Central pontine myelinolysis and rapid correction of hyponatremia.
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Biomedical subjects
Publications and source records attributed to R D Bell.
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The [14C]2-deoxyglucose (2-DG) technique has been widely utilized for quantitative measurement of local cerebral metabolic for glucose (1CMRG) in animals. The technique as presently used is limited by the energy of 14C beta-particles, which can travel relatively great distances in tissue. This results in limited audioradiographic resolution and in computed 14C concentrations which are a function of tissue section thickness. [3H]2-DG has less energetic beta-particles; hence, autoradiographs have better resolution and optical densities are independent of tissue thickness for sections greater than 5 micrometer. We have developed a method for quantitation of 1CMRG in rats using [3H]2-DG and a newly developed ultrasensitive X-ray film. Autoradiographic tissue standards were prepared by injecting rats with [3H]2-DG and assaying micro-samples of brain for 3H concentration. Ten rats were used in this study. Five rats received [3H]2-DG (300 muCi/100 g) and 5 rats received [14C]2-DG (7.5 muCi/100 g). The mean 1CMRG values for selected areas of the central nervous system demonstrated no significant difference (P greater than 0.05) between the [14C]2-DG and the [3H]2-DG groups. Values for 1CMRG from the [3H]2-DG group showed no variation attributable to inadequate microtome precision. The improved resolution obtained by utilizing [3H]2-DG is especially evident where gray matter (high 1CMRG) is immediately adjacent to white matter (low 1CMRG).
Diallate and Triallate are carbamate herbicides used mainly for the pre-emergence control of wild oats in various crops. The genetic activity of these compounds was studied using a battery of microbial and mammalian in vitro tests. In the Salmonella/mammalian-microsome assay, Diallate and Triallate show dose-related increases without metabolic activation in strains TA1535, TA100 and TA98, indicating that these compounds cause both frameshift and base-substitution mutations. Mutagenicity of both herbicides was enhanced greatly by incubation with Aroclor 1254 induced rat-liver S9. Genetic activity in mammalian cells was determined using a number of in vitro tests with Chinese hamster ovary (CHO) cells combined with metabolic activation as described above. Both Diallate and Triallate caused dose-related decreases in colony-forming ability, with concomitant dose-related increases in the frequencies of cells with chromosome damage and in the number of sister-chromatid exchanges. However, only Diallate caused a reduction in DNA molecular weight as determined by alkaline sucrose gradient (ASG) sedimentation. DNA damage was negligible even at concentrations of Triallate that reduced colony-forming ability to zero. This suggests that the lesions in DNA detected by the ASG technique are not necessarily related to those that produce chromosomal damage. These data, taken together, strongly implicate both Diallate and Triallate as capable of causing mutations in mammals. However the risk to man in terms of inherited disease or cancer remains to be established by appropriate in vivo methodology.
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This study investigated the relationship of age and sex with the range of motion of seventeen joint actions at eight joints. A sample of 190 male and female subjects ranging in age from 18 to 88 years were measured using a modified version of Leighton's (1942) procedures. The data were analyzed to obtain test-retest reliability, to determine significant differences in flexibility across age, and to assess sex differences in flexibility. The following conclusions were made: a general decline in flexibility of joints occurs with age; upper extremity joints do not readily reflect this decreased flexibility with age; the configuration of flexibility is specific to the joint action and; females have greater flexibility than males throughout life.
Previous research has indicated that endogenous opioids participate in the regulation of activity in the hypothalamic-pituitary-luteinizing hormone (LH) axis and mediate the negative feedback control exerted by testosterone. If this assumption is correct, then two predictions can be made. First, the effects of testosterone should be competitively inhibited by narcotic antagonists; and, second, opiates should mimic the acute and chronic effects of testosterone in the castrated male rat. The results of the present investigations support both of these predictions. We found that naloxone competitively antagonized the depressive effects of testosterone on serum LH in the castrated rat and, conversely, that testosterone competitively antagonized the LH-releasing properties of naloxone. In addition, morphine and testosterone both depressed serum LH levels in a dose-dependent fashion in the acutely castrated animal. Moreover, morphine was just as effective as testosterone in reversing the castration-induced fall in hypothalamic-LH-releasing hormone (LH-RH), which occurs in the chronically castrated male rat. On the other hand, morphine failed to reverse the long-term changes in pituitary LH content and increase in serum LH, which is consistent with prior observations that morphine affects only the hypothalamic aspect of the hypothalamic-pituitary-LH axis in the male rat. These results, thus, support the concept that an as yet unidentified opioid-containing neuronal system regulates activity in the hypothalamic-pituitary-LH axis and mediates the effects of testosterone on this axis.
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Small-amplitude sinusoidal displacements, in the frequency range 4-100 Hz, were applied to intact whole frog sartorius muscle whilst in a state of tetanus. At low frequencies the muscle was observed to do oscillatory work, while at higher frequencies it tended towards elastic behaviour. Frequency-response plots obtained were compared with those from other muscle preparations. Results were interpreted in terms of mechano-chemical transduction properties of muscle.
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The effects of ethanol and acetaldehyde on testicular steroidogenesis were examined in enzymatically dispersed cells of the rodent testes. We found that both compounds significantly inhibited the gonadotropin-stimulated biosynthesis of testosterone. Acetaldehyde was approximately 4000 times more potent than its parent compound, however. Moreover, in contrast to the effects of ethanol, acetaldehyde was effective at concentrations compatible with those found under in vivo conditions after acute ethanol administration. These data indicate that acetaldehyde is, at the least, probably an extremely important factor in the well-documented ethanol-induced inhibition of testicular steroidogenesis in vivo and further suggest that ethanol may be converted to acetaldehyde to produce its testicular toxicity. Finally, we have found that acetaldehyde blocks testicular steroidogenesis by selectively and specifically inhibiting the conversion of androstenedione to testosterone.
Possible mutagenic activity of lead chromate in mammalian cells was studied using assays for chromosome aberrations and sister-chromatid exchanges in cultured human lymphocytes, and DNA fragmentation as detected by alkaline-sucrose gradient sedimentation in cultured Chinese hamster ovary (CHO) cells. Lead chromate caused dose-related increases in chromosome aberration and sister-chromatid exchange in human lymphocytes. No increase in DNA damage was observed in CHO cells, possibly due to the relative insensitivity of the CHO cells and the limited solubility of lead chromate in tissue culture medium. The mutagenicity of lead chromate in human lymphocytes appears to be entirely due to the chromate ion since chromosome aberrations were induced by potassium chromate but not lead chloride.
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The effects of ethanol and acetaldehyde on testicular steroidogenesis were examined. We found that ethanol markedly inhibited the gonadotropin-stimulated production of testosterone in enzymatically dispersed cell preparations of the testes of adult rats. The effects of ethanol on testicular steroidogenesis appeared to be noncompetitive since testosterone production could not be restored to nondrug-treated levels even by extremely high concentrations of gonadotropin. Acetaldehyde also inhibited testicular steroidogenesis in vitro but was between 1000 and 4000 times more effective than ethanol. As little as 50 microM acetaldehyde was effective in suppressing testicular steroidogenesis, whereas much higher (200 mM) concentrations of ethanol were required. Our results further demonstrated that cell viability was unaffected by incubation with very high concentrations of ethanol and acetaldehyde, indicating that the two drugs did not simply irreversibly impair the ability of the dispersed cells to appropriately respond to stimulation by gonadotropins. These results suggest that ethanol directly inhibits testicular steroidogenesis, but that acetaldehyde is much more potent.
Needle biopsies from the vastus lateralis of 13 six-year-old Swiss children were analyzed for muscle fiber type populations and morphometrical characteristics. No significant differences existed between the males and females for fiber type distribution, maximum oxygen consumption, or any of the ultra-structural parameters investigated. The vastus lateralis muscle consisted of 19.7% fast twitch glycolytic (FG) fibers, 21.5% fast twitch oxidative glycolytic (FOG) fibers, and 5,9,% slow twitch oxidative (SO) fibers. Maximum oxygen consumption averaged 45.2 ml/kg min-1 when the subjects were considered as a single group. Morphometrically, it was found that the mean volume density of the central mitochondria was 5.54%, the mitochondrial/myofibrillar volume ratio was 6.68%, and the intracellular lipid volume was 0.46%. There was a significant correlation (r=0.69) between the mitochondrial volume density and the distribution of SO fibers as determined histochemically. It was concluded that the fiber type distribution pattern and ultrastructure of skeletal muscle in six-year-old children was not different from normal adult tissue.
Calcium and vitamin D metabolism were evaluated in 5 adult epileptic patients before and during treatment with phenytoin. Significant decreases occurred in serum concentrations of calcium, albumin, and 25-hydroxy-cholecalciferol. The decreases in serum calcium paralleled those in serum albumin. Significant increases occurred in serum alkaline phosphatase and 1 alpha, 25-dihydroxycholecalciferol, in urinary hydroxyproline, and in the fractional gastrointestinal absorption of calcium. Urinary cyclic adenosine monophosphate and serum parathyroid hormone did not change. The results suggest that the bone disease resulting from phenytoin therapy may be associated with a deficiency of 25-hydroxycholecalciferol and not of 1 alpha, 25-dihydroxycholecalciferol, and that reduced gastrointestinal absorption of calcium or changes in parathyroid function may not be necessary for the development of bone disease.
Lorazepam, a dichloro-3-hydroxy-1,4-benzodiazepine, has been shown to be a potent anticonvulsant in animal models of epilsepsy and has minimal depressant effects on respiration and circulation in humans. The effects of this compound were studied in status epilepticus. Twenty-five patients were given intravenous lorazepam during status epilepticus of varying cause. Four or 8 mg of the drug controlled status in 22 of the 25 patients. Although single seizures recurred in 5 of the 22 patients, none experienced recurrence of status during a prolonged follow-up period. Transient respiratory arrest occurred in 1 patient, but no other significant complications were observed. Studies of plasma drug levels suggest that most patients attain good seizure control at concentrations between 30 and 100 ng per milliliter. Clinical observations indicate that repetitive injections are not required for continuing control of seizures in patients whose seizures are initially controlled. Lorazepam appears to be an effective and safe drug for treatment of status epilepticus, with a duration of control longer than that achieved with diazepam.
Six cases of unusual parapharyngeal lesions are presented in detail along with discussions of the anatomy, pathology, clinical aspects, and treatment methods of lesions in the parapharyngeal space. Newer techniques of CT scanning and selective embolization are discussed as they apply to management of such lesions. A plasmalymphocytic tumor with amyloidosis is described. The authors believe that such a lesion has not been reported previously in the parapharyngeal space.