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We consider a decentralized supply chain that a manufacturer wholesales a product to a retailer who sells the product on a price-and-time dependent market with a two-stage strategy over the...

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a well-known and novel class of oral antihyperglycaemic drugs. DPP-4 inhibition facilitates ulcer healing in patients with diabetes. However, the actual mechanisms, which are independent of lower blood glucose levels, are still unknown. Therefore, the aim of this study was to analyse the effect of the DPP-4 inhibitor sitagliptin on wound healing through a glucose-independent pathway. In this study, DPP-4 inhibitors facilitate keratinocyte differentiation and the proliferation, increase blood flow in the cutaneous of wounds in healthy C57BL/6 mice. Additionally, the administration of the DPP-4 inhibitor ameliorates wound healing and enhances adiponectin expression in healthy C57BL/6 mice. Taken together, our results reveal a protective role for the DPP-4 inhibitor sitagliptin in wound healing by regulating adiponectin and phospho-eNOS levels in keratinocytes. Based on these results, the DPP-4 inhibitor may have therapeutic potential for healing wounds through a diabetes-independent mechanism.

The association between psoriasis and cardiovascular disease risk has been supported by recent epidemiological data. Patients with psoriasis have an increased adjusted relative risk for myocardial infarction. As such, the cardiovascular risk conferred by severe psoriasis may be comparable to what is seen with other well-established risk factors, such as diabetes mellitus. Previous studies demonstrated that low-density lipoprotein (LDL) plays critical roles during atherogenesis. It may be caused by the accumulation of macrophages and lipoprotein in the vessel wall. Oxidized LDL (ox-LDL) stimulates the expression of adhesion molecules, such as ICAM-1 and VCAM-1, on endothelial cells and increases the attachment of mononuclear cells and the endothelium. Even though previous evidence demonstrated that psoriasis patients have tortuous and dilated blood vessels in the dermis, which results in the leakage of ox-LDL, the leaked ox-LDL may increase the expression of adhesion molecules and cytokines, and disturb the static balance of osmosis. Therefore, exploration of the relationship between hyperlipidemia and psoriasis may be another novel treatment option for psoriasis and may represent the most promising strategy.

Mucocutaneous lesion appears in up to 40% of patients with primary systemic amyloidosis (AL amyloidosis). The cutaneous signs may be co-expressed with other organ involvement or even solely presented as the first clue. We reported a case of systemic AL amyloidosis who was initially presented as a solitary hemangioma with a purpuric halo. Excisional biopsy revealed a hemangioma with amyloid deposited in thickened vascular walls. Systemic AL amyloidosis was diagnosed after thorough survey. The stage of disease at the time of initial treatment is the greatest prognostic factor. To our knowledge, this is the first case of systemic AL amyloidosis initially presented as a purpuric halo around hemangioma in Taiwan. This target-like lesion should be linked to systemic AL amyloidosis and early diagnosis is extraordinary important.

We study a decentralized supply chain in which a manufacturer supplies a newsvendor-type item to a retailer in a stock-dependent demand market, considering temporary and permanent inventory shrinkages. The manufacturer offers a cheaper-wholesale-price, buy-all-back contract to operate the chain as a centralized supply chain. The purpose is to coordinate the chain and create a win–win situation by jointly determining the order quantity and negotiating the wholesale price. We consider the retailer's ignorance of inventory errors and unwillingness to share information, and we construct a range for the negotiated wholesale price in which it not only achieves Pareto efficiency but also encourages the retailer's cooperation with the inventory information. We find that the retailer bears more risk for inventory errors even when our contract is in place. We also learn that the impact of the stock-level demand stimulation effect on chain profit outweighs the impact of the inventory errors if the levels of inventory shrinkage are below our obtained upper bounds.

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoetm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-&alpha, stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoetm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-&alpha, stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.

Lycopene is the most abundant carotenoid in tomatoes, which has been identified to have the properties of anti-inflammation in addition to the capability to inhibit the expression of adhesion molecules. Intercellular adhesion molecules play a critical role in the pathogenesis of psoriasis. Here, we report that the topical use of a lycopene decreased imiquimod (IMQ)-induced psoriasis-like inflammatory responses, the progress of which was based on adhesion molecules. In vitro analysis showed that lycopene decreased keratinocyte and monocyte adhesion. Evidence suggests that intercellular adhesion molecule-1 (ICAM-1) is a main mediator of psoriasis pathogenesis. Therefore, it will be interesting to investigate the factors that contribute to the lycopene-mediated inhibition of ICAM-1 expression in psoriasis. We expect that lycopene will with potential value in the treatment of psoriasis.

Keloids is a fibroproliferative disease. The incidence of keloids among Asians has not been thoroughly studied. The objective of this study is to determine the incidence of keloids in Taiwan, which mainly consists of ethnic Chinese. Furthermore, we want to determine the comorbidity rate of other fibrosis-related diseases among keloid patients. This study was based on the National Health Insurance Research Database, which contains the data of 1 million randomly selected patients. Multivariate logistic regression analyses were employed to estimate the relative odds of keloids as a function of fibrosis-related diseases. The annual keloid incidence rate in Taiwan was 0.15 % for the general population. With a 1.33 ratio, women outnumbered men. Women with uterine leiomyoma have a 2.25-fold greater risk of keloids, compared with women without leiomyoma. We concluded that keloid incidence in Taiwan is approximately 0.15 %. Women with leiomyoma have a greater risk of keloids, this implicates that both diseases share a common etiopathological pathway.

We study a one-manufacturer and one-retailer type of supply chain that the manufacturer manufactures two newsvendor-type items and offers a buy-back contractual commitment to the retailer who sells the items in a stochastic demand market with various prices, allowing demand leakage from high-priced item to low-priced one. The objective of this study is to coordinate the chain by jointly determining wholesale prices, buy-back prices, retail prices and order sizes. We first derive a succinct model for the chain in which the manufacturers expected profit subject to the retailer’s optimal expected profit will be explored. And a solution method to the case of uniformly distributed error demand is subsequently proposed; accordingly, a series of examples along with graphical concavity and satisfying constraint of the manufacturer’s expected profit are conducted to validate our solution method.

Typical cutaneous non-tuberculous mycobacteria (NTM) infections show a histopathology pattern of granulomas with admixed Langhans giant cells, and abscesses may be observed in acute lesions. Herein, we describe a patient carrying a high titer of autoantibodies to interferon (IFN)-γ with disseminated Mycobacterium kansasii infection presenting with emperipolesis and Rosai-Dorfman disease (RDD)-like histopathological features characterized by remarkable, large, pale-staining "RD cells", which were CD68 and S100 positive and CD1a negative. The patient was misdiagnosed with RDD initially, but exhibited a poor response to all interventions. A re-biopsy revealed Langhans-type multinucleated giant cells; multiple definite acid-fast bacilli were also found. M. kansasii was isolated from cultured tissues. Anti-NTM treatment was initiated. After treatment, all lesions resolved almost completely within the following month. High-titer anti-IFN-γ autoantibodies were detected during follow up, leading to the diagnosis of adult-onset immunodeficiency syndrome. In conclusion, patients carrying high-titer autoantibodies to IFN-γ who also have a disseminated cutaneous M. kansasii infection may present with RDD-like histopathological features, which may be a pitfall in the diagnosis of disseminated cutaneous NTM infections.

The objective of this study is to optimize an overall expected profit in a two-period newsvendor setting by jointly determining these two items' order sizes and selling prices. The item in the second period is a product extension of the item in the first period. An inadequate inventory is intentionally placed in the first period in order to stimulate more sales in the second period. The first item's unsatisfied demand is assumed to be transferred to the second selling period with a certain shifting demand rate. The two items' stochastic demand is assumed to be in a linear-additive form consisting of a deterministic demand and an error demand that is exponentially distributed. Including the classical newsvendor model as a special case, we first propose a pertinent model that overshadows the classical newsvendor setting in terms of profit performances, and surprisingly find that the first item's error demand should be completely sacrificed when facing a high shifting demand rate. Afterwards, we modify the model to identify that our inadequate stock strategy is indeed practicable, and then extend the model to predetermine the two items' selling prices that ensure the existence of maximum of the expected profit. Possible triggered effects, such as an increasing primary demand, an increasing error demand and a cheaper purchasing cost in the second period, are also illustrated by examples.

Background Few studies have examined the association between autoimmune diseases and parkinsonism. Objective We sought to investigate the risk for parkinsonism during a 5-year follow-up period after a diagnosis of psoriasis using a population-based data set in Taiwan. Methods We identified 4885 patients with psoriasis for the study cohort and randomly selected 24,425 patients as a control cohort. Each subject was individually followed up for a 5-year period to identify those who subsequently developed parkinsonism. Results Stratified Cox proportional hazards regression showed that the adjusted hazard ratio for parkinsonism during the 5-year follow-up period for patients with psoriasis was 1.74 (95% confidence interval 1.35-2.20) that of control patients. Furthermore, the adjusted hazard ratios for parkinsonism within the 5-year follow-up period after the index date for subjects with psoriasis were similar between both sexes (1.78 and 1.66 for men and women, respectively). Limitation Our data set did not provide detailed information on the severity of psoriasis, or individual factors such as cigarette smoking, alcohol consumption, body mass index, and dietary patterns. Conclusion Patients with psoriasis were found to be at a significant risk of parkinsonism during a 5-year follow-up.

Background No prior study has investigated the possibility that scabies patients may be at an increased risk for developing pemphigoid. Objective To evaluate the risk of pemphigoid following scabies during a 3-year follow-up period using a Taiwanese population-based claims database and taking clinical and demographic characteristics into consideration. Methods This investigation consisted of a study group of 6793 subjects with a diagnosis of scabies and 33 965 randomly selected subjects used as a comparison group. Each patient was tracked for 3 years following their index dates to identify those who received a subsequent diagnosis of pemphigoid. Stratified Cox proportional hazards regressions were used to compute the hazard ratio (HR) of pemphigoid during the 3-year follow-up period. Results Of the 40 758 subjects, 52 (0.13%) had received a diagnosis of pemphigoid during the 3-year follow-up period; 33 (0.49% of the study group) were from the study group and 19 (0.06% of the comparison group) were from the comparison group. Compared to subjects without scabies, the HR for pemphigoid for subjects with scabies was 5.93 within the 3-year follow-up period following the index date after adjusting for monthly income, hypertension, diabetes, obesity, psoriasis, stroke, dementia, Parkinson's disease, coronary heart disease, schizophrenia or bipolar disorder, and after censoring those that died during the follow-up period. Conclusions This study detected an increased risk for pemphigoid among patients suffering from scabies. Physicians treating elderly patients with a history of scabies should be alert to the development of pemphigoid.

Background The most documented complication of scabies has been reported to be infection by group A streptococci, which has in turn been suggested to contribute to the development of glomerulonephritis. Objective This study aimed to investigate the risk of chronic kidney disease (CKD) subsequent to scabies utilizing a population-based dataset in Taiwan. Methods This retrospective matched-cohort study included 5071 subjects with scabies and 25 355 randomly selected comparison subjects. We individually tracked each subject for a 5-year period to identify those who subsequently received a diagnosis of CKD during the follow-up period. Stratified Cox proportional hazards regressions were performed to compute the hazard ratio (HR) of CKD during the 5-year follow-up period. Results The incidence rate of CKD during the 5-year follow-up period was 9.66 (8.51–10.93) per 1,000 person-years and 6.24 (5.82–6.69) per 1000 person-years for subjects with and without scabies respectively. The HR for CKD during the 5-year follow-up period for subjects with scabies was 1.34 (95% CI = 1.15–1.56) that of comparison subjects after adjusting for monthly income, hypertension, diabetes, obesity, stroke, coronary heart disease, chronic obstructive pulmonary disease, tobacco use disorder, hyperlipidemia and alcohol abuse during the 5-year follow-up period. Male subjects with scabies were 1.40 (95% CI = 1.14–1.71) times more likely than comparison subjects to suffer from subsequent CKD, and female study subjects were 1.27 (95% CI = 1.05–1.61) times more likely. Conclusions We concluded that there was an increased risk for CKD among patients suffering from scabies.

This study explores a Stackelberg game that consists of a manufacturer who is a leader manufacturing newsvendor-type products, and two retailers who are two followers selling the products in a stochastic demand market that is divided into two various prices sub-markets allowing demand leakage from a high-priced market to a low-priced market. The objective of the game is that the manufacturer offers a returns policy contract in an effort that not only to maximize its expected profit by determining wholesale price and buy-back price, but also to improve the two retailers’ expected profits by determining their prices and order sizes. We develop a simple solution procedure to the case of uniformly distributed demand, and thereby conduct a string of examples incorporating with the factors of demand leakage rate, consumers’ price-sensitivity and demand variability. Many significant contributions of this study include: the chain should give up some sales opportunity in high price-sensitive markets and then offset back from low price-sensitive ones; the two retailers jointly bear the entire risk of demand uncertainty; and the returns policy contract indeed outperforms a price-only contract although it is not the Pareto improvement to low-priced market segment.

Poroid neoplasm is a skin appendage tumor that has both benign and malignant counterparts. It has traditionally been regarded as of eccrine origin and has four types: intraepidermal poroma (hidroacanthoma simplex), poroma, dermal duct tumor, and poroid hidradenoma. Here we describe the case of a 64-year-old woman who had a verrucous, erythematous to brownish tumor on her left buttock for many years. Histopathology revealed an intra-epidermal poroid tumor with both benign and malignant parts. The benign part had intra-epidermal nests of poroid cells, which were smaller, monomorphic and sharply marginated from adjacent keratinocytes. The malignant part showed similar cell types, but had a higher nuclear/cytoplasmic ratio, pleomorphism, and prominent mitoses. Ductal structures were noted in neoplastic cells and an epithelial membrane antigen stain was strongly positive. Interestingly, peripheral palisading and primitive follicular germ formation were also observed in the neoplasm, which suggests follicular differentiation. We made a final diagnosis of porocarcinoma in situ with follicular differentiation, which may support the folliculosebaceous–apocrine unit theory, but a tumor with such a combination has not been described before.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an unusual entity with variable clinical manifestations and histopathological features. It is associated with a variety of immune-mediated systemic diseases, most commonly in rheumatoid arthritis. We report a 42-year-old female with a long-standing history of rheumatoid arthritis, presenting with multiple pruritic erythematous papules and nodules on the lower legs 1 month after beginning treatment with etanercept. Microscopic examination of a fully developed lesion showed a diffuse dense interstitial lymphohistiocytic infiltrate interspersed with palisaded granulomas consisting of epithelioid histiocytes and multinucleated giant cells surrounding central zones of degenerated collagen, neutrophils and leukocytoclastic debris. A diagnosis of PNGD was made on the basis of typical histopathologic features. Withdrawal of etanercept led to gradual resolution of the skin lesions, with no new skin lesions appearing afterwards. Although the correlation between the use of tumor necrosis factor-α (TNF-α) antagonists and the development of PNGD remains controversial and warrants further investigation, PNGD should be considered in the differential diagnosis of skin eruptions within a setting of anti-TNF-α therapy.

This study deals with the problem of jointly predetermining optimal replenishment schedule and selling prices toward hybrid retailers who sell products via in-stores and estores concurrently, where deteriorating item is considered with two declining demands in time and price. Under the circumstances, strict concavity of the proposed problem in selling prices is fi rst proven, and closed-form solutions for selling prices are thereby obtained. Next, when selling prices are fi xed, not only the strict pseudo-concavity in replenishment interval is shown, but also the optimal schedule uniquely exists if the criterion inequality holds, which is also a premise for positive profi t generation. Afterwards, three solution-fi nding sequences are defi ned, to which the convergent property is identifi ed, by which a simple algorithm for optimal solutions is presented. Finally, numerical examples are conducted to illustrate the proposed problems.

Background No previous study has investigated the incidence or risk of acute myocardial infarction (AMI) developing after the diagnosis of psoriasis in Asian populations. Objective We sought to evaluate the association between psoriasis and subsequent AMI during a 5-year follow-up period, using a nationwide Taiwanese population-based claims database, and taking clinical and demographic characteristics into consideration. Methods Our study cohort consisted of all patients with a first recorded diagnosis of psoriasis (N = 4752) between 1999 and 2001 and of patients without a diagnosis of psoriasis (N = 23,760) who were matched by age and sex (1:5) to the patients with psoriasis. Each patient was tracked using hospitalization data from 2001 until the end of 2006. Stratified Cox proportional hazard regressions (stratified by age and sex) were performed as a means of computing the 5-year AMI-free survivals after adjusting for possible confounding factors. Results Of the total sample, 70 patients (0.2%) had AMIs during the 5-year follow-up period: 22 (0.5% of the patients with psoriasis) from the study cohort and 48 (0.2%) from the comparison cohort. After adjusting for other factors, the hazard of AMI during the 5-year follow-up period was 2.10 times greater (95% confidence interval 1.27-3.43, P = .004) for patients with psoriasis than for comparison patients. Limitations We could not take into account some known risk factors for AMI, such as smoking and body mass index. Conclusions Psoriasis may confer an independent risk of AMI in Asian populations. We suggest that patients with psoriasis be made aware of the increased risk of AMI.

This paper extends the problem in Ouyang, Chen and Chuang [13] and Huang and Goyal [10] to new product introduction, under which demand is assumed to be the ramp type function of time, and supplier off ers retailer a full and partial deferral of payment to choose from. Ultimately, the determination of optimal order quantity and optimal payment policy minimizing total cost per unit time is explored. Six possible cases occur here, among which one of the most commonly seen will be mathematically analyzed, while the others are presented by numerical examples.

Cholesterol embolism (CE) is characterized by emboli containing cholesterol crystal in the arterioles, most commonly found in the skin and the kidney. The skin presentations of CE include livedo reticularis, blue toe syndrome, ulceration and gangrene. Cutaneous reactive angiomatosis (CRA) is a recently proposed term to describe a group of reactive vascular proliferation in skin caused by various diseases. Its occurrence in association with CE is extremely uncommon. An 82-year-old man with a history of cerebral infarction and on long-term warfarin therapy developed progressive, multiple violaceous papules and nodules on the dorsal feet, soles and toes, simulating Kaposi's sarcoma. Skin biopsy showed marked vascular endothelial cell proliferations characteristic of CRA affecting the full thickness of dermis. In addition, cholesterol crystal emboli were found in dermal arterioles. The skin lesions improved after the warfarin dose was reduced. We emphasize the possible presence of CE in a patient presented with CRA, especially in those with a pre-existing atherosclerotic disease, on anticoagulation therapy, or having a prior history of invasive vascular procedure. Yang Y-W, Chen C-L, Ho W-T, Wang K-H. Cutaneous reactive angiomatosis associated with cholesterol embolism.

Nowadays, return policies that provide customers with a period of probation and accept their returns if they are dissatisfied are become more popular. This study deals with inventory management under the return policy by jointly determining order quantity, selling price and selling period in response to non-instantaneous re-sales. To this end, two individual inventories, one for service and the other for recovery, were accordingly modeled in order to reflect time lag for being reserved. Maximization problem of profit per unit time is constructed in association with theoretical analysis with respect to three cases that happen frequently in practice. Finally, solution methodology is presented to conduct numerical examples from which many managerial insights are acquired.

In a highly competitive market, no matter for classical retailers or for mail order retailers, offering a return policy to entice customers to purchase items has become an inevitable strategy. This paper aims to investigate the problem of jointly determining order size, selling price and selling period of an inventory management for deteriorating items with resalable returns, in which we restrict the assumptions made by Vlachos and Dekker [9] and Mostard et al. [6] as follows: (1) returns are allowed only within a certain time frame, thereafter, no return is accepted; (2) money is fully reimbursed by retailer; (3) returns can be resold and returned several times per period. In addition, both the effects of deterioration and holding cost are incorporated to make our proposed model more realistic and pragmatic with regard to retail sales. Meanwhile, as proposed by Vlachosand Dekker [9], we defined return rate in terms of percentage of demand, and hence an average distribution approach to model inventory beh...

Background Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Objectives To investigate the clinicopathology, risk factors, and prognostic factors of MEN. Methods We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). Results Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. Limitations The study was limited by the small sample size. Conclusion MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation.

Clear cell fibrous papule (FP) is a rare variant of FP. We report a 39-year-old female patient who presented with a dome-shaped papule on the nose. The diagnosis of clear cell FP was made based on histological and immunohistochemical studies. Interestingly, scattered S-100 cells were admixed within the lesion, a finding hitherto not reported. The S-100 positivity may be misleading and should be cautiously interpreted.

Angioma serpiginosum is an uncommon, acquired vascular nevoid disorder with capillary dilation and proliferation in the papillary dermis. The eruptions are asymptomatic and characterized by grouped, erythematous to violaceous, serpiginous and punctate macules. The condition usually appears in females during adolescence on unilateral lower extremities and the buttocks. We report a rare case with a late onset and atypical distribution of lesions in a 48-year-old female patient who had groups of punctate lesions on her left foot for four to five years. Histopathological examination showed hyperkeratosis and multiple dilated and proliferated capillaries in the papillary dermis. Inflammation and extravasation of red blood cells were not found. According to the clinical and pathological findings, we established a diagnosis of angioma serpiginosum. She was treated with a pulsed dye laser, and the angiomatous lesions subsequently improved.

Because tyrosinase catalyzes melanin synthesis, tyrosinase inhibitors are important in cosmetic skin-whitening. Oxidative stress contributes to skin aging and can adversely affect skin health, which means antioxidants active in skin cells may support skin health. We examined 25 traditional Chinese herbal medicines that might be useful for skin-whitening and skin health. Extracts (100microg/mL) were tested for cytotoxicity on human epidermal melanocytes (HEMn); 12 exhibited low cytotoxicity. Their effects on tyrosinase and melanin inhibitory activities and free radical scavenging activities were further assessed. Phenolic contents were evaluated using Folin-Ciocalteu reagent. Four herbs, Pharbitis nil, Sophora japonica, Spatholobus suberectus, and Morus alba, exhibited potent inhibitory effects on tyrosinase (IC(50) values 24.9, 95.6, 83.9, and 78.3microg/mL, respectively). Melanin inhibition was not dose-dependent. Sophora japonica (IC(50): 14.46microg/mL, 1,1-diphenyl-2-picrylhydrazyl (DPPH); 1.95microg/mL, hydroxyl radical) and Spatholobus suberectus (IC(50): 10.51microg/mL, DPPH; 4.36microg/mL, hydroxyl radical) showed good antioxidative activities and high phenolic contents (255 and 189mg of gallic acid/g extract, respectively). Among active anti-tyrosinase extracts, Sophora japonica and Spatholobus suberectus were especially potent in HEMn cells in terms of free radical scavenging effects and high phenolic contents, making them the strongest candidates for cosmetic application found in the current study.

SummaryBackground Although psoriasis is seldom life threatening, very few studies have compared differences in health care service use between patients with and without psoriasis. Objectives To investigate differences in health care service use between patients with and without psoriasis. Methods Patient details and data on their use of health services were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. We included 3649 patients with psoriasis and 3649 without it. Each patient was followed for a 1-year period to estimate their utilization of health care resources. Student t-tests were used to compare differences in health care services use between patients with and without psoriasis. Results For dermatology services, patients with psoriasis had significantly more outpatient visits (3·5 vs. 0·9), and higher outpatient and total costs (US$148·00 vs. US$12·20 and US$581·60 vs. US$347·20, respectively) than those without psoriasis. For nondermatology services, patients with psoriasis had more outpatient visits (21·3 vs. 17·6), and higher outpatient and total costs (US$904·60 vs. US$663·50 and US$1335·50 vs. US$998·30, respectively) than those without psoriasis. For overall health care service use, patients with psoriasis had significantly more outpatient visits (24·8 vs. 18·5; P

Summary Background An uncommon histiocytosis primarily involving the lymph nodes, Rosai–Dorfman disease (RDD, originally called sinus histiocytosis with massive lymphadenopathy) involves extranodal sites in 43% of cases; cutaneous RDD (C-RDD) is a rare form of RDD limited to the skin. The clinicopathological diagnosis of C-RDD may sometimes be difficult, with different clinical profiles from those of its nodal counterpart, and occasionally misleading histological pictures. There have been few multipatient studies of C-RDD and documentation of its histological spectrum is rare. Objectives To identify the clinical and histopathological profiles, associated features, and the chronological changes of this rare histiocytosis. Methods From 1991 to 2002, patients diagnosed as having C-RDD were collected in four academic hospitals. Clinical presentations, treatments, and courses of each case were documented. In total, 21 biopsy specimens obtained from these patients were re-evaluated and scored microscopically with attention to the uncommon patterns and chronological evolution both clinically and histologically. Results We examined six patients with C-RDD, three men and three women. The mean age at the first visit was 43·7 years. The clinical presentations were mostly papules, nodules and plaques, varying with the duration and depth of lesions. Although the anatomical distribution was wide, the face was most commonly involved. Evolutional changes were identified clinically, as the lesions typically began with papules or plaques and grew to form nodules with satellite lesions and resolved with fibrotic plaques before complete remission. No patient had lymphadenopathy or extracutaneous lesions during follow-up (mean 50·5 months). At the end of follow-up, the lesions in four patients had completely resolved irrespective of treatment; two patients had persistent lesions. The histopathological pattern of the main infiltrate, the components of cells and the stromal responses showed dynamic changes according to the duration of lesions. The characteristic Rosai–Dorfman cells (RD cells) were found in association with a nodular or diffuse infiltrate in 15 lesions (71%). Four lesions (19%) demonstrated a patchy/interstitial pattern. One lesion (5%) assumed the pattern of a suppurative granuloma. RD cells were less readily found in these atypical patterns. Conspicuous proliferation of histiocytes associated with RD cells was found in three lesions, including xanthoma, localized Langerhans cell histiocytosis and xanthogranuloma. Along with lymphocytes, plasma cells were present in all lesions, often in large numbers with occasional binucleated or trinucleated cells. Variably found in the lesions were neutrophils (nine lesions, 43%) and eosinophils (13 lesions, 62%). The former occasionally formed microabscesses, while the latter were often few in number. Vascular proliferation was a relatively constant feature (90%). Fibrosis was found in 10 lesions (48%). Conclusions Our study further confirms that C-RDD is a distinct entity with different age and possibly race distributions from RDD. Compared with its nodal counterpart, C-RDD demonstrates a wider histopathological spectrum with different clinicopathological phases depending on duration of the lesions. Awareness of these features is helpful in making a correct diagnosis. The associations of C-RDD with other histiocytoses may have important implications for the pathogenesis of this rare histiocytosis.

Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol–SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol–SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol–SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) ( P < 10 –7 ). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol–SCAR, but only in 20 (15%) of 135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4–9780.9); corrected P value = 4.7 × 10 –24 ] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23–6665.26); corrected P value = 8.1 × 10 –18 ]. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol–SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition.

Background: Milium-like syringoma is a variant of syringoma first described in 1987. Only few cases have been reported in the literature. It may be misleading clinically, and its histogenesis has not been clarified. Case report: We present a case of periorbital milium-like syringoma, with studies on the histopathologic, histochemical, and immunohistochemical features. Results: Histology showed a large keratin-filled cyst in the upper portion of the lesion approximating the epidermis. Serial sections revealed that the cyst connected with the underlying syringomatous epithelial strands. Melanin was absent in the wall of the cyst, as demonstrated by Fontana–Masson stain. Cytokeratin 7 was expressed neither in the milia nor in the solid epithelial parts. Carcinoembryonic antigen (CEA) reactivity was seen in the luminal cells of the keratinous cysts. However, in the largest keratin-filled cyst clinically suggesting a milium, only the lower half of the cyst was positive for CEA. These results proved that the milia were part of syringoma with eccrine duct differentiation. Fusion of the upper half of the largest cyst with the epidermis may explain the absence of CEA positivity in this part, analogous with eccrine duct milia. Review of the literature indicated that this variant of syringoma occurs more often in Asians. Conclusion: We present evidence, and propose the histogenesis of milium-like syringoma, that it is a variant of syringoma with a prominent cystic component showing features of eccrine duct milia. Recognition of its nature is of therapeutic significance. Further studies are required to verify its clinical characteristics as compared with ordinary syringomas.

Background. Topical 5-fluorouracil (5-FU) is a standard treatment for Bowen's disease. However, its efficacy may be limited by the presence of stratum corneum. The Er:YAG laser has shown a dramatic enhancement effect on the delivery of 5-FU in vitro by ablation of the stratum corneum. The efficacy of laser-assisted delivery of 5-FU has not been tested in human. Objective. To see whether Er:YAG laser pretreatment can improve the efficacy of topical 5-FU in the treatment of Bowen's disease. Methods. Three target lesions from a patient with multiple Bowen's disease were selected for a half-side comparison study. The Er:YAG laser was used to remove the cornified layer on one side of each lesion, followed by twice-daily application of 5-FU cream to both sides. Clinical and histologic responses were compared. Results. Lesions pretreated with the Er:YAG laser showed more rapid clinical and histologic responses to topical 5-FU than those treated with 5-FU alone. Evaluation at 9 months after treatment showed no recurrences of lesions on both sides. Conclusions. Our preliminary study demonstrates that this Er:YAG laser-assisted modality is effective and shows accelerated clinical response and shortened treatment time compared with topical 5-FU as a single treatment.