Persistent severe amiodarone-induced photosensitivity.

Amiodarone, a benzofuran derivative, has been used therapeutically as an antiarrhythmic and coronary vasodilator in Europe since 1964. One of its commoner side effects is cutaneous photosensitivity; more rarely, after ingestion of the drug for around 12 months, a slate-grey or violaceous discoloration of sun-exposed sites may gradually develop. Both of these side effects usually resolve within 2 years of discontinuation of the drug. We now present a woman who developed both photosensitivity and a slate-grey discoloration whilst taking amiodarone; on discontinuation of the drug, the dyspigmentation gradually resolved, but the photosensitivity has persisted and the patient remains symptomatic more than 17 years later.

Audit of the use of psoralen photochemotherapy (PUVA) and narrowband UVB phototherapy in the treatment of psoriasis.

BACKGROUND: Psoralen photochemotherapy (PUVA), the combined use of psoralen and long wave ultraviolet (UVA) irradiation, was introduced around 1974 and its beneficial effects were rapidly confirmed worldwide. In an attempt to minimize its recognized long-term photocarcinogenic risk after some 150-200 exposures while also maintaining efficacy, however, the narrowband (311-312 nm) ultraviolet B (UVB) lamp (TL-01) was introduced in 1984, and has moved towards replacing PUVA except for severe or resistant disease. AIMS: To discover whether our use of these therapies complied with established British Photodermatology Group guidelines for PUVA and guidelines formulated within our unit for narrowband UVB. METHODS: The study was retrospective over 6 months from November 2001 to April 2002, all relevant information being obtained from the patients' hospital notes. RESULTS: Thirty-one patients received PUVA (18 oral, 11 bath and two uncertain because of missing notes) and 20 narrowband UVB during this period. CONCLUSIONS: Our PUVA and narrowband UVB phototherapy guidelines were shown to have been followed relatively closely with the following exceptions: one PUVA patient received a high cumulative exposure by mutual agreement because there was no other suitable therapy; a failure to measure minimal phototoxic doses (MPDs) in some PUVA patients; and slightly prolonged referral delays, but generally by patient choice.

Exacerbation of presumed chronic actinic dermatitis by cockpit visible light in an airline pilot with atopic eczema.

Chronic actinic dermatitis (CAD) is a persistent ultraviolet radiation- or visible light-induced eczema of predominantly the exposed areas of usually elderly people. We now present the case of a young pilot with atopic eczema who developed CAD, regularly exacerbated by exposure to visible light through his aircraft cockpit window.

A simple method to assess severity of polymorphic light eruption.

BACKGROUND: The severity of polymorphic light eruption (PLE) is highly variable. The results of studies of the prevalence, pathogenesis, provocation and treatment of PLE may be highly dependent on the severity of disease in the patients studied. OBJECTIVES: To produce a simple, valid and reproducible method to assess the severity of PLE. PATIENTS AND METHODS: Eighty patients were asked about the PLE they had experienced during the preceding 12 months, using a standardized interview comprising 16 questions. The answer to each question received a score. A PLE Severity Index (PLESI) was formulated, consisting of 10 questions, with a possible total score of 2-100. The internal consistency of the PLESI (the extent to which the responses to different questions correlated with each other) was assessed by reliability analysis, using Cronbach's method. Twenty patients were re-interviewed 7-27 days later to assess the repeatability of the PLESI. The ease of provocation of PLE by exposure at 24-h intervals to solar-simulated radiation was assessed on a five-point scale in nine of the 80 subjects (the EOPSSR score). RESULTS: The value of Cronbach's alpha for the PLESI was 0.77. The distribution of the PLESI was consistent with a normal distribution, with a mean value of 52.7 and standard deviation of 19.4. It had a coefficient of repeatability of 20.1. The PLESI was positively correlated with EOPSSR (rs =0.69, P = 0.039) and the number of years since onset of PLE (rs = 0.25, P = 0.03). There was no association between the PLESI and the duration of persistence of the eruption after ceasing sun exposure (rs = 0.12, P = 0.30), the development of tolerance as summer progressed (rs = -0.14, P = 0.39), gender (P = 0.50) or skin type (P = 0.87). CONCLUSIONS: This study has (i) validated the concept that a single score can reflect disease severity in PLE by showing that the principal characteristics of the condition, including, for example, the extent of anatomical distribution and the ease of provocation of the eruption, correlate with each other; (ii) formulated the PLESI, which is a simple, valid and reproducible way of assessing disease severity; we suggest it could be used worldwide to determine the severity of PLE among patients enrolled in future PLE research; (iii) shown that the ease with which the eruption is provoked by solar-simulated radiation correlates with the severity of the condition; and (iv) shown that the duration of persistence of the eruption after sun exposure does not correlate with the severity of the condition.

A comparison of six and 12 PUVA treatments in the prophylaxis of polymorphic light eruption.

Polymorphic light eruption (PLE) is a common condition for which the most effective treatment is prophylactic phototherapy. This is traditionally given in courses of approximately 12-15 exposures. We compared the effect of six and 12 treatments of psoralen-UVA (PUVA) therapy, in the prophylaxis of PLE, in a side-to-side within-patient comparison pilot study. In six out of eight patients, six treatments provided as much protection as 12 treatments. Five of these six patients had reported relatively mild disease in the previous year, in comparison to the other two patients. In view of the inconvenience and increased incidence of adverse effects associated with long treatment courses, we recommend the use of short courses, particularly in patients who are relatively mildly affected.

Erythrodermic chronic actinic dermatitis responding only to topical tacrolimus.

Chronic actinic dermatitis (CAD) is a disorder characterized by an often severe persistent eczematous eruption induced by exposure to ultraviolet radiation. Treatment involves photoprotective measures and topical corticosteroid therapy and in more severe cases, systemic immunosuppression. Occasionally, however, the condition can prove very resistant to all therapy and be severely disabling. We report a patient with CAD who resisted standard topical and systemic treatments, but responded to topical tacrolimus ointment 0.1% (Protopic).

X-ray crystallographic studies of protein-ligand interactions.

X-ray crystallography enables details of covalent and non-covalent interactions to be analysed quantitatively in three dimensions, thus providing the basis for the understanding of binding of ligands to proteins as well as modes of action such as cell-surface binding. This article is concerned with current methods employed for the X-ray analysis of protein structures complexed with ligands. It deals mainly with 'what can be done' in current research, rather than providing details of 'how to do it'. In recent years significant advances have been made in a variety of techniques: growing protein crystals from very small samples by scanning a wide range of conditions; X-ray intensity data collection and measurement through the use of charge-coupled devices and high-intensity, versatile synchrotron sources; cryo-crystallography which both stabilizes the crystals and provides improved data; methods for analysing and interpreting the structures, dependent, at least in part, on both structural and sequence databases; and improvements in hardware and software. To illustrate the type of results achievable two examples involving protein-sugar interactions are discussed: (i) SNAII (the lectin Sambucus nigra agglutinin-II from elder) N-terminal sugar-binding site where terminal sugar units in a glycosylation chain from a symmetry-related molecule bind and (ii) MLI (mistletoe lectin I) C-terminal sugar-binding site with lactose.

Vancomycin-induced linear IgA disease with autoantibodies to BP180 and LAD285.

Linear IgA disease (LAD) is an acquired autoimmune subepidermal bullous disease characterized by the linear deposition of IgA at the basement membrane zone. A minority of cases are induced by drugs, of which the most frequently implicated is vancomycin. The target antigens in idiopathic LAD are heterogeneous, but have not previously been reported in vancomycin-induced LAD. We report three cases, and in two of these we investigated the target antigens. In both we identified IgA antibodies to LAD285 and IgA and IgG antibodies (dual response) to BP180.

Early-onset hidradenitis suppurativa.

A 9-year-old girl developed hidradenitis suppurativa 3 months after the first signs of adrenarche. Such a close temporal relationship is consistent with the hypothesis that the disease is androgen dependent. Less than 2% of patients have onset of the disease before the age of 11 years. The exceptionally early age of onset in our patient may be partly explained by the fact that she had an early puberty.

X-ray and neutron structure of 1,8-(3,6,9-trioxaundecane-1,11-diyldioxy)-9,10-dihydro-10,10-dimethylanthracene-9-ol (P326); some pitfalls of automatic data collection.

The structure of the crown ether 1,8-(3,6,9-trioxaundecane-1,11-diyldioxy)-9,10-dihydro-10,10-dimethylanthracene-9-ol, C(24)H(30)O(6).H(2)O (1), code name P326, the parent compound for a series of derivatives, has been determined by both X-ray diffraction at room temperature and neutron diffraction at very low temperature. The unit cells are very similar at both temperatures and in both cases the crystals exhibit P2(1) symmetry with Z = 4 (two molecules, A and B, respectively, per asymmetric unit) and pseudosymmetry P2(1)/c. The higher symmetry is broken mainly by the two independent water molecules in the unit cell, some reflections which would be absent in P2(1)/c having strong intensities in both the X-ray and neutron data. In both molecules A and B hydrogen bonds involving the water molecule stabilize the macrocyclic ring structure, one involving the macrocyclic O(9) as a donor. Close contacts between the water and macrocyclic O atoms in each molecule also suggest the presence of two bifurcated hydrogen bonds, involving water HW2 to both O(16) and O(18), and water HW1 to both O(18) and O(20), respectively, with considerable variation in the geometry being present. Both molecules A and B exhibit very close pseudosymmetry across a plane perpendicular to the molecular plane and through atoms C(9) and O(18), and in addition are predominantly planar structures. The X-ray analysis failed to reveal one H atom per water molecule, each being subsequently included after location and refinement in the neutron analysis.

Homozygous variegate porphyria: a compound heterozygote with novel mutations in the protoporphyrinogen oxidase gene.

Homozygous variegate porphyria results from mutations in both alleles of the protoporphyrinogen oxidase (PPOX) gene. Our patient, a 36-year-old woman, has severe cutaneous manifestations. Her clinical and biochemical features are similar to the few other reported cases, including onset before 18 months of age, photosensitivity, absence of acute porphyric attacks, and elevated erythrocyte protoporphyrin. Mutation analysis of the PPOX gene revealed an in-frame 12 bp insert (c. 657-658 ins AAGGCCAGCGCC) encoding lysine-alanine-serine-alanine (KASA), and a G to A transition at the splice donor site of exon 11 (IVS 11-1 G-->A). Neither of these mutations has been reported previously. Our patient's mother has the splice site mutation and has had acute porphyric episodes. A maternal first cousin has the same mutation but no clinical manifestations. The medical and family history of our patient's father is uncertain.

The management of cutaneous leishmaniasis from Belize.

We report 20 patients who contracted cutaneous leishmaniasis in Central and South America, 18 of them in Belize. The diagnosis was confirmed by the polymerase chain reaction (PCR) in 79% of those tested; the corresponding figure for histology was 62%, touch smear 46%, and culture 11%. Results of PCR can be falsely positive, so treatment should not be based on PCR alone. Of the 20 cases 18 were healed 6 weeks after intravenous sodium stibogluconate 20 mg/kg per day for 20 days. We present a management protocol.

(24R)-24,25-Dihydroxycycloartan-3-one.

In the title compound, C(30)H(50)O(3), the three six-membered rings adopt chair, twist and twist-boat conformations. The five-membered ring is in a slightly distorted envelope conformation. The substituent on the five-membered ring is in an extended conformation, with its two hydroxyl O atoms forming an intramolecular hydrogen bond. One of these O atoms also forms an intermolecular hydrogen bond with the oxygen of the carbonyl group in a neighbouring molecule.

A double mesogen based on linked p-terphenyl units.

The structure of bis(4,4"-decyloxy-p-terphenyl-2'-ylmethyl) carbonate, C(79)H(110)O(7), (I), has been determined at 123 K. It is a new type of twin mesogen. No two adjacent aromatic rings are coplanar and the four decyloxy side chains are maximally extended. Molecules of the compound are packed along the crystallographic a axis. The molecular arrangement is a precursor of a smectic A phase.

Step-scan FTIR time-resolved spectroscopy study of excited-state dipole orientation in soluble metallopolymers.

Step-scan FTIR time-resolved spectroscopy (S2FTIR TRS) in acetonitrile-d3 has been used to probe the acceptor ligand in metal-to-ligand charge transfer (MLCT) excited states of amide-substituted polypyridyl complexes of RuII and in analogues appended to polystyrene. On the basis of ground-to-excited state shifts in v(C = O) of -31 cm-1 for the amide group in [RuII(bpy)2(bpyCONHEt')]2+ (bpyCONHEt' = 4'-methyl-2,2'-bipyridine-4-carboxamide-Et'; Et' = -CH2CH2BzCH2CH3) (1) and in the derivatized polystyrene abbreviated [PS-[CH2-CH2NHCObpy-RuII(bpy)2]20]40+ (3), the excited-state dipole is directed toward the amide-containing pyridyl group in the polymer side chain. Smaller shifts in v(C = O) of -17 cm-1 in [RuII(4,4'-(CONEt2)2bpy)2-(bpyCONHEt')]2+ (2) and in the derivatized polystyrene abbreviated [PS-[CH2CH2NHCObpy-RuII(4,4'-(CONEt2)2bpy)2]20]40+ (4) indicate that the excited-state dipole is directed toward one of the diamide bpy ligands. The nearly identical results for 1 and 3 and for 2 and 4 show that the molecular and electronic structures of the monomer excited states are largely retained in the polymer samples. These conclusions about dipole orientation in the polymers are potentially of importance in understanding intrastrand energy transfer dynamics. The excited-state dipole in 3 is oriented in the direction of the covalent link to the polymer backbone, and toward nearest neighbors. In 4, it is oriented away from the backbone.