Search PubMed⌕ Search

Biomedical subjects

I R White

Publications and source records attributed to I R White.

At least 19 recordsLinked to original sources
PubMed2003

A comparison of the alcohol-attributable mortality in four European countries.

BACKGROUND: Deaths due to alcohol consumption are an important component of all-cause mortality, particularly premature mortality. However, there are considerable regional variations, the reasons for which are unclear. METHODS: Estimates were made as reliably as possibly using vital statistics and best estimates of risk of the alcohol-attributable mortality, by age, sex and cause for four European countries (England and Wales, Germany, Denmark and Italy). Twenty-seven alcohol-related conditions were considered including the possible cardio-protective effects of alcohol. RESULTS: It was estimated that there are approximately 2% fewer deaths annually in England and Wales than would be expected in a non-drinking population and 0.3% fewer deaths among East German females. In West Germany, Denmark, Italy and among East German males there are more deaths caused by alcohol than are prevented (between 0.7 and 2.6% of all deaths). The highest age-specific proportion of alcohol-attributable deaths is found in East Germany where around 30% of deaths among males aged 25-44 years are due to drinking. Among young men in all four countries the largest contributor to alcohol-related deaths is road traffic accidents involving alcohol. CONCLUSIONS: Possible explanations for the variation in alcohol-attributable deaths between countries include different underlying heart disease rates, different patterns of alcohol consumption and beverage preferences, and different use of mortality classification. Differences in the reported alcohol consumption levels explain little of the variation in alcohol-attributable deaths. Estimating alcohol-attributable mortality by age and sex across countries may be a useful indicator for developing alcohol strategies and exploring ways of preventing premature mortality.

Adolescent↗
PubMed2003

Deodorants: an experimental provocation study with hydroxycitronellal.

Axillary dermatitis is a common problem, particularly in individuals with contact allergy to fragrances. Many individuals suspect their deodorant to be the causal product of their fragrance allergy. It has been shown that deodorants containing cinnamic aldehyde (cinnamal) can elicit axillary dermatitis in patients sensitized to this substance. The aim of the present investigation was to evaluate the importance of hydroxycitronellal used in deodorants for the development of axillary dermatitis, when applied by individuals with and without contact allergy to this fragrance chemical. Patch tests with deodorants and ethanolic solutions containing hydroxycitronellal, as well as repeated open application tests (ROAT) with roll-on deodorants with and without hydroxycitronellal at different concentrations, were performed in 14 dermatitis patients, 7 with and 7 without contact allergy to hydroxycitronellal. A positive ROAT was noted only in the patients hypersensitive to hydroxycitronellal (P < 0.001) and only in the axilla to which the deodorants containing hydroxycitronellal had been applied (P < 0.001). Deodorants containing hydroxycitronellal in the concentration range of 0.032-0.32% used twice daily on healthy skin in individuals hypersensitive to hydroxycitronellal can elicit axillary dermatitis in a few weeks.

Adolescent↗
PubMed2002

Contaminating resin acids have not caused the high rate of sensitivity to oak moss.

Commercially available oak moss absolute patch test material has recently been shown to contain resin acids of the type found in colophony (colophonium). We wished to assess whether the high frequency of positive patch tests to oak moss absolute at this institute was likely to reflect significant contamination by resin acids. The rate of positive reactions to colophony among our oak moss-allergic patients patch tested during 1984-2000 was retrospectively investigated. 25395 patients were tested to the European standard series during this period and 1963 (7.7%) were allergic to the fragrance mix. 342 of these patients were allergic to oak moss absolute, of whom 73 (21.3%) were allergic to colophony. In comparison, 115 (13.4%) of 861 fragrance mix-positive but oak moss-negative patients were allergic to colophony (p = 0.0002, Fisher's exact test). This strongly statistically significant association between oak moss absolute and colophony shows only a small increase in rates of allergy to colophony in oak moss-positive patients. Thus we conclude that contaminating resin acids have not alone caused the high rate of sensitivity to oak moss.

Acids↗
PubMed2002

Further important sensitizers in patients sensitive to fragrances.

In order to find sensitizers additional to the current fragrance mix (FM) a series of fragrance materials (series II) was evaluated in 6 dermatological centres in Europe. 11 of the test materials were essential oils, the remaining 7 being either mixtures of isomers or simple chemicals of frequent usage in the perfume industry. 1606 patients were consecutively tested with series II and 8% FM. Each patient was classified regarding a history of adverse reactions to scented products: certain, probable, questionable, none. Reactions to FM occurred most frequently in 11.4% of the subjects. The 6 materials with the highest reactivity after the FM were ylang-ylang oil (YY) I (2.6%), YY II (2.5%), lemongrass oil (1.6%), narcissus absolute (1.3%), jasmine absolute (1.2%) and sandalwood oil (0.9%). 48 (3.0%) of the patients reacted only to materials of series II and not to FM. 6.0% of 1606 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 22.9%, to series II and FM in 15.6% and to series II only in 5.2%. 63.5% of the patients reacting to both FM and 1 of the materials of series II had some type of positive fragrance history, which was higher in comparison to those with isolated reactions to FM (46.2% of 121) or to series II, respectively, (45.8% of 48). However, this difference was not statistically significant. In conclusion, the materials of series II identified a further subset of patients with a fragrance problem, which would have been missed by the current FM as the single screening tool for patch testing.

Dermatitis, Allergic Contact↗
PubMed2002

Comparative frequency of patch test reactions to topical antibiotics.

BACKGROUND: Neomycin, clioquinol and fusidic acid are all topical antibiotics widely used in dermatological practice in the U.K., either as a single agent or in combination with topical corticosteroids. However, an adverse effect of topical antibiotics is contact sensitization. OBJECTIVES: To examine the frequency of positive patch test reactions to fusidic acid, clioquinol and neomycin. METHODS: To compare the frequency of allergic patch test reactions over 1 year, we patch tested all patients attending the St John's Institute of Dermatology contact dermatitis clinic for one calendar year with fusidic acid, neomycin and clioquinol. RESULTS: We patch tested 1119 patients. Positive patch test reactions to neomycin were noted in 40 patients (3.6%), compared with eight patients (0.7%) to clioquinol and three patients (0.3%) to fusidic acid. The frequency of medicament allergy to neomycin was thus five times more common than to clioquinol and ten times more common than to fusidic acid. Although fusidic acid is not part of our extended standard series, it is in our medicaments series. Therefore, in the second part of our study, we reviewed all cases of positive patch test reactions to fusidic acid over the last 20 years. We found that the frequency of hypersensitivity has decreased since the early 1980s despite increasing usage; the current average frequency being 1.62 patch-tested patients per year (1.45%) of those patch tested to the medicaments series). The most common diagnosis in such patients was stasis dermatitis (54.2%). CONCLUSIONS: The frequency of fusidic acid allergy in an eczema population is low and is comparable with published data from over 10 years ago.

Administration, Topical↗
PubMed2002

Dermatitis caused by physical irritants.

BACKGROUND: Although physical irritant contact dermatitis (PICD) is a common occupational dermatosis, it is one of the least well understood because of its multiple types, lack of diagnostic test, and the many mechanisms involved in its production. OBJECTIVES: To characterize the materials and mechanisms of physical irritation of the skin. METHODS: We did a retrospective analysis over the past 20 years of all patients with a diagnosis of PICD at St John's Institute of Dermatology Contact Dermatitis Clinic. RESULTS: Of the 29,000 patients who attended the clinic over the study period, 392 patients were diagnosed with PICD and of these, 335 files were analysed. CONCLUSIONS: Our findings show that PICD accounted for 1.15% of all patients attending the contact clinic over the study period. Diverse occupations and materials were implicated. The most common cause of PICD was low humidity due to air-conditioning, which caused dermatitis of the face and neck in office workers due to drying out of the skin.

Adolescent↗
PubMed2002

Skin as a route of exposure to protein allergens.

Protein contact with skin is associated with a number of clinical conditions, including protein contact dermatitis and immunologic contact urticaria. This article reviews the clinical and other selected evidence that proteinaceous materials penetrate skin. It is concluded that whilst penetration of intact proteins through normal skin is extremely low and without consequence, any damage to the skin barrier may allow penetration. As a result, risk assessment for contact of protein with skin must take into account potential barrier impairment and thus the possibility of both the induction and the elicitation of allergic skin reactions.

Allergens↗
PubMed2002

Fragrance as an occupational allergen.

Sensitization to fragrance is believed to occur mainly outside the workplace. This study addresses the frequency of fragrance allergy in patch test patients of differing occupations during a 15 year period. The occupation most strongly associated with fragrance allergy in both sexes was health care work (positive tests in 11.7% of males and 10.4% of females). Retired individuals also had high rates of fragrance allergy (11.6% of males and 14.5% of females), and the prevalence of sensitization increased with advancing age. Health care workers and metal workers had statistically significantly higher rates of allergy to eugenol than did workers in other occupations. Food handlers had significantly higher rates of allergy to cinnamal and cinnamic alcohol. These findings suggest that sensitization to fragrance occurs more frequently in an occupational setting than is generally understood and could have implications for preventive measures.

Adult↗
PubMed2002

Further important sensitizers in patients sensitive to fragrances.

The aim of this study was to determine the frequency of responses to selected fragrance materials in consecutive patients patch tested in 6 dermatological centres in Europe. 1855 patients were evaluated with the 8% fragrance mix (FM) and 14 other frequently used well-defined fragrance chemicals (series I). Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Reactions to FM occurred in 11.3% of the subjects. The 6 substances with the highest reactivity following FM were Lyral (2.7%), citral (1.1%), farnesol P (0.5%), citronellol (0.4%), hexyl cinnamic aldehyde (0.3%), and coumarin (0.3%). 41 (2.2%) of the patients reacted only to materials of series I and not to FM. 6.6% of 1855 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 41.1%, to series I and FM in 12.0% and to series I only in 7.2%. 74.3% of the 39 patients reacting to both FM and 1 of the materials of series I had any type of positive fragrance history, which was significantly higher in comparison to those with isolated reactions to series I (53.6% of 41), p = 0.04. The study identified further sensitizers relevant for patch testing of patients with contact dermatitis, of which Lyral is the most important single chemical.

Allergens↗
PubMed2001

Randomized clinical trials with added rescue medication: some approaches to their analysis and interpretation.

Patients in some randomized clinical trials may start additional non-randomized medication because of an exacerbation of symptoms or insufficient therapeutic effect. Typically this rescue medication reduces the observed treatment effect in intention-to-treat analysis. We discuss methods of analysis which take account of rescue medication in order to achieve a more meaningful comparison of the randomized treatments, focusing on trials with a repeated quantitative outcome. Ignoring all data after rescue is likely to be biased because rescued patients are a highly selected group. Instead we propose using methods based on ranks or multilevel models. The rank-based methods assume that rescued patients have especially bad underlying outcomes. The multilevel regression model relates a patient's outcome to allocated treatment and rescue status at each time, and requires correct modelling of all prognostic factors which predict starting rescue medication and of the covariance between outcomes measured at different times. We also describe sensitivity analyses over a range of possible models for the effect of rescue medication. We illustrate these methods in a trial in Parkinson's disease. It appears that adjustment for rescue medication will not radically alter the randomized treatment comparison unless rescue medication is substantially imbalanced between randomized groups and has a substantial effect on the outcome.

Activities of Daily Living↗
PubMed2001

Evidence that inhibition of cathepsin-B contributes to the neuroprotective properties of caspase inhibitor Tyr-Val-Ala-Asp-chloromethyl ketone.

During the use of tetrapeptide and other proprietary caspase inhibitors in the study of neurodegeneration, we had concluded that mechanisms other than the inhibition of caspases contributed to the protective effects of certain caspase inhibitors. Here we report our studies to identify a target for and hence a mechanism by which the tetrapeptide inhibitor tyrosine-valine-alanine-aspartate-chloromethyl ketone (Ac-YVAD-cmk) is able to rescue neuronal cell cultures from cell death. Ac-YVAD-cmk rescued neuronal cells from cell death in response to oxidative stress and oxygen/glucose deprivation. Affinity labeling with biotinylated YVAD-cmk demonstrated distinct binding proteins for the inhibitor in cells from the central nervous system versus Jurkat cells. Binding to the novel target protein was displaced by class-specific protease inhibitors and suggested that the target is a cysteine protease. Affinity purification and sequencing identified the target as cathepsin-B. Cathepsin-B inhibitors competed with biotinylated YVAD-cmk for the target protein. The availability of the target for binding was reduced in cells that had been rescued by unlabeled inhibitor. Cathepsin-B inhibitors rescue hippocampal slices from cell death induced by oxygen/glucose deprivation. These data provide evidence to support a role for cathepsin-B in neuronal cell death, particularly that following ischemia.

Amino Acid Chloromethyl Ketones↗
PubMed2001

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↗
PubMed2001

Clinical allergy to cocamidopropyl betaine: reactivity to cocamidopropylamine and lack of reactivity to 3-dimethylaminopropylamine.

7 patients allergic to cocamidopropyl betaine (CAPB) were detected by positive patch test reactions to Tegobetaine L7TM. These patients were then asked to participate in further testing to its potential impurities, cocamidopropylamine and 3-dimethylaminopropylamine (DMAPA). 4 of the 7 patients were tested to purified CAPB and cocamidopropylamine, with 2 reacting to the purified betaine on allergy patch testing and 3 reacting to cocamidopropylamine 0.1%. At another date, 6 of the 7 were successfully recalled for testing to DMAPA in the presence of sodium lauryl sulfate (SLS) or pure CAPB; 1/6 reacted to DMAPA in water, but only at very high concentrations, at least 3 orders of magnitude higher than that to which skin exposure would occur from use of products containing CAPB. Both SLS and CAPB increased the number of reactions recorded to high levels of DMAPA. However, positive reactions to much lower concentrations of DMAPA (>or=100 ppm) were found in only 1/6 subjects and then only in the presence of the irritant SLS. 0/6 reacted to pure CAPB alone. Taken together, these results suggest that DMAPA is unlikely to be an important contact allergen in CAPB of appropriate quality. They also confirm that CAPB of suitable purity, where levels of both cocamidopropylamine and DMAPA are minimized, is unlikely to trigger reactions in those ostensibly allergic to the material.

Adult↗
PubMed2001

Human potency predictions for aldehydes using the local lymph node assay.

The murine local lymph node assay (LLNA) assesses skin sensitization potential as a function of proliferative responses induced in lymph nodes draining the site of topical exposure to test chemical. It has been shown that interpolation of LLNA dose-response data to define the concentration of test chemical required to induce a 3-fold stimulation of proliferation (EC3) offers the prospect of a quantitative index of the relative potency of a contact allergen. Initial studies have demonstrated that there exists a strong (inverse) correlation between EC3 values and contact allergenic potency in humans. Thus, materials with a low EC3 value were more potent contact allergens in humans. However, it is necessary to examine a wide range of allergens to demonstrate that such correlations are generally true. Thus, in the present study, 10 aldehydes of varying degrees of allergenicity in man were evaluated in the LLNA and their EC3 values derived. Formaldehyde was regarded as the strongest allergen in man and also had the lowest EC3 value, 0.35% (equivalent to 0.93% formalin). In contrast, the extremely weak allergen vanillin and the non-sensitizer ethyl vanillin both had EC3 values of >50%. For the remaining 7 aldehydes, there was a close similarity between what is judged to be their rank order of allergenicity in humans and EC3 values derived from analysis of LLNA data. These results support further the utility of EC3 determinations in the LLNA as a measure of the relative potency of a contact allergen.

Aldehydes↗
PubMed2001

Understanding fragrance allergy using an exposure-based risk assessment approach.

Conducting a sound skin sensitization risk assessment prior to the introduction of new ingredients and products into the market place is essential. The process by which low-molecular-weight chemicals induce and elicit skin sensitization is dependent on many factors, including the ability of the chemical to penetrate the skin, react with protein, and trigger a cell-mediated immune response. Based on our chemical, cellular and molecular understanding of allergic contact dermatitis, it is possible to carry out a quantitative risk assessment. Specifically, by estimating the exposure to the allergen and its allergenic potency, it is feasible to assess quantitatively the sensitization risk of an ingredient in a particular product type. This paper focuses on applying exposure-based risk assessment tools to understanding fragrance allergy for 2 hypothetical products containing the fragrance allergen cinnamic aldehyde. The risk assessment process predicts that an eau de toilette leave-on product containing 1000 ppm or more cinnamic aldehyde would pose an unacceptable risk of induction of skin sensitization, while a shampoo, containing the same level of cinnamic aldehyde, would pose an acceptable risk of induction of skin sensitization, based on limited exposure to the ingredient from a rinse-off product application.

Acrolein↗
PubMed2001

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↗