Pathological findings in 165 patients explored for malignant hyperthermia susceptibility

The pathological findings in 165 patients explored for malignant hyperthermia (MH) susceptibility are reported. The first group of 120 subjects were patients investigated for MH. These patients had suffered an attack of MH under anaesthetic or were members of families in which a subject had died of MH. In vitro contracture tests revealed 25 malignant hyperthermia susceptible (MHS) subjects, with positive contracture tests for halothane and caffeine, 5 malignant hyperthermia subjects with reaction to caffeine only (MHC), 3 malignant hyperthermia subjects with reaction to halothane only (MHH) and 87 malignant hyperthermia negative (MHN) subjects with normal contracture tests. The second group of 45 subjects had exertional heat stroke. In vitro contracture tests performed at least 3 months after the exertional heat stroke revealed 11 MHS, 6 MHC, 2 MHH subjects and 26 MHN. In both groups, whatever the in vitro contracture test results, pathological findings were heterogeneous and revealed various changes: rhabdomyolysis, mitochondrial myopathy, denervation, type II atrophy, AMPase deficiency, non-specific findings or normal features. Central core myopathy was only observed in the first subgroup and was the only disease significantly associated with MH. In contrast to previous reports, this study demonstrates the absence of a specific malignant hyperthermia or exertional heat stroke myopathy. Furthermore, the discovery of MHS subjects among the EHS group of patients highlights the need for systematic exploration of all these patients.     

Central acinic cell carcinoma of the mandible: Report of a case

Central acinic cell carcinoma is extremely rare; only six cases have been reported in the literature. An unusual case of central acinic cell carcinoma of the mandible in an 84-year-old Japanese woman is presented. This is thought to be the seventh case of central acinic cell carcinoma described in the English literature.     

Catecholaminergic activity of the baroreceptor areas of the brain in response to bilateral dorsolateral transection of medulla oblongata in rats

Central catecholaminergic activity was studied by measurement of norepinephrine (NE), epinephrine (EPI), their metabolites: total 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol in brain nuclei in response to bilateral dorsomedullary knife-cut (DMK-cut) in rats. In saline-pretreated conscious rats DMK-cut caused a marked hypertension, tachycardia and increases in plasma NE, EPI and vasopressin. Chlorisondamine (CHL) prevented the rise in plasma catecholamines and the tachycardia but failed to prevent the hypertension and the increment in plasma vasopressin. DMK-cut decreased NE and EPI in the nucleus tractus solitari (NTS) and A2 area; there were no catecholamine changes in A1 area or the periventricular nucleus but an increase in the paraventricular nucleus (PVN), the latter effect reversed by CHL, CHL alone or combined with DMK-cut had no effect on catecholamine concentrations in NTS-A2 area but lowered MHPG content. It is suggested that DMK-cut decreases the activity of the catecholaminergic system originating in A1 and terminating in PVN, where it causes catecholamine accumulation and may be involved in vasopressin release and thereby contribute to hypertension. In NTS-A2 area, however, the DMK-cut appears to increase catecholaminergic activity since catecholamines are depleted. Central effects of DMK-cut differ from those of ganglionic blockade-induced inhibition of the baroflex presumably due to sectioning of other pathways in addition to the primary baroreceptor input.     

Central venous versus mixed venous oxygen content

Mixed venous oxygen content (commonly measured as oxygen saturation) is a highly relevant parameter in the monitoring of critically ill patients; unfortunately, its measurement requires catheterization of the pulmonary artery. Though less invasive, the central venous oxygen saturation is an unsatisfactory substitute, due to fluctuations in perfusion distribution and regional oxygen extraction in the course of illness.
The present study examined the relation of oxygen contents in simultaneously withdrawn central venous and mixed venous blood samples from critically ill patients, in order to validate a hypothetical algorithm for the estimation of mixed venous oxygen content from a central venous sample: Although the proposed algorithm had a fairly high power of prediction, its merits in comparison to assuming simple proportionality between central venous and mixed venous oxygen content seemed marginal.
However, as it is likely that the results so far are mathematically coupled, further prospective studies are necessary.     

Threshold temporal integration of chromatic stimuli

We measured colorimetric purity thresholds as a function of stimulus duration for seven wavelengths between 430 and 650 nm. Purity thresholds were measured ina hue substitution mode. The purity-duration function showed decreasing purity as duration was increased to about 640 msec. Functions for different wavelengths could be fit by a fixed chromatic template displaced on the purity axis.Increment thresholds as a function of duration were measured for white and chromatic lights added to a homogenous white stimulus field. The “white” function showed no integration beyond 160 msec and was fit by an achromatic template. The wavelength functions were not parallel; wavelengths at the spectral extremes showed longer integration times, similar to the purity-duration functions. Increment data could be fit by a vector sum of chromatic and achromatic templates.     

Integration of human herpesvirus 6 in a Burkitt's lymphoma cell line

Human herpesvirus 6 (HHV-6) genome has been found in several human lymphoid malignancies, but configuration of the HHV-6 genome has not been well delineated. We established the HHV-6-positive, Epstein-Barr virus-negative Burkitt's lymphoma cell line Katata. In this study we investigated the status of the HHV-6 genome in Katata cells. Neither linear nor circular HHV-6 DNA was detected by Gardella gel analysis. The fluorescence in situ hybridization technique enabled us to directly visualize the integrated HHV-6 DNA at the single-cell level. Only one integrated site of viral DNA was detected in metaphase chromosomes and it was preferentially located at the long arm of chromosome 22 (22q13). Treatment of the cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or with calcium ionophore A23187 led to induction of the HHV-6 immediate-early gene as well as the late gene. Sodium n-butyrate also gave rise to expression of the HHV-6 genes. The TPA inducibility was synergistically enhanced when combined with A23187 or n-butyrate. Our study provides, for the first time, an in vitro model system of latent HHV-6 infection whose genome is integrated into host DNA of lymphoma cells.     

Disposition and activity in experimental allergic encephalomyelitis of flumizole, a nonacidic, nonsteroidal, anti-inflammatory agent

The nonacidic, nonsteroidal, anti-inflammatory agent, flumizole, penetrates the central nervous system of rats following oral drug administration, reaching concentrations in brain and spinal cord which are several-fold higher than plasma concentrations. Maximum drug concentrations in brain and plasma are achieved simultaneously and decay with similar half-lives (8 h). The drug is well absorbed orally and is excreted primarily with feces after biliary secretion. The distribution and elimination of flumizole is comparable in normal rats and in rats afflicted with experimental allergic encephalomyelitis; the drug is not selectively concentrated at either peripheral or central nervous system sites of inflammation. Flumizole is inactive in the rat model of the disorder under conditions that demonstrate therapeutic success with myelin basic protein.     

Acute dieldrin exposure in relation to brain monoamine oxidase activity and concentration of brain serotonin and 5-hydroxyindoleacetic acid

Rainbow trout, White Leghorn chickens and golden hamsters were administered dieldrin or the vehicle in various dosages and routes of injection. Whole brain serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were measured. In separate experiments, monoamine oxidase (MAO) activity was determined in brain homogenates incubated with pargyline or dieldrin. Serotonin content increased maximally at 10 mg/kg dieldrin. Brain MAO activity was significantly decreased by dieldrin in chicken and hamster, but trout enzyme activity was unaffected. The 5-HIAA content reflected MAO inhibition and interference with 5-HIAA transport from brain.     

The neurotoxicity of aflatoxin B1 in the rat

The effects of repeated intraperitoneal administration of aflatoxin B₁ on the peripheral and central nervous systems of rats were investigated. Biochemical markers of neurotoxicity were monitored in nervous tissues following aflatoxin B₁ dosage and after the cessation of aflatoxin B₁ administration. Aflatoxin B₁ increased the activities of β-glucoronidase and β-galactosidase in the central and peripheral nervous systems. Repeated exposure of rats to aflatoxin B₁ also activated Na⁺ K⁺-ATPase and inhibited Mg²⁺-ATPase. Nervous tissue levels of DNA and total protein increased while the concentrations of RNA and phospholipid were depressed by aflatoxin B₁. The alterations in these parameters were specific for each of the tissues examined during the recovery of the rats. The findings indicate that the repeated administration of aflatoxin B₁ to rats results in degeneration in the central and peripheral nervous systems that may be related to the overt toxicity observed following aflatoxin administration.     

Pathway choice by regenerating optic fibers following tectal lobectomy in the goldfish: Inferences from the study of gliosis in tectal efferent bundles

Cell counts in various fiber bundles of the goldfish brain have demonstrated a profound, but transient gliosis of tectal (and pretectal) efferent pathways following removal of a tectal lobe. In the majority of cases, the pathways which underwent gliosis were also those which were penetrated by regenerating optic fibers which had been sectioned by the tectal surgery. However, the dorsal trunk of the horizontal commissure on the intact side of the brain showed only a minimal gliotic response but was consistently innervated by the optic fibers. Conversely, the ansate commissure and the crossed tectobulbar tract invariably demonstrated a marked gliotic response but only rarely received more than minimal innervation by the regenerating fibers.These observations are discussed with regard to the modifications which they demand of the hypothesis that degenerating axon bundles in the goldfish brain are in some way attractive to regenerating axons.