Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle causing myoglobin and other intracellular proteins\\u000a and electrolytes to leak into the circulation. The development of rhabdomyolysis is associated with a wide variety of diseases,\\u000a injuries, medications and toxins. While the exact mechanisms responsible for all the causes are not fully understood, it is\\u000a clear that muscle damage can occur
W. H. Bagley; H. Yang; K. H. Shah
Rhabdomyolysis is a well-known clinical syndrome of muscle injury associated with myoglobinuria, electrolyte abnormalities, and often acute kidney injury (AKI). The pathophysiology involves injury to the myocyte membrane and/or altered energy production that results in increased intracellular calcium concentrations and initiation of destructive processes. Myoglobin has been identified as the primary muscle constituent contributing to renal damage in rhabdomyolysis. Although rhabdomyolysis was first described with crush injuries and trauma, more common causes in hospitalized patients at present include prescription and over-the-counter medications, alcohol, and illicit drugs. The diagnosis is confirmed by elevated creatine kinase levels, but additional testing is needed to evaluate for potential causes, electrolyte abnormalities, and AKI. Treatment is aimed at discontinuation of further skeletal muscle damage, prevention of acute renal failure, and rapid identification of potentially life-threatening complications. Review of existing published data reveals a lack of high-quality evidence to support many interventions that are often recommended for treating rhabdomyolysis. Early and aggressive fluid resuscitation to restore renal perfusion and increase urine flow is agreed on as the main intervention for preventing and treating AKI. There is little evidence other than from animal studies, retrospective observational studies, and case series to support the routine use of bicarbonate-containing fluids, mannitol, and loop diuretics. Hyperkalemia and compartment syndrome are additional complications of rhabdomyolysis that must be treated effectively. A definite need exists for well-designed prospective studies to determine the optimal management of rhabdomyolysis. PMID:24008958
Zimmerman, Janice L; Shen, Michael C
Forty Marine Corps recruits were hospitalized at the Naval Hospital, Beaufort, S. C., with acute exertional rhabdomyolysis following several days of excessive upper body calisthenics. After an uncomplicated hospital course, they returned to the regular tr...
M. A. Demos E. L. Gitin
Influenza virus is the most frequently reported viral cause of rhabdomyolysis. A 7-year-old child is presented with rhabdomyolysis associated with parainfluenza type 2 virus. Nine cases of rhabdomyolysis associated with parainfluenza virus have been reported. Complications may include electrolyte disturbances, acute renal failure, and compartment syndrome.
Kielbasa, Johanna M.; Chandrasekharan, Gopal M.; Holmes, Cynthia L.; Gomez, Michael R.
Rhabdomyolysis involves necrosis of skeletal muscle and may arise from multiple conditions both traumatic and nontraumatic. Bone imaging with Technetium-99m phosphates is a very sensitive indicator of acute muscle damage and may be used to visualize the extent of rhabdomyolysis and its resolution. A case of alcohol-induced rhabdomyolysis is presented.
Insect stings belonging to Hymenoptera defined as wasps, yellow jackets, bees, or hornets by human usually result in unserious clinical pictures that go with pain. Rhabdomyolysis following a bee sting is a rare condition. This paper emphasizes “rhabdomyolysis” as a rare complication of this frequently observed envenomation. Rare but severe clinical results may occur due to multiple bee stings, such as intravascular hemolysis, rhabdomyolysis, acute renal insufficiency, and hepatic dysfunction. In bee stings as in our case, clinicians should be alert for rhabdomyolysis in cases with generalized body and muscle pain. Early onset alkaline diuresis and management in patients with rhabdomyolysis are vital in protecting the renal functions and preventing morbidity and mortality.
Akdur, Okhan; Can, Serdar; Afacan, Goksu
The use of magnetic resonance (MR) imaging in two cases of rhabdomyolysis, one resulting from prolonged muscle compression and one from electrical burns, is described. The involved muscles were clearly demonstrated with MR. Recognition and assessment of the extent of rhabdomyolysis are important since life-threatening sequelae including severe metabolic disorders are possible. In one case, spin-echo and inversion-recovery MR imaging provided greater detail of muscle abnormalities than did 99mTc-pyrophosphate radionuclide scanning. Both cases illustrate the usefulness of MR in evaluation of skeletal muscle disorders.
Zagoria, R.J.; Karstaedt, N.; Koubek, T.D.
The present study describes a case of laxative-induced rhabdomyolysis in an elderly patient. An 87-year-old woman was hospitalized for the onset of confusion, tremors, an inability to walk, and a fever that she had been experiencing for 36 hours. She often took high dosages of lactulose and sorbitol syrup as a laxative (about 70 g/day). During her physical examination, the patient was confused, drowsy, and she presented hyposthenia in her upper and lower limbs, symmetric and diffuse moderate hyporeflexia, and her temperature was 37.8 degrees C. Laboratory tests revealed severe hyponatremia with hypokalemia, hypocalcemia, hypochloremia, and metabolic alkalosis. Moreover, rhabdomyolysis markers were found. The correction of hydroelectrolytic imbalances with saline, potassium and sodium chlorure, calcium gluconate was the first treatment. During her hospitalization the patient presented acute delirium, treated with haloperidol and prometazine chloridrate intramuscularly. She was discharged 12 days later, after resolution of symptoms, and normalized laboratory tests. Over-the-counter drugs such as laxatives are usually not considered dangerous; on the other hand, they may cause serum electrolytic imbalance and rhabdomyolysis. A careful monitoring of all the drugs taken by the elderly is one of the most important duties of a physician since drug interactions and their secondary effects may be fatal. PMID:20396636
Merante, Alfonso; Gareri, Pietro; Marigliano, Norma Maria; De Fazio, Salvatore; Bonacci, Elvira; Torchia, Carlo; Russo, Gaetano; Lacroce, Pasquale; Lacava, Roberto; Castagna, Alberto; De Sarro, Giovambattista; Ruotolo, Giovanni
The present study describes a case of laxative-induced rhabdomyolysis in an elderly patient. An 87-year-old woman was hospitalized for the onset of confusion, tremors, an inability to walk, and a fever that she had been experiencing for 36 hours. She often took high dosages of lactulose and sorbitol syrup as a laxative (about 70 g/day). During her physical examination, the patient was confused, drowsy, and she presented hyposthenia in her upper and lower limbs, symmetric and diffuse moderate hyporeflexia, and her temperature was 37.8°C. Laboratory tests revealed severe hyponatremia with hypokalemia, hypocalcemia, hypochloremia, and metabolic alkalosis. Moreover, rhabdomyolysis markers were found. The correction of hydroelectrolytic imbalances with saline, potassium and sodium chlorure, calcium gluconate was the first treatment. During her hospitalization the patient presented acute delirium, treated with haloperidol and prometazine chloridrate intramuscularly. She was discharged 12 days later, after resolution of symptoms, and normalized laboratory tests. Over-the-counter drugs such as laxatives are usually not considered dangerous; on the other hand, they may cause serum electrolytic imbalance and rhabdomyolysis. A careful monitoring of all the drugs taken by the elderly is one of the most important duties of a physician since drug interactions and their secondary effects may be fatal.
Merante, Alfonso; Gareri, Pietro; Marigliano, Norma Maria; De Fazio, Salvatore; Bonacci, Elvira; Torchia, Carlo; Russo, Gaetano; Lacroce, Pasquale; Lacava, Roberto; Castagna, Alberto; De Sarro, Giovambattista; Ruotolo, Giovanni
In several reported cases, rhabdomyolysis has been a manifestation of primary infection with HIV. However, other potential causes of rhabdomyolysis were either present or not excluded in most of those cases. We describe a patient in whom acute rhabdomyolysis was a presenting manifestation of primary HIV infection, and in whom other plausible causes of rhabdomyolysis were reasonably excluded. PMID:16845243
Delo, Daniel; Brett, Allan S; Postic, Bosko
Rhabdomyolysis is a disorder in which injury to muscle results in leakage of myocyte intracellular contents into the plasma. It has been associated with a tremendous number and diversity of clinical conditions and substances. Several physiological and biochemical mechanisms for this syndrome have been described. The most likely etiology of rhabdomyolysis in patients presenting to the emergency department is ingestion
John R Richards
A 12-year-old female presented with chronic diarrhea, fatigue, failure to thrive, sudden weakness of her upper and lower extremities and inability to walk. On neurological examination, atrophy was found of the lower extremity muscles, coupled with muscle weakness. Hypokalemia and a high creatine kinase (CK) level were detected. Antigliadin IgA, IgG and antiendomysial antibodies were positive. A duodenal biopsy revealed the classical findings of celiac disease. To our knowledge this is the first childhood case of celiac disease presenting with rhabdomyolysis. PMID:12728476
Ertekin, Vildan; Selimo?lu, Mukadder Ay?e; Tan, Hüseyin; Kiliçaslan, Buket
Acute rhabdomyolysis results from susceptible persons eating quail during the migrating season. The etiology is unknown. Muscular exercise is an important precipitating factor. In this paper the literature on this and related rhabdomyolytic and hemolytic ...
J. B. Bateman
Rhabdomyolysis is a clinical and a biochemical syndrome that occurs due to a skeletal muscle injury. The main cause of rhabdomyolysis is a muscle crush injury, toxins, ischaemia and metabolic disorders. Rare cases of rhabdomyolysis have been reported which had been caused by drugs and after insect stings. The breakdown products of the damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful for the kidneys and they may lead to kidney failure. The symptoms of rhabdomyolysis depend on the severity of the condition. The milder forms of rhabdomyolysis may not cause any muscle symptoms, and the diagnosis is based on abnormal blood tests. The most reliable test in the diagnosis of rhabdomyolysis is the blood level of Creatine Kinase (CK) which is released by the damaged muscles. Here in, we report an unusual case of flax seed induced rhabdomyolysis to alert the medical community about this rare complication.
Prasad, Anushre; Kumar, Ritesh; Ramanan, Harini; Khandige, Nalini; Prabhu, Krishnananda
Empiric antibiotic usage is very common in clinical practice and Trimethoprim-Sulfamethoxazole (TMP-SMX) is one such antibiotic used extensively in primary care practice. Some patients experience serious adverse effects to the antibiotics that markedly increase the morbidity and the cost of medical care. We describe one such patient, a previously healthy 40-year-old Hispanic female who developed myositis and rhabdomyolysis secondary to TMP-SMX. To the best of our knowledge, this is the first report of TMP-SMX-induced rhabdomyolysis in an immunocompetent host. PMID:23689093
Ainapurapu, Bujji; Kanakadandi, Uday B
Wasp sting is a relatively common arthropod assault, but is sometimes fatal because of anaphylaxis. Rhabdomyolysis is a serious condition, with destruction of striated muscles, and can be induced by various causes such as drugs, heart attacks, CRASH syndrome, and viper bites. Mass envenomation by multiple wasp stings can also cause rhabdomyolysis followed by acute renal failure, although it is extremely rare. We herein report a case who had an anaphylaxis-like reaction and rhabdomyolysis due to multiple wasp stings.
Ito, K.; Imafuku, S.; Nakayama, J.
. Acute renal failure (ARF) is an important complication of rhabdomyolysis. However, the contributing factors to the development\\u000a of ARF in children with rhabdomyolysis remain obscure. The aim of this study was to clarify the factors contributing to the\\u000a development of ARF in children with rhabdomyolysis. This is a retrospective review of the clinical characteristics, laboratory\\u000a data, pediatric risk of
Rhabdomyolysis is a clinical and laboratory syndrome that is caused by various etiologies, involving the skeletal muscle. Clarithromycin, like other macrolides, is an inhibitor of CYP450 3A4, the major enzyme responsible for the metabolism of several drugs, in particular some statins. Rhabdomyolysis related to macrolide–statin interaction has previously been described. To date, rhabdomyolysis induced by clarithromycin has been described in only one previous report. We describe the case of a 90-year-old Caucasian male, admitted to the University Hospital of Pisa for dyspnea, who developed rhabdomyolysis associated with clarithromycin administration.
Pasqualetti, Giuseppe; Bini, Giacomo; Tognini, Sara; Polini, Antonio; Monzani, Fabio
Rhabdomyolysis is a life threatening syndrome. It accounts for an estimated 8% to 15% of cases of acute renal failure and is associated with a mortality rate of 5%. In movement disorders, various causes of rhabdomyolysis have been reported including status dystonicus, myoclonus, generalized chorea and parkinsonism-hyperprexia syndrome in Parkinson’s disease (PD). Levodopa-induced dyskinesia leading to rhabdomyolysis is a very rare phenomenon in PD. We report a case of 76 years old PD patient with dyskinesia and rhabdomyolysis.
Bektas, Hesna; Deniz, Orhan; Temel, Sadiye; Keklikoglu, Hava Donmez; Akyol, Sener
Rhabdomyolysis is a life threatening syndrome. It accounts for an estimated 8% to 15% of cases of acute renal failure and is associated with a mortality rate of 5%. In movement disorders, various causes of rhabdomyolysis have been reported including status dystonicus, myoclonus, generalized chorea and parkinsonism-hyperprexia syndrome in Parkinson's disease (PD). Levodopa-induced dyskinesia leading to rhabdomyolysis is a very rare phenomenon in PD. We report a case of 76 years old PD patient with dyskinesia and rhabdomyolysis. PMID:24926408
Bekta?, Hesna; Deniz, Orhan; Temel, Sadiye; Kekliko?lu, Hava Dönmez; Akyol, Sener
Here, we report a case of massive rhabdomyolysis following an uncomplicated repair of a ventricular septal defect in a five-month-old baby. Postoperatively, the patient was hemodynamically stable but metabolic acidosis continued, accompanied by fever and delayed mental recovery. The next day, he became comatose and never regained consciousness thereafter. The computed tomography of the brain revealed a diffuse brain injury. The patient followed a downhill course and eventually died on postoperative day 33. An unusually high level of creatine phosphokinase was noticed, peaking (21,880 IU/L) on postoperative day 2, suggesting severe rhabdomyolysis. The relevant literature was reviewed, and the possibility of malignant hyperthermia obscured by cardiopulmonary bypass and hypothermia was addressed. PMID:24782976
Kim, Young Sam; Yoon, Yong Han; Kim, Joung Taek; Baek, Wan Ki
A case of severe rhabdomyolysis is reported in which, some seven and one-half weeks after its occurrence, a gallium scan was strongly positive, due to abscess formation in the damaged muscle. A bone scan was weakly positive in the same area, due to gallium photons. A review of the the reported cases reveals that bone scans are a very sensitive indicator of acute muscle damage and are useful to monitor its repair.
Rhabdomyolysis is a potentially life-threatening disorder that occurs as a primary disease or as a complication of a broad spectrum of other diseases. We report the first case of acute rhabdomyolysis after ingestion of Spirulina (Arthrospira platensis), a plantonic blue-green alga, as a dietary supplement. PMID:18434120
Mazokopakis, Elias E; Karefilakis, Christos M; Tsartsalis, Athanasios N; Milkas, Anastasios N; Ganotakis, Emmanuel S
Rhabdomyolysis is a potentially life-threatening disorder that occurs as a primary disease or as a complication of a broad spectrum of other diseases. We report the first case of acute rhabdomyolysis after ingestion of Spirulina (Arthrospira platensis), a plantonic blue-green alga, as a dietary supplement.
Elias E. Mazokopakis; Christos M. Karefilakis; Athanasios N. Tsartsalis; Anastasios N. Milkas; Emmanuel S. Ganotakis
Summary Severe potassium deficiency is an uncommon cause of rhabdomyolysis. We recently treated a 45-year-old patient with myalgia, serious generalized weakness, increased serum creatine kinase and myoglobin level as well as excessive hypokalemia. Histological examination of deltoid muscle biopsy showed rhabdomyolysis. After complete recovery of muscle damage by potassium substitution Bartter's syndrome proved to be the cause of initial and
H. Bierbach; J. Bohl; H. J. Göldner; J. Majdandzic
Extensive rhabdomyolysis is often lethal unless treated immediately. Early mortality arises from hypovolemic shock, hyperkalemia, acidosis and myoglobinuric acute kidney injury (AKI). Many individuals with rhabdomyolysis could be saved, and myoglobinuric AKI prevented, by early vigorous fluid resuscitation with ?12 l daily intravenous infusion of alkaline solution started at the scene of injury. This regimen stabilizes the circulation and mobilizes
Zaid A. Abassi; Ori S. Better
To evaluate the determinants of rhabdomyolysis in the diabetic state, we compared biochemical and clinical features of diabetic patients with (group 1, 41 patients) and without (group 2, 36 patients) rhabdomyolysis. There was no difference in values for serum potassium, bicarbonate, phosphate and calcium between the two groups. Nineteen patients in group 2 and 21 patients in group 1 were
Pravin C. Singhal; Mirel Abramovici; Shashidharan Ayer; Lionel Desroches
Twenty-one Marine recruits in three training programs at the Marine Corps Recruit Depot, Parris Island, SC, were prospectively studied for one week for the presence of myoglobinemia and development of clinical rhabdomyolysis. Myoglobinemia was found in tw...
M. A. Demos E. L. Gitin L. J. Kagen
Acute kidney injury occurs in 33-50% of patients with rhabdomyolysis and infections remain one of the major contributing factors. The incidence of rhabdomyolysis in non-hemorrhagic dengue virus infection is quite low and may go unnoticed, especially if the presentation is not florid. We report a case of a young male patient, sero-positive for dengue, with no hemorrhagic manifestations or hypotension, who developed rhabdomyolysis complicated by renal failure. The patient eventually needed dialysis support and later recovered fully. Clinicians need to be aware of the occurrence of rhabdomyolysis even in patients without the hemorrhagic manifestations of dengue viral infection and should employ early preventive strategies in such cases. PMID:24231486
Jha, Ratan; Gude, Dilip; Chennamsetty, Sashidhar
Exercise-induced rhabdomyolysis has been described in military recruits, trained athletes and daily runners. Statin use, quail ingestion, infection by Epstein-Barr virus (EBV), and hypothyroidism, though rare, are risk factors for the development of rhabdomyolysis. We describe the case of a 15-year-old female who presented with myalgias, weakness, and pigmenturia following marching band practice. Laboratory tests confirmed an elevated creatine kinase (CK) level as well as a profound hypothyroid state. Muscle biopsy revealed severe muscle necrosis and myositis. Treatment with levothyroxine resulted in obtaining an euthyroid state and regain of muscle strength as well as decrease in CK levels. Although rare, hypothyroidism should be considered as a potential cause of rhabdomyolysis in pediatric patients undergoing a myopathy workup.
Farias Moeller, Raquel; Zecavati, Nassim; Sherafat-Kazemzadeh, Rosa; Aleinikoff, Shoshana; Rennert, Wolfgang
(1) Rosuvastatin was not evaluated for its impact on morbidity or mortality. In premarketing trials its adverse effects seemed similar to those observed with other statins. In addition, there were questions concerning renal adverse effects, particularly dose-dependent proteinuria. Inadequate information was available to know whether the risk of rhabdomyolysis differed from that of other statins. (2) A review of adverse events reported to the FDA in late 2004 showed that reports of renal and muscular adverse events were more frequent with rosuvastatin than with other statins currently on the market. (3) Regulatory agencies analysed their results and issued warnings, but they withheld the raw data. This is regrettable, especially given the frequent use of the drug, the specific risks associated with this class, and the questions that were left unanswered in its initial clinical evaluation. Healthcare professionals and the public need access to more precise data on rosuvastatin. (4) In practice, it is better to select the two statins with the most thorough clinical assessments, namely simvastatin and pravastatin. PMID:17458050
Scrub typhus is the most common zoonosis of public health importance in rural areas of Asia, Northern Australia and Pacific Islands. The clinical spectrum of the disease varies from acute febrile illness to multi-organ involvement with systemic complications. Delay in diagnosis and treatment often lead to increased morbidity and mortality. Rhabdomyolysis is a rare complication seen in an infectious disease. We report a 50-year-old farmer with scrub typhus presented with rhabdomyolysis and acute renal failure who succumbed to the disease in hospital.
Kumar, Bhatrahalli Ashok Praveen; Kumar, Arinagnalli Subbanna Praveen; Sharvanan, E.
Exertional rhabdomyolysis is an uncommon diagnosis, but because its complications can be severe, clinicians need a thorough understanding of this syndrome. When skeletal muscle cell membranes are damaged, their intracellular contents enter the bloodstream and can cause potentially serious sequelae, even death. Intense exercise, some viral infections, and certain genetic disorders increase the risk. Serum creatine kinase levels are the diagnostic gold standard. The treatment of rhabdomyolysis consists of early detection, therapy for the underlying cause, measures to prevent renal failure, and correction of metabolic complications. PMID:20086405
Brown, Thomas P
Exercise induced rhabdomyolysis is well known, but has rarely been reported in high school students. This is the report of 119 cases in high school students who exercised vigorously (120 push ups in five minutes) in cold weather. Most of them developed muscle pain and dark urine within two to four days of the exercise.
A C-M Lin; C-M Lin; T-L Wang; J-G Leu
Rhabdomyolysis in equines occurs in horses due to physical overexertion or underlying pathologic myopathy. Methocarbamol is a muscle relaxant that can be used in equines to treat symptoms associated with Rhabdomyolysis. Methocarbamol is available as a solution for injection but is not commercially available as an oral suspension. This article focuses on the treatment of Tying-up caused by overexertion, and details the treatment of Rhabdomyolysis with an oral suspension that was prepared for a veterinarian by a compounding pharmacist. PMID:24459784
Pruitt, Bobby N
Rhabdomyolysis has been the theme in medical literature for the last fifty years. In these last decades, with statins being used in primary and secondary cardiovascular prevention events, this theme returns and statins are now pointed as the trigger to this almost always fatal complication. Rhabdomyolysis due to statins administration occurs mainly in association with other drugs. Our case reports on a patient with fatal statin-induced rhabdomyolysis whose medical history included diffuse atherosclerotic disease. PMID:16358092
Gama, Mirnaluci P Ribeiro; Pellegrinello, Silviane; Alonso, Sheyla Santos Quelle; Coelho, Juliana Filus; Martins, Caroline F Luz; Biagini, Gleyne Lopes Kujew
Rhabdomyolysis is a common clinical syndrome and accounts for 7% of all cases of acute kidney injury (AKI) in the USA. It\\u000a can result from a wide variety of disorders, such as trauma, exercise, medications and infection, but in the pediatric population,\\u000a infection and inherited disorders are the most common causes of rhabdomyolysis. Approximately half of patients with rhabdomyolysis\\u000a present
Essam F. Elsayed; Robert F. Reilly
Rhabdomyolysis is a syndrome caused by skeletal muscle cells destruction which can occur for many reasons, including prolonged immobilization. The main complication of the syndrome is the development of acute renal failure. Rhabdomyolysis and myoglobinuria are responsible for approximately 5% of all causes of acute renal failure in the USA. The cause of rhabdomyolysis is often multifactorial, and approximately 8–20% of such patients develop myoglobinuric acute renal failure.
Maggi, G.; Quinteros Hinojosa, F.; Villagran, M. J.; Guasch Arevalo, E.; Gilsanz Rodriguez, F.
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.
Coban, Yusuf Kenan
Rhabdomyolysis and acute renal failure can be a rare but serious complication resulting from compromising operative positions following some urologic and gynecologic procedures. We report a lethal case of rhabdomyolysis following radical perineal prostatectomy. The possibility of this complication must be considered prior to performing any operation in the exaggerated lithotomy position. Prevention, early diagnosis, and aggressive treatment are the
R. Grady Bruce; Frank H. Kim; J. William McRoberts
Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and
Ana L Huerta-Alardín; Joseph Varon; Paul E Marik
We report about a young female patient who suffered a rhabdomyolysis and a plexus lesion after heroin intoxication. A computer-tomography was made to reveal the extent of myonecrosis. A larger rhabdomyolysis of muscles of the pelvis and left thigh was seen. A residual paresis of the left N. peronaeus existed at discharge of the patient. PMID:1852029
Strohmaier, A; Friedrich, M
Hypothyroidism occurs relatively common and is a significant cause of morbidity and mortality during the course of chronic kidney disease. Rhabdomyolysis is a potentially life-threatening condition characterised by necrosis of muscular tissue and rarely associates with hypothyroidism. Here we describe a case of rhabdomyolysis due to severe hypothyroidism in a 56-year-old female hemodialysis patient. PMID:24803938
Tatar, Erhan; Isikyakar, Tolgay; Yeniay, Kezban Pinar; Uzuner, Hasan Huseyin; Sevinc Ok, Ebru
Hypothyroidism occurs relatively common and is a significant cause of morbidity and mortality during the course of chronic kidney disease. Rhabdomyolysis is a potentially life-threatening condition characterised by necrosis of muscular tissue and rarely associates with hypothyroidism. Here we describe a case of rhabdomyolysis due to severe hypothyroidism in a 56-year-old female hemodialysis patient.
Tatar, Erhan; Isikyakar, Tolgay; Yeniay, Kezban Pinar; Uzuner, Hasan Huseyin; Sevinc Ok, Ebru
A patient with exertional rhabdomyolysis and continuously elevated serum creatine kinase (CK) was investigated. The known causes of recurrent attacks of rhabdomyolysis were ruled out by appropriate histochemical and biochemical investigations. During ischaemic exercise tests an abnormal K(+)-efflux from exercising muscles was observed. The patient was found to have a deficiency of muscular Ca(2+)-ATPase. Dantrolene sodium therapy gave relief of
P J Poels; R A Wevers; J P Braakhekke; A A Benders; J H Veerkamp; E M Joosten
Rhabdomyolysis is a common clinical syndrome and accounts for 7% of all cases of acute kidney injury (AKI) in the USA. It can result from a wide variety of disorders, such as trauma, exercise, medications and infection, but in the pediatric population, infection and inherited disorders are the most common causes of rhabdomyolysis. Approximately half of patients with rhabdomyolysis present with the triad of myalgias, weakness and dark urine. The clinical suspicion, especially in the setting of trauma or drugs, is supported by elevated creatinine kinase levels and confirmed by the measurement of myoglobin levels in serum or urine. Muscle biopsy and genetic testing should be performed if rhabdomyolysis is recurrent or metabolic myopathy is suspected. Early recognition is important to prevent AKI through the use of aggressive hydration. Prevention is important in patients with inherited forms, but novel therapies may be developed with the better understanding of the pathophysiology and genetics of rhabdomyolysis. PMID:19529963
Elsayed, Essam F; Reilly, Robert F
Acute renal failure (ARF) following rhabdomyolysis is a well known entity. In this paper, we present an unusual cause for trauma that resulted in rhabdomyolysis associated with renal failure. Rhabdomyolysis resulted from human stampede that occurred in a mountain tunnel on the occasion of The Pilgrimage to Makkah in 1990. To the best of our knowledge, human stampede as a cause of rhabdomyolysis has not been reported in the literature. A total of eight patients were referred to our center. Laboratory investigations revealed rhabdomyolysis as well as evidence of moderate to severe renal impairment in all patients. They were treated with forced alkaline diuresis, but three required hemodialysis. All patients recovered. Treatment with forced alkaline diuresis was found to be useful in the treatment of these patients and instituting such treatment is worthwhile even in those cases where renal failure is established. PMID:18583757
Sheikh, I A; Shaheen, F A; El-Aqeil, N A; Al-Khader, A; Karsuwa, S
Described as the pathological breakdown of skeletal muscle tissue in response to major injury, traumatic rhabdomyolysis iwas first recorded, during the second world war, a far greater understanding of its pathology has informed pre-hospital assessment and management of the condition. This article describes the aetiology of the condition and explores associated complications, such as acute respiratory distress syndrome, hyperkalaemia, acute renal failure and compartment syndrome resulting from prolonged limb entrapment. The article also reviews the literature about management of the condition for hospital and out-of-hospital settings. PMID:24313421
Desjardins, Mathew; Strange, Barnaby
Ultrasound imaging of rhabdomyolysis previously has been reported in the literature, but differing descriptions of its appearance exist. In this report, we describe a relatively rare case of exertional rhabdomyolysis of the anterior arm muscles. This injury may appear sonographically different than more severe cases of rhabdomyolysis. Our patient was a young, active individual participating in a weight-lifting exercise as part of a physiology laboratory experiment. Ultrasound was helpful to assist in the diagnosis and rule out other conditions. He was treated conservatively and eventually made a complete recovery. PMID:24487127
Pierson, Elizabeth H; Bantum, Brian M; Schaefer, Michael P
Rhabdomyolysis results from acute damage of the skeletal muscle brought on by various conditions of which hypokalemia is a recognized, but less common condition. Although primary aldosteronism may cause severe hypokalemia leading to rhabdomyolysis, the patients may have potassium levels within the normal range on routine biochemistry. In addition, hypokalemia may be triggered by initiation of diuretic therapy for control of hypertension. Here, we describe a patient with an aldosterone secreting adrenal adenoma, who presented with acute rhabdomyolysis secondary to severe hypokalemia triggered by initiation of diuretic therapy.
Cooray, M. Samanthi A.; Bulugahapitiya, Uditha S.; Peiris, D. Natasha
Rhabdomyolysis results from acute damage of the skeletal muscle brought on by various conditions of which hypokalemia is a recognized, but less common condition. Although primary aldosteronism may cause severe hypokalemia leading to rhabdomyolysis, the patients may have potassium levels within the normal range on routine biochemistry. In addition, hypokalemia may be triggered by initiation of diuretic therapy for control of hypertension. Here, we describe a patient with an aldosterone secreting adrenal adenoma, who presented with acute rhabdomyolysis secondary to severe hypokalemia triggered by initiation of diuretic therapy. PMID:24251171
Cooray, M Samanthi A; Bulugahapitiya, Uditha S; Peiris, D Natasha
Rhabdomyolysis is a rare but potentially lethal clinical syndrome that results from acute muscle fiber necrosis with leakage of muscle constituents into blood. This devastating disease could be due to muscle compression caused by urologic positioning for a lengthy nephrectomy. In this regard, laparoscopic renal surgery may be a risk for the development of rhabdomyolysis. This phenomenon of massive muscle necrosis can produce secondary acute renal failure. The risk factors have to be managed carefully during anesthetic management. Here, we report a case of a patient with rhabdomyolysis that developed in the flexed lateral decubitus position during laparoscopic nephrectomy.
Kim, Tae Kwane; Lee, Myeong Ha
Clarithromycin is the most documented cytochrome P450 3A4 (CYP3A4) inhibitor to cause an adverse interaction with simvastatin. This particular case is of interest as rhabdomyolysis only occurred after an increase in the dose of clarithromycin. The patient developed raised cardiac biomarkers without any obvious cardiac issues, a phenomenon that has been linked to rhabdomyolysis previously. To date, there has been no reported effect of rhabdomyolysis on the structure and function of cardiac muscle. Clinicians need to be aware of prescribing concomitant medications that increase the risk of myopathy or inhibit the CYP3A4 enzyme. Our case suggests that troponin elevation could be associated with statin induced rhabdomyolysis, which may warrant further studies. PMID:25041770
Page, S R; Yee, K C
Background Rhabdomyolysis is a potentially life-threatening syndrome that can develop from a variety of causes. The aim of the work is to analyze the clinical spectrum and to evaluate the prevalence of various etiologies in children, who present to the emergency department (ED) with rhabdomyolysis. Methods During a 6-year study period, we retrospectively analyzed the medical charts of patients, aged 18 years or younger, with a definite diagnosis of rhabdomyolysis and serum creatinine phosphokinase (CK) levels greater than 1000IU/L. We analyzed the clinical spectrum and evaluated the potential risk factors of acute renal failure (ARF). Results Thirty-seven patients (mean age = 10.2 ± 5.5 years), including 26 males and 11 females, were enrolled in the study. Two of the most common presented symptoms in these 37 patients were muscle pain and muscle weakness (83.8% and 73%, respectively). Dark urine was reported in only 5.4% of the patients. The leading cause of rhabdomyolysis in the 0- to 9-year age group was presumed infection, and the leading cause in the 10- to 18-year age group was trauma and exercise. The incidence of ARF associated with rhabdomyolysis was 8.1 % and no child needed for renal replacement therapy (RRT). We did not identify any reliable predictors of ARF or need for RRT. Conclusions The classic triad of symptoms of rhabdomyolysis includes myalgia, weakness and dark urine are not always presented in children. The cause of rhabdomyolysis in younger age is different from that of teenager group. However, the prognosis of rhabdomyolysis was good with appropriate management.
Simvastatin is one of the most commonly prescribed CoA reductase inhibitors. The safety profile of this drug has been widely discussed in the medical and consumer advocacy communities. Like other statins, simvastatin can cause a serious and potentially life-threatening complication: rhabdomyolysis. We describe a case of simvastatin-induced rhabdomyolysis complicated by acute renal failure requiring urgent hemodialysis. The relative safety of
Abdelkarim Waness; Sami Bahlas; Saad Al Shohaib
Rhabdomyolysis is usually caused by muscle injury, drugs or alcohol and presents with muscle weakness and pain. It is characterized by rise in serum creatine kinase, aminotransferases and electrolytes as well as myoglobinuria. Myoglobinuria may cause acute kidney injury by direct proximal tubule cytotoxicity, renal vasoconstriction, intraluminal cast formation and distal tubule obstruction. Muscle pain and weakness as well as vascular injury have been reported after acupuncture. We report a case of severe rhabdomyolysis and acute kidney injury after acupuncture sessions. PMID:24821167
Papasotiriou, Marios; Betsi, Grigoria; Tsironi, Maria; Assimakopoulos, Georgios
. Inherent compromises in substrate metabolism, or impaired perfusion of muscle may contribute to the occurrence of exercise-induced\\u000a rhabdomyolysis. In this study, the lactate response of the elbow flexor muscles to light exercise was examined in eight subjects\\u000a (five males, three females) who previously demonstrated rhabdomyolysis with extreme swelling (ES; n=4) or no swelling (NS; n=4) of the upper arm
Stephen P. Sayers; Priscilla Clarkson; Jehangir J. Patel
The purpose of these studies was to establish whether acute exertional rhabdomyolysis could be produced in potassium- or magnesium-deficient dogs. In addition, attempts were made to induce exertional rhabdomyolysis in control dogs by repetitive exhaustive...
J. E. Olerud W. H. Pryor R. L. Eason H. W. Carroll
We report on an 11-year-old boy who developed rhabdomyolysis and acute renal failure following Salmonella enteritidis gastroenteritis. Rhabdomyolysis should be considered as a potentially fatal complication in patients with Salmonella gastroenteritis.
Koichi Asai; Shin-ichiro Tanaka; Masato Arai; Noriko Tanaka; Kumi Tsumura; Fumihide Kato; Kiyoshi Kikuchi
Trabectedin has been reported to occasionally induce rhabdomyolysis. In the present case, continuation of trabectedin was maintained despite suspected rhabdomyolysis related to trabectedin. Creatinine kinase levels dropped to normal levels. We suggest that continuation of trabectedin despite suspected rhabdomyolysis was safe in this specific patient.
Lamm, W.; Amann, G.; Brodowicz, T.
Objective The withdrawal of cerivastatin involved an uncommon but serious adverse reaction, rhabdomyolysis. The bimodal response--rhabdomyolysis in a small proportion of users-- points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis. Methods The study had two components: a candidate gene study to evaluate variants in CYP2C8, UGT1A1, UGT1A3, and SLCO1B1; and a genome-wide association (GWA) study to identify risk factors in other regions of the genome. 185 rhabdomyolysis cases were frequency matched to statin-using controls from the Cardiovascular Health Study (n=374) and the Heart and Vascular Health Study (n=358). Validation relied on functional studies. Results Permutation test results suggested an association between cerivastatin-associated rhabdomyolysis and variants in SLCO1B1 (p = 0.002), but not variants in CYP2C8 (p = 0.073) or the UGTs (p = 0.523). An additional copy of the minor allele of SLCO1B1 rs4149056 (p.Val174Ala) was associated with the risk of rhabdomyolysis (OR: 1.89, 95% CI: 1.40 to 2.56). In transfected cells, this variant reduced cerivastatin transport by 40% compared with the reference transporter (p < 0.001). The GWA identified an intronic variant (rs2819742) in the ryanodine receptor 2 gene (RYR2) as significant (p=1.74E-07). An additional copy of the minor allele of the RYR2 variant was associated with a reduced risk of rhabdomyolysis (OR: 0.48; 95% CI: 0.36 to 0.63). Conclusion We identified modest genetic risk factors for an extreme response to cerivastatin. Disabling genetic variants in the candidate genes were not responsible for the bimodal response to cerivastatin.
Marciante, Kristin D.; Durda, Jon P.; Heckbert, Susan R.; Lumley, Thomas; Rice, Ken; McKnight, Barbara; Totah, Rheem A.; Tamraz, Bani; Kroetz, Deanna L.; Fukushima, Hisayo; Kaspera, Rudiger; Bis, Joshua C.; Glazer, Nicole L.; Li, Guo; Austin, Thomas R.; Taylor, Kent D.; Rotter, Jerome I.; Jaquish, Cashell E.; Kwok, Pui-Yan; Tracy, Russell P.; Psaty, Bruce M.
Introduction: Rhabdomyolysis results from many causes including hypernatremia. Postpartum hypernatremia with osmotic cerebral demyelination is a rare cause of reversible rhabdomyolysis. Electromyographic studies in postpartum hypernatremia have not been reported. Materials and Methods: Electromyography (EMG) was performed in five women with postpartum hypernatremia and muscle biopsy was performed in one of them. Results: Among the five women presenting with postpartum hypernatremia associated with marked elevation of serum creatine kinase, four had quadriparesis. All had varying degrees of encephalopathy at admission and recovered without residual deficits after gradual correction of hypernatremia. Needle EMG revealed fibrillations with positive sharp waves in five patients and myotonic discharges in three patients. Serial EMG in one patient revealed the occurrence of transient fibrillations, positive sharp waves and myotonic discharges. Muscle biopsy revealed extensive rhabdomyolysis in one patient. Conclusion: EMG in hypernatremic rhabdomyolysis revealed spontaneous activity including fibrillations, positive sharp waves and myotonic discharges along with myopathic potentials. Electromyographic findings depend on the interval from the onset and the degree of rhabdomyolysis.
Naik, Karkal Ravishankar; Saroja, Aralikatte Onkarappa; Narayanappa, Gayatri
Purpose Fibrates are used to manage mixed dyslipidemia. However, these drugs have the potential risk of inducing rhabdomyolysis. This\\u000a paper gives an overview of the literature on rhabdomyolysis associated with fibrate therapy.\\u000a \\u000a \\u000a \\u000a Methods We reported a case of rhabdomyolysis induced by fenofibrate and reviewed the published rhabdomyolysis cases associated with\\u000a fibrate therapy.\\u000a \\u000a \\u000a \\u000a Results Seventy-six published rhabdomyolysis cases associated with fibrates were evaluated, and
Jianyong Wu; Yan Song; Heng Li; Jianghua Chen
Rhabdomyolysis ranges from an asymptomatic illness with elevated creatine kinase levels to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure, and disseminated intravascular coagulation. The most common causes are crush injury, overexertion, alcohol abuse, certain medicines, and toxic substances. A number of electrolyte abnormalities and endocrinopathies, including hypothyroidism, thyrotoxicosis, diabetic ketoacidosis, nonketotic hyperosmolar state, and hyperaldosteronism, cause rhabdomyolysis. Rhabdomyolysis and acute renal failure are unusual manifestations of pheochromocytoma. There are a few case reports with pheochromocytoma presenting rhabdomyolysis and acute renal failure. Herein, we report a case with pheochromocytoma crisis presenting with rhabdomyolysis and acute renal failure. PMID:24059440
Celik, Huseyin; Celik, Ozlem; Guldiken, Sibel; Inal, Volkan; Puyan, Fulya Oz; Tugrul, Armagan
Background Sturge-Weber syndrome is a congenital neurocutaneous disorder characterized by facial port-wine stain, leptomeningeal angioma, and neurological disorders. Sturge-Weber syndrome can coexist with other disorders in a few patients; however, muscular abnormalities have not been reported in patients with Sturge-Weber syndrome. Case presentation A Chinese girl presented with extensive port-wine stains, congenital bilateral glaucoma, and leptomeningeal angiomatosis. The neurocutaneous symptoms were consistent with the diagnostic criteria of Sturge-Weber syndrome. Meanwhile, episodes of rhabdomyolysis were supported by the recurrent symptoms as follows: exercise intolerance, hyperCKmia, elevated serum myoglobin, and renal failure. Myopathological features and high level of blood long-chain acyl-carnitine indicated that episodes of rhabdomyolysis might be caused by lipid metabolic myopathy. Causative mutations were not found in the CPT2, ACADVL, and GNAQ gene. Conclusions We report the first case that Sturge-Weber syndrome coexists with episodes of rhabdomyolysis associated with lipid metabolic myopathy.
An 85-year-old woman with renal impairment and hypothyroidism was commenced on high dose simvastatin (80 mg) for better lipid control. Shortly after this she developed severe muscular weakness and laboratory evidence of rhabdomyolysis. Despite having hypothyroidism controlled for years with L-thyroxine (100 mcg), her biochemistry now reflected a hypothyroid state with inadequate thyroid replacement. On discontinuing her simvastatin to treat her rhabdomyolysis, the patient's TSH level decreased to normal within 4 weeks without any change in L-thyroxine dosage. To our knowledge this is only the second case reported in the literature of a rare but important interaction between simvastatin and L-thyroxine and the first case reported with associated rhabdomyolysis. PMID:17098308
Kiernan, Thomas J; Rochford, Martin; McDermott, John H
The common causes of rhabdomyolysis include trauma, hypoxia, drugs, toxins, infections and hyperthermia. Operative insults, including direct trauma and ischemia, have the potential to cause the development of rhabdomyolysis. Pneumatic tourniquets used during arthroscopic knee surgery to prevent blood loss have led to many complications such as nerve paralysis and vascular injuries. Rhabdomyolysis can also be caused by prolonged pneumatic tourniquet application without a midapplication release, and also from an increased application pressure, but the actual incidence of this is low. In order to prevent rhabdomyolysis, the clinicians must be aware of such risks and follow strict guidelines for the application time, the midapplication release and also the inflation pressure. Vigorous hydration and postoperative patient surveillance are helpful to prevent rhabdomyolysis. We have recently experienced a case of rhabdomyolysis after the arthroscopic knee surgery, and the rhabdomyolysis could have been associated with the use of a pneumatic tourniquet.
Lee, Yong Gu; Park, Woong; Kim, Sang Hoon; Yun, Sang Pil; Jeong, Hun; Kim, Hyung Jong
We report an observation of acute rhabdomyolysis of gluteus maximum muscles occurring in a non-obese patient installed in supine position that underwent knee arthroscopy under spinal anaesthesia. The patient had insulin-dependent diabetes melitus with documented microangiopathy. The interest of this observation resides in the occurrence of the syndrome after a short period of time (one hour) of installation in the supine position in a patient that did not have any of the generally described risk factors of rhabdomyolysis. PMID:11530755
Bouché, P M; Chavagnac, B; Cognet, V; Banssillon, V
Rhabdomyolysis is an uncommon but life-threatening adverse effect of simvastatin therapy. A 73-year-old male on chronic simvastatin therapy received azithromycin for acute bronchitis. He presented with weakness of all extremities with a significant increase in creatinine phosphokinase levels and acute kidney injury. Simvastatin was stopped and supportive therapy with intravenous saline and bicarbonate was initiated. The serum creatinine and creatine phosphokinase returned to baseline in the next 7 days. Two months later, simvastatin was resumed without any recurrence of symptoms. Our case report highlights the rare description of rhabdomyolysis caused by a drug interaction between simvastatin with azithromycin.
Alreja, Gaurav; Inayatullah, Saqib; Goel, Saurabh; Braden, Gregory
Paraphenylene daimine (PPD) is a kind of aromatic amine that is widely used in several industrial products. Women also use PPD added to henna (Lawasonia alba) as a hair dye. Though rare in Western countries, PPD poisoning is quite common in East Africa, India and Middle Eastern countries because it is a traditional product at these countries. Different pathologies were described as caused by PPD ingestion including angioedema of head and neck, rhabdomyolysis, and acute renal failure. The authors report a case of systemic poisoning with PPD that lead to angioedema resulting in tracheostomy and rhabdomyolysis. PMID:23723080
Elevli, Murat; Civilibal, Mahmut; Ersoy, Ozlem; Demirkol, Demet; Gedik, Ahmet Hakan
Guillain-Barre syndrome (GBS) is a heterogenous group of peripheral-nerve disorders with similar clinical presentation characterized by acute, self-limited, progressive, bilateral and relatively symmetric ascending flaccid paralysis, which peaks in 2-4 weeks and then subsides. The usual complications, which occur in a patient of GBS are pneumonia, sepsis, pulmonary embolism, respiratory insufficiency and cardiac arrest. The clinical course of GBS complicated by acute rhabdomyolysis is extremely rare. We present the case of GBS with marked elevation in serum creatine kinase, serum myoglobin levels and persistent hyperkalemia as a result of associated acute rhabdomyolysis. PMID:24872655
Saxena, Amrish; Singh, Vineeta; Verma, Nitin
A patient with exertional rhabdomyolysis and continuously elevated serum creatine kinase (CK) was investigated. The known causes of recurrent attacks of rhabdomyolysis were ruled out by appropriate histochemical and biochemical investigations. During ischaemic exercise tests an abnormal K(+)-efflux from exercising muscles was observed. The patient was found to have a deficiency of muscular Ca(2+)-ATPase. Dantrolene sodium therapy gave relief of muscle symptoms and improved the exercise tolerance. Both the CK level and the K(+)-efflux in ischaemic forearm testing became normal on this therapy. Images
Poels, P J; Wevers, R A; Braakhekke, J P; Benders, A A; Veerkamp, J H; Joosten, E M
Guillain-Barre syndrome (GBS) is a heterogenous group of peripheral-nerve disorders with similar clinical presentation characterized by acute, self-limited, progressive, bilateral and relatively symmetric ascending flaccid paralysis, which peaks in 2-4 weeks and then subsides. The usual complications, which occur in a patient of GBS are pneumonia, sepsis, pulmonary embolism, respiratory insufficiency and cardiac arrest. The clinical course of GBS complicated by acute rhabdomyolysis is extremely rare. We present the case of GBS with marked elevation in serum creatine kinase, serum myoglobin levels and persistent hyperkalemia as a result of associated acute rhabdomyolysis.
Saxena, Amrish; Singh, Vineeta; Verma, Nitin
Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER. DNA samples derived from a laboratory-based study of persons who had never experienced an episode of ER (controls) and clinical ER cases referred for testing over the past several years were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes. These included angiotensin I converting enzyme (ACE), ?-actinin-3 (ACTN3), creatine kinase muscle isoform (CKMM), heat shock protein A1B (HSPA1B), interleukin 6 (IL6), myosin light chain kinase (MYLK), adenosine monophosphate deaminase 1 (AMPD1), and sickle cell trait (HbS). Population included 134 controls and 47 ER cases. The majority of ER cases were men (n = 42/47, 89.4 %); the five women with ER were Caucasian. Eighteen African Americans (56.3 %) were ER cases. Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM (odds ratio/OR = 3.1, confidence interval/CI 1.33-7.10), 3.0 times for the XX genotype of ACTN3 SNP (OR = 2.97, CI 1.30-3.37), and 5.7 times for an A allele of MYLK (OR = 21.35, CI 2.60-12.30). All persons with HbS were also ER cases. Three distinct polymorphisms were associated with ER. Further work will be required to replicate these findings and determine the mechanism(s) whereby these variants might confer susceptibility. PMID:23543093
Deuster, Patricia A; Contreras-Sesvold, Carmen L; O'Connor, Francis G; Campbell, William W; Kenney, Kimbra; Capacchione, John F; Landau, Mark E; Muldoon, Sheila M; Rushing, Elisabeth J; Heled, Yuval
Rhabdomyolysis is a major cause of acute renal failure, and recent experimental data have provided a better understanding of the pathophysiology of the renal dysfunction. Renal failure is due to renal vasoconstriction, tubular damage caused by oxidant injury, and possibly tubular obstruction. Recent studies have provided greater insight into the rationale behind current therapy and potential treatment strategies. This review
S. Holt; K. Moore
Rhabdomyolysis causes renal dysfunction associated with renal vasoconstriction, tubular toxicity and luminal obstruction. There is now accumulating evidence that renal injury, caused by lipid peroxidation, is important in the pathogenesis of renal failure. The proposed central role of free iron in this process is examined. Current data have shown that the heme center of myoglobin can initiate lipid peroxidation and
Steve Holt; Kevin Moore
We report the history of a seven year-old male boy with cough and fever, who developed rhabdomyolysis concomitant with Mycoplasma pneumoniae infection. The association between this organism and the muscular injury is rarely described in paediatric patients. This case then thus emphasizes that even seemingly mild M. pneumoniae airway infections may be complicated by invalidating neuromuscular sequelae. PMID:24651091
Consilvio, Nicola Pietro; Rapino, Daniele; Scaparrotta, Alessandra; Attanasi, Marina; Di Pillo, Sabrina; Chiarelli, Francesco; Savini, Vincenzo
Rhabdomyolysis is a common condition with potentially devastating complications, including acute renal failure, arrhythmias, and death. The standard of care is to use supportive measures such as aggressive fluid repletion to prevent kidney injury and attenuate clinical symptoms. Besides fluid management, few therapeutic options are available for the treatment of acute rhabdomyolysis. As a result, acute and refractory cases remain difficult to manage. We report a case of alcohol-induced rhabdomyolysis that responded dramatically to high-dose corticosteroids. A 55-year-old man presented to the emergency department for evaluation of diffuse muscle pain, weakness, and darkening urine. On admission, his creatine kinase (CK) level was 50,022 U/L. Despite aggressive fluid repletion, his CK level continued to increase, peaking at 401,280 U/L with a concomitant increase in muscle pain and urine darkening. On administration of high-dose corticosteroids, clinical symptoms and CK levels improved dramatically, and the patient was discharged 36 hours later with complete resolution of muscle pain and weakness. Given their low toxicity profile, short-term high-dose corticosteroids may be a valid treatment option for recurrent rhabdomyolysis unresponsive to fluid repletion. PMID:21964178
Antoon, James W; Chakraborti, Chayan
Hyperthyroidism can result in several musculoskeletal conditions such as thyrotoxic periodic paralysis, thyrotoxic myopathy, and thyroid ophthalmopathy. Rhabdomyolysis has been rarely reported to be associated with hyperthyroidism. We describe a 33-year-old man who presented with bilateral thigh pain and dark brown urine after regular squatting. He had a past medical history of hyperthyroidism but stopped taking it 2 months prior to admission. He was found to have rhabdomyolysis, myoglobinuria, and thyrotoxicosis. Presence of thyroid-stimulating immunoglobulins (TSI) and high radioiodine uptake confirmed a diagnosis of Graves' disease. He received aggressive fluid resuscitation and sodium bicarbonate intravenously along with monitoring fluid and electrolyte. Methimazole was also resumed. The patient responded to treatment and rhabdomyolysis gradually resolved. Therefore, nonstrenuous exercise can potentially induce rhabdomyolysis in patients with hyperthyroidism. Although hyperthyroidism is not widely recognized as a cause of rhabdomyolysis, it should be considered in the differential diagnosis of rhabdomyolysis.
Hyperthyroidism can result in several musculoskeletal conditions such as thyrotoxic periodic paralysis, thyrotoxic myopathy, and thyroid ophthalmopathy. Rhabdomyolysis has been rarely reported to be associated with hyperthyroidism. We describe a 33-year-old man who presented with bilateral thigh pain and dark brown urine after regular squatting. He had a past medical history of hyperthyroidism but stopped taking it 2 months prior to admission. He was found to have rhabdomyolysis, myoglobinuria, and thyrotoxicosis. Presence of thyroid-stimulating immunoglobulins (TSI) and high radioiodine uptake confirmed a diagnosis of Graves' disease. He received aggressive fluid resuscitation and sodium bicarbonate intravenously along with monitoring fluid and electrolyte. Methimazole was also resumed. The patient responded to treatment and rhabdomyolysis gradually resolved. Therefore, nonstrenuous exercise can potentially induce rhabdomyolysis in patients with hyperthyroidism. Although hyperthyroidism is not widely recognized as a cause of rhabdomyolysis, it should be considered in the differential diagnosis of rhabdomyolysis. PMID:24716006
Summachiwakij, Sarawut; Sachmechi, Issac
Main Outcome Measure Incidence rates of rhabdomyolysis per 10000 person- years of treatment, number needed to treat, and relative risk of rhabdomyolysis. Results In 252460 patients treated with lipid-lowering agents, 24 cases of hospi- talized rhabdomyolysis occurred during treatment. Average incidence per 10000 person- years for monotherapy with atorvastatin, pravastatin, or simvastatin was 0.44 (95% confidence interval (CI), 0.20-0.84); for
David J. Graham; Judy A. Staffa; Deborah Shatin; Susan E. Andrade; Jerry H. Gurwitz; K. Arnold Chan; Michael J. Goodman; Richard Platt
Self-induced water intoxication (SIWI) patients present with various neurological and non-neurological symptoms. However, it is reported that non-neurological manifestations such as rhabdomyolysis are comparatively rare. The mechanism underlying rhabdomyolysis remains controversial. To investigate this further, we evaluated 22 SIWI patients for rhabdomyolysis. We reviewed the records of 22 patients with SIWI and evaluated their clinical characteristics. These patients were divided
Seiji Morita; Sadaki Inokuchi; Rie Yamamoto; Shigeaki Inoue; Kouzo Tamura; Shiro Ohama; Yoshihide Nakagawa; Isotoshi Yamamoto
Rhabdomyolysis is a rare, but possible, complication of combination antiretroviral therapy (cART). We report a unique case of an HIV-positive patient on cART who came to our attention for suspected ischaemic heart disease. Coronary angiography was carried out and complicated in the following days by rhabdomyolysis. We discuss the possible links between rhabdomyolysis, iodinated contrast media and HAART. PMID:24256695
Sbrana, Francesco; Coceani, Michele; Iapoce, Riccardo; Petersen, Christina; Rovai, Daniele
Drug-induced myopathy and rhabdomyolysis are rare adverse drug reactions (ADR). They have been seen after the introduction of modern lipid-lowering drugs more regularly. The first description after medication with clofibrate dates back to 1968. Apparently, all fibrates can induce myopathy. It usually starts after a few days of medication, or after prolonged use, showing muscle weakness and\\/or pain. Concomitantly, the
A 25-year-old man with hepatocellular carcinoma developed severe muscular weakness and pain 15 days after transcatheter arterial\\u000a chemoembolization (TACE). The diagnosis of rhabdomyolysis was made based on myalgia localized in the bilateral upper extremities\\u000a (bilateral trapezius, deltoid, biceps brachii, and teres major muscles) on magnetic resonance imaging and increased levels\\u000a of muscle-derived serum enzymes. In this case, some drugs administered during
Kunishige Matake; Tsuyoshi Tajima; Kengo Yoshimitsu; Hiroyuki Irie; Hitoshi Aibe; Atsushi Sugitani; Hiroshi Honda
Pigment nephropathy accounts for approximately 3% of all cases of acute renal failure (ARF) in children. Studies of risk factors\\u000a associated with ARF and the need for renal replacement therapy (RRT) in children with rhabdomyolysis-associated pigment nephropathy\\u000a consist of retrospective case series with variable inclusion criteria. Our objective was to evaluate clinical and laboratory\\u000a characteristics, etiology, initial fluid therapy, prevalence
Diana Zepeda-Orozco; Bettina H. Ault; Deborah P. Jones
A Thoroughbred-Percheron crossbred gelding developed a fulminant cascade of sequelae following a severe episode of rhabdomyolysis. Complications may occur with rhabdomyolysis of any etiology. In warmblood horses with Percheron bloodlines, rhabdomyolysis may be secondary to polysaccharide storage disease, and aggressive therapy should be undertaken promptly to avoid the complications. PMID:9711389
Sprayberry, K A; Madigan, J; LeCouteur, R A; Valentine, B A
A Thoroughbred-Percheron crossbred gelding developed a fulminant cascade of sequelae following a severe episode of rhabdomyolysis. Complications may occur with rhabdomyolysis of any etiology. In warmblood horses with Percheron bloodlines, rhabdomyolysis may be secondary to polysaccharide storage disease, and aggressive therapy should be undertaken promptly to avoid the complications. Images Figure 1.
Sprayberry, K A; Madigan, J; LeCouteur, R A; Valentine, B A
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
Mendes, Polyana; Robles, Priscila Games; Mathur, Sunita
Importance Rhabdomyolysis is a known, but rare, complication of general anesthesia. To the authors’ knowledge, it has never before been reported following an ocular surgery, and we could find no similar cases in the surgical literature following any brief surgical procedure. We believe this case to be unique in those regards and aim to raise awareness among ophthalmologists of this postoperative complication, as timely intervention can prevent renal failure and death. Observations We report the case of a 58-year-old male who developed rhabdomyolysis following vitrectomy for retinal detachment repair under general anesthesia. The patient had several risk factors for this complication including morbid obesity, type II diabetes mellitus, and American Society of Anesthesia class III risk profile. His postoperative course was notable for significant myalgias in the postoperative recovery area, followed several hours later by oliguria, “root beer” colored urine, and a markedly elevated creatinine kinase level. He was hospitalized for two days for intravenous hydration and monitoring of his renal function and has fully recovered. Relevance As the prevalence of obesity and type II diabetes mellitus increase worldwide, ophthalmologists need to be aware of the signs and symptoms of postoperative rhabdomyolysis. Treatment often requires inpatient hospitalization to prevent the associated morbidity and mortality.
Campbell, John P; Soelberg, Cobin; Lauer, Andreas K
The medical literature contains only a few reports of rhabdomyolysis occurring in patients with dengue fever. We report the case of a 25-year-old Jamaican man who was admitted to a private hospital four days after the onset of an acute febrile illness with fever, myalgia, and generalized weakness. Dengue fever was confirmed with a positive test for the dengue antigen, nonstructural protein 1. He remained well and was discharged on day 6 of his illness. On day 8, he started to pass red urine and was subsequently admitted to the University Hospital of the West Indies. On admission he was found to have myoglobinuria and an elevated creatine phosphokinase (CPK) of 325,600?U/L, leading to a diagnosis of rhabdomyolysis. Dengue IgM was positive. He was treated with aggressive hydration and had close monitoring of his urine output, creatinine, and CPK levels. His hospital course was uneventful without the development of acute renal failure and he was discharged after 14 days in hospital, with a CPK level of 2463?U/L. This case highlights that severe rhabdomyolysis may occur in patients with dengue fever and that early and aggressive treatment may prevent severe complications such as acute renal failure and death.
Sargeant, Tanya; Harris, Tricia; Wilks, Rohan; Barned, Sydney; Galloway-Blake, Karen; Ferguson, Trevor
Background: The combination of bi- carbonate and mannitol (BIC\\/MAN) is commonly used to prevent renal failure (RF) in patients with rhabdomyolysis de- spite the absence of sufficient evidence validating its use. The purpose of this study was to determine whether BIC\\/ MAN is effective in preventing RF in patients with rhabdomyolysis caused by trauma. Methods: This study was a review
Carlos V. R. Brown; Peter Rhee; Linda Chan; Kelly Evans; Demetrios Demetriades; George C. Velmahos
Propofol, a central-acting sedative agent, has been im- plicated in the development of rhabdomyolysis in chil- dren. We describe two adults who developed rhabdo- myolysis after receiving high rates of propofol infusion. Rhabdomyolysis of both skeletal and cardiac muscle was suggested in both patients by marked increases of creatine kinase (>170 000 U\\/L) and cardiac troponin I (11 and 46
Edward B. Stelow; Vandita P. Johari; Stephen A. Smith; John T. Crosson; Fred S. Apple
Rhabdomyolysis associated with fenofibrate monotherapy is extremely rare. Here, we report a rare case of rhabdomyolysis of the psoas muscle in an 82-year-old man with chronic myelogenous leukemia (CML). He was prescribed fenofibrate because of a hypertriglyceridemia. The patient reported generalized muscle pain and right abdominal pain while receiving fenofibrate monotherapy. An abdominal computed tomography scan and an abdominal ultrasound
Kazuya Kato; Astushi Nagase; Minoru Matsuda; Yurina Kato; Kazuhiko Onodera; Takako Kawakami; Mineko Higuchi; Yoshiaki Iwasaki; Masahiko Taniguchi; Hiroyuki Furukawa
We report an interaction between erythromycin and simvastatin resulting in life-threatening rhabdomyolysis in an elderly patient. Drugs that inhibit CYP3A4 enzyme can cause elevated serum levels of statins which amplifies the risk of statin-induced rhabdomyolysis. Physicians should be aware of potential drug interactions of statins, which are widely used in the community. PMID:23589735
Fallah, Alireza; Deep, Maitri; Smallwood, David; Hughes, Peter
There is a growing list of muscle lesions exhibiting concentration of bone-seeking /sup 99m/Tc-labeled phosphate complexes; however, rhabdomyolysis due to cold injury has not been included. We performed a multiradiopharmaceutical study that yielded interesting results on a patient who sustained frostbite injury of the legs that led to rhabdomyolysis and acute renal failure.
Rosenthall, L.; Kloiber, R.; Gagnon, R.; Damtew, B.; Lough, J.
An extended two compartment model is proposed to describe the dynamics of myoglobin in rhabdomyolysis patients undergoing dialysis. Before using clinical data to estimate the model's unknown parameters, structural identifiability analysis was performed to determine the parameters uniqueness given certain clinical observations. A Taylor series expansion method was implemented which found that the model was structurally globally/uniquely identifiable for both on- and off-dialysis phases. The fitted model was then used in a predictive capacity showing that the use of Theralite high cut-off (HCO) or HCO 1100 dialyser gave a significant reduction in myoglobin renal exposure compared to standard haemodialysis (HD). PMID:24008249
Keir, R; Evans, N D; Hutchison, C A; Vigano, M R; Stella, A; Fabbrini, P; Storr, M; Chappell, M J
We present a case of heat stroke (HS) and acute kidney injury (AKI) due to severe rhabdomyolysis in a 14-year-old previously healthy female patient. When she was practicing strenuous exercise she suffered acute seizures and high fever. These symptoms were followed by coma and multiple organ failure (MOF), which included AKI, encephalopathy, fulminant hepatic failure (FHF), and disseminated intravascular coagulation (DIC). The patient was managed in the ICU with renal replacement therapy, ventilatory support, and other vital supporting measures. After three weeks of ICU treatment she made a full recovery.
Trujillo, Maximo H.; Fragachan G., Carlos
Rhabdomyolysis is associated with infectious diseases in approximately 5% of cases and acute kidney injury occurs in 33-50% of cases. Gangrenous myositis is a deep seated infection of the subcutaneous and muscular tissues. We report the case of an 18 year-old man who was admitted to the emergency room with leg pain, fever, nausea, vomiting and oliguria. Physical examination showed moderate dehydration, peripheral cyanosis and skin necrosis with severe myalgia and no subcutaneous gas. Laboratory findings at admission were: serum urea 111 mg/dL, creatinine 1.3 mg/dL, potassium 6.3 mEq/L, creatine kinase (CK) 112,452 IU/L, aspartate amino transaminase (AST) 1116 IU/L, alanine amino transaminase (ALT) 1841 IU/L, pH 7.31, bicarbonate (HCO3) 11 mEq/L and lactate 4.3 mmol/L. Emergency hemodyalisis was started, and antibiotics were given due to high suspicion for bacterial infection. The patient developed respiratory insufficiency and septic shock needing mechanical ventilation and vasoactive drugs. He presented spontaneous gangrenous myositis in both legs and in his left arm. After 26 sessions of hemodialysis, partial recovery of renal function was observed. He was discharged from the ICU after 38 days, still with leg pain. Acute kidney injury due to rhabdomyolysis should be considered as a possible complication of gangrenous myositis. PMID:19260387
Daher, Elizabeth F; Lima, Rafael S A; Silva Júnior, Geraldo B; Almeida, João Paulo C; Siqueira, Francisco Júlio W S; Santos, Silvia Q; Silva, Stephanie W; Libório, Alexandre B
Acute exertional rhabdomyolysis is a syndrome that is being diagnosed with greater frequency by the military physician. It is characterized by muscle pain, weakness, soreness, induration, and myoglobinuria. This occurs after an episode of very vigorous ph...
E. L. Gitin M. A. Demos
This study was conducted to determine, on a prospective basis, the incidence of acute exertional rhabdomyolysis (AER) among recruits at the Marine Corps Recruit Depot, San Diego, California. Blood samples were taken from each of 337 voluteer recruits on e...
J. E. Olerud L. D. Homer H. W. Carroll
Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that statin-induced muscle injury was aggravated by hypothyroidism resulting in her full-blown rhabdomyolysis. Although this patient was successfully treated with continuous venovenous hemofiltration and L-thyroxin replacement, rhabdomyolysis with acute kidney injury is a potentially life-threatening disorder. Physicians must pay special attention to the possible presence of subclinical hypothyroidism when administering statins in patients with hypercholesterolemia.
Ahn, Pyoung; Min, Hyun-Jun; Park, Sang-Hyun; Lee, Byoung-Mu; Choi, Myung-Jin; Yoon, Jong-Woo
Genetic muscular disorders are known risk factors for rhabdomyolysis, which may result in acute kidney injury. Recurrent episodes of acute kidney injury can lead to chronic kidney disease and eventually end-stage renal failure. We describe a patient with chronic kidney disease that developed in the setting of recurrent rhabdomyolysis, resulting in the requirement for renal transplantation. After transplantation, the maintenance of tacrolimus trough concentrations above what is typically prescribed for standard renal transplant recipients appeared to confer protection from further episodes of rhabdomyolysis. This is consistent with previous case series that demonstrated a therapeutic benefit of the calcineurin inhibitor cyclosporine in collagen VI myopathies in the nontransplant population. This case report suggests the potential application of higher tacrolimus targets in patients who have undergone renal transplantation in the setting of recurrent rhabdomyolysis leading to end-stage renal failure. PMID:23429166
Sathyan, Sharad; Baskharoun, Rawya; Perlman, Alan S
A 44-year-old Caucasian woman presented to the emergency room with worsening low back pain and loss of cutaneous sensation over the paraspinal muscles from T10 to S1. The patient had ingested the attention-deficit disorder medication dextroamphetamine before engaging in intense physical exercise with subsequent consumption of 3 alcoholic beverages before developing symptoms. The patient's creatine kinase levels remained elevated for 8 days with constant severe pain under standard treatment for rhabdomyolysis. Despite stabilization of pain and laboratory values at discharge, the patient continues to experience low paraspinal back pain. In patients with risk factors for rhabdomyolysis, the use of dextroamphetamine should be monitored closely. Outside our findings, there is no literature linking dextroamphetamine with rhabdomyolysis at nontoxic concentrations or with use of the supplement caffeine containing weight loss supplement, Hydroxycut. The authors believe that further research into the potential role of dextroamphetamine use in the setting of other risk factors for rhabdomyolysis is warranted. PMID:23276898
Santoro, Jonathan D; Black, Jeanette M; Hamm, L Lee
The most common cause of recurrent rhabdomyolysis in childhood is inherited metabolic disorders. Carnitine palmitoyl transferase II (CPT II) deficiency is a lipidosis and is a common cause of inherited recurrent myoglobinuria. The disease is inherited in autosomal recessive trait, and the clinical phenotype ranges from a severe and multisystemic infantile form to a milder muscle form, which is characterized with rhabdomyolysis and myoglobinuria. Exercise, infection, fasting, and cold are the most important triggering factors of rhabdomyolysis in CPT II deficiency. The severity of attacks is highly variable and some of these attacks may be complicated by acute renal failure. We report a case of a 13-year-old girl with recurrent rhabdomyolysis due to CPT II deficiency whose last attack was complicated by acute renal failure. PMID:24786990
Topçu, Yasemin; Bayram, Erhan; Karao?lu, Pakize; Yi?, Uluç; Bayram, Meral; Kurul, Semra Hiz
In 2011, there were 435 incident episodes of rhabdomyolysis likely due to physical exertion and/or heat stress ("exertional rhabdomyolysis") among U.S. service members. The annual rates of exertional rhabdomyolysis nearly doubled from 2007 to 2011. The highest incidence rates occurred in males, black, non-Hispanics, service members younger than 20 years of age and in the Marine Corps and Army. Most cases were diagnosed at installations that support basic combat/recruit training centers or major Army and Marine Corps combat units. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members -- particularly recruits -- present with muscular pain, swelling, limited range of motion, or the excretion of dark urine possibly due to myoglobinuria after strenuous physical activity, particularly in hot, humid weather. PMID:22452718
ObjectiveTo evaluate the risk factors for the development of acute renal failure (ARF) in severe rhabdomyolysis.DesignObservational historical cohort study.SettingGeneral intensive care unit of a university hospital.PatientsTwenty-six patients with severe rhabdomyolysis, who were admitted between July 1996 and July 2001.Measurements and resultsClinical and laboratory data were reviewed and groups were stratified according to presence or absence of acute renal failure. The
Arthur R. de Meijer; Bernard G. Fikkers; Marinus H. de Keijzer; Baziel G. M. van Engelen; Joost P. H. Drenth
CONTEXT: Lipid-lowering agents are widely prescribed in the United States. Reliable estimates of rhabdomyolysis risk with various lipid-lowering agents are not available.\\u000aOBJECTIVE: To estimate the incidence of rhabdomyolysis in patients treated with different statins and fibrates, alone and in combination, in the ambulatory setting.\\u000aDESIGN, SETTING, AND PATIENTS: Drug-specific inception cohorts of statin and fibrate users were established using
David J. Graham; Judy A. Staffa; Deborah Shatin; Susan E. Andrade; Stephanie D. Schech; Jerry H. Gurwitz; K. Arnold Chan; Michael J. Goodman; Richard Platt
A case of rhabdomyolysis induced by exertional heat stroke in a police officer recruit is reported. Technetium-99m methylene diphosphonate scintigraphy demonstrated marked uptake of the injured skeletal muscle. This bone-scanning agent provided an excellent means of localizing and evaluating the muscle injury of rhabdomyolysis. Nuclear medicine physicians should be aware of the special conditions and causes in which bone scan may demonstrate striking findings. PMID:2083137
Mochizuki, T; Tauxe, W N; Perper, J A
A 14-year-old professional basketball player developed symptoms of influenza which was subsequently confirmed to be caused by influenza A (H3N2). He was given a 5-day course of oseltamivir. Two days after completing the course, he resumed basketball and developed rhabdomyolysis associated with acute renal failure and disseminated intravascular coagulation. This appears to be the first report of exercise-induced rhabdomyolysis associated with influenza A (H3N2). PMID:21262116
Sevketoglu, E; Kural, B; Beskardes, A E; Hatipoglu, S
We present a rare case of para-influenza type 1 virus-induced rhabdomyolysis, complicated by acute renal failure (ARF). The\\u000a child underwent continuous venovenous haemofiltration and has shown full clinical and biochemical recovery. ARF due to rhabdomyolysis\\u000a in para-influenza type 1 infection in a child has, to the best of our knowledge, not been previously reported.
Renata Vrsalovic; Goran Tesovic; Branko Mise
Severe hyperkalaemia is one of the complications of the non-traumatic rhabdomyolysis, which have been related to drug abuse, alcohol, etc. We report on a case of bilateral tibial compartment syndrome, severe hyperkalaemia and rhabdomyolysis after drug abuse. A 35-year-old male intravenous drug user was admitted to the emergency department after being found unconscious in his cell of the prison. Physical
J. Ochoa-Gómez; A. Villar-Arias; Irune Aresti; Pedro Marco-Aguilar
Massive envenomations by honey bees are capable of causing multiorgan dysfunction as a result of the direct toxic effects of the large venom load received. Although all varieties of honey bee have the potential for these attacks, the Africanized honey bee (Apis mellifera scutellata) is the most commonly implicated subspecies. In the United States, the Africanized strain is found primarily in the southwestern states and is known for its highly defensive behavior if disturbed. Mechanisms behind the multiorgan dysfunction produced by these mass envenomations are not clearly understood. We present a case of a 13-year-old male who was stung by approximately 700 honey bees and developed progressive upper-body swelling and systemic manifestations of mass envenomation including rhabdomyolysis, renal insufficiency, and a transient transaminase elevation. PMID:16396886
Betten, David P; Richardson, William H; Tong, Tri C; Clark, Richard F
Rhabdomyolysis is a known complication of statin therapy and may be triggered by a pharmacokinetic interaction between a statin and a second medication. Fatal statin-induced rhabdomyolysis has an incidence of 0.15 deaths/million prescriptions. We describe 4 cases of severe rhabdomyolysis with the common feature of atorvastatin use and coadministration of fusidic acid. All cases involved long-term therapy with atorvastatin; fusidic acid was introduced for treatment of osteomyelitis or septic arthritis. Three cases occurred in the setting of diabetes mellitus, with 2 in patients with end-stage renal disease, suggesting increased susceptibility to atorvastatin-fusidic acid-induced rhabdomyolysis in these patient populations. Of the 4 patients in this series, 3 died. Fusidic acid is a unique bacteriostatic antimicrobial agent with principal antistaphylococcal activity. There have been isolated reports of rhabdomyolysis attributed to the interaction of statins and fusidic acid, the cause of which is unclear. Fusidic acid does not inhibit the cytochrome P450 3A4 isoenzyme responsible for atorvastatin metabolism; increased atorvastatin levels due to inhibition of the glucuronidation pathway may be responsible. Considering the low frequency of fusidic acid use, the appearance of 4 such cases within a short time and in a small population suggests the probability that development of this potentially fatal complication may be relatively high. PMID:20888103
Magee, Ciara N; Medani, Samar A; Leavey, Sean F; Conlon, Peter J; Clarkson, Michael R
Rhabdomyolysis associated with fenofibrate monotherapy is extremely rare. Here, we report a rare case of rhabdomyolysis of the psoas muscle in an 82-year-old man with chronic myelogenous leukemia (CML). He was prescribed fenofibrate because of a hypertriglyceridemia. The patient reported generalized muscle pain and right abdominal pain while receiving fenofibrate monotherapy. An abdominal computed tomography scan and an abdominal ultrasound showed a large and low attenuation and high echogenicity, respectively, in the right middle abdominal area. Laboratory values included a serum creatine concentration of 4.1 mg/dl and a creatinine phosphokinase concentration of 5,882 IU/l. During laparotomy, a large hematoma and necrotic mass was identified in the right psoas muscle. Histological examination revealed that the resected specimens were of the psoas muscle with irregular fiber sizes, degenerating fibers surrounding the inflammatory reaction, and fiber necrosis that is typical for polymyositis. Based on these findings and the clinical history, a diagnosis of fenofibrate-induced rhabdomyolysis was made. To the best of our knowledge, no patient has ever been diagnosed with fulminant psoas rhabdomyolysis due to a fenofibrate monotherapy. This report details the rare case of rhabdomyolysis in a patient with CML associated with fenofibrate monotherapy and offers a review of the literature. PMID:21960954
Kato, Kazuya; Nagase, Astushi; Matsuda, Minoru; Kato, Yurina; Onodera, Kazuhiko; Kawakami, Takako; Higuchi, Mineko; Iwasaki, Yoshiaki; Taniguchi, Masahiko; Furukawa, Hiroyuki
Among active component U.S. service members in 2013, there were 378 incident episodes of rhabdomyolysis likely due to physical exertion or heat stress (exertional rhabdomyolysis). The annual incidence rates of exertional rhabdomyolysis increased 33 percent during 2009-2013. In 2013, the highest incidence rates occurred in service members who were male; younger than 20 years of age; either Asian/Pacific Islander or black, non-Hispanic; members of the Marine Corps and Army; recruit trainees; and in combat-specific occupations. Incidence rates were higher among service members with homes of record from the Northeast compared to other regions of the United States. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain and swelling, limited range of motion, or the excretion of dark urine (e.g., myoglobinuria) after strenuous physical activity, particularly in hot, humid weather. PMID:24684616
Renal histology results are very scarce in dengue-associated rhabdomyolysis patients developing acute kidney injury (AKI). We report a case of dengue fever-induced AKI associated to rhabdomyolysis with a renal biopsy showing acute tubular necrosis (ATN) and renal deposition of myoglobin. A 28-year-old patient who presented dengue fever (DF) complicated by severe AKI and rhabdomyolysis is described. The patient required hemodialysis for three weeks. A renal biopsy revealed ATN with positive staining for myoglobin in the renal tubuli. The patient was discharged with recovered renal function. In conclusion, this case report described a biopsy proven ATN associated to DF-induced rhabdomyolysis, in which renal deposition of myoglobin was demonstrated. We suggest that serum creatine phosphokinase should be monitored in DF patients to allow for an early diagnosis of rhabdomyolysis and the institution of renal protective measures.
Repizo, Liliany P.; Malheiros, Denise M.; Yu, Luis; Barros, Rui T.; Burdmann, Emmanuel A.
Renal histology results are very scarce in dengue-associated rhabdomyolysis patients developing acute kidney injury (AKI). We report a case of dengue fever-induced AKI associated to rhabdomyolysis with a renal biopsy showing acute tubular necrosis (ATN) and renal deposition of myoglobin. A 28-year-old patient who presented dengue fever (DF) complicated by severe AKI and rhabdomyolysis is described. The patient required hemodialysis for three weeks. A renal biopsy revealed ATN with positive staining for myoglobin in the renal tubuli. The patient was discharged with recovered renal function. In conclusion, this case report described a biopsy proven ATN associated to DF-induced rhabdomyolysis, in which renal deposition of myoglobin was demonstrated. We suggest that serum creatine phosphokinase should be monitored in DF patients to allow for an early diagnosis of rhabdomyolysis and the institution of renal protective measures. PMID:24553615
Repizo, Liliany P; Malheiros, Denise M; Yu, Luis; Barros, Rui T; Burdmann, Emmanuel A
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.
Boutaud, Olivier; Roberts, L. Jackson
Introduction. Acute renal failure (ARF) develops in 33% of the patients with rhabdomyolysis. The main etiologic factors are alcoholism, trauma, exercise overexertion, and drugs. In this report we present a rare case of ARF secondary to probably donepezil-induced rhabdomyolysis. Case Presentation. An 84-year-old male patient was admitted to the emergency department with a complaint of generalized weakness and reduced consciousness for two days. He had a history of Alzheimer's disease for one year and he had taken donepezil 5?mg daily for two months. The patient's physical examination revealed apathy, loss of cooperation, and decreased muscle strength. Laboratory studies revealed the following: urea: 128?mg/dL; Creatinine 6.06 mg/dL; creatine kinase: 3613 mg/dL. Donepezil was discontinued and the patient's renal function tests improved gradually. Conclusion. Rhabdomyolysis-induced acute renal failure may develop secondary to donepezil therapy.
Sahin, Osman Zikrullah; Ayaz, Teslime; Yuce, Suleyman; Sumer, Fatih
We report the case of a 33-year-old male with hypothyroidism who developed acute renal impairment with rhabdomyolysis after strenuous physical activity (snow shoveling). His thyroid function test confirmed marked hypothyroidism. Severe elevation of serum CK consistent with rhabdomyolysis was noted and an elevated creatinine indicated acute renal impairment. Patient's condition improved significantly after starting him on thyroid hormone replacement therapy and aggressive hydration. Acute renal impairment with rhabdomyolysis in patients with hypothyroidism is quite rare and we expect that this case report adds to the existing literature on this subject. We also emphasize that thyroid status should be evaluated in patients with unexplained acute renal impairment and presenting with the symptoms of muscle involvement. PMID:24822067
Naz, Arshi; Issa, Mayada
We report the case of a 33-year-old male with hypothyroidism who developed acute renal impairment with rhabdomyolysis after strenuous physical activity (snow shoveling). His thyroid function test confirmed marked hypothyroidism. Severe elevation of serum CK consistent with rhabdomyolysis was noted and an elevated creatinine indicated acute renal impairment. Patient's condition improved significantly after starting him on thyroid hormone replacement therapy and aggressive hydration. Acute renal impairment with rhabdomyolysis in patients with hypothyroidism is quite rare and we expect that this case report adds to the existing literature on this subject. We also emphasize that thyroid status should be evaluated in patients with unexplained acute renal impairment and presenting with the symptoms of muscle involvement.
Introduction. Acute renal failure (ARF) develops in 33% of the patients with rhabdomyolysis. The main etiologic factors are alcoholism, trauma, exercise overexertion, and drugs. In this report we present a rare case of ARF secondary to probably donepezil-induced rhabdomyolysis. Case Presentation. An 84-year-old male patient was admitted to the emergency department with a complaint of generalized weakness and reduced consciousness for two days. He had a history of Alzheimer's disease for one year and he had taken donepezil 5?mg daily for two months. The patient's physical examination revealed apathy, loss of cooperation, and decreased muscle strength. Laboratory studies revealed the following: urea: 128?mg/dL; Creatinine 6.06 mg/dL; creatine kinase: 3613 mg/dL. Donepezil was discontinued and the patient's renal function tests improved gradually. Conclusion. Rhabdomyolysis-induced acute renal failure may develop secondary to donepezil therapy. PMID:24864216
Sahin, Osman Zikrullah; Ayaz, Teslime; Yuce, Suleyman; Sumer, Fatih; Sahin, Serap Baydur
Rhabdomyolysis (RM) is a potentially fatal or disabling clinical syndrome resulting in muscle necrosis and leakage of muscle constituents into the blood. Lactic acidosis and more serious complications such as acute renal failure may occur in up to half of recognized cases, so accurate diagnosis is required. We present three cases in which RM occurred in patients undergoing neurosurgical procedures performed in the lateral position. A review of the literature is provided together with a framework for the prevention of this surgical complication. Three patients underwent neurosurgical procedures in the lateral position for left facial/glossopharyngeal neuralgia, for jugular foramen tumor, and for a petroclival meningioma, respectively. All patients were obese and all three showed massive postoperative elevation in creatine kinase (CK) levels characteristic of RM. Myoglobinuria was identified in two patients and all three showed hyperintensity of the hip gird muscles in the short tau inversion recovery sequence magnetic resonance imaging. All recovered spontaneously and none went on to develop renal failure. A literature review showed that RM has been rarely reported after neurosurgery. However, the duration of procedures of the cases of reported RM indicates that the prevalence of the condition is likely highly under-recognized in neurosurgery. This is particularly important given the rising obesity rates seen in many countries. Obese patients undergoing long neurosurgical procedures, particularly in the lateral position, should be suspected of RM and should be closely monitored for CK levels, myoglobinuria, and acidosis. We outline a framework of strategies for the prevention of the condition. PMID:22940824
De Tommasi, Claudio; Cusimano, Michael D
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.
Shah, S V; Reddy, K
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.
Patel, R.; Mishkin, F.S.
The aim of the work was to study the possibility of development, clinical picture and outcome of rhabdomyolysis (R) caused by physical activity in young conscript personnel. It included 141 men aged 18-25 years. Group I was comprised of 48 patients treated in a military hospital, group 2 consisted of 98 healthy conscripts examined before and 12 days after regular physical exercises. General clinical examination was supplemented by measuring blood CPK. LDH, AST, ALT, and myoglobin levels. Erroneous diagnosis was made in 32 cases of group 1.37 (77.08%) subjects fell ill within the first month of service, the main symptoms being myalgia, muscular tissue compaction, and brown urine. Renal dysfunction occurred in 31 (61.58%) patients. Acute renal insufficiency with oligo/anuria developed in 9 (18.75%) patients and was treated by hemodialysis. All patients had elevated CPK, LDH, AST, ALT levels. CPK increased to 98050.0 +/- 12245. 1 U/l vs 300.4 +/- 57.3 U/l in control. All patients recovered In group 2 there were no cases of R but 29 (31.2%) subjects suffered myalgia and 84 (90.32%) had elevated CPC levels (up to 759 +/- 172.6 U/l on the average). Physical activity in servicemen may cause R with the highest risk of its development during the first month after conscription, i.e. in the period of adaptation. This finding should be taken into account in the organization of medical control of the subscripts' health. PMID:23789455
Zharski?, S L; Slobodianiuk, O N; Slobodianiuk, S N
A previously fit and healthy 8-year-old boy died following severe complications of influenza A. He developed lethargy and vomiting before presentation. On presentation to medical attention, on day 4 of his illness, he was in extremis and had extensive myositis, rhabdomyolysis, renal failure and compartment syndrome, which were resistant to supportive medical management.
Skellett, Sophie Clare; Dhesi, Rosepal
A previously asymptomatic 30 year old man presented with rhabdomyolysis, muscle weakness, and acute encephalopathy after strenuous exertion in the cold without adequate food intake. Serum and muscle carnitine concentrations were decreased. Urinary excretion of carnitine and glycine esters and biochemical examination of skeletal muscle and fibroblasts led to the diagnosis of medium chain acyl-CoA dehydrogenase (MCAD) deficiency. A point
W. Ruitenbeek; P. J. E. Poels; D. M. Turnbull; B. Garavaglia; R. A. Chalmers; R W Taylor; F. J. M. Gabreëls
Introduction Leuprolide acetate is a synthetic analog of gonadotropin-releasing hormone used for the treatment of prostate cancer. Its side effects are hot flashes, nausea, and fatigue. We report a case of a patient with proximal inflammatory myopathy accompanied by severe rhabdomyolysis and renal failure following the second application of leuprolide acetate. Drug withdrawal and steroid therapy resulted in remission within six weeks of the diagnosis. To the best of our knowledge, our case report describes the second case of leuprolide acetate-induced inflammatory myopathy and the first case of severe leuprolide acetate-induced rhabdomyolysis and renal failure in the literature. Case presentation A 64-year-old Swiss Caucasian man was admitted to the hospital because of progressive proximal muscle weakness, dyspnea, and oliguria. He had been treated twice with leuprolide acetate in monthly doses. We performed a muscle biopsy, which excluded other causes of myopathy. The patient's renal failure and rhabdomyolysis were treated with rehydration and steroid therapy. Conclusion The aim of our case report is to highlight the rare but severe side effects associated with leuprolide acetate therapy used to treat patients with inflammatory myopathy: severe rhabdomyolysis and renal failure.
In 2012, there were 402 incident episodes of rhabdomyolysis likely due to physical exertion and/or heat stress ("exertional rhabdomyolysis") among U.S. service members. The annual rates of exertional rhabdomyolysis increased 30 percent from 2008 to 2012. Th e highest incidence rates occurred in males, black, non-Hispanic service members, service members younger than 20 years of age, members of the Army and Marine Corps, recruit trainees, and those in combat-specific occupations. Incidence rates were higher among service members with homes of record from the Northeast compared to other regions of the U.S. Most cases were diagnosed at installations that support basic combat/recruit training or major Army or Marine Corps ground combat units. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members - particularly recruits - present with muscular pain and swelling, limited range of motion, and/or the excretion of dark urine (e.g., myoglobinuria) after strenuous physical activity, particularly in hot, humid weather. PMID:23550931
Drug induced myopathy has been reported with the use of fibric acid derivatives, hydroxymethyl- glutaryl coenzyme A (HMG - CoA) reductase inhibitors and nicotinic acid. Over the last three decades, hypolipemiants like fibric acid derivatives and statins have been increasingly recognised as causes of rhabdomyolysis and acute renal failure especially during combination therapy and in the presence of underlying renal
M D Kamaliah; L D Sanjay
We report the athletic, the clinical, and the pathological details of a case of fatal rhabdomyolysis during training in a college football player with sickle cell trait (SCT) who collapsed minutes after running 16 successive sprints of 100 yd each. The player, 19 yr old, African American, was apparently healthy when he took the field for the conditioning run. No exertional heat illness was present. After collapsing on-field, the player soon went into coma and developed fulminant rhabdomyolysis, profound lactic acidosis, acute myoglobinuric renal failure, refractory hyperkalemia, and disseminated intravascular coagulation. Despite intensive care in the hospital, he died about 15 h after admission, likely from a hyperkalemic cardiac arrhythmia; the terminal rhythm was pulseless electrical activity. The forensic autopsy confirmed that the cause of death was acute exertional rhabdomyolysis associated with SCT. Counting this case, at least 15 college football players with SCT have died from complications of exertional sickling, as have younger football players and other athletes. In SCT, maximal, sustained exercise evokes four forces that can foster sickling: hypoxemia, acidosis, hyperthermia, and red cell dehydration. The setting, the clinical and laboratory features, and the clinicopathological correlation here suggest that the fulminant rhabdomyolysis and its fatal sequelae were from exertional sickling. These data suggest that screening and simple precautions for SCT may be warranted to prevent tragedies like this and enable all athletes with SCT to thrive in their sports. PMID:20010136
Anzalone, Mary L; Green, Valerie S; Buja, Maximillian; Sanchez, Luis A; Harrykissoon, Rajesh I; Eichner, E Randy
Background Post-operative rhabdomyolysis is a well-known complication, especially after bariatric and orthopaedic surgeries. There are few published reports of rhabdomyolysis following cardiac surgery. Acute kidney injury had been distinguished as a serious complication of cardiac surgery. We report a case of 55-years-old male patient who developed rhabdomyolysis precipitated acute kidney injury after coronary artery bypass graft. Case presentation The patient underwent urgent coronary artery bypass graft surgery, with a long duration of surgery due to technical difficulty during grafting. He developed rhabdomyolysis induced acute kidney injury necessitating hemodialysis. The patient in turn developed heart failure, which along with acute kidney injury lead to prolonged ventilation. There was supervening sepsis with prolonged intensive care unity stay and eventually prolonged hospitalization. The peak creatine kinase level was 39000 IU/mL and peak myoglobin was 40000 ng/ml. Reviewing the patient, surgery was prolonged due to technical difficulties encountered during grafting, leading to rhabdomyolysis induced acute kidney injury. The pre-operative use of statins by the patient could also have contributed to the development of rhabdomyolysis. He developed post-operative right heart failure and sepsis. The patient’s renal function gradually improved over 4 week’s duration. Favorable outcome could be achieved but after prolonged course of renal replacement therapy in the form of hemodialysis. Conclusion Prolonged duration of surgery is a well-recognized risk factor in the development of rhabdomyolysis. Early recognition of rhabdomyolysis induced acute kidney injury is important in reducing the post-operative morbidity and mortality in patients. A protocol based approach could be applied for early recognition and management.
Antiretroviral medications, specifically tenofovir, have been linked to acute tubular necrosis in humans with a suggested mechanism of direct tubular injury. Rhabdomyolysis has rarely been described in patients on highly active antiretroviral therapy (HAART). To the best of our knowledge, severe recurrent rhabdomyolysis-induced acute kidney injury (AKI) in a HIV-infected patient on two different triple antiretroviral regimens has not been reported. We present a HIV-positive patient who first developed heme pigment-induced oliguric AKI due to non-traumatic rhabdomyolysis, 5 days after initiation of triple antiretroviral therapy. Renal function normalized 2 months after discontinuation of antiretroviral therapy. Two weeks after reinitiating a different HAART regimen, our patient developed a recurrent episode of severe rhabdomyolysis-induced AKI. Both rhabdomyolysis and AKI resolved after discontinuation of the second antiretroviral regimen. First tenofovir and subsequently abacavir seem to be the likely culprits in our case. We also briefly discuss tenofovir nephrotoxicity followed by a literature review on rhabdomyolysis in HIV-infected patients. PMID:23883141
Spiegel, Louis R; Schrier, Peter B; Shah, Hitesh H
Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder. This paper describes the case of a 39-year-old Sudanese male who presented to the emergency room with fever, jaundice, decreased level of consciousness, and worsening kidney function for 7 days, a high lactate dehydrogenase level (1947), severe thrombocytopenia (platelets 8), and numerous schistocytes in the peripheral blood smear. The patient was admitted with a diagnosis of TTP for plasma exchange. Fourteen days later, his creatinine kinase (CK) level rose to >50,000 IU; rhabdomyolysis was suggested. Continuous venovenous hemodialysis (CVVHD) was started. The patient’s CK level remained high, despite CVVHD, until the 6th day, after which this parameter gradually started to decrease. This report highlights a resistant case of TTP that presented with concomitant severe rhabdomyolysis, which demanded aggressive, continuous intervention.
Qahtani, Saad Al
Carnitine palmitoyltransferase (CPT) makes the fatty acids available through beta-oxidation. Deficiency of CPT causes difficulties of muscle cells to metabolize fatty acid. In affected patients, exercise, fast for a prolonged period, and stress, lead to exhaustion of the store of glucose in the body, and rhabdomyolysis may occur, since muscle can not utilize fatty acid as an alternative energy source. Therefore, anesthetic management of CPT deficiency needs infusion of glucose continuously, avoiding the use of the drugs that cause rhabdomyolysis and suppressing the surgical stress. A 67-year-old man, who had previous history of rhabdmyolysis during the postoperative period, and diagnosed CPT deficiency was scheduled for total gastrectomy. General anesthesia was induced with remifentanil, thiamylal and rocuronium after epidural catheter insertion. During surgery, general anesthesia was maintained with remifentanil, sevoflurane, and blood glucose was monitored frequently, with continuous glucose infusion. No complications occurred during anesthesia and perioperative course was uneventful. PMID:23544345
Nakamura, Sayaka; Sugita, Michiko; Nakahara, Eriko; Yamamoto, Tatsuo
A 70-year-old male patient was admitted complaining of weakness and pain in his arms and lower limbs. His serum creatine kinase and serum creatinine were markedly elevated (36,248 IU/L and 2.8 mg/dL, respectively). He had taken dexketoprofen trometamol because of a common cold, which had developed the previous night. Acute kidney injury caused by dexketoprofen-induced rhabdomyolysis was diagnosed by ruling out other possible causes, such as dermato/polymyositis, myxedema, brucellosis, and hepatitis. Dexketoprofen administration was stopped. As diuresis did not restore spontaneously, the patient was treated with I.V. alkaline solutions and mannitol. Hemodialysis was performed because of anuria and severe metabolic acidosis. The patient's renal function later recovered. In conclusion, dexketoprofen may be a potential risk factor for acute kidney injury and rhabdomyolysis. PMID:21553112
Sav, Tansu; Unal, Aydin; Erden, Abdulsamet; Gunal, Ali Ihsan
This case study reports the clinical details and pathologic mechanisms of a nonfatal case of rhabdomyolysis secondary to heat exhaustion and sickle cell trait (SCT) resulting in acute renal failure. A 19-year-old African American male college football player collapsed after running 5 intervals of 300 m during a preseason conditioning test. After 17 days of treatment, the athlete was released from the hospital to a short-term noncritical care facility for further treatment and dialysis. Scientific literature reports that at least 15 college football players with SCT have died as a result of a sickling crisis after intense physical exertion. This case study presents the clinical importance of prompt medical treatment and sustained low-efficiency dialysis in treating rhabdomyolysis and its sequelae after collapse in an SCT athlete. PMID:22894971
Shelmadine, Brian D; Baltensperger, Austin; Wilson, Ronald L; Bowden, Rodney G
Administration of simvastatin (80 mg/kg, po. evening dose) and gemfibrozil (600 mg/kg, po twice) for 30 days produced significant decrease in the level of reduced glutathione, superoxide dismutase, catalase and increase in the level of lipid peroxidation and various serum parameters (creatine phosphokinase, lactate dehydrogenase, serum glutamate oxaloacetate transaminase, creatinine, urea and blood urea nitrogen). This suggested involvement of oxidative stress in rhabdomyolysis. Increase in the level of reduced glutathione, superoxide dismutase, catalase and decrease in the level of lipid peroxidation and serum parameters after administration of antioxidant CoQ10 (10 mg/kg.ip) proved the protective effect of CoQ10 in rhabdomyolysis. PMID:16235714
Farswan, Mamta; Rathod, S P; Upaganlawar, A B; Semwal, Arvind
A 16-year-old boy presented with acute kidney injury (AKI) which was attributed to chronic heavy cola consumption. Habitual\\u000a heavy cola ingestion might lead to hypokalemic rhabdomyolysis by its glycyrrhizin content. AKI has been described rarely in\\u000a association with this clinical picture. It is important for physicians to keep heavy cola and other soft drink consumption\\u000a in mind as a cause
Belde Kasap; Alper Soylu; Benhur ?irvan Çetin; Seçil A. Çamlar; Mehmet A. Türkmen; Salih Kavukçu
Rhabdomyolysis precipitated by multitherapy is most frequently described during statin treatment, due to impairment of statin clearance by drugs sharing cytochrome P450 biotransformation pathway. Modulation of membrane transporters for drug efflux, operated by substrates, can also affect drugs' tissue levels. We report rhabdomyolysis in an elderly patient, in multitreatment with different potentially myotoxic medications, taking place seven months after atorvastatin discontinuation. Affected by ischaemic heart disease, arterial hypertension and dementia-related behaviour disturbances, the patient was receiving angiotensin 2-receptor inhibitors, beta-blockers, vasodilators, diuretics, salycilates, allopurinol, proton pump inhibitors, antipsychotics and antidepressants. He had taken atorvastatin for 14 years, with constantly normal creatine-kinase plasma levels. Two months after addition of the antianginal drug ranolazine, creatine-kinase mildly increased and atorvastatin was withdrawn. Nonetheless, creatine-kinase progressively rose, with severe weakness and rhabdomyolysis developing seven months later. Muscle biopsy showed a necrotizing myopathy with no inflammation or autoimmune changes. After ranolazine withdrawal, creatine-kinase and myoglobin returned to normal levels and strength was restored. Several psychotropic and cardiovascular medications prescribed to the patient share either cytochrome P450 biotransformation and permeability-glycoprotein efflux transport. In the event of cardiovascular/neuropsychiatric polypharmacy in geriatric patients, the risk of muscle severe adverse effects from pharmacokinetic drug-drug interaction should be considered beyond the direct myotoxicity of statins. PMID:24252882
Ginanneschi, Federica; Volpi, Nila; Giannini, Fabio; Rocchi, Raffaele; Donati, Donatella; Aglianò, Margherita; Lorenzoni, Paola; Rossi, Alessandro
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.
Ekins, Sean; Diao, Lei; Polli, James E.
Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are associated with myopathy, myalgias, myositis, and rhabdomyolysis. Rhabdoymyolysis is a rare complication and may cause acute renal failure, which may be fatal. In such cases, alternative therapies should be considered. In this review, we attempted to elucidate the lipid management options in patients with rhabdomyolysis and coronary artery disease. We also describe a case report of a patient who developed rhabdomyolysis from dual antilipid therapy followed by acute renal failure and non-ST elevation myocardial infarction. Such a complex case has not been reported in the literature, and lipid management options may include niacin, omega 3-fatty acids, or bile acid sequestrants. Once alternative therapies are initiated, monitoring a patient closely with evaluation for associated adverse events should be performed. PMID:21192242
Kar, Subrata; Chockalingam, Anand
A 10-year-old girl manifested unexplained muscle aches and high creatine phosphokinase (CPK) concentrations attributed to rhabdomyolysis in association with severe hypothyroidism due to autoimmune thyroiditis. The response to therapy strongly suggested that hypothyroidism was the cause of rhabdomyolysis. Hypothyroidism is a rare cause of rhabdomyolysis. It should always be considered in a patient with muscular symptoms and elevated CPK concentrations. In addition, the patient developed other uncommon manifestations of hypothyroidism such as pericardial effusion, acute renal failure, and acquired von Willebrand disease. After thyroxine replacement, the symptoms and abnormal findings disappeared. The patient was also diagnosed as having celiac disease, which is often associated with autoimmune thyroiditis. Conditions accompanying autoimmune thyroid disease may result from altered thyroid function and from the presence of other autoimmune diseases. The butterfly-shaped thyroid gland has a tremendous impact on metabolism, which may be compared to a phenomenon termed the "Butterfly Effect". PMID:18341381
Galli-Tsinopoulou, Assimina; Stylianou, Charilaos; Kokka, Paraskevi; Paraskevi, Kokka; Panagopoulou, Paraskevi; Paraskevi, Panagopoulou; Nousia-Arvanitakis, Sanda
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.
The A to G transition mutation at position 3260 of the mitochondrial genome is usually associated with cardiomyopathy and myopathy. One Japanese kindred reported the phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS syndrome) in association with the A3260G mtDNA mutation. We describe the first Caucasian cases of MELAS syndrome associated with the A3260G mutation. Furthermore, this mutation was associated with exercise-induced rhabdomyolysis, hearing loss, seizures, cardiomyopathy, and autism in the large kindred. We conclude that the A3260G mtDNA mutation is associated with wide phenotypic heterogeneity with MELAS and other "classical" mitochondrial phenotypes being manifestations. PMID:20965148
Connolly, Barbara S; Feigenbaum, Annette S J; Robinson, Brian H; Dipchand, Anne I; Simon, David K; Tarnopolsky, Mark A
A 70–year-old male patient was admitted complaining of weakness and pain in his arms and lower limbs. His serum creatine kinase\\u000a and serum creatinine were markedly elevated (36,248 IU\\/L and 2.8 mg\\/dL, respectively). He had taken dexketoprofen trometamol\\u000a because of a common cold, which had developed the previous night. Acute kidney injury caused by dexketoprofen-induced rhabdomyolysis\\u000a was diagnosed by ruling out other
Tansu Sav; Aydin Unal; Abdulsamet Erden; Ali Ihsan Gunal
This is the first paper to report the association of cancer chemotherapy with rhabdomyolysis in children. A previously healthy, 15-year-old Japanese female was diagnosed as having alveolar rhabdomyosarcoma. She received the first cycle of multi-agent chemotherapy without any adverse effects. However, she developed severe acute rhabdomyolysis shortly after the second cycle of multi-agent chemotherapy, which consisted of etoposide, ifosfamide, actinomycin-D and vincristine. Her condition deteriorated rapidly and she was treated with mechanical ventilation and fluid replacement. After further evaluation, anticancer drugs were thought to be responsible for the rhabdomyolysis. PMID:24019778
Matsuzaki, Hiroshi; Koga, Yuhki; Suminoe, Aiko; Oba, Utako; Takimoto, Tomohito; Hara, Toshiro
This is the first paper to report the association of cancer chemotherapy with rhabdomyolysis in children. A previously healthy, 15-year-old Japanese female was diagnosed as having alveolar rhabdomyosarcoma. She received the first cycle of multi-agent chemotherapy without any adverse effects. However, she developed severe acute rhabdomyolysis shortly after the second cycle of multi-agent chemotherapy, which consisted of etoposide, ifosfamide, actinomycin-D and vincristine. Her condition deteriorated rapidly and she was treated with mechanical ventilation and fluid replacement. After further evaluation, anticancer drugs were thought to be responsible for the rhabdomyolysis.
Matsuzaki, Hiroshi; Koga, Yuhki; Suminoe, Aiko; Oba, Utako; Takimoto, Tomohito; Hara, Toshiro
Background Because neither the incidence and risk factors for rhabdomyolysis in the ICU nor the dynamics of its main complication, i.e., rhabdomyolysis-induced acute kidney injury (AKI) are well known, we retrospectively studied a large population of adult ICU patients (n?=?1,769). Methods CK and sMb (serum myoglobin) and uMb (urinary myoglobin) were studied as markers of rhabdomyolysis and AKI (RIFLE criteria). Hemodialysis and mortality were used as outcome variables. Results Prolonged surgery, trauma, and vascular occlusions are associated with increasing CK values. CK correlates with sMb (p?0.001) and peaks significantly later than sMb or uMb. The logistic regression showed a positive correlation between CK and the development of AKI, with an OR of 2.21. Univariate logistic regression suggests that elevations of sMb and uMb are associated with the development of AKI, with odds ratios of 7.87 and 1.61 respectively. The ROC curve showed that for all three markers a significant correlation with AKI, for sMb with the greatest area under the curve. The best cutoff values for prediction of AKI were CK?>?773 U/l; sMb?>?368 ?g/l and uMb?>?38 ?g/l respectively. Conclusions Because it also has extrarenal elimination kinetics, our data suggest that measuring myoglobin in patients at risk for rhabdomyolysis in the ICU may be useful.
We present 2 cases of fulminant malignant hyperthermia (MH), complicated with massive rhabdomyolysis. The patients were successfully treated in the intensive care unit of our university teaching hospital, despite the lack of availability of dantrolene in our country, by early application of continuous veno-venous hemofiltration (CVVH). Both male patients developed fulminant malignant hyperthermia during anesthesia for oromaxillofacial surgery. CVVH was employed when the values of creatine phosphokinase (CPK), myoglobin (Mb), and lactate dehydrogenase (LDH) increased significantly. After emergency treatment and CVVH therapy, the values of CPK, Mb, and LDH in the blood plasma of the patients decreased significantly. The complications, including acute renal failure, disseminated intravascular coagulation, and acute respiratory distress syndrome were also treated without any obvious organ damage. Early detection and management are the keys to treat MH successfully. CVVH is a valuable therapeutic application in the initial/critical management of severe rhabdomyolysis. If these complications occur even with initial treatment with dantrolene, our experiences may be useful adjunctive treatments to consider. PMID:23506280
Fang, Shudong; Xu, Hui; Zhu, Yesen; Jiang, Hong
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
Vavlukis, M; Eftimov, A; Zafirovska, P; Caparovska, E; Pocesta, B; Kedev, S; Dimovski, A J
A 34-year-old male patient visited the emergency room with complaint of right wrist drop and foot drop. The day before, he was intoxicated and fell asleep in a room containing barbeque briquettes; After waking up, he noticed that his right wrist and foot were dropped. Upon physical examination, his right wrist extensor, thumb extensor, ankle dorsiflexor, and big toe extensor showed Medical Research Council (MRC) grade 1 power. The initial laboratory tests suggested rhabdomyolysis induced by unrelieved pressure on the right side during sleep. Right foot drop was improved after conservative care and elevated muscle enzyme became normalized with hydration therapy with no resultant acute renal failure. However, the wrist drop did not show improvement and a hard mass was palpated on the follow-up physical examination. Ultrasonography and magnetic resonance imaging studies were conducted and an abnormal mass in the lateral head of the tricep was detected. Axonopathy was suggested by the electrodiagnostic examination. A surgical decompression was done and a fibrotic cord lesion compressing the radial nerve was detected. After adhesiolysis, his wrist extensor power improved to MRC grade 4. Herein, we describe a compressive radial neuropathy associated with rhabdomyolysis successfully treated with surgery and provide a brief review of the related literature.
Kim, Ji Yong; Lee, Jang-Woo; Cha, Sung Oh
We present 2 cases of fulminant malignant hyperthermia (MH), complicated with massive rhabdomyolysis. The patients were successfully treated in the intensive care unit of our university teaching hospital, despite the lack of availability of dantrolene in our country, by early application of continuous veno-venous hemofiltration (CVVH). Both male patients developed fulminant malignant hyperthermia during anesthesia for oromaxillofacial surgery. CVVH was employed when the values of creatine phosphokinase (CPK), myoglobin (Mb), and lactate dehydrogenase (LDH) increased significantly. After emergency treatment and CVVH therapy, the values of CPK, Mb, and LDH in the blood plasma of the patients decreased significantly. The complications, including acute renal failure, disseminated intravascular coagulation, and acute respiratory distress syndrome were also treated without any obvious organ damage. Early detection and management are the keys to treat MH successfully. CVVH is a valuable therapeutic application in the initial/critical management of severe rhabdomyolysis. If these complications occur even with initial treatment with dantrolene, our experiences may be useful adjunctive treatments to consider.
Fang, Shudong; Xu, Hui; Zhu, Yesen; Jiang, Hong
Four Quarter Horses (9 months to 7 years of age) with submandibular lymphadenopathy and firm muscles (palpation of which elicited signs of pain) were evaluated; in general, the horses had a stiff gait, and 3 horses became recumbent. Streptococcus equi was cultured from aspirates of lymph nodes or samples of purulent material collected from the auditory tube diverticula. Once the horses were recumbent, their condition deteriorated rapidly despite aggressive antimicrobial and antiinflammatory treatment, necessitating euthanasia within 24 to 48 hours. One horse did not become recumbent and recovered completely. Among the 4 horses, common clinicopathologic findings included neutrophilia, hyperfibrinogenemia, and high serum activities of creatine kinase and aspartate aminotransferase. Necropsies of the 3 euthanatized horses revealed large, pale areas most prominent in the semimembranosus, semitendinosus, sublumbar, and gluteal muscles that were characterized histologically by severe acute myonecrosis and macrophage infiltration of necrotic myofibers. Streptococcus equi was identified in sections of affected muscle by use of immunofluorescent stains for Lancefield group C carbohydrate and S. equi M protein. In the 4 horses of this report, acute severe rhabdomyolysis without clinical evidence of muscle atrophy or infarction was associated with S. equi infection; rhabdomyolysis was attributed to either an inflammatory cascade resembling streptococcal toxic shock or potentially direct toxic effects of S. equi within muscle tissue. PMID:16342530
Sponseller, Beatrice T; Valberg, Stephanie J; Tennent-Brown, Brett S; Foreman, Jonathan H; Kumar, Pawan; Timoney, John F
We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment. PMID:24179353
Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja
Exertional rhabdomyolysis (ER) is a common medical condition encountered by primary care and sports medicine providers. Although the majority of individuals with ER follow an expected and unremarkable clinical course without any adverse long-term sequelae or increased risk for recurrence, in others, the condition can serve as an 'unmasker' of an underlying condition that portends future risk. We present two cases of warfighters with a history of recurrent ER who presented to our facility for further evaluation and a return to duty determination. We describe the definition, pathophysiology, epidemiology, etiology, and clinical course of ER. In addition, we introduce 'high-risk' criteria for ER to assist in identifying individuals needing further testing and work-up. Finally we present a suggested algorithm that details the work-up of these individuals with high-risk ER to help identify underlying conditions that may lead to recurrence. PMID:24614425
Szczepanik, Michelle E; Heled, Yuval; Capacchione, John; Campbell, William; Deuster, Patricia; O'Connor, Francis G
The goal of this study was to integrate systems pharmacology and biochemical flux to delineate drug-induced rhabdomyolysis by leveraging prior knowledge and publicly accessible data. A list of 211 rhabdomyolysis-inducing drugs (RIDs) was compiled and curated from multiple sources. Extended pharmacological network analysis revealed that the intermediators directly interacting with the pharmacological targets of RIDs were significantly enriched with functions such as regulation of cell cycle, apoptosis, and ubiquitin-mediated proteolysis. A total of 78 intermediators were shown to be significantly connected to at least five RIDs, including estrogen receptor 1 (ESR1), synuclein gamma (SNCG), and janus kinase 2 (JAK2). Transcriptomic analysis of RIDs profiled in Connectivity Map on the global scale revealed that multiple pathways are perturbed by RIDs, including ErbB signaling and lipid metabolism pathways, and that carnitine palmitoyl transferase 2 (CPT2) was in the top 1 percent of the most differentially perturbed genes. CPT2 was downregulated by nine drugs that perturbed the genes significantly enriched in oxidative phosphorylation and energy-metabolism pathways. With statins as the use case, biochemical pathway analysis on the local scale implicated a role for CPT2 in statin-induced perturbation of energy homeostasis, which is in agreement with reports of statin-CPT2 interaction. Considering the complexity of human biology, an integrative multiple-approach analysis composed of a biochemical flux network, pharmacological on- and off-target networks, and transcriptomic signature is important for understanding drug safety and for providing insight into clinical gene-drug interactions. PMID:24422454
Hur, Junguk; Liu, Zhichao; Tong, Weida; Laaksonen, Reijo; Bai, Jane P F
Background: Rhabdomyolysis occurs when injury to skeletal muscle disrupts the integrity of the sarcolemmal membrane, allowing\\u000a release of intracellular proteins into the circulation. Serious complications, such as hyperkalemia, hypocalcemia, hyperphosphatemia,\\u000a compartment syndrome, cardiac dysrhythmias, disseminated intravascular coagulation, and acute renal failure can develop if\\u000a diagnosis and treatment are delayed. Methods: A morbidly obese patient is presented who developed this rare
Jason P. Wiltshire; Timothy Custer
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
David Bostanjian; Gary J. Anthone; Nahid Hamoui; Peter F. Crookes
The current dietary treatment of long-chain fatty acid oxidation defects (high carbohydrate with medium-even-chain triglycerides and reduced amounts of long-chain fats) fails, in many cases, to prevent cardiomyopathy, rhabdomyolysis, and muscle weakness. We hypothesized that the apparent defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis). We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function. We fed subjects with long-chain defects a controlled diet in which the fat component was switched from medium-even-chain triglycerides to triheptanoin. In three patients with very-long-chain acyl-CoA dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others. There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders.
Roe, Charles R.; Sweetman, Lawrence; Roe, Diane S.; David, France; Brunengraber, Henri
The current dietary treatment of long-chain fatty acid oxidation defects (high carbohydrate with medium-even-chain triglycerides and reduced amounts of long-chain fats) fails, in many cases, to prevent cardiomyopathy, rhabdomyolysis, and muscle weakness. We hypothesized that the apparent defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis). We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function. We fed subjects with long-chain defects a controlled diet in which the fat component was switched from medium-even-chain triglycerides to triheptanoin. In three patients with very-long-chain acyl-CoA dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others. There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders. PMID:12122118
Roe, Charles R; Sweetman, Lawrence; Roe, Diane S; David, France; Brunengraber, Henri
Objective: To describe a case of exertional rhabdomyolysis in a collegiate American football player after preventive cold-water immersion. Background: A healthy man (19 years old) participated in full-contact football practice followed by conditioning (2.5 hours). After practice, he entered a coach-mandated post-practice cold-water immersion and had no signs of heat illness before developing leg cramps, for which he presented to the athletic training staff. After 10 minutes of repeated stretching, massage, and replacement of electrolyte-filled fluids, he was transported to the emergency room. Laboratory tests indicated a creatine kinase (CK) level of 2545 IU/L (normal range, 45–260 IU/L), CK-myoglobin fraction of 8.5 ng/mL (normal < 6.7 ng/mL), and CK-myoglobin relative index of 30% (normal range, 25%– 30%). Myoglobin was measured at 499 ng/mL (normal = 80 ng/mL). The attending physician treated the athlete with intravenous fluids. Differential Diagnosis: Exercise-associated muscle cramps, dehydration, exertional rhabdomyolysis. Treatment: The patient was treated with rest and rehydration. One week after the incident, he began biking and swimming. Eighteen days later, the patient continued to demonstrate elevated CK levels (527 IU/L) but described no other symptoms and was allowed to return to football practice as tolerated. Two months after the incident, his CK level remained high (1900 IU/L). Uniqueness: The athlete demonstrated no signs of heat illness upon entering the cold-water immersion but experienced severe leg cramping after immersion, resulting in a diagnosis of exertional rhabdomyolysis. Previously described cases have not linked cold-water immersion with the pathogenesis of rhabdomyolysis. Conclusions: In this football player, CK levels appeared to be a poor indicator of rhabdomyolysis. Our patient demonstrated no other signs of the illness weeks after the incident, yet his elevated CK levels persisted. Cold-water immersion immediately after exercise should be monitored by the athletic training staff and may not be appropriate to prevent muscle damage, given the lack of supporting evidence.
Kahanov, Leamor; Eberman, Lindsey E.; Wasik, Mitchell; Alvey, Thurman
Very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency (MIM 201475) is a rare inherited disorder with three forms of clinical presentation: a severe early-onset form; an intermediate form with childhood onset; and an adult-onset form, of mild severity. During adolescence and adulthood, exercise intolerance, myalgia and recurrent episodes of rhabdomyolysis are the main clinical features. The authors present a case of a 13-year old female, with severe myalgia and dark urine after prolonged exercise. Analytical evaluation showed marked elevation plasma creatine kinase and myoglobin. The increased levels of tetradecenoyl carnitine in patient’s dried blood spot suggested a VLCAD deficiency, which was confirmed by molecular study. Family history is remarkable for first grade consanguinity of parents and a 19-year old brother with records of repeated similar episodes after moderate intensity physical efforts which was subsequently also diagnosed with VLCAD deficiency. This is one of the first cases of late-onset of disease diagnosed in Portugal.
Oliveira, Sara Freitas; Pinho, Liliana; Rocha, Hugo; Nogueira, Celia; Vilarinho, Laura; Dinis, Maria Jose; Silva, Conceicao
A 46-year old man with a chronic hepatitis C virus infection received triple therapy with ribavirin, pegylated interferon and telaprevir. The patient also received simvastatin. One month after starting the antiviral therapy, the patient was admitted to the hospital because he developed rhabdomyolysis. At admission simvastatin and all antiviral drugs were discontinued because toxicity due to a drug-drug interaction was suspected. The creatine kinase peaked at 62,246 IU/L and the patient was treated with intravenous normal saline. The patient's renal function remained unaffected. Fourteen days after hospitalization, creatine kinase level had returned to 230 IU/L and the patient was discharged. Telaprevir was considered the probable causative agent of an interaction with simvastatin according to the Drug Interaction Probability Scale. The interaction is due to inhibition of CYP3A4-mediated simvastatin clearance. Simvastatin plasma concentration increased 30 times in this patient and statin induced muscle toxicity is related to the concentration of the statin in blood. In conclusion, with this case we illustrate that telaprevir as well as statins are susceptible to clinical relevant drug-drug interactions. PMID:24927617
Kanter, Clara Tmm de; Luin, Matthijs van; Solas, Caroline; Burger, David M; Vrolijk, Jan Maarten
Recurrent exertional rhabdomyolysis is a heritable disorder that results in painful skeletal muscle cramping with exercise in up to 10% of all Thoroughbred racehorses. Here, we report a genome-wide association study with 48 282 SNPs analyzed among 48 case and 37 control Thoroughbreds. The most significant SNPs spanned approximately 13 Mb on ECA16, and the P-value of the most significant SNP after correcting for population structure was 8.0 × 10(-6) . This region on ECA16 was further evaluated by genotyping 247 SNPs in both the initial population and a second population of 34 case and 98 control Thoroughbreds. Several SNPs across the 13-Mb region on ECA16 showed significance when each population was analyzed separately; however, the exact positions of the most significant SNPs within this region on ECA16 varied between populations. This variability in location may be attributed to lack of power owing to insufficient sample sizes within each population individually, or to the relative distribution of long, conserved haplotypes, characteristic of the Thoroughbred breed. Future genome-wide association studies with additional horses would likely improve the power to resolve casual loci located on ECA16 and increase the likelihood of detecting any additional loci on other chromosomes contributing to disease susceptibility. PMID:22497487
Fritz, K L; McCue, M E; Valberg, S J; Rendahl, A K; Mickelson, J R
Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS). However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA). In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.
Sa, Young Kyoung; Yang, Hyeon; Jung, Hee Kyoung; Son, Jang Won; Lee, Seong Su; Kim, Seong Rae; Cha, Bong Yeon; Son, Ho Young; Pae, Chi-Un
Summary Recurrent exertional rhabdomyolysis is a heritable disorder that results in painful skeletal muscle cramping with exercise in up to 10% of all Thoroughbred racehorses. Here we report a genome-wide association study with 48,282 SNPs analyzed among 48 case and 37 control Thoroughbreds. The most significant SNPs spanned approximately 13 Mb on ECA16, and the p-value of the most significant SNP after correcting for population structure was 8.0 × 10?6. This region on ECA16 was further evaluated by genotyping 247 SNPs in both the initial population and a second population of 34 case and 98 control Thoroughbreds. Several SNPs across the 13 Mb region on ECA16 showed significance when each population was analyzed separately; however, the exact positions of the most significant SNPs within this region on ECA16 varied between populations. This variability in location may be attributed to lack of power due to insufficient sample sizes within each population individually, or to the relative distribution of long conserved haplotypes, which are characteristic of the Thoroughbred breed. Future genome-wide association studies with additional horses would likely improve the power to resolve casual loci located on ECA16 and increase the likelihood of detecting any additional loci on other chromosomes contributing to disease susceptibility.
Fritz, K.L.; McCue, M.E.; Valberg, S.J.; Rendahl, A.K.; Mickelson, J.R.
Exercise-induced rhabdomyolysis related to military training, marathon running, and other forms of strenuous exercise has been reported. The incidence of acute kidney injury appears to be lower in exercise-induced cases. We present 2 cases of exercise-induced rhabdomyolysis following spinning classes, one of which was further complicated by acute compartment syndrome requiring bilateral fasciotomies of the anterior thigh and acute kidney injury. With vigorous hydration and urine pH monitoring, both patients exhibited good mobility, sensation, and renal function on discharge. PMID:24982706
DeFilippis, Ersilia M; Kleiman, David A; Derman, Peter B; DiFelice, Gregory S; Eachempati, Soumitra R
We report an adult case of late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by episodic recurrent rhabdomyolysis and acute renal failure after the age of 46. Muscle biopsy revealed lipid storage myopathy and the finding of serum acylcarnitine and urine organic acid analyses were consistent with MADD. A compound heterozygous mutation was identified in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene, including a novel missense mutation, which confirmed the diagnosis of MADD. After administration of riboflavin and L-carnitine, the muscle weakness and fatigability gradually improved. Acylcarnitine and urine organic acid were also normalized after supplementation. Thus, MADD should be included in one of the differential diagnoses for adult recurrent rhabdomyolysis. Gene analysis is useful to confirm the diagnosis, and early diagnosis is important because riboflavin treatment has been effective in a significant number of patients with MADD. PMID:22041377
Izumi, Rumiko; Suzuki, Naoki; Nagata, Mari; Hasegawa, Takafumi; Abe, Yu; Saito, Yuka; Mochizuki, Hiroshi; Tateyama, Maki; Aoki, Masashi
Objective Genetic variation in drug metabolizing enzymes and membrane transporters as well as concomitant drug therapy can modulate the beneficial and the deleterious effects of drugs. We investigated whether patients exhibiting rhabdomyolysis who were taking cerivastatin possess functional genetic variants in SLCO1B1 and whether they were on concomitant medications that inhibit OATP1B1, resulting in accumulation of cerivastatin. Methods This study had three components: (a) resequencing the SLCO1B1 gene in 122 patients who developed rhabdomyolysis while on cerivastatin; (b) functional evaluation of the identified SLCO1B1 nonsynonymous variants and haplotypes in in-vitro HEK293/FRT cells stably transfected with pcDNA5/FRT empty vector, SLCO1B1 reference, variants, and haplotypes; and (c) in-vitro screening of 15 drugs commonly used among the rhabdomyolysis cases for inhibition of OATP1B1-mediated uptake of cerivastatin in HEK293/FRT cells stably transfected with reference SLCO1B1. Results The resequencing of the SLCO1B1 gene identified 54 variants. In-vitro functional analysis of SLCO1B1 nonsynonymous variants and haplotypes showed that the V174A, R57Q, and P155T variants, a novel frameshift insertion, OATP1B1*14 and OATP1B1*15 haplotype were associated with a significant reduction (P<0.001) in cerivastatin uptake (32, 18, 72, 3.4, 2.1 and 5.7% of reference, respectively). Furthermore, clopidogrel and seven other drugs were shown to inhibit OATP1B1-mediated uptake of cerivastatin. Conclusion Reduced function of OATP1B1 related to genetic variation and drug–drug interactions likely contributed to cerivastatin-induced rhabdomyolysis. Although cerivastatin is no longer in clinical use, these findings may translate to related statins and other substrates of OATP1B1.
Tamraz, Bani; Fukushima, Hisayo; Wolfe, Alan R.; Kaspera, Rudiger; Totah, Rheem A.; Floyd, James S.; Ma, Benjamin; Chu, Catherine; Marciante, Kristin D.; Heckbert, Susan R.; Psaty, Bruce M.; Kroetz, Deanna L.; Kwok, Pui-Yan
Background/Aim: Rhabdomyolysis is associated with the release of myoglobin into the circulation, promoting acute kidney injury (AKI). In severe rhabdomyolysis, dialysis-dependent AKI doubles mortality. Standard blood purification techniques have limited efficacy in removing myoglobin. We describe high cut-off (HCO) renal replacement therapy (RRT) as a novel approach for extracorporeal elimination of myoglobin in rhabdomyolysis-associated AKI. Methods: With an in vivo molecular cut-off at 45 kDa, HCO filters are effective in removing myoglobin (17.8 kDa). Clearances across standard and HCO filters using continuous or intermittent RRT are reviewed in a case series of 11 patients with severe rhabdomyolysis and dialysis-dependent AKI. Results: Median myoglobin clearance across standard high-flux filters was 3.3 (interquartile range 2.3-3.9) ml/min for sustained low-efficiency daily dialysis (SLEDD) batch hemodialysis (HD) and 3.7 (2.9-6.7) ml/min for conventional HD. Respective clearances using HCO filters (membrane surface area: 1.1 m(2)) were 21.7 (20.3-26.1) ml/min (SLEDD) and 44.2 (41.3-47.0) ml/min (HD). Corrected for filter size, up to 20-fold higher clearances were obtained using HCO filters, resulting in profound and sustained reduction of plasma myoglobin concentration. Conclusions: As a novel approach, HCO RRT allows for rapid and effective removal of myoglobin from the circulation. In light of the pathogenic role in AKI, reducing exposure of the kidney to myoglobin may improve renal recovery and patient outcome. Our data pave the way for prospective trials, addressing this issue. PMID:23327834
Heyne, Nils; Guthoff, Martina; Krieger, Julia; Haap, Michael; Häring, Hans-Ulrich
Statin medications diminish cholesterol biosynthesis and are commonly prescribed to reduce cardiovascular disease. Statins also reduce production of ubiquinol, a vital component of mitochondrial energy production; ubiquinol reduction may contribute to rhabdomyolysis. Human rhabdomyosarcoma cells were treated with either ethanol and dimethyl sulfoxide (DMSO) control, or simvastatin at 5 µM or 10 µM, or simvastatin at 5 µM with ubiquinol at 0.5 µM or 1.0 µM for 24 h or 48 h. PGC-1? RNA levels were determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mitochondrial content was determined using flow cytometry and immunocytochemistry. Metabolism was determined by quantification of extracellular acidification rate and oxygen consumption rate. Treatment of human rhabdomyosarcoma cells with simvastatin significantly reduced oxidative, total metabolism, and cellular ATP content in a time- and dose-dependent manner which was rescued by concurrent treatment with ubiquinol. Treatment with simvastatin significantly reduced mitochondrial content as well as cell viability which were both rescued by simultaneous treatment with ubiquinol. This work demonstrates that the addition of ubiquinol to current statin treatment regimens may protect muscle cells from myopathies. PMID:23624330
Vaughan, Roger A; Garcia-Smith, Randi; Bisoffi, Marco; Conn, Carole A; Trujillo, Kristina A
Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important. Cancer Immunol Res; 2(1); 15-18. ©2014 AACR. PMID:24778161
Min, Le; Hodi, F Stephen
A questionnaire was used to determine the incidence of exertional rhabdomyolysis and the factors that might have contributed to its occurrence among 423 polo horses in 11 yards. The yards were selected at random, six of them with 111 horses, in north-eastern USA, and five with 312 horses in south-east England. During the 1999/2000 season the incidence of the condition was 7.3 per cent (9 per cent in the USA and 6.7 per cent in England). The incidence in mares was similar in the two countries, 8.4 per cent in the USA and 8.0 per cent in England, but the incidence in geldings in the USA (10 per cent) was much higher than in England (1.5 per cent). A more excitable than average temperament was reported in 71 per cent of the horses with the condition, and most cases occurred after a game (chukka) in which the horse was perceived to be not fit enough for the level of play demanded. Sixty-four per cent of the cases occurred early in the season and on average each episode resulted in the loss of 7.6 training days. PMID:12019532
McGowan, C M; Posner, R E; Christley, R M
A schizophrenic woman, aged 45, was admitted complaining of high fever, oliguria, blackish urine, muscle swelling and pain. She had been treated for the past 3 years with haloperidol (8 mg), levomepromazine (150 mg), chlorpromazine (75 mg), lithium carbonate (600 mg), bromocriptine mesilate (7.5 mg), etizolam (1 mg), and flunitrazepam (2 mg), Physical examination revealed her to be an obese and uncommunicatable woman with swelling and weakness of the extremities and abdominal distension without borborygmus. Urine was dark brown and (+) for protein and occult blood. Blood chemistry analysis revealed BUN 71 mg/dl, creatinine 6.8 mg/dl, CPK 143,850 IU and myoglobin 3,980 ng/ml. PRA on the 11th hospital day was 96 ng/ml/hour. This patient fulfilled the Levenson's diagnostic criteria for manifestations of neuroleptic malignant syndrome (NMS). High PRA did not decrease after cessation of the diuretics. After treatment with dantrolene sodium and 10 treatments with hemodialysis, azotemia disappeared with the start of diuresis. The PRA also decreased to the normal level. Characteristic acceleration of the central sympathetic stimuli in NMS seemed to have induced hyperreninemia, which together with rhabdomyolysis, might have contributed to the development of acute renal failure. PMID:7815749
Fujisawa, K; Maruyama, Y; Nakamura, K; Nagase, M
Abstract Acute kidney injury (AKI) is a manifestation of rhabdomyolysis (RM). Extracellular myoglobin accumulating in the kidney after RM promotes oxidative damage, which is implicated in AKI. Aim: To test whether selenium (Se) supplementation diminishes AKI and improves renal function. Results: Dietary selenite increased Se in the renal cortex, as demonstrated by X-ray fluorescence microscopy. Experimental RM-stimulated AKI as judged by increased urinary protein/creatinine, clusterin, and kidney injury molecule-1 (KIM-1), decreased creatinine clearance (CCr), increased plasma urea, and damage to renal tubules. Concentrations of cholesterylester (hydro)peroxides and F2-isoprostanes increased in plasma and renal tissues after RM, while aortic and renal cyclic guanidine monophosphate (cGMP; marker of nitric oxide (NO) bioavailability) decreased. Renal superoxide dismutase-1, phospho-P65, TNF? gene, MCP-1 protein, and the 3-chloro-tyrosine/tyrosine ratio (Cl-Tyr/Tyr; marker of neutrophil activation) all increased after RM. Dietary Se significantly decreased renal lipid oxidation, phospho-P65, TNF? gene expression, MCP-1 and Cl-Tyr/Tyr, improved NO bioavailability in aorta but not in the renal microvasculature, and inhibited proteinuria. However, CCr, plasma urea and creatinine, urinary clusterin, and histopathological assessment of AKI remained unchanged. Except for the Se++ group, renal angiotensin-receptor-1/2 gene/protein expression increased after RM with parallel increases in MEK1/2 inhibitor-sensitive MAPkinase (ERK) activity. Innovation: We employed synchrotron radiation to identify Se distribution in kidneys, in addition to assessing reno-protection after RM. Conclusion: Se treatment has some potential as a therapeutic for AKI as it inhibits oxidative damage and inflammation and decreases proteinuria, albeit histopathological changes to the kidney and some plasma and urinary markers of AKI remain unaffected after RM. Antioxid Redox Signal. 18, 756–769.
Shanu, Anu; Groebler, Ludwig; Kim, Hyun Bo; Wood, Sarah; Weekley, Claire M.; Aitken, Jade B.; Harris, Hugh H.
Four sequential Tc-99m pyrophosphate (PYP) imaging studies were performed in a 28-year-old man with high fever and exudate pharyngitis associated with renal failure. Radiotracer localization in the left ventricle (LV), lungs, kidneys, and skeletal muscles were seen in two, initial imaging studies. In the second and third imaging studies, area of increase in activity was seen in the left-sided bowel. In studies done two months later (in the third study), the radioactivity in the skeletal muscles was no longer seen. Studies obtained nine months (in the fourth study) after the first imaging showed less radiotracer localization in the LV, lungs, and kidneys as compared to that seen in the initial study. Myocardial necrosis and microcalcification were proved by LV biopsy. The exact mechanism of extraosseous bone-imaging agent localization is unknown. However, this phenomenon may be related to renal failure, rhabdomyolysis, hypercalcemia, hyperphosphatemia, or elevated parathyroid hormone. The Tc-99m PYP imaging study is useful and sensitive in the detection of extraosseous tissue calcification and monitoring of the disease process. PMID:2544339
Shih, W J; Flueck, J; O'Connor, W; Domstad, P A
Recurrent exertional rhabdomyolysis (RER) is frequently observed in race horses like trotters. Some predisposing genetic factors have been described in epidemiological studies. However, the exact aetiology is still unknown. A calcium homeostasis disruption was suspected in previous experimental studies, and we suggested that a transcriptome analysis of RER muscles would be a possible way to investigate the pathway disorder. The purpose of this study was to compare the gene expression profile of RER vs. control muscles in the French Trotter to determine any metabolic or structural disruption. Total RNA was extracted from the gluteal medius and longissimus lumborum muscles after biopsies in 15 French Trotter horses, including 10 controls and 5 RER horses affected by 'tying-up' with high plasmatic muscular enzyme activities. Gene expression analysis was performed on the muscle biopsies using a 25K oligonucleotide microarray, which consisted of 24,009 mouse and 384 horse probes. Transcriptome analysis revealed 191 genes significantly modulated in RER vs. control muscles (P < 0.05). Many genes involved in fatty acid oxidation (CD36/FAT, SLC25A17), the Krebs cycle (SLC25A11, SLC25A12, MDH2) and the mitochondrial respiratory chain were severely down-regulated (tRNA, MT-ND5, MT-ND6, MT-COX1). According to the down-regulation of RYR1, SLC8A1 and UCP2 and up-regulation of APP and HSPA5, the muscle fibre calcium homeostasis seemed to be greatly affected by an increased cytosolic calcium and a depletion of the sarcoplasmic reticulum calcium. Gene expression analysis suggested an alteration of ATP synthesis, with severe mitochondrial dysfunction that could explain the disruption of cytosolic calcium homeostasis and inhibition of muscular relaxation. PMID:22486498
Barrey, E; Jayr, L; Mucher, E; Gospodnetic, S; Joly, F; Benech, P; Alibert, O; Gidrol, X; Mata, X; Vaiman, A; Guérin, G
Risk factors for pseudoaldosteronism with rhabdomyolysis caused by consumption of drugs containing licorice and differences between incidence of these conditions in Japan and other countries: case report and literature review.
Abstract Background: The pathogenesis of licorice-induced pseudoaldosteronism is thought to involve the inhibition of 11?-hydroxysteroid dehydrogenase type 2 by glycyrrhetinic acid. Some risk factors have been reported, but differences between Japan and other countries have not been reported. Case Presentation: A 79-year-old woman was hospitalized because of pseudoaldosteronism with rhabdomyolysis caused by ingestion of herbal medicines containing licorice. She had been prescribed shakuyakukanzobushito (decocted, 3?g of licorice) and keishikajutsubuto (decocted, 2?g of licorice) for the treatment of lower back pain and had been taking antihypertensive agents for the treatment of essential hypertension. After taking the herbal medicines for 2 weeks, the patient developed weakness of the extremities and pain in both thighs. On admission, she had hypertension, oliguria, an elevated serum creatine kinase level, hypokalemia, alkalemia associated with metabolic alkalosis, low plasma renin activity, and low plasma aldosterone levels. Intravenous and oral potassium supplementation and the administration of spironolactone resulted in the normalization of her condition within approximately 2 weeks. Discussion: An analysis of case reports of pseudoaldosteronism with rhabdomyolysis revealed that in Japan, most cases occurred in elderly women with essential hypertension and were caused by drugs such as herbal medicines. In contrast, in other countries, many cases involved younger men, and the dominant causes were foods containing licorice. The use of herbal medicines is increasing all over the world, and when a patient with risk factors is prescribed an herbal medicine containing licorice, careful follow-up is required. PMID:24620820
Yoshino, Tetsuhiro; Yanagawa, Tatsuo; Watanabe, Kenji
Rhabdomyolysis (RM) caused by severe burn releases extracellular myoglobin (Mb) that accumulates in the kidney. Extracellular Mb is a pro-oxidant. This study tested whether supplementation with tert-butyl-bisphenol (BP) or vitamin E (Vit E, as ?-tocopherol) at 0.12% w/w in the diet inhibits acute renal failure (ARF) in an animal model of RM. After RM-induction in rats, creatinine clearance decreased (p < 0.01), proteinuria increased (p < 0.001) and renal-tubule damage was detected. Accompanying ARF, biomarkers of oxidative stress (lipid oxidation and hemeoxygenase-1 (HO-1) gene and protein activity) increased in the kidney (p < 0.05). Supplemented BP or Vit E decreased lipid oxidation (p < 0.05) and HO-1 gene/activity and restored aortic cyclic guanylyl monophosphate in control animals (p < 0.001), yet ARF was unaffected. Antioxidant supplementation inhibited oxidative stress, yet was unable to ameliorate ARF in this animal model indicating that oxidative stress in kidney and vascular cells may not be causally related to renal dysfunction elicited by RM. PMID:21726176
Kim, Hyun Bo; Shanu, Anu; Wood, Sarah; Parry, Sarah N; Collet, Michael; McMahon, Aisling; Witting, Paul K
Cosupplementation with a synthetic, lipid-soluble polyphenol and vitamin C inhibits oxidative damage and improves vascular function yet does not inhibit acute renal injury in an animal model of rhabdomyolysis.
We investigated whether cosupplementation with synthetic tetra-tert-butyl bisphenol (BP) and vitamin C (Vit C) ameliorated oxidative stress and acute kidney injury (AKI) in an animal model of acute rhabdomyolysis (RM). Rats were divided into groups: Sham and Control (normal chow), and BP (receiving 0.12% w/w BP in the diet; 4 weeks) with or without Vit C (100mg/kg ascorbate in PBS ip at 72, 48, and 24h before RM induction). All animals (except the Sham) were treated with 50% v/v glycerol/PBS (6 mL/kg injected into the hind leg) to induce RM. After 24h, urine, plasma, kidneys, and aortae were harvested. Lipid oxidation (assessed as cholesteryl ester hydroperoxides and hydroxides and F(2)-isoprostanes accumulation) increased in the kidney and plasma and this was coupled with decreased aortic levels of cyclic guanylylmonophosphate (cGMP). In renal tissues, RM stimulated glutathione peroxidase (GPx)-4, superoxide dismutase (SOD)-1/2 and nuclear factor kappa-beta (NF??) gene expression and promoted AKI as judged by formation of tubular casts, damaged epithelia, and increased urinary levels of total protein, kidney-injury molecule-1 (KIM-1), and clusterin. Supplementation with BP±Vit C inhibited the two indices of lipid oxidation, down-regulated GPx-4, SOD1/2, and NF-?? gene responses and restored aortic cGMP, yet renal dysfunction and altered kidney morphology persisted. By contrast, supplementation with Vit C alone inhibited oxidative stress and diminished cast formation and proteinuria, while other plasma and urinary markers of AKI remained elevated. These data indicate that lipid- and water-soluble antioxidants may differ in terms of their therapeutic impact on RM-induced renal dysfunction. PMID:22343418
Groebler, Ludwig K; Wang, Xiao Suo; Kim, Hyun Bo; Shanu, Anu; Hossain, Farjaneh; McMahon, Aisling C; Witting, Paul K
In eight young men undergoing heavy repetitive exertion a syndrome of severe myalgia, myoglobinuria, elevated muscle-cell enzymes, and impaired muscle function persisting for weeks or months has been observed. Transient azotemia was present in six of the ...
R. F. Smith
Each year, especially in the United States, young and middle aged men die from a variety of causes during or following intense physical exertion. For unknown reasons, death and disability as a consequence of physical effort are virtually unknown in women, despite the fact that they participate heavily in competitive sports.The most important complications of exhaustive exercise are shown in
James P Knochel
Specimens of blood from 330 Marine recruits at the Marine Corps Recruit Depot, Parris Island, South Carolina, were obtained daily during the first week of their recruit training. Each sample was analyzed for serum myoglobin, CPK, GOT and LDH. It was found...
M. A. Demos E. L. Gitin
Background Hypokalemia induced by diuretic abuse is a life-threatening emergency. Case presentation A 22-years-old female nurse with a body mass index 18 suffered from myalgias, vomiting and diarrhea. Blood tests revealed hypokalemia with a lowest value of 1.1 mmol/l, moderate hyponatremia, metabolic alkalosis, mild renal insufficiency and creatinphosphokinase-elevation. Since hypokalemia and alkalosis were unexplained, she was asked for diuretic-intake. She confessed that she has taken 250 mg furosemide/day for the last 4 months to improve the shape of her muscles. Furosemide tablets were given to her by a physician attending the gym where she exercised. After electrolyte substitution, laboratory abnormalities regressed and no cardiac arrests were observed. Psychiatric investigation diagnosed an adjustment disorder. Conclusion Furosemide abuse has to be considered even in underweight individuals, especially if they have a psychiatric instability or work in health care institutions.
Lightning strikes cause injuries in multiple systems and organs. Early recognition of lightning injury syndromes and anticipation of harmful complications can improve outcomes for these patients. The author has presented a case report of a patient who was struck by lightning and exhibited extensive soft tissue injury with myoglobinuria. He was treated with delayed fasciotomy and had evidence of severe muscle injury with markedly elevated creatine kinase levels that gradually improved with aggressive fluid infusion. The patient did not require alkalinization of urine, mannitol, or dialysis, and his renal function remained normal. PMID:22929530
Navarrete, Norberto; Aldana, Norberto Navarrete
Bone formation and regeneration is a prolonged process that requires a slow drug release system to assist in the long-term recovery. A drug-delivery system is developed that allows for the controlled release of simvastin, without exhibiting the side effects associated with high concentrations of simvastatin, and is still capable of inducing constant bone formation. PMID:23184712
Chou, Joshua; Ito, Tomoko; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce
A 39-year-old man presenting with acute delirium is reported who suffered an unexpected cardiac arrest shortly after being\\u000a sedated. Death followed 2 days later from hypoxic-ischemic encephalopathy. At autopsy, marked pallor and edema of his left\\u000a sternomastoid muscle was observed which was shown on microscopy to be due to confluent coagulative necrosis. Myoglobin casts\\u000a in his renal tubules corresponded to an
Roger W. Byard; Glenda Summersides; Amanda Thompson
A 41-year-old woman presented in the Emergency Department with suspected compartment syndrome of lower left leg (creatine kinase [CK]: 12,502 IU/L, Cr: 4.31 mg/dL). Fasciotomy of the four limb compartments was conducted. By day 2, the patient presented oliguria during previous 24 h, so daily intermittent dialysis was carried out. On day 12, the patient presented an episode of bacteremia due to Staphylococcus hominis. Treatment with vancomycin was initiated and was changed after 4 days to daptomycin due to unsatisfactory clinical progression (6 mg/kg every 48 h, according to renal function and patient's weight) (CK: 2,972 IU/L). After 15 days of treatment, the dose of daptomycin was increased to 6 mg/kg every 24 h (CrCL: 46 mL/min, CK: 83 IU/L). The antibiotic was continued for another 4 days. Fourteen days later, the patient was discharged (CK: 26 IU/L). Daptomycin could be prescribed in some patients with elevated CK values. A cut-off value of baseline CK for use of daptomycin needs to be determined.
Ferrandez, Olivia; Urbina, Olatz; Luque, Sonia; Espona, Merce; Berenguer, Nuria; Grau, Santiago
A 41-year-old woman presented in the Emergency Department with suspected compartment syndrome of lower left leg (creatine kinase [CK]: 12,502 IU/L, Cr: 4.31 mg/dL). Fasciotomy of the four limb compartments was conducted. By day 2, the patient presented oliguria during previous 24 h, so daily intermittent dialysis was carried out. On day 12, the patient presented an episode of bacteremia due to Staphylococcus hominis. Treatment with vancomycin was initiated and was changed after 4 days to daptomycin due to unsatisfactory clinical progression (6 mg/kg every 48 h, according to renal function and patient's weight) (CK: 2,972 IU/L). After 15 days of treatment, the dose of daptomycin was increased to 6 mg/kg every 24 h (CrCL: 46 mL/min, CK: 83 IU/L). The antibiotic was continued for another 4 days. Fourteen days later, the patient was discharged (CK: 26 IU/L). Daptomycin could be prescribed in some patients with elevated CK values. A cut-off value of baseline CK for use of daptomycin needs to be determined. PMID:23716901
Ferrández, Olivia; Urbina, Olatz; Luque, Sònia; Espona, Mercè; Berenguer, Nuria; Grau, Santiago
A new case of phosphoglycerate kinase (PGK) deficiency is described. The propositus displayed episodes of rhabdo- myolysis crises and acute renal failure but did not exhibit any sign of hemolysis. A severe deficiency in phospho- glycerate kinase was revealed in muscle and was also found in erythrocytes, white cells and platelets. A partial defect in the same enzyme was present
Raymonde Rosa; Claude George; Michel Fardeau; Marie-Claude Calvin; Maurice Rapin; Jean Rosa
Sirs: We report about a 47-year-old male who acutely developed muscle weakness of the lower extremities accompanied by a tingling paraesthesia. By the next day the weakness had progressed and involved the thoracolumbar spine, the posterior neck, left shoulder and the finger flexors of the left hand. The patient had been feeling well until 5 days prior to admission, when
Christian Templin; Mechthild Westhoff-Bleck; Jelena-Rima Ghadri
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
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
Sepsis sometimes occurs in traumatic rhabdomyolysis; however, the possibility that injection of endotoxin from Gram-negative bacteria may affect the severity of renal injury during rhabdomyolysis has not been directly examined. The aims of this study were: (i) to examine whether injection of glycerol, which causes rhabdomyolysis, simultaneously with a low dose of endotoxin will result in acute renal failure (ARF)
Y. Zurovsky; I. Zadok
Four sequential Tc-99m pyrophosphate (PYP) imaging studies were performed in a 28-year-old man with high fever and exudate pharyngitis associated with renal failure. Radiotracer localization in the left ventricle (LV), lungs, kidneys, and skeletal muscles were seen in two, initial imaging studies. In the second and third imaging studies, area of increase in activity was seen in the left-sided bowel.
WEI-JEN SHIH; JAMES FLUECK; W. OConnor; PEGGY A. DOMSTAD
Bezafibrate therapy has been shown to improve beta-oxidation of fatty acids and to reduce episodes of rhabdomyolysis in patients with carnitine palmitoyltransferase type-2 (CPT2) deficiency. We report the efficacy of fenofibrate in a patient with CPT2 deficiency, in whom beta-oxidation was improved but an episode of rhabdomyolysis nevertheless occurred. This suggests additional methods to avoid rhabdomyolysis in patients with CPT2 deficiency should accompany fibrate therapy, including avoidance of muscular overexertion, dehydration, and heat exposure.
Hamilton-Craig, I.; Yudi, M.; Johnson, L.; Jayasinghe, R.
We report a case of myoglobinuria secondary to prolonged seizures. The child showed ''hot kidneys'' with bone scintigraphy. The disease entity and etiologies of nontraumatic rhabdomyolysis are discussed.
Sheth, K.J.; Sty, J.R.; Johnson, F.; Tisdale, P.
Heme protein-induced tubular cytoresistance: Expression at the plasma membrane level. Following experimental rhabdomyolysis, animals become resistant to heme protein-induced acute renal failure (ARF). The goals of this study were to: (a) ascertain whether this resistance, previously documented only in vivo, is expressed directly at the proximal tubular cell level; (b) determine whether heme proteinuria (vs. other consequences of rhabdomyolysis) is
Richard A Zager
Rhabdomyolysis or crush syndrome is a pathology caused by muscle injury resulting in acute renal failure. The latest data give strong evidence that this syndrome caused by accumulation of muscle breakdown products in the blood stream is associated with oxidative stress with primary role of mitochondria. In order to evaluate the significance of oxidative stress under rhabdomyolysis we explored the
Egor Y. Plotnikov; Anastasia A. Chupyrkina; Irina B. Pevzner; Nickolaj K. Isaev; Dmitry B. Zorov
Rhabdomyolysis is a syndrome characterized by muscle injury, most frequently due to muscle crushing and trauma. However, it may also be induced by non-traumatic causes, for example by means of stinging by Africanized bees. We describe two cases of rhabdomyolysis that presented dialytic acute renal failure after several bee stings. PMID:19448945
Daher, Elizabeth De Francesco; Oliveira, Rodrigo Alves de; Silva, Leila Silveira Vieira da; Silva, Emanuel Maurício Bezerra E; Morais, Talita Peixoto de
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.
Tolesani Junior, Oswaldo; Roderjan, Christian Nejm; do Carmo Neto, Edgard; Ponte, Micheli Mikaeli; Seabra, Mariana Cristina Pelli; Knibel, Marcos Freitas
Salmonella infection can cause an asymptomatic intestinal carrier state or clinical diseases such as enterocolitis presenting abdominal pain, fever, vomiting, or diarrhea. Salmonella usually invades Peyer's patch of terminal ileum or ascending colon. Sepsis is not common and acute renal failure secondary to rhabdomyolysis is rare. The causes of rhabdomyolysis are trauma, excessive exercise, alcohol, seizure, metabolic abnormality, and infection. Infections account for less than 5% of the reported causes of rhabdomyolysis and resulting acute renal failure. The mechanisms underlying rhabdomyolysis due to infection are direct muscle invasion, toxin production, and nonspecific effects that can occur with infections such as fever, dehydration, acidosis, and electrolyte imbalance. We report a case of sepsis and acute renal failure secondary to rhabdomyolysis associated with Salmonella infection. PMID:19077503
Kim, Chul Han; Suk, Ki Tae; Kim, Jae Woo
... plays an essential role in activating the RYR1 channel to release calcium ions into muscle cells. Although this gene is thought ... malignant hyperthermia? acidosis ; autosomal ; autosomal dominant ; calcium ; cell ; ... pharmacogenetics ; pharmacogenomics ; protein ; rhabdomyolysis ; surgery ; surgical ; ...
Ineffective energy metabolism has been documented as an etiologic factor in exertional rhabdomyolysis. The importance of potassium ion as a cofactor in enzymatic reactions necessary for normal energy metabolism has been well established. Since rhabdomyoly...
J. E. Olerud W. H. Pryor R. L. Eason H. W. Carroll
Exertional and/or environmental heat stroke (ES) and exertional rhabdomyolysis (ER) has been reported in patients with diagnosis of Malignant Hyperthermia (MH). MH is a life-threatening pharmacogenetic disorder caused by mutations in the ryanodine recepto...
J. Capacchione N. Sambuughin R. Bunger S. L. Hamilton S. M. Muldoon
We present acute phosphate nephropathy in a 28-year-old man, which was developed after a car accident due to rhabdomyolysis. Treatment of acute kidney injury was done with administration of sodium bicarbonate. PMID:24878951
Monfared, Ali; Habibzadeh, Seyed Mahmoud; Mesbah, Seyed Alireza
A spectrum of disease from myalgia to rhabdomyolysis exists as classic side-effect of lipid-lowering treatment (LLT). While myopathy has generated considerable interest, mild musculo-skeletal symptoms are poorly assessed.
Sylvia Franc; Sylvie Dejager; Eric Bruckert; Marina Chauvenet; Philippe Giral; Gérard Turpin
Rhabdomyolysis induced by exercise is a very well known entity, several cases has been reported in the literature related with strenuous activities, weight lifting, marathon running, overexertion in an untrained person, knee bends, etc. We reported an interesting case of exercise-induced rhabdomyolysis in a 25 year old Hispanic male, after resuming his regular physical activity, with the highest creatine kinase described in the literature, successfully treated with aggressive hydration only and no complications.
Casares, Pablo; Marull, Jorge
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.
Floyd, James S.; Kaspera, Rudiger; 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.
Background: Carnitine palmitoyltransferase II (CPT II) deficiency is an important cause of recurrent rhabdomyolysis in children and adults. Current treatment includes dietary fat restriction, with increased carbohydrate intake and exercise restriction to avoid muscle pain and rhabdomyolysis. Methods: CPT II enzyme assay, DNA mutation analysis, quantitative analysis of acylcarnitines in blood and cultured fibroblasts, urinary organic acids, the standardized 36-item Short-Form Health Status survey (SF-36) version 2, and bioelectric impedance for body fat composition. Diet treatment with triheptanoin at 30% to 35% of total daily caloric intake was used for all patients. Results: Seven patients with CPT II deficiency were studied from 7 to 61 months on the triheptanoin (anaplerotic) diet. Five had previous episodes of rhabdomyolysis requiring hospitalizations and muscle pain on exertion prior to the diet (two younger patients had not had rhabdomyolysis). While on the diet, only two patients experienced mild muscle pain with exercise. During short periods of noncompliance, two patients experienced rhabdomyolysis with exercise. None experienced rhabdomyolysis or hospitalizations while on the diet. All patients returned to normal physical activities including strenuous sports. Exercise restriction was eliminated. Previously abnormal SF-36 physical composite scores returned to normal levels that persisted for the duration of the therapy in all five symptomatic patients. Conclusions: The triheptanoin diet seems to be an effective therapy for adult-onset carnitine palmitoyltransferase II deficiency. GLOSSARY ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATP = adenosine triphosphate; BHP = ?-hydroxypentanoate; BKP = ?-ketopentanoate; BKP-CoA = ?-ketopentanoyl–coenzyme A; BUN = blood urea nitrogen; CAC = citric acid cycle; CoA = coenzyme A; CPK = creatine phosphokinase; CPT II = carnitine palmitoyltransferase II; LDL = low-density lipoprotein; MCT = medium-chain triglyceride; PCS = physical composite score; SF-36 = 36-item Short-Form Health Status survey.
Roe, C R.; Yang, B-Z; Brunengraber, H; Roe, D S.; Wallace, M; Garritson, B K.
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.
Veerappan, Ilangovan; Abraham, Anila; Hariharan, Somasundaram
After initiation of ibuprofen therapy, a 45-year-old woman developed muscle weakness and tenderness with rhabdomyolysis, culminating in respiratory failure. A muscle biopsy specimen showed a vacuolar myopathy, and markedly decreased muscle carnitine content and carnitine palmitoyltransferase activity. Following recovery, muscle carnitine content was normal but carnitine palmitoyltransferase activity was still abnormally low. The ratio of palmitoyl-coenzyme A plus carnitine to palmitoylcarnitine oxidation by muscle mitochondria isolated from the patient was markedly decreased. The authors conclude that transiently decreased muscle carnitine content interacted with partial deficiency of carnitine palmitoyltransferase-A to produce rhabdomyolysis and respiratory failure and that ibuprofen may have precipitated the clinical event.
Ross, N.S.; Hoppel, C.L.
Hypokalemic paralysis is a medical emergency due to the risks of cardiac arrhythmia, respiratory failure, and rhabdomyolysis. Besides supplementing patients with KCl to hasten recovery, the astute physician must search for the underlying cause to avoid missing a treatable and curable disorder. We report on an elderly Korean man who presented with marked limb paralysis, myalgias, and mild hypertension. He
Chih-Jen Cheng; Yeong-Hwang Chen; Tom Chau; Shih-Hua Lin
A young male survived hyperpyrexia (42.9 degrees C) following MDMA ("Ecstasy") ingestion. He developed convulsions, rhabdomyolysis, metabolic acidosis, and respiratory failure. This was successfully managed by assisted ventilation, aggressive fluid therapy, and the early administration of dantrolene, in addition to cooling measures. This is the first report of a survivor with such a severe hyperpyrexia. Images Figure 1
Mallick, A; Bodenham, A R
We report a case of a patient with carnitine palmityl deficiency in active labour. We discuss the metabolic and energetic implications of obstetrical labour in regard with the mitochondrial myopathy and we propose an optimal management. Neuroaxial analgesia and glucose infusion are indicated in early labour because it is necessary to alleviate stress and pain in order to avoid rhabdomyolysis
J. M Moundras; G Wattrisse; B Leroy; J Decocq; R Krivosic-Horber
Combined use of niacin with a statin is an attractive option, since these types of medication have the best records in clinical trials for reduction in cardiovascular events and improvement in progression\\/regression of coronary lesions. In early use, the niacin–statin combination generated a few case reports documenting severe myopathy and rhabdomyolysis. Subsequent prospective trials in >400 patients, however, have not
John R Guyton; David M Capuzzi
AIM: Many cirrhotic patients have muscular symptoms and rhabdomyolysis. However, myopathy associated with liver cirrhosis has not been established as a disease entity. We evaluated the clinical significance of acute myopathy associated with liver cirrhosis. METHODS: We retrospectively reviewed the medical records of 5 440 cirrhotic patients who had been admit- ted to Gyeongsang National University Hospital from Au- gust
Ok-Jae Lee; Jee-Hyang Yoon; Eun-Jeong Lee; Hyun-Jin Kim; Tae-Hyo Kim
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
Loukianos S. Rallidis; Katerina Fountoulaki; Maria Anastasiou-Nana
BackgroundStatins are widely used drugs to reduce LDL cholesterol and risk for cardiovascular disease. Varying degrees of myopathies occur with statin use, ranging from mild myalgic symptoms alone to documented muscle damage and rhabdomyolysis. The activity of creatine kinase (CK) above a population-based reference range has been used to differentiate myalgias from documented myositic injury due to statins. However, because
Alan H. B. Wu; Andrew Smith; Frank Wians
We describe a case of extreme mixed overdose of calcium channel blockers, ?-blockers and statins. The patient was successfully treated with aggressive resuscitation including cardiac pacing and multiorgan support, glucagon and high-dose insulin for toxicity related to calcium channel blockade and ?-blockade, and ubiquinone for treating severe presumed statin-induced rhabdomyolysis and muscle weakness. PMID:24907219
Thakrar, Reena; Shulman, Rob; Bellingan, Geoff; Singer, Mervyn
Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The…
Kollberg, Gittan; Tulinius, Mar; Melberg, Atle; Darin, Niklas; Andersen, Oluf; Holmgren, Daniel; Oldfors, Anders; Holme, Elisabeth
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.
Balasubramanian, Deepak; Subramanian, Saravanan; Thangaraju, Pugazhenthan; Shanmugam, Kani
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
Balasubramanian, Deepak; Subramanian, Saravanan; Thangaraju, Pugazhenthan; Shanmugam, Kani
Fatal massive peripheral zonal hepatic necrosis developed in a 47-year-old man who accidentally ingested a solution of methyl ethyl ketone peroxide (MEKP) in dimethyl phtalate. Such solutions contain about 10% active oxygen. The clinical course was characterized by temporary cardiac arrest, abdominal burns, severe metabolic acidosis, rapid hepatic failure, rhabdomyolysis and respiratory insufficiency. A fatal outcome resulted 4 d afterwards
P. J. Karhunen; I. Ojanperä; K. Lalu; E. Vuori
In previous studies, inhibition of cholesterol synthesis by HMG CoA reductase inhibitors (HMGRI) was associated with myotoxicity in cultures of neonatal rat skeletal myotubes, and rhabdomyolysis in rats, rabbits, and humansin vivo. In vitromyotoxicity was directly related to HMGRI-induced depletion of mevalonate, farnesol, and geranylgeraniol, since supplementation with these intermediate metabolites abrogated the toxicity. Both farnesol and geranylgeraniol are required
Oliver P. Flint; Barbara A. Masters; Richard E. Gregg; Stephen K. Durham
Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted
A J Ellis; J A Wendon; B Portmann; R Williams
Purpose: We sought to determine whether a case of rhabdomyolysis was a probable adverse reaction associated with pregabalin (Lyrica) and simvastatin (Zocor). Pregabalin is not recognized as a cause of rhabdomyolysis, but statins are known to cause it. Patient Summary: A 70-year-old man with a history of fibromyalgia, type-2 diabetes, hypercholesterolemia, and chronic back pain presented to the emergency department with altered mental status, limb weakness, twitching, and slurred speech. He was taking multiple pain and neuropathic medications and had recently started taking lisinopril (e.g., Zestril) and simvastatin. His pregabalin dose was also increased from 50 mg to 100 mg three times daily. On admission, serum creatinine (SCr) and creatine phosphokinase (CPK) levels were 1.5 mg/dL (normal, 0.7–1.5 mg/dL) and 1,391 units/L (normal, 30–170 units/L), respectively. Metformin (Glucophage) was discontinued, and insulin was started. He was alert and oriented. The review of symptoms was normal except for leg weakness. He had no seizure activity. Simvastatin was discontinued, and the patient was aggressively hydrated. The following day, the SCr level was 1.6 mg/dL and the CPK level was 14,191 units/L. Pregabalin was then discontinued. The rhabdomyolysis resulted from simvastatin and perhaps also pregabalin. The Naranjo Causality Algorithm indicates a probable relationship between rhabdomyolysis and combined therapy. Three days later, the patient had significantly improved, and CPK began to decline. His discharge plan included all prior medications except simvastatin and pregabalin. Conclusion: It is not well known that pregabalin can cause rhabdomyolysis, and there is only one published report on pregabalin-induced hepatotoxicity. When different therapies are combined, the risk of rhabdomyolysis may be increased. The cause of rhabdomyolysis in our patient might be related to decreased renal elimination of both pregabalin and simvastatin (e.g., renal tubular reabsorption). It is important to be aware of this potentially serious and possibly life-threatening reaction especially when medication doses are increased or combined with other agents with similar safety issues.
Kaufman, Michele B.; Choy, Mary
Acute kidney injury (AKI) is a well-documented complication of massive attack by Africanised bees and can be observed 48-72 h after the accident. We report a case of Africanised bees attack followed by severe and lethal AKI. A 56-year-old man was admitted to emergency department after a massive attack of Africanised bees (>1000 bee stings). He was unconscious, presenting with hypotension and tachycardia. Mechanical ventilation, volume expansion and care for anaphylaxis were instituted. The patient was transferred to the intensive care unit (ICU) and after 48 h he developed rhabdomyolysis, oliguria, increased creatinine levels, hyperkalaemia and refractory acidosis. A diagnosis of AKI secondary to rhabdomyolysis and shock was made. The patient was treated with a prolonged course of haemodialysis. However, he progressed to refractory shock and died 5 days after admission. PMID:24618864
Bridi, Ramaiane A; Balbi, Andre Luis; Neves, Precil M; Ponce, Daniela
Two symptomatic patients with heterozygous carnitine palmitoyltransferase II (CPT II) deficiency are reported. Patient 1, a 21-year-old female professional tennis player, suffered from exercise-induced attacks of muscle pain, burning sensations and proximal weakness. Patient 2, a 30-year-old male amateur marathon runner developed muscle cramps and rhabdomyolysis upon extensive exercise and insolation-induced fever. In both patients, the common p.S113L mutation was found in heterozygote state. No second mutation could be found upon sequencing of all the exons of CPT2 gene including exon-intron boundaries. Biochemically, residual CPT activity in muscle homogenate upon inhibition by malonyl-CoA and Triton-X-100 was intermediate between controls and patients with mutations on both alleles. Although CPT II deficiency is an autosomal recessive disorder, the reported patients indicate that heterozygotes might also have typical attacks of myalgia, pareses or rhabdomyolysis. PMID:23184072
Joshi, Pushpa Raj; Deschauer, Marcus; Zierz, Stephan
Cerivastatin was recently withdrawn from the market because of 52 deaths attributed to drug-related rhabdomyolysis that lead to kidney failure. The risk was found to be higher among patients who received the full dose (0.8 mg/day) and those who received gemfibrozil concomitantly. Rhabdomyolysis was 10 times more common with cerivastatin than the other five approved statins. We address three important questions raised by this withdrawal. Should we continue to approve drugs on surrogate efficacy? Are all statins interchangeable? Do the benefits outweigh the risks of statins? We conclude that decisions regarding the use of drugs should be based on direct evidence from long-term clinical outcome trials.
Furberg, Curt D; Pitt, Bertram
We recently observed a 45-year-old patient with a history of psychiatric illness who presented with severe hyperthermia (rectal\\u000a temperature above 41 °C) with intense rhabdomyolysis and liver cytolysis during tetrabenazine therapy for neuroleptic tardive\\u000a dyskinesia. In addition to tetrabenazine, this patient took lorazepam and two antidepressant drugs: clomipramine, a potent\\u000a serotonin-reuptake inhibitor, and mianserin. Hyperthermia responded to parenteral sodium dantrolene
E. Stevens; A. Roman; M. Houa; D. Razavi; N. Jaspar
We present a case of delayed, acute bilateral exertional compartment syndrome of the anterior thigh induced by callisthenic exercise. Symptoms consisted of pain out of proportion to examination findings, inability to ambulate, and severe pain with knee flexion. Treatment consisted of bilateral thigh fasciotomies and supportive therapy for concomitant rhabdomyolysis. Full strength, range of motion, and return to all military duties were achieved by 4 months postinjury. PMID:22934383
McDonald, Lucas S; Mitchell, Ronald J; Deaton, Travis G
Background: Statins (3-hydroxy-3-methylglutaryl co- enzyme A reductase inhibitors) are widely used for the treatment of hypercholesterolemia and coronary heart dis- ease and for the prevention of stroke. There have been various adverse effects, most commonly affecting muscle and ranging from myalgia to rhabdomyolysis. These ad- verse effects may be due to a coenzyme Q10 (CoQ10) de- ficiency because inhibition of
Tatjana Rundek; Ali Naini; Ralph Sacco; Kristen Coates; Salvatore DiMauro
Primary hypothyroidism is a chronic and insidious disease caused by failure of thyroid hormone production. We observed a 38-year-old woman admitted to our hospital due to progressive proximal weakness, muscle pain and fatigue during mild exercise. Laboratory tests showed features of rhabdomyolysis and hypothyroidism. After examination of the thyroid, we reached a diagnosis of Hashimoto’s thyroiditis and hypothyroid myopathy. Hypothyroidism
Maria Mastropasqua; Gaetano Spagna; Valentina Baldini; Ilaria Tedesco; Anna Paggi
We report a case of systemic poisoning with para-phenylenediamine (PPD) presenting with characteristic features of severe angioneurotic edema, rhabdomyolysis and intravascular hemolysis with hemoglobinuria culminating in acute renal failure. Though rare in western countries, such poisoning is not uncommon in East Africa, Indian subcontinent and Middle East countries. We discuss here the clinical features and key management issues of systemic PPD poisoning. PMID:15354985
Anuradha, S; Arora, Sandeep; Mehrotra, S; Arora, A; Kar, P
Hair dye poisoning has been emerging as one of the important causes of intentional self harm in the developing world. Hair dyes contain paraphenylene-diamine and a host of other chemicals that can cause rhabdomyolysis, laryngeal edema, severe metabolic acidosis and acute renal failure. Intervention at the right time has been shown to improve the outcome. In this article, we review the various manifestations, clinical features and treatment modalities for hair dye poisoning.
Sampathkumar, Krishnaswamy; Yesudas, Sooraj
A 77-year-old male patient presented with rhabdomyolysis. He developed progressive respiratory failure and acute respiratory distress syndrome during his hospital stay requiring mechanical ventilation. An electrocardiogram during mechanical ventilation showed findings suggestive of ST elevation myocardial infarction. Closer review showed dome and spike findings that have been likened to a "spiked helmet." This finding has been associated with significant mortality. We discuss this under-recognized finding and the potential contributing mechanisms. PMID:24872654
Agarwal, Ajay; Janz, Timothy G; Garikipati, Naga V
A 64-year-old woman who previously suffered myalgia with lower dose simvastatin was given just one high dose of simvastatin and developed rhabdomyolysis. This was a potentially life-threatening complication. Fortunately she recovered with conservative management and did not require haemofiltration. This case reminds us of the risks of statins and the caution that needs to be exercised when prescribing these medications to patients with a history of intolerances. PMID:23929614
Tayal, Upasana; Carroll, Richard
Background: Statins are associated with muscle complaints ranging from myalgia to rhabdomyolysis. We studied the genetic contribution to the risk of the statin-induced myopathy by comparing frequencies of mutant alleles of candidate genes in case and control groups.Methods: We studied ten Japanese patients with abnormal increase in plasma creatinine kinase or severe muscle complaints, in comparison with control patients (n=26)
K. Morimoto; S. Ueda; N. Seki; Y. Igawa; Y. Kameyama; A. Shimizu; T. Oishi; M. Hosokawa; K. Iesato; S. Mori; Y. Saito; K. Chiba
Many different classes of medications can cause toxic myopathy. One of the most frequently implicated classes is the statins.\\u000a Statin myotoxicity ranges from asymptomatic creatine kinase elevations or myalgias to muscle necrosis and fatal rhabdomyolysis.\\u000a Statins may also cause an autoimmune myopathy requiring immunosuppressive treatment. The mechanisms of statin myotoxicity\\u000a are unclear. If unrecognized in its early manifestations, complications from
Kristofer A. Radcliffe; William W. Campbell
Coffey RJ, Edgar TS, Francisco GE, Graziani V, Meythaler JM, Ridgely PM, Sadiq SA, Turner MS. Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome. 2002;83:735-41. Objective: To suggest guidelines for the prevention, recognition, and management of a life-threatening syndrome (high fever, altered mental status, profound muscular rigidity that sometimes progressed to fatal rhabdomyolysis) in patients
Robert J. Coffey; Terence S. Edgar; Gerard E. Francisco; Virginia Graziani; Jay M. Meythaler; Patrick M. Ridgely; Saud A. Sadiq; Michael S. Turner
Rhabdomyolysis or crush syndrome is a pathology caused by muscle injury resulting in acute renal failure. The latest data give strong evidence that this syndrome caused by accumulation of muscle breakdown products in the blood stream is associated with oxidative stress with primary role of mitochondria. In order to evaluate the significance of oxidative stress under rhabdomyolysis we explored the direct effect of myoglobin on renal tubules and isolated kidney mitochondria while measuring mitochondrial respiratory control, production of reactive oxygen and nitrogen species and lipid peroxidation. In parallel, we evaluated mitochondrial damage under myoglobinurea in vivo. An increase of lipid peroxidation products in kidney mitochondria and release of cytochrome c was detected on the first day of myoglobinuria. In mitochondria incubated with myoglobin we detected respiratory control drop, uncoupling of oxidative phosphorylation, an increase of lipid peroxidation products and stimulated NO synthesis. Mitochondrial pore inhibitor, cyclosporine A, mitochondria-targeted antioxidant (SkQ1) and deferoxamine (Fe-chelator and ferryl-myoglobin reducer) abrogated these events. Similar effects (oxidative stress and mitochondrial dysfunction) were revealed when myoglobin was added to isolated renal tubules. Thus, rhabdomyolysis can be considered as oxidative stress-mediated pathology with mitochondria to be the primary target and possibly the source of reactive oxygen and nitrogen species. We speculate that rhabdomyolysis-induced kidney damage involves direct interaction of myoglobin with mitochondria possibly resulting in iron ions release from myoglobin's heme, which promotes the peroxidation of mitochondrial membranes. Usage of mitochondrial permeability transition blockers, Fe-chelators or mitochondria-targeted antioxidants, may bring salvage from this pathology. PMID:19545623
Plotnikov, Egor Y; Chupyrkina, Anastasia A; Pevzner, Irina B; Isaev, Nickolaj K; Zorov, Dmitry B
Malignant hyperthermia is a hypermetabolic response to inhalation agents (such as halothane, sevoflurane, and desflurane), succinylcholine, vigorous exercise, and heat. Reactions develop more frequently in males than females (2?:?1). The classical signs of malignant hyperthermia are hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity and rhabdomyolysis. In this case report, we present a case of delayed onset malignant hyperthermia-like reaction after the second exposure to sevoflurane.
Turhan, K. Sanem Cakar; Baytas, Volkan; Batislam, Yesim; Ozatamer, Oya
Repeated exposure to electro-muscular incapacitating devices could result in repetitive, sustained muscle contraction, with little or no muscle recovery period. Therefore, rhabdomyolysis and other physiological responses, including acidosis, hyperkalaemia, and altered levels of muscle enzymes in the blood, would be likely to occur. Experiments were performed to investigate effects of repeated exposures of TASER1 International's Advanced TASER1 X26 on muscle
James R. Jauchem; Clifford J. Sherry; David A. Fines; Michael C. Cook
Background\\/Aims: Hepatocyte growth factor (HGF), a multi-potent growth factor, is known to promote regeneration of damaged renal epithelial cells. Glycerol injection into rats induces severe acute renal failure (ARF) with ischemia and tubular necrosis, a model which shares many features with human ARF or rhabdomyolysis. We investigated the efficacy of HGF in this glycerol-induced ARF rat model. Methods: ARF was
Tomokazu Nagano; Ikue Mori-Kudo; Atsushi Tsuchida; Takao Kawamura; Mutsuo Taiji; Hiroshi Noguchi
We report a 29-year-old patient with McArdle's disease and myasthenia gravis. She had been debilitated with McArdle's disease since childhood (with marked rhabdomyolysis) and was obese. Myasthenia gravis was diagnosed at 24 years of age. After 3 months of aerobic exercise training, her exercise capacity increased significantly and she regained the ability to live independently. We conclude that even patients with profound neuromuscular diseases may benefit from carefully prescribed exercise training. PMID:16967472
Lucia, Alejandro; Maté-Muñoz, José L; Pérez, Margarita; Foster, Carl; Gutiérrez-Rivas, Eduardo; Arenas, Joaquín
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (statins) are mainly considered for long-term use and often constitute part of a multiple-drug regime. Besides common adverse drug effects, such as nausea, abdominal discomfort and headaches, all statins harbour the risk of myopathy and fatal rhabdomyolysis. Usually, the frequency of myopathy is low but the incidence increases during concomitant drug therapy. Statins do not
M. Igel; T. Sudhop; K. von Bergmann
Lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl–coenzyme A inhibitors (statins), are widely used in the treatment and prevention of atherosclerotic disease. The benefits of statins are well documented. However, lipid-lowering drugs may cause myopathy, even rhabdomyolysis, the risk of which is increased by certain interactions. Simvastatin, lovastatin, and atorvastatin are metabolized by cytochrome P450 (CYP) 3A4 (simvastatin acid is also metabolized by CYP2C8);
Pertti J. Neuvonen; Mikko Niemi; Janne T. Backman
McArdle's disease (myophosphorylase deficiency), an uncommon autosomal recessive metabolic disorder, is characterized clinically by exercise intolerance beginning in childhood, myalgia, cramps, exercise-induced rhabdomyolysis, "second wind" phenomenon, elevated Creatine Kinase (CK) levels at rest, and previous episodes of raised CK levels following exercise. Several mutations in the PYGM gene and geographic variations have been described. We report three biopsy confirmed cases of McArdle's disease. PMID:22234204
Krishnamoorthy, Naveen; Santosh, Vani; Yasha, T C; Mahadevan, Anita; Shankar, S K; Jethwani, Dilip; Taly, A B; Bhanu, K; Gayathri, N
A 77-year-old male patient presented with rhabdomyolysis. He developed progressive respiratory failure and acute respiratory distress syndrome during his hospital stay requiring mechanical ventilation. An electrocardiogram during mechanical ventilation showed findings suggestive of ST elevation myocardial infarction. Closer review showed dome and spike findings that have been likened to a “spiked helmet.” This finding has been associated with significant mortality. We discuss this under-recognized finding and the potential contributing mechanisms.
Agarwal, Ajay; Janz, Timothy G.; Garikipati, Naga V.
In vitrodata support that extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), members of mitogen-activated protein (MAP) kinases, mediate the signal transduction pathways responsible for the cell proliferation. However,in vivorole of these MAP kinases is poorly understood. Intramuscular injection of 50% glycerol solution induces acute renal failure in rats. This injury is known as a model of rhabdomyolysis in
Shino Ishizuka; Tomohiro Yano; Kiyokazu Hagiwara; Masayoshi Sone; Hiroshi Nihei; Hisashi Ozasa; Saburo Horikawa
Exertional rhabdomyolysis is a complex and poorly understood entity. The inflammatory system has an important role in muscle\\u000a injury and repair. Serum creatine kinase (CK) is often used as systemic biomarker representing muscle damage. Considerable\\u000a variation exists in CK response between different subjects. Genetic elements may act as predisposition factors for exertional\\u000a srhabdomyolysis. Based on their biological activity, we hypothesized
Chen Yamin; José Alberto Ramos Duarte; José Manuel Fernandes Oliveira; Offer Amir; Moran Sagiv; Nir Eynon; Michael Sagiv; Ruthie E. Amir
Objectives. – To appreciate the severity of a patient with acute limb ischaemia, to know how to manage these patients during the perioperative period.Data sources. – References were obtained from Pubmed data bank (http:\\/\\/www.ncbi.nlm.nih.gov\\/entrez\\/query.fcgi) using the following keywords: acute limb, ischaemia, prognosis, complications, rhabdomyolysis, hyperkalaemia, compartment syndrome, fasciotomy.Data synthesis. – Ischaemia of the lower limbs is a medico-surgical emergency. The
V. Piriou; P. Feugier; S. Granger; P. Y. Gueugniaud
Hyperkalemia is an unusual complication in peritoneal dialysis patients, having a prevalence of around 0.8% among the continuous\\u000a ambulatory peritoneal dialysis (CAPD) population. The main cause of hyperkalemia in this group is the release of potassium\\u000a from sources such as gross haematomas and rhabdomyolysis. However, there is no previous report regarding hyperkalemia induced\\u000a by intracellular potassium shift into the intravascular
Carlos G. Musso; Karina Luque; Carlos Schreck; Nora Imperiali; Luis Algarnati
Disorders of mitochondrial fatty acid oxidation are a common cause of exercise-induced rhabdomyolysis and myoglobinuria. We report three adult patients from a family with symptoms of recurrent exercise-induced rhabdomyolysis. This presentation closely resembles adult-type carnitine palmitoyltransferase II deficiency except that these patients had an associated peripheral neuropathy. Investigation of fatty acid oxidation in the patients revealed a deficiency of the mitochondrial trifunctional enzyme of beta-oxidation, a newly described fatty acid oxidation disorder with multiorgan involvement and a usually fatal outcome in early childhood. Our cases therefore represent a new phenotype of the disease, which is characterized by recurrent rhabdomyolysis and peripheral neuropathy, but without involvement of other organs, and which is associated with prolonged survival beyond the fourth decade. A low-fat/high-carbohydrate diet proved beneficial in one of the patients, drastically reducing the frequency of rhabdomyolytic episodes. Our findings suggest that mitochondrial trifunctional enzyme deficiency should be considered in patients with recurrent episodes of myoglobinuria and peripheral neuropathy presenting in later life. PMID:8871579
Schaefer, J; Jackson, S; Dick, D J; Turnbull, D M
Introduction. Acute kidney injury (AKI) necessitating continuous renal replacement therapy (CRRT) is a severe complication in trauma patients (TP). We wanted to assess daily duration of CRRT and its impact on uremic control in TP. Material and Methods. We retrospectively reviewed adult TP, with or without rhabdomyolysis, with AKI undergoing CRRT. Data on daily CRRT duration and causes for temporary stops were collected from the first five CRRT days. Uremic control was assessed by daily changes in serum urea (?urea) and creatinine (?creatinine) concentrations. Results. Thirty-six TP were included with a total of 150 CRRT days, 17 (43%) with rhabdomyolysis. The median (interquartile range (IQR)) time per day with CRRT was 19 (15–21) hours. There was a significant correlation between daily CRRT duration and ?urea (r = 0.60, P?0.001) and ?creatinine (r = 0.43; P = 0.012). CRRT pauses were caused by filter clotting (54%), therapeutic interventions (25%), catheter related problems (10%), filter timeout (6%), and diagnostic procedures (6%). Rhabdomyolysis did not affect the CRRT data. Conclusions. TP undergoing CRRT had short daily CRRT duration causing reduced uremic control. Clinicians should modify their daily clinical practice to improve technical skills and achieve sufficient dialysis dose.
Beitland, Sigrid; Sunde, Kjetil; Moen, Harald; Os, Ingrid
Introduction. Acute kidney injury (AKI) necessitating continuous renal replacement therapy (CRRT) is a severe complication in trauma patients (TP). We wanted to assess daily duration of CRRT and its impact on uremic control in TP. Material and Methods. We retrospectively reviewed adult TP, with or without rhabdomyolysis, with AKI undergoing CRRT. Data on daily CRRT duration and causes for temporary stops were collected from the first five CRRT days. Uremic control was assessed by daily changes in serum urea (?urea) and creatinine (?creatinine) concentrations. Results. Thirty-six TP were included with a total of 150 CRRT days, 17 (43%) with rhabdomyolysis. The median (interquartile range (IQR)) time per day with CRRT was 19 (15-21) hours. There was a significant correlation between daily CRRT duration and ?urea (r = 0.60, P?0.001) and ?creatinine (r = 0.43; P = 0.012). CRRT pauses were caused by filter clotting (54%), therapeutic interventions (25%), catheter related problems (10%), filter timeout (6%), and diagnostic procedures (6%). Rhabdomyolysis did not affect the CRRT data. Conclusions. TP undergoing CRRT had short daily CRRT duration causing reduced uremic control. Clinicians should modify their daily clinical practice to improve technical skills and achieve sufficient dialysis dose. PMID:22666569
Beitland, Sigrid; Sunde, Kjetil; Moen, Harald; Os, Ingrid
Statins are an established class of drugs with proven efficacy in cardiovascular risk reduction. The concern over statin safety was first raised with the revelation of myopathy and rhabdomyolysis with the use of now withdrawn cerivastatin. Enhanced understanding of the mechanisms behind adverse effects of statins including an insight into the pharmacokinetic properties have minimised fear of statin use among clinicians. Studies reveal that occurrence of myopathy and rhabdomyolysis are rare 1/100000 patient-years. The risk of myopathy/rhabdomyolysis varies between statins due to varying pharmacokinetic profiles. This explains the differing abilities of statins to adverse effects and drug interaction potentials that precipitate adverse effects. Higher dose of rosuvastatin (80 mg/day) was associated with proteinuria and hematuria while lower doses were devoid of such effects. Awareness of drugs interacting with statins and knowledge of certain combinations such as statin and fibrates together with monitoring of altered creatine kinase activity may greatly minimise associated adverse effects. Statins also asymptomatically raise levels of hepatic transaminases but are not correlated with hepatotoxicity. Statins are safe and well tolerated including more recent potent statins such as, rosuvastatin. The benefits of intensive statin use in cardiovascular risk reduction greatly outweigh risks. The present review discusses underlying causes of statin-associated adverse effects including management in high risk groups. PMID:23961479
Maji, Debasish; Shaikh, Shehla; Solanki, Dharmesh; Gaurav, Kumar
Background/Aims Coagulopathy is a common complication of snakebite, but there is little information on the clinical importance of coagulopathy. We analyzed the characteristics of coagulopathy after envenomation. Methods Ninety-eight patients who experienced snakebite were enrolled in this study. We divided all the patients into three groups by the ISTH DIC scoring system: the normal, simple coagulopathy and DIC groups. The coagulopathy group included both the simple coagulopathy and DIC groups. We then conducted a case-control study. Results There was a significant decrease in the Hct, protein, albumin, ALP and cholesterol levels in the coagulopathy group, and only the cholesterol level was deceased in the DIC group (p<0.05). Leukocytosis and rhabdomyolysis were significantly associated with coagulopathy, and hemolysis and rhabdomyolysis were associated with DIC (p<0.05). The presence of rhabdomyolysis was considered a risk factor for coagulopathy (p<0.05). These conditions continued for up to six to seven days after the snakebite. Conclusions Evaluation of coagulopathy with using these characteristics is helpful to properly manage the patients who experience snakebite.
Kim, Jae Seok; Yang, Jae Won; Kim, Min Soo; Han, Seung Tae; Kim, Bi Ro; Shin, Myung Sang; Lee, Jong In; Han, Byoung Geun
Since its introduction in 1982, isotretinoin has revolutionized acne treatment, targeting the underlying mechanism of the disease, with effective and long-lasting results. During the first decade of its marketing, several cases of hyperCKemia and rhabdomyolysis were linked to isotretinon therapy. A special concern was given to the possible triggering of muscle toxicity by vigorous exercise. These potential effects discouraged the prescription of isotretinoin to physically active patients or required them to abstain from exercise during treatment. Common musculoskeletal adverse effects of isotretinoin include muscle or joint pains. HyperCKemia is frequently found in patients receiving treatment for rare cases of rhabdomyolysis. Isotretinoin-associated muscle toxicity is usually detected in asymptomatic patients, even though symptoms can appear without hyperCKemia. A possible synergistic effect of isotretinoin and exercise is plausible, although supported by weak evidence and mediated by an unknown mechanism. There are only two reports of myoglobinuria and no reports of decreased renal function in exercising patient under treatment. In conclusion, we believe that current data should not deter physicians from offering isotretinoin to physically active patients nor require them to abstain from exercise. Physicians must explain to patients the possible side effects of treatment, ask them to refrain from an unusual change in their exercise regimen and advise them to avoid other triggers of rhabdomyolysis. Patients should be aware of possible signs of muscle toxicity and inform their doctors about any relevant symptoms. PMID:24716429
Dalal, Adam; Ben-Barak, Shira; Zlotogorski, Abraham; Constantini, Naama
Cerivastatin, a lipid-lowering agent, was voluntarily withdrawn from the market because of high risk of rhabdomyolysis when used as monotherapy and as comedication with fibrates, especially gemfibrozil. Thereafter, investigators found a five-fold increase in the area under the curve (AUC) when cerivastatin was used as comedication with gemfibrozil and theorized that the increase was associated with inhibition of the hepatic uptake and metabolism. By contrast, a number of pharmacoepidemiological investigations--one of which involved evaluation of the Food and Drug Administration (FDA) database for suspected adverse drug reactions and 11 cohort studies of statin and fibrate users in United States showed the risk of rhabdomyolysis to be greater in cerivastatin than in other statins used in either monotherapy or in comedication with fibrates, especially gemfibrozil. This incident regarding risk of rhabdomyolysis in cerivastatin monotherapy was taken to court in the United States and unpublished company (manufacturer of cerivastatin) documents were opened. The incident was then analyzed and discussed in the Journal of American Medical Association (JAMA) as a concern of the current US post-marketing surveillance system. The company's action and timing were judged and found to be inappropriate (although companies of this sort generally have insurmountable conflicts of interest), and the work of the US regulatory system and funding for post-marketing safety management were found to be insufficient. On the basis of the current situation, the authors and editors recommend further improvement of post-marketing regulations including the establishment of an independent drug safety board to oversee post-marketing surveillance. Among the opened, unpublished data, was the finding that cerivastatin obviously induced myopathy in a dose-dependent manner when administrated as monotherapy. As for other statins, only limited data was available for the relationship between the dosage and the rate of myopathy. For the safety use of statins, this should be clarified by proper surveillance system. PMID:16541751
Saito, Mitsuo; Hirata-Koizumi, Mutsuko; Miyake, Shinji; Hasegawa, Ryuichi
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.
Kapoor, Prashant; Greipp, Patricia T.; Schaefer, Eric W.; Mandrekar, Sumithra J.; Kamal, Arif H.; Gonzalez-Paz, Natalia C.; Kumar, Shaji; Greipp, Philip R.
Carnitine-acylcarnitine translocase (CACT) and carnitine palmitoyltransferase II (CPT2) are key enzymes for transporting long-chain fatty acids into mitochondria. Deficiencies of these enzymes, which are clinically characterized by life-threatening non-ketotic hypoglycemia and rhabdomyolysis, cannot be distinguished by acylcarnitine analysis performed using tandem mass spectrometry. We had previously reported the CPT2 genetic structure and its role in CPT2 deficiency. Here, we analyzed the CACT gene in 2 patients diagnosed clinically with CACT deficiency, 18 patients with non-traumatic rhabdomyolysis and 58 healthy individuals, all of whom were confirmed to have normal CPT2 genotypes. To facilitate CACT genotyping, we used heat-denaturing high-performance liquid chromatography (DHPLC), which helped identify five distinct patterns. The abnormal heteroduplex fragments were subjected to CACT-specific DNA sequencing. We found that one patient with CACT deficiency, Case 1, carried c.576G>A and c.199-10t>g mutations, whereas Case 2 was heterozygous for c.106-2a>t and c.576G>A. We also found that one patient with non-traumatic rhabdomyolysis and one healthy individual were heterozygous for c.804delG and the synonymous mutation c.516T>C, respectively. In summary, c.576G>A, c.106-2a>t and c.516T>C are novel CACT gene mutations. Among the five mutations identified, three were responsible for CACT deficiency. We have also demonstrated the successful screening of CACT mutations by DHPLC. PMID:24088670
Fukushima, Takao; Kaneoka, Hidetoshi; Yasuno, Tetsuhiko; Sasaguri, Yukari; Tokuyasu, Tomoko; Tokoro, Kuniko; Fukao, Toshiyuki; Saito, Takao
Wasp stings can result in multi system involvement ranging from intravascular hemolysis, rhabdomyolysis, acute renal failure cardiac involvement, hepatic dysfunction and occasionally thrombocytopenia and coagulopathy. We report here a case of eight year old boy presented with history of wasp sting followed by scanty micturation, generalized swelling and respiratory distress. After admission renal replacement therapy along with oral Prednisolone was started as serum creatinine level was gradually increasing. Kidney biopsy reveled Acute Interstitial Nephritis (AIN). Diagnosis was made of acute renal failure due to AIN following wasp stings. PMID:23982560
Jesmin, T; Muinuddin, G; Hossain, M M; Rahman, M H; Mamun, A A
Abstract Rhabdomyolysis contributes to 7-10% of total AKI cases. Myoglobinuria as a cause of acute renal allograft dysfunction is extremely uncommon. Renal allograft recipient on cyclosporine or tacrolimus can develop myoglobinuria in presence of other precipitating factors. Present case describes an interesting report of myoglobinuria in a patient with post transplant diabetic nephropathy mimicking acute graft rejection. Clinically myoglobinuria presenting as renal allograft dysfunction is diagnosis of exclusion and renal biopsy is extremely important in making a correct diagnosis and planning optimal management in such cases. PMID:24826952
Gupta, Pallav; Sharma, Amit; Khullar, Dinesh
Histopathological interpretation of semimembranosus muscle samples from an adult Warmblood mare with clinical signs suggestive of exertional rhabdomyolysis and intermittent mild elevations in muscle enzyme activities revealed abundant sarcoplasmic vacuoles in all fibre-types containing fine, apparently proteinaceous debris. Vacuolar contents stained lightly with PAS, but did not appear to contain amylopectate, lipid or acid phosphatase and their periphery was unstained with dystrophin immunohistochemistry. Electron microscopy revealed that vacuoles were not membrane bound. No vacuoles were detected in muscle samples evaluated at post mortem following 4 months of rest. To our knowledge, this is the first report of a presumed primary vacuolar myopathy in a horse. PMID:23623568
Massey, C A; Walmsley, G L; Gliddon, T P; Piercy, R J
A young male patient was admitted to our hospital with history of dysuria, recurrent vomiting, severe muscle pain and weakness which was induced by a session of rigorous exercise for the first time in the local gymnasium. He was subsequently diagnosed with exercise-induced acute kidney injury and rhabdomyolysis and managed accordingly. Later on during follow-up he was found to have extreme hypouricaemia (serum uric acid 0.2 mg/dl) and was subsequently diagnosed with renal hypouricaemia. Biochemical investigations on other family members of the patient revealed hereditary renal hypouricaemia in the family. PMID:24783397
Sural, Saubhik; Chakraborty, Sutirtha
Prospective studies of snake bite patients in Chittagong, Bangladesh, included five cases of bites by greater black kraits (Bungarus niger), proven by examination of the snakes that had been responsible. This species was previously known only from India, Nepal, Bhutan and Burma. The index case presented with descending flaccid paralysis typical of neurotoxic envenoming by all Bungarus species, but later developed generalized rhabdomyolysis (peak serum creatine kinase concentration 29,960 units/l) with myoglobinuria and acute renal failure from which he succumbed. Among the other four patients, one died of respiratory paralysis in a peripheral hospital and three recovered after developing paralysis, requiring mechanical ventilation in one patient. One patient suffered severe generalized myalgia and odynophagia associated with a modest increase in serum creatine kinase concentration. These are the first cases of Bungarus niger envenoming to be reported from any country. Generalized rhabdomyolysis has not been previously recognized as a feature of envenoming by any terrestrial Asian elapid snake, but a review of the literature suggests that venoms of some populations of Bungarus candidus and Bungarus multicinctus in Thailand and Vietnam may also have this effect in human victims. To investigate this unexpected property of Bungarus niger venom, venom from the snake responsible for one of the human cases of neuro-myotoxic envenoming was injected into one hind limb of rats and saline into the other under buprenorphine analgesia. All animals developed paralysis of the venom-injected limb within two hours. Twenty-four hours later, the soleus muscles were compared histopathologically and cytochemically. Results indicated a predominantly pre-synaptic action (?-bungarotoxins) of Bungarus niger venom at neuromuscular junctions, causing loss of synaptophysin and the degeneration of the terminal components of the motor innervation of rat skeletal muscle. There was oedema and necrosis of extrafusal muscle fibres in envenomed rat soleus muscles confirming the myotoxic effect of Bungarus niger venom, attributable to phospholipases A?. This study has demonstrated that Bungarus niger is widely distributed in Bangladesh and confirms the risk of fatal neuro-myotoxic envenoming, especially as no specific antivenom is currently manufactured. The unexpected finding of rhabdomyolysis should prompt further investigation of the venom components responsible. The practical implications of having to treat patients with rhabdomyolysis and consequent acute renal failure, in addition to the more familiar respiratory failure associated with krait bite envenoming, should not be underestimated in a country that is poorly equipped to deal with such emergencies. PMID:20855420
Faiz, Abul; Ghose, Aniruddha; Ahsan, Farid; Rahman, Ridwanur; Amin, Robed; Hassan, Mahtab Uddin; Chowdhury, A Wahed; Kuch, Ulrich; Rocha, Thalita; Harris, John B; Theakston, R David G; Warrell, David A
A 54-year-old man presented to our emergency department with fever and dyspnoea. He required vigorous haemodynamic support and mechanical ventilation for hypotensive distributive shock with hypoalbuminaemia, haemoconcentration, rhabdomyolysis and acute renal failure, consistent with idiopathic systemic capillary leak syndrome. Left lung consolidation and hypoxaemia were observed 6?days after admission. Sputum smear revealed the presence of acute angled branching hyphae, consistent with a diagnosis of invasive pulmonary aspergillosis. Antifungal therapy was administered and mechanical ventilation discontinued on day 66. The patient recovered and was discharged from the hospital on day 185. PMID:24859554
Hayama, Manabu; Shime, Nobuaki; Mio, Tadashi
Hymenoptera stings are self-limiting events or due to allergic reactions. Sometimes envenomation with Hymenoptera can cause rare complications such as acute encephalopathy, peripheral neuritis, acute renal failure, nephrotic syndrome, silent myocardial infarction, rhabdomyolysis, conjunctivitis, corneal infiltration, lens subluxation, and optic neuropathy. The mechanism of peripheral nervous system damage is not clearly known. In our studied case after bee sting on face between the eyebrows with little erythema and 1 × 1?cm in size, bilateral blindness developed and gradually improved. Lateral movement of eyes was restricted with no pain. Involvement of cranial nerves including II, V, and VI was found. With conservative therapy after a year significant improvement has been achieved.
Motamed, Hassan; Forouzan, Arash; Rasooli, Fatemeh; Majidi, Alireza; Maleki Verki, Mohammadreza
Organophosphorus poisoning is common in rural Asia. Clinical features result from overactivity of acetylcholine receptors. Blackish discoloration of urine is not a feature of organophosphorus poisoning. Only one case of black colored urine following quinalphos poisoning has been reported in literature. We report two cases of organophosphorus poisoning from two different compounds, following which patients passed black colored urine, in the absence of haemolysis or rhabdomyolysis. These cases indicate that blackish discoloration of urine in organophosphorus poisoning might not be as uncommon as it was believed to be. Besides, urinary excretion of metabolites might be an underlying mechanism, rather than hemolysis.
Mookkappan, Sudhagar; Shanmugham, Vijay; Kulirankal, Kiran
Lumbar plexopathy is characterized by an abrupt onset of sensory disturbances, weakness, and loss of deep tendon reflexes of lower extremities. The various causes of lumbar plexopathy include trauma, infections, space-occupying lesion, vascular diseases, metabolic diseases, and the use of drugs such as heroin. Postoperative rhabdomyolysis occurs secondary to prolonged muscle compression due to surgical positioning. Herein, we report a case of lumbar plexopathy, complicating an injury to the paraspinal muscle and iliopsoas muscle that occurred in the flexed lateral decubitus position following radical nephrectomy.
Lee, Young-Bok; Jeong, Eui-Kyun
Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a clinical syndrome associated with mitochondrial abnormalities. In approximately 80% of patients, the syndrome is associated with the A3243G mutation. However, it has been realized that the A3243G mutation is not uncommon in the general population and is found in many patients with clinical presentations other than MELAS. We present four patients who presented with rhabdomyolysis, muscle fatigue, external ophthalmoplegia and myoclonic jerks respectively. These patients were all found to have the A3243G mutation on muscle biopsy. These patients illustrate the variety of presentations associated with A3243G mutation. PMID:22747555
Blum, S; Robertson, T; Klingberg, S; Henderson, R D; McCombe, P
Cocaine use has increased considerably during the last twenty years and several related complications can be identified. Clinical features of cocaine intoxication are variable, but predominantly involve cardiovascular events. Chest pain is the most main complaint; myocardial ischemia must be ruled out. Other cardiovascular manifestations are left ventricular dysfunction, arrhythmia, endocarditis and aortic dissection. Non-cardiac complications include neurological (seizures, stroke, cerebral hemorrhage), respiratory (asthma, interstitial pneumonitis, pulmonary edema), renal (acute renal failure, rhabdomyolysis) and obstetrical disorders. Detection of cocaine in the urine provides the diagnosis. Symptomatic treatment is generally given, combining conventional treatment of the complication and broad use of benzodiazepines. PMID:12218880
Guerot, Emmanuel; Sanchez, Olivier; Diehl, Jean-Luc; Fagon, Jean-Yves
Background Lifestyle modifications including exercise are beneficial and fundamentally part of the therapy of metabolic syndrome, although in most of the cases medical interventions are also required to reach the target values in the laboratory parameters. Statin and fibrate combination therapy is considered to be safe and effective in dyslipidaemia and metabolic syndrome. However, increased physical activity can enhance the statin and fibrate-associated myopathy. Myositis and the rare but life-threatening rhabdomyolysis are causing a conflict between exercise and statin-fibrate therapy, which is yet to be resolved. Case presentation We present a case of a 43-year-old Caucasian man with metabolic syndrome who had the side-effect of exercise and drug-associated myositis. The patient had only transient moderate complaints and rhabdomyolysis could be avoided with the one-month creatine kinase control, a test which is not recommended routinely by the new guidelines. Conclusions We would like to turn the spotlight on the possible complications of statin-fibrate therapy and exercise, when strict follow-up is recommended. In this condition high number of patients can be affected and the responsibility of general practitioners is accentuated.
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
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
1,4-butanediol (1,4-BD) is an industrial solvent that is metabolized to gamma-hydroxybutyrate (GHB), a gamma-aminobutyric acid agonist and central nervous system depressant. GHB and its analogues are popular drugs of abuse. Withdrawal from these agents is characterized by autonomic instability and altered mental status. We report a case of withdrawal from 1,4-BD lasting 6 days and complicated by new onset of seizures and rhabdomyolysis. In addition, we conducted a systematic review of the English literature pertaining to withdrawal from GHB, 1,4-BD and gamma-butyrolactone (GBL). Data collected from source articles included last use prior to symptom onset, clinical features on presentation, duration of symptoms and outcome. Twenty-seven studies with 57 episodes of withdrawal were included. Thirty-six cases (63%) involved GHB, 3 cases (5%) involved 1,4-BD and 18 (32%) involved GBL. The most common patient symptoms were tremor (67%), hallucinations (63%), tachycardia (63%) and insomnia (58%). Seizures and rhabdomyolysis each occurred in 7% of cases, but only 1 death occurred. Emergency physicians must consider withdrawal from these agents when patients present with clinical features suggestive of a sedative-hypnotic withdrawal syndrome. PMID:18226321
Wojtowicz, Jeremy M; Yarema, Mark C; Wax, Paul M
Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation, producing equimolar amounts of carbon monoxide, iron, and biliverdin. Induction of HO-1 is a beneficial response to tissue injury in diverse animal models of diseases including acute kidney injury. In vitro analysis has shown that the human HO-1 gene is transcriptionally regulated by changes in chromatin conformation, but whether such control occurs in vivo is not known. To enable such an analysis, we generated transgenic mice, harboring an 87-kb bacterial artificial chromosome expressing human HO-1 mRNA and protein and bred these mice with HO-1 knockout mice to generate humanized BAC transgenic mice. This successfully rescued the phenotype of the knockout mice including reduced birth rates, tissue iron overload, splenomegaly, anemia, leukocytosis, dendritic cell abnormalities, and survival after acute kidney injury induced by rhabdomyolysis or cisplatin nephrotoxicity. Transcription factors such as USF1/2, JunB, Sp1, and CTCF were found to associate with regulatory regions of the human HO-1 gene in the kidney following rhabdomyolysis. Chromosome conformation capture and ChIP-loop assays confirmed this in the formation of chromatin looping in vivo. Thus, these bacterial artificial chromosome humanized HO-1 mice are a valuable model to study the human HO-1 gene, providing insight to the in vivo architecture of the gene in acute kidney injury and other diseases. PMID:22495295
Kim, Junghyun; Zarjou, Abolfazl; Traylor, Amie M; Bolisetty, Subhashini; Jaimes, Edgar A; Hull, Travis D; George, James F; Mikhail, Fady M; Agarwal, Anupam
This review summarizes the literature regarding long-term adverse effects of proton pump inhibitors (PPIs). A PubMed search (1966 to February 2013) for English language studies was conducted using key terms PPI: omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole, pneumonia, Clostridium difficile, osteoporosis, risk of fractures, thrombocytopenia, rhabdomyolysis, anemia, iron deficiency, hypomagnesemia, vitamin B?? and nephritis. The risk of pneumonia was increased 27-39% in short-term use of PPIs in three meta-analyses. C. difficile infections were also associated with the use of PPIs (odds ratio: 2.15; 95% CI: 1.81-2.55; p < 0.00001). This effect appears to be dose related. The US FDA has recently issued a warning regarding fractures and the impaired magnesium absorption associated with the use of PPI. Thrombocytopenia, iron deficiency, vitamin B12 deficiency, rhabdomyolysis and acute interstitial nephritis have also been reported with the use of PPIs. There is mounting evidence that PPIs are associated with serious adverse effects. Practitioners should be vigilant and counsel patients accordingly. PMID:23927671
Wilhelm, Sheila M; Rjater, Ryan G; Kale-Pradhan, Pramodini B
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.
Systemic inflammatory response with rhabdomyolysis and consequent multiorgan failure is a known sequela of psychotropic drug abuse. However, in cases with uncertain past medical history the initial diagnosis can be challenging. Here we report the case of a 21-year-old male who was admitted to the intensive care unit with severe neurological impairment caused by amphetamine intoxication. First laboratory investigations revealed extremely high serum procalcitonin (PCT) levels reaching a maximum concentration of 1640?ng/mL on the second day of observation. Although PCT has high sensitivity and specificity in differentiating bacterial sepsis from nonbacterial inflammation, our case report shows for the first time that it can be extremely elevated following serious amphetamine intoxication without bacterial infection.
Lovas, Andras; Agoston, Zsuzsanna; Kesmarky, Klara; Hankovszky, Peter; Molnar, Zsolt
Background Hornet stings are generally associated with local and occasionally anaphylactic reactions. Rarely systemic complications like acute renal failure can occur following multiple stings. Renal failure is usually due to development of acute tubular necrosis as a result of intravascular haemolysis, rhabdomyolysis or shock. Rarely it can be following development of acute tubulo-interstitial nephritis. Case presentation We describe a young male, who was stung on face, head, shoulders and upper limbs by multiple hornets (Vespa orientalis). He developed acute renal failure as a result of acute tubulo-interstitial nephritis and responded to steroids. Conclusion Rare causes of acute renal failure like tubulo-interstitial nephritis should be considered in a patient with persistent oliguria and azotemia following multiple hornet stings. Renal biopsy should be undertaken early, as institution of steroid therapy may help in recovery of renal function
Sharma, Aman; Wanchu, Ajay; Mahesha, V; Sakhuja, V; Bambery, Pradeep; Singh, Surjit
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.
Rachaiah, Niranjan M; Jayappagowda, Lokesh A; Siddabyrappa, Harsha B; Bharath, Venkatesh K
We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury. PMID:10095180
Peces, R; Navascués, R A; Baltar, J; Seco, M; Alvarez, J
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
Durand, M-F; Pommier, P; Chazalette, A; de Haro, L
Hair dye containing paraphenylenediamine (PPD) is widely used in India because of its free availability and low cost. PPD produces local as well as systemic toxic effects when applied topically and/or ingested. It is highly toxic when taken by mouth and the outcome depends mainly on the dose taken. Important clinical manifestations are angioedema leading to dysphasia and respiratory distress, rhabdomyolysis, intravascular hemolysis, acute renal failure and hepatic necrosis. Myocarditis or fatal arrhythmia may also occur in PPD poisoning. Mainstay of management is early recognition and supportive measures as there is no specific antidote. We hereby report a young female who presented to us with features of angioedema, cardiac manifestation and hepatic dysfunction after ingesting PPD, which was treated successfully. In the absence of laboratory facilities, clinical features like angioedema and chocolate brown-colored urine could be suggestive of PPD poisoning. PMID:23563473
Chaudhary, S C; Sawlani, K K; Singh, K
A case report is presented of a young man admitted to a general hospital with leukocytosis, elevated temperature, right lower lobe infiltrate, and confusion. A diagnosis of rhabdomyolysis, acute renal failure, and Legionnaire's disease was made. The patient subsequently had a respiratory arrest and died on the 29th hospital day. This triad is currently an enigma in the field of internal medicine. The diagnosis of each entity is elusive, and in many cases must be made by the astute clinician. Diagnostic features along with early intervention measures and their expected outcomes are discussed. Recognition of the interrelationship of these diseases, risk factors, and vague clinical presentations might allow further prospective intervention methods and diagnostic procedures to be undertaken to avoid the fatal consequences seen in this disease triad.
Boucree, Michael C.
Background Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder that is characterized by involuntary eye movements and myoclonus. OMS exhibits various etiologies, including paraneoplastic, parainfectious, toxic-metabolic, and idiopathic causes. The exact immunopathogenesis and pathophysiology of OMS are uncertain. Case Report We report the case of a 19-year-old male who developed opsoclonus and myoclonus several days after a flu-like illness. Serological tests revealed acute mumps infection. The findings of cerebrospinal fluid examinations and brain magnetic resonance imaging were normal. During the early phase of the illness, he suffered from opsoclonus and myoclonus that was so severe as to cause acute renal failure due to rhabdomyolysis. After therapies including intravenous immunoglobulin, the patient gradually improved and had fully recovered 2 months later. Conclusions This is the first report of OMS associated with mumps infection in Korea. Mumps infection should be considered in patients with OMS.
Bentazone is a herbicide widely used in the agrochemical field and acts by interference in photosynthesis in plants. Case reports of bentazone poisoning in humans are rare, but hepatorenal damage and death have been described, though the mechanism of toxicity remains speculative. We describe 2 cases of acute bentazone poisoning and compare these with other literature reports. The clinical picture included nausea, vomiting, diarrhea, abdominal pain with gastrointestinal corrosive injury, dyspnea and acute hepatorenal dysfunction. Respiratory failure, acute hepatitis, acute renal failure requiring hemodialysis, and death occurred following a large ingested dose of 1,764 mg/kg. Bentazone may have direct organ toxicity, especially in liver and kidney, in subjects with renal hypoperfusion, rhabdomyolysis, preexisting renal disease or concomitant nephrotoxic drug consumption. Aggressive supportive therapy, hydration and measures to prevent renal hypoperfusion are essential to reverse acute renal failure. PMID:18446722
Wu, I-Wen; Wu, Mai-Szu; Lin, Ja-Liang
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.
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)
Statins are among the most commonly prescribed medications that significantly reduce cardiovascular risk in selected individuals. However, these drugs can also be associated with muscle symptoms ranging from mild myalgias to severe rhabdomyolysis. Although statin myotoxicity is usually self-limited, in some instances statin-exposed subjects can develop an autoimmune myopathy typically characterized by progressive weakness, muscle enzyme elevations, a necrotizing myopathy on muscle biopsy, and autoantibodies that recognize 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the pharmacologic target of statins. These antibodies are also found in some autoimmune myopathy patients without statin exposure. Importantly, anti-HMGCR antibodies are not found in the vast majority of statin-exposed subjects without autoimmune myopathy, including those with self-limited statin intolerance. Thus, testing for these antibodies may help differentiate those with self-limited statin myopathy who recover after statin discontinuation from those with a progressive statin-associated autoimmune myopathy who typically require immunosuppressive therapy. PMID:23519993
Mohassel, Payam; Mammen, Andrew L
"Bath salts" are becoming recognized as a frequently abused and highly addictive substance that can be obtained legally in some areas. These agents contain stimulant compounds, such as methylenedioxopyrrovalerone and mephedrone, that have been associated with sympathomimetic effects and psychotic features, such as paranoia, delusions, agitation, and confusion. They may have a benign course; however, intoxication with these agents may lead to severe cardiovascular and neurologic complications and death. We report a case of recurrent acute kidney injury associated with repeated bath salts intoxication. The patient, who presented with neurologic and cardiovascular symptoms and signs, also developed rhabdomyolysis, hyperuricemia, and metabolic acidosis as part of the clinical presentation. Bath salts intoxication should be included on the list of substances that can cause acute kidney injury and other metabolic abnormalities. PMID:22119408
Adebamiro, Adedotun; Perazella, Mark A
Metabolic myopathies represent a small percentage of rhabdomyolysis causes that could lead to acute kidney injury (AKI). This could be prevented if this condition is suspected and timely treated. Carnitine palmityl transferase (CPT) deficiency is the most frequent metabolic myopathy and should be considered whenever recurrent myoglobinuria is suspected, and distinguished from the second frequent one, McArdle disease. We present a case of a patient with two medically misinterpreted episodes of AKI in whom the subsequent diagnosis of CPT deficiency was established based on high index of clinical suspicion and correlation of clinical manifestations to specific metabolic defects. Application of simple measures and lifestyle changes improved our patient's life quality and prevented potential new life-threatening complications. PMID:23560446
Ale?kovi?-Halilovi?, Mirna; Meši?, Enisa; Sinanovi?, Osman; Zuki?, Sanela; Mustedanagi?, Jasminka
Newborn screening (NBS) has rapidly changed since its origins in the 1960s. Beginning with a single condition, then a handful in the 1990 s, NBS has expanded in the past decade to allow the detection of many disorders of amino-acid, organic-acid, and fatty-acid metabolism. These conditions often present with recurrent acute attacks of metabolic acidosis, hypoglycemia, liver failure, and hyperammonemia that may be prevented with initiation of early treatment. Renal disease is an important component of these disorders and is a frequent source of morbidity. Hemodialysis is often required for hyperammonemia in the organic acidemias and urea-cycle disorders. Rhabdomyolysis with renal failure is a frequent complication in fatty-acid oxidation disorders. Newer screening methods are under investigation to detect lysosomal storage diseases, primary immunodeficiencies, and primary renal disorders. These advances will present many challenges to nephrologists and pediatricians with respect to closely monitoring and caring for children with such disorders. PMID:21947256
Merritt, J Lawrence; Askenazi, David; Hahn, Si Houn
We report the anesthetic management with total intravenous anesthesia of a 61-year-old male diagnosed with limb-girdle muscular dystrophy admitted for replacement of ascending aorta due to an aortic aneurysm. Limb-girdle muscular dystrophy belongs to a genetically heterogeneous group of muscular dystrophies involving shoulder and hip girdles. Although the risk of malignant hyperthermia does not seem to be increased in these patients compared with the general population, the exposure to inhaled anesthetics and succinylcholine should probably be avoided because these patients have a predisposition to hyperkalemia and rhabdomyolysis. We chose to use total intravenous anesthesia with propofol, remifentanil and muscle relaxants to reduce oxygen consumption, and later to reduce the doses of propofol and remifentanil. The combination of a carefully planned anesthetic strategy, anesthetic depth, and neuromuscular blockade monitoring is explained. PMID:24035539
López Álvarez, A; Román Fernández, A; Vilanova Vázquez, V; Corujeira Rivera, M C; Areán González, I; Valiño Hortas, C
This article reviews the literature on equine atypical myopathy (AM), an acute, severe rhabdomyolysis that occurs in horses at pasture. The prevalence, mortality, clinical signs, pathology, potential aetiology, typical aspects, diagnosis, treatment, and prognosis are described. Horse management, characteristic weather conditions, and possible preventive measures are also discussed. In addition, the characteristics of 54 highly probable or confirmed cases of equine AM occurring between autumn 2009 (27 cases) and spring 2010 (27 cases) in the Netherlands are described. Of the 54 affected horses, nineteen were mares, eleven geldings, and eight stallions; the sex of the other sixteen horses was not recorded. The mortality rate (74.5%) was in the same range as that reported in earlier studies. Many cases were reported at about the same time. Thirty-five horses had been pastured near maple trees, and in fifteen cases the maple trees were known to be infected with the fungus Rhytisma acerinum. PMID:22930982
Sas, A M C; van der Kolk, J H; Dank, M; Westermann, C M
A 45 year-old man went to the emergency room due to disease duration of 15 days of insidious onset and progressive course. It began with symmetrical weakness and pain in feet and ankles that extends upward to the knees. Later, this progressed to paraparesis with Creatine phosphokinase levels of 44,270 U/L and respiratory failure that required mechanical ventilation. Electromyography and muscle biopsy of quadriceps were made. The patient responded to corticotherapy in pulses and supporting management. The presentation of ascending paresis suggested the diagnosis of Guillain-Barré syndrome. However, the degree of muscle involvement with rhabdomyolysis explains the neurological damage by itself. The biopsy revealed pathological criteria for necrotizing autoimmune myopathy (NAM), as well as other clinical and laboratory evidence. Patient disease continued and reached criteria for systemic lupus erythematosus (SLE). To our best knowledge, this is the first report of the NAM and SLE association. PMID:23906548
García-Reynoso, Marco Julio; Veramendi-Espinoza, Liz Eliana; Ruiz-Garcia, Henry Jeison
Total body Tc-99m pyrophosphate scintigraphy was performed on 11 ''ultramarathon'' runners to assess the ability of nuclear medicine techniques to evaluate skeletal-muscle injury due to exercise. We found increased muscle radionuclide concentration in 90% of the runners. The pattern of muscle uptake correlated with the regions of maximum pain. The detection of exercise-induced rhabdomyolysis appeared to be best when scintigraphy was performed within 48 hr after the race, and to be almost undetectable after about a week. It was possible to differentiate muscle injury from joint and osseous abnormalities such as bone infarct or stress fracture. Although 77% of the runners had elevated serum creatine kinase MB activity, cardiac scintigraphy showed no evidence of myocardial injury.
Matin, P.; Lang, G.; Carretta, R.; Simon, G.
Component wear after total knee arthroplasty (TKA) with extruded metallosis in the extra-articular tissue of the calf secondary to a periprosthetic fracture is a rare complication. A 77-year-old man with a failed Insall-Burstein II TKA prosthesis presented with calf cellulitis after a fall. Radiologic evaluation revealed severe osteolysis and loosening of prosthetic components and an intramuscular abscess communicating with the medullary canal of the tibia through an undisplaced periprosthetic fracture. The patient developed rhabdomyolysis with acute renal failure. Drainage of the calf abscess showed staining of the muscles with wear debris and metallosis. The patient subsequently had debridement and excision of the infected TKA implant. Prompt diagnosis of this condition should be suspected in cases of failed arthroplasty with osteolysis and periprosthetic fracture. PMID:18534390
Tan, Gek Meng; Lynne, Goh; Sarbjit, Singh
Patients with neuromuscular disorders are at high risk of intraoperative and postoperative complications. General anesthesia in these patients may exacerbate respiratory and cardiovascular failure due to a marked sensitivity to several anesthetic drugs. Moreover, succinylcholine and halogenated agents can trigger life-threatening reactions, such as malignant hyperthermia, rhabdomyolysis and severe hyperkalemia. Therefore, regional anesthesia should be used whenever possible. If general anesthesia is unavoidable, special precautions must be taken. In particular, for patients at increased risk of respiratory complications (i.e., postoperative atelectasis, acute respiratory failure, nosocomial infections), noninvasive ventilation associated with aggressive airway clearance techniques can successfully treat upper airway obstruction, hypoventilation and airway secretion retention, avoiding prolonged intubation and tracheotomy. Anesthesia and perioperative management of patients with neuromuscular disorders are described in this article. To grade the strength of recommendations and the quality of evidence we adopted the GRADE approach. In case of low-quality evidence, these recommendations represent the collective opinion of the expert panel. PMID:23419334
Racca, F; Mongini, T; Wolfler, A; Vianello, A; Cutrera, R; Del Sorbo, L; Capello, E C; Gregoretti, C; Massa, R; De Luca, D; Conti, G; Tegazzin, V; Toscano, A; Ranieri, V M
We present a case of a 49-year-old man, with a 10-year history of bronchial asthma and nasal polyposis, who developed acutely painful paraplegia and paresthesias. Laboratory data showed elevated blood creatine kinase levels and myoglobinuria, which were diagnostic for rhabdomyolysis but only partially explained the neurological deficit. Electrophysiological studies revealed a sensorimotor neuropathy of multiple mononeuritis type. The patient also had leucocytosis with marked eosinophilia and antineutrophil cytoplasmic autoantibodies. Bronchial biopsies showed inflammatory infiltrates with a prevalence of eosinophils. All these findings led us to diagnose eosinophilic granulomatosis with polyangiitis, a systemic vasculitis with almost constant respiratory tract involvement and good response to corticosteroid treatment. This can also affect other organs including the nervous system, while muscular involvement is unusual. Some diseases deserve attention in differential diagnosis. Histology can support the diagnosis which remains essentially clinical. Steroid sparing agents/immunosuppressants are suggested for extensive disease. PMID:24980994
Sorino, Claudio; Agati, Sergio; Milani, Giuseppe; Maspero, Annarosa
Polymyositis is a rare and gradually progressive autoimmune disease of skeletal muscle. Two main types of renal involvement have been described: acute tubular necrosis related to rhabdomyolysis and glomerulonephritis. However, cases of overflow proteinuria related to polymyositis have rarely been reported. Herein, we report a case of a 41-year-old male who presented with edema of both lower extremities. Laboratory studies revealed elevated creatine phosphokinase level, hypoalbuminemia, and a moderate amount of proteinuria, although albuminuria was not dominant. Urine electrophoresis showed an abnormally restricted zone in the ?-fraction, which suggested overflow proteinuria of non-glomerular origin. Despite intravenous hydration, his serum creatine phosphokinase level did not decrease and his symptoms did not improve. Electromyography showed myopathy, and muscle biopsy revealed findings consistent with polymyositis. After corticosteroid therapy, his creatine phosphokinase level and proteinuria decreased and his clinical symptoms improved. This case demonstrates an atypical presentation of polymyositis manifested by overflow proteinuria.
Kim, Hyun Ho; Kim, Jae Young; Kim, Sung Jun; Park, Eun Su; Shin, Seok Joon; Kang, Kwi Young; Hong, Yeon Sik; Yoon, Hye Eun
Fatal massive peripheral zonal hepatic necrosis developed in a 47-year-old man who accidentally ingested a solution of methyl ethyl ketone peroxide (MEKP) in dimethyl phthalate. Such solutions contain about 10% active oxygen. The clinical course was characterized by temporary cardiac arrest, abdominal burns, severe metabolic acidosis, rapid hepatic failure, rhabdomyolysis and respiratory insufficiency. A fatal outcome resulted 4 d afterwards from hepatic coma associated with blood coagulation disorders. Microscopical examination revealed massive periportal hepatic necrosis accompanied by atypical pseudoductular proliferation. The proliferating cells were probably of bile duct origin and exhibited atypia and mitoses. The pathogenetic mechanism may involve lipid peroxidation caused by free oxygen radicals derived from MEKP. PMID:2375889
Karhunen, P J; Ojanperä, I; Lalu, K; Vuori, E
Dyslipidemia is an independent risk factor of cardiovascular diseases. The statins are a milestone in the primary and second prevention of cardiovascular diseases and significantly improved its prognosis. Along with the long-term treatment with statins in combination with other hypolipidemic drugs or alone, its safety has attracted a particular attention in clinic, such as the elevation of transaminase and rhabdomyolysis, which have raised an idea of developing the other types of lipid-lowering agents from botanic materials. Traditional Chinese medicine (TCM) has been used in clinical practice for more than 2000 years in China and showed some beneficial effects for human health and many diseases. Recently, many studies demonstrated a favorable effect of TCM for treating dyslipidemia; however, its mechanism remains unclear or totally unknown. The progress and perspective of studies on dyslipidemia with single Chinese herb and its monomers or effective extracts during the past 10 years are discussed in the present review.
Guo, Ming; Liu, Yue; Gao, Zhu-Ye; Shi, Da-zhuo
Objective Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. Methods After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Results Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Conclusions Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.
Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi
Background Crohn’s disease is a relapsing, systemic inflammatory disease affecting the gastrointestinal tract with associated extraintestinal manifestations and immune disorders. Among the few cases reported, the association of Crohn’s disease with polymyositis varies in its complexity and severity. We report here the first known case of inflammatory polymyositis leading to rhabdomyolysis in a male patient diagnosed with Crohn’s ileocolitis. Case presentation A 42-year-old previously healthy man presented with acute polymyositis leading to rhabdomyolysis. The acute nature of the illness raised the suspicion of an infective, toxic, or metabolic insult, which was excluded during further investigations. Prolonged low-grade fever and raised inflammatory markers led to the suspicion of inflammatory polymyositis, which was confirmed by electromyography and muscle histology. In the absence of an infective cause, the concurrent association of prolonged diarrhea containing blood and mucous after recovery from an acute phase of myositis proved a diagnostic challenge. Ileocolonoscopy findings of extensive aphthous ulceration with skip lesions extending to the terminal ileum, and histology showing polymorph infiltration of the lamina propria, transmural involvement, and micro abscess formation was suggestive of Crohn’s disease. Sensory motor axonal peripheral neuropathy, which is another rare association of inflammatory bowel disease, was also present. Conclusion An unrecognized genetic predisposition or altered gut permeability causing disruption of the gut immune barrier triggering an immune response against skeletal muscles may have contributed to this unique association. Both polymyositis and Crohn’s ileocolitis responded well to corticosteroids and azathioprine, which is supportive of their immune pathogenesis. Myositis can be considered to be a rare extraintestinal manifestation of Crohn’s disease and can be used in the differential diagnosis of corticosteroid or hypokalemia-induced myopathy in Crohn’s disease.
The spread of Africanized bees in the American continent has increased the number of severe envenomation after swarm attacks. Acute renal failure (ARF) is one of the major hazards in surviving patients. To assess the mechanisms of bee venom-induced ARF, rats were evaluated before, up to 70 min and 24h after 0.5mg/kg of venom injection. Control rats received saline. Bee venom caused an early and significant reduction in glomerular filtration rate (GFR, inulin clearance, 0.84+/-0.05 to 0.40+/-0.08 ml/min/100g, p<0.0001) and renal blood flow (RBF, laser Doppler flowmetry), which was more severe in the cortical (-72%) than in the medullary area (-48%), without systemic blood pressure decrease. Creatine phosphokinase, lactic dehydrogenase (LDH) and serum glutamic oxaloacetic transaminase increased significantly, pointing to rhabdomyolysis, whereas serum glutamic pyruvic transaminase and hematocrit remained stable. Twenty-four hours after venom, RBF recovered but GFR remained significantly impaired. Renal histology showed acute tubular injury and a massive tubular deposition of myoglobin. Venom was added to isolated rat proximal tubules (PT) suspension subjected to normoxia and hypoxia/reoxygenation (H/R) for direct nephrotoxicity evaluation. After 60 min of incubation, 0.1, 2 and 10 microg of venom induced significant increases in LDH release: 47%, 64% and 86%, respectively, vs. 21% in control PT while 2 microg of venom enhanced H/R injury (85% vs. 55%, p<0.01). These results indicate that vasoconstriction, direct nephrotoxicity and rhabdomyolysis are important mechanisms in the installation of bee venom-induced ARF that may occur even without hemolysis or hypotension. PMID:16774771
Grisotto, Luciana S D; Mendes, Glória E; Castro, Isac; Baptista, Maria A S F; Alves, Venancio A; Yu, Luis; Burdmann, Emmanuel A
Objectives To evaluate the cost-effectiveness of statins for primary prevention of myocardial infarction (MI) and stroke in patients with chronic kidney disease (CKD). Background Patients with CKD have an elevated risk of MI and stroke. Although HMG Co-A reductase inhibitors (“statins”) may prevent cardiovascular events in patients with non-dialysis-requiring CKD, adverse drug effects and competing risks could materially influence net effects and clinical decision-making. Methods We developed a decision-analytic model of CKD and cardiovascular disease (CVD) to determine the cost-effectiveness of low-cost generic statins for primary CVD prevention in men and women with hypertension and mild-to-moderate CKD. Outcomes included MI and stroke rates, discounted quality adjusted life years (QALYs) and lifetime costs (2010 USD), and incremental cost-effectiveness ratios. Results For 65 year-old men with moderate hypertension and mild-to-moderate CKD, statins reduced the combined rate of MI and stroke, yielded 0.10 QALYs, and increased costs by $1,800 ($18,000 per QALY gained). For patients with lower baseline cardiovascular risks, health and economic benefits were smaller; for 65 year-old women, statins yielded 0.06 QALYs and increased costs by $1,900 ($33,400 per QALY gained). Results were sensitive to rates of rhabdomyolysis and drug costs. Statins are less cost-effective when obtained at average retail prices, particularly in patients at lower CVD risk. Conclusions While statins reduce absolute CVD risk in patients with CKD, increased risk of rhabdomyolysis, and competing risks associated with progressive CKD, partly offset these gains. Low-cost generic statins appear cost-effective for primary prevention of CVD in patients with mild-to-moderate CKD and hypertension.
Erickson, Kevin F.; Japa, Sohan; Owens, Douglas K.; Chertow, Glenn M.; Garber, Alan M.; Goldhaber-Fiebert, Jeremy D.
Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1) in 2009. The pathogenesis of these influenza-associated myopathies (IAM) remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1) isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes) were highly susceptible to infection by both influenza A(H1N1) isolates, whereas undifferentiated cells (i. e. myoblasts) were partially resistant. The receptors for influenza viruses, ?2-6 and ?2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP) expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients.
Desdouits, Marion; Munier, Sandie; Prevost, Marie-Christine; Jeannin, Patricia; Butler-Browne, Gillian; Ozden, Simona; Gessain, Antoine; Van Der Werf, Sylvie; Naffakh, Nadia; Ceccaldi, Pierre-Emmanuel
General mitochondrial trifunctional protein (TFP) deficiency leads to a wide clinical spectrum of disease ranging from severe neonatal/infantile cardiomyopathy and early death to mild chronic progressive sensorimotor poly-neuropathy with episodic rhabdomyolysis. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency resulting from the common Glu510Gln mutation usually gives rise to a moderately severe phenotype with multiorgan involvement with high morbidity and mortality. However, isolated LCHAD deficiency can also be consistent with long-term survival in patients identified and treated from an early age. We present biochemical, clinical and mutation data in 9 patients spanning the full spectrum of disease. Fibroblast acylcarnitine profiling shows good correlation with clinical phenotype using the ratio C18(OH)/(C14(OH)+C12(OH)). This ratio shows a gradation of values, from high in four patients with severe neonatal disease (2.5+/-0.8), to low in two neuromyopathic patients (0.35, 0.2). Fibroblast fatty acid oxidation flux assays also show correlation with the patient phenotype, when expressed either as percentage residual activity with palmitate or as a ratio of percentage activity of myristate/oleate (M/O ratio). Fibroblasts from four patients with severe neonatal disease gave an M/O ratio of 4.0+/-0.6 compared to 1.97 and 1.62 in two neuromyopathic patients. Specific enzyme assay of LCHAD and long-chain 3-ketothiolase activity in patient cells shows lack of correlation with phenotype. These results show that measurements in intact cells, which allow all determinative and modifying cellular factors to be present, better reflect patient phenotype. Mutation analysis reveals a number of alpha- and beta-subunit mutations. Peripheral sensorimotor polyneuropathy, often as the initial major presenting feature but usually later accompanied by episodic rhabdomyolysis, is a manifestation of mild TFP protein deficiency. The mild clinical presentation and relative difficulty in diagnosis suggest that this form of TFP is probably underdiagnosed. PMID:15902556
Olpin, S E; Clark, S; Andresen, B S; Bischoff, C; Olsen, R K J; Gregersen, N; Chakrapani, A; Downing, M; Manning, N J; Sharrard, M; Bonham, J R; Muntoni, F; Turnbull, D N; Pourfarzam, M
Introduction Operation on the infrarenal aorta and large arteries of the lower extremities may cause rhabdomyolysis of the skeletal muscle, which in turn may induce remote kidney injury. NIM-811 (N-metyl-4-isoleucine-cyclosporine) is a mitochondria specific drug, which can prevent ischemic-reperfusion (IR) injury, by inhibiting mitochondrial permeability transition pores (mPTP). Objectives Our aim was to reduce damages in the skeletal muscle and the kidney after IR of the lower limb with NIM-811. Materials and methods Wistar rats underwent 180 minutes of bilateral lower limb ischemia and 240 minutes of reperfusion. Four animal groups were formed called Sham (receiving vehicle and sham surgery), NIM-Sham (receiving NIM-811 and sham surgery), IR (receiving vehicle and surgery), and NIM-IR (receiving NIM-811 and surgery). Serum, urine and histological samples were taken at the end of reperfusion. NADH-tetrazolium staining, muscle Wet/Dry (W/D) ratio calculations, laser Doppler-flowmetry (LDF) and mean arterial pressure (MAP) monitoring were performed. Renal peroxynitrite concentration, serum TNF-? and IL-6 levels were measured. Results Less significant histopathological changes were observable in the NIM-IR group as compared with the IR group. Serum K+ and necroenzyme levels were significantly lower in the NIM-IR group than in the IR group (LDH: p<0.001; CK: p<0.001; K+: p?=?0.017). Muscle mitochondrial viability proved to be significantly higher (p?=?0.001) and renal function parameters were significantly better (creatinine: p?=?0.016; FENa: p<0.001) in the NIM-IR group in comparison to the IR group. Serum TNF-? and IL-6 levels were significantly lower (TNF-?: p?=?0.003, IL-6: p?=?0.040) as well as W/D ratio and peroxynitrite concentration were significantly lower (p?=?0.014; p<0.001) in the NIM-IR group than in the IR group. Conclusion NIM-811 could have the potential of reducing rhabdomyolysis and impairment of the kidney after lower limb IR injury.
Garbaisz, David; Turoczi, Zsolt; Aranyi, Peter; Fulop, Andras; Rosero, Oliver; Hermesz, Edit; Ferencz, Agnes; Lotz, Gabor; Harsanyi, Laszlo; Szijarto, Attila
Background: Renal failure is an important adverse effect of drug poisoning. Determining the prevalence and etiology of this serious side effect could help us find appropriate strategies for the prevention of renal failure in most affected patients. Objectives: The present study is aimed to identify drugs that induce renal failure and also to find the prevalence of renal failure in patients referred to emergency departments with the chief complaint of drug poisoning, in order to plan better therapeutic strategies to minimize the mortality associated with drug poisoning induced renal failure. Patients and Methods: This cross-sectional study surveyed 1500 poisoned patients referred to the Emergency Department of Baharloo Hospital in Tehran during 2010. Demographic data including age and gender as well as clinical data including type of medication, duration of hospital stay, and presence of renal failure were recorded. Mann-Whitney U test and chi-squared statistics were used to analyze the results. Results: A total number of 435 patients were poisoned with several drugs, 118 patients were intoxicated with sedative-hypnotic drugs, 279 patients were exposed to opium, and 478 patients were administered to other drugs. The method of intoxication included oral 84.3%, injective 9%, inhalation 4.3% and finally a combination of methods 2.3%. Laboratory results revealed that 134 cases had renal failure and 242 had rhabdomyolysis. The incidence of rhabdomyolysis and renal failure increased significantly with age, and also with time of admission to the hospital. Renal failure was reported in 25.1% of patients exposed to opium, vs. 18.2% of patients poisoned with aluminum phosphide, 16.7% of those with organophosphate, 8% with multiple drugs, 6.7% with alcohol, heavy metals and acids, and 1.7% with sedative hypnotics. Conclusions: Based on the findings of this study, there is a high probability of renal failure for patients poisoned with drugs such as opium, aluminum phosphide, and multiple drugs as well as the patients with delayed admission to the hospital, and it is necessary to seek appropriate treatment to prevent this significant side effect.
Arefi, Mohammad; Taghaddosinejad, Fakhroddin; Salamaty, Peyman; Soroosh, Davood; Ashraf, Hami; Ebrahimi, Mohsen
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
Farmer, J A; Gotto, A M
Hemolytic uremic syndrome (HUS) has been associated with a variety of infective as well as non-infective causes. HUS as a toxic manifestation of exposure to herbicides/pesticides has not been reported so far in literature. We report a subject who presented with clinical features of features of HUS after intentional suicidal ingestion of the herbicidal agent monochloroacetic acid (MCA). A 55-year-old farmer was admitted with a history of consumption of monochloroacetic acid with vomiting, hematochezia and oligo-anuria. Our investigations revealed severe renal failure, metabolic acidosis, anemia, and thrombocytopenia with evidence of intravascular hemolysis. He was treated for HUS with plasma transfusions and haemodialysis in view of renal failure. During the course of hospital admission he developed acute antero-septal myocardial infarction and subsequently succumbed to the disease. MCA is used as an herbicidal agent and also a bleaching agent for silkworm cocoons. The toxicity of MCA has included metabolic acidosis, rhabdomyolysis and renal failure; however HUS has not been described in the literature. Extra -renal manifestations of HUS such as cardiomyopathy have also been infrequently described. This case is presented to highlight an as yet unknown toxicity of MCA. PMID:17538244
Nayak, Shobhana G; Satish, Renuka; Gokulnath
The broad spectrum of heat-related injury (HRI) and its associated lesions is well described in the human literature, with rare reports of similar findings in farm animals. In the current case series, lesions from 4 of 8 lambs that presented with clinical signs of heat stress are reported. Gross lesions at necropsy consisted of acute renal swelling and pallor in 2 of 4 lambs, muscle pallor in 2 of 4 lambs, and chronic bronchointerstitial pneumonia in each of the 4 lambs. Histological lesions considered heat-related included acute renal tubular necrosis, pigment casts, tubular epithelial regeneration, multifocal myocyte degeneration, necrosis, and dropout with histiocytic influx and regeneration. Chronic, bronchointerstitial pneumonia, present in each lamb, was considered a condition predisposing to HRI. Compatibility between observed lesions and those reported in human beings with injury secondary to elevated body temperatures established a diagnosis of HRI in these animals. Diagnostic pathologists should consider HRI in lambs with histological evidence of renal tubular necrosis and/or rhabdomyolysis and even in cases where the clinical picture is strongly suggestive but lesions are not demonstrable. PMID:22585957
Sula, Mee Ja M; Winslow, Christine M; Boileau, Melanie J; Barker, L D; Panciera, Roger J
Backround This retrospective study was undertaken to determine the incidence of kidney dysfunction (KD) and to identify potential risk factors contributing to development of KD in orthopaedic population following an elective or emergency surgery. Methods A total of 1025 patients were admitted in our institution over a period of one year with various indications. Eight hundred and ninety-three patients (87.1%) had a surgical procedure. There were 42 (52.5%) male and 38 (47.5%) female with a mean age of 72?years (range: 47 to 87?years). We evaluated the following potential risk factors: age, comorbidities, shock, hypotension, heart failure, medications (antibiotics, NSAIDs, opiates), rhabdomyolysis, imaging contrast agents and pre-existing KD. Results The overall incidence of KD was 8.9%. Sixty-eight patients developed acute renal injury (AKI) and 12 patients developed acute on chronic kidney disease (CKD). In sixty-six (82.5%) patients renal function was reversed to initial preoperative status. Perioperative dehydration (p?=?0.002), history of diabetes mellitus (p?=?0.003), pre-existing KD (p?=?0.004), perioperative shock (p?=?0.021) and administration of non-steroid anti-inflammatory drugs (NSAIDs) (p?=?0.028) or nephrotoxic antibiotics (p?=?0.037) were statistically significantly correlated with the development of postoperative KD and failure to gain the preoperative renal function. Conclusion We conclude that every patient with risk factor for postoperative KD should be under closed evaluation and monitoring.
A recurrent exon 1 nonsense mutation in the DMD gene, p.Trp3X (c.9G>A), was first ascertained in a proband with no symptoms until age 20 and who walked until the age of 62. Six other unrelated kindreds carrying a p.Trp3X mutation were subsequently ascertained, five from North America and one from Italy. In six of the seven kindreds, the proband presented in childhood incidental to elevated creatine kinase levels detected in the context of other illnesses, or in the setting of cramps with or without rhabdomyolysis. Genetic analysis by high density SNP genotyping demonstrates that the six North American families share a 3.7 Mbp haplotype surrounding the p.Trp3X allele, signifying that this is a founder mutation in these individuals. The size of the founder haplotype and the structure of shared genome-wide segments suggests that the minimal age of this mutation is >6 generations. The discovery of the first DMD founder mutation, associated with a mild Becker phenotype, suggests that the prevalence of hypomorphic dystrophin mutations should be re-examined with the use of improved genomic analysis.
Flanigan, Kevin M.; Dunn, Diane M.; von Niederhausern, Andrew; Howard, Michael T.; Mendell, Jerry; Connolly, Anne; Saunders, Carol; Modrcin, Ann; Dasouki, Majed; Comi, Giacomo P.; Bo, Roberto Del; Pickart, Angela; Jacobson, Richard; Finkel, Richard; Medne, Livija; Weiss, Robert B.
Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted but subsequently died, histological examination showing widespread microvesicular fatty change. Four patients presented with acute liver failure without hyperthermia. All four fulfilled criteria for transplantation, one died before a donor organ became available, and two died within one month post-transplantation of overwhelming sepsis. Histological examination showed submassive lobular collapse. Two patients presented with abdominal pain and jaundice and recovered over a period of three weeks; histological examination showed a lobular hepatitis with cholestasis. Patients developing jaundice or with evidence of hepatic failure particularly encephalopathy and prolongation of the international normalised ratio, or both, whether or not preceded by hyperthermia, should be referred to a specialised liver unit as liver transplantation probably provides the only chance of recovery. Images Figure 1 Figure 2 Figure 3
Ellis, A J; Wendon, J A; Portmann, B; Williams, R
Recently the Paediatric Association of the Netherlands (NVK) published a new guideline on the treatment of diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar syndrome (HHS) in children and adolescents. DKA comprises hyperglycaemia, ketosis and acidosis. Cerebral oedema is a feared, life-threatening complication of DKA. HHS is characterized by hyperglycaemia, hyperosmolarity, severe dehydration, and little or no ketone production. Multi-organ failure, rhabdomyolysis and thrombosis are the most common complications. The NVK guideline distinguishes between treatment of DKA and treatment of HHS, in contrast with the draft version of the Netherlands Association of Internal Medicine guideline on diabetes. To prevent cerebral oedema in children with DKA, it is necessary that both rehydration and metabolic correction are done slowly and carefully. Use of hypotonic fluids is not recommended. Correction of hyperglycaemia is of secondary importance and insulin should be started at a low dosage. Correction of intravascular hypovolaemia is the most important treatment in children with HHS. If adequate fluid replacement does not cause serum glucose levels to drop sufficiently, then administration of insulin should be considered. Fluid replacement is the initial treatment of HHS. Insulin administration should be considered when serum glucose concentrations are no longer declining adequately with fluid administration alone. PMID:24326136
Mul, Dick; Meijer, Caroline R
Dantrolene is a skeletal muscle relaxant used commonly in performance horses to prevent exertional rhabdomyolysis. The goal of the study reported here was to begin to characterize cytochrome P450-mediated metabolism of dantrolene in the horse and describe the pharmacokinetics of the compound, formulated as a capsule or a compounded paste formulation, following oral administration. Dantrolene is rapidly metabolized to 5-hydroxydantrolene both in vivo and in vitro. Preliminary work with equine liver microsomes suggest that two enzymes are responsible for the metabolism of dantrolene, as evidenced by two distinct K(m) values, one at high and one at low substrate concentrations. For the pharmacokinetic portion of the study, a randomized, balanced 2-way crossover design was employed wherein eight healthy horses received a single oral dose of either capsules or paste followed by a 4 week washout period prior to administration of the second formulation to the same horse. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 96 h postdrug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry and data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentrations were 28.9 ± 21.6 and 37.8 ± 12.8 ng/mL for capsules and paste, respectively and occurred at 3.8 h for both formulations. Dantrolene and its major metabolite were both below the limit of detection in both plasma and urine by 168 h postadministration. PMID:21492188
DiMaio Knych, H K; Arthur, R M; Taylor, A; Moeller, B C; Stanley, S D
Background Carbon monoxide (CO) intoxication is a leading cause of severe neuropsychological impairments. Peripheral nerve injury has rarely been reported. It consists usually in a demyelinating polyneuropathy or mononeuropathy affecting mainly the lower limbs. Isolated involvement of both upper extremities has been described in only 4 patients related to root damage. We report the first case of bilateral brachial plexus injury following CO poisoning and review all previous CO-induced neuropathy described in literature. Case presentation After being unconscious for three hours, a 42 years old man experienced bilateral brachial weakness associated with edema of the face and the upper limbs. Neurological examination showed a brachial diplegia, distal vibratory, thermic and algic hypoesthesia, deep tendon areflexia in upper limbs. There was no sensory or motor deficit in lower extremities. No cognitive disturbances were detected. Creatine kinase was elevated. Electroneuromyogram patterns were compatible with the diagnosis of bilateral C5 D1 brachial axonal plexus injury predominant on the left side. Clinical course after hyperbaric oxygen therapy was marked by a complete recovery of neurological disorders. Conclusion Peripheral neuropathy is an unusual complication of CO intoxication. Bilateral brachial plexus impairment is exceptional. Various mechanisms have been implicated including nerve compression secondary to rhabdomyolysis, nerve ischemia due to hypoxia and direct nerve toxicity of carbon monoxide. Prognosis is commonly excellent without any sequelae.
Poisonous snakebite is a rare complication of pregnancy. It has been suggested that snakebite poisoning during pregnancy may cause fetal loss. We report a case of intrauterine fetal death after a poisonous snakebite in the first trimester of pregnancy. A 29-year-old pregnant Japanese woman was admitted to hospital after being bitten by a pit viper on her right heel. The patient was at 10 weeks of gestation. In response to the bite, her right leg became extremely swollen, and paralysis of the right oculomotor nerve was observed. Intravenous administration of cepharanthine, ulinastatin, hydrocortisone sodium succinate, gabexate mesylate and antibiotics was started. Laboratory data suggested the presence of rhabdomyolysis. One week after admission, although she improved clinically and symptomatically, transvaginal ultrasonography revealed intrauterine fetal death. No vaginal bleeding was observed. A dilatation and curettage was performed. The patient made an uneventful recovery and was discharged from hospital 17 days after the snakebite. Consistent with other reports, in the first trimester intrauterine fetal death may especially occur when the mother has systemic symptoms, although its mechanism remains unclear. PMID:14691344
Nasu, Kaei; Ueda, Tami; Miyakawa, Isao
Background Critically ill patients including trauma patients are at high risk of urinary tract infection (UTI). The composition of urine in trauma patients may be modified due to inflammation, systemic stress, rhabdomyolysis, life support treatment and/or urinary catheter insertion. Methods Prospective, single-centre, observational study conducted in patients with severe trauma and without a history of UTIs or recent antibiotic treatment. The 24-hour urine samples were collected on the first and the fifth days and the growth of Escherichia coli in urine from patients and healthy volunteers was compared. Biochemical and hormonal modifications in urine that could potentially influence bacterial growth were explored. Results Growth of E. coli in urine from trauma patients was significantly higher on days 1 and 5 than in urine of healthy volunteers. Several significant modifications of urine composition could explain these findings. On days 1 and 5, trauma patients had an increase in glycosuria, in urine iron concentration, and in the concentrations of several amino acids compared to healthy volunteers. On day 1, the urinary osmotic pressure was significantly lower than for healthy volunteers. Conclusion We showed that urine of trauma patients facilitated growth of E. coli when compared to urine from healthy volunteers. This effect was present in the first 24 hours and until at least the fifth day after trauma. This phenomenon may be involved in the pathophysiology of UTIs in trauma patients. Further studies are required to define the exact causes of such modifications.
We aimed to describe the characteristics, clinical course, management and outcome of patients presenting to Perth teaching hospitals after envenoming by Tiger snakes. We undertook a chart review from six Perth teaching hospitals over a 16 year period from 1990 to 2005. Data were collected by a trained investigator using a preformatted data abstraction tool. We included patients bitten in the appropriate geographical area, with defibrination coagulopathy and positive Venom Detection Kit result for Tiger snake or response to specific antivenom. Of 381 charts reviewed, 23 patients were envenomed by a Tiger snake. The mean age was 36 years, 83% were male and all were bitten on a limb. First aid was applied poorly and all patients were symptomatic on presentation. Six patients developed rhabdomyolysis, one renal failure, four clinical bleeding, three neurotoxicity, one non-fatal respiratory arrest and one fatal cardiac arrest. All patients received antivenom, 13 received adrenaline premedication, with two mild allergic reactions developing in non-premedicated patients. The average dose of antivenom was four ampoules. Mean hospital stay was 2.6 days. This is the largest series of Tiger snake envenoming reported in Australia. Only one patient of 23 (4%) died, despite all patients being significantly envenomed. With rapid antivenom treatment and modem emergency and intensive care management, most patients envenomed by Tiger snakes survive. PMID:19681421
Scop, J; Little, M; Jelinek, G A; Daly, F F S
Background Electroporation of skeletal muscle after injection of naked DNA was shown by others to increase transgene expression. Information regarding tissue damage caused by electroporation is conflicting. It is also not well known how plasmid electroporation compares with transfection by adenoviral vectors. To investigate these questions the most used protocol for muscle electroporation was used, i.e. 8 pulses of 200 V/cm and 20 ms at a frequency of 1 Hz. Results Intra-muscular DNA transfer of pLuciferase was increased by 2 logs after electroporation, confirming data described by others. However, the blood levels of the encoded protein were still lower than those obtained after injection of first generation adenoviral vectors. Also, the electroporation procedure, on its own, caused severe muscle damage consisting of rhabdomyolysis and infiltration, whereas the adenoviral vectors caused only a slight infiltration. As damage of targeted tissue may be an advantage in the case of tumour transfection, we also compared the two transfection methods in tumour tissue. In case of poorly permissive tumours, adenoviral vectors cannot transfect more than 2% of the tumour tissue without inducing significant liver damage. In contrast, the electroporation seems to offer a wider therapeutic window since it does not cause any systemic toxicity and still induce's significant transfection. Conclusions Plasmid electroporation of the muscle induce severe local damage and is of no advantage over adenoviral vectors for obtaining high blood levels of a vector encoded protein. In contrast, electroporation of tumours might be safer than adenoviral gene transfer.
Lefesvre, Pierre; Attema, Joline; van Bekkum, Dirk
Fatty acids are a major fuel for the body and fatty acid oxidation is particularly important during fasting, sustained aerobic exercise and stress. The myocardium and resting skeletal muscle utilise long-chain fatty acids as a major source of energy. Inherited disorders affecting fatty acid oxidation seriously compromise the function of muscle and other highly energy-dependent tissues such as brain, nerve, heart, kidney and liver. Such defects encompass a wide spectrum of clinical disease, presenting in the neonatal period or infancy with recurrent hypoketotic hypoglycaemic encephalopathy, liver dysfunction, hyperammonaemia and often cardiac dysfunction. In older children, adolescence or adults there is often exercise intolerance with episodic myalgia or rhabdomyolysis in association with prolonged aerobic exercise or other exacerbating factors. Some disorders are particularly associated with toxic metabolites that may contribute to encephalopathy, polyneuropathy, axonopathy and pigmentary retinopathy. The phenotypic diversity encountered in defects of fat oxidation is partly explained by genotype/phenotype correlation and certain identifiable environmental factors but there remain many unresolved questions regarding the complex interaction of genetic, epigenetic and environmental influences that dictate phenotypic expression. It is becoming increasingly clear that the view that most inherited disorders are purely monogenic diseases is a naive concept. In the future our approach to understanding the phenotypic diversity and management of patients will be more realistically achieved from a polygenic perspective. PMID:23674167
Olpin, Simon E
Serotonin syndrome is a potentially life-threatening drug effect. It may be misdiagnosed because it has mostly been reported in adults. Case Report. An 8-year-old girl with behavioral problems and medicated with risperidone and sertraline was admitted in the emergency department after she had taken voluntarily 1500?mg of sertraline (50?mg/kg). At admission, she had marked agitation, visual hallucinations, diaphoresis, flushing, and tremor. She had fever and periods of hypertension. She also showed generalized rigidity and involuntary movements. She was treated with fluids and iv diazepam, midazolam, clemastine, and biperiden. As the patient presented a severe insomnia and a progressive rhabdomyolysis, she was transferred to pediatric intensive care unit (ICU), where she was under treatment with cyproheptadine, mechanical ventilation, and muscular paralysis for 11 days. She was discharged from hospital a few days later with no neurological sequelae. Conclusions. Serotonin syndrome is still not well recognized by physicians. In our patient, the diagnosis was made early due to the history of overdose with serotonin reuptake inhibitors and the triad of mental, neurological, and autonomic signs. Parents must be educated to prevent children from having free access to drugs, avoiding self-medication or overdose.
Garrido, Ana; Brito, Hernani; Oliveira, Maria Jose; Santos, Fatima
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.
We present three fatal intoxications of methylone, a cathinone derivative. Blood was analyzed with a routine alkaline liquid-liquid extraction and analyzed by gas chromatography coupled with a mass spectrometer (GC-MS). Methylone was identified by a full scan mass spectral comparison to an analytical standard of methylone. For a definitive and conclusive confirmation and quantitation, methylone was also derivatized with heptafluorobutyric anhydride and analyzed by GC-MS. In all three fatalities, the deceased exhibited seizure-like activity and elevated body temperatures (103.9, 105.9 and 107°F) before death. Two of the three cases also exhibited metabolic acidosis. One of the three cases had prolonged treatment and hospitalization before death with symptoms similar to sympathomimetic toxicity, including metabolic acidosis, rhabdomyolysis, acute renal failure and disseminated intravascular coagulation. The laboratory results for this patient over the 24 h period of hospitalization were significant for increased lactate, liver transaminases, creatinine, myoglobin, creatine kinase and clotting times, and decreased pH, glucose and calcium. Peripheral blood methylone concentrations in the three fatal cases were 0.84, 3.3 and 0.56 mg/L. In conlusion, peripheral blood methylone concentrations in excess of 0.5 mg/L may result in death due to its toxic properties, which can include elevated body temperature and other sympathomimetic-like symptoms. PMID:22589523
Pearson, Julia M; Hargraves, Tiffanie L; Hair, Laura S; Massucci, Charles J; Frazee, C Clinton; Garg, Uttam; Pietak, B Robert
Thoracic vertebral compression fractures are a known complication of generalized tetanus. The authors report the first known case of an L-2 burst fracture leading to cauda equina syndrome, as a result of generalized tetanus. This 51-year-old man had generalized tetanus with a constellation of symptoms including compartment syndrome requiring fasciotomies, severe axial spasms and spasms of the extremities, autonomic dysreflexia, hypercarbic respiratory failure, and rhabdomyolysis. During the course of his illness, areflexic paraparesis developed in his lower extremities. He was found to have an L-2 burst fracture with retropulsion of a bone fragment resulting in cauda equina syndrome. Operative intervention was undertaken to decompress the cauda equina and stabilize the spine. The natural progression of tetanus can be complex, with a mixed picture ranging from spasms plus increased tone and reflexes to reduced tone and reflexes as presynaptic nerve terminals become damaged. The authors suggest that all sudden changes in the neurological examination should prompt consideration of diagnostic imaging before attributing such changes to natural progression of the disease. PMID:21854128
Wilson, Thomas J; Orringer, Daniel A; Sullivan, Stephen E; Patil, Parag G
Mitochondrial trifunctional protein (MTP) is a hetero-octamer composed of four ?- and four ?-subunits that catalyzes the final three steps of mitochondrial ?-oxidation of long chain fatty acids. HADHA and HADHB encode the ?-subunit and the ?-subunit of MTP, respectively. To date, only two cases with MTP deficiency have been reported to be associated with hypoparathyroidism and peripheral polyneuropathy. Here, we report on two siblings with autosomal recessive infantile onset hypoparathyroidism, peripheral polyneuropathy, and rhabdomyolysis. Sequence analysis of HADHA and HADHB in both siblings shows that they were homozygous for a mutation in exon 14 of HADHB (c.1175C>T, [p.A392V]) and the parents were heterozygous for the mutation. Biochemical analysis revealed that the patients had MTP deficiency. Structural analysis indicated that the A392V mutation identified in this study and the N389D mutation previously reported to be associated with hypoparathyroidism are both located near the active site of MTP and affect the conformation of the ?-subunit. Thus, the present patients are the second and third cases of MTP deficiency associated with missense HADHB mutation and infantile onset hypoparathyroidism. Since MTP deficiency is a treatable disease, MTP deficiency should be considered when patients have hypoparathyroidism as the initial presenting feature in infancy. PMID:24664533
Naiki, Misako; Ochi, Nobuhiko; Kato, Yusuke S; Purevsuren, Jamiyan; Yamada, Kenichiro; Kimura, Reiko; Fukushi, Daisuke; Hara, Shinya; Yamada, Yasukazu; Kumagai, Toshiyuki; Yamaguchi, Seiji; Wakamatsu, Nobuaki
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.
Siegel, A.J.; Silverman, L.M.; Holman, B.L.
Acute limb ischemia is a complication of severe peripheral arterial disease that can be a threatening limb as well as life. Multiple procedures exist today to help revascularize extremities; however, even with the latest technologies, surgical amputation of the limb may still be necessary. Cryoamputation, or physiologic amputation, is a method used to treat patients who are hemodynamically unstable for the operating room and who are in need of urgent amputation owing to arterial ischemia. This procedure is used in the rare instance where not only a persons' limb is threatened, but also their life. This is a case study regarding one patient who presented to the hospital with limb-threatening ischemia who became hemodynamically unstable owing to the rhabdomyolysis associated with the ischemia of his lower extremity. Cryoamputation was used to stabilize the patient and prevent further deterioration, so that he could safely undergo surgical amputation of the limb without an increase in mortality risk. Cryoamputation must be followed by formal surgical amputation when the patient is hemodynamically stabilized. It is not a limb salvaging, procedure but it is a life-saving procedure. This case study demonstrates the usefulness of the procedure and discusses the technique used for cryoamputation. PMID:24534085
Long, Jeri; Hall, Virginia
The positive health benefits of statins extend beyond the cardiovascular and include increased flow mediated dilation, decreased atrial fibrillation, modest antihypertensive effects and reduced risks of malignancies. Prominent among the statin side-effects are myalgia and muscular weakness, which may be associated with a rise in circulating creatine kinase values. In increasing severity and decreasing incidence, the statin-induced muscle related conditions are myalgia, myopathy with elevated creatine kinase (CK) levels with or without symptoms, and rhabdomyolysis. Statin use may increase CK levels without decreasing average muscle strength or exercise performance. In one large study, only about 2 % had myalgia that could be attributed to statin use. A novel current hypothesis is that statins optimize cardiac mitochondrial function but impair the vulnerable skeletal muscle by inducing different levels of reactive oxygen species (ROS) in these two sites. In an important observational study, both statins and exercise reduced the adverse outcomes of cardiovascular disease, and the effects were additive. The major unresolved problem is that either can cause muscular symptoms with elevation of blood creatine kinase levels. There is, as yet, no clearly defined outcomes based policy to deal with such symptoms from use of either statins or exercise or both. A reasonable practical approach is to assess the creatine kinase levels, and if elevated to reduce the statin dose or the intensity of exercise. PMID:23934075
Opie, Lionel H
The statins are widely used worldwide to reduce risk for cardiovascular events in both the primary and secondary prevention settings. Although generally quite safe, the statins can be associated with a variety of serious side adverse effects, including myalgia, myopathy, and changes in plasma enzymes of hepatic origin. Although rare, the most serious of these is rhabdomyolysis. Several drugs can interfere with the metabolism and disposal of the statins, thereby increasing risk for adverse events. It is important that clinicians treating patients with statins be aware of the potential for drug-drug interactions between each statin and specific other drugs and take measures to prevent them. The prediction of potential drug-drug interactions derives from basic pharmacokinetic principles. Certain drug interactions are predicted by measuring the effect of interacting drugs on blood plasma concentrations of the statin. Individual patient variations resulting in part from polymorphisms in the metabolizing enzymes confound some of these predictions. Based on these known effects, a new classification for predicting statin drug interactions is proposed. This report discusses likely prescription and nonprescription interactions as well as potential alternatives for special populations. PMID:24793440
Kellick, Kenneth A; Bottorff, Michael; Toth, Peter P
The 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors (statins) are among the most common medications prescribed worldwide, but their efficacy and toxicity vary between individuals. One of the major factors contributing to intolerance and non-compliance are the muscle side-effects, which range from mild myalgia through to severe life-threatening rhabdomyolysis. One way to address this is pharmacogenomic screening, which aims to individualize therapy to maximize efficacy whilst avoiding toxicity. Genes encoding proteins involved in the metabolism of statins as well as genes known to cause inherited muscle disorders have been investigated. To-date only polymorphisms in the SLCO1B1 gene, which encodes the protein responsible for hepatic uptake of statins, and the COQ2 gene, important in the synthesis of coenzyme Q10, have been validated as being strongly associated with statin-induced myopathy. The aim of this review is to summarize studies investigating genetic factors predisposing to statin myopathy and myalgia, as the first step towards pharmacogenomic screening to identify at risk individuals. PMID:24176465
Needham, M; Mastaglia, F L
Necrotizing autoimmune myopathies are included in the spectrum of inflammatory myopathies, together with polymyosis, dermatopolymyosis and inclusion body myositis, despite the characteristic feature of marked muscular necrosis without inflammatory infiltrates. The clinical presentation is highly variable, often similar to the other inflammatory myopathies. The most common finding is nevertheless the severe form with rhabdomyolysis. The creatine kinase level is elevated (around 10,000IU/l) and electromyography shows myopathic changes with increased spontaneous activities reflecting the importance of the muscular necrosis. Muscle biopsy is required for diagnosis, revealing active necrosis of the muscle fibers without inflammatory invasion by CDA+ or CD8+ T-cells. Deposition of a microvascular membrane attack complex (C5b9) is often noted, whereas the upregulation of MHC class 1 is rarely detected. Signs of endomysial microangiopathy are frequently reported. Necrotizing autoimmune myopathies can be associated with antisignal recognition particle (SRP) antibodies or more rarely with the usual inflammatory myopathy antibodies. Paraneoplasic forms are described but remain exceptional. Lastly, necrotizing autoimmune myopathies, sometimes associated with statin therapy, have been recently described. They are linked with an antibody directed against 3-hydroxy-3-methyglutaryl-coenzyme A. Treatment is based on corticosteroid therapy, immunosuppressive drugs or intravenous immunoglobulins. Response is variable, depending on the clinical form. PMID:23999024
Petiot, P; Choumert, A; Hamelin, L; Devic, P; Streichenberger, N
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
Carr, D F; O'Meara, H; Jorgensen, A L; Campbell, J; Hobbs, M; McCann, G; van Staa, T; Pirmohamed, M
Clinical symptoms of neuromuscular diseases vary according to age and type of primary involvement (spinal motor neuron, nerve, neuromuscular junction or muscle). Tools at our disposal for diagnostic purposes are graduated based on the age of the patient and diagnostic suspicions generated by the clinical workup. Seven clinical presentations can be identified that all require technical facilities specifically dedicated to pediatric neuromuscular diseases: congenital hypomobility and arthrogryposis, paralytic hypotonia in infancy, motor delay and chronic walking difficulties after the age of 18 months, progressive walking difficulties after the age of 3 years, effort intolerance and acute rhabdomyolysis, acute motor symptoms or fatigability, and variability of symptoms. Electrophysiological investigation, particularly electromyography, is a valuable tool where neurogenic involvement or neuromuscular block is suspected. However, the technique is difficult to perform in children. Muscle biopsy is generally the key investigation and can be performed at any age. Molecular biology helps to improve diagnostic strategy. Muscle MRI, in combination with clinical evaluation, assists the selection of appropriate genetic tests and more generally the identification of genetically distinct forms of neuromuscular disorder. None of these are by any means routine investigations, and only a specialized multidisciplinary clinical approach can permit correct diagnosis and proper follow-up. PMID:23622354
Fardeau, Michel; Desguerre, Isabelle
Infectious myositis may be caused by a broad range of bacterial, fungal, parasitic, and viral agents. Infectious myositis is overall uncommon given the relative resistance of the musculature to infection. For example, inciting events, including trauma, surgery, or the presence of foreign bodies or devitalized tissue, are often present in cases of bacterial myositis. Bacterial causes are categorized by clinical presentation, anatomic location, and causative organisms into the categories of pyomyositis, psoas abscess, Staphylococcus aureus myositis, group A streptococcal necrotizing myositis, group B streptococcal myositis, clostridial gas gangrene, and nonclostridial myositis. Fungal myositis is rare and usually occurs among immunocompromised hosts. Parasitic myositis is most commonly a result of trichinosis or cystericercosis, but other protozoa or helminths may be involved. A parasitic cause of myositis is suggested by the travel history and presence of eosinophilia. Viruses may cause diffuse muscle involvement with clinical manifestations, such as benign acute myositis (most commonly due to influenza virus), pleurodynia (coxsackievirus B), acute rhabdomyolysis, or an immune-mediated polymyositis. The diagnosis of myositis is suggested by the clinical picture and radiologic imaging, and the etiologic agent is confirmed by microbiologic or serologic testing. Therapy is based on the clinical presentation and the underlying pathogen.
Crum-Cianflone, Nancy F.
Cocaine is a drug notorious for its ability to adversely affect almost any organ in the body and cause a plethora of biochemical abnormalities secondary to its severe vasoconstrictive properties. These abnormalities are not exclusively seen in habitual users or cases of overdose, and may sometimes cause confusion as to the underlying pathology. We describe a case of a young female who presented to the Accident and Emergency department in the early hours of the morning complaining of muscle weakness following the inhalation of a small quantity of an 'unknown substance' the previous night. Investigations showed life-threatening hyperkalaemia with a potassium of 9.0 mmol/L, evidence of rhabdomyolysis, acute renal as well as liver failure, disseminated intravascular coagulopathy and a raised troponin of 7000 ng/L, which later peaked to 15,600 ng/L. Four days later, she became hypoxic as a result of adult respiratory distress syndrome with grossly abnormal chest X-ray appearances. Following intensive therapy, she made a dramatic recovery and was discharged from hospital 20 days from presentation. This case highlights the importance of biochemical profiling in patients presenting with possible drug use, even in the absence of significant symptoms. PMID:22113955
Elnenaei, Manal O; Heneghen, Michael A; Moniz, Caje
We describe the case of a patient with severe lactic acidosis, as well as presenting some data on its incidence, diagnosis, prognostic factors, and the most appropriate treatment. A 76 year-old male patient with diabetes on treatment with metformin, hypertension, dyslipaemia, and with mild cognitive impairment, was admitted to the Intensive Care Unit in a state of circulatory shock, requiring aggressive treatment with vasopressors and volume. The patient had acute kidney injury with an anuria of 3 days, probably secondary to dehydration to vomiting and to NSAIDs. As a result of the acute renal damage, the patient suffered a severe metformin-associated lactic acidosis. The rest of the causes of metabolic acidosis with an increased anion gap were ruled out, as well as a possible sepsis or rhabdomyolysis. Metformin-associated lactic acidosis is an uncommon metabolic condition, but with a high mortality. To reduce the mortality of these patients, it is important to make an early diagnosis using the clinical records, physical examination, and laboratory tests, with an early resuscitation with volume, vasopressors, bicarbonate, and renal replacement therapy. PMID:22609263
Vives, M; Romano, J; Stoll, E; Lafuente, A; Nagore, D; Monedero, P
Many different drugs and agents may cause nephrotoxic acute kidney injury (AKI) in children. Predisposing factors such as age, pharmacogenetics, underlying disease, the dosage of the toxin, and concomitant medication determine and influence the severity of nephrotoxic insult. In childhood AKI, incidence, prevalence, and etiology are not well defined. Pediatric retrospective studies have reported incidences of AKI in pediatric intensive care units (PICU) of between 8% and 30%. It is widely recognized that neonates have higher rates of AKI, especially following cardiac surgery, severe asphyxia, or premature birth. The only two prospective studies in children found incidence rates of 4.5% and 2.5% of AKI in children admitted to PICU, respectively. Nephrotoxic drugs account for about 16% of all AKIs most commonly associated with AKI in older children and adolescents. Nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, amphotericin B, antiviral agents, angiotensin-converting enzyme (ACE) inhibitors, calcineurin inhibitors, radiocontrast media, and cytostatics are the most important drugs to indicate AKI as significant risk factor in children. Direct pathophysiological mechanisms of nephrotoxicity include constriction of intrarenal vessels, acute tubular necrosis, acute interstitial nephritis, and-more infrequently-tubular obstruction. Furthermore, AKI may also be caused indirectly by rhabdomyolysis. Frequent therapeutic measures consist of avoiding dehydration and concomitant nephrotoxic medication, especially in children with preexisting impaired renal function. PMID:18228043
Rhabdomyolysis is associated with acute renal failure. The following study first characterized myoglobin in vitro toxicity using renal cortical slices isolated from male Fischer 344 rats. This model provided interaction between various cells within the nephron and provides myoglobin access predominantly through the basolateral membrane. Second, this study examined the effect of deferoxamine (DFX) and glutathione on myoglobin toxicity to determine the role of radicals and iron. Renal cortical slices were incubated for 30-120 min with 0, 4, 10 or 12 mg/ml myoglobin. Myoglobin was pretreated with 4 mM ascorbic acid prior to addition to the slices to ensure that myoglobin was in its reduced state. In other experiments tissues were pretreated for 15 min with 0.1 mM of the iron chelator DFX or 30 min with 1 mM glutathione prior to co-incubation with myoglobin. Finally, slices were pretreated with 1 mM glutathione for 30 min, rinsed and incubated only with myoglobin. Early event changes occurred within a 60 min exposure and included a decline in pyruvate-stimulated gluconeogenesis, increased lipid peroxidation levels and decreased glutathione levels. Loss of ATP levels and increased lactate dehydrogenase (LDH) release required a 120 min exposure to myoglobin. DFX reduced myoglobin induced effects on LDH leakage but had no effect on gluconeogenesis suggesting that myoglobin toxicity had an iron dependent (LDH) and independent (gluconeogenesis) pathway. Pretreatment with glutathione provided complete protection and was mediated by intracellular events. PMID:12499114
Minigh, Jennifer L; Valentovic, Monica A
Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid ?-oxidation. Three main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan's anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin. PMID:20691590
Laforêt, Pascal; Vianey-Saban, Christine
Omega-3 polyunsaturated fatty acids are found in fish oil and they have been shown to mitigate the risk of cardiovascular disease. Omega-3 fatty acids are essential fatty acids because they cannot be synthesized de novo and must be consumed from dietary sources such as marine fish. It reduces fatal and nonfatal myocardial infarction, stroke, coronary artery disease, sudden cardiac death, and all-cause mortality. It also has beneficial effects in mortality reduction after a myocardial infarction. Omacor is a highly potent form of Omega-3 fatty acids that lowers plasma triglycerides. In patients with severe hypertriglyceridemia who are refractory to statins, it helps augment triglyceride reduction. Omacor also increases high-density lipoprotein and decreases low-density lipoprotein levels. It is well tolerated with minimal adverse effects and no known interactions causing rhabdomyolysis. In high doses, Omacor has pronounced cardiovascular benefits with improvement of triglycerides and various lipid parameters. Omega-3 fatty acids have also been shown to have beneficial effects on arrhythmias, inflammation, and heart failure. It may also decrease platelet aggregation and induce vasodilation. Omega-3 fatty acids also reduce atherosclerotic plaque formation and stabilize plaques preventing plaque rupture leading to acute coronary syndrome. Moreover, omega-3 fatty acids may have antioxidant properties that improve endothelial function and may contribute to its antiatherosclerotic benefits. In this review, we sought to provide the current literature on the use of omega-3 fatty acids and the potent formulation Omacor in the treatment of coronary artery disease. PMID:21975796
Bariatric surgical procedures are increasingly common. In this review, we characterize the neurologic complications of such procedures, including their mechanisms, frequency, and prognosis. Literature review yielded 50 case reports of 96 patients with neurologic symptoms after bariatric procedures. The most common presentations were peripheral neuropathy in 60 (62%) and encephalopathy in 30 (31%). Among the 60 patients with peripheral neuropathy, 40 (67%) had a polyneuropathy and 18 (30%) had mononeuropathies, which included 17 (94%) with meralgia paresthetica and 1 with foot drop. Neurologic emergencies including Wernicke's encephalopathy, rhabdomyolysis, and Guillain-Barré syndrome were also reported. In 18 surgical series reported between 1976 and 2004, 133 of 9996 patients (1.3%) were recognized to have neurologic complications (range: 0.08-16%). The only prospective study reported a neurologic complication rate of 4.6%, and a controlled retrospective study identified 16% of patients with peripheral neuropathy. There is evidence to suggest a role for inflammation or an immunologic mechanism in neuropathy after gastric bypass. Micronutrient deficiencies following gastric bypass were evaluated in 957 patients in 8 reports. A total of 236 (25%) had vitamin B(12) deficiency and 11 (1%) had thiamine deficiency. Routine monitoring of micronutrient levels and prompt recognition of neurological complications can reduce morbidity associated with these procedures. PMID:15973660
Koffman, Boyd M; Greenfield, L John; Ali, Imran I; Pirzada, Noor A
The spectrum of RYR1 mutation associated disease encompasses congenital myopathies, exercise induced rhabdomyolysis, malignant hyperthermia susceptibility and King-Denborough syndrome. We report the clinical phenotype of two siblings who presented in infancy with hypotonia and striking fatigable ptosis. Their response to pyridostigimine was striking, but genetic screening for congenital myasthenic syndromes was negative, prompting further evaluation. Muscle MRI was abnormal with a selective pattern of involvement evocative of RYR1-related myopathy. This directed sequencing of the RYR1 gene, which revealed two heterozygous c.6721C>T (p.Arg2241X) nonsense mutations and novel c.8888T>C (p.Leu2963Pro) mutations in both siblings. These cases broaden the RYR1-related disease spectrum to include a myasthenic-like phenotype, including partial response to pyridostigimine. RYR1-related myopathy should be considered in the presence of fatigable weakness especially if muscle imaging demonstrates structural abnormalities. Single fibre electromyography can also be helpful in cases like this. PMID:24951453
Illingworth, M A; Main, M; Pitt, M; Feng, L; Sewry, C A; Gunny, R; Vorstman, E; Beeson, D; Manzur, A; Muntoni, F; Robb, S A
Propofol is a short-acting intravenous anesthetic agent widely used for sedation in anesthesia and intensive care. However, during the last 15 years there have been quite a lot of publications reporting unexplained deaths among pediatric and adult critically ill patients. These cases shared common symptoms and signs unrelated with initial admission diagnosis and were under long-term propofol infusion at high doses. A new syndrome called 'propofol infusion syndrome' was defined, including cardiovascular instability, metabolic acidosis, hyperkalaemia and rhabdomyolysis, with no evidence for other known causes of myocardial failure. One common denominator in these patients was the presence of hypoxia and tissue hypoperfusion. It seems that during states of increased metabolic demand, the reduced energy production related to an inhibitory propofol action at the level of mitochondrial oxidative phosphorylation and lipid metabolism may lead to the manifestation of the syndrome. Furthermore, cases of early toxicity due to failure in cellular energy production with development of lactic acidosis have been also described during anesthesia. For the above reasons, recommendations for the limitation of propofol use have been devised by various institutions, whereas physicians need to be cautious when using prolonged propofol sedation and alert for early signs of toxicity. PMID:18652104
Papaioannou, V; Dragoumanis, C; Theodorou, V; Pneumatikos, I
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
Yin, Xia; Feng, Tao; Shang, Jian-Hua; Zhao, Yun-Li; Wang, Fang; Li, Zheng-Hui; Dong, Ze-Jun; Luo, Xiao-Dong; Liu, Ji-Kai
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.
Lucato, Rui V.; Abdulkader, Regina C. R. M.; Barbaro, Katia C.; Mendes, Gloria E.; Castro, Isac; Baptista, Maria A. S. F.; Cury, Patricia M.; Malheiros, Denise M. C.; Schor, Nestor; Yu, Luis; Burdmann, Emmanuel A.
Introduction The purpose of this study was to test the hypothesis that Malignant Hyperthermia model mice (RyR1Y522S/wt) are more vulnerable to exercise-induced muscle injury and fatigability and adapt less to run training. Methods Following 6 weeks of voluntary wheel running, we measured anterior crural muscle fatigability, muscle injury, and cytochrome oxidase (COX) and citrate synthase (CS). Results Although RyR1Y522S/wt mice ran without experiencing MH episodes, they ran 42% less distance than wild type (WT) mice. Muscles from WT mice exhibited increased fatigue resistance and COX content after training. Muscles from RyR1Y522S/wt mice demonstrated no significant change in fatigability or COX and CS after training. However, muscles from RyR1Y522S/wt mice displayed less intrinsic fatigability and greater COX/CS content and muscle damage than WT mice. Discussion RyR1Y522S/wt mice can run without experiencing rhabdomyolysis, and their inability to adapt to training appears to stem from intrinsic enhancement of mitochondrial enzymes and fatigue resistance.
Rouviere, Clement; Corona, Benjamin T.; Ingalls, Christopher P.
Elderly patients commonly receive statin drugs for the primary or secondary prevention of cardiovascular and cerebrovascular events. Elderly patients also commonly receive antidepressant drugs, usually selective serotonin reuptake inhibitors (SSRIs), for the treatment of depression, anxiety, or other conditions. SSRIs are associated with many pharmacokinetic drug interactions related to the inhibition of the cytochrome P450 (CYP) metabolic pathways. There is concern that drugs that inhibit statin metabolism can trigger statin adverse effects, especially myopathy (which can be potentially serious, if rhabdomyolysis occurs). However, a detailed literature review of statin metabolism and of SSRI effects on CYP enzymes suggests that escitalopram, citalopram, and paroxetine are almost certain to be safe with all statins, and rosuvastatin, pitavastatin, and pravastatin are almost certain to be safe with all SSRIs. Even though other SSRI-statin combinations may theoretically be associated with risks, the magnitude of the pharmacokinetic interaction is likely to be below the threshold for clinical significance. Risk, if at all, lies in combining fluvoxamine with atorvastatin, simvastatin, or lovastatin, and even this risk can be minimized by using lower statin doses and monitoring the patient. PMID:24602259
Skeletal muscle necrosis is a common manifestation of viperid snakebite envenomations. Venoms from snakes of the genus Bothrops, such as that of B. asper, induce muscle tissue damage at the site of venom injection, provoking severe local pathology which often results in permanent sequelae. In contrast, the venom of the South American rattlesnake Crotalus durissus terrificus, induces a clinical picture of systemic myotoxicity, i.e., rhabdomyolysis, together with neurotoxicity. It is known that molecules released from damaged muscle might act as ‘danger’ signals. These are known as ‘alarmins’, and contribute to the inflammatory reaction by activating the innate immune system. Here we show that the venoms of B. asper and C. d. terrificus release the mitochondrial markers mtDNA (from the matrix) and cytochrome c (Cyt c) from the intermembrane space, from ex vivo mouse tibialis anterior muscles. Cyt c was released to a similar extent by the two venoms whereas B. asper venom induced the release of higher amounts of mtDNA, thus reflecting hitherto some differences in their pathological action on muscle mitochondria. At variance, injection of these venoms in mice resulted in a different time-course of mtDNA release, with B. asper venom inducing an early onset increment in plasma levels and C. d. terrificus venom provoking a delayed release. We suggest that the release of mitochondrial ‘alarmins’ might contribute to the local and systemic inflammatory events characteristic of snakebite envenomations.
Zornetta, Irene; Caccin, Paola; Fernandez, Julian; Lomonte, Bruno; Gutierrez, Jose Maria; Montecucco, Cesare
Abstract Context. In order to report the outcome of a patient who developed compartment syndrome after South American rattlesnake (Crotalus durissus terrificus) envenomation, confirmed by subfascial pressure measurement and magnetic resonance imaging (MRI). Case details. A 63-year-old male was admitted 1 h after being bitten on the right elbow by a "large" snake, which was not brought for identification. Physical and laboratory features upon admission revealed two fang marks, local tense swelling, paresthesia, intense local pain, hypertension, coagulopathy, and CK = 1530 U/L (RV < 170 U/L). The case was initially treated with bothropic antivenom (80 mL, intravenously), with no improvement. Evolution within 13-14 h post-bite revealed generalized myalgia, muscle weakness, palpebral ptosis, and severe rhabdomyolysis (CK = 126,160 U/L) compatible with envenoming by C. d. terrificus. The patient was then treated with crotalic antivenom (200 mL, intravenously), fluid replacement, and urine alkalinization. Twenty-four-hour post-bite MRI showed marked muscular edema in the anterior compartment of the right forearm, with a high subfascial pressure (40 mmHg) being detected 1 h later. ELISA of a blood sample obtained upon admission, before antivenom infusion, revealed a high serum concentration of C. d. terrificus venom. No fasciotomy was performed and the patient was discharged seven days later without sequelae. Conclusion. Snakebite by C. d. terrificus with subfascial venom injection may lead to increased intracompartmental pressure. PMID:24940645
Bucaretchi, F; De Capitani, E M; Hyslop, S; Mello, S M; Fernandes, C B; Bergo, F; Nascimento, F B P
Statins are widely used and have been proven to be effective in the prevention of atherosclerotic vascular disease events, primarily by reducing plasma low-density lipoprotein cholesterol concentrations. Although statins are generally well tolerated and present an excellent safety profile, adverse effects from muscle toxicity and liver enzyme abnormalities may occur in some patients. Myopathy and rhabdomyolysis are rare with statin monotherapy at the approved dose ranges, but the risk increases with use of higher doses, interacting drugs and genetic predisposition. Asymptomatic increases in liver transaminases with statin treatment do not seem to be associated with an increased risk of liver disease. Therefore, statin treatment can be safely used in patients with mild to moderately abnormal liver tests that are potentially attributable to nonalcoholic fatty liver disease and can improve liver tests and reduce cardiovascular morbidity in this group of patients. The risks of other unfavorable effects such as the slightly increased risk of new-onset diabetes and potentially increased risk of haemorrhagic stroke are much smaller than the cardiovascular benefits with the use of statins.
Hu, Miao; Cheung, Bernard M.Y.
Genetic polymorphisms may explain why certain individuals will develop exertional rhabdomyolysis (ER) or markedly elevated serum creatine kinase (CK) levels following exertion, while others in the same environment, performing the same exertion, do not. Prospectively, 499 recruits were evaluated during the initial fortnight of Army basic training. Serum CK levels were determined before and during that time. Eleven candidate genetic polymorphisms were studied and compared to CK levels. No subjects developed ER. Baseline CK was significantly greater in interleukin-6 G174C GG and myosin light chain kinase 2 (MLCK 2) AA subjects. Intertraining levels were significantly greater in angiotensin I-converting enzyme D/D and interleukin-6 GG subjects. Among African-Americans, those with MLCK2 AA had greater baseline CK (1,352 +/- 1,102.8 IU/L) than AC and CC genotypes (536.9 +/- 500.6). African-American men have the highest baseline levels and are more likely to have MLCK AA genotype. Whether this finding is associated with an increased incidence of ER requires further study. PMID:23198514
Landau, Mark E; Kenney, Kimbra; Deuster, Patricia; Gonzalez, Rodney S; Contreras-Sesvold, Carmen; Sambuughin, Nyamkhishig; O'Connor, Francis G; Campbell, William W
Exertional sickling from sickle cell trait (SCT) can pose a grave risk for some military recruits and is a troubling cause of death in college athletes. We report the cases of two U.S. Army recruits with undetected SCT who collapsed and soon died from metabolic complications of exertional sickling as they struggled to finish in time the 2-mile run of the Army Physical Fitness Test, having failed this test on prior attempts. These cases are similar to other military cases and to recent sickling deaths in college track and football. Research shows how and why, in the face of SCT, during intense exercise bouts, sickle cells can quickly form and lead to fulminant rhabdomyolysis that can be fatal. Increasing evidence suggests that, in the military and in sports, the proximate trigger for most cases of fatal sickling collapse is intensity. If this hypothesis is correct, that sickling collapse is an intensity syndrome, it raises vital questions about how best to train military recruits with SCT. PMID:22338981
Ferster, Kenneth; Eichner, E Randy
We report a case of drug-related toxicity after liver transplantation for hepatocellular carcinoma in a HIV-HCV co-infected patient. Before transplant the patient was on a triple antiretroviral therapy (zidovudine and lamivudine and efavirenz) with a stable CD4+ cell count >500 cells/microL. Liver transplantation was performed with a liver graft showing a 10% of macrosteatosis and with a graft-to-recipient body weight ratio of 1.3. Immunosuppression was achieved with tacrolimus, azathioprine and steroids. The antiretroviral therapy was resumed in the first postoperative day as the early graft function was in the normal range. After a few hours the patient showed myoglobinuria, rhabdomyolysis and a fast-deteriorating graft function. All drugs were withdrawn except steroids and an empiric therapy with riboflavin and glutathione was maintained for five days until myoglobinuria ended. Nevertheless the serum levels of tacrolimus remained in the therapeutic range for six days when it was reintroduced at a reduced dosage (0.01 mg/kg/die). The postoperative course was complicated by tense ascites and severe hyperbilirubinemia without any rejection episodes. The patient was discharged 48 days post-transplantation with a good liver function. During the following year no signs of aggressive HCV-HIV recurrences were observed and the patient is maintaining a CD4+ cells count >400 without antiretroviral therapy. PMID:15143883
Antonini, Mario; Ettorre, Giuseppe Maria; Vennarecci, Giovanni; D'Offizi, Gianpiero; Narciso, Pasquale; Del Nonno, Franca; Perracchio, Letizia; Visco, Giuseppe; Santoro, Eugenio
Plastoquinone, a very effective electron carrier and antioxidant of chloroplasts, was conjugated with decyltriphenylphosphonium to obtain a cation easily penetrating through membranes. This cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H(2) from its oxidized form that appears as a result of the antioxidant activity of SkQ1H(2). SkQ1H(2) prevents oxidation of cardiolipin, a mitochondrial phospholipid that is especially sensitive to attack by reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H(2)O(2)-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (cataract, retinopathies, achromotrichia, osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of ?-galactosidase, phosphorylation of H2AX histones, etc.) and (iii) lower tissue damage and save the lives of young animals after treatments resulting in kidney ischemia, rhabdomyolysis, heart attack, arrhythmia, and stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondria-mediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast "biochemical suicide" of an organism after a severe metabolic crisis. PMID:21269268
Skulachev, M V; Antonenko, Y N; Anisimov, V N; Chernyak, B V; Cherepanov, D A; Chistyakov, V A; Egorov, M V; Kolosova, N G; Korshunova, G A; Lyamzaev, K G; Plotnikov, E Y; Roginsky, V A; Savchenko, A Y; Severina, I I; Severin, F F; Shkurat, T P; Tashlitsky, V N; Shidlovsky, K M; Vyssokikh, M Y; Zamyatnin, A A; Zorov, D B; Skulachev, V P
Background Peripheral embolism to the lower extremities may mimic disc prolapse with severe consequences. Case report A 71-year-old male with a history of chronic alcoholism developed low back pain radiating to both lower extremities in a nonradicular distribution and bilateral dysesthesias of the distal lower legs after lifting a heavy weight. Given that magnetic resonance imaging (MRI) of the lumbar spine showed disc herniation in L3/4 and L4/5, he was scheduled for laminectomy but was unable to undergo surgery due to thrombocytopenia. After transfer to another hospital, persistence of symptoms and signs, absent pulses on the distal lower legs, and rhabdomyolysis with temporary renal insufficiency, peripheral embolism with compartment syndrome was suspected. Magnetic resonance angiography revealed occlusion of the right superficial femoral artery and long high-grade stenosis of the left superficial and profound femoral arteries and distal arteries. He successfully underwent embolectomy and fasciotomy. Conclusions If lumbar pain is not radicular, peripheral pulses are minimally palpable, and distal limbs are cold and show livid decolorization, peripheral embolism is much more likely than disc herniation, particularly if the patient’s history is positive for atrial fibrillation. MRI of the lumbar spine must be interpreted in conjunction with clinical presentation.
Bastovansky, Adam; Ziegler, Kathrin; Stollberger, Claudia; Finsterer, Josef
Abstract Rhabdomyolysis caused by severe burn releases extracellular myoglobin (Mb) that accumulates in the kidney and urine (maximum [Mb] approximately 50 microM) (termed myoglobinuria). Extracellular Mb can be a pro-oxidant. This study cultured Madin-Darby-canine-kidney-Type-II (MDCK II) cells in the presence of Mb and tested whether supplementation with a synthetic tert-butyl-polyphenol (tert-butyl-bisphenol; t-BP) protects these renal cells from dysfunction. In the absence of t-BP, cells exposed to 0-100 microM Mb for 24 h showed a dose-dependent decrease in ATP and the total thiol (TSH) redox status without loss of viability. Gene expression of superoxide dismutases-1/2, haemoxygenase-1 and tumour necrosis factor increased and receptor-mediated endocytosis of transferrin and monolayer permeability decreased significantly. Supplementation with t-BP before Mb-insult maintained ATP and the TSH redox status, diminished antioxidant/pro-inflammatory gene responses, enhanced monolayer permissiveness and restored transferrin uptake. Overall, bolstering the total antioxidant capacity of the kidney may protect against oxidative stress induced by experimental myoglobinuria. PMID:20528578
Shanu, Anu; Parry, Sarah N; Wood, Sarah; Rodas, Elicia; Witting, Paul K
In this article, de novo cholesterol synthesis, its inhibition by HMG-CoA reductase inhibitors (statins) and clinical pharmacology aspects of the statins have been reviewed. Statins are available in both active and pro-drug forms. Their affinity to bind and subsequently to inhibit HMG-CoA reductase activity is approximately 3 orders of magnitude higher than that of natural substrate (HMG-CoA). All members of this group of lipid-lowering agents are, to a varying degree, absorbed from the gut. However, their bioavailability depends on their lipophobicity and their concomitant use with meals. The interaction between HMG-CoA reductase inhibitors and other lipid-lowering agents has been reviewed in more detail. One major side-effect of lipid-lowering combination therapy is myopathy with or without rhabdomyolysis. Combination of statins with gemfibrozil seems to increase risk of this adverse event, particularly in patients with renal impairment, more than combination with other lipid-lowering agents. Combination therapy with other agents including anticoagulants, antihypertensive, anti-inflammatory, oral hypoglycemic and antifungal agents as well as beta-blockers, H2 blockers, cyclosporine and digoxin has been also reviewed. The pleiotropic non-lipid lowering properties of statins and their effects on the quality of lipoprotein particles, the activities of cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase as well as their possible synergistic effects with n-3 fatty acids, phytosterols, vitamin E and aspirin in reducing cardiovascular events warrant further investigation. PMID:10503952
Moghadasian, M H
We report the case of a 36-year-old woman who developed right upper and lower limb paralysis with sensory deficit after sedative drug overdose with prolonged immobilization. Due to the initial motor and sensory deficit pattern, brachial plexus injury or C8/T1 radiculopathy was suspected. Subsequent nerve conduction study/electromyography proved the lesion level to be brachial plexus. Painful swelling of the right buttock was suggestive of gluteal compartment syndrome. Elevation of serum creatine phosphokinase and urinary occult blood indicated rhabdomyolysis. The patient received medical treatment and rehabilitation; 2 years after the injury, her right upper and lower limb function had recovered nearly completely. As it is easy to develop complications such as muscle atrophy and joint contracture during the paralytic period of brachial plexopathy and lumbosacral plexopathy, early intervention with rehabilitation is necessary to ensure that the future limb function of the patient can be recovered. Our patient had suspected gluteal compartment syndrome that developed after prolonged compression, with the complication of concomitant lumbosacral plexus injury and brachial plexus injury, which is rarely reported in the literature. A satisfactory outcome was achieved with nonsurgical management. PMID:17116618
Kao, Chung-Lan; Yuan, Chia-Hei; Cheng, Yuan-Yang; Chan, Rai-Chi
Statins are widely used to treat hypercholesterolemia but can lead to a number of side effects in muscle, including rhabdomyolysis. Our recent findings implicated the induction of atrogin-1, a gene required for the development of muscle atrophy, in statin-induced muscle damage. Since statins inhibit many biochemical reactions besides cholesterol synthesis, we sought to define the statin-inhibited pathways responsible for atrogin-1 expression and muscle damage. We report here that lovastatin-induced atrogin-1 expression and muscle damage in cultured mouse myotubes and zebrafish can be prevented in the presence of geranylgeranol but not farnesol. Further, inhibitors of the transfer of geranylgeranyl isoprene units to protein targets cause statin muscle damage and atrogin-1 induction in cultured cells and in fish. These findings support the concept that dysfunction of small GTP-binding proteins lead to statin-induced muscle damage since these molecules require modification by geranylgeranyl moieties for their cellular localization and activity. Collectively, our animal and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be regulated by novel signaling pathways.—Cao, P., Hanai, J., Tanksale, P., Imamura, S., Sukhatme, V. P., Lecker, S. H. Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect.
Cao, Peirang; Hanai, Jun-ichi; Tanksale, Preeti; Imamura, Shintaro; Sukhatme, Vikas P.; Lecker, Stewart H.
It is generally accepted that mitochondrial production of reactive oxygen species is nonlinearly related to the value of the mitochondrial membrane potential with significant increment at values exceeding 150 mV. Due to this, high values of the membrane potential are highly dangerous, specifically under pathological conditions associated with oxidative stress. Mild uncoupling of oxidative phosphorylation is an approach to preventing hyperpolarization of the mitochondrial membrane. We confirmed data obtained earlier in our group that dodecylrhodamine 19 (C(12)R1) (a penetrating cation from SkQ family not possessing a plastoquinone group) has uncoupling properties, this fact making it highly potent for use in prevention of pathologies associated with oxidative stress induced by mitochondrial hyperpolarization. Further experiments showed that C(12)R1 provided nephroprotection under ischemia/reperfusion of the kidney as well as under rhabdomyolysis through diminishing of renal dysfunction manifested by elevated level of blood creatinine and urea. Similar nephroprotective properties were observed for low doses (275 nmol/kg) of the conventional uncoupler 2,4-dinitrophenol. Another penetrating cation that did not demonstrate protonophorous activity (SkQR4) had no effect on renal dysfunction. In experiments with induced ischemic stroke, C(12)R1 did not have any effect on the area of ischemic damage, but it significantly lowered neurological deficit. We conclude that beneficial effects of penetrating cation derivatives of rhodamine 19 in renal pathologies and brain ischemia may be at least partially explained by uncoupling of oxidation and phosphorylation. PMID:23157263
Plotnikov, E Y; Silachev, D N; Jankauskas, S S; Rokitskaya, T I; Chupyrkina, A A; Pevzner, I B; Zorova, L D; Isaev, N K; Antonenko, Y N; Skulachev, V P; Zorov, D B
Bruising is a frequent and often sentinel injury in children who are victims of physical abuse. Children who are evaluated in an emergency department for bruising, which may be due to abuse, present a challenge to physicians; the injuries themselves are medically minor and their severity can only be described qualitatively with photographs. Nonetheless, bruising in an infant or bruising in unusual locations in young children can indicate violence and risk. These children also present a challenge to the Child Protective Services system because the injuries generally resolve quickly without medical treatment and do not result in long-term sequelae. Creatine phosphokinase (CPK) is released from injured muscle and results in increased serum CPK concentrations. We report on a case of isolated bruising due to child physical abuse in which serum CPK concentrations were markedly increased, demonstrating clinically unsuspected rhabdomyolysis. The increased serum CPK concentrations provided important quantitative information about the seriousness of the bruising. A subsequent chart review of children evaluated by our hospital's child protection team for isolated bruising during a 6-year period demonstrated that there were other children with bruising due to abuse who also had increased serum CPK concentrations. This information suggests that increased serum CPK in children with bruising due to abuse may be more common than previously thought and that this information may have the potential to be used to provide quantitative, objective information about the seriousness of the bruising. We recommend that physicians consider measuring serum CPK in children with bruising due to physical abuse. PMID:23222104
Sussman, Stephanie; Squires, Janet; Stitt, Rodger; Zuckerbraun, Noel; Berger, Rachel P
Recently, the widely consumed yellow tricholoma Tricholoma flavovirens caused delayed rhabdomyolysis and fatalities in humans in France and Poland and triggered elevated plasma creatine kinase activities in mice. Furthermore, the highly appreciated king boletus (Boletus edulis) caused similar responses in experimental mice. Because of this, it was hypothesized that other fungi could also contain chemical compounds that would cause similar myotoxic effects. To test the suspected myotoxicity of other wild mushrooms consumed by tradition, 86 mice were exposed for 5 days to 3, 6, or 9 g/kg body mass/day of edible mushrooms representing diverse genera (Russula spp, Cantharellus cibarius, Albatrellus ovinus, and Leccinium versipelle) mixed with regular laboratory rodent diet. The plasma creatine kinase activity increased with all studied mushroom species at 9 g/kg body mass/day, whereas the histologic appearance of muscle and liver samples was unaffected. The results support the hypothesis that the previously observed toxic effects are not specific to T. flavovirens, but probably represent an unspecific response requiring individual sensitivity and a significant amount of ingested mushroom to manifest itself. PMID:16446499
Nieminen, Petteri; Kirsi, Markku; Mustonen, Anne-Mari
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
Bédry, R; Gromb, S
Acute compartment syndrome is a surgical emergency. A high index of suspicion is needed in cases of severe contusion, especially if patient complaints seem to outweigh physical findings. Acute surgical fasciotomy is an effective treatment and should be carried out expeditiously if compartment pressures are elevated over 70 mm Hg in order to avoid complications such as chronic disability due to contractures or rhabdomyolysis with acute renal failure. Chronic exertional compartment syndrome most often occurs in the anterior or the lateral compartment. Patients have only exercise-related symptoms and recover quickly after resting from the inciting activity. Diagnosis is difficult, but the anterior compartment pressure may be checked fairly readily with a handheld pressure catheter. Deep posterior compartment problems are harder to check because of the difficulty in reaching this area. Thallium stress testing appears promising for diagnosing both anterior and posterior problems and may augment, or even replace, the catheter measurement in the deep posterior and perhaps even the anterior compartment. Thallium stress testing is noninvasive and may be a more physiologic measurement. Fasciotomy may be indicated if conservative treatment lacks efficacy. For unknown reasons, the deep posterior compartment does not respond as quickly, or as well, to fasciotomy as the anterior compartment. PMID:10086040
Swain, R; Ross, D
With mixed dyslipidemia of the atherogenic dyslipidemia type, once the LDL-c objectives have been achieved through statin treatment, there is often a residual risk, for which the addition of a fibrate is recommended. The combination of statins and fibrates has been limited by the possibility of drug interactions, which mostly result in myopathy. Interactions between statins and other drugs are caused by pharmacokinetic mechanisms, mainly by changing the metabolism of statins in the CYP450 enzyme system, in the hepatic glucuronidation pathway or in the transporters responsible for statin distribution in tissues. The most significant adverse eff ect of statins is myopathy, which can also be induced by fibrates and is more frequent when the 2 drugs (statins and fibrates) are combined. This adverse eff ect manifests clinically as myalgia, muscle weakness, increased CK levels and, in its most severe form, rhabdomyolysis. This interaction mainly aff ects gemfibrozil due to its specific action on the CYP450 enzyme system and that interferes with the hepatic glucuronidation of statins by using the same isoenzymes and with organic anion transporters in the liver. When combining statins, we should use other fibric acid derivatives, preferably fenofibrate. PMID:25043540
Santos, Pedro González
Abstract Context. A new group of novel psychoactive substance, the N-methoxybenzyl (NBOMe) derivatives of substituted phenethylamine, has recently emerged on the drug market, among which 25I-NBOMe and 25B-NBOMe have previously been implicated in clinical intoxications and fatalities. We report two cases of acute intoxication associated with these substances. Case details. Two male patients (17 and 31 years of age) had ingested drugs labelled as 'NBOMe' or 'Holland film' and developed confusion, agitation, hypertension, tachycardia, hyperthermia, sweating and dilated pupils. Other features included convulsion, rhabdomyolysis and deranged liver function. The patients required benzodiazepines and other drugs for the control of symptoms. Urine samples from both patients were analysed using liquid-chromatography tandem mass spectrometry (LC-MS/MS) following glucuronidase digestion and solid-phase extraction. Identification was based upon comparison of the retention time and enhanced product ion scan with reference standards. In both urine samples, 25B-NBOMe was detected. Additionally, 25C-NBOMe was identified in one of the urine samples. Discussion. The NBOMe compounds are highly potent 5HT2A receptor agonists and are also agonists at alpha-adrenergic receptors, which likely account for their serotonergic and sympathomimetic symptoms. The clinical testing of NBOMe drugs is not commonly available. Clinicians as well as laboratory staff play an important role in facilitating the detection of this group of potentially dangerous emerging drugs. PMID:24779864
Tang, M H Y; Ching, C K; Tsui, M S H; Chu, F K C; Mak, T W L
Tropical Australia has an amazing diversity of venomous fauna, from "the world's most venomous creature," the multi-tentacled (chirodropid) box jellyfish Chironex fleckeri, to aggressive spiders whose venom remains to be characterized. All genera of highly venomous Australasian elapid snakes are present, except for tiger snakes. Most notable is the taipan (Oxyuranus scutellatus), with the most efficient "snap-release" biting mechanism of any snake and venom components causing the full constellation of clinical envenoming features: coagulopathy from fibrinogen depletion (procoagulant), neurotoxicity (predominantly presynaptic neurotoxin) and rhabdomyolysis (myotoxin). Brown snakes (Pseudonaja textilis and P. nuchalis) now account for most snake bite fatalities in Australia, as a result of severe coagulopathy and a poorly defined early scenario of collapse, postulated to be caused by profound hypotension caused by transient myocardial dysfunction associated with prothrombin activation. Other venomous entities include paralyzing ticks, the blue-ringed octopus, stone fish and other marine animals with venomous spines, paralyzing cone shells, and a wide range of jellyfish including Carukia barnesi and possibly other four-tentacled (carybdeid) box jellyfish causing the Irukandji syndrome. PMID:10688264
Currie, B J
Adverse reactions to genral anesthesia, which partly resembled malignant hyperthermia (MH), were more frequent in muscular dystrophy than in controls. In the present study, 35 cases so far reported in Duchenne or Becker muscular dystrophy (DMD or BMD) were analyzed and their pathogenesis was discussed. Cardiac involvements were sole manifestations in 7 cases. In other 28 cases, the acute rhabdomyolysis was the most prevailing manifestation. About 60% of myolysis cases were associated with muscle contracture (rigidity) or other hypermetabolic signs such as hypercapnia, hyperthermia and metabolic acidosis. Cases with BMD were more hyperthermic than with DMD. These results suggest Ca ion-induced hypermetabolic reactions are also present in dystrophinopathy, which have been assumed as core syndromes of the classical (gene-defined) MH. However, question whether the abnormal Ca ion is from the extracellular or intracellular stores is still unclear. Circumstancial evidences suggest that the Ca-induced Ca release (CICR) mechanism might also be involved. Endogenous redox modulators such as nitric oxide or reactive oxygen species in the dystrophic muscle might contribute to the perturbed Ca ion homeostasis. PMID:18326302
Takagi, Akio; Nakase, Hirofumi
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.
Sharkey, P K; Rinaldi, M G; Dunn, J F; Hardin, T C; Fetchick, R J; Graybill, J R
Lightning strike is a rare natural phenomenon, which carries a risk of dramatic medical complications to multiple organ systems and a high risk of fatality. The known complications include but are not limited to: myocardial infarction, arrhythmia, cardiac contusion, stroke, cutaneous burns, respiratory disorders, neurological disorders, acute kidney injury and death. We report a case of a healthy young man who suffered a lightning injury and discuss the cardiovascular complications of lightning injury, ranging from ECG changes to death. The patient in our case, a 27-year old previously healthy male, developed a syndrome of rhabdomyolysis and symptomatic cardiogenic pulmonary edema. Electrocardiographic findings included transient T-wave inversions, late transition shift and long QT. His clinical condition improved with supportive measures. Early recognition of lightning injury syndromes and anticipation of complications may help us improve outcomes for these patients. Evaluation of patients having experienced a lightning injury should include a minimum of a detailed history and physical examination, 12-lead ECG and drawing of baseline troponins. Prolonged electrocardiographical monitoring (for monitoring of ventricular arrhythmias) and assessment for signs and symptoms of hemodynamic compromise may be warranted.
McIntyre, William F; Simpson, Christopher S; Redfearn, Damian P; Abdollah, Hoshiar; Baranchuk, Adrian
Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefi ts with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identifi ed for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity.
Kim, Sun Young; Moon, Aree
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.
Nakata, Kensei; Sakata, Koh-ichi; Someya, Masanori; Miura, Katsutoshi; Hayashi, Junichi; Hori, Masakazu; Takagi, Masaru; Himi, Tetsuo; Kondo, Atsushi; Hareyama, Masato
A 15 year old girl with a family history of type 1 multiple endocrine adenomatosis presented with reversible neurological disturbances, hypoglycaemia and hyperinsulinaemia. Initial radiology was normal, but portal venous sampling suggested an insulinoma in the tail of the pancreas which was removed with conservation of the spleen. Hypoglycaemia persisted despite high doses of diazoxide and intravenous dextrose. A second laparotomy revealed a pancreatic endocrine tumour and sub-total pancreatectomy was performed. Histology revealed islet cell microadenomatosis. Hypoglycaemia persisted despite treatment with somatostatin analogues and 40% intravenous dextrose was required to maintain normoglycaemia. A possible lesion near the splenic hilum on computed tomographic scan was reported as a splenunculus although further peripheral, hepatic and portal venous sampling suggested hepatic or systemic lesions. A positron emission scan and selective visceral angiography suggested a lesion in the left upper quadrant. Acute lactic acidosis, rhabdomyolysis and renal failure supervened. Post mortem revealed the putative 'splenunculus' to be a residual insulinoma, whilst the splenic vein was thrombosed, accounting in part for discrepant venous sampling data. Hyperinsulinaemia in type 1 multiple endocrine adenomatosis may require more aggressive surgical and hormonal intervention than when dealing with solitary insulinomas. Insulinomas may mimic developmental abnormalities on computed tomographic scanning. Images Figure 1
Winocour, P. H.; Moriarty, K. J.; Hales, C. N.; Adams, J.; Reeve, R.; Wynick, D.; Allison, D.; Bloom, S. R.; Anderson, D. C.
HMG-CoA reductase inhibitors (statins) are the mainstay in the pharmacologic management of dyslipidemia. Since they are widely prescribed, their safety remains an issue of concern. Rosuvastatin has been proven to be efficacious in improving serum lipid profiles. Recently published data from the JUPITER study confirmed the efficacy of this statin in primary prevention for older patients with multiple risk factors and evidence of inflammation. Rosuvastatin exhibits high hydrophilicity and hepatoselectivity, as well as low systemic bioavailability, while undergoing minimal metabolism via the cytochrome P450 system. Therefore, rosuvastatin has an interesting pharmacokinetic profile that is different from that of other statins. However, it remains to be established whether this may translate into a better safety profile and fewer drug-drug interactions for this statin compared with others. Herein, we review evidence with regard to the safety of this statin as well as its interactions with agents commonly prescribed in the clinical setting. As with other statins, rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure. Asymptomatic liver enzyme elevations occur with rosuvastatin at a similarly low incidence as with other statins. Rosuvastatin treatment has also been associated with adverse effects related to the gastrointestinal tract and central nervous system, which are also commonly observed with many other drugs. Proteinuria induced by rosuvastatin is likely to be associated with a statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. Higher doses of rosuvastatin have been associated with cases of renal failure. Also, the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney. Furthermore, rhabdomyolysis, considered a class effect of statins, is known to involve renal damage. Concerns have been raised by findings from the JUPITER study suggesting that rosuvastatin may slightly increase the incidence of physician-reported diabetes mellitus, as well as the levels of glycated hemoglobin in older patients with multiple risk factors and low-grade inflammation. Clinical trials proposed no increase in the incidence of neoplasias with rosuvastatin treatment compared with placebo. Drugs that antagonize organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin are more likely to interact with this statin. Clinicians should be cautious when rosuvastatin is co-administered with vitamin K antagonists, cyclosporine (ciclosporin), gemfibrozil, and antiretroviral agents since a potential pharmacokinetic interaction with those drugs may increase the risk of toxicity. On the other hand, rosuvastatin combination treatment with fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin (rifampicin), or clopidogrel seems to be safe, as there is no evidence to support any pharmacokinetic or pharmacodynamic interaction of rosuvastatin with any of these drugs. Rosuvastatin therefore appears to be relatively safe and well tolerated, sharing the adverse effects that are considered class effects of statins. Practitioners of all medical practices should be alert when rosuvastatin is prescribed concomitantly with agents that may increase the risk of rosuvastatin-associated toxicity. PMID:20104931
Kostapanos, Michael S; Milionis, Haralampos J; Elisaf, Moses S
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.
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-Reglat, Annie; Fieschi, Marius; Sturkenboom, Miriam; van der Lei, Johan; Pariente, Antoine; Trifiro, Gianluca
Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines.
Paillet-Loilier, Magalie; Cesbron, Alexandre; Le Boisselier, Reynald; Bourgine, Joanna; Debruyne, Daniele
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.
Golomb, Beatrice A.; Evans, Marcella A.
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.
Ngoepe, Mpho; Choonara, Yahya E.; Tyagi, Charu; Tomar, Lomas Kumar; du Toit, Lisa C.; Kumar, Pradeep; Ndesendo, Valence M. K.; Pillay, Viness
Recent advances in biosensor design and sensing efficacy need to be amalgamated with research in responsive drug delivery systems for building superior health or illness regimes and ensuring good patient compliance. A variety of illnesses require continuous monitoring in order to have efficient illness intervention. Physicochemical changes in the body can signify the occurrence of an illness before it manifests. Even with the usage of sensors that allow diagnosis and prognosis of the illness, medical intervention still has its downfalls. Late detection of illness can reduce the efficacy of therapeutics. Furthermore, the conventional modes of treatment can cause side-effects such as tissue damage (chemotherapy and rhabdomyolysis) and induce other forms of illness (hepatotoxicity). The use of drug delivery systems enables the lowering of side-effects with subsequent improvement in patient compliance. Chronic illnesses require continuous monitoring and medical intervention for efficient treatment to be achieved. Therefore, designing a responsive system that will reciprocate to the physicochemical changes may offer superior therapeutic activity. In this respect, integration of biosensors and drug delivery is a proficient approach and requires designing an implantable system that has a closed loop system. This offers regulation of the changes by means of releasing a therapeutic agent whenever illness biomarkers prevail. Proper selection of biomarkers is vital as this is key for diagnosis and a stimulation factor for responsive drug delivery. By detecting an illness before it manifests by means of biomarkers levels, therapeutic dosing would relate to the severity of such changes. In this review various biosensors and drug delivery systems are discussed in order to assess the challenges and future perspectives of integrating biosensors and drug delivery systems for detection and management of chronic illness. PMID:23771157
Ngoepe, Mpho; Choonara, Yahya E; Tyagi, Charu; Tomar, Lomas Kumar; du Toit, Lisa C; Kumar, Pradeep; Ndesendo, Valence M K; Pillay, Viness
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
Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy.
Statins effectively lower low-density lipoprotein cholesterol (LDL-C), reducing cardiovascular morbidity and mortality. Most patients tolerate statins well, but approximately 10% to 20% experience side effects (primarily muscle-related) contributing to diminished compliance or discontinuation of statin therapy and subsequent increase in cardiovascular risk. Statin-intolerant patients require more effective therapies for lowering LDL-C. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a compelling target for LDL-C-lowering therapy. Evolocumab (AMG 145) is a fully human monoclonal antibody that binds PCSK9, inhibiting its interaction with the LDL receptor to preserve LDL-receptor recycling and reduce LDL-C. Phase 2 studies have demonstrated the safety, tolerability, and preliminary efficacy of subcutaneous evolocumab in diverse populations, including statin-intolerant patients. This article describes the rationale and design of the Goal Achievement After Utilizing an anti-PCSK9 Antibody in Statin-Intolerant Subjects 2 (GAUSS-2) trial, a randomized, double-blind, ezetimibe-controlled, multicenter phase 3 study to evaluate the effects of 12?weeks of evolocumab 140?mg every 2?weeks or 420?mg every month in statin-intolerant patients with hypercholesterolemia. Eligible subjects were unable to tolerate effective doses of ?2 statins because of myalgia, myopathy, myositis, or rhabdomyolysis that resolved with statin discontinuation. The primary objective of the study is to assess the effects of evolocumab on percentage change from baseline in LDL-C. Secondary objectives include evaluation of safety and tolerability, comparison of the effects of evolocumab vs ezetimibe on absolute change from baseline in LDL-C, and percentage changes from baseline in other lipids. Recruitment of approximately 300 subjects was completed in August 2013. PMID:24477778
Cho, Leslie; Rocco, Michael; Colquhoun, David; Sullivan, David; Rosenson, Robert S; Dent, Ricardo; Xue, Allen; Scott, Rob; Wasserman, Scott M; Stroes, Erik
Most mushroom intoxications become evident within 12 hours with vomiting and diarrhea. They can be divided into incidents with a short latency (less than four hours) and incidents with a long latency (longer than four hours). As a rule of thumb amatoxin poisonings must be considered in case of symptoms appearing with a long latency (8-12-18 h), especially after consumption of non-controlled wild mushrooms. Shorter latencies do not exclude amatoxin poisoning. Large meals of mushrooms, which are rich in chitin, mixed meals and individual factors, may shorten latency and disguise amatoxin poisoning. Any vomiting and diarrhea after mushroom consumption is suspicious. Unless the mushrooms are not to be identified within 30 minutes by an expert, specific treatment for amatoxin poisoning must be started. Identification shall be achieved by macroscopic or microscopic means; and urine analysis for amatoxins are crucial. By commencing treatment before analysis, mortality rates may be as low as 5%. Current standards in amatoxin poisoning treatment can be obtained at the Swiss Toxicological Information Centre (Phone 145), where contacts to mycologists are available as well. Emergency mycologists are listed on the website www.vapko.ch. Of the 18 different syndromes we present the most common and most important in Switzerland. In an overview all of them are listed. Early gastrointestinal syndrome with its short latency of less than 4 h and indigestion with a very variable latency are the most common. Psychotropic symptoms after consumptions of fly agaric and panther cap are rare, in case of psilocybin-containing mushrooms, symptoms are frequent, but hardly ever lead to medical treatment. In case of renal failure and rhabdomyolysis of unknown origin, completing a patient's history by questioning nutritional habits might reveal causal relationship with ingestion of orellanin-containing mushrooms or tricholoma equestre respectively. Mushrooms in the backyard are attractive for children. We discuss possible approaches. PMID:19401986
Flammer, René; Schenk-Jäger, Katharina M
In patients with mixed dyslipidemia characterized by increased triglycerides (TG), decreased high-density lipoprotein (HDL) cholesterol, and increased low-density lipoprotein (LDL) cholesterol, monotherapy with lipid-altering drugs often fails to achieve all lipid targets. This multicenter, double-blind, active-controlled study evaluated ABT-335 (fenofibric acid) in combination with 2 doses of atorvastatin in patients with mixed dyslipidemia. A total of 613 patients with LDL cholesterol > or =130 mg/dl, TG > or =150 mg/dl, and HDL cholesterol <40 mg/dl for men and <50 mg/dl for women were randomly assigned to ABT-335 (135 mg), atorvastatin (20, 40, or 80 mg), or combination therapy (ABT-335 + atorvastatin 20 or 40 mg) and treated for 12 weeks. Combination therapy with ABT-335 + atorvastatin 20 mg resulted in significantly greater improvements in TG (-45.6% vs -16.5%) and HDL cholesterol (14.0% vs 6.3%) compared with atorvastatin 20 mg and LDL cholesterol (-33.7% vs -3.4%) compared with ABT-335. Similarly, significantly greater improvements were observed with ABT-335 + atorvastatin 40 mg in TG (-42.1% vs -23.2%) and HDL cholesterol (12.6% vs 5.3%) compared with atorvastatin 40 mg and LDL cholesterol (-35.4% vs -3.4%) compared with ABT-335 monotherapy. Combination therapy also improved multiple secondary variables. Combination therapy was generally well tolerated with a safety profile consistent with those of ABT-335 and atorvastatin monotherapies. No rhabdomyolysis was reported. In conclusion, ABT-335 + atorvastatin combination therapy resulted in more effective control of multiple lipid parameters than either monotherapy and may be an appropriate therapy for patients with mixed dyslipidemia. PMID:19195513
Goldberg, Anne C; Bays, Harold E; Ballantyne, Christie M; Kelly, Maureen T; Buttler, Susan M; Setze, Carolyn M; Sleep, Darryl J; Stolzenbach, James C
Twenty free-ranging spectacled eiders (Somateria fischeri; 10 male, 10 female), 11 free-ranging king eiders (Somateria spectabilis; 6 male, 5 female), and 20 female common eiders (Somateria mollissima) were anesthetized with propofol, bupivacaine, and ketoprofen for the surgical implantation of satellite transmitters. Propofol was given to induce and maintain anesthesia (mean total dose, 26.2-45.6 mg/kg IV), bupivacaine (2-10 mg/kg SC) was infused into the incision site for local analgesia, and ketoprofen (2-5 mg/kg IM) was given at the time of surgery for postoperative analgesia. Four of 10 male spectacled eiders and 5 of 6 male king eiders died within 1-4 days after surgery. None of the female spectacled or common eiders and only 1 of the 5 female king eiders died during the same postoperative period. Histopathologic findings in 2 dead male king eiders were severe renal tubular necrosis, acute rhabdomyolysis, and mild visceral gout. Necropsy findings in 3 other dead male king eiders were consistent with visceral gout. We suspect that the perioperative use of ketoprofen caused lethal renal damage in the male eiders. Male eiders may be more susceptible to renal damage than females because of behavioral differences during their short stay on land in mating season. The combination of propofol, bupivacaine, and ketoprofen should not be used to anesthetize free-ranging male eiders, and nonsteroidal anti-inflammatory drugs should not be used perioperatively in any bird that may be predisposed to renal insufficiency.
Mulcahy, D. M.; Tuomi, P.; Larsen, R. S.
"Bath salts" is a well known street drug which can cause several cardiovascular and neuropsychiatric symptoms. However, only one case of acute kidney injury has been reported in the literature. We present a case with sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury following the use of bath salts. A 37-year-old man with past medical history of hypertension and depression was brought to the emergency center with body shaking. Three days before admission he injected 3 doses of bath salts intravenously and felt eye pain with blurry vision followed by a metallic taste, strange smells, profuse sweating, and body shaking. At presentation he had a sympathomimetic syndrome including high blood pressure, tachycardia, tachypnea, and hyperhydrosis with choreoathetotic movements. Laboratory testing revealed leukocytosis and acute kidney injury with a BUN of 95 mg/ dL and a creatinine of 15.2 mg/dL. Creatine kinase was 4,457 IU/dL. Urine drug screen is negative for amphetamine, cannabinoids, and cocaine; blood alcohol level was zero. During his ICU stay he became disoriented and agitated. Supportive treatment with 7.2 liters of intravenous fluid over 3 days, haloperidol, and lorazepam gradually improved his symptoms and his renal failure. Bath salts contain 3,4-methylenedioxypyrovalerone, a psychoactive norepinephrine and dopamine reuptake inhibitor. Choreoathetosis in this patient could be explained through dopaminergic effect of bath salts or uremic encephalopathy. The mechanism for acute kidney injury from bath salts may involve direct drug effects though norepinephrine and dopamine-induced vasoconstriction (renal ischemia), rhabdomyolysis, hyperthermia, and/or volume contraction. PMID:24356039
Sutamtewagul, Grerk; Sood, Vineeta; Nugent, Kenneth
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
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
Background Ezetimibe (Zetia®) is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia. Statin, an inhibitor of cholesterol synthesis, is the first-choice drug to reduce low-density lipoprotein-cholesterol (LDL-C) for patients with hypercholesterolemia, due to its strong effect to lower the circulating LDL-C levels. Because a high dose of statins cause concern about rhabdomyolysis, it is sometimes difficult to achieve the guideline-recommended levels of LDL-C in high-risk patients with hypercholesterolemia treated with statin monotherapy. Ezetimibe has been reported to reduce LDL-C safely with both monotherapy and combination therapy with statins. Results To investigate the effect of ezetimibe as "add-on" therapy to statin on hypercholesterolemia, we examined biomarkers and vascular endothelial function in 14 patients with hypercholesterolemia before and after the 22-week ezetimibe add-on therapy. Ezetimibe add-on therapy reduced LDL-C by 24% compared with baseline (p < 0.005), with 13 patients (93%) reaching their LDL cholesterol goals. Of the Ezetimibe add-on therapy significantly improved not only LDL-C, high-density lipoprotein-cholesterol (HDL-C), and apolipoprotein (apo)B levels, but also reduced levels of triglyceride (TG), the ratio of LDL/HDL-C, the ratio of apoB/apoA-I, and a biomarker for oxidative stress (d-ROMs). Furthermore, ezetimibe add-on therapy improved vascular endothelial function in high-risk patients with hypercholesterolemia. Conclusion In conclusion, ezetimibe as add-on therapy to statin might be a therapeutic good option for high-risk patients with atherosclerosis.
Yamaoka-Tojo, Minako; Tojo, Taiki; Kosugi, Rie; Hatakeyama, Yuko; Yoshida, Yuki; Machida, Yoji; Aoyama, Naoyoshi; Masuda, Takashi; Izumi, Tohru
Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines. PMID:24966713
Paillet-Loilier, Magalie; Cesbron, Alexandre; Le Boisselier, Reynald; Bourgine, Joanna; Debruyne, Danièle
Para-phenylenediamine (PPD) is a common chromophoric ingredient in oxidative hair-dyes. In some African countries like Sudan, Egypt and Morocco but also in India this chemical is used alone or in combination with colouring extracts like Henna for dyeing of the hair or the skin. Excessive dermal exposure to PPD mainly leads to the N-mono- and N,N?-diacetylated products (MAPPD, DAPPD) by N-acetyltransferase 1 and 2 (NAT1 and 2) catalyzed reactions. Metabolites and PPD are mainly excreted via renal clearance. Despite a low risk of intoxication when used in due form, there are numerous cases of acute intoxication in those countries every year. At the ENT Hospital - Khartoum (Sudan) alone more than 300 cases are reported every year (?10% fatal), mostly caused by either an accidental or intended (suicidal) high systemic exposure to pure PPD. Intoxication leads to a severe clinical syndrome including laryngeal edema, rhabdomyolysis and subsequent renal failure, neurotoxicity and acute toxic hepatitis. To date, there is no defined clinical treatment or antidote available and treatment is largely supportive. Herein, we show the development of a quick on-site identification assay to facilitate differential diagnosis in the clinic and, more importantly, the implementation of an advanced analytical platform for future in-depth investigations of PPD intoxication and metabolism is described. The current work shows a sensitive (?25 µM) wet chemistry assay, a validated MALDI-MS/MS and HPLC-UV assay for the determination of PPD and its metabolites in human urine. We show the feasibility of the methods for measuring PPD over a range of 50–1000 µM. The validation criteria included linearity, lower limit of quantification (LLOQ), accuracy and precision, recovery and stability. Finally, PPD concentrations were determined in clinical urine samples of cases of acute intoxication and the applied technique was expanded to identify MAPPD and DAPPD in the identical samples.
Hooff, Gero P.; van Huizen, Nick A.; Meesters, Roland J. W.; Zijlstra, Eduard E.; Abdelraheem, Mohamed; Abdelraheem, Waleed; Hamdouk, Mohamed; Lindemans, Jan; Luider, Theo M.
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.
La Guardia, P. G.; Alberici, L. C.; Ravagnani, F. G.; Catharino, R. R.; Vercesi, A. E.
Maternal microchimerism (MMc) can persist for years in a child, and has been implicated in the pathogenesis of chronic inflammatory autoimmune diseases. Chimeric cells may either contribute to disease by acting as immune targets or expand in response to signals of injury, inflammation or repair. We investigated the role of maternal cells in tissue injury in the absence of autoimmunity by quantifying MMc by quantitative PCR in acute and chronic models of renal injury: (1) reversible acute renal injury, inflammation and regeneration induced by rhabdomyolysis and (2) chronic injury leading to fibrosis after unilateral ureteral obstruction. We found that MMc is common in the mouse kidney. In mice congenic with their mothers neither acute nor chronic renal injury with fibrosis influenced the levels or prevalence of MMc. Maternal cells expressing MHC antigens not shared by offspring (H2b/d) were detected at lower levels in all groups of homozygous H2b/b or H2d/d offspring, with or without renal injury, suggesting that partial tolerance to low levels of alloantigens may regulate the homeostatic levels of maternal cells within tissues. Maternal cells homozygous for H2b were lost in H2b/d offspring only after acute renal failure, suggesting that an inflammatory stimulus led to loss of tolerance to homozygous maternal cells. The study suggests that elevated MMc previously found in association with human autoimmune diseases may not be a response to non-specific injury or inflammatory signals, but rather a primary event integral to the pathogenesis of autoimmunity.
Howsmon, Rebecca; Munro, Andrew; Blair, Kendall M; Fisher, Edward; Hermes, Heidi; Zager, Richard; Stevens, Anne M
Carnitine plays an essential role in the transfer of long-chain fatty acids across the inner mitochondrial membrane. This transfer requires enzymes and transporters that accumulate carnitine within the cell (OCTN2 carnitine transporter), conjugate it with long chain fatty acids (carnitine palmitoyl transferase 1, CPT1), transfer the acylcarnitine across the inner plasma membrane (carnitine-acylcarnitine translocase, CACT), and conjugate the fatty acid back to Coenzyme A for subsequent beta oxidation (carnitine palmitoyl transferase 2, CPT2). Deficiency of the OCTN2 carnitine transporter causes primary carnitine deficiency, characterized by increased losses of carnitine in the urine and decreased carnitine accumulation in tissues. Patients can present with hypoketotic hypoglycemia and hepatic encephalopathy, or with skeletal and cardiac myopathy. This disease responds to carnitine supplementation. Defects in the liver isoform of CPT1 present with recurrent attacks of fasting hypoketotic hypoglycemia. The heart and the muscle, which express a genetically distinct form of CPT1, are usually unaffected. These patients can have elevated levels of plasma carnitine. CACT deficiency presents in most cases in the neonatal period with hypoglycemia, hyperammonemia, and cardiomyopathy with arrhythmia leading to cardiac arrest. Plasma carnitine levels are extremely low. Deficiency of CPT2 present more frequently in adults with rhabdomyolysis triggered by prolonged exercise. More severe variants of CPT2 deficiency present in the neonatal period similarly to CACT deficiency associated or not with multiple congenital anomalies. Treatment for deficiency of CPT1, CPT2, and CACT consists in a low-fat diet supplemented with medium chain triglycerides that can be metabolized by mitochondria independently from carnitine, carnitine supplements, and avoidance of fasting and sustained exercise. PMID:16602102
Longo, Nicola; Amat di San Filippo, Cristina; Pasquali, Marzia
Abstract Background and Purpose: Because of recent advances in minimally invasive surgical techniques, robot-assisted radical prostatectomy (RARP) has become the primary treatment option in prostate cancer. RARP, however, necessitates patients to be placed in a steep Trendelenberg position, which presents multiple opportunities for complications relating to the positioning of the patient. Our study aims to study the prevalence and demographic predictors of these positioning complications and assess their impacts on length of stay (LOS) and total cost. Patients and Methods: We included patients who underwent RP from 2008 to 2009 using data extracted from the Nationwide Inpatient Sample database. Positioning complications (eye, nerve, compartment syndrome/rhabdomyolysis) were identified using patient-level diagnosis and procedural International Classification of Disease, 9th edition, Clinical Modification codes. Logistic regression models assessed relationships between demographic factors and occurrence of complications and the effects of them on prolonged LOS and total inpatient cost. Results: Positioning complications occurred in 0.4% of cases with eye complications contributing the most to this frequency. Laparoscopic RP procedure (odds ratio [OR]=2.88, P<0.01) and comorbidities (OR=2.34, P<0.01) were highly associated with increased odds of positioning complication occurrence, whereas RARP procedures (OR=0.93, P>0.4) were not associated with positioning complications. Having positioning complications increased a patient's odds of having increased inpatient costs and extended LOS by almost 400% and 300%, respectively. Conclusion: The steep Trendelenberg position used in RARP was not shown to be associated with patient positioning-related complications in this sample. The occurrence of positioning-related complications, however, places huge burdens on total inpatient costs and LOS. PMID:24428586
Wen, Timothy; Deibert, Christopher M; Siringo, Frank S; Spencer, Benjamin A
Myoglobinuric acute renal failure (ARF) is a uremic syndrome caused by traumatic or non-traumatic skeletal muscle breakdown and intracellular elements that are released into the bloodstream. We hypothesized that hyperbaric oxygen (HBO) therapy could be beneficial in the treatment of myoglobinuric ARF caused by rhabdomyolysis. A total of 32 rats were used in the study. The rats were divided into four groups: control, control+hyperbaric oxygen (control+HBO), ARF, and ARF+hyperbaric oxygen (ARF+HBO). Glycerol (8 ml/kg) was injected into the hind legs of each of the rats in ARF and ARF+HBO groups. 2.5 atmospheric absolute HBO was applied to the rats in the control+HBO and ARF+HBO groups for 90 min on two consecutive days. Plasma urea, creatinine, sodium, potassium, calcium, aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, creatinine kinase and urine creatinine and sodium were examined. Creatinine clearance and fractional sodium excretion could then be calculated. Superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) levels were assessed in renal tissue. Tissue samples were evaluated by Hematoxylin-eosin, PCNA and TUNEL staining histopathologically. MDA levels were found to be significantly decreased whereas SOD and CAT were twofold higher in the ARF+HBO group compared to the ARF group. Renal function tests were ameliorated by HBO therapy. Semiquantitative evaluation of histopathological findings indicated that necrosis and cast formation was decreased by HBO therapy and TUNEL staining showed that apoptosis was inhibited. PCNA staining showed that HBO therapy did not increase regeneration. Ultimately, we conclude that, in accordance with our hypothesis, HBO could be beneficial in the treatment of myoglobinuric ARF. PMID:22311626
Ayvaz, Suleyman; Aksu, Burhan; Kanter, Mehmet; Uzun, Hafize; Erboga, Mustafa; Colak, Alkin; Basaran, Umit Nusret; Pul, Mehmet
Metabolic myopathies are inborn errors of metabolism that result in impaired energy production due to defects in glycogen, lipid, mitochondrial, and possibly adenine nucleotide metabolism. Fatty acid oxidation defects (FAOD), glycogen storage disease, and mitochondrial myopathies represent the 3 main groups of disorders, and some consider myoadenylate deaminase (AMPD1 deficiency) to be a metabolic myopathy. Clinically, a variety of neuromuscular presentations are seen at different ages of life. Newborns and infants commonly present with hypotonia and multisystem involvement (liver and brain), whereas onset later in life usually presents with exercise intolerance with or without progressive muscle weakness and myoglobinuria. In general, the glycogen storage diseases result in high-intensity exercise intolerance, whereas the FAODs and the mitochondrial myopathies manifest predominately during endurance-type activity or under fasted or other metabolically stressful conditions. The clinical examination is often normal, and testing requires various combinations of exercise stress testing, serum creatine kinase activity and lactate concentration determination, urine organic acids, muscle biopsy, neuroimaging, and specific genetic testing for the diagnosis of a specific metabolic myopathy. Prenatal screening is available in many countries for several of the FAODs through liquid chromatography-tandem mass spectrometry. Early identification of these conditions with lifestyle measures, nutritional intervention, and cofactor treatment is important to prevent or delay the onset of muscle weakness and to avoid potential life-threatening complications such as rhabdomyolysis with resultant renal failure or hepatic failure. This article will review the key clinical features, diagnostic tests, and treatment recommendations for the more common metabolic myopathies, with an emphasis on mitochondrial myopathies. PMID:19258857
van Adel, Brian A; Tarnopolsky, Mark A
Background Massive wasp stings have been greatly underestimated and have not been systematically studied. The aim of this study was to identify the clinical features and treatment strategies of severe wasp stings. Methods and Findings A multicenter retrospective study was undertaken in 35 hospitals and medical centers including 12 tertiary care hospitals and 23 secondary care hospitals in the Hubei Province, China. The detailed clinical data of 1091 hospitalized wasp sting patients were investigated. Over three-fourths (76.9%) of the cases had 10 or more stings and the in-hospital mortality of patients was 5.1%. Forty-eight patients died of organ injury following toxic reactions to the stings, whereas six died from anaphylactic shock. The in-hospital mortality in patients with >10 stings was higher than that of ?10 stings (5.2% vs. 1.0%, p?=?0.02). Acute kidney injury (AKI) was seen in 21.0% patients and most patients required blood purification therapy. Rhabdomyolysis was seen in 24.1% patients, hemolysis in 19.2% patients, liver injury in 30.1% patients, and coagulopathy in 22.5% patients. Regression analysis revealed that high creatinine level, shock, oliguria, and anemia were risk factors for death. Blood purification therapy was beneficial for patients with ?20 stings and delayed hospital admission of patients (?4 hours after sting). Conclusions In China, most patients with multiple wasp stings presented with toxic reactions and multiple organ dysfunction caused by the venom rather than an anaphylactic reaction. AKI is the prominent clinical manifestation of wasp stings with toxic reaction. High creatinine levels, shock, oliguria, and anemia were risk factors for death.
Ding, Fengfei; Xie, Minjie; Lv, Jiagao; Yao, Jihua; Pan, Dengji; Sun, Qian; Liu, Chenchen; Chen, Tie; Li, Shusheng; Wang, Wei
Patients with very long-chain acyl-CoA dehydrogenase (VLCAD) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)/mitochondrial trifunctional protein (MTP) deficiency, disorders of the mitochondrial long-chain fatty acid oxidation, can present with hypoketotic hypoglycemia, rhabdomyolysis, and cardiomyopathy. In addition, patients with LCHAD/MTP deficiency may suffer from retinopathy and peripheral neuropathy. Until recently, there was no indication of intrauterine morbidity in these disorders. This observation was in line with the widely accepted view that fatty acid oxidation (FAO) does not play a significant role during fetal life. However, the high incidence of the gestational complications acute fatty liver of pregnancy and hemolysis, elevated liver enzymes, and low platelets syndrome observed in mothers carrying a LCHAD/MTP-deficient child and the recent reports of fetal hydrops due to cardiomyopathy in MTP deficiency, as well as the high incidence of intrauterine growth retardation in children with LCHAD/MTP deficiency, suggest that FAO may play an important role during fetal development. In this study, using in situ hybridization of the VLCAD and the LCHAD mRNA, we report on the expression of genes involved in the mitochondrial oxidation of long-chain fatty acids during early human development. Furthermore, we measured the enzymatic activity of the VLCAD, LCHAD, and carnitine palmitoyl-CoA transferase 2 (CPT2) enzymes in different human fetal tissues. Human embryos (at d 35 and 49 of development) and separate tissues (5-20 wk of development) were used. The results show a strong expression of VLCAD and LCHAD mRNA and a high enzymatic activity of VLCAD, LCHAD, and CPT2 in a number of tissues, such as liver and heart. In addition, high expression of LCHAD mRNA was observed in the neural retina and CNS. The observed pattern of expression during early human development is well in line with the spectrum of clinical signs and symptoms reported in patients with VLCAD or LCHAD/MTP deficiency. PMID:15845636
Oey, Nadia A; den Boer, Margarethe E J; Wijburg, Frits A; Vekemans, Michel; Augé, Joëlle; Steiner, Céline; Wanders, Ronald J A; Waterham, Hans R; Ruiter, Jos P N; Attié-Bitach, Tania
The object of this review is to provide the definitions and criteria for diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS), and convey current knowledge of the causes of permanent disability or mortality from complications of these conditions, of the risk factors for DKA and HHS, and of early indicators and contemporary treatment of suspected cerebral edema. The frequency of DKA at onset of type 1 diabetes mellitus (DM1) varies from 10-70%, depending on availability of health care and frequency of diabetes. At the onset of type 2 diabetes (DM2), DKA occurs in 5-52%. One study reported HHS in approximately 4% of new patients with DM2. Recurrent DKA rates are equally dependent on variability in medical services and socio-economic circumstances, and are estimated to be eight episodes per 100 patient years, with 20% of patients accounting for 80% of the episodes. Mortality for each episode of DKA internationally varies from 0.15-0.31%, with idiopathic cerebral edema accounting for two-thirds or more of this mortality. Other causes of death or disability include untreated DKA or HHS, hypokalemia, hypophosphatemia, hypoglycemia, other intracerebral complications, peripheral venous thrombosis, mucormycosis, rhabdomyolysis, acute pancreatitis, acute renal failure, sepsis, aspiration pneumonia, and other pulmonary complications. Population-based studies from the UK, Australia, the USA, and Canada report cerebral edema incidence in DKA of 0.5-2.0%. Published information does not support the notion that treatment factors are causal in cerebral edema. Younger age, greater severity of acidosis, degree of hypocapnia, and severity of dehydration have been suggested as risk factors in several studies. Bimodal distribution of the time of onset of cerebral edema and wide variation in brain imaging findings suggest the variability and likely multiple causation of the clinical picture. Functional brain scanning has indicated that DKA is accompanied by increased cerebral blood flow suggesting that the predominant mechanism of edema formation is a vasogenic process. A method of monitoring for diagnostic and major and minor signs of cerebral edema has been proposed and tested which indicates that intervention will be required in five individuals to provide early intervention for a single case of cerebral edema. The preferred intervention of mannitol infusion has typically been accompanied by intubation and hyperventilation, but recent evidence indicates outcome is adversely affected by aggressive hyperventilation. The prevention of DKA and HHS at the onset of diabetes mellitus requires a high degree of awareness and suspicion by primary care providers; prevention of recurrent DKA necessitates a diligent team effort. PMID:17315523
Rosenbloom, Arlan L
Aims Niacin has potentially favourable effects on lipids, but its effect on cardiovascular outcomes is uncertain. HPS2-THRIVE is a large randomized trial assessing the effects of extended release (ER) niacin in patients at high risk of vascular events. Methods and results Prior to randomization, 42 424 patients with occlusive arterial disease were given simvastatin 40 mg plus, if required, ezetimibe 10 mg daily to standardize their low-density lipoprotein (LDL)-lowering therapy. The ability to remain compliant with ER niacin 2 g plus laropiprant 40 mg daily (ERN/LRPT) for ?1 month was then assessed in 38 369 patients and about one-third were excluded (mainly due to niacin side effects). A total of 25 673 patients were randomized between ERN/LRPT daily vs. placebo and were followed for a median of 3.9 years. By the end of the study, 25% of participants allocated ERN/LRPT vs. 17% allocated placebo had stopped their study treatment. The most common medical reasons for stopping ERN/LRPT were related to skin, gastrointestinal, diabetes, and musculoskeletal side effects. When added to statin-based LDL-lowering therapy, allocation to ERN/LRPT increased the risk of definite myopathy [75 (0.16%/year) vs. 17 (0.04%/year): risk ratio 4.4; 95% CI 2.6–7.5; P < 0.0001]; 7 vs. 5 were rhabdomyolysis. Any myopathy (definite or incipient) was more common among participants in China [138 (0.66%/year) vs. 27 (0.13%/year)] than among those in Europe [17 (0.07%/year) vs. 11 (0.04%/year)]. Consecutive alanine transaminase >3× upper limit of normal, in the absence of muscle damage, was seen in 48 (0.10%/year) ERN/LRPT vs. 30 (0.06%/year) placebo allocated participants. Conclusion The risk of myopathy was increased by adding ERN/LRPT to simvastatin 40 mg daily (with or without ezetimibe), particularly in Chinese patients whose myopathy rates on simvastatin were higher. Despite the side effects of ERN/LRPT, among individuals who were able to tolerate it for ?1 month, three-quarters continued to take it for ?4 years.
Haynes, Richard; Jiang, Lixin; Hopewell, Jemma C; Li, Jing; Chen, Fang; Parish, Sarah; Landray, Martin J.; Collins, Rory; Armitage, Jane; Collins, R.; Armitage, J.; Baigent, C.; Chen, Z.; Landray, M.; Chen, Y.; Jiang, L.; Pedersen, T.; Landray, M.; Bowman, L.; Chen, F.; Hill, M.; Haynes, R.; Knott, C.; Rahimi, K.; Tobert, J.; Sleight, P.; Simpson, D.; Parish, S.; Baxter, A.; Lay, M.; Bray, C.; Wincott, E.; Leijenhorst, G.; Skattebol, A.; Moen, G.; Mitchel, Y.; Kuznetsova, O.; MacMahon, S.; Kjekshus, J.; Hill, C.; Lam, T.H.; Sandercock, P.; Peto, R.; Hopewell, J.C.
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+.
Abstract Context. 5-(2-aminopropyl)indole (5-IT) is a new psychoactive substance (NPS; "legal high" or "research chemical") structurally related to indoleamines and substituted phenethylamines and implicated in several fatalities. We describe the clinical characteristics and results of laboratory investigations of 14 analytically confirmed nonfatal cases of 5-IT intoxication within the Swedish STRIDA project. Study design. Observational case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals in Sweden in 2012. Patients and methods. Blood and/or urine samples were collected from intoxicated patients presenting to emergency departments and intensive care units over the country. Analysis of NPS was performed using an LC-MS/MS multi-component method. Clinical data were collected when caregivers consulted the Poisons Information Centre and also retrieved from medical records. The severity of poisoning was graded retrospectively using the Poisoning Severity Score (PSS). Results. Eleven male and three female patients (age: 21-53 years, median: 27) tested positive for 5-IT in 2012, all cases appearing in April-July. The 5-IT concentration in serum ranged between 0.015 and 0.59 ?g/mL (median: 0.22; n = 8) and in urine between 0.005 and 24.7 ?g/mL (median: 5.95; n = 12). Five intoxications were indicated to be caused by 5-IT alone, whereas additional psychoactive substances were detected in the other nine cases. Six (43%) of fourteen cases were graded as severe (PSS 3), five (36%) as moderate (PSS 2), and three (21%) as minor (PSS 1) poisonings. In the severe cases, agitation, hallucinations, dilated pupils without light reaction, tachycardia, hypertension, hyperthermia, myoclonus, muscle rigidity, arrhythmias, seizures, rhabdomyolysis, and/or renal failure were noted. Conclusions. The results demonstrated that severe clinical toxicity was commonly present in patients with analytically confirmed 5-IT exposure. The clinical features are consistent with a sympathomimetic toxidrome, and some patients also displayed symptoms associated with serotonin toxicity. PMID:24895941
Bäckberg, M; Beck, O; Hultén, P; Rosengren-Holmberg, J; Helander, A
Introduction Distigmine, a long-acting anti-cholinesterase, is associated with side effects such as Parkinsonism, cholinergic crisis, and rhabdomyolysis. We report a spinal cord injury patient, who developed marked hydronephrosis and hydroureter after distigmine therapy, which led to a series of complications over subsequent years. Case presentation A 38-year-old male developed T-9 paraplegia in 1989. Intravenous urography, performed in 1989, showed normal kidneys, ureters and bladder. He was prescribed distigmine bromide orally and was allowed to pass urine spontaneously. In 1992, intravenous urography showed bilateral marked hydronephrosis and hydroureter. Distigmine was discontinued. He continued to pass urine spontaneously. In 2006, intravenous urography showed moderate dilatation of both pelvicalyceal systems and ureters down to the level of urinary bladder. This patient was performing self-catheterisation only once a day. He was advised to do catheterisations at least three times a day. In December 2008, this patient developed haematuriawhich lasted for nearly four months.. He received trimethoprim, then cephalexin, followed by Macrodantin, amoxicillin and ciprofloxacin. In February 2009, intravenous urography showed calculus at the lower pole of left kidney. Both kidneys were moderately hydronephrotic. Ureters were dilated down to the bladder. Dilute contrast was seen in the bladder due to residual urine. This patient was advised to perform six catheterisations a day, and take propiverine hydrochloride 15 mg, three times a day. Microbiology of urine showed Klebsiella oxytoca, Pseudomonas aeruginosa, and Enterococcus faecalis. Cystoscopy revealed papillary lesions in bladder neck and trigone. Transurethral resection was performed. Histology showed marked chronic cystitis including follicular cystitis and papillary/polypoid cystitis. There was no evidence of malignancy. Conclusion Distigmine therapy resulted in marked bilateral hydronephrosis and hydroureter. Persistence of hydronephrosis after omitting distigmine, and presence of residual urine in bladder over many years probably predisposed to formation of polypoid cystitis and follicular cystitis, and contributed to prolonged haematuria, which occurred after an episode of urine infection. This case illustrates the dangers of prescribing distigmine to promote spontaneous voiding in spinal cord injury patients. Instead of using distigmine, spinal cord injury patients should be advised to consider intermittent catheterisation together with oxybutynin or propiverine to achieve complete, low-pressure emptying of urinary bladder.
Mansour, Paul; Soni, Bakul M; Hughes, Peter L; Singh, Gurpreet; Oo, Tun
While the crucial role of haemoglobin in aerobic exercise has been well accepted, there is still a great deal of controversy about the optimal haematological parameters in the athletic population. The initial part of this review will examine the question of anaemia in athletes. The most common finding in athletes is a dilutional pseudoanaemia that is caused by a plasma volume expansion, rather than an actual blood loss. It is not a pathological state and normalises with training cessation in 3 to 5 days. This entity should be distinguished from conditions associated with lowered blood counts, such as intravascular haemolysis or iron deficiency anaemia. The evaluation of true anaemia states in the athlete must take into account not only blood losses secondary to exercise, such as foot strike haemolysis or iron losses through sweat, but non-athletic causes as well. Depending on the age and sex of the athlete, consideration must be given to evaluation of the gastrointestinal or genitourinary systems for blood loss. Finally, a comprehensive nutritional history must be taken, as athletes, especially women, are frequently not consuming adequate dietary iron. The second section of the paper will deal with the very contentious issue of sickle cell trait. While there have been studies demonstrating an increased risk of sudden death in people with sickle cell trait, it is still quite rare and should not be used as a restriction to activity. Further, studies have demonstrated that patients with sickle cell trait have an exercise capacity that is probably normal or near normal. However, in the cases of sudden death, it has been secondary to rhabdomyolysis occurring among sickle cell trait athletes performing at intense exertion under hot conditions, soon after arriving at altitude. The recommendations are that athletes with sickle cell trait adhere to compliance with the general guidelines for fluid replacement and acclimatisation to hot conditions and altitude. The final section of the paper examines the issue of haematological manipulation for the purposes of ergogenic improvement. Although experiments with blood doping revealed improvements in running time to exhaustion and maximal oxygen uptake, the introduction of recombinant erythropoietin has rendered blood doping little more than a historical footnote. However, the improvements in performance are not without risk, and the use of exogenous erythropoietin has the potential for increased viscosity of the blood and thrombosis with potentially fatal results. Until a definitive test is developed for detection of exogenous erythropoietin, it will continue to be a part of elite athletics. PMID:10688281
Shaskey, D J; Green, G A
The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy. PMID:1659647
Love, L A; Leff, R L; Fraser, D D; Targoff, I N; Dalakas, M; Plotz, P H; Miller, F W
Background/Aims Statins are the mainstay of lipid-lowering therapy in contemporary medicine because of their well-established efficacy for reducing cardiovascular disease (CVD) morbidity and mortality in various at-risk populations. However, as many as 20% of individuals with a clinical indication for statin therapy are unable to take a daily statin due to some degree of intolerance. It is unknown what the most appropriate treatment is for these patients. We analyzed how this cohort of patients at high risk for cardiovascular morbidity and mortality is managed in contemporary cardiology. Methods Using our electronic health record (EHR) database, EPIC software, we identified patients who were older than 18 years with a high-risk indication for statin therapy; known coronary artery disease, known atherosclerotic disease, or diabetes. We identified those patients as statin intolerant if they had no recent history of statin use and were documented to have been prescribed at least one statin in the past. Results A total of 63,624 high-risk patients met the eligibility criteria, with over 85% (54,536 patients) receiving a statin, although 5.1% (2,794 patients) were taking a ubiquinol supplement. Of the 9,088 (14.3%) statin intolerant patients, ~1/3 had tried 2 or more statins. Only 21% (1879 patients) were identified as having a statin allergy and 48 (0.5%) had a history of rhabdomyolysis with statin use. We found that 4448 patients (48.9%) were on alternative lipid-lowering medications with omega 3 supplements being most common (28.3%, 1257 patients) followed by ezetimibe (17.2%, 764 patients), fibrates (10.8%, 482 patients), and niacin (5.2%, 229 patients). Conclusions Management of statin intolerance in a high-risk contemporary cohort of patients is challenging for modern-day health care providers. No strategies have been studied to assess long-term outcomes leading to marked variability in management. A clinical trial is warranted to assess the best treatment approach for this subset of the population who are at high risk for adverse cardiac events.
Saeed, Bilal; Wright, Eric; Evans, Michael; Lewis, Meredith; Steinhubl, Steven
This study reports on acute renal failure (ARF) due to multiple stings by Africanized bees (AB) occurring in 43 cases collected between 1982 and 2007 (at the Nephrology Section, University of Antioquia School of Medicine and San Vicente de Paul University Hospital, Medellin, Colombia). No intervention on patient care was performed except for responding the Nephrology consult and prescribing dialysis. Data obtained from the medical records included demography; clinical presentation; laboratory results on admission; evolution of renal function to document improvement and normalization; intervals between stings and outcomes; number of dialysis sessions; length of follow-up and hospitalization; survival; and mortality. Not all patients had complete data and therefore, the number of observations is included where required. Mean age was 56 ± 26 yr (range 2-96); 37 (86%) were men; 38 (of 41 cases) came from rural areas (91%); 22 (of 39) were farmers (56.4%); 33 (of 41) lived in Medellin or in the department of Antioquia (80.5%). Number of stings per patient: ~ 900. Interval between stings and ARF < 48 hours: in 31 cases (72.1%; mean 2.6 ± 2.6 days; range 1-12); 37 (of 43) required dialysis (86%); mean number of sessions: 4.7 ± 3.3 (range 1-12). Survival occurred in 36 cases (83.7%) and mortality, in 7, all > 60 yr (16.3%). At last follow-up, renal function improvement was documented in 36 (83.7%) and normalization in 15 of them (41.7%). Interval until initiation of diuresis: 10.6 ± 6.8 days (range 1-25). Duration of hospitalization: 16.9 ± 8.7 days (range 1-39). Follow-up: 25.2 ± 18.3 days (range 1-75). Hematuria and oliguria occurred before 24 hours; there was an increase of CPK in 90%, of ALT in 96%, of AST in 89%, of DHL in 95%, and of BUN and creatinine in 100%. Based on our findings and on the review of the available information, we propose that this type of ARF occurs as a result of rhabdomyolysis with subsequent myoglobinuria, which lead to nephrotoxic acute tubular necrosis; a variable degree of direct nephrotoxicity, not quantifiable with current diagnostic methods, is also probably involved. A better knowledge of this entity by the medical community could improve care and prognosis of the patients who develop it. PMID:20613852
Mejía Vélez, G
Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should be interpreted considering the athlete's body-mass index (BMI) and phase of the competitive season; use of cystatin C could be a reliable alternative to creatinine. Exercise and training induce adaptations in glucose metabolism which improve glucose utilization in athletes and are beneficial for reducing insulin insensitivity in nonathletes. Glucose metabolism differs slightly for different sports disciplines, as revealed in laboratory levels. Sport activities induce a blood lipid profile superior to that of sedentary subjects. There are few reports for a definitive conclusion, however. The differences between athletes and sedentary subjects are mainly due to high-density lipoprotein cholesterol (HDLC) concentrations in physically active individuals, although some differences among sport disciplines exist. The effect of sports on serum and urinary markers for bone metabolism is not univocal; further studies are needed to establish the real and effective influence of sport on bone turnover and especially to establish its beneficial effect. PMID:22397027
Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna
1. It has long been thought that death adder venoms are devoid of myotoxic activity based on studies done on Acanthophis antarcticus (Common death adder) venom. However, a recent clinical study reported rhabdomyolysis in patients following death adder envenomations, in Papua New Guinea, by a species thought to be different to A. antarcticus. Consequently, the present study examined A. rugosus (Irian Jayan death adder) venom for myotoxicity, and isolated the first myotoxin (acanmyotoxin-1) from a death adder venom. 2. A. rugosus (10-50 micro g ml(-1)) and acanmyotoxin-1 (MW 13811; 0.1-1 micro M) were screened for myotoxicity using the chick directly (0.1 Hz, 2 ms, supramaximal V) stimulated biventer cervicis nerve-muscle (CBCNM) preparation. A significant contracture of skeletal muscle and/or inhibition of direct twitches were considered signs of myotoxicity. This was confirmed by histological examination. 3. High phospholipase A(2) (PLA(2)) activity was detected in both A. rugosus venom (140.2+/-10.4 micro mol min(-1) mg(-1); n=6) and acanmyotoxin-1 (153.4+/-11 micro mol min(-1) mg(-1); n=6). Both A. rugosus venom (10-50 micro g ml(-1)) and acanmyotoxin-1 (0.1-1 micro M) caused dose-dependent inhibition of direct twitches and increase in baseline tension (n=4-6). In addition, dose-dependent morphological changes in skeletal muscle were observed. 4. Prior incubation (10 min) of CSL death adder antivenom (5 units ml(-1); n=4) or inactivation of PLA(2) activity with 4-bromophenacyl bromide (1.8 mM; n=4) prevented the myotoxicity caused by acanmyotoxin-1 (1 micro M). 5. Acanmyotoxin-1 (0.1 micro M; n=4) displayed no significant neurotoxicity when it was examined using the indirectly (0.1 Hz, 0.2 ms, supramaximal V) stimulated CBCNM preparation. 6. In conclusion, clinicians may need to be mindful of possible myotoxicity following death adder envenomation in Irian Jaya. PMID:12540524
Wickramaratna, Janith C; Fry, Bryan G; Aguilar, Marie-Isabel; Kini, R Manjunatha; Hodgson, Wayne C
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.
Scarpioni, Roberto; Ricardi, Marco; Albertazzi, Vittorio; Melfa, Luigi
Recent advances in medical and device therapies in heart failure have improved the survival of patients with heart failure. However, due to the limited availability of suitable heart donors, left ventricular assist devices (LVADs) have become an important tool as a bridge-to-heart transplantation for patients with refractory heart failure in Singapore. We report our experience with the HeartMate II (HMII) LVAD (Thoratec Corporation, Pleasanton, CA, USA) as a bridge-to-heart transplant in our center from 2009 to 2012. This was a retrospective review of 23 consecutive patients who underwent HMII LVAD implantation in our center between May 2009 and December 2012. All patients were classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels 1 to 3 and underwent LVAD implantation as a bridge-to-heart transplant. There were 17 male and 6 female patients. The mean age was 43.6 years old (range 14 to 64). The etiologies of heart failure included ischemic heart disease , idiopathic dilated cardiomyopathy , viral myocarditis , and chemotherapy-induced cardiomyopathy . Nine patients were INTERMACS level 1, 12 patients level 2, and two patients level 3. All patients successfully underwent HMII LVAD implantation. There was no mortality within the first 30 postoperative days. Postoperative complications included stroke with full neurological recovery (21.7%), mediastinal infection (21.7%), cardiac tamponade or mediastinal collection requiring reopening of the chest (39.1%), cardiac arrhythmia (13.0%), and pump thrombosis with pump replacement (4.3%). All patients were discharged from hospital after LVAD implantation. Three patients experienced driveline infections during outpatient follow-up. There were 19 readmissions due to the following conditions: sub-therapeutic anticoagulation (13.0%), gastrointestinal bleeding (13.0%), suspected pump thrombosis (13.0%), transient ischemic attack (8.7%), arrhythmia (8.7%), congestive cardiac failure due to severe aortic regurgitation (8.7%), right ventricular failure (4.3%), rhabdomyolysis (4.3%), and hematuria (4.3%). Post-LVAD implantation, 20 patients were functionally New York Heart Association (NYHA) class I, while 3 reported NYHA III symptoms. Three patients were successfully bridged to heart transplantation. One patient was successfully explanted 11 months after LVAD implantation. There were two mortalities during the follow-up period. The average duration of LVAD support was 522 days (range 47 to 1316 days). The HeartMate II LVAD has proven to be effective in our Asian population. Driveline infection rate remains low even in the tropical hot, humid climate in Singapore. With more patients ending up on extended periods of LVAD support, increased emphasis in the detection and management of long-term complications of ventricular assist devices will be needed. PMID:24392937
Lim, Choon Pin; Sivathasan, Cumaraswamy; Tan, Teing Ee; Lim, Chong Hee; Kerk, Ka Lee; Sim, David Kheng Leng
Sudden unexpected natural death (SUND) has several characteristics, such as unknown clinical history, very short course to death, evidence of trauma, interference of postmortem changes and social implications of diagnosis. From these points, SUND involves important challenges in forensic pathology. Presented here are the highlights of our SUND studies which allow scientific speculation into the antemortem pathophysiological course to death and a subsequent accurate diagnosis of the cause of death in SUND cases. 1. Forensic problems of SUND of unknown etiology 1) Do sudden infant death syndrome (SIDS) studies continue endlessly? In Japan there are many cases of sudden unexpected infant death (SUID) which were regarded as SIDS, often without postmortem examination. Pure SIDS should be a diagnosis of exclusion under thorough postmortem examination. Additionally, many SIDS studies have focused on pathogenesis of pure SIDS based on the analysis of so-called SIDS cases described above. In this sense, SIDS studies may continue forever. To clarify whether SIDS is an onion type, that is a heterogeneous disease entity, or bamboo shoot type, a single disease entity with a single cause, it is more vital to accurately search autopsy findings to exclude the cause of death, rather than to study pathogenesis of SIDS. Thereafter, pure SIDS will be carved in relief and we could study the pathogenesis, if it remains in the future. Present in 40% of our SUID cases examined was the existence of viral infection as a cause of death. 2) Pokkuri disease It has long been believed that the main branches of coronary arteries in Pokkuri-disease cases are macroscopically hypoplastic and cause sudden cardiac death. However, our two-dimensional morphometric analysis of the main branches, such as wall thickness, degree of stenosis, lumen area, area within internal elastic lamina, showed no significant differences between Pokkuri-disease cases and age and sex-matched control cases. 2. Information for grasping antemortem pathophysiological state in SUND cases 1) Standardization of the degree of cardiac hypertrophy based on heart weight. In the course of our preliminary examination, we found that heart weight correlates significantly with body length and weight. Therefore, we tried to standardize the range of normotrophy, hypertrophy and hypoplasia/atrophy of the heart based on the correlation between heart weight and body type index calculated by body length and weight (Broca's index). 2) Evaluation of the clinical laboratory data in cadaveric blood. We examined 32 clinical laboratory parameters in cadaveric blood samples obtained from 192 autopsy cases. Behaviour of the laboratory parameters in cadaveric blood in relation to postmortem interval was divided into four types: increased, decreased, no particular tendency and remaining between upper and lower normal value. Parameters included in the last type, which is a useful tool for speculation of antemortem pathophysiology were T-Bil, TTT, ZTT, BUN, Cre, UA, alpha 1- and beta 2-microglobin, T-Chol, GHA1c, TP, A/G, Hb and Hct. A case was demonstrated in which values of clinical laboratory parameters in agonar stage were the same as in cadaveric blood obtained at autopsy. This indicates that caution is necessary in evaluating clinical laboratory data in agonar patients in the emergency room. 3) Diagnostic evaluation of immunohistochemical myoglobin staining in the kidney In order to evaluate the diagnostic value of myoglobin (Mb) staining in the kidney in medicolegal autopsy cases, Mb staining was carried out on the kidney sections of 141 victims, including 59 natural and 82 unnatural deaths. At the same time, Serum and Urine GFR parameters were measured and systemic histological changes were observed on some sections of each kidney. The incidence of Mb positive cases was 74.6% in unnatural, and 25.4% in natural death, indicating the importance of nontraumatic rhabdomyolysis in natural death cases. PMID:8583687
Antidiuretic hormone (ADH), or arginine vasopressin (AVP), is primarily regulated through plasma osmolarity, as well as non-osmotic stimuli including blood volume and stress. Links between water-electrolyte and carbohydrate metabolism have also been recently demonstrated. AVP acts via the intermediary of three types of receptors: V1a, or V1, which exerts vasoconstrictive effects; pituitary gland V1b, or V3, which participates in the secretion of ACTH; and renal V2, which reduces the excretion of pure water by combining with water channels (aquaporin 2). Antidiuresis syndrome is a form of euvolaemic, hypoosmolar hyponatraemia, which is characterised by a negative free water clearance with inappropriate urine osmolality and intracellular hyper-hydration in the absence of renal, adrenal and thyroid insufficiency. Ninety percent of cases of antidiuresis syndrome occur in association with hypersecretion of vasopressin, while vasopressin is undetectable in 10% of cases. Thus the term "antidiuresis syndrome" is more appropriate than the classic name "syndrome of inappropriate ADH secretion" (SIADH). The clinical symptoms, morbidity and mortality of hyponatraemia are related to its severity, as well as to the rapidity of its onset and duration. Even in cases of moderate hyponatraemia that are considered asymptomatic, there is a very high risk of falls due to gait and attention disorders, as well as rhabdomyolysis, which increases the fracture risk. The aetiological diagnosis of hyponatraemia is based on the analysis of calculated or measured plasma osmolality (POsm), as well as blood volume (skin tenting of dehydration, oedema). Hyperglycaemia and hypertriglyceridaemia lead to hyper- and normoosmolar hyponatraemia, respectively. Salt loss of gastrointestinal, renal, cutaneous and sometimes cerebral origin is hypovolaemic, hypoosmolar hyponatraemia (skin tenting), whereas oedema is present with hypervolaemic, hypoosmolar hyponatraemia of heart failure, nephrotic syndrome and cirrhosis. Some endocrinopathies (glucocorticoid deficiency and hypothyroidism) are associated with euvolaemic, hypoosmolar hyponatraemia, which must be distinguished from SIADH. Independent of adrenal insufficiency, isolated hypoaldosteronism can also be accompanied by hypersecretion of vasopressin secondary to hypovolaemia, which responds to mineralocorticoid administration. The causes of SIADH are classic: neoplastic (notably small-cell lung cancer), iatrogenic (particularly psychoactive drugs, chemotherapy), lung and cerebral. Some causes have been recently described: familial hyponatraemia via X-linked recessive disease caused by an activating mutation of the vasopressin 2 receptor; and corticotropin insufficiency related to drug interference between some inhaled glucocorticoids and cytochrome p450 inhibitors, such as the antiretroviral drugs and itraconazole, etc. SIADH in marathon runners exposes them to a risk of hypotonic encephalopathy with fatal cerebral oedema. SIADH treatment is based on water restriction and demeclocycline. V2 receptor antagonists are still not marketed in France. These aquaretics seem effective clinically and biologically, without demonstrated improvement to date of mortality in eu- and hypervolaemic hyponatraemia. Obviously treatment of a corticotropic deficit, even subtle, should not be overlooked, as well as the introduction of fludrocortisone in isolated hypoaldosteronism and discontinuation of iatrogenic drugs. PMID:22119069
Vantyghem, Marie-Christine; Balavoine, Anne-Sophie; Wémeau, Jean-Louis; Douillard, Claire