Biomedical subjects
Publications and source records attributed to S A George.
PUVA and UVB phototherapy are very effective and popular treatments for a variety of dermatological problems. This article gives an overview of the possible acute and chronic adverse effects of these therapies.
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A 2-year-old girl presented with a history of an erythematous rash which occurred immediately after exposure to sunlight and had been a problem since birth. Extensive laboratory investigations to exclude genophotodermatoses, photosensitivity secondary to metabolic disorders and photoaggravated dermatoses were negative. Monochromator irradiation phototesting demonstrated immediate erythematous flares to all ultraviolet B (UVB), UVA and visible wavelengths up to 500 nm. A diagnosis of solar urticaria was made and she responded to loratidine 10 mg daily. We believe this is the first report of solar urticaria, confirmed by phototesting with a monochromator so early in life.
OBJECTIVE: To compare the pharmacokinetic profile of gentamicin given as a once daily dose as against the conventional twelve hourly dose in preterm neonates. DESIGN: Randomized double blind study. SETTING: Tertiary level Neonatal Intensive Care Unit. SUBJECTS: Eighteen preterms admitted during the period January 1994 to May 1994. METHODS: The babies were randomly assigned to receive either the once daily (plan O, 4 mg/kg Q 24 h) or the conventional (plan C, 2.5 mg/kg Q 12 h) gentamicin dosage regimen. Blood was collected for the first peak level one hour after the first dose of gentamicin. Trough and peak-2 levels were collected before and one hour after the dose due at 48 hours, respectively. Assays were done using fluorescence immunoassay and the pharmacokinetic estimations were calculated using the three measured levels on a simplified one-compartment open model. Serum concentration time curves were plotted using the computerized Bayesian forecasting. Student 't' and Mann-Whitney U tests were applied as required. MAIN OUTCOME MEASURES: Initial peak levels and steady state trough and peak levels in both groups. RESULTS: Optimum therapeutic peak level after the first dose was achieved only with the once daily gentamicin regimen (mean level 5.88 vs 3.88 micrograms/ml p = 0.000). Mean trough levels remained over 2 micrograms/ml in the conventional regimen (2.76 vs 1.96 micrograms/ml p = 0.019) group. Mean peak levels at the steady state were not significantly different in either regimen (6.65 vs 5.45 micrograms/ml in conventional p = 0.177). None of the neonates showed nephrotoxicity. CONCLUSION: Once daily dose (4 mg/kg) of gentamicin has logistic and monetary benefits in addition to the obvious pharmacokinetic advantage.
Brachioradial pruritus (BRP) is an uncommon localized pruritic dermatosis only previously described from the tropics and subtropics. We report two cases in British residents who had a history of prolonged ultraviolet radiation exposure, and who responded to strict photoprotection of the affected sites.
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In an open study of 21 severely affected adult atopic dermatitis patients, air-conditioned narrow-band UVB phototherapy using the Philips TL-01 lamp three times weekly for 12 weeks resulted in a 68% reduction in atopic dermatitis severity scores, with a concomitant 88% reduction in potent topical steroid use. Follow-up at 24 weeks revealed that six patients had relapsed to > 70% of pre-phototherapy severity scores; the remaining 15 continued to derive long-term benefit. The mean value of potent topical steroid use remained 50% below pre-phototherapy needs. Narrow-band UVB (TL-01) phototherapy appears an effective, steroid-sparing treatment for chronic severe atopic dermatitis, offering long-term benefits in the majority of those treated.
Despite a widely held belief that the use of emollients prior to broad-band UVB irradiation accelerates clearance of psoriasis, only one single-blind controlled study exists in support of this. No similar study has been carried out with photochemotherapy (PUVA) or narrow-band UVB (311-313 nm) phototherapy. As some emollients absorb UV radiation, and thereby inhibit psoriasis clearance, there is a need to identify emollients suitable for pre-irradiation use. Coconut oil may be useful in this respect. In two randomized groups of patients with chronic plaque psoriasis undergoing either routine PUVA (n = 14) or narrow-band UVB phototherapy (n = 15), a single-blind controlled (half-body) study was undertaken to assess the effect of pre-irradiation application of coconut oil. Patients were given PUVA twice weekly, or TL-01 therapy thrice weekly. The initial UV dose was 70% of previously determined minimal phototoxic (MPD) or minimal erythema doses (MED), with 40% incremental steps at each visit (reduced if adverse effects occurred). Psoriasis severity was scored on each side after every three treatments. No significant acceleration of psoriasis clearance was seen in either group. We do not, therefore, recommend the routine use of emollients prior to PUVA or TL-01 therapy when using near erythemogenic irradiation regimens.
Twenty-five patients suffering from severe polymorphic light eruption (PLE) were randomized to either photochemotherapy (PUVA) or narrow-band phototherapy (TL-01 UVB) treatment in early spring; patients receiving UVB were given placebo tablets to achieve a matching therapy procedure. During the 4 months following treatment, patient exposure to solar UVB was monitored with polysulphone badges. PLE occurrence, severity, and restriction of outdoor activity were recorded, using weekly diary-sheets. Analysis of covariance on this data, using the logarithm of UVB exposure as the explanatory variable, showed no significant differences between the treatments. TL-01 UVB is an effective alternative to PUVA in the management of PLE.
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Thirty-nine patients with psoriasis undergoing PUVA participated in a prospective double-blind study of acute non-phototoxic adverse effects comparing the liquid formulations of 8-methoxypsoralen (0.6 mg/kg) and 5-methoxypsoralen (1.2 mg/kg). A much higher number of patients experienced nausea (8-MOP = 51.3%, 5-MOP = 7.7%) and pruritus (8-MOP = 71.8%, 5-MOP = 43.6%) than has been reported for crystalline tablets. No attempt was made to compare therapeutic efficacy between liquid and crystalline tablet formulations or between 8-MOP and 5-MOP, which both appeared to be effective. The high incidence of adverse effects suggests that current dosage recommendations be reviewed.
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Under normal visual stimulation, simultaneous recording from ganglion cells in the retina and from the axons of these cells in the brain revealed activity-dependent differences in the velocity of impulse propagation. In frog ganglion cells, spikes initiated 5-500 ms after a previous impulse showed supernormal increases in conduction velocity of up to 17%; spikes initiated 500-2000 ms after a previous one traveled more slowly than a spike initiated after a long period of rest. Cat ganglion cell impulses showed much smaller supernormality (maximum 3%), but exhibited pronounced slowing due to refractoriness and long-term fatigue associated with their high levels of spontaneous activity.
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In the isolated chick retina, the propagation velocity of Spreading Depression (SD) was approximately doubled and the frequency of spontaneous waves was substantially increased with solutions bubbled with 5% CO2 instead of air, at constant pH (7.5-7.6). There was no effect on SD of raised pO2. Large changes of pH (to 6.4 and 9.4) produced, respectively, decreases and increases of velocity; but there was no clear pH dependence with changes less than 0.5 pH units. The resting [K+]0 and the elevation during SD, measured with K+ sensitive micro-electrodes, were not consistently altered with 5% CO2 when there was faster conduction. The effect of raised pCO2 is opposite to that observed previously in rat cortex in vivo, which afforded evidence for a similarity between SD and the disturbance in the aura phase of migraine attacks. The effects in vivo must presumably be due to factors not acting in the isolated chick retina.