Quality of life in epidermolysis bullosa.

The quality of life of people with epidermolysis bullosa (EB) living in Scotland was assessed by postal questionnaire using the Dermatology Life Quality Index (DLQI) and the Children's Dermatology Life Quality Index (CDLQI). There were 143 people with EB simplex (EBS) and 99 individuals with non-Hallopeau--Siemens subtypes of dystrophic EB (DEB). A further six individuals had the severe Hallopeau--Siemens subtype of DEB (RDEB-HS). The overall response was 48% (EBS 52%, DEB 40% and RDEB-HS 83%). Impairment of quality of life (QOL) was greatest in those with RDEB-HS, mean scores (adults, 18; children, 22) exceeding those of any skin disorder previously assessed. The effect on QOL of EBS and other subtypes of DEB was similar to that of moderately severe psoriasis and eczema. EBS had a greater impact on QOL than the non-Hallopeau--Siemens subtypes of DEB (EBS adults mean score, 10.7; EBS children mean score, 15; DEB adults mean score, 7.5; DEB children mean score, 11.5).

The clinical spectrum of dystrophic epidermolysis bullosa.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a genodermatosis resulting from mutations in COL7A1, the gene encoding type VII collagen. The site and specific nature of the underlying mutation determine the clinical phenotype, which ranges widely from a severe mutilating condition to a relatively mild disorder. OBJECTIVES: To document the clinical spectrum of DEB within a defined complete population. METHODS: Since 1992, when compilation of the U.K. epidermolysis bullosa register began, an exhaustive search for DEB sufferers within the Scottish population has been undertaken and their clinical features comprehensively recorded. RESULTS: One hundred and twenty-eight DEB sufferers have been identified within the Scottish population. In descending order, the frequencies of the different forms of DEB were dominant DEB (DDEB) in 88 individuals (68%), DEB of uncertain inheritance in 24 (19%) and recessive DEB (RDEB) in 16 patients (13%). Within this latter group, nine (7%) had the mutilating Hallopeau-Siemens subtype (RDEB-HS), five (4%) had localized (RDEB-loc) and two (2%) had a predominantly flexural (inverse) form of RDEB. During the study, two patients with RDEB died from squamous cell carcinomas (SCCs), one originating in the skin and the second arising in the oesophagus. Gastrointestinal problems such as dysphagia, constipation and anal fissures, and restriction of mouth opening were experienced by the majority of patients with RDEB and by a significant minority of DDEB sufferers. Pseudosyndactyly was most severe in RDEB-HS, all those over 9 years of age having mitten deformities of the hands. Milder pseudosyndactyly or flexion contractures of the fingers were present in younger patients with this subtype, in most adults suffering from other subtypes of RDEB and in 6% of those with DDEB. External ear involvement, a feature not often reported in DEB, was common in RDEB and also occurred in a minority of those with DDEB. Pruriginous lesions and albopapuloid lesions were each present in both DDEB and RDEB. CONCLUSIONS: Most patients with DEB have relatively mild dominantly inherited disease, only a minority suffering from severe recessive subtypes. Scarring, gastrointestinal involvement, albopapuloid lesions and a pruriginosa-like pattern each occur in both DDEB and RDEB. With increasing age, SCC is a major cause of morbidity and mortality.

Dynamos in asymptotic-giant-branch stars as the origin of magnetic fields shaping planetary nebulae.

Planetary nebulae are thought to be formed when a slow wind from the progenitor giant star is overtaken by a subsequent fast wind generated as the star enters its white dwarf stage. A shock forms near the boundary between the winds, creating the relatively dense shell characteristic of a planetary nebula. A spherically symmetric wind will produce a spherically symmetric shell, yet over half of known planetary nebulae are not spherical; rather, they are elliptical or bipolar in shape. A magnetic field could launch and collimate a bipolar outflow, but the origin of such a field has hitherto been unclear, and some previous work has even suggested that a field could not be generated. Here we show that an asymptotic-giant-branch (AGB) star can indeed generate a strong magnetic field, having as its origin a dynamo at the interface between the rapidly rotating core and the more slowly rotating envelope of the star. The fields are strong enough to shape the bipolar outflows that produce the observed bipolar planetary nebulae. Magnetic braking of the stellar core during this process may also explain the puzzlingly slow rotation of most white dwarf stars.

Laryngeal involvement in the Dowling-Meara variant of epidermolysis bullosa simplex with keratin mutations of severely disruptive potential.

The clinical features of the Dowling-Meara variant of epidermolysis bullosa simplex (EBS-DM) can, in an infant, be indistinguishable from other severe forms of epidermolysis bullosa (EB). Two unrelated infants with no family history of skin disease are described who, within hours of birth, developed extensive blistering of skin and oral mucosae and who both subsequently developed hoarse cries. Despite this superficial resemblance to other forms of EB, electron microscopy revealed a basal cell rupture and keratin aggregates characteristic of EBS-DM in the skin of both infants and in the vocal cord epithelium of one. Molecular analysis confirmed the diagnosis by identification of mis-sense point mutations in basal cell keratin genes in both cases. One patient carries a point mutation in keratin 14 (converting arginine at position 125 to histidine) and the other has a novel point mutation in keratin 5 (converting serine at position 181 to proline). Hoarseness is not a well documented feature of EBS-DM and is usually associated with junctional EB. These two patients demonstrate that the presence of a hoarse cry in an infant affected by severe EB does not necessarily indicate a poor prognosis.

The clinical spectrum of epidermolysis bullosa simplex.

As part of the U.K. National Epidermolysis Bullosa Register, we have systematically recorded clinical information on 130 (77%) of the 168 known Scottish epidermolysis bullosa simplex (EBS) sufferers. Three subtypes of EBS were recognized: Dowling-Meara (EBS-DM), Weber-Cockayne (EBS-WC) and Köbner (EBS-Kb), seen in 5%, 42% and 53% of patients, respectively. As there is considerable overlap between EBS-WC and EBS-Kb, with both phenotypes frequently seen within the same pedigree, EBS-WC is best regarded as a milder variant of EBS-Kb rather than a separate disorder. Improvement with age is common in all variants of EBS, but is not invariable. Pain due to acral blistering in EBS-Kb/EBS-WC has a more marked impact on life-style than the blisters of EBS-DM. Oral blistering, nail involvement and aplasia cutis congenita occur in all EBS subtypes and laryngeal involvement is a feature of EBS-DM. Seasonal variation is not seen in EBS-DM but is common in EBS-Kb/EBS-WC.

Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in the integrin beta4 gene (ITGB4) in two unrelated patients with mild disease.

Junctional epidermolysis bullosa associated with pyloric atresia (EB-PA; OMIM 226730) is a rare autosomal recessively inherited disease in which mucocutaneous fragility is associated with gastrointestinal atresia. This disease is usually fatal within the first few weeks or months of life even following surgical correction of the intestinal obstruction. Recently, mutations in the genes encoding the epithelial integrin alpha6beta4 (ITGA6 and ITGB4) have been identified in several patients with EB-PA. We report two unrelated patients with this disease who have survived into early childhood with mild cutaneous involvement, in whom we have identified pathogenetic mutations in ITGB4. The first patient was a compound heterozygote for a splice site mutation in exon 30 (3793 + 1G-to-A) and a non-sense mutation in exon 36 (W1478X), and the second was a compound heterozygote for a missense mutation in exon 3 (C38R) and a 1 bp deletion in exon 36 (4776delG). Although the non-sense and deletion mutations are predicted to result in markedly reduced beta4 integrin mRNA levels, the presence of the missense or splice site mutation on the second allele may enable the synthesis of some functional, albeit perturbed, beta4 polypeptide. Determination of the molecular mechanisms in these two cases increases our understanding of EB-PA and may enable correlation between genotype and phenotype.

The prevalence of epidermolysis bullosa in Scotland.

The prevalence of epidermolysis bullosa (EB) in Britain and most other countries is unknown. Patients suffering from the inherited forms of EB and living in Scotland have been traced. Two hundred and fifty-nine affected people from 76 families have been identified, of whom 211 were clinically assessed. One-third of these Scottish EB sufferers had never been seen by a dermatologist. In Lothian, where there appears to be a relatively high prevalence of EB, 75% of patients were unknown to their general practitioners. The point prevalence of all forms of EB at the outset of the study was 49.0 per million, comprising EB simplex 28.6 per million and dystrophic EB 20.4 per million. Extrapolation of accurate data available for the Lothians suggests that the point prevalence of all forms of EB in Scotland is in excess of these figures.

Lipoatrophy with human insulin.

We describe a case of lipoatrophy that was secondary to human insulin. The patient had only ever been treated with human insulin, and the lipoatrophy appeared to partially resolve with continued use of the same insulin preparations. Possible underlying pathogenic mechanisms are discussed.

Dense astrophysical plasmas.

Degenerate bodies composed primarily of dense hydrogen and helium plasmas range from giant planets to the so far hypothetical brown dwarfs. More massive objects begin their lives as nondegenerate stars and may end as white dwarfs, composed primarily of carbon and oxygen, or as neutron stars, with solid crusts of iron or heavier elements and cores of neutron matter. The physical properties of dense plasmas that are necessary to construct theoretical models of such degenerate stars include the equation of state, transport properties, and nuclear reaction rates.

Binary Pulsar PSR 1913 + 16: Model for Its Origin.

The existing observational data for the binary pulsar PSR 1913 + 16 are sufficient to give a rather well-defined model for the system. On the basis of evolutionary considerations, the pulsar must be a neutron star near the upper mass limit of 1.2 solar masses (M.). The orbital inclination is probably high, i>/= 700, and the mass of the unseen companion probably lies close to the upper limit of the range 0.25 M. to 1.0 M.. The secondary cannot be a main sequence star and is probably a degenerate helium dwarf. At the 5.6-kiloparsec distance indicated by the dispersion measure, the magnetic dipole model gives an age of approximately 4 x 104 years, a rate of change of the pulsar period of P approximately 2 nanoseconds per day, and a surface magnetic field strength approximately (1/3) that of the Crab pulsar. The pulsar is fainter than an apparent magnitude V approximately + 26.5 and is at least approximately 80 times fainter than the Crab pulsar in the x-ray band. The companion star should be fainter than V approximately + 30, and a radio supernova remnant may be detectable near the position of the pulsar at a flux level of