PubMed HealthSearch

Biomedical subjects

R Marks

Publications and source records attributed to R Marks.

At least 37 records · Page 2Linked to original sources

Dyspepsia due to eosinophilic gastroenteritis.

Classical eosinophilic gastroenteritis is a rare disease but may be misdiagnosed in clinical practice. We report eosinophilic gastroenteritis that was diagnosed in six patients (four males and two females; mean age 31.5 years) using standard criteria (presence of gastrointestinal symptoms, a predominant eosinophilic infiltrate on biopsy, and exclusion of other causes of eosinophilia). All had gastric mucosal disease and presented with dyspepsia. The median duration of symptoms prior to diagnosis was three months (range five weeks to 13 years). Epigastric pain or discomfort was the most common symptom (100%) followed by anorexia, nausea, and vomiting (67%, 67% and 33%, respectively). None had diarrhea. Half the patients had a history of allergy, while 67% had peripheral eosinophilia. All responded to oral steroids within two months; one third needed to continue on a small dose of maintenance steroids to remain in remission. A high degree of suspicion and biopsy at upper endoscopy is necessary for diagnosis of this rare disease.

Adolescent

What do children aged 5 to 11 years old know about the sun and skin cancer? The practical difficulties of international collaborative research when analysis of language is involved.

The objective of this study was to determine the perceptions of primary school children about sun exposure and skin cancer, and the language they use about these issues, as a basis for the design of health promotional materials. In all, 2857 children in five European countries took part in the study and were compared with 641 Australian children participating in a similar study, since the latter have been exposed to more intensive health education about the sun. The 'draw and write' technique was used. In Europe the level of awareness about the risks of excessive sun exposure and the need to protect the skin was considerably lower than in Australia, although there was some variation within northern Europe. Amongst the European children acknowledging a need to protect the skin, the principal means of protection quoted was the use of suncreams, with inadequate awareness of the value of clothing, hats and shade. European children expressed greater approval of suntans than did the Australian children. Some methodological problems were encountered as a result of nuances in the languages involved, emphasizing difficulties in international research of this type.

Age Factors

A new keratin 2e mutation in ichthyosis bullosa of Siemens.

Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin condition with features similar to epidermolytic hyperkeratosis (EH). Clinical symptoms are characterized by mild hyperkeratosis with an acral distribution. Histology shows epidermolysis of upper spinous and granular cells, whereas ultrastructurally, tonofilaments form perinuclear aggregates. IBS has been linked to the type II keratin cluster on chromosome 12q, and K2e mutations have recently been identified in IBS patients. We have studied genomic DNA from two IBS families and in both cases heterozygous point mutations were found in the 2B helical domain of K2e. One family had an established mutation in codon 493 (E493K), whereas the other had an unreported mutation in the adjacent codon (E494K). Both mutations were confirmed by allele-specific PCR. These data reinforce the hypothesis that mutations in the TYRKLLEGEE motif of the 2B helix are deleterious to keratin filament network integrity and provide further evidence for the involvement of K2e mutations in IBS.

Adolescent

Descriptive epidemiology of acne vulgaris in the community.

Acne is a common skin condition. No universally accepted standardized classification system for acne vulgaris exists, although there is a strong need for it. Thus, the clinical definition of acne has been unclear in many studies. The reported prevalence of acne varies from 35 to over 90% of adolescents at some stage. In some studies the prevalence of comedones approaches 100% in both sexes during adolescence. The prevalence of acne varies between sexes and age groups, appearing earlier in females than in males, possibly reflecting the earlier onset of puberty. There is a greater severity of acne in males than in females in the late teens, which is compatible with androgens being a potent stimulus to sebum secretion. The prevalence of acne at a given age has been shown to be highly dependent on the degree of sexual maturity. Acne commonly shows a premenstrual increase in women. Some studies have detected seasonal variability in acne vulgaris, with the colder months associated with exacerbation and the warmer months showing improvement. Other studies have not confirmed these findings. Several studies that have investigated the psychosocial impact of acne have had conflicting results. The prevalence of severe acne has decreased over the past 20 years due to improved treatment. The general prevalence figure for acne may be confounded by treatment and this factor needs to be accounted for when collecting data.

Acne Vulgaris

Behavioural dynamics of a clinical trial of sunscreens for reducing solar keratoses in Victoria, Australia.

OBJECTIVE: To determine whether the behaviour of participants based on perception of treatment group in a randomised trial contributed to clinical outcome. DESIGN: A double blind randomised controlled trial of the effect of daily application of SPF 17 broad spectrum sunscreen cream (or placebo) on solar keratoses. SETTING: A rural city in Victoria, Australia. Residents aged 40 years or over were invited by letter to attend for a skin cancer screening check. Of these, 588 people with between one and 30 solar keratoses enrolled in the trial and 431 completed the trial, which extended over a six month period that included summer. Participants' perceptions of their treatment allocation, adherence with the treatment regimen, adoption of other sun protection behaviours, side effects, and perceptions of change in condition were measured at two monthly intervals. RESULTS: There were no significant differences between those who completed the study and those that did not for sex, age, treatment group, skin type, number of solar keratoses or correct perception of treatment group. Thirty per cent of those completing the study correctly guessed their treatment allocation, and people were just as likely to be right as to be wrong when they stated their opinion about their treatment allocation (z = 1.04; p = 0.15). Study group, skin type, amount of time spent outdoors, presence of side effects, perceptions of change in skin condition did not significantly predict correct perception of treatment allocation. Multivariate analysis of variance indicated that adoption of other sun protection and adherence with cream use were not significantly affected by actual treatment allocation, correct perception of treatment allocation nor by their interaction. Poisson regression analysis showed a significantly lower difference ratio of solar keratoses in the sunscreen group compared with the placebo base cream group (OR 0.55; CI = 0.46, 0.64), and for women compared with men (OR = 0.76; CI = 0.63, 0.93) but no independent effect of any of the indices of other sun protection or adherence. CONCLUSIONS: A sufficient level of commitment to study procedures was achieved, so that trial participants did not adopt other behaviours that affected treatment outcomes. It is recommended that the potential threat to validity posed by the behaviour of participants be recognised at an early stage in planning of clinical trials, so that strategies to deal with this can be integrated into study protocols.

Adult

Clinical features in four patients with Angelman syndrome resulting from paternal uniparental disomy.

Angelman syndrome (AS) is a complex neurological disorder with different genetic aetiologies. It is not known whether the clinical features vary depending on the genetic mechanism. We report four patients with AS owing to uniparental disomy (UPD). There were two males and two females, with a mean age of 8 years (range 7 to 11 years). All patients had a happy disposition, hyperactive behaviour, and the characteristic facial phenotype of AS, but in three there was a normal head circumference, two had epilepsy, ataxic movements were mild in three, the mean age of onset of walking was 2.4 years, and there was some sign language in all four patients. Our cases add further weight to the previously reported impressions of a milder phenotype in cases of AS resulting from UPD than in deleted AS patients. Patients suspected of having AS, but who are considered atypical, warrant DNA testing.

Abnormalities, Multiple

Keratinocyte growth stimulation by granulocyte-macrophage colony-stimulating factor (GM-CSF).

Human granulocyte-macrophage colony stimulating factor (GM-CSF) is a 22 kD glycoprotein derived from activated T cells, endothelial cells, fibroblasts and macrophages. It stimulates the proliferation and differentiation of haematopoietic cells and certain nonhaematopoietic cells. This study investigated the effect of GM-CSF on cultured human keratinocytes and determined whether these cells express GM-CSF receptors. Measurement of keratinocyte growth by image analysis showed that GM-CSF mildly stimulated the growth of keratinocytes. With 4 ng/ml GM-CSF the growth of primary keratinocytes and subcultured keratinocytes was only stimulated up to 25% and 18% of the control cell level, respectively. Human keratinocytes were incubated with GM-CSF at 4 ng/ml for 4 days to induce receptor expression. These cells showed only a weak positive reaction on affinity labelling using digoxigenated GM-CSF. We conclude that keratinocyte growth may be stimulated by GM-CSF but that the presence of GM-CSF receptors on these cells is equivocal.

Cell Division

Non-invasive in vivo techniques to differentiate photodamage and ageing in human skin.

It is important to differentiate skin changes due to the intrinsic ageing process from those due to chronic photodamage in the development of therapies to assist the latter condition, and in this study we have used instrumental techniques to differentiate between changes in a range of properties of skin due to ageing and those due to photodamage, especially with regard to elasticity. We measured three sites of differing sun exposure in a group of younger and in a group of older subjects. A pulsed A-scan ultrasound system was used to measure skin thickness, and a uniaxial extensometer was employed to assess elastic properties. Skin surface roughness measurements were made using silicone rubber impressions and a stylus profilometer. We demonstrated significant differences in skin roughness between young and old subjects at every site and differences between sun-exposed and sun-protected sites only in the older group. Parameters of the elastic properties of skin differed between the groups, and also between sites of most different sun exposure. The uniaxial extensometer can demonstrate a loss of the skin's elasticity predominantly by photodamage, and the roughness of the skin surface can be shown to increase mostly by chronological ageing but to decrease modestly by photodamage. This demonstrates that differences between the two processes can be quantified, and indeed they should be.

Adult

Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis.

A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.

Adolescent

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

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

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

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

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

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