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Biomedical subjects

S M Clark

Publications and source records attributed to S M Clark.

At least 19 recordsLinked to original sources

Temporal changes in sebum excretion and propionibacterial colonization in preadolescent children with and without acne.

BACKGROUND: It is generally accepted that the onset of sebum secretion occurs before puberty in boys and girls as a result of increasing androgen output during the adrenarche. Propionibacteria are part of the commensal skin flora and, in adults, are found in highest numbers in sebum-rich areas of skin such as the face and upper trunk. Previous studies investigating the association between sebum output and propionibacterial population densities have been cross-sectional and have been carried out mainly in adults. OBJECTIVES: The purpose of this study was to examine the association between the onset of sebum secretion and expansion of the propionibacterial flora in a population of early adolescent children aged between 5.5 and 12 years, and to evaluate the temporal relation between the two factors longitudinally. In addition, the study aimed to evaluate the change with age in sebaceous gland activity and propionibacterial colonization on the skin and in the nares between children who developed acne and those who did not. METHODS: Biannual examinations of volunteers included age, pubertal (Tanner) stage, weight and height, lesion counting on the face, propionibacterial colonization on the skin surface and in the nares and sebum secretion. A longitudinal analysis based on all observations of each subject throughout the study was applied to examine the change of sebaceous gland activity and propionibacterial colonization with age and pubertal stage. A generalized estimating equation was used with a 0.05 level of significance. RESULTS: The commencement of sebum production was asynchronous, with only a small number of follicles initially starting to secrete sebum onto the skin surface. The number of secreting follicles and the area of sebum increased with age and pubertal stage (P < 0.0001, P < 0.05, respectively). Numbers of propionibacteria on the skin tended to increase after the age of 9 years, but not significantly so. In contrast, numbers of propionibacteria in the nares increased significantly with age (P < 0.0001) but not with pubertal maturation. Children who developed acne had higher sebum output and propionibacterial densities with increasing age than children who did not develop acne. This effect was significant for the increase of total sebum area with age in pubertal children (P = 0.0023), the increase in number of secreting follicles with age (P = 0.020) in prepubertal children, and the increase in propionibacteria densities in the nares with age (P = 0.0005) in pubertal children. Sebaceous gland activity and propionibacterial numbers on the skin surface remained unchanged with increasing age in children who did not develop acne. Propionibacterial population densities in the nares increased with age regardless of the development of acne. CONCLUSIONS: Onset of sebum secretion and consequently expansion of the propionibacterial skin flora occur earlier in children who develop acne than in children of the same age and pubertal status who do not develop acne. These observations suggest that postponing the onset of sebum production or the expansion of the propionibacterial skin flora until after puberty may represent ways of preventing the disease or minimizing its severity. Determinants of propionibacterial colonization on the skin and in the nares may be different.

Acne Vulgaris↗

Allergic contact dermatitis in children: should pattern of dermatitis determine referral? A retrospective study of 500 children tested between 1995 and 2004 in one U.K. centre.

BACKGROUND: Allergic contact dermatitis (ACD) increases with age, and a prevalence of between 13.3% and 24.5% has been reported. Patch testing infants may be particularly difficult, and false-positive reactions may occur. OBJECTIVES: The purpose of this retrospective study was to determine whether the site of primary dermatitis in children could predict a diagnosis of ACD. The current frequency of sensitization in children was also evaluated and the main sensitizing substances among children were verified. METHODS: Between 1995 and 2004, 500 children were patch tested and entered on to the patch test database at Leeds General Infirmary. Analysis of the database included identifying the presenting patterns of eczema and reviewing the patch test results for each child. RESULTS: Of the children, 133 (27%) had one or more positive patch test result. The effect of age on the likelihood of a positive patch test was highly significant (P < 0.001). Girls were significantly more likely to have a positive patch test compared with boys: odds ratio for a positive test 0.62 (95% confidence interval 0.41-0.95; P = 0.029). Type IV allergy to nickel (33%) was the most frequent finding. Reactions to fragrance mix (18%), cobalt (11%), mercapto chemicals, Myroxylon pereirae and p-phenylenediamine (each 8%) were the next most common. No statistical significance was found in the relationship between the site of primary dermatosis and a positive patch test result. CONCLUSIONS: The pattern of presenting dermatitis in children should not determine referral for patch testing. Any child with persistent eczema should be referred for patch testing.

Adolescent↗

Killed Mycobacterium vaccae suspension in children with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The hygiene hypothesis is often proposed to explain the high prevalence of atopy in the western world. Dysregulation of the immune system may result from inadequate exposure to micro-organisms such as mycobacteria. A small trial suggested that a killed extract of Mycobacterium vaccae ameliorates atopic dermatitis (AD). OBJECTIVES: To confirm in a large clinical trial whether killed M. vaccae ameliorates AD in 5-16-year-old children. METHODS: This was a randomized, placebo-controlled, double-blind, multi-centre study of the effect of intradermal injection of killed M. vaccae (0.1 or 1 mg) on patients, aged 5-16, with moderate-to-severe AD. Patients were followed up for 24 weeks. The primary end point was the change in severity of AD at 12 weeks, assessed using the six area, six-sign, atopic dermatitis (SASSAD) score. Secondary end points included changes in disease extent, patient's global assessment and children's dermatology life quality index. RESULTS: There were 166 patients randomized. The mean SASSAD score fell to a similar degree at week 12 in all treatment arms: from 33 to 24, (26%) in the high-dose group, from 30 to 23 (25%) in the low-dose group and from 36 to 27 (24%) in the placebo group (P>0.05). Secondary end points followed the same trend. Adverse events were generally those expected to occur in this population. Injection site reactions occurred in 32 patients at week 4. CONCLUSIONS: M. vaccae was no more effective than the placebo in ameliorating the severity of AD.

Adolescent↗

Unilateral naevoid trichoepitheliomas on the face of a child.

Trichoepitheliomas are benign epidermal appendage tumours that present most commonly as solitary lesions, and less often as multiple, symmetrically distributed lesions on the face, scalp, neck and trunk. Only a few patients have been reported in whom trichoepitheliomas were found as unusually configured linear or plaque-like confluent lesions, all of which occurred in patients with skin types V or VI. We describe a white girl with a hemifacial plaque of confluent naevoid trichoepitheliomas, the first report of such lesions in a white patient.

Child↗

Iron spin transition in Earth's mantle.

High-pressure Mössbauer spectroscopy on several compositions across the (Mg,Fe)O magnesiowüstite solid solution confirms that ferrous iron (Fe(2+)) undergoes a high-spin to low-spin transition at pressures and for compositions relevant to the bulk of the Earth's mantle. High-resolution x-ray diffraction measurements document a volume change of 4-5% across the pressure-induced spin transition, which is thus expected to cause seismological anomalies in the lower mantle. The spin transition can lead to dissociation of Fe-bearing phases such as magnesiowüstite, and it reveals an unexpected richness in mineral properties and phase equilibria for the Earth's deep interior.

Journal Article↗

A new paradigm to extend diffraction measurements beyond the megabar regime.

The possibility of using X-ray diffraction to precisely monitor crystal structure at the extremes of pressure and temperature produced by shock-wave loading is explored. A summary of the advantages of using various X-ray sources for this work and an outline of the necessary experimental layout is given.

Journal Article↗

A SAXS/WAXS XAFS study of crystallisation in cordierite glass.

New Cr X-ray absorption fine structure (XAFS) data have been combined with the results of small angle X-ray scattering (SAXS) and wide angle X-ray scattering (WAXS) experiments to probe in detail the crystallisation mechanism in cordierite (Mg2Al4Si5O18) glass doped with 0.34 mol% Cr2O3. By direct comparison with chromo-aluminate spinels (MgCr2xAl2(1 - x)O4) Cr XAFS is used to determine the composition of the devitrified Cr species. This is identified as MgCr(0.18)Al(1.82)O4, which can be directly related to the Cr content in the starting glass and as a result the total crystalline volume in the fully developed ceramic is predicted to be 4%. In situ WAXS not only reveals the presence of the spinel phase but also a silica-rich stuffed quartz phase. This grows independently of the spinel and is probably nucleated from the glass surface. From our knowledge of the compositions of both crystalline phases we are able to deduce that the SAXS contrast between the surrounding glass and the spinel crystallites is 30 times greater than that between the quartz crystallites and the glass matrix, and therefore dominates the measured scattered intensity and the SAXS invariant that is derived from it. As a consequence we are able to show that the spinel crystalline volume fraction inherent in the SAXS is in close agreement with the 4% value obtained from the Cr XAFS. Furthermore in situ SAXS reveals the gradual development of the spinel particle size and shape during heat treatment. This is conducted in the super-cooled region just above the glass transition temperature, Tg. By employing a two-step annealing process nucleation can be separated from growth and from time-resolved SAXS measurements the alumino-chromate nanocrystals are found to be closely monodispersed. Over a total time course of 600 min they grow from rough crystallites to smooth spherical particles of radius 21 +/- 2 nm, with a final density of (1.2 +/- 0.4) x 10(21) m(-3). As the process of ceramic formation takes place in the viscous melt, growth is indeed found to be limited by diffusion and is complete when all the Cr is exhausted. We use this comprehensive in situ study of crystallisation in cordierite glass to demonstrate the advantages of combining SAXS, WAXS and XAFS for probing the time-resolved chemistry, the microstructure and its development from nucleation sites, that underpins the processing of nanoparticle ceramics.

Journal Article↗

A case of childhood dermatofibrosarcoma protuberans without detected cytogenetic abnormality.

Dermatofibrosarcoma protuberans (DFSP) is a rare, infiltrative skin tumour of intermediate malignancy, with a limited potential for metastasis but a high rate of recurrence; specific cytogenetic abnormalities are now known. Childhood DFSP has been considered a rarity in the past, but it is now recognized that many cases of childhood DFSP are diagnosed only in adulthood. Despite advances in the understanding of its pathogenesis as well as the development of valuable immunohistochemical and cytogenetic diagnostic techniques, there often remains a significant delay between the initial presentation and diagnosis of DFSP. We report a case of childhood DFSP in which the diagnosis was reached only after a nodular lesion developed in a plaque that was initially present. Causes for delay between initial presentation and diagnosis in childhood DFSP are discussed. Histology and immunostaining in our patient showed the typical features of DFSP, but the G-banded cytogenetic analysis of short-term tissue culture was negative. However, this technique offers only a detection rate between 50% and 80%. Clinicians should be aware of the limitations of newer diagnostic techniques. Increasing recognition amongst paediatricians and paediatric dermatologists that childhood DFSP is not as rare as once believed will probably lead to the use of newer diagnostic methods at an earlier stage, and so reduce the delay between the onset of symptoms and diagnosis.

Biopsy↗

Comedogenesis: some aetiological, clinical and therapeutic strategies.

Hypercornification is an early feature of acne and usually precedes inflammation. It is associated with ductal hyperproliferation, and there are many controlling factors such as androgens, retinoids, sebum composition and cytokines. Cycling of normal follicles and of comedones may explain the natural resolution of comedones and, in the longer term, resolution of the disease itself. There is a need to tailor treatment according to comedonal type. Suboptimal therapy can often result from inappropriate assessments of comedones, especially microcomedones, sandpaper comedones, submarine comedones and macrocomedones. Macrocomedones can produce devastating acne flares, particularly if patients are inappropriately prescribed oral isotretinoin. Gentle cautery under topical local anaesthesia is a useful therapy in the treatment of such lesions. The newer retinoids and new formulations of all-trans-retinoic acid show a better benefit/risk ratio.

Acne Vulgaris↗

Laser treatment of erythema and telangiectasia associated with rosacea.

The response of rosacea-associated erythema and telangiectasia to treatment with the pulsed tunable dye laser (PDL) was evaluated in 12 patients. Improvements in erythema, telangiectasia, flushing, the physician's and the patient's perception of overall severity, treatment tolerability, and the adverse side effects were examined. With the sole exception of the patient's assessment of overall severity we have found highly significant improvements in all other parameters evaluated, with excellent tolerance of treatment. We therefore conclude that the PDL is a safe and effective treatment for the erythemato-telangiectatic component of rosacea.

Adult↗

Exercise in the reduction of cardiovascular events. Lessons from epidemiologic trials.

In conclusion, much has been learned about the effects of exercise in reducing events in those with CHD. Some data are confusing, however, and some gaping holes exist in our understanding. Hopefully, new data forthcoming in the next 5 to 10 years will clear up this picture significantly. Meanwhile, cardiovascular exercise, coupled with other risk factor reduction, has been firmly established as a lifesaving and life-improving tool in those who have developed manifestations of CHD.

Cardiovascular Diseases↗

In situ EXAFS, X-ray diffraction and photoluminescence for high-pressure studies.

A new facility for simultaneous extended X-ray absorption of fine structure (EXAFS), X-ray diffraction and photoluminescence measurements under high pressures has been developed for use on station 9.3 at the Daresbury Laboratory Synchrotron Radiation Source. This high-pressure facility can be used at any suitable beamline at a synchrotron source. Full remote operation of the rig allows simultaneous collection of optical and structural data while varying the pressure. The set-up is very flexible and can be tailored for a particular experiment, such as time- or temperature-dependent measurements. A new approach to the collection of high-pressure EXAFS data is also presented. The approach significantly shortens the experimental times and allows a dramatic increase in the quality of EXAFS data collected. It also opens up the possibility for EXAFS data collection at any pressure which can be generated using a diamond cell. The high quality of data collected is demonstrated with a GaN case study. Particular attention will be paid to the use of energy-dispersive EXAFS and quick-scanning EXAFS techniques under pressure.

Journal Article↗

Site-directed cross-linking of b to the alpha, beta, and a subunits of the Escherichia coli ATP synthase.

The b subunit dimer of the Escherichia coli ATP synthase, along with the delta subunit, is thought to act as a stator to hold the alpha(3)beta(3) hexamer stationary relative to the a subunit as the gammaepsilonc(9-12) complex rotates. Despite their essential nature, the contacts between b and the alpha, beta, and a subunits remain largely undefined. We have introduced cysteine residues individually at various positions within the wild type membrane-bound b subunit, or within b(24-156), a truncated, soluble version consisting only of the hydrophilic C-terminal domain. The introduced cysteine residues were modified with a photoactivatable cross-linking agent, and cross-linking to subunits of the F(1) sector or to complete F(1)F(0) was attempted. Cross-linking in both the full-length and truncated forms of b was obtained at positions 92 (to alpha and beta), and 109 and 110 (to alpha only). Mass spectrometric analysis of peptide fragments derived from the b(24-156)A92C cross-link revealed that cross-linking took place within the region of alpha between Ile-464 and Met-483. This result indicates that the b dimer interacts with the alpha subunit near a non-catalytic alpha/beta interface. A cysteine residue introduced in place of the highly conserved arginine at position 36 of the b subunit could be cross-linked to the a subunit of F(0) in membrane-bound ATP synthase, implying that at least 10 residues of the polar domain of b are adjacent to residues of a. Sites of cross-linking between b(24-156)A92C and beta as well as b(24-156)I109C and alpha are proposed based on the mass spectrometric data, and these sites are discussed in terms of the structure of b and its interactions with the rest of the complex.

Amino Acid Substitution↗

Rapid methods for the calibration of solid-state detectors.

A complementary pair of rapid methods for the energy calibration of solid-state detectors have been developed. Each method requires only a single measurement from either (i) a glass sample containing elements chosen to produce fluorescence lines over a suitable energy range when exposed to a polychromatic beam of X-rays, or (ii) a powder diffraction standard in the presence of diffraction slits. The fluorescent glass method has the advantage of allowing simultaneous energy calibration of a number of detectors without requiring diffraction slits. There is the potential for the glass material to be incorporated into virtually any sample holder to allow a continuous in situ calibration. Complementary observations of a powder diffraction standard allow simultaneous calibration of diffraction 2theta and monitoring of the detector for drift.

Journal Article↗

Men's attitudes regarding genetic testing for hereditary prostate cancer risk.

OBJECTIVES: Little is known about the attitudes of men unselected for a family history for prostate cancer concerning genetic testing for prostate cancer risk or genetic testing for inherited cancer predisposition. To explore this, we examined the interest in molecular testing for hereditary prostate cancer (HPC) predisposition among a self-selected cohort of 342 men presenting for prostate cancer screening. METHODS: Participants were surveyed concerning their attitudes about DNA testing for HPC predisposition and knowledge of prostate cancer-associated risk factors, including heredity. RESULTS: Of the participants completing the survey, 92% expressed interest in learning about DNA testing, and 89% stated that they would undergo DNA analysis for HPC predisposition, if available. Twenty-eight percent of respondents failed to demonstrate an adequate understanding of the concept of "inherited tendency." The demonstrated level of understanding of this concept did not differ by the respondent's family history, although it varied by race. An interest in learning about or undergoing testing did not vary by race, family history, or demonstrated understanding of the concept of inherited risk. CONCLUSIONS: Among men presenting for routine prostate cancer screening, interest in learning about testing for HPC predisposition and in having such testing performed may be high. The data also provide evidence that, in a population of men unselected for family history, interest in molecular testing for this common, male-specific cancer may parallel the high interest level demonstrated among women in DNA testing for inherited breast and ovarian cancer risk.

Adult↗