Biomedical subjects
Publications and source records attributed to J R Gibson.
Azelaic acid 20% cream (AZELEX) is a novel anti-acne agent with antimicrobial activity and keratinization-normalizing properties. In acne it is broadly comparable in efficacy to 0.05% tretinoin, 5% benzoyl peroxide, and 2% erythromycin, but is less irritating than tretinoin and benzoyl peroxide.
The development of new topical anti-acne therapies reflects the need for medications that address the requirements and concerns of an increasingly mature and demanding acne patient population. Some of the topical agents currently under investigation in the United States include several alpha-hydroxy acids (AHAs), the retinoids tazarotene and adapalene, and azelaic acid. All of these agents appear to exert their effect on acne through some effect on the process of keratinization and/or the thickness of the stratum corneum. Azelaic acid also has significant antimicrobial activity relevant to its efficacy in acne vulgaris. While azelaic acid has already been used successfully in many parts of the world for several years, the potential roles of the new retinoids in acne therapy are just beginning to be clarified. The properties of AHAs suggest that they may also be of value in the treatment of acne, but further systematic evaluation is needed.
In this study we have evaluated the ability of three typing methods, pulsed field gel electrophoresis (PFGE), phage-typing and ribotyping, to discriminate not only between strains of differing serotypes but also between strains within a single serotype, heat stable serotype 2 (HS2). Forty-five isolates derived from cases of campylobacter enteritis occurring in the Cardiff area were examined. These included 18, mostly HS2, strains associated with an outbreak. The typing results for these and a further 39 epidemiologically unrelated strains of serotype HS2 were compared. This is the first report documenting the use of PFGE in an epidemiological investigation of Campylobacter jejuni in the UK. The results presented suggest that this technique is the most discriminatory of the three subtyping methods examined.
DNAse-positive strains of Campylobacter jejuni degrade their chromosomal DNA during standard preparative procedures before pulsed-field gel electrophoresis (PFGE). A simple method for inactivation of this DNAse activity is described. Formaldehyde fixation of the bacterial cells resulted in the preservation of the DNA in a state suitable for restriction digestion and subsequent electrophoretic analysis.
"This research note is a follow-up to a comparative study of Soviet interregional migration during the years 1971-75 and 1981-85.... The recent publication of the last (and scarce) statistical yearbook for the U.S.S.R....makes it possible to calculate regional net migration balances for the final five-year period of the Soviet Union's existence (1986-1990)...on the basis of the residual method, and to compare the results with those for 1981-85 in the original study. This will be the last such update, not only because the U.S.S.R. no longer exists and no more Soviet statistical yearbooks will be issued, but also because the amount of error entailed by the residual method as a result of increased emigration would be unacceptable."
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Oligonucleotide primers designed from repetitive extragenic palindromic (REP) sequences were used to PCR-amplify Salmonella DNA. Unpurified template DNA, present in crude cell extracts, yielded an essentially identical banding pattern to that arising from the use of purified DNA. However, the PCR product derived from the crude preparations did not survive storage at 4 degrees C. This post-PCR DNA degradation, attributed to endogenous Salmonella nucleases, was inhibited by the addition of EDTA, or storage at -20 degrees C.
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1. Many lines of evidence suggest that signals relayed by the magnocellular and parvocellular subdivisions of the primate lateral geniculate nucleus (LGN) maintain their segregation in cortical processing. We have examined two response properties of units in the striate cortex of macaque monkeys, latency and transience, with the goal of assessing whether they might be used to infer specific geniculate contributions. Recordings were made from 298 isolated units and 1,129 multiunit sites in the striate cortex in four monkeys. Excitotoxin lesions that selectively affected one or the other LGN subdivision were made in three animals to demonstrate directly the magnocellular and parvocellular contributions. An additional 435 single units and 551 multiunit sites were recorded after the ablations. 2. Most units in striate cortex had visual response latencies in the range of 30-50 ms under the stimulus conditions used. The earliest neuronal responses in striate cortex differed appreciably between individuals. The shortest latency recorded in the four animals ranged from 20 to 31 ms. Comparable values were obtained from both single unit and multiunit sites. After lesions were made in the magnocellular subdivision of the LGN in two animals, the shortest response latencies were 7 and 10 ms later than before the ablations. A larger lesion in the parvocellular subdivision of another animal produced no such shift. Thus it appears that the first 7-10 ms of cortical activation can be attributed to activation relayed by the magnocellular layers of the LGN. 3. The units with the shortest latencies were all found in layers 4C or 6 and their responses were among the most transient in striate cortex. Furthermore, their responses all showed a pronounced periodicity at a frequency of 50-100 Hz. This periodicity was stimulus locked, and the responses of all short-latency units oscillated in phase. 4. An index of response transience was computed for the units recorded in striate cortex. The distribution of this index was unimodal and gave no suggestion of distinct contributions from the geniculate subdivisions. Magnocellular and the parvocellular lesions affected the overall transience of responses in striate cortex. The changes, however, were very small; extremely transient responses and extremely sustained responses survived both types of lesions. 5. A characteristic profile was observed in the response latencies in superficial layers. Latencies appeared to increase monotonically from layer 4 toward the surface of cortex, with the most superficial neurons not becoming active until 15 ms after responses were observed in layer 4C.(ABSTRACT TRUNCATED AT 400 WORDS)
In a double-blind, two-period crossover study, 24 healthy volunteers were evaluated to establish the time of onset of action of activity of acrivastine in suppressing the weal and flare response to intradermally injected histamine. Volunteers received single doses of 8 mg acrivastine and placebo according to a fully randomized, balanced treatment plan. Acrivastine significantly (P less than 0.002) reduced the flare response induced by 0.4 micrograms histamine challenge 15 min after oral acrivastine dosing when compared with placebo. A significant (P less than 0.001) reduction of the weal response was noted at 25 min, although trends in this direction were already present at earlier time points.
Both halobetasol propionate and clobetasol 17-propionate exerted very marked antiinflammatory, antiproliferative, and vasoconstrictive effects during evaluation in a range of dermatopharmacologic models. Halobetasol propionate was distinctly more potent than clobetasol 17-propionate in the ultraviolet-induced dermatitis inhibition assay in guinea pigs and in the rat model of oxazolone-induced late inflammatory reaction. Halobetasol propionate was slightly more potent than clobetasol 17-propionate in inhibiting croton oil-induced ear edema in rats and mice and in the mouse model of oxazolone-induced early inflammatory reaction. In the cotton-pellet granuloma assay in rats and the epidermal hyperplasia inhibition assay in guinea pigs, halobetasol propionate was distinctly superior to clobetasol 17-propionate. There was a trend in favor of halobetasol propionate in the cutaneous vasoconstriction assay performed in volunteers with ethanol solutions of halobetasol propionate and clobetasol 17-propionate. In a further vasoconstriction assay, performed with a 0.05% concentration of both halobetasol propionate and clobetasol 17-propionate in cream and ointment formulations, halobetasol propionate ointment yielded the highest blanching score. In a hypothalamic-pituitary-adrenal axis study in volunteers, effects of 0.05% halobetasol propionate ointment and 0.05% clobetasol 17-propionate ointment on serum cortisol levels were similar. The overall efficacy trends demonstrated in these dermatopharmacologic studies are in agreement with predictions made from corticosteroid structure and activity relationships and the results of two clinical trials comparing halobetasol propionate and clobetasol 17-propionate ointments in the treatment of plaque psoriasis.
The results of two studies are presented that reveal the efficacy and safety of 0.05% halobetasol ointment in the treatment of patients with plaque psoriasis of at least moderate severity. Both multicenter studies were randomized, double-blind, and vehicle controlled, and study medications were applied twice daily for 2 weeks. One study was a paired-comparison (PC); the other study was of parallel-group (PG) design. Both studies called for evaluations at entry (week 0) and after 1 and 2 weeks of treatment. The PC study enrolled 100 patients; the PG study enrolled 110 patients; 204 patients provided efficacy data over both studies. In the PC study, plaque elevation, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistical (p less than or equal to 0.0003) and clinical significance (all greater than 1-unit difference on the rating scale) favoring 0.05% halobetasol ointment over vehicle. Pruritus (initially mild) and total score also showed statistically significant treatment differences favoring halobetasol at the final evaluation. Patient global responses for "effectiveness" and "overall rating" favored 0.05% halobetasol ointment over vehicle. In the PG study, induration, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistically and clinically significant differences favoring 0.05% halobetasol ointment over vehicle. Physician's global evaluation favored 0.05% halobetasol ointment over vehicle after 2 weeks of use. No patients were released from either study because of adverse events. No systemic adverse events or findings of skin atrophy were reported in these studies. Reports of "stings" or "burns" were equally divided between halobetasol and its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
The efficacy and safety of halobetasol propionate 0.05% cream, an ultra high-potency corticosteroid preparation, was evaluated in a double-blind, vehicle-controlled, paired comparison study. Patients' psoriatic lesions were evaluated before treatment and after 1 and 2 weeks of twice-daily treatment with halobetasol propionate and vehicle. Response measures (plaque elevation, erythema, scaling, and pruritus) were evaluated with a 4-point severity scale whereby the sum provided a total score. Patient self-assessment measures were obtained at the 2-week visit by categorizing his or her global responses to queries about each treatment's "effectiveness" and "overall rating." All efficacy parameters, as judged by the physician, showed statistically significant (p = 0.0001) treatment differences favoring halobetasol propionate at both week 1 and week 2 evaluations. Patient global responses for "effectiveness" and "overall rating" favored halobetasol propionate 0.05% cream over vehicle after 2 weeks of use. No systemic adverse drug effects were reported during the study. No patient was discontinued from the study because of an adverse event, and there was no evidence of skin atrophy after 2 weeks of treatment with either agent. Patient reports of "stings" or "burns" were equally distributed between the active and vehicle treatment groups. This trial demonstrates that halobetasol propionate 0.05% cream is clinically beneficial and without evidence of significant risk in the treatment of plaque psoriasis.
Six investigators evaluated 0.05% halobetasol propionate cream and its vehicle in 111 patients with chronic atopic dermatitis and several other eczematous dermatoses. Patients applied treatment twice daily to bilateral lesions for 14 days. Investigators graded pruritus, erythema, scaling, papulation, and lichenification using 4-point severity scales on days 0, 7, and 14. On day 14 patients provided an assessment of efficacy for both treatments. Statistically significant differences favoring halobetasol propionate over the vehicle were seen for all signs and symptoms (p less than 0.001). Substantial improvements were achieved by the active treatment by day 7 (p less than 0.001). Patients assessments of efficacy were significantly higher for halobetasol cream than for vehicle (p less than 0.001). No instances of systemic effects or skin atrophy were reported and adverse experiences were limited to burning or stinging and other minor, nonspecific complaints distributed uniformly between active treatment and vehicle. These results demonstrate that 0.05% halobetasol propionate cream is highly effective in the treatment of atopic dermatitis and other eczematous dermatoses.
In-vivo studies suggest that chlorine-releasing antiseptic agents inhibit wound healing. Studies which have used cell culture systems to evaluate cytotoxicity have generated conflicting results for the toxicity of free-chlorine agents relative to other antiseptics. Here we examine the following three factors which may influence the toxicity of individual agents within a cell culture assay: (1) cell number; (2) duration of exposure; and (3) the nature of the antiseptic diluent. Three agents (sodium hypochlorite, chlorhexidine and hydrogen peroxide) were tested on transformed human keratinocytes (SVK 14 cells). It was found that increasing cell number, and using serum or medium as a diluent, reduced the toxicity of all agents but had the greatest effect on sodium hypochlorite. In contrast, increasing the duration of exposure increased the toxicity of all agents but had the greatest effect on hydrogen peroxide. These observations may explain the high toxicity of hydrogen peroxide and relatively low toxicity of sodium hypochlorite which have been observed in vitro and are the reverse of in-vivo findings. Culture systems in which high cell numbers are coupled with an agent diluted in serum or medium, and a long exposure time, seem likely to decrease the toxicity of chlorine-releasing agents relative to hydrogen peroxide.
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"The publication in 1987 of a Soviet compendium of population statistics has made possible the calculation of net migration balances for the U.S.S.R.'s 20 large economic planning regions.... This paper compares the results for 1981-1985 and 1971-1975 and finds that Siberia has changed from a net loser to a net gainer of migrants, that the shift of population to the southern regions has been reversed, and that the traditional rural outflow from central-eastern European Russia has diminished. Nevertheless, the acclimatization of newcomers in the eastern regions, the stabilization of rural dwellers in the central regions, and the mobility of rural residents in Central Asia and the Transcaucasus all remain insufficient to overcome regional imbalances in labour." (SUMMARY IN FRE)
The cytotoxic effects of a range of antiseptic agents were examined on cultured human fibroblasts and basal keratinocytes and compared to those on a transformed keratinocyte line (SVK 14 cells). Cells were exposed to chlorhexidine, hydrogen peroxide and sodium hypochlorite for 15 min and cell viability was assessed 24 h later with a colorimetric assay which utilizes the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). At concentrations recommended for wound cleansing all agents produced 100% killing of all cell types. The results show that fibroblasts and keratinocytes, cells which are fundamental to the wound healing process are equally sensitive to the effects of the antiseptic agents tested, and are highly susceptible to the effects of free-chlorine containing agents. These observations are of particular importance to the use of cultured keratinocytes (culture grafts) to enhance wound healing; the application of antiseptics to such wounds is contraindicated. All three cell types tested showed similar susceptibilities to the agents tested. These findings suggest that the transformed cell line, which has the advantage of immortality and ready availability, can replace fibroblasts and keratinocytes in studies designed to investigate the adverse effects of antiseptic agents in vitro. Comparison of the ED50 concentration for each agent on all cell types to the standard use concentration produced a ranking order of toxicity which showed chlorhexidine to be the least toxic agent and sodium hypochlorite the most.(ABSTRACT TRUNCATED AT 250 WORDS)