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Biomedical subjects

I R White

Publications and source records attributed to I R White.

At least 19 recordsLinked to original sources

Principal component analysis of mass spectra of peptides generated from the tryptic digestion of protein mixtures.

Principal component analysis (PCA) has been used to analyse mass spectral peptide profiles obtained from the enzymatic digestion of standard protein mixtures. Scores and loadings plots clearly revealed peptide fragments that differentiated one protein mixture from another. Peptide map search results identified with a high degree of certainty any additional proteins in these mixtures. As a proof-of-concept this methodology was applied to hepatic protein mixtures obtained from rats treated with two hepatotoxic compounds: methapyriline and SB-219994. Liver proteins were extracted, pre-separated by one-dimensional polyacrylamide gel electrophoresis, subjected to tryptic digestion and analysed by mass spectrometry. Two up-regulated proteins, glutathione S-transferase with methapyrilene and peroxisomal bifunctional enzyme with SB-219994, were identified in this manner.

Amino Acid Sequence↗

Changing frequency of thiuram allergy in healthcare workers with hand dermatitis.

BACKGROUND: Healthcare workers (clinical, allied/paramedical professions and ancillary workers) may have prolonged contact with natural rubber latex devices, particularly in the form of natural rubber latex gloves. OBJECTIVES: To examine the changing frequency of type IV thiuram allergy in healthcare workers with hand dermatitis over a 16-year period. METHODS: During the study period, 450 healthcare workers (352 women and 98 men) with hand dermatitis were investigated, and their patch test results were analysed retrospectively. RESULTS: On average, a thiuram-positive patch test was noted in 12% of individuals, with a peak incidence of 27% of the patients patch tested in 1994. Comparison of results between 1983--88 and 1989--93 showed a statistically significant increase in the incidence of thiuram-positive patch tests (odds ratio 2.55, 95% confidence interval 1.25--5.20, P = 0.01). CONCLUSIONS: We have documented a changing frequency of thiuram-positive patch tests in healthcare workers with hand dermatitis since 1983. This may reflect changes in degree of exposure to thiurams in medical gloves during this period.

Adolescent↗

Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: a meta-analytical approach.

The relation between meat consumption and colorectal cancer risk remains controversial. In this report, we quantitatively reviewed the prospective observational studies that have analyzed the relation between meat consumption and colorectal cancer. We conducted electronic searches of MEDLINE, EMBASE, and CANCERLIT databases through to the end of June 1999 and manual searches of references from retrieved articles. We used both fixed and random-effects meta-analytical techniques to estimate the overall association and to investigate possible sources of heterogeneity among studies. Thirteen studies were eligible for inclusion in the meta-analysis. Pooled results indicate that a daily increase of 100 g of all meat or red meat is associated with a significant 12-17% increased risk of colorectal cancer. The marginally significant between-study heterogeneity for all meat and red meat was explained by a number of study-level covariates. A significant 49% increased risk was found for a daily increase of 25 g of processed meat. The individual study estimates for processed meat showed no detectable heterogeneity. On the basis of this quantitative review of prospective studies, the overall association between meat consumption and risk of colorectal cancer appears to be positive, with marginal heterogeneity between studies. The finding for processed meat and data from experimental studies suggests that it may also be an important predictor of colorectal cancer risk. However, because only a few of the studies reviewed here attempted to examine the independent effect of meat intake on colorectal cancer risk, the possibility that the overall association may be confounded or modified by other factors cannot be excluded.

Adult↗

Patch testing with corticosteroid mixes in Europe. A multicentre study of the EECDRG.

This study investigated whether a corticosteroid mix containing tixocortol pivalate, budesonide, and hydrocortisone-17-butyrate could detect contact allergy to corticosteroids. 2 corticosteroid mixes, 1 with a high (mix I) and 1 with a low (mix II) concentration and the 3 individual constituents, each at 2 concentrations, were inserted into the standard series of 16 participating clinics. Tests were read on day (D) 3 or 4. 5432 patients were tested, and 110 (2.0%) had positive reactions to at least 1 of the 8 test preparations. Of the 8 preparations, mix I identified most allergic patients, followed by mix II, budesonide 0.10%, budesonide 0.002%, and tixocortol pivalate, both concentrations (1.0 and 0.10%) tracing the same number. With the mixes, 53.2-59.6% of tixocortol pivalate allergy was missed. 47 patients were allergic to either concentration of tixocortol pivalate, 25% of these only to 1.0% and another 25% only to 0.10%. Testing with mix I and tixocortol pivalate 0.10% picked up 98/110, testing with tixocortol pivalate 1.0% and 0.10% and budesonide 0.10% picked up 105/110. 3379 patients were read on both D3 or D4 as well as on D7. Without a late reading (D7), up to 30% of contact allergy to corticosteroid markers was missed.

Administration, Topical↗

The importance of exposure estimation in the assessment of skin sensitization risk.

The development of new ingredients and products for the consumer market requires a thorough assessment of their potential for skin sensitization and the possible clinical manifestation of allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization reactions is complex and dependent on many factors relevant to the ability of the chemical to penetrate the skin, react with protein, and trigger the cell-mediated immune response. These major factors include inherent potency, chemical dose, duration and frequency of exposure, vehicle or product matrix, and occlusion. The fact that a chemical is a contact allergen does not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragrances, preservatives) are known skin allergens. However, all allergens show dose-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptably low incidences of skin sensitization under foreseeable conditions of exposure. The critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests (including cross-species comparisons), and, at least for known potent allergens, there is remarkable similarity in threshold dose/unit area determinations across species. The dose/unit area calculation enables a judgment of the sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) as a case study.

Animals↗

Use of the local lymph node assay for the estimation of relative contact allergenic potency.

The effective toxicological evaluation of skin sensitization demands that potential contact allergens are identified and that the likely risks of sensitization among exposed populations assessed. By definition, chemicals which possess the toxicological property of skin sensitization potentially are capable of causing allergic contact dermatitis (ACD) in humans. However, this hazard is not an all-or-none phenomenon; clear dose-response relationships can be discerned and thresholds identified for both the induction of sensitization and the elicitation of contact dermatitis. Commonly, these parameters are grouped under the heading of potency, determination of which is vital for risk assessment. In the present investigation, the local lymph node assay (LLNA) has been employed to determine the relative potency of a range of 20 chemicals. The parameter used is the estimated concentration required to produce a 3-fold increase in draining lymph-node cell proliferative activity, the EC3 value. These measurements have been compared with an assessment of the human sensitizing potency of the 20 selected chemicals, each being assigned to 1 of 5 classes based on their human sensitizing potency. The EC3 value, derived from LLNA work carried out in acetone/ olive oil vehicle, correlated well with the human classification, with the strongest sensitizers having low EC3 values (<O.1%), weaker sensitizers having EC3 values generally in the 1-10% range, and non-sensitizing chemicals having EC3 values in excess of 100%. In conclusion, the derivation of the EC3 for a chemical provides an objective and quantitative estimate of potency that is of considerable utility for skin sensitization risk assessment.

Allergens↗

Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships.

Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application test on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test reactions was obtained by gas chromatography-mass spectrometry. From the compounds identified, those that contained a "structural alert" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.

Aldehydes↗

The frequency of fragrance allergy in a patch-test population over a 17-year period.

Fragrances are widely encountered in our daily environment and are known to be a common cause of allergic contact dermatitis. We have reviewed our patch test data from 1980 to 1996 to establish whether the pattern of fragrance allergy has changed with time. During this period, 25,545 patients (10,450 male, 15,005 female) were patch tested with the European standard series. The mean annual frequency of positive reactions to the fragrance mix was 8.5% in females (range 6.1-10.9) and 6.7% in males (range 5.1-12.9). Females were 1.3 times more likely to be allergic to fragrance (P < 0.001, 95% confidence interval, CI 1.17-1.41). Males with fragrance allergy were older than females by 5.6 years (mean age 48.2 vs. 42.6 years; P < 0.001, 95% CI 3.9-7.3). The incidence of a concomitant positive patch test to balsam of Peru in fragrance-sensitive patients showed wide variation, suggesting that it is not a reliable marker of fragrance allergy. There was a positive correlation between the isomers isoeugenol and eugenol. Oak moss remained the most common overall allergen throughout the study, positive in 38.3% of females and 35.6% of males who were tested to the constituents of the fragrance mix. During the period of the study the incidence of positive tests to oak moss increased by 5% yearly (P = 0.001, 95% CI 2.2-8.7). The frequency of allergic reactions to eugenol and geraniol remained relatively constant. Isoeugenol and alpha-amyl cinnamic aldehyde sensitivity increased and hydroxycitronellal showed a slow decline. There was a striking reduction in the frequency of sensitivity to cinnamic aldehyde (by 18% yearly; P < 0.001, 95% CI 14.3-21.0) and cinnamic alcohol (by 9% yearly; P < 0.001, 95% CI 5.2-12.9); these are now uncommon fragrance allergens. These data show temporal trends which may reflect the frequency of population exposure to individual fragrances.

Acrolein↗

Descriptive epidemiology of hand dermatitis at the St John's contact dermatitis clinic 1983-97.

For 15 years, hand dermatitis accounted for a quarter of patients seen in this clinic. The highest proportion occurred in women aged 17-30 years. Overall, the male to female ratio was 0.8, which contrasts with population-based studies. Catering was most frequently associated with occupational hand dermatitis. Other frequent occupational associations included metalworking, hairdressing, healthcare and mechanical work.

Adult↗

Reliability of the Camberwell Assessment of Need--European Version. EPSILON Study 6. European Psychiatric Services: Inputs Linked to Outcome Domains and Needs.

BACKGROUND: The five-country European Psychiatric Services: Inputs Linked to Outcome Domains and Needs (EPSILON) Study aimed to develop standardised and reliable outcome instruments for people with schizophrenia. This paper reports reliability findings for the Camberwell Assessment of Need--European Version (CAN-EU). METHOD: The CAN-EU was administered in each country, at two points in time to assess test-retest reliability, and was rated by two interviewers at the first administration. Cronbach's alpha, test-retest reliability and interrater reliability were compared between the five sites. Reliability coefficients and standard errors of measurement for summary scores were estimated. RESULTS: Sites varied in levels and spread of needs. Alphas were 0.48, 0.58 and 0.64 for total, met and unmet needs respectively. Test-retest reliability estimates, pooled over sites, were 0.85 for the total needs, 0.69 for met needs and 0.78 for unmet needs. Pooled estimates for interrater reliability were higher, at 0.94, 0.85 and 0.79 for total, met and unmet needs respectively. There were statistically significant differences in interrater reliability between sites. CONCLUSION: The results confirm the feasibility of using CAN-EU across sites in Europe and its psychometric adequacy.

Adolescent↗

Methodology of a multi-site reliability study. EPSILON Study 3. European Psychiatric Services: Inputs Linked to Outcome Domains and Needs.

BACKGROUND: The European Psychiatric Services: Inputs Linked to Outcome Domains and Needs (EPSILON) Study aims to produce standardised versions in five European languages of instruments measuring needs for care, family or caregiving burden, satisfaction with services, quality of life, and socio-demographic and service receipt. AIMS: To describe background, rationale and design of the reliability study, focusing on reliable instruments, reliability testing theory, a general reliability testing procedure and sample size requirements. METHOD: A strict protocol was developed, consisting of definitions of the specific reliability measures used, the statistical methods used to assess these reliability coefficients, the development of statistical programmes to make inter-centre reliability comparisons, criteria for good reliability, and a general format for the reliability analysis. CONCLUSION: The reliability analyses are based on classical test theory. Reliability measures used are Cronbach's alpha, Cohen's kappa and the intraclass correlation coefficient. Intersite comparisons were extended with a comparison of the standard error of measurement. Criteria for good reliability may need to be adapted for this type of study. The consequences of low reliability, and reliability differing between sites, must be considered before pooling data.

Adult↗