Biomedical subjects
Publications and source records attributed to J K Wilkin.
Rosacea is a dynamic facial dermatosis characterized by exacerbations and remissions which affects middle-aged men and women, most of whom flush easily. It is a conspicuous, yet treatable condition. Oral and topical antibiotics, as well as changes in lifestyle and elimination of aggravating factors, are necessary for control. Nurses facilitate compliance with the treatment regimen and optimize patient self-esteem.
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The effect of nadolol versus placebo on both flushing provoked in a laboratory setting and spontaneous flushing was studied in 15 patients with erythematous telangiectatic rosacea. The intensity of the flushing reactions was assessed in the laboratory by the cutaneous perfusion index method with laser-Doppler velocimetry. No effect of nadolol on the flushing reactions provoked in the laboratory was detected.
Red lunulae are associated with rheumatoid arthritis, systemic lupus erythematosus, alopecia areata, cardiac failure, hepatic cirrhosis, lymphogranuloma venereum, psoriasis, carbon monoxide poisoning, twenty-nail dystrophy, and reticulosarcoma. We examined four patients with red lunulae. Three had chronic obstructive pulmonary disease. Two of these three were alcohol abusers and were without any of the conditions previously associated with red lunulae. Two of the four also had palmar erythema. Histopathologic examination of the red lunula in one of the four cases did not show signs of neovascularization. We report our findings in these patients, which suggest that red lunulae result from increased arteriolar blood flow, a vasodilatory capacitance phenomenon, or changes in the optical properties of the overlying nail so that normal blood vessels become more apparent.
Cutaneous vasomotion has not been actively investigated until recently. This is hardly surprising, as it has not been a reproducible phenomenon. During recent studies on various physiological and pharmacological vascular problems, we identified experimental conditions in which cutaneous vasomotion commonly occurred. We then characterized four methods that routinely provoke human cutaneous vasomotion in vivo, in order to further characterize this physiological phenomenon. Although several adaptive advantages may exist for vasomotion, the most compelling theory can be derived mathematically from Poiseuille's law. Because the flow of a liquid through a vessel is proportional to the fourth power of the radius, it can be demonstrated that the resistance of a vessel with a constant diameter is greater than that of a vessel of the same average diameter in which the diameter changes sinusoidally. Importantly, the rhythmicity originates within the vascular tissue, and there appears to be electromechanical coupling. The cation effluxes demonstrate oscillatory behavior that may be driven by the availability of adenosine triphosphate. Substrate and product concentrations can alter the activity of the allosteric enzyme, phosphofructokinase, which may control the oscillations in ATP concentration. Despite the qualitatively different provocative agents, the cutaneous rhythmic oscillatory vasomotion always first appears after a peak in erythrocyte flux, and it disappears before reaching resting flux levels. Thus, cutaneous rhythmic oscillatory vasomotion is a midrange phenomenon, most likely corresponding to the "oscillatory domain" of glycolysis. Finally, a common feature of tissue preparations for the study of vasomotion is that anesthesia was not used. We have shown that this inhibitory effect of anesthetic agents may persist well beyond "anesthesia," and this suppression may be of clinical importance in the patient with microcirculatory compromise undergoing surgery.
Forearm cutaneous blood flow was monitored continuously by laser Doppler velocimetry in 12 normal human subjects before and after a 5-min topical challenge with 5 M propionaldehyde. The aldehyde challenge routinely provoked an increase in cutaneous blood flow. During the recovery phase from peak stimulated blood flow to a lower, stable, resting level of flow, the cutaneous blood flow exhibited rhythmic oscillatory activity. Three stages of oscillatory vasomotion were defined to characterize changes: the first 5 min after onset (I), the 5-min span bracketing the temporal midpoint (II), and the final 5 min (III). The average period, wave height, and erythrocyte flux decreased during these three stages of oscillatory vasomotion. These changes and the temporal characteristics of onset and disappearance of oscillatory vasomotion suggest an origin of the oscillations in the slow wave activity of vascular smooth muscle.
Despite the systemic nature of many agents that provoke flushing reactions, the erythema is most prominent in the "blush area." To elucidate the physiologic basis for such a limited distribution, two types of flushing challenges were studied in normal volunteers. Nicotinic acid provokes flushing through a direct action of vasodilator prostaglandins on vascular smooth muscle. The flushing reaction provoked by oral thermal challenge is mediated via neural mechanisms. Both agents led to increases in cutaneous blood flow at both malar and forearm sites. Both absolute and proportional increases were consistent with the view that the greater vascular capacitance in the visible, superficial cutaneous vasculature in the blush area accounts for the limited distribution of flushing in response to a systemic stimulus.
Twelve healthy subjects of Oriental ancestry were challenged with topical applications of lower aliphatic alcohols and aldehydes after topical pretreatment consisting of 4-methylpyrazole in hydrophilic ointment on the volar aspect of one forearm and hydrophilic ointment alone on the contralateral volar forearm. Cutaneous blood flow was monitored by laser Doppler velocimetry. Pretreatment with 4-methylpyrazole, a specific inhibitor of alcohol dehydrogenase, led to a significant decrease in the cutaneous vascular response to the alcohols as a group, but did not lead to changes in the cutaneous vascular response to the aldehydes as a group. Among the individual alcohols, pretreatment with 4-methylpyrazole reduced the response significantly to all concentrations of 1-propanol and 1-butanol. The means of the vascular response to the different concentrations of ethanol decreased, but not significantly. Additionally, 4-methylpyrazole did not have an independent effect on cutaneous blood flow. These results are consistent with the view that the cutaneous vascular reaction to primary alcohols applied topically to the skin of Orientals is provoked, in large part, by the corresponding aldehyde.
2,4-Dinitrochlorobenzene (DNCB) is used for immunotherapy of alopecia areata and verruca vulgaris. We initially postulated that the presence of mutagenic contaminants in commercially available DNCB might account for part of its mutagenicity. We have now characterized changes in the dose-mutagenic response curve of 99% DNCB modified by adding 1% concentrations of known contaminants: 1-chloro-2-nitrobenzene; 1,3-dinitrobenzene; and 2,4-dichloronitrobenzene. Dose-response curves were generated using Salmonella typhimurium tester strains TA-98 and TA-100 at concentrations of 0, 1, 5, 10, 25, 50, and 100 micrograms per plate in a modified Ames assay. We observed a linear dose-response relationship with a slight, but nonsignificant, shift to the right when contaminants were added. We conclude that DNCB is itself mutagenic, and that contaminants play a minor role in its observed mutagenicity.
The photochemical conversion of diphenylcyclopropenone to diphenylacetylene has recently been reported. Diphenylcyclopropenone is used in the treatment of alopecia areata and is nonmutagenic in a limited Ames assay. We examined diphenylcyclopropenone and diphenylacetylene, as well as synthetic precursors of diphenylcyclopropenone--dibenzylketone and alpha,alpha'-dibromodibenzylketone--for mutagenicity against TA100, TA98, TA102, UTH8413, and UTH8414. All compounds were nonmutagenic except alpha,alpha'-dibromodibenzylketone, which was a potent mutagen in TA100 with and without S-9 activation. The effect of photochemical activation of diphenylcyclopropenone in the presence of bacteria demonstrated mutagenicity in UTH8413 (two times background) at 10 micrograms/plate with S-9 microsomal activation. 8-Methoxypsoralen produces a mutagenic response in TA102 at 0.1 microgram/plate with 60 seconds of exposure to 350 nm light. In vitro photochemically activated Ames assay with S-9 microsomal fraction may enhance the trapping of short-lived photochemically produced high-energy mutagenic intermediates. This technique offers exciting opportunities to trap high-energy intermediates that may play an important role in mutagenesis. This method can be applied to a variety of topically applied dermatologic agents, potentially subjected to photochemical changes in normal use.
The effect of naltrexone vs. placebo on alcohol-provoked flushing was studied in 20 healthy subjects of Oriental ancestry and 20 healthy white subjects. The intensity of the flushing reactions was assessed by two independent methods, the cutaneous perfusion index by laser Doppler velocimetry and the change in malar thermal circulation index by telethermometry. No effect of naltrexone on alcohol-provoked flushing was detected with either method in either racial group. The incidence of abdominal discomfort and nausea associated with naltrexone treatment was much greater among Orientals than whites.
Two recently observed patients with sternocostoclavicular hyperostosis exemplify the characteristic presentation of this rheumatologic disorder. We describe its manifestations, review the literature on this subject, and discuss clinical and radiologic aspects, including the frequently associated dermatologic disorder palmoplantar pustulosis. Sternocostoclavicular hyperostosis is an increasingly common diagnosis, and practicing physicians should be aware of the distinctive features that allow accurate differentiation from psoriatic arthritis and other diseases.
The substrate utilization rates of human cutaneous alcohol dehydrogenase were determined for 7 lower aliphatic primary alcohols: ethanol, propanol, butanol, pentanol, 2-methylpropanol, 3-methylbutanol, and 2,2-dimethyl-propanol. 1-Pentanol gave the highest relative activity and 2,2-dimethylpropanol the lowest. The frequency of erythemogenesis was determined in vivo for these 7 lower aliphatic primary alcohols. The frequency of erythemogenesis correlated strongly and significantly with the rate of substrate utilization by alcohol dehydrogenase. These results are consistent with the view that the reaction to primary alcohols applied topically to human skin is provoked, in large part, by the corresponding aldehyde.
Two theories, myogenic and metabolic, have been proposed for reactive hyperemia. Since the metabolic theory implies that the changes in flow rate during reactive hyperemia must be explained in terms of changes in concentration of a vasodilator metabolite produced during anoxia, the rate of rise to peak reactive hyperemic flow should discriminate between these two possible mechanisms. Accordingly, changes in human cutaneous blood flow were monitored during postocclusive reactive hyperemia. The absolute values of both the rate of rise from zero blood flow to peak reactive hyperemic flow and the rate of recovery from peak reactive hyperemic flow to resting levels decrease with increasing durations of arterial occlusion. The time-dependent decrease in both rates is compatible with viscoelastic characteristics of the wall of resistance vessels and is not consistent with changes in concentration of a hypothesized vasodilator metabolite produced during occlusion.
Serial subtraction and multiplication problems were performed orally by 21 healthy human subjects during two three-minute periods separated by a 22-minute rest interval. During the period of mental activity, cutaneous blood flow in the finger fell to 59%, digital cutaneous pulse pressure fell to 62%, and heart rate increased by 24% of the subjects' initial baseline values. Cutaneous blood flow in the malar region did not change. Because vasomotor control of the finger skin is principally vasoconstrictor and that of the malar area vasodilator, these results suggest that mental activity unrelated to obvious stress may provoke changes in cutaneous blood flow in areas controlled by sympathetic vasoconstrictor fibers. Simultaneous changes in digital cutaneous blood flow, digital cutaneous pulse pressure, and heart rate indicate an autonomic-mediated effect.
It is a widely accepted opinion that some of the spots produced on the forearm and hand by external compression of the brachial artery are the visible evidence of an intraosseous shunt in the humerus. These spots were first evaluated systematically by Bier in 1898. Additional studies were conducted by Rehberg and Carrier in 1922 and by Wolf in 1924, the latter's conclusions providing the currently accepted view. We examined these spots with laser Doppler velocimetry and found no differences in cutaneous perfusion among spots of different coloration. Further, there was no difference between any of the spots produced by occluding the brachial artery and values obtained from the forearm of postmortem subjects. It appears that the differences in coloration are not due to an intraosseous vascular shunt at the level of the mid humerus but, instead, are due to a capacitance phenomenon with venodilation in the dark areas and venoconstriction in the pale areas.
Monosodium glutamate is widely regarded as the provocative agent in the "Chinese restaurant syndrome," of which flushing is regarded as part of the reaction. Six subjects were monitored by laser Doppler velocimetry for changes in facial cutaneous blood flow during challenge with monosodium glutamate and its cyclization product, pyroglutamate. Additionally, records of patients challenged with monosodium glutamate in the laboratory were reviewed. No flushing was provoked among the twenty-four people tested, eighteen of whom gave a positive history of Chinese restaurant syndrome flushing. These results indicate that monosodium glutamate-provoked flushing, if it exists at all, must be rare. Monosodium glutamate and its cyclization product, pyroglutamate, may provoke edema and associated symptoms.