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Biomedical subjects

R Marks

Publications and source records attributed to R Marks.

At least 127 records · Page 7Linked to original sources
PubMed1997

Treatment of psoriasis with intermittent short course cyclosporin (Neoral). A multicentre study.

A 1 year, prospective multicentre study was performed to investigate the efficacy and safety of intermittent treatment with cyclosporin in psoriasis vulgaris. Subjects received cyclosporin (Neoral) 5 mg/kg per day until achieving 90% reduction in area affected, or for a maximum of 12 weeks. Those failing to demonstrate a satisfactory response were withdrawn. When further treatment was required, cyclosporin was recommenced. This cycle was repeated up to three times. Psoriasis activity was recorded using the area affected and sign scores for erythema, scaling and infiltration. Overall assessments of response and tolerability were recorded. Forty-one subjects, mean age 36, mean PASI 12.8, entered the first treatment period. Thirty-three received a second period of treatment and 16 a third. Eighteen failed to complete the study as planned: five were withdrawn due to adverse events, four due to treatment failure and nine due to protocol violations. At the end of each treatment period, significant improvements were seen in all efficacy parameters. Overall response was graded as 'considerable improvement' or 'minimal or no symptoms', by over 80% of subjects and investigators. Median intervals to relapse for subjects remaining in the study were 72 days (range 28-329) and 53 days (range 14-141) after periods 1 and 2, respectively. There were significant increases in mean serum creatinine and blood pressure during each treatment period. However, there were no significant differences in either parameter between baseline and the final follow-up visit. At the end of each treatment period, overall tolerability of the treatment was considered 'good' or 'very good' by over 80% of subjects and investigators.

Adult↗
PubMed1997

Transdermal nicotine suppresses cutaneous inflammation.

BACKGROUND: Cigarette smoking significantly alters the inflammatory response in the skin following application of irritants and rubefacients. The mechanism of this effect is unknown. There are thousands of components in cigarette smoke that may be pharmacologically important, but there is evidence to suggest that nicotine may play an important role in the observed effect on the inflammatory process. DESIGN: This was an interventional study to assess cutaneous responsiveness to different stimuli after transdermal nicotine administration in volunteer subjects. Cutaneous testing was performed at baseline and at weeks 2 and 4 (the end) of the study. SETTING: The department of Dermatology, University Hospital of Wales, Cardiff. PARTICIPANTS: Ten lifelong nonsmokers were recruited for the study. INTERVENTION: Nicotine patches were applied daily for 1 month. MAIN OUTCOME MEASURES: The following tests were performed: application of 2 times the minimal irritancy dose of sodium lauryl sulfate, irradiation with 2 times the minimal erythema dose of UV-B, measurement of cutaneous vasodilation following application of ethyl and hexyl nicotinate, and reactive hyperemia following arterial occlusion. RESULTS: There was a significant reduction in the cutaneous inflammatory response to sodium lauryl sulfate (P < .001) and irradiation with UV-B (P < .003) and a reduction in reactive hyperemia (P < .03) after 2 weeks of treatment, which returned values to normal at 4 weeks. There was no change in blood flow following application of topical nicotinates. CONCLUSIONS: Nicotine administration via a transdermal delivery system suppresses the cutaneous inflammatory response to sodium lauryl sulfate and UV-B, as well as triggers a transient suppression of reactive hyperemia following arterial occlusion. The apparent anti-inflammatory effects of smoking cigarettes can therefore only partially be explained as a long-term effect of nicotine.

Administration, Cutaneous↗
PubMed1997

Clinical safety of tazarotene in the treatment of plaque psoriasis.

Oral retinoids are effective in the treatment of psoriasis, but their use is limited by concerns for teratogenic potential and systemic side effects. Tazarotene is a novel acetylenic retinoid undergoing clinical trials for the topical treatment of mild-to-moderate plaque psoriasis. The safety and tolerability of tazarotene 0.1% and 0.05% gels were examined in a series of preclinical and clinical trials. In preclinical studies topically applied tazarotene gel was nonmutagenic, noncarcinogenic, and nonteratogenic. Tazarotene gel was not sensitizing, phototoxic, or photosensitizing in a series of studies in human volunteers. Treatment-related systemic adverse effects were not observed in clinical trials involving approximately 2000 patients treated with tazarotene 0.1% or 0.05% gel for periods of up to 1 year. Adverse effects appear limited to manageable, mainly mild-to-moderate local skin irritation.

Administration, Oral↗
PubMed1997

The prevalence of seborrhoeic keratoses in an Australian population: does exposure to sunlight play a part in their frequency?

Although seborrhoeic keratoses (SKs) appear to be very common, there are very few studies reporting details of age-specific prevalence, distribution or possible cause. We report details on the frequency, nature and distribution of SKs in 100 Australian adults in the age groups 15-25, 26-50, 51-75 and those aged more than 75 years. There was an increase in prevalence of SKs from 12% of 15-25 year olds to 100% of those aged more than 50 years. The median number of lesions in those with them also increased with age from six per person in 15-25 year olds to 69 per person in those aged more than 75 years. There was no difference in prevalence or numbers of lesions/person between males and females. SKs on exposed areas were more often flat and more than 3 mm in diameter than those on the non-exposed areas. There was a higher prevalence of SKs on the exposed areas than non-exposed areas when taking into account the surface area. The data in this study demonstrate an increased frequency of SKs compared with those reported from the United Kingdom recently and from Australasia in the past, a phenomenon paralleling the changing frequency of skin cancer in these populations. This fact, plus the finding that SKs were more common as a function of skin surface area on the exposed areas of the body, suggests that sunlight may play a part in their development in those people who are predisposed to develop them.

Adolescent↗
PubMed1997

Positioning errors produced by persons with knee joint disease when vision is occluded.

This study examined the effect of occluding static vision on the ability of persons with knee joint disease and impaired position sense to actively reproduce knee angles in a one-legged standing position. The subjects, six women with knee joint disease, ages 54-75 years each performed a series of two knee repositioning tasks in the ranges of 20-40 degrees flexion on two different occasions, both with, and without visual feedback. On each occasion, the leg was marked with reflective markers and the resultant sagittal plane knee angles were photographed. Whilst the absolute differences between the criterion and the matching knee angles calculated from these records showed vision to have an effect on positioning accuracy (p = 0.04), there were no differences in mean absolute constant errors between the two experimental paradigms, indicating similar perceptual judgment in memory. However, variability in performance tended to be greater when vision was occluded (p = 0.08). These findings suggest that while visual sources of information may play a minor role in the knee positioning bias towards target overestimation apparent in this group, supplementary visual cues may help to promote more consistent positioning performance.

Aged↗
PubMed1997

The effect of restricting arm swing during normal locomotion.

This work examined possible perturbations in contra-lateral upper and lower limb motion, movement variability, and thoracic rotation, when a healthy mature adult walked a distance of 12 m at self-paced speed with and without unilateral passive arm restraint. The 2-dimensional walking data captured from 11 reflective markers placed on the subject's right side were recorded sagitally along the plane of progression using an electronic camera and Peak-5 Performance Video-system. The positional data were calculated off-line and differentiated with respect to one representative stride using Lab View software. Data were analyzed for 5 successive trials of normal walking; 5 successive walking trials with unilateral passive restraint; and a further 4 without restraint. Under the restrained condition the results showed: a) A significant decline in horizontal displacement of the limbs; b) higher variability of the trajectories generated, particularly at the ankle; c) a trend towards greater thoracic rotation on the unrestrained side; and d) altered angular velocity profiles for all upper and lower limb joints and trunk, which did not always return to baseline values after restraint removal. Since motivation level, environment, and methodology was consistent across trials, the findings suggest relatively stereotyped locomotor patterns in mature humans can be readily modulated in response to task constraints.

Adult↗
PubMed1996

Translocation of the retinoblastoma gene product during mitosis.

This study reports the immunocytochemical localization of the retinoblastoma gene product within synchronized normal human keratinocytes. Data suggest that mitotic spindles function in the transport of the retinoblastoma tumor suppressor gene product during cell division. A diffuse anti-pRB reactivity was detected within the nuclei of G1-phase keratinocytes, although staining was not evident within the nucleoli. During S-phase and G2-phase the anti-pRB reactivity was localized to discrete regions within the nuclear compartment. The anti-pRB reactivity of M-phase cells was localized to the mitotic spindles and microtubule nucleation centers. Immunoprecipitation and Western blotting of the pRB antigen from synchronized keratinocytes showed that the apparent polypeptide molecular weight of pRB increased from 105 kDa during G1-phase to 115 kDa during M-phase. Immunoprecipitation of the pRB antigen from mitotic spindles resulted in the coprecipitation of two polypeptides with apparent polypeptide molecular weights of 115 and 50 kDa. Western blotting of the immunoprecipitates from purified keratinocyte mitotic spindles showed that beta-tubulin was the 50-kDa polypeptide associated with hyperphosphorylated pRB.

Biological Transport↗
PubMed1996

In vivo photoinduction of metallothionein in human skin by ultraviolet irradiation.

The aims of this study were to confirm and substantiate the in vivo cutaneous induction of metallothionein (MT) in human skin by UVR, which we have reported in brief previously, and to make a preliminary attempt to characterize the time course of this phenomenon. Buttock skin in 32 volunteers was irradiated with 2 MED of UVB and biopsies were taken at 24 h from matched non-irradiated and irradiated sites. In the kinetic study, skin biopsies from six volunteers were taken at 0, 2, 8, 24, and 48 h after 2 MED UVB irradiation. MT was immunolocalized in formalin-fixed, paraffin-embedded tissue with the monoclonal antibody E9 by an indirect immunoperoxidase method. Statistically significant differences between immunocytochemical scores were identified between non-irradiated (NI) and irradiated (I) skin within suprabasal keratinocytes (mean: NI = 1.2, I = 5.1; P = 0.01), superficial dermal fibroblasts (mean: NI = 2, I = 43; P < 0.001), mid-dermal fibroblasts (mean: NI = 0, I = 27; P < 0.001), and deep dermal fibroblasts (mean: NI = 0, I = 11; P < 0.001). In the kinetic study, no consistent rise in MT score with time was observed for the epidermal component. In dermal fibroblasts, however, the first statistically significant rise in immunocytochemically detectable MT was detected at 2 h and this was found to plateau beyond 8 h. These results confirm that ambient levels of UV irradiation are capable of inducing MT in human skin in vivo. Taken together with the relative rapidity of the response, this suggests a physiological photoprotective role for MT in human skin cells. The lack of a kinetic increase in epidermal MT may be due to high basal levels. Induction of MT in dermal fibroblasts may reflect the effects of a diffusible factor released from keratinocytes after UVR.

Buttocks↗
PubMed1996

Evaluation of the reliability of reflective marker placements.

This study determined the reliability of recording knee angle coordinates in the sagittal plane during erect stance by use of skin reflective markers. To this end, 32 healthy male and female subjects participated in three standardised test sessions of 1 hour duration spaced at 1- and 4-week intervals. At each session, markers were placed on three bony landmarks of the leg and their coordinates were photographed with the leg in extension and semi-flexion. The resultant knee angles, calculated from lines drawn on the photographs marking the coordinate sites, were subjected to separate repeated measures analysis of variance statistical procedures. The results showed that both sets of measurements could be carried out reliably when repeated within a single test session (R = 0.87). However, when repeated over time, neither measurement reached the criterion for acceptable reliability (set at R > or = 0.80). The magnitude of the method error was also higher between test sessions for both angles than it was for tests repeated within the sessions. These data suggest that whereas knee coordinates recorded on a single day can be reproduced reliably, they may be less useful for evaluating knee angle changes over time.

Adult↗
PubMed1996

Further evidence of impaired position sense in knee osteoarthritis.

The knee joint position sense of a control group of healthy women was compared with that of women diagnosed as having severe osteoarthritis (OA) of the knee. Movements monitored were multi-joint when weightbearing on one leg. All subjects completed two angle rematching tests on two separate test occasions, and the criterion and reproduction angles which lay in the range of 15-45 degrees knee flexion were recorded photographically on each occasion. The results showed that the OA group performed the rematching tests with less accuracy than the controls (p < 0.05). Additionally, the OA group displayed significantly higher average flexion error magnitudes than the controls. These results suggest that joint position sense is less accurate and may be systematically distorted during multi-joint movements of the affected legs of a high proportion of women with severe knee OA. They further suggest that to improve their functional performance, patients with knee OA probably require a carefully constructed sensorimotor rehabilitation programme in which pain, effusion and fatigue are minimised.

Adolescent↗
PubMed1996

A study of white dermographism in atopic dermatitis.

Vascular responses of 15 adults with atopic dermatitis (AD), 15 with psoriasis and 15 with normal skin were studied using an automated dermographometer we have designed. The type of colour change, time to onset and the duration of responses were recorded after a constant stroking force was applied to the skin of each subject. Of the 15 patients with atopic dermatitis, 11 had white dermographism (WD) with abnormal looking skin and four had red dermographism (RD) with normal looking skin. All the control subjects had RD. WD in AD had a significantly longer time to onset and shorter duration of response than RD in controls (P < 0.01), whereas RD in AD had a significantly shorter duration of response than RD in controls (P < 0.01). WD in AD changed to RD after topical corticosteroid treatment and this post-treatment RD was quantitatively similar to the RD in AD. We have quantified, for the first time, a subnormal form of RD in clinically normal skin of patients with AD, which is different from that of the RD in normal subjects. We have also shown that WD in AD is altered to this subnormal form of RD after treatment with topical coricosteroids.

Adolescent↗
PubMed1996

Non-melanoma skin cancer and solar keratoses. I. Methods and descriptive results of the South Wales Skin Cancer Study.

This study aimed to describe the prevalence and incidence of solar keratoses and skin cancers and the natural history of solar keratoses in a random population sample. It was a cross-sectional study, with follow-up, conducted in South Wales, and involved 1034 subjects aged 60 years and over drawn from the Family Health Services Authority register. The main outcome measures were detection of the presence of solar keratoses and skin cancers on sun-exposed skin and photographic validation of solar keratoses and biopsy confirmation of cancers wherever possible. We found that solar keratosis prevalence was 23% (95% confidence interval 19.5-26.5) and that of skin cancer (all types) 2% (95% confidence interval 1.0-3.5). The incidence rate of solar keratoses was 149 lesions per 1000 person-years and of non-melanoma skin cancer 9 per 1000 person-years. In all 21% (95% CL 16-26) of solar keratoses regressed spontaneously during follow-up. None underwent malignant change. We believe that the failure of individuals to seek medical advice and the variable under-registration of non-melanoma skin cancer makes population-based study important. The high prevalence and incidence of malignant and pre-malignant skin lesions in this random sample raise major public health concerns. The high rate of spontaneous regression of solar keratoses and the low rate of malignant change challenges conventional views about the need for routine treatment of these lesions.

Adult↗
PubMed1996

Non-melanoma skin cancer and solar keratoses II analytical results of the South Wales Skin Cancer Study.

This study aimed to identify risk markers for prevalent solar keratoses (SKs) and squamous cell carcinomata (SCC) combined, for incident SKs and for spontaneous remission of SKs and to evaluate primary preventative measures. It was a cross-sectional study, with follow-up, conducted in South Wales, and involved 1034 subjects aged 60 years and over. The main outcome measures were the presence of and changes in SKs, and presence of skin cancers, on sun-exposed skin, and risk factors for prevalent SKs/SCCs and for incidence and remission of SKs. We found that variables independently associated with prevalent SKs/SCCs were: age [80 + years vs 60-64 years, odds ratio (OR) 3.7]; sex (male vs female OR 2.2); cumulative sun exposure (top quintile vs bottom quintile OR 3.3) and skin type (skin type 1 vs 4 OR 12.4). Use of sunscreen or protective clothing was not protective after controlling for confounders. Males and those who sunbathe infrequently showed greater remission of SKs. Older subjects and those spending most time in the sun in the preceeding 2 years were most likely to develop new SKs. We conclude that the risk factors identified are consistent with results from sunnier countries. The failure of sunscreen or clothing to emerge as protective raises doubts as to whether these measures are as effective in routine use in the general population as theoretical considerations and the limited trial evidence would predict. Recently reported sun exposure appears to influence the risk of developing new SKs.

Aged↗