Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from] 7 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 μmol · 1^-1 ryanodine. After pretreatment with 1 μimol · 1^-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8±1.8 min) and MHN (46.0±4.2 min) muscle specimens than after ryanodine alone (MHS 4.8±0.7 min), (MHN 13.7±0.9 min). They were no longer observed in either group after pretreatment with 5 μimol · 1^-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependendy, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.     

心肌和骨骼肌对低血钙不同反应性机理的初步研究

本实验采用枸椽酸钠等静脉输入复制家兔低血钙。实验动物血钙显著下降,同时出现骨骼肌抽搐和心肌收缩性下降。测定骨骼肌匀浆钙含量在低血钙前、后均比心肌匀浆高。认为这两种肌肉细胞内固有钙含量的差异,是低血钙时骨骼肌收缩亢进和心肌收缩性下降的原因之一,其次为神经肌肉的兴奋性改变。     

Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes

Summary The effects of sodium salts of various bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle were studied in vitro. Primary, conjugated, and secondary bile acids were studied in a concentration range of 10^–9–10^–6 mol/l, which corresponds to concentrations found in the plasm of patients with cholestatic jaundice. In general, the bile acid induced a negative inotropic effect which was manifested as a reduction in active tension, maximum rate of tension activation, and maximum rate of tension relaxation. Twitch duration and time to peak tension were unaffected by the bile acids. The negative inotropism was associated with a reduction in ventricular action potential duration. Resting potential, action potential amplitude, and maximum upstroke velocity of phase 0 depolarization were unaffected. Voltage clamp experiments in rat ventricular myocytes demonstrated that sodium taurocholate decreased the slow inward current and slightly increased the outward potassium current. Hence, these effects on the membrane currents are probably responsible for the negative inotropic effect. Send offprint requests to O. Binah at the above address     

Muscle mass index in haemodialysis patients: a comparison of indices obtained by routine clinical examinations.

BACKGROUND: Measurement of muscle mass is useful for evaluating protein nutritional status. Various methods for estimating muscle mass in haemodialysis patients have recently been developed. METHODS: The validity of the estimate of creatinine production calculated with the creatinine kinetic model (CKM) was examined in 46 haemodialysis patients by comparing it with the actual creatinine production, this being determined from the sum of creatinine appearing in the dialysate and the estimated metabolic degradation. The correlation of various other muscle mass indices with creatinine production was also investigated in these patients. RESULTS: The estimate of creatinine production using CKM was significantly correlated with creatinine production calculated from the spent dialysate plus an estimate for the extra-renal creatinine degradation (r=0.90, P<0.001). A Bland-Altman analysis revealed that the mean prediction error for the estimate of creatinine production by CKM was +0.10 g/day and the limits of agreement were +0.34 to -0.14 g/day. The cross-sectional area of the thigh muscle measured by computed tomography (CT) was also significantly correlated with creatinine production (r=-0.86, P<0.01). In contrast, the correlations of 3-methylhistidine production measured in the spent dialysate, the mid-upper arm muscle circumference and the skeletal muscle mass estimated by an anthropometric prediction model with creatinine production were lower (r<0.82). CONCLUSION: Creatinine production calculated using CKM and CT measurement of thigh muscle area are valid methods for estimating muscle mass during routine clinical examinations of haemodialysis patients.     

Spindle-cell glioblastoma or gliosarcoma?

'Gliosarcomas' have long been considered to be mixed gliomas and sarcomas. The present study failed to define criteria which clearly delineate 'gliosarcomas' from glioblastoma multiforme and suggests that 'gliosarcomas' should be considered as spindle cell glioblastomas. A total of six cases originally diagnosed as 'gliosarcomas' were compared with four cases of glioblastoma multiforme. No clinical or prognostic features were defined which would clearly separate 'gliosarcomas' from glioblastoma multiforme. Macroscopically, biopsies from 'gliosarcomas' ranged from firm, apparently well-circumscribed tumours to poorly circumscribed lesions with a soft consistency resembling glioblastoma multiforme. Histology revealed a continuous spectrum in which 'gliosarcomas' with large reticulin-rich areas of spindle cells merged with typical glioblastomas containing only small islands of spindle cells and reticulin staining. Immunocytochemistry for glial fibrillary acidic protein (GFAP); S100 protein and alpha-smooth muscle actin (ASMA) showed that the majority of cells in reticulin-poor areas of 'gliosarcoma' and glioblastomas expressed S100 protein and GFAP; many expressed ASMA and some expressed both GFAP and ASMA. Spindle cells in reticulin-rich areas of 'gliosarcomas' and glioblastomas most frequently expressed ASMA but many cells also expressed S100 protein and GFAP; some cells expressed both GFAP and ASMA. The results of this study and a review of the literature suggests that there is a clinical, radiological and pathological continuum with glioblastoma and 'gliosarcoma' at different ends of the spectrum. It is suggested, therefore, that most, if not all, 'gliosarcomas' be redesignated as spindle cell glioblastomas and not be considered as a mixture of glioma and sarcoma.     

快速有效的治疗落枕新法

落枕是一种冬春季常见病,虽然治疗的方法很多，但往往收不到快速、有效和彻底的效果,本文以个案经验和病例调查为基础，提供一种快速有效的自我治疗方法，并期望能够得到广大患者的进一步验证。     

Organization of the trigeminal and facial motor nuclei in the hagfish, Eptatretus burgeri: a retrograde HRP study

We studied the trigeminal and facial motor nuclei of the hagfish by the retrograde HRP method. We distinguished 4 components in a single column of the motor nuclei of the trigeminal nerve and the facial nerve, viz., the pars magnocellularis of the trigeminal motor nucleus (mVm), the anterior part of the pars parvocellularis of the trigeminal motor nucleus (mVp1), the posterior part of the pars parvocellularis of the trigeminal motor nucleus (mVp2) and the facial motor nucleus (mVII). Although in Nissl preparations only the mVm could be distinguished from the rest of the nucleus, the boundaries of the other 3 components were clearly demarcated in HRP preparations. Intramuscular injections into two representative antagonistic jaw muscles revealed that there was no apparent topological organization of the neurons pertaining to the opening and closing muscles in the mVm and mVp1, but both antagonistic muscles were innervated bilaterally. Although the hagfish does possess a cartilaginous jaw, the organization pattern of the motor nuclei of the jaw muscles seems to be the most primitive of all living vertebrates.     

Intubating conditions after vecuronium and atracurium given in divided doses (the priming technique)

Intubating conditions have been assessed at 60 s following administration of vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 given either as a single dose after induction of anaesthesia with thiopentone or in divided doses; vecuronium 0.015 mg kg-1 followed 4 or 6 min later by 0.085 mg kg-1, or atracurium 0.075 mg kg-1 followed 4 or 6 min later by 0.425 mg kg-1. In the divided dose groups the smaller initial (priming) dose was given prior to induction of anaesthesia. Onset and duration of clinical relaxation were assessed using a peripheral nerve stimulator. The intubating conditions at 60 s improved significantly, with the use of relaxants in divided doses being acceptable in 80 and 70% of patients, respectively, with vecuronium and atracurium, but the conditions are not as good as those commonly found using suxamethonium. Priming at 6 min has no advantage over priming at 4 min. The onset of complete block was accelerated with priming, but the difference was not significant. The duration of clinical relaxation of vecuronium was significantly prolonged by giving it in divided doses. Unpleasant awareness of muscle weakness was observed in 15 patients, requiring early induction of anaesthesia in five of them.