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J K Walton

Publications and source records attributed to J K Walton.

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Modulating role of dopamine on anesthetic requirements.

The influence of dopamine on halothane anesthetic requirements was determined in mice. Halothane anesthetic requirement was defined as the minimum anesthetic concentration (MAC) that prevented 50% animals from moving in response to a supramaximal stimulus. Levodopa (L-DOPA) dose-dependently decreased halothane MAC to a maximum of 49% of control; over the same dose range L-DOPA increased striatal dopamine nearly 4-fold. The MAC-reducing effect of L-DOPA was attenuated by selective antagonism of the D2 dopamine receptor with YM-09151-2 while selective blockade of the D1 dopamine receptor with SCH-23390 did not alter L-DOPA's effect on the MAC for halothane. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) decreased striatal dopamine by 82% and increased the MAC for halothane by 27%. Repletion of striatal dopamine with L-DOPA, in MPTP-treated mice, restored the MAC for halothane back to the control state. The regression line derived from the plot of halothane MAC versus striatal dopamine content shows a highly significant correlation between the two variables (r2 = 0.94). These are the first results to suggest that anesthetic requirements can be modulated directly and precisely by increasing or decreasing the content of a single neurotransmitter in the central nervous system.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Failed vasectomy.

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Expert Testimony

Aging results in an unusual expression of Drosophila heat shock proteins.

We used high-resolution two-dimensional polyacrylamide gel electrophoresis to evaluate the effect of aging on the heat shock response in Drosophila melanogaster. Although the aging process is not well understood at the molecular level, recent observations suggest that quantitative changes in gene expression occur as these fruit flies approach senescence. Such genetic alterations are in accord with our present data, which clearly show marked differences in the synthesis of heat shock proteins between young and old fruit flies. In 10-day-old flies, a heat shock of 20 min results in the expression of 14 new proteins as detectable by two-dimensional electrophoresis of [35S]methionine-labeled polypeptides, whereas identical treatment of 45-day-old flies leads to the expression of at least 50 new or highly up-regulated proteins. In addition, there is also a concomitant increase in the rate of synthesis of a number of the normal proteins in the older animals. Microdensitometric determinations of the low molecular weight heat shock polypeptides on autoradiographs of five age groups revealed that their maximum expression occurs at 47 days for a population of flies with a mean life span of 33.7 days. Moreover, a heat shock effect similar to that observed in senescent flies occurs in young flies fed canavanine, an arginine analogue, before heat shock.

Aging

Dexmedetomidine diminishes halothane anesthetic requirements in rats through a postsynaptic alpha 2 adrenergic receptor.

The effect of 4(5)-[1-(2,3-dimethylphenyl)ethyl]imidazole (medetomidine), the alpha 2 adrenergic agonist, on anesthetic requirements was investigated in rats anesthetized with halothane. Halothane MAC was determined before and after either dexmedetomidine (d-enantiomer) or levomedetomidine (l-enantiomer) 10, 30, and 100 micrograms/kg or vehicle ip. There was a dose-dependent decrease in MAC with the d-, but not the l-, stereoisomer. At the highest dose of dexmedetomidine (100 micrograms/kg), halothane could be discontinued for up to 30 min with no response to tail clamping. To determine whether alpha 2 adrenoreceptors mediated this effect of dexmedetomidine on MAC, cohorts of rats were pretreated with idazoxan, 10 mg/kg ip, a highly selective alpha 2 antagonist. This completely prevented the reduction of MAC caused by dexmedetomidine. To determine whether the reduction of MAC caused by dexmedetomidine was mediated in part through either opiate or adenosine receptors, groups of rats were pretreated with either naltrexone, 5 mg/kg ip, an opiate antagonist, or 8-phenyltheophylline, 2.5 mg/kg ip, an A1 adenosine antagonist. These two pretreatments did not alter the reduction of MAC by dexmedetomidine. To determine whether postsynaptic mechanisms mediate the anesthetic effect of dexmedetomidine, rats were depleted of central catecholamine stores with either n-(2-chloroethyl)-n-ethyl-2-bromobenzylamine (DSP-4) or reserpine and alpha-methyl-para-tyrosine and MAC was determined before and after each dose of dexmedetomidine. While the catecholamine-depleted rats had a lower basal MAC than the vehicle controls, there was still a profound reduction in halothane MAC after administration of dexmedetomidine. The reduction of MAC by dexmedetomidine was blocked with idazoxan in the catecholamine depleted rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Association between symptomatology and uroflowmetry in benign prostatic hypertrophy.

The symptoms of 128 consecutive patients (mean age 65 years) with benign prostatic hypertrophy were assessed and compared with flowmetry recordings. The 84 patients (65%) with peak flow rates greater than or equal to 2 standard deviations from the mean were considered to have abnormal flowmetry and their symptoms were compared with those of the 44 men with normal peak flows. No significant correlation between peak flow rate and age was found within this group. Symptoms of poor stream, nocturia, post-micturition dribble and nocturnal or full-bladder hesitancy were present in over two-thirds of the whole series. Poor stream, hesitancy and nocturnal or full-bladder hesitancy were found to have significant associations with abnormal flowmetry recordings but also to have a high incidence within the normal flowmetry group. Discriminant analysis was unable to define a symptom complex which would accurately predict those within our group with abnormal peak flows. It was concluded that symptomatology and flowmetry evidence of lower urinary tract obstruction are not associated and subjective and objective evidence must be considered independently in selecting candidates for prostatectomy.

Aged

Spermatic cord torsion in the neonate.

Three cases of spermatic cord torsion in neonates are presented. Support is given to the nonoperative management of both the unaffected contralateral testis and late presentation cases.

Humans

Complications from prolonged catheterisation prior to prostatectomy.

This paper studies 46 patients with urinary retention who came to prostatic surgery some time later. With prophylactic antibiotics used in cases with urinary infection the risk of surgery is not increased, despite an average period between catheterisation and surgery of one month.

Anti-Bacterial Agents

Fracture of the penis with laceration of the urethra.

Two patients are described with severe injury to the penis sustained during sexual intercourse. The literature is reviewed. A conservative approach to management with suprapubic urinary diversion led to acceptable results.

Adult

A New Zealand experience of staghorn calculus surgery.

Sixty-one patients with staghorn calculi who have undergone surgery at the Auckland Department of Urology since 1972 have been reviewed. Maoris have been shown to have a higher disease incidence than Europeans. In those cases followed longer than one year true stone recurrences was 14%. A significant number of patients have developed obstruction in the pelviureteric region, and the reasons for this and possible preventive measures are discussed.

Ethnicity