Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank.

Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.

Prevention of malignant melanoma.

The results of Primary Prevention programs, aiming at the decrease of melanoma incidence, were less encouraging than those of Secondary prevention which aims at an early diagnosis of malignant melanoma. Australia was the country with the best results obtained in both Prevention strategies, especially in avoiding intense, though intermittent, UV exposure. The success of these programs encouraged health authorities to initiate their application to other disorders. New sunscreens containing substances correcting the UV-damaged DNA may offer a promising result in the decades to come. However, so far no one epidemiological study has proved the prevention of malignant melanoma with the use of sun protecting agents. A meta-analysis verified the connection between melanoma and solarium use. The protective role of vitamin D in the development of prostate, breast and colon cancer was shown in a meta-analysis. The authors, however, suggest that fair-skinned persons should take oral supplementation of vitamin D, instead of exposing themselves to the sun. The Hellenic Society of Dermatology and Venereology published the results of 5-year-prevention programs in Greece. Their favorable results in the early diagnosis of melanoma justify an intense continuation of these efforts.

Intermittent vs. continuous 1-year cyclosporin use in chronic plaque psoriasis.

OBJECTIVE: To comparatively assess the impact of intermittent and continuous cyclosporine (CyA) administration in chronic plaque psoriasis. METHODS: A two-step procedure was followed for the 51 patients who were randomly assigned in the study. CyA in doses 2.5 mg kg(-1) day(-1) escalated up to 5 mg kg(-1) day(-1) for efficacy reasons, were given to all patients during the initial 12-week step. Only patients who achieved a minimum 50% reduction of baseline PASI could enter the 2nd step, which lasted for nine additional months. Subjects on the intermittent schedule stopped all therapy to receive other 12-week course(s) if and when they relapsed. Patients on the continuous schedule continued CyA therapy at the lowest, individualized, effective dose. RESULTS: 78% of all patients achieved a PASI-75, with subjects on continuous treatment manifesting greater improvement (92% vs 62%, P= 0.008). The decrease of DLQI was 89%, without any difference between the two schedules (P= 0.214). The median effective and maintenance doses were 3 (2.5-3.8) and 1.8 (0.7-3) mg kg(-1) day(-1), respectively for intermittent and continuous schedules. A significant correlation was observed between the clinical parameters and DLQI change at 1 year, for both groups of patients. Dose modifications for safety reasons were necessary in 5 patients, but no treatment discontinuation was required. Patients on the continuous regimen received 139% of the mean cumulative annual CyA dose of Intermittent therapy. CONCLUSION: The significantly higher annual cumulative dose required for the continuous CyA regimen compared to intermittent, leads to the suggestion that the first modality may offer higher physical improvement but must remain an option for those patients who do not respond or are uncooperative with intermittent CyA use.

Plasmapheresis in toxic epidermal necrolysis.

BACKGROUND: The treatment of toxic epidermal necrolysis (TEN) is usually based on the removal of the offending drug(s), fluid replacement, nutritional support, and local management. The mortality and morbidity, however, remain high and the death rate may be reduced to 10% only in special centers that use biologic dressings. Plasma exchange (PE) was proven efficacious in small series of patients and of no particular value in others. METHODS: Seven patients suffering from severe TEN covering 30%-80% of body surface area and having two or four mucous membranes involved, were included in this open study. Malignancy (Hodgkin's disease, brain tumor) and a variety of medicaments (carbamazepine, allopurinol, diphenylhydantoin, cefaclor, amoxicyllin with clavullanic acid) were considered as causally implicated. One to four PEs of 2.5 L were given on alternate days in six patients and on a daily basis in the seventh. RESULTS: All patients recovered successfully from their disease. No new lesions appeared after the first PE in four patients. Neither adverse reactions from this therapy nor sequelae from TEN were observed after a long follow-up lasting up to 8 years. CONCLUSIONS: Although PE is expensive and requires easy venous access to be performed, it could be listed in the first line of TEN therapy. The method is safe and efficacious, providing prompt relief from pain and rapid cessation of necrolysis. The alternate day PEs are considered preferable to the everyday regimen.