Novel corneal features in two males with incontinentia pigmenti.

Incontinentia pigmenti (IP) is a rare X linked genetic disorder, which predominantly affects females. The mutations are usually lethal in males. Two male cases are presented; a genetic mosaic for the common IP deletion and another in whom the genetic abnormality has not yet been characterised. Emphasis is placed on the ocular features present in this disorder and in particular a novel corneal feature and its possible aetiology.

Neutron diffraction and atomistic simulation studies of Mg doped apatite-type oxide ion conductors.

In this paper, detailed studies of the effect of Mg doping in the apatite-type oxide ion conductor La9.33Si6O26 are reported. Mg is confirmed as an ambisite dopant, capable of substituting for both La and Si, depending on the starting composition. A large enhancement in the conductivity is observed for Si site substitution, with a reduction for substitution on the La site. Neutron powder diffraction studies show that in agreement with cation size expectations, an enlargement of the unit cell is observed on Mg substitution for Si, with a corresponding increase in the size of the tetrahedral sites. For Mg substitution on the La site, a contraction of the unit cell is observed, and the neutron diffraction results indicate that there is preferential occupancy of Mg on the La2 (1/3, 2/3, approximately 0.5) site. Atomistic simulation studies show significant local structural changes affecting the oxide ion channels in both cases. Mg doping on the Si site leads to a local expansion of the channels, while doping on the La site results in a large displacement of the silicate O4 site, such that it encroaches the oxide ion channels. The observed differences in conductivities are discussed with respect to these observations.

Colophony allergy: a review.

Colophony is a complex mixture of over 100 compounds derived from pine trees. It has countless applications at home and at work and exposure to colophony and modified-colophony is universal. It is the oxidation products of unmodified and modified colophony and some of the new resin acids synthesized during modification that are the principle allergens in colophony. The neutral fraction may account for a small % of positive reactions. When screening for allergy using unmodified gum rosin, allergy to modified rosin will not be revealed. When patients react to both materials, it is probably due to unmodified colophony present in both, rather than a cross-reaction. Relevant positive reactions may be missed if only colophony 20% pet is relied upon as the screening material.

Susceptibility of Malassezia furfur subgroups to terbinafine.

Malassezia furfur, the fungus causing pityriasis versicolor, has been reported to be sensitive to terbinafine in vitro but although topical therapy is effective in the treatment of pityriasis versicolor, oral therapy is not. This phenomenon was investigated by determining the susceptibility to terbinafine of different M. furfur subgroups in vivo (during topical or oral application) and in vitro. All M. furfur subgroups were suppressed (approximately 10-fold) by topical terbinafine. Oral treatment resulted in no significant suppression of cutaneous M. furfur populations with the exception of a single subgroup (A), which was reduced to undetectable levels on the skin of eight of 10 patients receiving oral terbinafine. Isolates of subgroup A were also markedly more susceptible to terbinafine in laboratory tests. The importance of the recognition of distinct subgroups within the cutaneous lipophilic yeasts when evaluating their antifungal susceptibility and their role in disease is discussed.

Audit of Finn Chamber patch test preparation.

Reproducibility of patch test reactions is an important aspect of patch testing. Thin layer rapid use epicutaneous tests (TRUE Test) are preloaded with allergen, whereas Finn Chambers are empty discs that have allergen applied from a syringe. The amount of allergen applied to each Finn Chamber is therefore potentially variable depending on technique. This may increase the risk of non-reproducibility of reactions. We have performed an audit of patch test preparation in our department looking at weight variation of both individual Finn Chambers and 3 completed panels before and after allergen application. We found that the variance in weight was not significant for 2 of the 3 panels and single Finn Chambers with allergen in petrolatum. The variance in weight was significant for single Finn Chambers with allergen in solution and the third panel, which contains an allergen in solution. The clinical significance of these results is unclear.

Urinary leukotriene E4 levels in patients with atopic dermatitis.

Leukotriene synthesis may be increased in a variety of inflammatory diseases. Urinary leukotriene E4 is a stable metabolite of leukotrienes C4 and D4 which has previously been found to be increased in exacerbations of severe asthma and after antigen inhalation. Levels of urinary LTE4 in seven patients during and after a severe flare of atopic dermatitis were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Mean urinary LTE4 levels (+/- SEM) were not increased during (16.7 +/- 3.7 pg/mumol) or after (16.9 +/- 4.8 mumol) the acute exacerbation of atopic dermatitis when compared with the normal range (mean = 23.8 [95% confidence interval 19.9-28.2] pg/mumol creatinine). These findings do not provide evidence of cysteine leukotriene involvement in the pathogenesis of atopic dermatitis.

Development of apatite-type oxide ion conductors.

Research into materials displaying oxide ion conductivity is attracting considerable attention due to their potential technological applications in devices such as Solid Oxide Fuel Cells. In this paper, recent work on apatite-type oxide ion conductors is reviewed, showing that a wide range of cation substitutions are possible, due to the flexibility of the apatite structure in accommodating a range of ion sizes. The conductivity studies on these doped samples show that to achieve high oxide ion conduction, non-stoichiometry in terms of cation vacancies and/or oxygen excess is required, with the latter resulting in the highest conductivities. In contrast to most common oxide ion conductors, e.g. perovskite and fluorite in which oxide ion conduction proceeds via oxygen vacancies, the research on these apatite systems suggests that the conductivity involves interstitial oxide ions. With further optimization of these materials, particularly in terms of the Ge-containing systems, significant improvements in conductivity are likely, leading to the very real possibility of the application of apatite-type electrolytes in fuel cell and other applications.

Effects of H1- and H2-antihistamines on platelet-activating factor and bradykinin-induced inflammatory responses in human skin.

Previous studies show that oral antihistamines affect the weal and flare response to intradermal injections of the inflammatory mediators platelet-activating factor (PAF) and bradykinin (BK). The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on weal and flare responses to PAF and BK in healthy non-atopic human volunteers. The effects of doxepin on PAF responses were investigated, as there is evidence that doxepin may have direct anti-PAF effects in addition to its known antihistaminic actions. Terfenadine significantly reduced weal and flare responses to PAF (mean reduction 53 and 73%, respectively) and flare responses to BK (mean reduction 78%) but had no effect on weal responses to BK. Doxepin significantly reduced both weal and flare responses to PAF (mean reduction 43 and 68%, respectively, at higher doses of PAF). Cimetidine had no effect on weal or flare responses to PAF or BK. These findings suggest that the flare response to intradermal BK is mediated via histamine release while the weal response is not. The effects of the various antagonists of PAF-induced responses suggest that its effects too may be mediated via histamine, the similarity of the effects of terfenadine and doxepin on these responses indicating that the effects of doxepin may be due to its known antihistamine activity rather than to any specific PAF-antagonistic properties. Platelet-activating factor (PAF) is a phospholipid which is released from a wide range of cell types and also from vascular endothelium. PAF is formed by the conversion of ether-linked phospholipids initially to the biologically inactive lyso-PAF and then by acetylation to PAF. Intradermal injection of PAF in human skin causes vasodilatation and increased vascular permeability, producing a weal and flare response with accompanying pruritus. Bradykinin (BK) is a vasoactive polypeptide formed by the action of enzymes known as kallikreins on inactive precursors called kininogens. Its effects include an increase in blood flow and vascular permeability and stimulation of the release of prostaglandins and histamine. On intradermal injection in human skin it causes a weal and flare response with associated pain rather than pruritus. Previous studies have suggested that the weal and flare response to PAF may be mediated in part by histamine release. Given that BK is known to cause histamine release it appears possible that the responses to both compounds may be modified by conventional antihistamines. Experiments based on this premise have found that antihistamines have a pronounced effect on the flare response to PAF but a less marked effect on weal responses. The weal response to BK was unaffected by systemic antihistamines but studies have produced conflicting results with regard to effects on the flare response. The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on PAF- and BK-induced weal and flare responses in healthy, non-atopic human volunteers. Based on the treatment of cold urticaria it has been suggested that doxepin, which has known H1- and H2-antagonistic effects, may in addition show specific anti-PAF activity. We compared the effects of doxepin on PAF-induced intradermal responses with those of terfenadine and cimetidine in this study.

A fatal case of scleredema of Buschke.

Scleredema of Buschke is a rare disorder characterized by the development of areas of skin induration which usually resolve spontaneously. It is occasionally associated with a benign gammopathy, and rarely with myelomatosis. We describe a 60-year-old woman with extensive skin changes, who developed IgA myeloma. Unusually, her skin disease did not respond to conventional myeloma therapy. Death occurred as a consequence of the progressive skin disease.

Doping strategies to optimise the oxide ion conductivity in apatite-type ionic conductors.

The apatite-type phases, La(9.33+x)(Si/Ge)(6)O(26+3x/2), have recently been attracting considerable interest as potential electrolytes for solid oxide fuel cells. In this paper we report results from a range of doping studies in the Si based systems, aimed at determining the key features required for the optimisation of the conductivities. Systems examined have included alkaline earth doping on the rare earth site, and P, B, Ga, V doping on the Si site. By suitable doping strategies, factors such as the level of cation vacancies and oxygen excess have been investigated. The results show that the oxide ion conductivities of these apatite systems are maximised by the incorporation of either oxygen excess or cation vacancies, with the former producing the best oxide ion conductors. In terms of samples containing cation vacancies, conductivities are enhanced by doping lower valent ions, Ga, B, on the Si site. The presence of higher valent ions on these sites, e.g. P, appears to inhibit the incorporation of excess oxygen within the channels, and so limits the maximum conductivity that can be obtained. Overall the results suggest that the tetrahedral sites play a key role in the conduction properties of these materials, supporting recent modelling studies, which have suggested that these tetrahedra aid in the motion of the oxide ions down the conduction channels by co-operative displacements.

The British standard series of contact dermatitis allergens: validation in clinical practice and value for clinical governance.

BACKGROUND: All centres use an empirically determined set of 'standard' test allergens for patch testing that contain the commoner environmental sensitizers. Objectives To assess the validity of the British standard series of 12 allergens used in addition to the 23 already in the European standard series. PATIENTS AND METHODS: Results for 3062 consecutive patients patch tested in seven centres across the United Kingdom during the year 2000 were analysed. RESULTS: The additional allergens from the British series and positive rates were: methyl dibromoglutaronitrile 2.4%, carba mix 1.6%, tixocortol pivalate 1.5%, ethylenediamine 1.3%, cetearyl alcohol 0.8%, 2-bromo-2-nitropane-1,3-diol 0.8%, diazolidinyl urea 0.7%, chlorocresol 0.6%, budesonide 0.6%, fusidic acid 0.5%, imidazolidinyl urea 0.5%, and chloroxylenol 0.4%. The allergens with the lowest positive rate in the European standard series were primin at 0.6% and isopropyl-phenyl-para-phenylenediamine at 0.4%. CONCLUSIONS: The 12 allergens in the British series should continue being tested as a standard addition to the European series within the U.K. The collection of data in this manner to allow comparisons between centres shows differences that reflect selection criteria and interpretation of results, and offers a useful tool for audit and clinical governance. Testing fewer than 1 : 2150 population may indicate underprovision of service. Similarly, rates of sensitization for nickel contact allergy above 26% and for fragrance mix above 16% (the upper 95% confidence intervals) should stimulate inquiry into the reasons behind this.

Type-IV hypersensitivity to betamethasone valerate and clobetasol propionate: results of a multicentre study.

BACKGROUND: Most studies investigating steroid allergy have been performed with tixocortol pivalate, hydrocortisone butyrate and budesonide. Betnovate and Dermovate are widely prescribed in the U.K. but little is known about the frequency of sensitization to them. OBJECTIVES: To determine the optimum method to detect contact allergy to betamethasone valerate (BV) and clobetasol propionate (CP). METHODS: Seven centres tested consecutive patients attending for investigation of suspected allergic contact dermatitis to these steroids at a range of concentrations in different vehicles. RESULTS: Of 1562 patients tested, 16 (1%) reacted to either BV or CP. Ten patients (0.7%) reacted to BV and 13 (0.8%) to CP. Two patients of a further centre were included in analysis of dilutions and vehicles. Sixteen of a total of 25 reactions (64%) were identified with a 1% dilution in ethanol. CONCLUSIONS: Consideration should be given to adding BV and CP to a standard allergy series, given that both are frequently used in the treatment of eczema and that most patients sensitized to them are not identified with currently used markers of steroid allergy. If patch tests to BV and CP are initially negative, but an allergy is suspected, the patient should be further investigated. Further studies are required to identify the ideal patch test material.

Twice-daily vs. once-daily inpatient dithranol for psoriasis.

The aim of this study was to compare the efficacy and tolerability of twice-daily vs. once-daily regimes of dithranol (anthralin) in Lassar's paste. Over a 4-year period, 61 inpatients with stable plaque psoriasis gave informed consent and entered a randomized controlled trial, having twice or once-daily application of dithranol in Lassar's paste as part of otherwise standard Ingram's regime. Primary outcome measurements were time required in hospital, nursing time, changes in total body surface area affected by psoriasis and thickness of a target plaque and in some patients, an assessment of the recurrence of psoriasis. Doctors were blinded as to the regime being used. At entry, mean patient age, lesional surface area and target plaque thickness were comparable in both groups and no patient had received systemic therapy in the preceding 3 months. Forty-two patients completed the study, two (11%) in the twice-daily group withdrawing due to skin irritation or 'burning'. Mean lesional surface area and target plaque thickness were similar in both groups at hospital discharge. Mean (+/- SD) time spent in hospital was not significantly different in each group, being 13.3 (+/- 6.2) days and 13.9 (+/- 4.5) days for the twice-daily and once-daily groups, respectively (P = 0.36). Duration of hospitalization did not correlate with surface area or plaque thickness on admission. Mean (+/- SD) nursing time spent on treatment was significantly greater in the twice-daily group, at 0.82 (+/- 0.33) hours per day compared with 0.51(+/- 0.25) hours per day in the once-daily group. Relapse rate at 6 months was not different between the two groups.