Severity of polymorphic light eruption in pre- and post-menopausal women: a comparative study.

BACKGROUND: Polymorphic light eruption (PLE) is approximately four times more common in women than in men and often begins in young adult life. It is hypothesized that patients with PLE have an inherent resistance to UVL-induced immunosuppression, which is a physiological phenomenon in normal healthy individuals. Consequently, in PLE there is a delayed-type hypersensitivity reaction to a UVL-modified skin antigen, which results in an inflammatory reaction and a variable rash. The female hormone, 17ß-oestradiol, has been shown to inhibit UVL-induced physiological suppression of contact hypersensitivity responses. This has been postulated to account for the female preponderance of PLE. If 17ß-oestradiol plays a significant part in the disease, one might hypothesize that the severity of PLE might reduce in women after menopause. OBJECTIVES: To compare the severity of PLE in pre-menopausal women with that in post-menopausal women. METHODS: Eighteen pre-menopausal and 18 post-menopausal women with PLE had their Polymorphic Light Eruption Severity Index (PLESI) scored by a single investigator. RESULTS: Pre-menopausal women (mean age 40 years; range 25-50) had a mean PLESI of 54.8 (range 0-86, SD 20.2). Post-menopausal women (mean age 63 years; range 53-78) had a mean PLESI of 36.8 (range 0-74, SD 18.2). A significant difference in mean PLESI values between pre- and post-menopausal women was noted (18.0; 95% CI 4.9-31.0; P = 0.008). At the time of the study, three subjects in the pre-menopausal group and one subject in the post-menopausal group were on oestrogen preparations. Even after excluding the four patients on oral oestrogens, there remained a statistically significant difference in the mean PLESI scores between the pre-menopausal and post-menopausal groups (55.10 vs. 36.64; difference of 18.46, 95% CI: 4.0-32.91; P = 0.014). CONCLUSIONS: The severity of PLE was significantly less in post-menopausal women as compared with pre-menopausal women.

New mutation identified in two sisters with adult-onset erythropoietic protoporphyria.

BACKGROUND: Erythropoietic protoporphyria (EPP; OMIM #177000) is a rare disease that usually presents in infancy or early childhood. The uncommon adult-onset EPP is often associated with acquired somatic mutations of the FECH gene, secondary to blood dyscracias. METHODS: We investigated two sisters with adult-onset EPP. RESULTS: We found a novel germline mutation in the FECH gene, in trans with the common hypomorphic IVS3-48C allele. CONCLUSIONS: The adult presentation and identical genotypes of the two sisters suggests that the late development of the condition is to an extent a function of the mutation. The exact mechanism for this delayed penetrance is not clear, although these atypical cases raise the possibility of other genetic or nongenetic disease-modifying factors.

Autosomal dominant chronic mucocutaneous candidiasis and primary hypothyroidism complicated by oesophageal carcinoma.

We describe three generations of a white family with autosomal dominant chronic mucocutaneous candidiasis (CMCC) and primary hypothyroidism, which was complicated by squamous cell carcinoma (SCC) of the oesophagus in the index case. We report this family to increase awareness of this rare autosomal dominant variant of CMCC endocrinopathy syndrome associated with primary hypothyroidism without evidence of autoimmune endocrinopathy, and to highlight the risk of developing oesophageal SCC at a young age as a fatal complication of CMCC.

Candidaemia in a large teaching hospital: a clinical audit.

BACKGROUND: Candidaemias are associated with significant morbidity and mortality. The British Society of Medical Mycology and Infectious Diseases Society of America recently published audit standards, to address the changing epidemiology of candidaemia and to improve outcomes. AIM: To investigate the local epidemiology of candidaemia and the standard of care in a large teaching hospital. DESIGN: Retrospective audit. METHODS: Data were obtained for all candidaemia episodes over the 4-year period ending July 2004, from the medical and nursing notes, laboratory computer and patient administration system. RESULTS: We identified 92 episodes in 90 patients. The main predisposing factors were being on an intensive care unit, having a central venous catheter, and (for neonates) prematurity. Central venous catheters were removed at a mean 1.8 days following candidaemia; 79% (37/47) were removed within 48 h (the audit standard). Identification and susceptibility tests were performed for 94.7% of isolates. All were susceptible to amphotericin B; 87% were susceptible to fluconazole. Antifungal treatment was started within 24 h of a positive blood culture in 84% of episodes. Initial antifungal therapy was appropriate in 95% (61/64) of treated cases. Most patients (81%) who survived or completed their intended course of treatment before death received at least 2 weeks treatment. However, only 45% of those transferred to other hospitals had accompanying guidance on the intended further duration of therapy. Thirty-day mortality was 41%. After adjustment for age, the presence of Candida-related complications was associated with an odds ratio for mortality of 6.5 (95% CI 1.2-36.5, p = 0.03). DISCUSSION: Overall the audit standards set by the BSMM and IDSA were met, and discrepancies did not lead to a change in outcome. Improved intravenous catheter care, a more pro-active approach to searching for complications, and improvement in the inter-hospital transfer process, will assist in reducing morbidity and mortality.

Vanadyl-induced Fenton-like reaction in RNA. An ESR and spin trapping study.

Vanadyl (VO2+) complexed to RNA reacts with hydrogen peroxide in a Fenton-like manner producing hydroxyl radicals (.OH). The hydroxyl radicals can be spin trapped with 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) forming the DMPO-OH spin adduct. In addition, in the presence of ethanol the formation of the hydroxyethyl radical adduct of DMPO (DMPO-ETOH) confirms the production of hydroxyl radicals by the RNA/VO2+ complex. When the reaction between the RNA/VO2+ complex and H2O2 is carried out in the presence of the spin trap 2-methyl-2-nitrosopropane (MNP), radicals produced in the reaction of .OH with RNA are trapped. Base hydrolysis of the MNP-RNA adducts (pH 12) followed by a reduction in the pH to pH 7 after hydrolysis is complete, yields an MNP adduct with a well-resolved ESR spectrum identical to the ESR spectrum obtained from analogous experiments with poly U. The ESR spectrum consists of a triplet of sextets (aN = 1.48 mT, a beta N = 0.25 mT and a beta H = 0.14 mT), indicating that the unpaired nitroxide electron interacts with the nuclei of a beta-nitrogen and beta-hydrogen. The results suggest that the .OH generated in the RNA/VO2+ reaction with H2O2 add to the C(5) carbon of uracil forming a C(6) carbon centered radical. This radical is subsequently spin trapped by MNP.

ESR study of electron transfer reactions between gamma-irradiated pyrimidines, adriamycin and oxygen.

Solid pyrimidine nucleic acid bases (cytosine, thymine, and uracil) were gamma-irradiated (50 KGy) and dissolved in deaerated solutions of adriamycin in water and dimethylsulfoxide (DMSO). Analogous experiments using unirradiated pyrimidines as controls were also performed. In water only gamma-irradiated cytosine showed a reaction with the adriamycin yielding a single ESR peak (g = 2.0033) consistent with the adriamycin semiquinone radical. Since the unirradiated cytosine gave no reaction, the result suggests an electron transfer from cytosine radicals (generated by gamma-radiolysis) to adriamycin. In DMSO the three gamma-irradiated and unirradiated pyrimidines reacted with adriamycin yielding the adriamycin semiquinone radical observed by ESR. These results suggest that in DMSO an electron is transferred to adriamycin from the pyrimidine radicals and from the parent pyrimidine molecules. However, the process is on the order of 10(5) times more efficient for the pyrimidine radicals. Superoxide radicals (O2-.) were formed following addition of oxygen to the deaerated DMSO solutions containing adriamycin semiquinone radicals. O2-. was spin trapped using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The results show a possible reaction sequence in which an electron transferred to adriamycin, by pyrimidine radicals and parent pyrimidine molecules, is subsequently transferred to dissolved oxygen.

Photogeneration of superoxide by adriamycin and daunomycin. An electron spin resonance and spin trapping study.

The hydroxyl and superoxide anion spin adducts of DMPO and 4-MePyBN, respectively, were obtained during photoirradiation of adriamycin and daunomycin solutions with visible light. Ethanol and dimethyl sulfoxide did not scavenge hydroxyl radicals in the photoirradiated drug solutions. Furthermore, the hydroxyl-DMPO spin adduct is not formed in the photolysis of air-free drug solutions, indicating that hydroxyl radicals are not directly produced in the photochemical reactions. Instead, the observed hydroxyl-DMPO is formed from the decay of the superoxide anion-DMPO spin adduct. The mechanism for generating the superoxide anion radical appears to be a direct electron transfer from the photoexcited adriamycin and daunomycin to dissolved oxygen.

Reaction of disodium cromoglycate with hydrated electrons.

A possible mechanism by which disodium cromoglycate (DSCG) prevents a decrease in regional cerebral blood flow but not hypotension in primates following whole body gamma-irradiation was studied. Several studies have implicated superoxide radicals (O2-.) in intestinal and cerebral vascular disorders following ischemia and ionizing radiation, respectively. O2-. is formed during radiolysis in the reaction between hydrated electrons (e-aq) and dissolved oxygen. For this reason, the efficiency of DSCG to scavenge e-q and possibly prevent the formation of O2-. was studied. Hydrated electrons were produced by photolysis of potassium ferrocyanide solutions. The rate constant, k = 2.92 x 10(10) M-1s-1 for the reaction between e-aq and DSCG was determined in competition experiments using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). This spin trap reacts rapidly with e-aq followed by protonation to yield the ESR observable DMPO-H spin adduct. The results show that DSCG is an efficient e-aq scavenger and may effectively compete with oxygen for e-aq preventing the radiolytic formation of O2-..