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PubMed1995

Neuroleptic malignant syndrome and malignant hyperthermia: end of a controversy?

Two primary hypotheses have been proposed to explain the pathophysiology of the neuroleptic malignant syndrome (NMS): 1) that NMS is produced by abrupt and extensive central dopamine receptor blockade by neuroleptics, particularly in nigrostriatal and hypothalamic pathways; and 2) that NMS, like malignant hyperthermia (MH), results from a preexisting defect in skeletal muscle metabolism that is unmasked or provoked by neuroleptic exposure. To evaluate these models, the authors review studies published since 1980 of the clinical features, epidemiology, risk factors, laboratory assessment, and relevant animal models of NMS and MH. Data from these studies suggest that although NMS and MH are clinically similar, they are pharmacologically distinct, implying that cross-reactivity between triggering agents is unlikely to occur.

Animals↗

PubMed1989

[The malignant neuroleptic syndrome and malignant hyperthermia].

We report on a patient with neuroleptic malignant syndrome (NMS) caused by a therapy for endogenous depression. The symptoms were hyperpyrexia (39.2 degrees C), rigidity, elevated creatine kinase (CK: 594 U/l) and coma. After transfer from an outside hospital, he was treated, at first without effect with dantrolene p.o. (80 mg q.i.d.) and i.v. (1 mg/kg-1/h-1). Clinical improvement and temperature reduction were noted when the levels of neuroleptic drugs fell during unspecific intensive care with mechanical ventilation, sedation (flunitrazepam, barbiturates), relaxation (pancuronium), and hydration. After uncomplicated weaning from the ventilator the patient became more cooperative and was returned to the psychiatric ward. Further treatment took the form of combined drug therapy with biperiden and flunitrazepam and in addition a series of 12 electroconvulsive therapies (ECT). The elevated CK levels initially decreased, serum potassium levels were found to be within normal limits, and myoglobinuria was not detected during the further course. Trigger agents for NMS are antipsychotic drugs such as thioxanthenes, phenothiazines and butyrophenones. Because the signs and symptoms are so similar to those of malignant hyperthermia (MH), it has been suggested that NMS and MH are related diseases. The postulated mechanisms of NMS become apparent in the CNS, whereas those of MH affect the muscle cell itself. An abnormal in vitro contraction test after NMS should suggest to triggering of MH crisis after succinylcholine administration in anaesthesia for ECT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Monoclonal antibody Ber-EP4: its use in the differential diagnosis of malignant mesothelioma and carcinoma in cell blocks of malignant effusions and FNA specimens.

Formol sublimate-fixed cell blocks derived from 129 malignant pleural (and some peritoneal) effusions, 8 benign effusions with reactive mesothelial cells, and 23 FNA specimens, were immunostained with monoclonal antibody Ber-EP4 to assess its ability to distinguish malignant mesothelioma (MM) from carcinoma. Only 2 of 44 (4%) well-characterized MM were Ber-EP4+, while none of 8 benign mesothelial proliferations reacted with the antibody. Fifty-seven percent of 23 pulmonary adenocarcinomas (AC) and 60% of 43 pulmonary carcinomas of all other histological types were Ber-EP4+. Of 40 metastatic AC originating from breast, gastrointestinal tract, ovary, endometrium, and kidney, 80% were Ber-EP4+. The predictive value of positive Ber-EP4 staining in distinguishing AC from MM was 96%. The predictive value of a negative Ber-EP4 in excluding MM was 70%, when the differential diagnosis was adenocarcinoma. These results suggest that Ber-EP4 is helpful in differentiating MM and AC if used together with other discriminating antibodies.

Antibodies, Monoclonal↗

PubMed1999

Eltanolone (5-beta-pregnanolone) does not trigger, and attenuates halothane triggering of, malignant hyperthermia in malignant hyperthermia susceptible swine.

Eltanolone is the lipid emulsion formulation, for intravenous use, of the steroid anaesthetic 5-beta-pregnanolone. We have screened this agent in malignant hyperthermia susceptible (MHS) Landrace swine to assess its potential to trigger the Malignant Hyperthermia (MH) syndrome in MHS subjects or to influence halothane triggering of MH in such patients. Administered in anaesthetic concentration, eltanolone did not trigger the MH syndrome in MHS swine. When co-administered in low dosage with halothane, the drug prevented initiation of the MH syndrome in four of eight pigs and attenuated its progress in the remainder.

Anesthetics, Inhalation↗

PubMed1976

The use of procaine in acquired malignant hyperthermia in a patient with malignant melanoma metastatic to the parathyroid gland: a case report.

The use of intravenous procaine in the treatment of hyperpyrexia in a patient with hyperparathyroidism has not been previously reported. A case of metastatic malignant melanoma precipitating the syndrome of hypertonicity of muscle, hyperpyrexia, acidemia, hypercalcemia and elevated serum parathormone levels is presented. Mithramycin was used in an attempt to reduce elevated serum calcium concentrations. The use of intravenous procaine in "caffeine rigor" and malignant hyperthermia due to succinylcholine and halothane formed the basis for its trial in this case. The relationship between cyclic AMP and calcium ions is discussed in postulating mechanism of procaine action.

Humans↗

PubMed2002

Malignant pleomorphic adenoma (malignant mixed tumor) of the trachea: a case report and review of the literature.

A case of malignant mixed tumor of the trachea in a 56-year-old man is described. His tumor was removed by segmental tracheal resection, and end-to-end anastomosis was performed. Histologically, the tumor was characterized by a biphasic composition showing admixtures of epithelial elements in varying proportions; these were cytologically atypical with prominent mitotic figures. However, stromal elements were osteoid and mixoid with a benign appearance. The patient had no evidence of disease in the head and neck region and had no history of previous surgery for a salivary gland tumor. These findings were interpreted as indicative of malignant pleomorphic adenoma of the trachea.

Adenoma, Pleomorphic↗

PubMed1984

A protocol for the investigation of malignant hyperpyrexia (MH) susceptibility. The European Malignant Hyperpyrexia Group.

A European Malignant Hyperpyrexia Group has been formed to facilitate exchange of information between centres performing in vitro muscle testing for malignant hyperpyrexia susceptibility. Data have been collected according to a protocol agreed by the Group. Based on these results, test criteria have been established to allow the following diagnoses to be made: MH susceptible (MHS); MH normal (MHN) or MH equivocal (MHE). It is accepted that MHE classified patients will be under permanent review, pending the collection of further data.

Biopsy↗

PubMed1998

Multicentre evaluation of ryanodine contracture testing in malignant hyperthermia. The European Malignant Hyperthermia Group.

A common protocol for in vitro contracture testing using the plant alkaloid ryanodine has been used by the European Malignant Hyperthermia Group since 1993. This protocol describes a test using I mumol/litre of high purity ryanodine (98%) added as a single bolus dose. The main aim of this study was to compare the results obtained with this test between laboratories with a view to assessing the validity of adopting common diagnostic end-points for use in future collaborative studies. In order to do this it was first necessary to determine the optimum cut-off values of the end-points for discriminating between patients diagnosed as susceptible or not to malignant hyperthermia. The end-points under evaluation were expressed in terms of time after application of ryanodine at which a certain degree of contracture develops. In this study, four end-points were investigated: time to initial contracture development (Ot); time to development of a 10-mN contracture (10t); time from addition of ryanodine to when baseline tension exceeds pre-drug tension (0tp); and time for contracture to reach 10 mN above pre-drug baseline tension (10tp). This protocol was developed initially and used by three investigating centres and the initial assessment of the end-points and their discriminatory ability was made using the first 100 patients from each of centres 1 and 2, and the first 90 patients from centre No. 3. Optimal cut-off values for each of the end-points were determined using logistic regression analysis. Discriminatory ability was improved by combining the Ot and 10t end-points (P < 0.05) but not significantly by combining the 0tp and 10tp end-points. Both methods of categorization were highly sensitive and specific compared with the current standard diagnostic tests. Results from eight additional diagnostic centres which have used the ryanodine contracture test more recently, while indicating that susceptible and normal individuals can be distinguished within a single laboratory, produced a level of variability between testing centres for the ryanodine contracture test that is incompatible with the use of common cut-off values. Possible causes for this variability between laboratories are discussed.

Evaluation Studies as Topic↗

PubMed1998

The sensitivity and specificity of the caffeine-halothane contracture test: a report from the North American Malignant Hyperthermia Registry. The North American Malignant Hyperthermia Registry of MHAUS.

BACKGROUND: The caffeine-halothane contracture test (CHCT) is the only recognized laboratory test to diagnose malignant hyperthermia (MH). The authors report the results of their analysis of pooled data from the North American Malignant Hyperthermia Registry database to determine the sensitivity and specificity of the CHCT. METHODS: The MH Clinical Grading Scale was used to identify 32 case subjects who were "almost certain" to be MH susceptible based on clinical criteria alone. Their CHCT results were compared with those of a group of 120 control subjects considered to be at low risk for MH. Diagnostic thresholds of the CHCT were adjusted, and its component tests were combined to generate receiver operating characteristic curves. The maximal Youden index for each component test was chosen as the diagnostic threshold indicative of MH susceptibility. RESULTS: The highest sensitivity (97%; 95% CI, 84-100%) was achieved with a two-component test with thresholds of > or = 0.5 g contracture for 3% halothane, > or = 0.3 g contracture at 2 mM caffeine, or both, considered positive for MH. The test specificity was 78% (95% CI, 69-85%). The addition of other CHCT component tests did not improve CHCT sensitivity or specificity. CONCLUSION: The CHCT achieves high sensitivity and acceptable specificity as a clinical laboratory diagnostic test when it is performed according to published standards. However, it cannot be used as a screening test because of the low prevalence of MH in the general population.

Adult↗

PubMed1994

Transforming growth factor-beta 1 (TGF-beta 1)- and beta 2-like activities in malignant pleural effusions caused by malignant mesothelioma or primary lung cancer.

We investigated the levels of TGF-beta in malignant pleural effusions (MPE) caused by malignant mesothelioma (MESO) or primary lung cancer. TGF-beta levels in MPE caused by MESO were 283.9 +/- 219.2 pm (mean +/- s.d.) and were three to six times higher than those due to primary lung cancers (P < 0.01 or P < 0.05). We also evaluated TGF-beta 1- and beta 2-like activities in MPE using specific polyclonal antibodies. Although TGF-beta 1-like activity could be detected in all cases, TGF-beta 2-like activities were detected in five of seven in MESO and in a few cases with primary lung cancer. These results demonstrate that the levels of total TGF-beta and TGF-beta 2-like activity may be clinically useful to differentiate MESO from primary lung cancer. Our data also suggest that TGF-beta may help further characterize the clinical features of MESO.

Carcinoma, Small Cell↗

PubMed1981

Malignant catarrhal fever. I. Response of American cattle to malignant catarrhal virus isolated in Kenya.

Fifty-three American cattle were inoculated with malignant catarrhal fever virus isolated from a wildebeest in Kenya. Three animals showed the mild form of the disease and recovered, and 47 showed the severe form of the disease. The other three did not react. Of the 47 cattle, 28 died, 16 were killed for the collection of specimens and three recovered. The incubation period for the 47 cattle ranged from 16 to 29 days and the course of the fatal disease for 28 cattle averaged three to 23 days. Virus titration of specimens from nine infected steers yielded a mean titer of 10(4)/TCID50 per gm for lymph nodes, 10(3) TCID50 per mL for buffy coats and 10(2.3) TCID50 per gm for spleens. Smaller amounts of virus were found in the liver, kidneys, adrenals and thyroids. Malignant catarrhal fever virus was also found in nasal secretions and saliva of viremic cattle. Viral infectivity was shown in bovine buffy coat cells stored at 4 degrees C for two days but was immediately destroyed upon freezing even when glycerine or dimethylsulfoxide was added. Viral particles were not found in infected animal tissues by electron microscopy. The disease was successfully transmitted in steers by intratracheal intubation and by aerosol inhalation but not by contact.

Animals↗

PubMed1997

Changes in ryanodine-induced contractures by stimulus frequency in malignant hyperthermia susceptible and malignant hyperthermia nonsusceptible dog skeletal muscle.

Elective diagnosis of malignant hyperthermia depends on halothane and caffeine contracture testing of biopsied skeletal muscle. Ryanodine-induced contractures may provide greater sensitivity and specificity for malignant hyperthermia (MH) diagnosis. This study investigated the effects of ryanodine concentration and stimulus frequency to distinguish between MH susceptible (MHS) and MH non-susceptible (MHN) dogs. Increasing ryanodine concentrations (1, 2.5 and 5 microM) increased peak isometric contracture tension, but similar responses in MHS and MHN muscle precluded use for diagnosis. Time to tension onset and to peak tension decreased with increasing ryanodine concentration, and these times were shorter in MH skeletal muscle. Increasing stimulus frequency (0.1, 0.5 and 1 Hz) decreased the time to tension onset and to peak tension, but the effect was greater in MHN muscle which decreased the difference between MHN and MHS muscle responses. When ryanodine contracture tension onset time was selected to detect MHS muscle, combinations of either 0.1 Hz and 1 microM ryanodine or 0.5 Hz and 1 microM ryanodine reduced the probabilty of a false diagnosis to less than 1%. Similar studies performed on human muscle might identify optimal stimulus frequency and ryanodine concentration for detecting MH in patients.

Animals↗

PubMed1985

Malignant lymphoma and malignant angioendotheliomatosis: one disease.

A patient was diagnosed as having angioendotheliomatosis proliferans systemisata (APS) based on characteristic clinical and histologic features. A few days later, malignant lymphoma involving the gut was discovered. Immunohistochemical and electronmicroscopic studies confirmed the nonendothelial and lymphoid nature of intravascular tumor cells. This is the sixth case in which malignant lymphoma has been shown to involve the vessels of the skin (and probably of other organs) in a pattern identical to that seen in APS.

Aged↗

PubMed1985

Histopathologic and immunohistochemical study of malignant tumors of peripheral nerve sheath (malignant schwannoma).

Histologic and immunochemical analyses were performed on 38 cases and 33 cases of malignant tumors of the peripheral nerve sheath, respectively. The histologic features consisted of either closely packed or loosely arranged interlacing fascicles of slender spindle cells that showed a wavy pattern. Although no characteristic findings indicative of neurogenic differentiation could be confirmed with anti-S-100-protein, a fair number of positive cells were seen in the area where the tumor cells were loosely arranged and displayed a wavy pattern. When anti-neuron-specific enolase (NSE) and anti-neurofilament antibody (68K, 200K) were applied, they were found to be positive in cells differentiating to ganglion cells and in epithelial cells. Since S-100-protein-positive cells indicate a differentiation to Schwann cells and NSE-positive cells and neurofilament-positive cells to nerve cells, it was concluded that immunohistochemistry can serve as an effective supplementary method for the diagnosis of malignant tumors of the peripheral nerve sheath.

Adolescent↗

PubMed2003

Coenzyme Q differentially modulates phospholipid hydroperoxide glutathione peroxidase gene expression and free radicals production in malignant and non-malignant prostate cells.

The aim of this study was to investigate the role of coenzyme Q on the mRNA abundance of PHGPx and the reactive oxygen species (ROS) production in two different cell lines from human prostate, a line of non cancer cells (PNT2) and a line of cancer cells (PC3). Results showed that malignant cells markedly differ in their response to coenzyme Q compared to non-malignant cells, with no changes in PHGPx expression and greater ROS production. Furthermore coenzyme Q supplementation significantly lowered cell growth of the PC3 cancer line without affecting the PNT2. If these results are confirmed with additional experiments, it could represent a novel and interesting approach on the biomedical use of coenzyme Q10 in cancer therapy.

Cell Line↗

PubMed1984

Epitopes immunologically related to glycophorin A on human malignant and non-malignant cells in culture.

Nine monoclonal antibodies specific to different antigenic determinants on the cyanogen bromide fragments CNBr3 (1-8) and CNBr1 (9-81) of glycophorin A, the major sialoglycoprotein of human red blood cells, were used for the detection of similar or cross-reactive epitope(s) on nucleated somatic cells. A panel of human malignant and non-malignant cells consisting of erythroleukemia, melanoma and carcinomas of breast, cervix, larynx, nasopharynx and colon, as well as human fibroblasts and mammary cells, were tested using a sensitive enzyme-linked immunoassay. The presence of glycophorin-like epitopes were demonstrated, in varying concentrations, on all cells tested. These epitropes were found to be localized on the cell membranes by indirect immunofluorescence.

Antibodies, Monoclonal↗

PubMed1980

Chemical and hematological screening in patients with malignant and non-malignant conditions.

The value of multiphasic automated laboratory tests in differentiating stages of malignancy and in detecting recurrence of cancer was studied. Chemical SMA-12 tests (including calcium, phosphate, glucose, BUN, uric acid, cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase (AP), lactic dehydrogenase (LDH) and SGOT) and hematological SMA-4 tests (including hematocrit, hemoglobin, WBC and RBC counts) were performed in 1,578 patients. Baseline data obtained from 582 patients with benign, and 996 patients with malignant, lesions were subdivided according to age, sex, primary site, and extent of cancer. With advancing stages of cancer, there was a significant increase of AP and LDH, but decrease of albumin and hemoglobin. Among patients who had sequential tests, there was a significant decrease of uric acid and LDH with control of cancer, and increase of AP with development of distant dissemination.

Adult↗

PubMed1988

Malignant fibrous histiocytoma (MFH) arising within a cholecystectomy incision: a cause-and-effect relationship is possible between previous surgery and the development of a malignant fibrous histiocytoma within the operative site.

We present a report of a patient who, after an uneventful cholecystectomy, developed an incisional mass that proved to be a malignant fibrous histiocytoma and had to be excised. Five months later, the patient developed a similar incisional mass, which was shown to be a malignant fibrous histiocytoma and again had to be excised. The rarity of such a case and the details of the patient's case history are reported. The implications of a possible relationship between previous surgery, the patient's healing response, and the development of these tumors are discussed.

Cholecystectomy↗