The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI): grading disease severity and assessing responsiveness to clinical change in epidermolysis bullosa.

BACKGROUND: The lack of validated outcome measures for epidermolysis bullosa (EB) presents major barriers to evaluating disease severity and comparing the efficacy of therapies. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) was recently introduced as a valid and reliable instrument for EB; however, its interpretation for use in clinical practice and clinical trials is yet to be defined. OBJECTIVE: To assess the interpretability of the EBDASI in classifying patients according to disease severity and clinical response. METHODS: A total of 53 outpatients with EB at two interstate institutions were prospectively evaluated. At each visit, the principal dermatologist completed the EBDASI and global assessments of disease severity and change. Classifications for mild, moderate and severe disease using the EBDASI were determined using receiver operating characteristic curves. Minimal clinically important differences for the EBDASI activity subscale were calculated and compared with the standard error of measurement. RESULTS: Total EBDASI score ranges of 0-42, 43-106 and 107-506 corresponded to mild, moderate and severe disease respectively. Reduction in EBDASI activity scores of greater than 9 indicated clinically significant improvement. An increase of 3 in the activity score indicated deterioration. CONCLUSION: The EBDASI is a responsive tool and may be useful in characterizing disease severity and response. The cut-offs proposed in this study provide the first practical guide for interpreting the EBDASI, further supporting its use for longitudinal patient assessment and in clinical trials.

Clinical heterogeneity in recessive epidermolysis bullosa due to mutations in the keratin 14 gene, KRT14.

BACKGROUND: Epidermolysis bullosa simplex (EBS), the most common subtype of EB, is usually inherited as an autosomal dominant trait caused by mutations in either the keratin 5 (KRT5) or keratin 14 (KRT14) genes. Recessive EBS (R-EBS) is extremely rare. METHODS: We present the first Australian patient diagnosed with R-EBS, to our knowledge, and a comprehensive review of genotypes and phenotypes of R-EBS reported cases. RESULTS: The female proband, of Turkish descent with consanguineous parentage, was referred to us at the age of 8 years. Clinically, she had a severe phenotype including generalized blisters, mucosal involvement and EB naevi. Immunofluorescence mapping and electron microscopy were consistent with a diagnosis of EBS. Staining for Keratin 14 (K14) was negative. The basal layer, however, reacted with monoclonal antibodies to keratins 6 (K6) and 16 (K16). Mutation screening from genomic DNA showed that the proband was homozygous for the truncation mutation Y204X in exon 3 of KRT14, and both unaffected parents were heterozygous for a single KRT14 Y204X mutation. The phenotype of our patient is reported in more detail and with longer follow-up than those of others published in the literature. DISCUSSION: The proband's phenotype was severe as an infant but improved with age, suggesting that an alternative keratin is pairing with K5 in her skin to compensate for the loss of K14--a novel biological compensatory mechanism. It is interesting that K6 and K16 were expressed, as these are normally positive in hyperproliferative skin disorders.

Rashes in infants. Pitfalls and masquerades.

BACKGROUND: Physiological and pathological skin eruptions are extremely common in neonates and are often presented to the general practitioner as either a primary or incidental problem at consultation. OBJECTIVE: To discuss the presentation and treatment of common dermatological conditions presenting in the first six months of life. DISCUSSION: Common conditions such as pityrosporum folliculitis, neonatal acne, cradle cap, eczema and food allergy are discussed. The rarer conditions of zinc deficiency and neonatal lupus are described because they may pose significant potential medical consequences.

Comparison of moxifloxacin and cefuroxime axetil in the treatment of acute maxillary sinusitis. Sinusitis Infection Study Group.

The aim of this prospective, multicenter, randomized, double-masked clinical trial was to compare the efficacy and safety of moxifloxacin with those of cefuroxime axetil for the treatment of community-acquired acute sinusitis. Five hundred forty-two adult patients with symptoms and radiographic evidence of acute maxillary sinusitis received a 10-day oral regimen of either moxifloxacin (400 mg once daily) or cefuroxime axetil (250 mg twice daily). Acute signs and symptoms at presentation had lasted >7 days but <4 weeks. Clinical response at the end of therapy (7 to 14 days after treatment) was the primary efficacy variable. Four hundred fifty-seven of the patients (223 moxifloxacin, 234 cefuroxime axetil) were included in the clinical efficacy analysis. Moxifloxacin was found to be similar in effectiveness to cefuroxime axetil at the end-of-therapy visit (90% vs. 89%, respectively; 95% confidence interval, -5.1% to 6.2%). Clinical relapse at the follow-up visit was reported for only 8 patients (3 moxifloxacin, 5 cefuroxime axetil). No clinically significant differences were observed with respect to the number of patients experiencing a successful clinical response based on demographic or infection characteristics. Five of the 542 enrolled patients were lost to follow-up. Of the 537 patients in the intent-to-treat population, drug-related adverse events were reported in 37% of moxifloxacin-treated patients and in 26% of cefuroxime axetil-treated patients (P = 0.006). Adverse-event profiles were comparable in the 2 treatment groups, with the exception of nausea, which was reported by 11% of moxifloxacin-treated patients compared with 4% of cef uroxime axetil-treated patients (P = 0.003). In this study, moxifloxacin was as effective as cefuroxime axetil in the treatment of community-acquired acute sinusitis.

The subgaleal pulley suture.

The repair of scalp defects is often complicated by moderate tension on the wound edges. A subgaleal version of the 'pulley' suture, which may be helpful in closing wounds in this setting, is described.

Spitz naevi misdiagnosed histologically as melanoma: prevalence and clinical profile.

A Spitz naevus is a benign melanocytic tumour that may histologically resemble a malignant melanoma. Data was retrospectively gathered from patients who attended the Victorian Melanoma Service to determine the prevalence of Spitz naevi pathologically misdiagnosed as melanoma. Assessment of the clinical characteristics of these patients was also performed and compared to those with correctly diagnosed melanoma. It was found that 6.5% of all melanomas referred were in fact Spitz naevi and that Spitz naevi represented the majority of pathologically misdiagnosed melanomas. The Spitz naevi were more likely to be on the lower extremities and were no average, considerably smaller than the melanomas. Patients with Spitz naevi were more likely to be younger, female, have fewer dysplastic naevi and have brown eyes. One hundred per cent of the Spitz naevi were brought to the attention of the initial doctor by the patient compared to 72% of the melanomas. This study concludes that Spitz naevi that are pathologically misdiagnosed as melanomas retain the clinical characteristics of other Spitz naevi and that greater clinicopathological communication may reduce the frequency of diagnostic error.

Fixed drug eruption to tartrazine.

An 11-year-old girl with a recurrent fixed drug eruption to tartrazine on the dorsum of the left hand is presented. Oral provocation tests to both the suspected food, an artificially coloured cheese crisp, and to tartrazine were positive. This case highlights fire need to consider artificial flavours, colours and preservatives as potential culprits in classic drug eruptions.

The problem of generalizing to a language population: a "random" controversy.

The rationale behind the use of item statistics as well as objections to their use are reviewed. It is argued that investigators conducting language research with disordered populations should follow the example of those conducting language research with normal populations and consider calculating item statistics if they wish their results to generalize beyond the specific items tested.

A 31P-NMR study of mono- and dimagnesium complexes of adenosine 5'-triphosphate and model systems.

31P-NMR chemical shifts and spin-lattice relaxation times of ATP (adenosine 5'-triphosphate), ribose 5'-triphosphate and tripolyphosphate show closely similar behaviour in aqueous solution at pH 7.5 on titration with Mg2+. The results are interpreted in terms of formation of 1 : 1 and 2 : 1 (dimagnesium) complexes with Mg2+ bound exclusively to the triphosphate chain. Stability constants for these complexes are reported. It is suggested that the predominant form of the 1 : 1 complexes has Mg2+ bound in tridentate manner (via non-bridging oxygen) to the alpha, beta and gamma phosphorus atoms; whilst that of the 2 : 1 complexes has each Mg2+ bound in bidentate manner, one to the alpha and beta, and the other to the beta and gamma, phosphorus positions.

Nitrogenase of Klebsiella pneumoniae. Water proton NMR relaxation studies on the binding of divalent metal ions and nucleotides to the iron protein.

Interactions between the iron protein, Kp2, of nitrogenase manganese ions, magnesium ions, and the nucleotides ATP or ADP, have been studied in aqueous solution by monitoring the water proton NMR relaxation rate enhancement caused by Mn2+. Binding of Mn2+ to a molecule of Kp2 occurs at four sites, indistinguishable within experimental error, having a Kd = 350 +/- 50 micron. The Mn2+ - Kp2 complex has a low characteristic enhancement (epsilonb = 6 +/- 0.5). All four sites can alternatively bind Mg2+, not necessarily with the same dissociation constant, but with a mean Kd = 1.7 +/- 0.3 mM. Ternary complexes with the configuration EMS or (formula: see text) are formed between Kp2, Mn2+ and nucleotide (ATP or ADP). The ternary complexes with Mg2+ in place of Mn2+ probably have the latter configuration. A novel treatment of enhancement data (a 'high metal' approximation) is given.