Pimecrolimus and narrowband UVB as monotherapy or combination therapy in children and adolescents with atopic dermatitis.
(33/159)
Topical pimecrolimus and narrowband ultraviolet B (UVB) are both known to be effective in treating atopic dermatitis. We compared the clinical efficacy of monotherapy with either twice daily topical 1% pimecrolimus cream or twice weekly narrowband UVB, and combination therapy in 26 children and adolescents with moderate to severe atopic dermatitis in a half-side manner for 6 weeks. Twenty-four patients completed the study. Monotherapy and combination therapy notably reduced the scores of the Eczema Area and Severity Index ( p = 0.002) and the severity of pruritus ( p < or = 0.004). There was no significant difference in therapeutic efficacy among the treatment regimens at week 6. In conclusion, because of the lack of short-term additive therapeutic efficacy, concomitant use of pimecrolimus and narrowband UVB is inadvisable in treating moderate to severe atopic dermatitis in children and adolescents. (+info)
Photoadaptation during narrowband ultraviolet-B therapy is independent of skin type: a study of 352 patients.
(34/159)
Understanding how photoadaptation differs between individuals is important when considering susceptibility to the beneficial and harmful effects of sunlight exposure and when determining optimal phototherapy regimens. Most narrowband UVB (NB-UVB) regimens start with 70% of the minimal erythema dose (MED) with 20% increments at each treatment thereafter. We retrospectively studied 352 skin types I-IV psoriatic patients having twice weekly treatment with this regimen. Patients with high skin types tended to have high MEDs (P<0.001). By session 20 the proportion of patients who had developed erythema was approximately 60% regardless of MED. Among patients who developed erythema, the number of treatments before erythema occurred did not differ between skin types (P=0.33). We conclude that patients with high skin types photoadapt approximately equally per physical unit of UVR in comparison to those with low skin types, but they have greater photoadaptation in absolute terms because they are able to tolerate a higher initial dose of radiation. Differences in skin type or MED are not associated with clinically important differences in tendency to erythema during a standard 70/20% NB-UVB twice-weekly regimen. This regimen is suitable for all skin types I-IV patients regardless of skin type or MED. (+info)
UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study.
(35/159)
BACKGROUND: Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). METHODS: We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. DISCUSSION: In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB phototherapy. TRIAL REGISTRATION: Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT00150930. (+info)
Viral gene expression during the establishment of human cytomegalovirus latent infection in myeloid progenitor cells.
(36/159)
Human cytomegalovirus (HCMV) establishes and maintains a latent infection in myeloid cells and can reactivate to cause serious disease in allograft recipients. To better understand the molecular events associated with the establishment of latency, we tracked the virus following infection of primary human myeloid progenitor cells at days 1, 2, 3, 5, and 11. At all time points, the viral genome was maintained in most cells at approximately 10 copies. Infectious virus was not detected, but virus could be reactivated by extended fibroblast coculture. In contrast to wild-type HCMV, the viral genome was rapidly lost from myeloid progenitors infected with ultraviolet (UV)-inactivated virus, suggesting viral gene expression was required for efficient establishment of latency. To identify viral genes associated with the establishment phase, RNA from each time point was interrogated using custom-made HCMV gene microarrays. Using this approach, we detected expression of viral RNAs at all time points. The pattern of expression differed from that which occurs during productive infection, and decreased over time. This study provides evidence that a molecular pathway into latency is associated with expression of a unique subset of viral transcripts. Viral genes expressed during the establishment phase may serve as targets for therapies to interrupt this process. (+info)
Epidemic influenza and vitamin D.
(37/159)
In 1981, R. Edgar Hope-Simpson proposed that a 'seasonal stimulus' intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggers robust seasonal vitamin D production in the skin; vitamin D deficiency is common in the winter, and activated vitamin D, 1,25(OH)2D, a steroid hormone, has profound effects on human immunity. 1,25(OH)2D acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the 'oxidative burst' potential of macrophages. Perhaps most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection. Volunteers inoculated with live attenuated influenza virus are more likely to develop fever and serological evidence of an immune response in the winter. Vitamin D deficiency predisposes children to respiratory infections. Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An interventional study showed that vitamin D reduces the incidence of respiratory infections in children. We conclude that vitamin D, or lack of it, may be Hope-Simpson's 'seasonal stimulus'. (+info)
Photoadaptation: a path toward rational phototherapy protocols.
(38/159)
Photoadaptation is defined as the diminished future response to equivalent doses of irradiation. It is most often estimated in vivo by looking at changes in the minimal erythema dose with subsequent doses of UV radiation. Although photoadaptation's mechanism of action is poorly understood, Palmer et al. help clarify the clinical significance of photoadaptation for the dosimetry of UV-based phototherapy. (+info)
Critical role for mitochondrial oxidative phosphorylation in the activation of tumor suppressors Bax and Bak.
(39/159)
BACKGROUND: Activation of Bax and Bak, which act to permeabilize the mitochondrial membrane, is an essential step in the cell death response and therefore in the suppression of tumorigenesis. However, the mechanisms that regulate activation are poorly understood. METHODS: Bax and Bak activation (conformational change and dimerization) was monitored in Rat-1 fibroblasts and human cancer cells subjected to endoplasmic reticulum (ER) stress, DNA damage, or tumor necrosis factor-alpha (TNF-alpha) treatment. Pharmacologic inhibitors of reactive oxygen species production, electron transport in the respiratory chain, oxidative phosphorylation, and appropriate controls were used to identify potential modes by which Bax and Bak activation and the cell death response are controlled. The oligomerization state of Bax and Bak was determined by cross-linking and subsequent immunoblot analysis; Bax conformational change was analyzed by immunoprecipitation and immunoblotting with an antibody specific for the active conformation. Cell death was evaluated by dye exclusion. RESULTS: In both fibroblasts and human cancer cells subjected to cell death stimuli, inhibition of oxidative phosphorylation by use of antimycin A or oligomycin prevented ER stress-, DNA damage-, and TNF-alpha-induced Bax and Bak activation and cell death (UV-induced Rat-1 cell death at 15 hours: control, mean = 33.6%, 95% confidence interval [CI] = 18.8% to 48.4%; antimycin A, mean = 10.0%, 95% CI = 0% to 21.7%; oligomycin, mean = 13.1%, 95% CI = 5.7% to 20.5%; tunicamycin-induced MCF-7 cell death at 9 hours: control, mean = 29.2%, 95% CI = 21.6% to 36.8%; antimycin A, mean = 15.3%, 95% CI = 0.8% to 29.8%; oligomycin, mean = 11.5%, 95% CI = 3.9% to 19.1%; TNF-alpha-induced MCF-7 cell death at 6 hours: control, mean = 24.0%, 95% CI = 12.6% to 35.4%; antimycin A, mean = 8.9%, 95% CI = 3.9% to 13.9%; oligomycin, mean = 13.3%, 95% CI = 10.4% to 16.2%). Increasing and decreasing glycolytic adenosine triphosphate production, by adding glucose and 2-deoxy-D-glucose to the cell growth medium, respectively, neither reversed nor recapitulated, respectively, the effect of compromised oxidative phosphorylation on Bax and Bak activation. CONCLUSION: Oxidative phosphorylation is required for the activation of Bax and Bak and cell death triggered by disparate death stimuli. The reliance of tumor cells on glycolysis in preference to oxidative phosphorylation even under normoxic conditions (Warburg effect) may therefore be a potential means by which these cells evade programmed cell death. (+info)
Condom leukoderma.
(40/159)
Contact dermatitis from natural latex of condom has been reported and is attributed to latex sensitivity. Chemical leukoderma from rubber condom is probably not reported. Here we present a case of chemical leukoderma in a 32-year-old male who developed depigmentation around the shaft of the penis in a circumferential pattern. Since the lesion was solitary and the site corresponded to the point of maximum contact of the condom, a diagnosis of contact leukoderma due to latex condom was thought of. Patch testing was done with mercaptobenzothiazole (MBT), dusting powder present in the condom and condom latex as such. The patient tested positive (3+) with mercaptobenzothiazole and the condom latex. On discontinuation of condom use and with UVB phototherapy, lesions repigmented in eight weeks. (+info)