Malignent hyperthemia

Variants in the ryanodine receptor-1 gene (RYR1) have been associated with a wide range of neuromuscular conditions, including various congenital myopathies and malignant hyperthermia (MH). More recently, a number of RYR1 variants, mostly MH-associated, have been demonstrated to contribute to rhabdomyolysis events not directly related to anesthesia in otherwise healthy individuals. This review focuses on RYR1-related rhabdomyolysis in the context of several clinical presentations (i.e., exertional rhabdomyolysis, exertional heat illnesses and MH), and conditions involving a similar hypermetabolic state, in which RYR1 variants may be present (i...

Esophageal cancer is a highly malignant and lethal disease with a low 5-year survival rate. Therefore, an effective treatment modality is required. To investigate the treatment efficacy and toxicity of radio-, chemo- and hyper-thermotherapy combined trimodality on locally advanced esophageal cancer, the medical records of 78 patients with pathologically confirmed esophageal cancer treated with chemoradiotherapy plus hyperthemia at our institution were retrospectively investigated and the 3-year outcome was carefully assessed...

Potentially fatal operating room events have become largely preventable with advances in anesthesia and surgical technique. Nonetheless, some lethal emergencies remain unpredictable and can occur whenever general anesthesia is given. We describe a case of malignant hyperthermia encountered and treated during surgical operations concurrent with an overseas humanitarian assistance mission. This case highlights the clinical diversity of malignant hyperthemia as well as the importance of preparation for any potential adverse event wherever trigger agents may be used from the mundane to exotic locales...

Hyperthermia is selectively cytotoxic for malignant cells due to inhibition of oxidative metabolism causing lower pH in the microenvironment of the malignant cells and tumor. The increased acidity increases lysosymal activity and subsequent cell death. Hyperthermia alone as a primary treatment modality for malignancy has largely been abandoned due to high morbidity and mortality and high recurrence rates. Advances in administration and monitoring of hyperthermia, especially for regional applications, has allowed for the use of hyperthemia in conjunction with other modalities of antineoplastic therapy...

Malignant hyperthermia is a potentially fatal genetic myopathy that presents when the patient is under anesthesia. It manifests as a hypermetabolic state involving tachycardia, hypercarbia, base deficit, rigidity and fever. Many of the hallmark traits of an acute malignant hyperthermic crisis overlap with signs and symptoms of an emergent abdominal condition. Historically, there has been a reluctance in local community hospitals to manage patients known to be susceptible to malignant hyperthemia, and this is a source of frustration for many families in which there is a history of this condition...

Limb-sparing procedures have been well established for dealing with malignant bone tumors. Unfortunately, these procedures have different problems. We used an alternative operation combined with microwave-induced hyperthemia to modify the surgical methods. Thermotherapy with microwave intracorporeal irradiation was used to treat 112 patients with bone tumors. In this series, 79 had malignant tumors and 33 aggressive benigh tumors. Postoperatively, immune therapy was carried out regularly. The patients immunologic functions were monitored by assay of the subpopulation of T cells, IL-2 and sIL-2R (soluble IL-2 receptor)...

A large series of Swedish nuclear families, in which malignant hyperthermia (MH) reactions had occurred during anaesthesia, have been examined with respect to malignant hyperthermia susceptibility. In vitro contracture tests (IVCT) of muscle strips were conducted to diagnose MH status. Included in this series were some families where only one of the parents was tested by IVCT, while in 79 of the families both parents were tested by IVCT. Six known mutations in the gene encoding the calcium release channel of sarcoplasmic reticulum in skeletal muscle (the RYR1 gene), believed to cause MHS in man, were searched for in 41 nuclear families...

We have previously demonstrated that syngeneic marrow mixed with H-2 haploidentical marrow transplantation could provide not only protection against graft-versus-host disease (GVHD) but also anti-leukemic (GVL) effects in mice. In the present studies, we report clinical observations using autologous marrow mixed with HLA-haploidentical allogeneic marrow transplantation for treatment of patients with malignant blood diseases. Sixteen cases, including 12 with acute leukemia and four with advanced malignant lymphoma, were treated by autologous marrow, which was purged in vitro by hyperthemia (42...

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At least three myopathies have been associated with malignant hyperthemia (MH). The clinical manifestations of MH are variable and depend on the nature of the underlying myopathy and the anesthetic agents administered. Unless muscle relaxants are used, fever and muscle rigidity may be delayed at onset. Tachycardia and tachypnea are often the earliest manifestations and can occur immediately or several hours into a surgical procedure. Life-threatening cardiac arrhythmias may result from hyperkalemia and acidosis...

Malignant hyperthemia, which can be initiated in susceptible humans and swine by the volatile anesthetic halothane, appears to result from abnormal responses in skeletal muscle. We have inferred the primary defect in susceptible muscles by observing their responses to certain drugs. Furthermore, we compared the responses of cut muscle cell preparations, such as those used in the diagnostic caffeine test, with those of intact muscle cells. Specifically, we investigated the effects of halothane, caffeine, succinylcholine and catecholamines on the mechanical properties of intact muscle cells from normal pigs, mice and frogs and susceptible pigs...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

We present 8 cases of centrally-originating hyperthermic syndrome, the initial cause being either neuroleptic malingnant syndrome, hyperthemia after discontinuance of antiparkinsonian therapy or heatstroke. We review the physiological and neurochemical mechanisms involved in thermoregulation, emphasizing the role of dopamine. A single mechanism, consistent with pharmacological or neuropathological impairment of the dopaminergic system, could be responsible for all the cases of hyperthermic syndrome presented...

Testing in vitro are used to locate malignant hyperthemia susceptible subjects. They use muscular contraction in response to anesthetic administration, particularly Halothane. They allow to classify subjects in three classes: susceptible, non susceptible and intermediate. Halothane was dosed by chromatography in the three compartments of a bath for isolated organs with a muscular fiber during steady concentrations were given and after wash out. Partition coefficient were determinated and compared to a calculated model...

We investigated German Landrace pigs from a special breeding program producing animals which were of three genotypes with respect to in vivo halothane inhalation (i.e., exposure to 3% halothane for up to 3 min): (1) Hal NN, i.e. homozygous normal exhibiting no response; (2) Hal Nn, i.e. heterozygous, also responding with a normal reaction; and (3) Hal nn, i.e. homozygous for the 'halothane gene n' which exhibited signs of malignant hyperthemia (MH). Additional characteristics of these three groups of animals were studied using accepted methodology from the fields of animal science, clinical testing, and food science...

The action of ionizing radiation on the metabolic heat production by cancers has been investigated on a group of 24 small breast carcinomas (T1 and T2), all treated exclusively by radiotherapy under equivalent conditions (60Co) and then followed up regularly (mean recall period of five years). Following techniques have been used: intratumoral thermometry and fluvography for computing the specific heat power of the tumour, infrared thermography for analysing the skin thermal pattern quantitatively. Comparison between clinical, radiographical and thermal findings has more especially shown; a) the constant agreement between the final loco-regional results of radiotherapy and the evolution of both the heat production by the tumour and the related hyperthermia on the skin; b) the early appearance of the thermal signs of either a regression or a recurrence of the tumour, compared with the corresponding morphological signs...

The effect of tubocurarine and pancuronium on the initiation or prevention of porcine malignant hyperthermia (MH) was investigated in Pietrain pigs. Tubocurarine 0.6 mg/kg body weight inhibited a suxamethonium-induced response in three pigs, but failed to prevent a fatal halothane-induced response in a further four pigs. Pancuronium 0.2 mg/kg body weight was given to six pigs before a halothane challenge. Three animals developed MH and died; the remainder succembed only after reversal of the neuromuscular blockade...

An 8-year-old boy underwent general anesthesia and experienced an episode of malignant hyperthemia, characterized by elevated temperature, cardiac arrhythmias, markedly elevated serum enzymes (SGOT, LDH, and CPK), proteinuria, and hemoglobinuria. Sixty-six days after anesthesia a skeletal muscle biopsy was obtained for examination by electron and light microscopy, which showed skeletal muscle cells with abnormally numerous mitochondria, enlarged, and variable in shape. Some contained abnormal cristae. There were more lysosomes than normal, and lipofuscin was increased in quantity...

To examine the function of sarcoplasmic reticulum (SR) in malignant hyperthermia, SR was isolated from semitendinosus muscle of normal and genetically susceptible Poland China swine. Determinations included rate of calcium binding (oxalate absent), rate and capacity of calcium uptake (oxalate present), and spontaneous calcium release (in the absence of ionic depolarization or calcium) with and without halothane, using the millipore filtration technique. Rate of calcium binding, and rate and capacity of calcium uptake were decreased, and spontaneous calcium release was greater in SR fragments from susceptible swine as compared to those from normal swine...