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Biomedical subjects

Makoto Kawashima

Publications and source records attributed to Makoto Kawashima.

At least 19 recordsLinked to original sources

Effect of standard medication on quality of life of patients with atopic dermatitis.

Patients with atopic dermatitis present with debilitating symptoms, including pruritus and subsequent excoriation, which significantly reduces their quality of life (QOL). At present, the standard therapy for atopic dermatitis constitutes a topical steroid and/or a topical immunomodulator, an emollient and an oral antihistamine, although few studies have reported the effect of this treatment regimen on QOL. The current study aimed to verify the efficacy of the standard therapy for both clinical symptom severity and patient QOL, assessed using the validated Skindex-16 questionnaire. Atopic dermatitis patients receiving the standard therapy (n=771) were enrolled in the current phase IV, multicenter, 12-week, open-label study. The Rajka and Langeland scale (used to rate the severity of atopic dermatitis symptoms) and the Skindex-16 QOL questionnaire were completed at weeks 0 (baseline), 4 and 12. Of 415 patients completing the questionnaire at all time points (per-protocol population), 95.2% were prescribed the antihistamine fexofenadine HCl 60 mg. There were significant improvements in symptoms, emotions and functioning scale scores at weeks 4 and 12 compared with baseline (P<0.005). Discomfort associated with itching, as assessed by item 1 on the Skindex-16, improved over the treatment period (score decreased by >or=1 and >or=2 in 75.2% and 50.9% of patients, respectively). Significant (P<0.005) improvements from baseline in global scores were also observed at weeks 4 and 12, and for week 12 compared with week 4. Severity scores improved significantly (P<0.005) from weeks 0-4 and from weeks 4-12. The standard therapy was generally well tolerated with only mild adverse events reported (0.5%). These data suggest that patients with atopic dermatitis and associated pruritus experience significant improvements in both symptom severity and QOL when receiving standard therapy.

Adult↗

Application of the Food and Drug Administration (FDA) bioequivalent guidance of topical dermatological corticosteroid in yellow-skinned Japanese population: validation study using a chromameter.

The American Food and Drug Administration (FDA) bioequivalent guidance of topical dermatological corticosteroids in 1995 (the Guidance) requires measurement of the skin blanching response with a chromameter for evaluation of cutaneously applied corticosteroid formulations. The Japanese government decided to apply the same guidelines in 2003, despite there having been no reported trial for the yellow-skinned races. The purpose of this study was to obtain basic data of corticosteroid-induced skin blanching response measured with a chromameter on yellow-skinned races. Four studies were performed according to the Japanese version of the Guidance for Industry using a chromameter on the forearms of healthy Japanese volunteers. This involved: (i) a validation study of proper duration of treatment exposure (dose duration); (ii) a comparison study of two dermatological corticosteroid products that represented different potency classes; (iii) inspection of reproducibility using right and left forearms; and (iv) study of seasonal difference. We showed that: (i) the same medication can give different values of ED(50) (the dose duration required to achieve 50% of the fitted areas under the effect curves [AUEC](max) value) under different dose durations; (ii) ED(50) do not always represent the potency of the corticosteroid; (iii) the results of AUEC at maximum duration were similar, but AUEC at an approximate ED(50) duration time varied widely; and (iv) the results of AUEC were different according to season. In conclusion the dose duration relationships, determination of the AUEC(max), and the ED(50) could be obtained on yellow-skinned races using the FDA method. However, negligible differences were found in our study regarding dose duration, reproducibility and seasonal change.

Administration, Cutaneous↗

Quality of life in patients with atopic dermatitis: impact of tacrolimus ointment.

BACKGROUND: Atopic dermatitis (AD), a significant problem in Japan, has a major impact on health-related quality of life (QOL). The development of steroid phobia in patients with AD may restrict the therapeutic options available to these patients. Tacrolimus ointment is a safe and effective nonsteroid treatment for AD. It may be an appropriate alternative for patients with AD and steroid phobia. The aim of this study was to determine the impact of AD on QOL and to investigate the effect of tacrolimus ointment on QOL in patients with steroid phobia. METHODS: Firstly, QOL scores were investigated in patients with AD and steroid phobia using the World Health Organization Quality of Life instrument, WHOQOL-26, and were compared with QOL scores from a previous study in volunteers from Tokyo, Japan. Secondly, patients with steroid phobia received tacrolimus ointment treatment for 12 weeks. Quality of life scores were assessed using WHOQOL-26 at baseline and study end. RESULTS: The overall mean QOL score of 106 patients with AD was significantly lower than that of 708 volunteers (3.1 +/- 0.5 vs. 3.3 +/- 0.5, P < 0.001). The overall QOL score improved from 2.9 +/- 0.4 at baseline to 3.3 +/- 0.4 following 12 weeks' tacrolimus ointment treatment in 35 patients with AD and steroid phobia (P < 0.001). CONCLUSIONS: Atopic dermatitis significantly lowers QOL. Tacrolimus ointment is associated with a significant improvement in QOL in patients with steroid phobia, indicating that it is an effective alternative to topical corticosteroids in these patients.

Attitude to Health↗

Absorbability of estrone and 17beta-estradiol in water onto activated carbon.

With a view to reducing pollution in the aquatic environment, estrone (E1) and 17beta-estradiol (E2) were tested for their absorbability in water onto activated carbons (ACs) with various pore-size distributions. In batch-type adsorption measurements, all adsorption isotherms obtained were found to fit a Freundlich equation. In case of eight different kinds of commercial AC in pure water, the amount adsorbed at equilibrium concentration of 1 microg/L was in the range of 25.6-73.5mg/g for E1 and 21.3-67.6 mg/g for E2. In case of pre-used ACs in water sand-filtered for use as drinking water, the amount adsorbed at 1 microg/L was in the range of 3.5-8.2mg/g for E2. In the case of two commercial ACs in river water and in effluent from secondary clarifier at municipal sewage treatment plant (MSTP), both originally containing E2, was in the range of 0.1-0.2 and 0.3-1 microg/g, respectively, at 1 ng/L. The difference of amount adsorbed onto AC was discussed in view of hydrophobicity of target chemicals, specific surface area and mean pore diameter of AC, and the difference in the absorbability and the ratios of co-present substances for the target compound.

Absorption↗

Prevalence of human papillomavirus DNA sequences in verrucous carcinoma of the lip: genomic and therapeutic approaches.

We examined the presence of human papillomavirus (HPV) DNA sequences in tissues of verrucous carcinoma (VC) of the lip. Detection and typing of HPV DNA was performed using polymerase chain reaction with sequence analysis and restriction fragment length polymorphism analysis. All tissues of VC contained HPV DNA and one of recurrent case was infected with four different HPV DNAs including high risk types. Seven different HPV types were detected in VC, of which (accession no. in EMBL/GeneBank/DDBJ databases) has been described as a partial sequences from an unknown HPV type. Sequence analysis showed that HPVX is related to HPV-20 (74.8% sequence homology). These results indicate that various mucosal and cutaneous HPVs of high risk types are associated with the one of pathogenesis of VC of the lip. In addition, the relationship between VC of the lip and HPV infection is discussed, as is therapy against VC.

Adult↗

A novel method to control the balance of skin microflora Part 2. A study to assess the effect of a cream containing farnesol and xylitol on atopic dry skin.

BACKGROUND: It is recognized that colonization by Staphylococcus aureus (SA) on the skin is one of the factors that can worsen atopic dermatitis (AD). Antibiotics and germicides are not the best choice to remove bacteria from the skin of AD patients, because of problems of irritation to the skin and bacterial resistance. We therefore turned our attention to the biofilm of SA with the aim of removing only SA from the skin surface of AD patients. We found that xylitol (X) and farnesol (F) synergistically inhibited biofilm formation by SA and dissolved biofilm formed in vivo (Part 1). OBJECTIVE: To test whether application of AD for 1 week with FX cream can reduce SA without affecting Staphylococcus epidermidis. METHODS: A randomized, double-blind, placebo-controlled right-and-left comparison study was performed. The arms of 17 patients with dry-type AD were applied with skin-care cream including/or not including a 0.02% F and 5% X combination for 1 week. The clinical response, biophysical assessment of the skin surface and counts of skin microflora were recorded before and after 1 week of therapy. RESULTS: The ratio of SA in total bacteria at sites to which FX cream had been applied was significantly decreased after 1 week (P = 0.007), compared with before application and with placebo sites (P = 0.045). The mean skin conductance (a parameter indicating the state of hydration of the skin surface) of FX cream sites was increased significantly compared with the conductance before application (P = 0.0001) and at placebo sites (P = 0.002). CONCLUSION: This study provides evidence supporting the idea that cream containing F and X is a useful skin-care agent for atopic dry skin colonized by SA.

Administration, Cutaneous↗

A case of symptomatic primary HIV infection.

A 30-year-old homosexual Japanese man had fourteen days of fever, malaise, appetite loss, sore throat, and four days of diarrhea and slightly congested eyes before he developed a skin eruption. He presented with measles-like exanthems on his face, trunk, and extremities. Deep red enanthems were seen on his left buccal mucosa opposite the premolar teeth, and whitish enanthems were seen on the buccal and gingival mucosa. HIV RNA was detected at the high concentration of 5.8 x 10(6) copies /ml in his serum. Cerebrospinal fluid examination revealed aseptic meningitis with 5,488 copies /ml of HIV RNA. Anti-HIV 1 antibodies against Gp160 and p24 tested by Western blot assay showed seroconversion on day 5 of his admission, seven days after he developed the skin eruptions. The fever lasted for three weeks from the initial onset, and the skin eruptions lasted for twelve days. Histopathologically, a mononuclear cell infiltration was seen mainly in the upper dermis surrounding small vessels and sweat ducts, with CD8+ cytotoxic T lymphocytes predominant. Additionally, CD1a+ putative interdigitating dendritic cells had also infiltrated perivascularly, and were surrounded by CD8+ and CD4+ T cells. In situ hybridization study failed to detect HIV products in skin biopsy specimens. Our findings suggested that CD8+ T cells and their interaction with CD1a+ dendritic cells in the skin may be important in inducing skin manifestations in acute HIV infections.

Adult↗

Intrahepatic flow disturbance by clomipramine in the isolated perfused rat liver.

Intrahepatic flow disturbance may have important pharmacological and toxicological significance. However, apart from pathological conditions, flow disturbance by drugs has received little attention. In the isolated perfused rat liver (IPRL), we found that infusion of tricyclic antidepressants increased portal perfusion pressure (PP) with a coincidental decrease in oxygen uptake at concentrations of 3-30 microM; the order of potency was clomipramine > amitriptyline > imipramine approximately nortriptyline >> desipramine. The characteristics of clomipramine action were as follows: (1) The extrahepatic portal vein was much less sensitive to clomipramine than the IPRL. (2) Changes in PP and oxygen uptake required Ca(2+) in the perfusate and were inhibited by papaverine, staurosporine, sodium nitroprusside and indomethacin. (3) Compared with endothelin-1, clomipramine produced a greater decrease in the ratio of oxygen uptake/PP together with a greater overflow of loaded indocyanine green for an increase in PP by about 2 cm H(2)O. (4) Vital staining with trypan blue and rhodamine 6G and histological examinations revealed that 3-10 microM clomipramine produced marked flow redistribution due to the constriction of portal vein branches. Portal flow was short-circuited to the hepatic vein at a deeper and hilar portion of the liver, with minimal perfusion of the periphery. These results demonstrate an example of drug-induced intrahepatic flow disturbance in vitro. Its contribution to the development of toxicity in vivo remains to be studied.

Animals↗

The epidermal stem cell factor is over-expressed in lentigo senilis: implication for the mechanism of hyperpigmentation.

We previously reported that accentuated expression of the endothelin-1 (ET-1)/endothelin B receptor (ET(B)R) cascade is involved in the mechanism of hyperpigmentation in lentigo senilis (LS) lesions. The paracrine mechanism underlying ultraviolet B (UVB)-induced hyperpigmentation in the skin may involve the stimulation of the ET-1/ET(B)R cascade as well as the stem cell factor (SCF)/SCF receptor cascade. Therefore, we used RT-PCR and immunohistochemistry to determine whether accentuated expression of the SCF/SCF receptor cascade is also associated with the mechanism of hyperpigmentation in epidermal LS lesions. RT-PCR analysis demonstrated the increased expression of mRNA transcripts for SCF (n=7), but not for SCF receptor (n=6) or growth-related oncogene alpha (GROalpha) (n=4) in LS lesions. Immunohistochemistry revealed markedly stronger staining for SCF but not for GROalpha or basic fibroblast growth factor (bFGF) in the lesional epidermis compared with the perilesional epidermis. This increased staining for SCF was corroborated by western blotting analysis for SCF expression in the lesional epidermis. These findings suggest that in addition to the stimulated expression of the ET-1/ET(B)R cascade, the accentuated expression of SCF in lesional skin plays an important role in the mechanism involved in the epidermal hyperpigmentation of LS.

Aged↗

Eosinophilic pustular folliculitis following autologous peripheral blood stem-cell transplantation.

We describe a case of eosinophilic pustular folliculitis (EPF) occurring after autologous peripheral blood stem-cell transplantation for non-Hodgkin's lymphoma and successfully treated with oral and topical indomethacin. Including ours, the reported cases of EPF with HIV-negative hematological disease have shown clinical features similar to those of HIV-associated EPF, however the prognosis is better than that for HIV-associated EPF, which usually shows a persistent course. EPF with HIV-negative hematological disease can be classified as a unique group in EPF.

Administration, Oral↗

Two cases of desmoplastic trichoepithelioma.

Desmoplastic trichoepithelioma is a rare tumor that usually exhibits the distinct clinical features of a solitary granuloma annulare-like growth on the face. We experienced two cases of desmoplastic trichoepithelioma, one of which showed unusual clinical features and the other of which was a typical case. The first case was a 20-year-old female who presented with a five year history of a solitary yellowish nodule, 5 mm in diameter, centrally between the eyebrows. There was no central dimple or elevated border. The other case was a 40-year-old female who presented with a ten year history of a solitary nodule, 6 mm in diameter on her left cheek. The latter lesion had a typical depressed area in the center of the nodule with elevated borders and could be clinically diagnosed as desmoplastic trichoepithelioma. The histopathological examination revealed that both of them were desmoplastic trichoepithelioma. Histopathological comparison of the two specimens suggested that the clinical dimple in the center of the first tumor might be the result of stromal dystrophic changes induced by the tumor.

Adult↗

A cross-sectional analysis of quality of life in Japanese acne patients using the Japanese version of Skindex-16.

We measured the quality of life of Japanese patients with acne using the Japanese version of Skindex-16, a semantically equivalent and validated translation of the original version produced by Chren et al. A total of 210 acne patients were enrolled in this study. The results showed that patients with acne experienced more severe emotional effects from their skin disease than functional or symptomatic effects. The scores for emotional aspects were related to the severity of the patients' acne following a prescribed scale, but the scores were high even when the patients only had a few comedones. Akaike's information criterion showed that the scores for symptoms were related to the severity of the patients' acne, and the patients' emotions were related to the interval between clinic visits. To improve patients' quality of life, treatment of comedones should be fully respected. In addition, dermatologists should encourage patients to visit clinics regularly to help them improve the emotional aspects of their quality of life.

Acne Vulgaris↗

Measurement of the impact of atopic dermatitis on patients' quality of life: a cross-sectional and longitudinal questionnaire study using the Japanese version of Skindex-16.

The impact of atopic dermatitis on patients' quality of life was measured using the Japanese version of Skindex-16 in a cross-sectional and longitudinal questionnaire study. One hundred sixty-two adult patients completed Skindex-16 and were followed-up with a standard medical therapy. Three to six months after the initial testing, 135 (83.3%) of the patients again completed Skindex-16 and also answered a general question about whether their skin condition had improved, remained the same, or become worse. The scores of Skindex-16 of 162 patients with atopic dermatitis were significantly higher than those of patients with isolated lesions, particularly in the Symptoms and Emotions scales. Patients with severe atopic dermatitis showed significantly higher scores in the three scales (Symptoms, Emotions, and Functioning), and there was a significant positive correlation between the severity and the 3-scale scores. After the follow-up period, 78 of 135 patients (57.8%) reported that their skin condition had improved. Forty-six patients (34.1%) reported that their skin condition had remained the same, and 11 (8.1%) became worse. Among the patients who said their dermatitis had improved, the scores of Skindex-16 significantly decreased. On the other hand, patients who reported their dermatitis worse showed an increase in the scores. These findings suggest that Skindex-16 responsively measures the disease severity and clinical change in the estimation of the effects of atopic dermatitis on patients' quality of life. This practical and sensitive, skin-disease specific, quality-of-life instrument is valuable for assessing patients' outcomes, especially their response to therapy, and is useful to understanding and improving the quality of life of patients suffering with atopic dermatitis.

Adolescent↗

Down-regulated PAR-2 is associated in part with interrupted melanosome transfer in pigmented basal cell epithelioma.

In pigmented basal cell epithelioma (BCE), there seems to be an abnormal transfer of melanized melanosomes from proliferating melanocytes to basaloid tumor cells. In this study, the interruption of that melanosome transfer was studied with special respect to the altered function of a phagocytic receptor, protease-activated receptor (PAR)-2 in the basaloid tumor cells. We used electron microscopy to clarify the disrupted transfer at the ultrastructural level and then performed immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to examine the regulation of a phagocytic receptor, PAR-2, expressed on basaloid tumor cells. Electron microscopic analysis revealed that basaloid tumor cells of pigmented BCE have a significantly lower population of melanosomes ( approximately 16.4%) than do normal keratinocytes located in the perilesional normal epidermis ( approximately 91.0%). In contrast, in pigmented seborrheic keratosis (SK), a similarly pigmented epidermal tumor, the distribution of melanin granules does not differ between the lesional ( approximately 93.9%) and the perilesional normal epidermis ( approximately 92.2 %), indicating that interrupted melanosome transfer occurs in BCE but not in all pigmented epithelial tumors. RT-PCR analysis demonstrated that the expression of PAR-2 mRNA transcripts in basaloid cells is significantly decreased in pigmented BCE compared with the perilesional normal epidermis. In contrast, in pigmented SK, where melanosome transfer to basaloid tumor cells is not interrupted, the expression of PAR-2 mRNA transcripts is comparable between the basaloid tumor cells and the perilesional normal epidermis. Immunohistochemistry demonstrated that basaloid cells in pigmented BCE have less immunostaining for PAR-2 than do keratinocytes in the perilesional normal epidermis whereas in pigmented SK, there is no difference in immunostaining for PAR-2 between the basaloid tumor and the perilesional normal epidermis. These findings suggest that the decreased expression of PAR-2 in the basaloid cells is associated in part with the observed interruption of melanosome transfer in pigmented BCE.

Aged↗