction syndrome. Chemical and toxicological studies of serum and urine samples collected on the poisoning day at 1:40 p.m. confirmed that amphetamine and MXE had been taken earlier that day. Concentration of amphetamine in the serum (0.06 ?g/ml) was within the non-toxic range, while MXE (0.32 ?g/ml) was within the toxic range of concentrations. Amphetamine was also detected in the patient's hair, which suggested a possibility of its use within the last dozen weeks or so. The serious clinical course of intoxication and co-existence of amphetamine and MXE in the patient's blood and urine suggest the possibility of adverse interactions between them. PMID:25060403

  18. Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro

    PubMed Central

    de Luna, Noemí; Brull, Astrid; Guiu, Josep Maria; Lucia, Alejandro; Martin, Miguel Angel; Arenas, Joaquin; Martí, Ramon; Andreu, Antoni L.; Pinós, Tomàs

    2015-01-01

    ABSTRACT McArdle disease, also termed ‘glycogen storage disease type V’, is a disorder of skeletal muscle carbohydrate metabolism caused by inherited deficiency of the muscle-specific isoform of glycogen phosphorylase (GP-MM). It is an autosomic recessive disorder that is caused by mutations in the PYGM gene and typically presents with exercise intolerance, i.e. episodes of early exertional fatigue frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL) and brain (GP-BB) isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is the main GP isoform found in human and rat foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in McArdle mice that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal muscle from individuals with McArdle disease. We treated mouse primary skeletal muscle cultures in vitro with sodium valproate (VPA), a histone deacetylase inhibitor. After VPA treatment, myotubes expressed GP-BB and a dose-dependent decrease in glycogen accumulation was also observed. Thus, this in vitro model could be useful for high-throughput screening of new drugs to treat this disease. The immortalization of these primary skeletal muscle cultures could provide a never-ending source of cells for this experimental model. Furthermore, VPA could be considered as a gene-expression modulator, allowing compensatory expression of GP-BB and decreased glycogen accumulation in skeletal muscle of individuals with McArdle disease. PMID:25762569

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2010-01-01

    Organic cation/carnitine transporter (OCTN2; SLC22A5) is an important transporter for L-carnitine homeostasis, but can be inhibited by drugs, which may cause L-carnitine deficiency and possibly other OCTN2-mediated drug-drug interactions. One objective was to develop a quantitative structure–activity relationship (QSAR) of OCTN2 inhibitors, in order to predict and identify other potential OCTN2 inhibitors and infer potential clinical interactions. A second objective was to assess two high renal clearance drugs that interact with OCTN2 in vitro (cetirizine and cephaloridine) for possible OCTN2-mediated drug-drug interactions. Using previously generated in vitro data of 22 drugs, a 3D quantitative pharmacophore model and a Bayesian machine learning model were developed. The four pharmacophore features include two hydrophobic groups, one hydrogen-bond acceptor, and one positive ionizable center. The Bayesian machine learning model was developed using simple interpretable descriptors and function class fingerprints of maximum diameter 6 (FCFP_6). An external test set of 27 molecules, including 15 newly identified OCTN2 inhibitors, and a literature test set of 22 molecules were used to validate both models. The computational models afforded good capability to identify structurally diverse OCTN2 inhibitors, providing a valuable tool to predict new inhibitors efficiently. Inhibition results confirmed our previously observed association between rhabdomyolysis and Cmax/Ki ratio. The two high renal clearance drugs cetirizine and cephaloridine were found not to be OCTN2 substrates and their diminished elimination by other drugs is concluded not to be mediated by OCTN2. PMID:20831193

  1. SLCO1B1 Polymorphisms and Statin-Induced Myopathy

    PubMed Central

    Stewart, Alison

    2013-01-01

    Statin drugs are highly effective in lowering blood concentrations of LDL-cholesterol, with concomitant reduction in risk of major cardiovascular events. Although statins are generally regarded as safe and well-tolerated, some users develop muscle symptoms that are mostly mild but in rare cases can lead to life-threatening rhabdomyolysis. The SEARCH genome-wide association study, which has been independently replicated, found a significant association between the rs4149056 (c.521T>C) single-nucleotide polymorphism (SNP) in the SLCO1B1 gene, and myopathy in individuals taking 80 mg simvastatin per day, with an odds ratio of 4.5 per rs4149056 C allele. The purpose of this paper is to assemble evidence relating to the analytical validity, clinical validity and clinical utility of using SLCO1B1 rs4149056 genotyping to inform choice and dose of statin treatment, with the aim of minimising statin-induced myopathy and increasing adherence to therapy. Genotyping assays for the rs4149056 SNP appear to be robust and accurate, though direct evidence for the performance of array-based platforms in genotyping individual SNPs was not found. Using data from the SEARCH study, calculated values for the clinical sensitivity, specificity, positive- and negative-predictive values of a test for the C allele to predict definite or incipient myopathy during 5 years of 80 mg/day simvastatin use were 70.4%, 73.7%, 4.1% and 99.4% respectively. There is a need for studies comparing the clinical validity of SLCO1B1 rs4149056 genotyping with risk scores for myopathy based on other factors such as racial background, statin type and dose, gender, body mass index, co-medications and co-morbidities. No direct evidence was found for clinical utility of statin prescription guided by SLCO1B1 genotype. PMID:24459608

  2. Procoagulant activity in patients with sickle cell trait.

    PubMed

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

    2012-06-01

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

  3. The determinants of transverse tubular volume in resting skeletal muscle.

    PubMed

    Sim, Jingwei; Fraser, James A

    2014-12-15

    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

  4. The determinants of transverse tubular volume in resting skeletal muscle

    PubMed Central

    Sim, Jingwei; Fraser, James A

    2014-01-01

    The transverse tubular (t)-system of skeletal muscle couples sarcolemmal electrical excitation with contraction deep within the fibre. Exercise, pathology and the composition of the extracellular fluid (ECF) can alter t-system volume (t-volume). T-volume changes are thought to contribute to fatigue, rhabdomyolysis and disruption of excitation–contraction coupling. However, mechanisms that underlie t-volume changes are poorly understood. A multicompartment, history-independent computer model of rat skeletal muscle was developed to define the minimum conditions for t-volume stability. It was found that the t-system tends to swell due to net ionic fluxes from the ECF across the access resistance. However, a stable t-volume is possible when this is offset by a net efflux from the t-system to the cell and thence to the ECF, forming a net ion cycle ECF?t-system?sarcoplasm?ECF that ultimately depends on Na+/K+-ATPase activity. Membrane properties that maximize this circuit flux decrease t-volume, including PNa(t) > PNa(s), PK(t) < PK(s) and N(t) < N(s) [P, permeability; N, Na+/K+-ATPase density; (t), t-system membrane; (s), sarcolemma]. Hydrostatic pressures, fixed charges and/or osmoles in the t-system can influence the magnitude of t-volume changes that result from alterations in this circuit flux. Using a parameter set derived from literature values where possible, this novel theory of t-volume was tested against data from previous experiments where t-volume was measured during manipulations of ECF composition. Predicted t-volume changes correlated satisfactorily. The present work provides a robust, unifying theoretical framework for understanding the determinants of t-volume. PMID:25384782

  5. A study on the effect of cimetidine and l-carnitine on myoglobinuric acute kidney injury in male rats.

    PubMed

    Estaphan, Suzanne; Eissa, Hassan; Elattar, Samah; Rashed, Laila; Farouk, Mira

    2015-07-01

    Myoglobinuric acute renal failure is the most important life threatening complication of rhabdomyolysis. Iron, free radicals, nitric oxide and cytochrome p450 are involved in the pathogenesis of mARF. The aim of this study is to compare the effect of cimetidine, l-carnitine and both agents together on mARF in rats. Forty rats were divided into 5 groups; group I: control rats, group II: myoglobinuric ARF rats, group III: mARF rats received l-carnitine (200mg/kg, i.p.), group IV: mARF rats received cimetidine (150mg/kg i.p.) and group V: mARF rats received both agents together. 48h after glycerol injection, systolic blood pressure was measured. Urine and blood samples were collected to evaluate urine volume, GFR, BUN, creatinine, K, Na, serum creatine kinase, NO and glutathione levels. Kidney specimens were taken to investigate renal cytochrome p450 and for histological examinations. Cimetidine treatment significantly decreased creatinine, BUN, K, Na, SBP and creatine kinase and increased GFR and urine volume compared to group II. l-carnitine exerted similar changes except for the effect on K and GFR. NO was significantly decreased, while renal glutathione and cytochrome p450 were significantly increased in groups treated with l-carnitine or cimetidine as compared to group II. Combined treatment further improved renal functions, creatine kinase, oxidative stress parameters and SBP as compared to each therapy alone. The histological changes confirmed the biochemical findings. Cimetidine and l-carnitine have protective effects - almost equally - against mARF. Using both agents together, minimises the renal injury. PMID:25930980

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

    PubMed Central

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

    2015-01-01

    Background Paramethoxymethamphetamine (PMMA) is a ring-substituted amphetamine similar in structure to 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”), but substantially more toxic. We describe the clinical features of fatal exposures in the provinces of Alberta and British Columbia, Canada. Methods We conducted a retrospective case series on deaths in Alberta and BC between June 2011 and April 2012 for which forensic toxicologic analysis was positive for PMMA and the drug was implicated as the primary toxic agent. Data collected included patient demographics, exposure history, clinical features, investigations, therapy provided and postmortem toxicologic findings. Results A total of 27 PMMA-associated deaths (20 in Alberta, 7 in BC) were reported in the 11-month period. The median age was 24 (range 14–52) years, and 22 (81%) were male. Ten patients were pronounced dead at the scene, and 17 died in hospital. The median time from exposure to death was 17 (range 5–264) hours. The median first-recorded vital signs (and ranges) were: heart rate 160 (86–201) beats/min, blood pressure 89/43 (69/30–162/83) mm Hg, respiratory rate 40 (26–48) breaths/min, oxygen saturation 81% (68%–100%) and temperature 39.4°C (34–43.8°C). Sixteen of the 17 people who died in hospital presented with clinical features consistent with serotonin syndrome. End-organ dysfunction included hepatic (30%) and acute kidney injury (85%), rhabdomyolysis (54%), coagulopathy (61%) and cardiac ischemia (15%). Other drugs identified on toxicologic analysis were MDMA (n = 27), cocaine or its metabolite benzoylecgonine (n = 14) and methamphetamine (n = 12). Interpretation Exposure to PMMA was characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. In addition to PMMA, multiple synthetic amphetamines were present on toxicologic analysis. When evaluating patients suspected of exposure to sympathomimetic drugs of abuse, clinicians must anticipate multiple clinical effects from the increased release of dopamine, serotonin, norepinephrine and other neurotransmitters. PMID:25844375

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

    PubMed Central

    Ngoepe, Mpho; Choonara, Yahya E.; Tyagi, Charu; Tomar, Lomas Kumar; du Toit, Lisa C.; Kumar, Pradeep; Ndesendo, Valence M. K.; Pillay, Viness

    2013-01-01

    Recent advances in biosensor design and sensing efficacy need to be amalgamated with research in responsive drug delivery systems for building superior health or illness regimes and ensuring good patient compliance. A variety of illnesses require continuous monitoring in order to have efficient illness intervention. Physicochemical changes in the body can signify the occurrence of an illness before it manifests. Even with the usage of sensors that allow diagnosis and prognosis of the illness, medical intervention still has its downfalls. Late detection of illness can reduce the efficacy of therapeutics. Furthermore, the conventional modes of treatment can cause side-effects such as tissue damage (chemotherapy and rhabdomyolysis) and induce other forms of illness (hepatotoxicity). The use of drug delivery systems enables the lowering of side-effects with subsequent improvement in patient compliance. Chronic illnesses require continuous monitoring and medical intervention for efficient treatment to be achieved. Therefore, designing a responsive system that will reciprocate to the physicochemical changes may offer superior therapeutic activity. In this respect, integration of biosensors and drug delivery is a proficient approach and requires designing an implantable system that has a closed loop system. This offers regulation of the changes by means of releasing a therapeutic agent whenever illness biomarkers prevail. Proper selection of biomarkers is vital as this is key for diagnosis and a stimulation factor for responsive drug delivery. By detecting an illness before it manifests by means of biomarkers levels, therapeutic dosing would relate to the severity of such changes. In this review various biosensors and drug delivery systems are discussed in order to assess the challenges and future perspectives of integrating biosensors and drug delivery systems for detection and management of chronic illness. PMID:23771157

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

    PubMed Central

    2014-01-01

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

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

    USGS Publications Warehouse

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

    2003-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    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

    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

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

    PubMed

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

    2014-01-01

    Association of statins with autoimmune disorders is rarely reported. We report a case of an apparently healthy 76-year-old woman who was on long-term statin therapy presenting with severe rhabdomyolysis, autoimmune hepatitis, and positive lupus antibodies. Patient presented with complaints of worsening fatigue, leg cramps, and progressive weakening of lower extremities over 3 weeks. The patient was on simvastatin daily for several years. Clinical examination on admission included muscle tenderness, lower extremity edema, and ascites. Her laboratory values on admission showed elevated creatine kinase and transaminases. Immunologic workup revealed positive ANA, anti-dsDNA and anti-SSA antibodies. F-actin antibody was also positive at high titer. Magnetic resonance imaging of the lower extremities showed findings consistent with myositis. Patient underwent biopsy of the thigh muscles, which showed inflammatory myositis. Liver biopsy was characteristic of autoimmune hepatitis. Patient responded well to immunosuppressive therapy with azathioprine and prednisone. Although statins are generally considered safe, recent data from long-term follow-up on patients who are on statins for long duration suggest that prolonged exposure to statins may trigger autoimmune reactions. The exact mechanism of statin-induced autoimmune reaction is unclear. Statins, as proapoptotic agents, release nuclear antigen into the circulation and may induce the production of pathogenic autoantibodies. The role of statins in inducing an endoplasmic reticular stress response with associated upregulation of major histocompatibility complex-1 expression and antigen presentation by muscle fibers has also been reported. Systemic immunosuppressive therapy has proven to be effective in many reported cases. PMID:23782756

  13. Mechanism-based inactivation of cytochrome P450 3A4 by mibefradil through heme destruction.

    PubMed

    Foti, Robert S; Rock, Dan A; Pearson, Josh T; Wahlstrom, Jan L; Wienkers, Larry C

    2011-07-01

    Mibefradil (Posicor) was developed as a calcium channel blocker for the treatment of chronic hypertension. The compound was withdrawn from the market in 1998 because of the potential for rhabdomyolysis, renal failure, or bradycardia when it was coadministered with other drugs. Mibefradil has previously been shown to be a potent reversible (IC(50) = 0.3-2 ?M) and mechanism-based (K(i) = 2.3 ?M; k(inact) = 0.4 min(-1)) inhibitor of CYP3A4-catalyzed statin metabolism. At present, the mechanism of CYP3A4 inactivation by mibefradil is not known. Mechanism-based inactivation experiments and spectral studies were used to examine the mechanism of CYP3A4 inactivation by mibefradil and its major metabolite, des-methoxyacetyl mibefradil (Ro 40-5966), in vitro. Both mibefradil and Ro 40-5966 were shown to exhibit type I binding characteristics (K(s) = 0.69 ± 0.06 and 1.39 ± 0.04 ?M, respectively) toward CYP3A4. Complete K(i)/k(inact) experiments were performed, revealing a rapid and irreversible decrease in CYP3A4-catalyzed 1'-hydroxymidazolam formation. Approximately 70% of CYP3A4 activity was lost in the first minute of incubation with mibefradil, and inactivation was nonlinear after 2 min. Ro 40-5966 also resulted in time-dependent inhibition of CYP3A4, albeit to a lesser extent than mibefradil. The decrease in CYP3A4 activity in the presence of mibefradil and NADPH was subsequently shown to have a good correlation with the time-dependent loss of CO binding, which, coupled with the lack of stable heme and/or apoprotein adducts, suggests heme destruction as the mechanism of inactivation of CYP3A4 by mibefradil. PMID:21447734

  14. The role of microRNAs in equine medicine: a review.

    PubMed

    van der Kolk, J H; Pacholewska, A; Gerber, V

    2015-06-01

    The search for new markers of diseases in human as well as veterinary medicine is ongoing. Recently, microRNAs (miRNAs or miRs) have emerged as potential new biomarkers. MiRNAs are short sequences of RNA (?22 nucleotides) that regulate gene expression via their target messenger RNA (mRNA). Circulating miRNAs in blood can be used as novel diagnostic markers for diseases due to their evolutionary conservation and stability. As a consequence of their systemic and manifold effects on the gene expression in various target organs, the concept that miRNAs could function as hormones has been suggested. This review summarizes the biogenesis, maturation, and stability of miRNAs and discusses their use as potential biomarkers in equine medicine. To date, over 700 equine miRNAs are identified with distinct subsets of miRNAs differentially expressed in a tissue-specific manner. A physiological involvement of various miRNAs in the regulation of cell survival, steroidogenesis, and differentiation during follicle selection and ovulation in the monovular equine ovary has been demonstrated. Furthermore, miRNAs might be used as novel diagnostic markers for myopathies such as polysaccharide storage myopathy and recurrent exertional rhabdomyolysis as well as osteochondrosis. Preliminary data indicate that miRNAs in blood might play important roles in equine glucose metabolism pathway. Of note, breed differences have been reported regarding the normal equine miRNA signature. For disease prevention, it is of utmost importance to identify disease-associated biomarkers which help detect diseases before symptoms appear. As such, circulating miRNAs represent promising novel diagnostic markers in equine medicine. PMID:25695624

  15. Movement disorder emergencies in childhood.

    PubMed

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

    2011-09-01

    The literature on paediatric acute-onset movement disorders is scattered. In a prospective cohort of 52 children (21 male; age range 2mo-15y), the commonest were chorea, dystonia, tremor, myoclonus, and Parkinsonism in descending order of frequency. In this series of mainly previously well children with cryptogenic acute movement disorders, three groups were recognised: (1) Psychogenic disorders (n = 12), typically >10 years of age, more likely to be female and to have tremor and myoclonus (2) Inflammatory or autoimmune disorders (n = 22), including N-methyl-d-aspartate receptor encephalitis, opsoclonus-myoclonus, Sydenham chorea, systemic lupus erythematosus, acute necrotizing encephalopathy (which may be autosomal dominant), and other encephalitides and (3) Non-inflammatory disorders (n = 18), including drug-induced movement disorder, post-pump chorea, metabolic, e.g. glutaric aciduria, and vascular disease, e.g. moyamoya. Other important non-inflammatory movement disorders, typically seen in symptomatic children with underlying aetiologies such as trauma, severe cerebral palsy, epileptic encephalopathy, Down syndrome and Rett syndrome, include dystonic posturing secondary to gastro-oesophageal reflux (Sandifer syndrome) and Paroxysmal Autonomic Instability with Dystonia (PAID) or autonomic 'storming'. Status dystonicus may present in children with known extrapyramidal disorders, such as cerebral palsy or during changes in management e.g. introduction or withdrawal of neuroleptic drugs or failure of intrathecal baclofen infusion; the main risk in terms of mortality is renal failure from rhabdomyolysis. Although the evidence base is weak, as many of the inflammatory/autoimmune conditions are treatable with steroids, immunoglobulin, plasmapheresis, or cyclophosphamide, it is important to make an early diagnosis where possible. Outcome in survivors is variable. Using illustrative case histories, this review draws attention to the practical difficulties in diagnosis and management of this important group of patients. PMID:21835657

  16. Inborn errors of cytoplasmic triglyceride metabolism.

    PubMed

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

    2015-01-01

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

  17. Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism

    PubMed Central

    Golomb, Beatrice A.; Evans, Marcella A.

    2009-01-01

    HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like all medications have potential for adverse effects (AEs). Here we review the statin AE literature, first focusing on muscle AEs as the most reported problem both in the literature and by patients. Evidence regarding the statin muscle AE mechanism, dose effect, drug interactions, and genetic predisposition is examined. We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials (RCTs), muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 (CYP)3A4 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence supports a mitochondrial foundation for muscle AEs associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many non-muscle statin AEs. Evidence from RCTs and studies of other designs indicates existence of additional statin-associated AEs, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients. Awareness and vigilance for AEs should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity. PMID:19159124

  18. Safety of low-density lipoprotein cholestrol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial).

    PubMed

    März, W; Wollschläger, H; Klein, G; Neiss, A; Wehling, M

    1999-07-01

    Reduction in plasma lipids has been recognized as one of the primary cardiovascular risk reduction strategies in the secondary prevention of coronary heart disease (CHD). The primary end points of TARGET TANGIBLE were the safety (adverse events and laboratory measurements) and efficacy (responder rates) of therapy with atorvastatin versus simvastatin with the aim of achieving low-density lipoprotein (LDL) cholesterol lowering to < or =100 mg/dl (2.6 mmol/L). A total of 3,748 CHD patients with LDL cholesterol levels > or =130 mg/dl (3.4 mmol/L) entered a run-in diet phase of 6 weeks without any lipid-lowering drug therapy. At the end of the diet phase, 2,856 patients met the lipid criteria and were randomized to active treatment for 14 weeks. Patients received 10 to 40 mg of either drug in an optional titration design at 2:1 randomization for atorvastatin versus simvastatin. Adverse event rates were statistically equivalent (p<0.01) for simvastatin (35.7%) and for atorvastatin patients (36.3%). Both drugs were well tolerated; <5% of patients in both groups were withdrawn due to adverse events. In all, 37 atorvastatin patients (2%) and 27 simvastatin patients (3%) had serious adverse events. Drug-related side effects (elevations in creatine kinase, liver enzymes) occurred in both groups at similar rates with 10 atorvastatin patients (0.5%) and 5 simvastatin patients (0.5%) presenting confirmed transaminase elevations >3 x the upper limit of the normal range. Significantly fewer patients in the atorvastatin group (n = 724) required titration to 40 mg compared with the simvastatin group (n = 514) (38% vs. 54%, respectively; p<0.001). Atorvastatin resulted in a significantly greater number of patients reaching the LDL cholesterol goal than those treated with simvastatin, with 67% of atorvastatin patients and 53% of simvastatin patients reaching the target LDL cholesterol level of < or =100 mg/dl (2.6 mmol/L) (p<0.001). Both atorvastatin and simvastatin are safe for use by patients in the secondary prevention of CHD, with patients in both drug groups having similar adverse event rates. Despite the use of concomitant medications there was no drug-induced rhabdomyolysis with either atorvastatin or simvastatin. PMID:10404843

  19. Hyperlipidemia after liver transplantation: natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin.

    PubMed

    Imagawa, D K; Dawson, S; Holt, C D; Kirk, P S; Kaldas, F M; Shackleton, C R; Seu, P; Rudich, S M; Kinkhabwala, M M; Martin, P; Goldstein, L I; Murray, N G; Terasaki, P I; Busuttil, R W

    1996-10-15

    This study was designed to determine the frequency of hyperlipidemia after orthotopic liver transplantation and whether treatment with a hydroxy-methylglutaryl coenzyme A reductase inhibitor was safe and efficacious. Cholesterol levels were assessed in 45 consecutive adult liver transplants (mean +/- SE). Four of 22 patients on cyclosporine (CsA) (18%) and three of 23 patients on FK506 (13%) had levels >225 mg/dl at 12 months (cholesterol levels for patients on CsA [total n=22]: pre-Tx = 140+/-11, 1 month = 183+/-36,3 months = 221+/-12, 6 months = 211+/-11, 12 months = 202+/-14 [P<0.01 vs. pre-Tx]; FK506 [total n=23]: Pre-Tx = 151+/-13, 1 month = 187+/-22, 3 months = 188+/-10, 6 months = 184+/-13, 12 months = 164+/-9 [P=0.02 vs. CsA]). A separate cohort of patients with stable graft function, cholesterol >225 mg/dl, and two additional risk factors for coronary artery disease were started on pravastatin. Ninety-eight patients were enrolled. Sixteen patients (16%) discontinued the drug because of subjective complaints. No episodes of rhabdomyolysis or hepatotoxicity occurred (cholesterol levels for patients on CsA [total n=65]: pretreatment = 251+/-7, 6 months = 220+/-7 [P=0.01 vs. pretreatment], 12 months = 224+/-8 [P=0.01 vs. pretreatment]; FK506 [total n=17]: pretreatment = 251+/-17, 6 months = 219+/-17, 12 months = 208+/-17 [P=0.08 vs. pretreatment]). Natural killer cells isolated from normal volunteers (n=14) exhibited 27+/-9% specific lysis. Patients on FK506 or cyclosporine-based immunosuppression alone (n=11) exhibited 20+/-4% specific lysis. Standard immunosuppression plus pravastatin (n=10) decreased lysis to 0.2+/-10% (P<0.02 vs. controls and standard immunosuppression). We conclude: (1) posttransplant hyperlipidemia occurs less frequently in liver transplant patients than in renal or cardiac transplants; (2) pravastatin is safe and efficacious for cholesterol reduction in liver transplant patients; and (3) pravastatin coadministered with standard immunosuppression reduces natural killer cell-specific lysis in these recipients. PMID:8878387

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

    PubMed Central

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

    2012-01-01

    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

  1. Renal biopsy in patients with type 2 diabetes mellitus: indications and nature of the lesions

    PubMed Central

    Ghani, Amal Abdel; Al Waheeb, Salah; Al Sahow, Ali; Hussain, Naser

    2009-01-01

    BACKGROUND AND OBJECTIVES: The prevalence of non diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus varies widely depending on the selection criteria and the populations being studied. The aim of this study was to evaluate the renal biopsies performed on type 2 diabetic patients for suspicion of NDRD and to correlate the pathological with the clinical and laboratory findings. SUBJECTS AND METHODS: We selected and reviewed biopsies performed on type 2 diabetics for clinically suspected NDRD from January 2006 to December 2008 at a single hospital. Clinical and laboratory data were analyzed in relation to the histopathology findings. Patients were grouped into either group I with isolated DGS or group II with NDRD on top of DGS. RESULTS: Thirty-one biopsies were performed on type 2 diabetic patients; Seventeen patients (54.8%) were males. Mean age was 50.68 (11.29) years. The mean duration of diabetes was 9.33 (3.6) years. Renal biopsy showed that among the studied group 14 patients (45.2%) showed NDRD on top of DGS. Crescentic glomerulonephritis was the commonest finding seen in 3 cases (21.4% of group II cases) followed by acute tubulointerstitial nephritis and hypertensive changes each was seen in 2 cases (14.4%). Other findings included IgA nephropathy, primary focal segmental glomerulosclerosis, rhabdomyolysis, membranoproliferative glomerulonephritis each of them was seen in one case (7.1%). Group I had a significantly higher level of proteinuria 4.97 (2.08) gm/24 hrs urine than group II 2.72 (1.09) gm/24 hrs urine (P=.003). There was no significant difference between the two groups in age, duration of diabetes, gender, presence of hypertension, hematuria, serum creatinine or glomerular filtration rate. CONCLUSION: The present study showed that crescentic glomerulonephritis is the commonest NDRD among diabetic patients. A higher level of proteinuria was reported among those with NDRD superimposed on DGS. So, Renal biopsy should be performed in diabetics when the clinical scenario is atypical. PMID:19847082

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

    PubMed Central

    2013-01-01

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

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

    PubMed

    Quinlivan, Rosaline; Martinuzzi, Andrea; Schoser, Benedikt

    2014-01-01

    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