Current state of vitiligo therapy – evidence-based analysis of the literature

Vitiligo is a skin disease with a worldwide prevalence ranging from 0.5% to 4%. Conservative therapies include photochemotherapy, phototherapy with UVB radiation (broadband UVB 290–320 nm, narrow band UVB 311 nm), systemic steroids and pseudocatalase. Modern therapeutic options include treatment with topical immunomodulators (tacrolimus, pimecrolimus), analogues of vitamin D3, excimer laser and surgery/transplantation. Our analysis compares these therapies for vitiligo and the evidence levels supporting their effectiveness. Conclusions: The face and neck respond best to all therapeutic approaches, while the acral areas are least responsive. For generalized vitiligo, phototherapy with UVB radiation is most effective with the fewest side effects; PUVA is the second best choice.Topical corticosteroids are the preferred drugs for localized vitiligo. They may be replaced by topical immunomodulators which display comparable effectiveness and fewer side effects.The effectiveness of vitamin D analogues is controversial with limited data. Surgical therapy can be very successful, but requires an experienced surgeon and is very demanding of time and facilities, thus limiting its widespread use. L-phenylalanine therapy appears effective on the face but enjoys neither widespread use nor extensive data support. No single therapy for vitiligo can be regarded as the most effective as the success of each treatment modality depends on the type and location of vitiligo.     

锁骨上神经营养血管皮瓣的应用解剖

目的为临床应用锁骨上神经营养血管皮瓣提供解剖学依据。方法在36侧经股动脉插管灌注红色乳胶溶液的成人尸体标本上,对锁骨上神经营养血管的横径、长度及穿深筋膜点的位置,进行了观测,并在标本上模拟手术设计。结果锁骨上神经营养血管包括颈升动脉肌皮支、颈横动脉颈段皮支、胸廓内动脉穿支、胸肩峰动脉胸肌支与肩峰支皮动脉,其穿深筋膜点外径分别为0.75、1.12、1.36、0.70、0.79mm;且穿深筋膜点位置相对恒定,节段性地分布于锁骨上神经,为整段皮神经提供营养。结论以上述节段动脉为蒂,设计锁骨上神经营养血管皮瓣。     

Impact of Increasing Margin Around the Lumpectomy Cavity to Define the Planning Target Volume for 3D Conformal External Beam Accelerated Partial Breast Irradiation

The purpose of this study was to evaluate the dose to normal tissues as a function of increasing margins around the lumpectomy cavity in accelerated partial breast irradiation (APBI) using 3D-conformal radiotherapy (3DCRT). Eight patients with Stage 0-I breast cancer underwent treatment planning for 3DCRT APBI. The clinical target volume (CTV) was defined as a 15-mm expansion around the cavity limited by the chest wall and skin. Three planning target volumes (PTV1, PTV2, PTV3) were generated for each patient using a 0, 5-, and 10-mm expansion around the CTV, for a total margin of 15, 20, and 25 mm. Three treatment plans were generated for every patient using the 3 PTVs, and dose-volume analysis was performed for each plan. For each 5-mm increase in margin, the mean PTV:total breast volume ratio increased 10% and the relative increase in the mean ipsilateral breast dose was 15%. The mean volume of ipsilateral breast tissue receiving 75%, 50%, and 25% of the prescribed dose increased 6% to 7% for every 5 mm increase in PTV margin. Compared to lesions located in the upper outer quadrant, plans for medially located tumors revealed higher mean ipsilateral breast doses and 20% to 22% more ipsilateral breast tissue encompassed by the 25% IDL. The use of 3DCRT for APBI delivers higher doses to normal breast tissue as the PTV increases around the lumpectomy cavity. Efforts should be made to minimize the overall PTV when this technique is used. Ongoing studies will be necessary to determine the clinical relevance of these findings.     

Does the Farnsworth D15 test predict the ability to name colours?

Background: The Farnsworth D15 test is designed to categorise colour vision deficiency as severe or moderate. The level of difficulty of the test was set so that those who passed it should be able to recognise surface colour codes, such as those used for electrical wiring. The test is widely used to provide advice to patients with abnormal colour vision and is often used for occupational selection when reliable recognition of surface colour codes is required. However, there has been only one previous study of the correlation between performance at the D15 test and the naming of surface colour codes and there has been no study of whether a person who passes the D15 can reliably name surface colours. Methods: One hundred and two people aged 11 to 65 years with abnormal colour vision were recruited from consecutively presenting optometric patients and were asked to name the colours of fabric, paint and cotton thread samples. There were 10 colours in each class of material and the samples were presented in a large (five to 10 degree angular subtense) and small size (2.5 deg and a single thread). The errors made were compared to those made by an age‐matched control group of equal size with normal colour vision. Results: The correlations between the Farnsworth D15 colour confusion index and colour naming errors were 0.62 for the large stimuli and 0.73 for the small stimuli. Its sensitivity and specificity identifymg those who made more errors than the worst performing colour normal person were 0.80 and 0.69 (large stimuli) and 0.75 and 0.71 (small stimuli). A Nagel anomaloscope range of less than 35 scale units provides essentially the same sensitivity and specificity. Conclusions: About 40 per cent of those with abnormal colour vision can name the main colours correctly under good visibility conditions. The D15 test is an imperfect predictor of those who can name surface colour codes correctly but it does provide useful information for general counselling. It is not suitable as a single test for occupational selection because it will pass 20 per cent who cannot name surface colours correctly and fail 30 per cent who can. In occupations in which recognition of surface colour codes is of critical importance, it may be best not to select people with abnormal colour vision because of the lack of a colour vision test that is a perfect predictor of the ability to recognise surface colours.     

Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans

1 Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia.
2 Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N -demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms.
3 After a single, oral 30  mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes.
4 The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL C _max 59  nmol l⁻¹ and AUC (0, t h) 144  nmol l⁻¹h, mean MDL C _max 183  nmol l⁻¹ and AUC 2627  nmol l⁻¹h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL C _max 356  nmol l⁻¹ and AUC 10512  nmol l⁻¹h, MDL concentrations below limit of quantitation).
5 We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism.     

Vitamin a cost-effectiveness model

To assist in the selection of a preferable vitamin A deficiency control policy, a model has been developed to organize information on program costs and program-related effects. The model was designed to compare three approaches: (1) diet modification; (2) fortification of processed foods; and (3) periodic large doses. Health effects projected are rates of specific eye pathologies associated with vitamin A deficiency (xerophthalmia), and mortalities within age cohorts. Effectiveness is calculated as a function of coverage, biological efficacy, and incidence of vitamin A deficiency. The model was applied to data from the Province of West Java in Indonesia. The results of this application suggest that funding level considerations are an important factor in selecting a preferred control strategy. In addition to determining the relative resource requirements of alternative interventions aimed at reducing the morbidity and mortality effects of vitamin A deficiencies, the model, using marginal cost and marginal effectiveness information, can serve as a guide to the most efficient allocation of resources for each type of intervention.     

复方丹参注射液与维生素B6、C注射液配伍稳定性试验

本文观察了复方丹参注射液与维生素B6、维生素C注射液的配伍稳定性，结果表明复方丹参注射液与维生素B6注射液可以在4h内配伍使用，而不能与维生素C配伍。     

HFE codon 63/282 (H63D/C282Y) dimorphism in German patients with genetic hemochromatosis

Abstract: Genetic hemochromatosis (GH) is closely associated with genes of the major histocompatibility complex (MHC) on chromosome 6. Recently, a candidate gene for GH, with structural similarities to MHC class I genes, designated HLA-H and presently named HFE, has been cloned. The HFE gene is localized telomeric to the MHC and several reports have indicated that the HFE gene is mutated in GH patients. In the present study we have analyzed the relationship of HFE gene variants and disease manifestation in GH patients and family members. Fifty-seven patients with GH, 73 family members and 153 healthy blood donors were studied for the amino acid dimorphism at codon 63 (His63Asp=H63D) and codon 282 (Cys282Tyr= C282Y) of the HFE gene. The codon 63 and 282 dimorphism were defined by PCR amplification of genomic DNA samples and restriction enzyme digestion using RsaI/SnaBI for C282Y and Bcll/Mbo 1 for H63D. Ferritin, transferrin serum levels and total iron-binding capacity were determined prior to therapeutic intervention. The Tyr-282 substitution occurred in 53 (93%) of patients compared with 8 (5.2%) of controls (OR=169, P >0.0001). Fifty-one (90%) patients were Tyr-282 homozygous. In contrast, the Asp-63 substitution was present in 5 (8.8%) of the patients compared with 34 (22%) of controls (OR=0.39, P =NS) with none of the patients being homozygous. In Tyr-282 homozygous GH patients serum ferritin levels, transferrin saturation, liver iron and liver iron index were elevated significantly compared to Tyr-282-negative patients, whereas no difference was observed between Tyr/Cys-282 heterozygous and Tyr-282-negative patients.