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Biomedical subjects

R Marks

Publications and source records attributed to R Marks.

At least 19 recordsLinked to original sources

Trends in the incidence of non-melanocytic skin cancer (NMSC) treated in Australia 1985-1995: are primary prevention programs starting to have an effect?

Non-melanocytic skin cancer (NMSC) is the most common cancer in Australia, but data on its incidence are not routinely collected by cancer registries. National surveys were conducted in 1985, 1990 and 1995 to estimate NMSC incidence. Trends in incidence between 1985 and 1995 have been examined to determine the impact of primary prevention campaigns aimed at controlling skin cancer in Australia. National random household surveys of Australians aged over 13 years were used to estimate NMSC incidence in 1985, 1990 and 1995. Age- and sex-specific rates by survey year were modelled using Poisson regression. Basal cell carcinoma (BCC) rates in 1995 were 788 per 100,000, an increase of 19% since 1985. Squamous cell carcinoma (SCC) rates rose by 93% over the same period, from 166 to 321 per 100,000. The ratio of BCC:SCC changed from 4:1 in 1985 to 2.5:1 in 1995. BCC rates in latitudes <29 degrees S remained at about 3 times those in latitudes >37 degrees S over the decade. The ratio of SCC incidence between these latitudes changed from around 7:1 to 3:1 over the same period. Although NMSC incidence rates continue to rise, there have been reductions in BCC observed in younger age groups. Incidence rates of NMSC continue to rise in Australia, but there is evidence of a reduction in BCC incidence in younger cohorts. This is evidence that public health campaigns to reduce sun exposure may be having a beneficial effect on skin cancer rates.

Adolescent

GMDP for psoriasis.

Explore the source record for details and available documents.

Acetylmuramyl-Alanyl-Isoglutamine

Mechanisms of recovery from experimental autoimmune encephalomyelitis: T cell deletion and immune deviation in myelin basic protein T cell receptor transgenic mice.

Experimental autoimmune encephalomyelitis (EAE) is a Th1-type cell-mediated autoimmune disease directed against central nervous system (CNS) myelin antigens such as myelin basic protein (MBP). EaE is usually characterized by spontaneous remission of clinical disease and immune pathology despite the persistence of self myelin antigens in the central nervous system. Following induction of an acute episode of EAE, spontaneous remission also occurs in MBP T cell receptor (TCR) transgenic mice even through most T cells express a TCT specific for MBP. To investigate the mechanisms of recovery associated with EAE, we examined the behavior of MBP-specific T cells in the MBP TCR transgenic mouse model during disease progression and recovery. We found that recovery from EAE was associated with three major immunologic changes: (1) deletion of encephalitogenic T cells in the brain; (2) deviation of MBP-specific transgenic (Tg+) T cells both in the periphery and in the central nervous system from INF- gamma secretin Th1 type cells to cells that secrete IL-4, IL-10, and TGF- beta ; and (3) deletion of Tg+ T cells in the thymus through apoptosis. Thus spontaneous recovery from a classic Th1 type organ specific autoimmune disease is associated with two mechanisms of immune tolerance, deletion of autoreactive cells and immune deviation of autoreactive cells to a non-pathogenic phenotype.

Animals

Pharmacokinetics and safety review of tazarotene.

The safety profile of tazarotene is superior to that of orally administered retinoids. The limited percutaneous penetration of tazarotene limits its systemic absorption and this, combined with its rapid metabolism in the skin and the plasma to the more water-soluble active metabolite, tazarotenic acid, helps prevent accumulation of the drug in fat containing tissues. Urinary and fecal elimination are virtually complete within 2 to 3 days and 7 days after dosing, respectively. Tazarotene also exhibits no indication of mutagenicity, carcinogenicity, phototoxic potential, photoallergic potential, or contact sensitization.

Administration, Cutaneous

A methodology report of a randomized prospective clinical trial to assess velopharyngeal function for speech following palatal surgery.

Cleft lip and palate occurs in approximately 1 in every 750 live human births, making it one of the most common congenital malformations. Surgical closure of the palatal cleft does not always result in a velopharyngeal port capable of supporting normal speech. The University of Florida (UF), in collaboration with the University of São Paulo (USP), is engaging in a 5-year prospective, randomized controlled study to compare velopharyngeal function for speech outcomes between patients undergoing palatoplasty for complete unilateral cleft lip and palate performed using the von Langenbeck procedure with intravelar velarplasty and those receiving the Furlow double-reversing Z-plasty palatoplasty. The von Langenbeck procedure was selected as the time-tested standard against which the Furlow procedure could be judged. The Furlow procedure, a relatively new operation, has been reported to yield substantially higher rates of velopharyngeal competency for speech than have most other reported series and theoretically should result in less disturbance to midfacial growth. A total of 608 patients will be entered into one of two age categories. Inclusion of two age groups will allow a comparison of results between patients having surgery before 1 year of age (9-12 months) and patients undergoing surgery at approximately 1.5 years of age (15-18 months). Speech data will be collected and will be available for definitive analysis throughout the last 3 years of the study. Collection of preliminary growth data will require more than 5 years; growth analysis is anticipated to continue until all patients have reached maturity. The Hospital for Research and Rehabilitation of Patients with Cleft Lip and Palate at the University of São Paulo (USP-HPRLLP) in Bauru, Brazil, is uniquely situated for conducting this study. The well-equipped and modern facilities are staffed by well-trained specialists representing all disciplines in cleft-palate management. In addition, an already existing social services network throughout Brazil will ensure excellent follow-up of study cases. The clinical caseload at this institution currently exceeds 22,000, and more than 1200 new cases are added annually. This project represents a unique opportunity to obtain prospective data from a large number of subjects while controlling the variables that have traditionally plagued cleft-palate studies. This study is designed to determine which of the two proposed surgical procedures is superior in constructing a velum capable of affecting velopharyngeal competency for the development of normal speech.

Cleft Palate

Celtic ancestry, HLA phenotype and increased risk of skin cancer.

Individuals of Celtic ancestry are claimed to be at greater risk of skin cancer than non-Celts, and various positive and negative associations between certain human leucocyte antigen (HLA) phenotypes and the development of skin cancer have been described. The aims of this study were to determine whether any HLA phenotypes are associated either with Celtic or non-Celtic ancestry, or skin type. One thousand and ten members of the Welsh Bone Marrow Donor Registry (WBMDR), whose HLA phenotypes are known, were asked to complete a questionnaire which enquired as to their family origins and their 'Index of Celtic Ancestry' scored out of 12. Three groups were identified: non-Celts (score < 3), Celts (score > 9), and a subset of the Celts--'high scoring' Celts (score > 10). Details of hair and eye colour and skin type were also requested. Skin type and HLA-A, -B, -DR and -DQ frequencies were compared between the three groups (Celts, non-Celts and 'high scoring' Celts), and a random indigenous population of 9196 members of the WBMDR. Seven hundred and thirty-six replies were received (279 male, 457 female, mean age 31 years). One hundred and forty-four Celts, 51 'high scoring' Celts and 170 non-Celts were identified. Forty-six (32%) Celts had skin type I or II compared with 36 (21%) non-Celts (P = 0.039), and 37 (73%) 'high scoring' Celts had skin type I or II (P < 0.0001). However, there were no significant differences between the groups with regard to hair colour, eye colour or number of episodes of painful sunburn. The frequency of HLA-DR4 was 32% in the non-Celtic group, 44% in the Celtic group (not significant), and 53% in the 'high scoring' Celts (P = 0.008). However, the difference was not significant after correction. There were no significant associations between skin type and HLA phenotype. HLA-DR4 is known to be associated with an increased risk of both basal cell carcinoma and malignant melanoma and its increased frequency in Celts may be an independent risk factor for skin cancer in addition to skin type.

Adult

The prevalence of common skin conditions in Australian school students: 1. Common, plane and plantar viral warts.

Although viral warts are common, their exact frequency in the community is often underestimated and not well recorded. A random sample of 2491 students from schools throughout the State of Victoria, Australia were examined by dermatologists and dermatology registrars to record the prevalence of common, plantar and plane warts. The overall prevalence of warts adjusted for the age and sex of Victorian school children was 22% (95% confidence interval (CI) 20.1-20.7) varying from 12% (95% CI 9.4-15.7) in 4-6 year olds to 24% (95% CI 18.3-30.4) in 16-18 year olds. Common warts were the most frequent (16%) compared with plantar warts (6%) and plane warts (2%). There was no difference in the overall frequency of warts between males and females and there was no difference in frequency between those who had eczema and those who did not. Almost 40% of those found to have warts on examination had indicated on the survey questionnaire that they did not have any of these lesions. Of those who knew that they had warts, only 38% had used any treatment for them. These data, the first community-based prevalence data on warts ever published from Australia, confirm that warts are indeed common. They suggest the need for education programmes in schools on the nature of these lesions and the treatment available.

Adolescent

Choice of long-term strategy for the management of patients with severe esophagitis: a cost-utility analysis.

BACKGROUND & AIMS: Omeprazole has shown remarkable efficacy and safety in the treatment of patients with gastroesophageal reflux disease (GERD); similarly, laparoscopic techniques have allowed less morbidity in patients undergoing fundoplication procedures. Concerns about the long-term cost and safety of both strategies have prompted a debate of their role in long-term management of patients with severe erosive esophagitis. METHODS: A cost-utility analysis was performed to compare two strategies: laparoscopic Nissen fundoplication (LNF) vs. omeprazole. A two-stage Markov model was used to obtain cost and efficacy estimates; all estimates were discounted at 3% per year. The time horizon was 5 years. Sensitivity analyses were performed on all relevant variables. RESULTS: Both strategies were similarly effective (4.33 quality-adjusted life years per patient), with omeprazole less expensive than LNF ($6053 vs. $9482 per patient). At 10 years, LNF and omeprazole costs were similar. Efficacy estimates were extremely sensitive to changes in quality of life associated with postoperative symptoms and long-term use of medication. CONCLUSIONS: Medical therapy is the preferred treatment strategy for most patients with severe erosive esophagitis. Individuals with a long life expectancy are good candidates for LNF if postoperative morbidity is low and GERD symptoms remain abated for many years.

Adult

Who removes pigmented skin lesions?

BACKGROUND: Increasing numbers of pigmented skin lesions are being removed because of concern about possible malignancy. OBJECTIVE: Our purpose was to determine the ratio of benign to malignant pigmented tumors removed by different categories of physician and to verify whether any improvement had occurred after 5 years of educational programs. METHODS: All pigmented lesions submitted to a major histopathology service in the years 1989 and 1994 were assessed as to the category of physician who removed the lesion, tumor type, and age and sex of the patient. RESULTS: Dermatologists had the lowest benign/malignant ratio and general practitioners had the highest. General practitioners appeared to have difficulty differentiating both seborrheic keratoses and melanocytic nevi from malignant lesions; the frequency of these benign lesions was highly dependent on the age of the patient. During the 5-year period we observed an improvement among general practitioners in the benign/malignant ratio for melanocytic nevi, but not for seborrheic keratoses. CONCLUSION: There is room for improvement by physicians in differentiating both melanocytic nevi and seborrheic keratoses from melanomas. This is especially true for general practitioners, from whom the public in Australia and in other countries is encouraged to first seek advice about a suspect pigmented lesion.

Adult

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