Disulfiram-like reaction associated with carmofur after celiac plexus alcohol block.
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Biomedical subjects
Publications and source records attributed to Y Mizoi.
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The effects of polymorphism of aldehyde dehydrogenase (ALDH) and obesity (body weight/lean body mass) on the rate of ethanol elimination were studied. One hundred and forty subjects of healthy Japanese male volunteers who ingested 0.4 g/kg of ethanol were divided into two groups, i.e., a normal ALDH group with a low Km isozyme of ALDH and a deficient group. They were further divided into three groups in which the obesity increased in the order group A, B, C. Ethanol elimination (ER) and beta were significantly higher in the normal ALDH group than in the deficient group. In the normal ALDH subjects, beta of group C(0.187 mg/ml/hr) was higher than that of group B(0.155 mg/ml/hr). No difference in ER was observed among the three groups of the obesity in each ALDH group. Distribution volume of ethanol, r, estimated by Watson's method (0.65 to 0.89) was more accurate than Widmark's r(0.5 to 1.00). Ethanol elimination rate in the normal ALDH subjects was greater than that in Caucasian reported by other authors. Body weight was correlated well with liver weight in 135 autopsy materials.
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Serotonin S2 and dopamine D2 receptors in the prefrontal cortex and caudate nucleus of postmortem brains of chronic schizophrenics were studied using 3H-ketanserin and 3H-spiperone, respectively. In the prefrontal cortex of schizophrenics, we found a significant decrease in the maximum number of 3H-ketanserin binding sites (Bmax), with no change in the dissociation constant (Kd). Conversely, both Bmax and Kd of 3H-spiperone binding to the caudate nucleus were significantly increased in the schizophrenic patients. There were no differences in receptor indices between patients who were taking neuroleptics until their death and those who had taken none for 2 months or more prior to death. These findings suggest that alterations in S2 receptors in the prefrontal cortex may reflect the disease process, per se, and that the increase in the number of D2 receptors in the caudate nucleus of schizophrenics is not due solely to neuroleptic medication.
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In the course of celiac plexus alcohol block, facial flushing, palpitations, and hypotension are occasionally incurred in some patients. We hypothesized that the phenomenon represents acetaldehyde syndrome, not response to increased blood levels of ethanol as might be supposed. In order to prove our hypothesis, we selected five patients scheduled to undergo celiac plexus alcohol block, and, with their consent, we measured blood concentration of ethanol and acetaldehyde before and for 6 hr after the block. We also determined the phenotypes of aldehyde dehydrogenase (ALDH) in their hair roots. We found that "flushers" are found exclusively among subjects without ALDH I, and that their blood levels of acetaldehyde were significantly higher than those of "non-flushers" within 10 min after the block. The flushers also gave histories of facial flushing after ingestion of small amounts of ethanol. On the basis of such histories one can anticipate whether acetaldehyde syndrome is likely or unlikely to accompany the block.
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Normal Japanese subjects were divided into two groups, i.e., one with both low and high Km isozymes of aldehyde dehydrogenase for acetaldehyde, and the other deficient in the low Km isozyme. After intake of 0.4 g/kg alcohol, the deficient subjects showed high level of blood acetaldehyde, facial flushing and the other dysphoric symptoms, including increase of pulse rate, decrease of diastolic blood pressure, changes of pulse wave in the fingertip, and elevation of the arterial pressure and blood flow rate in common carotid arteries as well as increase of plasma catecholamines level. In contrast, subjects with normal ALDH did not show these changes. From the observation of liver specimens obtained at autopsy, the frequency of deficient phenotype of ALDH in Japanese was presumed to be about 36%.